Antonio M.

Esquinas
Editor

Noninvasive
Mechanical Ventilation

Theory, Equipment, and

Clinical Applications
Second Edition

123
Noninvasive Mechanical Ventilation
Antonio M. Esquinas
Editor

Noninvasive Mechanical
Ventilation
Theory, Equipment, and Clinical
Applications

Second Edition
Editor
Antonio M. Esquinas
Murcia
Spain

ISBN 978-3-319-21652-2 ISBN 978-3-319-21653-9 (eBook)

DOI 10.1007/978-3-319-21653-9

Library of Congress Control Number: 2015956540

Springer Cham Heidelberg New York Dordrecht London

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To my wife Rosario
Preface

Despite significant technological advances in medicine today, the reality of every-

day practice continues to reveal that not everyone can apply and know the limits of
the technologies used in the treatment of respiratory failure.
Nowadays, in the treatment of acute respiratory failure in various medical spe-
cialties, the use of noninvasive mechanical ventilation continues to show a positive
end result. There are few hospitals that have the necessary equipment to make its
implementation possible. However, as we will see in this second edition, there are
still several points of controversy, and important advances continue to be made, not
only in new indications but also in the equipment (mechanical ventilator, interfaces)
and patient–ventilator interaction. This gives scope for improving our understand-
ing and maintains a growing interest in new possibilities.
In this second edition, we have analyzed the impact of published studies on the
effects of potential, new noninvasive ventilation treatments and clinical practice,
described by well-known researchers as well as other emerging groups of young
researchers.
Experience and new insights make this book a basic reference to understanding
and encouraging new ideas.
Personally, I want to thank all authors for trusting and contributing their time and
efforts in the development of this book. Finally, if I wanted to point out that we must
not stop this research inertia on noninvasive mechanical ventilation, knowing com-
municate well their knowledge and limits, and never forget that our end reference
points problems and circumstances that our patients during noninvasive mechanical
ventilation raising to us day to day.
This technique is still a life-saving treatment, relieves pain for many patients, and
gives encouragement. However, many aspects need to be reinvestigated and research
is necessary to resolve open controversies which indicate the failures of noninvasive
ventilation, methodology, and therapy. The question of what are the limits of nonin-
vasive ventilation and where needs to be addressed.

vii
viii Preface

As Albert Einstein said, “We cannot solve our problems with the same thinking
we used when we created them.” We hope that this second edition becomes a useful
reference that serves this modest reflection.

Murcia, Spain Antonio M. Esquinas, MD, PhD, FCCP

Contents

Part I Rational, Interface, Equipment and Ventilatory

Modes of Non Invasive Mechanical Ventilation

1 Rationale of Noninvasive Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Nicolino Ambrosino
2 Cardiopulmonary Function Interactions during
Noninvasive Mechanical Ventilation: Key Topics
and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Angelo Petroianni
3 Noninvasive Ventilation with Oral Mask:
Key Determinants and Clinical Evidence . . . . . . . . . . . . . . . . . . . . . . . . 21
Dilek Ozcengiz and Ersel Gulec
4 Nasal Pillow for Sleep Apnea Syndrome:
Key Technical Determinants and Clinical Evidence . . . . . . . . . . . . . . . 27
Yoshinori Matsuoka
5 ICU Ventilators Versus BiPAP Ventilators
in Noninvasive Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Tamer Fahmy and Sameh Salim
6 Ventilators for Noninvasive Mechanical Ventilation:
Theory and Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Raffaele Scala
7 Ventilatory Modes and Settings During
Noninvasive Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Claudio Rabec and Daniel Rodenstein
8 Software for Home Ventilators and Leak Compensation:
Key Technical and Practical Applications . . . . . . . . . . . . . . . . . . . . . . . 81
Patrick Pasquina, Jean-Paul Janssens, Olivier Contal, and Dan Adler
9 Maintenance Protocol for Home Ventilation Circuits . . . . . . . . . . . . . . 89
Michel Toussaint and Gregory Reychler

ix
x Contents

10 Noninvasive Open Ventilation (NIOV™) Therapy:

Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Heidi A. Pelchat, Patrick L. Williams, and Alex H. Gifford
11 Transnasal Insufflation: A New Approach in the Treatment
of Obstructive Sleep Apnea Syndrome? . . . . . . . . . . . . . . . . . . . . . . . . 105
Giuseppe Fiorentino, Antonio Pisano, and Daniela G. Giordano
12 Exhalation Ports and Interface: Key Technical Determinants
and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Henry K.H. Kwok
13 Technological Aspects and Safe Use of Noninvasive
Mechanical Ventilation Devices: Key Technical
and Practical Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Sven Stieglitz
14 CPAP Device Therapy for Noninvasive Mechanical
Ventilation in Hypoxemic Respiratory Failure:
Key Technical Topics and Clinical Implications . . . . . . . . . . . . . . . . . 131
Rodolfo Ferrari
15 Noninvasive Neurally Adjusted Ventilatory Assist (NIV-NAVA)
in Children and Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Jennifer Beck, Yun Liu, and Christer Sinderby
16 Off-Cycling During NIV in Chronic Obstructive
Pulmonary Disease: Clinical Implications . . . . . . . . . . . . . . . . . . . . . . 153
Lars-Olav Harnisch and Onnen Moerer

Part II Monitoring Respiratory Care, Phisiotherapy and Rehabilitation

17 Monitoring Patients During Noninvasive Ventilation:

The Clinical Point of View . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
G. Caironi, G. Gadda, R. Rossi, and Andrea Bellone
18 Monitoring Accuracy of Home Mechanical Ventilators:
Key Technical Elements and Clinical Implications . . . . . . . . . . . . . . . 173
Manel Luján, Xavier Pomares, and Ana Sogo
19 Capnography as a Tool to Improve Noninvasive Ventilation:
Technical Key Topics and Clinical Implications . . . . . . . . . . . . . . . . . 179
Eren Fatma Akcil, Ozlem Korkmaz Dilmen, and Yusuf Tunali
20 Humidification for Noninvasive Ventilation:
Key Technical Determinants and Clinical Evidence . . . . . . . . . . . . . . 183
Aylin Ugurlu Ozsancak and Antonio M. Esquinas
21 NIV Aerosol Therapy: Key Technical Determinants
and Clinical Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Serpil Ocal and Arzu Topeli
Contents xi

22 Skin Breakdown in Patients with Acute Respiratory

Failure Undergoing Noninvasive Ventilation: Key Topics . . . . . . . . . . 199
Samantha Torres Grams and Wellington Pereira Yamaguti
23 Nutrition During Noninvasive Ventilation:
Clinical Determinants and Key Practical Recommendations . . . . . . . 203
Anneli Reeves, Khoa Tran, and Peter Collins
24 Mechanical Insufflation-Exsufflation as Adjunctive
Therapy During Noninvasive Ventilation with Airways
Encumbrance: Key Technical Topics and Clinical
Indications in Critical Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Andrea Vianello, Oreste Marrone, and Grazia Crescimanno
25 Role of Complementary Chest Physiotherapy Techniques:
Strategies to Prevent Failure During Noninvasive
Mechanical Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Sergio R.M. Mateus
26 Noninvasive Ventilation in Cardiovascular Rehabilitation . . . . . . . . . 223
Vinicius Zacarias Maldaner da Silva, Gerson Cipriano Jr.,
and Graziela Franca Bernadelli Cipriano
27 Noninvasive Ventilation: Factors Influencing Carbon
Dioxide Rebreathing – Key Practical Implications . . . . . . . . . . . . . . . 229
Jacek Nasiłowski

Part III Clinical Applications: Pre and Intra Hospital

28 Noninvasive Mechanical Ventilation in Hypoxemic

Respiratory Failure: Determinants of Response
and Patients’ Flow Chart Recommendations – Key Topics
and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Roberto Cosentini and Tommaso Maraffi
29 Noninvasive Mechanical Ventilation in Acute Exacerbations
of Chronic Obstructive Pulmonary Disease:
Key Determinants of Early and Late Failure . . . . . . . . . . . . . . . . . . . . 249
Oya Baydar and Ezgi Ozyilmaz
30 Noninvasive Ventilation in the Prehospital Setting:
Key Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Patrick Chaftari, Maria Teresa Cruz Carreras, and Jayne Viets-Upchurch
31 Equipment Technology for Noninvasive Ventilation
in the Pre-hospital Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Steven C. LeCroy
32 Intra-hospital Transport of Patients during Noninvasive
Ventilatory Support: Key Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Antonio Javier Domínguez Petit and Antonio M. Esquinas
xii Contents

Part IV Hospital Critical Care Applications: Acute Chronic Exacerbations

33 Respiratory Mechanics in COPD Patients Who

Failed Noninvasive Ventilation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Vittorio Antonaglia, Massimo Ferluga, and Umberto Lucangelo
34 Impact of Comorbidities on Noninvasive Mechanical Ventilation
Response: Key Practical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Szymon Skoczyński
35 Noninvasive Continuous Positive Airway Pressure
Response in Bronchiectasis Exacerbations:
Key Practical Aspects and Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
Annia Schreiber, Andrea Antonelli, and Cesare Gregoretti
36 Noninvasive Mechanical Ventilation in Asthma Exacerbation:
Key Practical Aspects and Clinical Evidence . . . . . . . . . . . . . . . . . . . . 313
Guniz M. Koksal and Emre Erbabacan
37 Acute Applications of Noninvasive Ventilation in Obesity
Hypoventilation Syndrome: Evidence and Key Practical
Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Malcolm Lemyze
38 Noninvasive Ventilation in Chest Wall Deformities:
When and Why . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Dhruva Chaudhry and Rahul Roshan
39 Noninvasive Mechanical Ventilation in Duchenne
Muscular Dystrophy: What Have We Learned? . . . . . . . . . . . . . . . . . 333
Giuseppe Fiorentino, Antonio Pisano, and Anna Annunziata
40 Noninvasive Ventilation in Amyotrophic Lateral
Sclerosis: Key Technical and Practical Applications . . . . . . . . . . . . . . 339
Bart Vrijsen, Dries Testelmans, and Bertien Buyse
41 Noninvasive Ventilation in Myasthenic Crises . . . . . . . . . . . . . . . . . . . 345
Susana Pinto and Mamede de Carvalho

Part V Hospital Critical Care Applications:

Critical Care Acute Hypoxemic Respiratory Failure

42 Noninvasive Ventilation in Acute Cardiogenic

Pulmonary Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Chiara Lazzeri, Serafina Valente, Adriano Peris,
and Gian Franco Gensini
43 Is NIV Safe and Effective in Patients with ACPE Due to Diastolic
Dysfunction? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Andrea Bellone, Massimiliano Etteri, Guido Caironi,
Giorgio Gadda, and Roberto Rossi
Contents xiii

44 Noninvasive Mechanical Ventilation in Acute Cardiogenic

Pulmonary Edema and Cardiac Procedures: How to Choose
the Most Appropriate Mode and Improve Its Programming . . . . . . . 367
Javier Mendoza Vázquez
45 Practical Approach to the Use of Noninvasive Ventilation
in Patients with ACPE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
Jacobo Bacariza Blanco and Antonio M. Esquinas
46 Noninvasive Ventilation in Acute and Chronic Heart
Failure: Evidence and Key Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Simon G. Pearse and Martin R. Cowie
47 Noninvasive Ventilation in Drug Overdose: Is It a Potentially
Safe Application? Key Practical Implications . . . . . . . . . . . . . . . . . . . 393
Michalis Agrafiotis, Evangelia Serasli, and Venetia Tsara
48 Atelectasis and Noninvasive Mechanical Ventilation . . . . . . . . . . . . . . 401
Paulo Matos
49 Noninvasive Ventilation in Patients with Severe
Community-Acquired Pneumonia: What Have We Learned?
Key Response Determinants and Practical Implications . . . . . . . . . . 405
Michele Carron and Francesco Zarantonello
50 Noninvasive Ventilation in Acute Respiratory
Distress Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
Seval Urkmez and Yalim Dikmen
51 Noninvasive Mechanical Ventilation in Transfusion-Related
Acute Lung Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Sami Alsolamy, Hasan M. Al-Dorzi, and Yaseen M. Arabi
52 Noninvasive Ventilation in Patients with Blunt Chest Trauma:
What Have We Learned? Key Response Determinants
and Practical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Abhijit Duggal and Tasnim Sinuff
53 Noninvasive Ventilation in Acute Respiratory Failure
and Severe Neurological Deterioration . . . . . . . . . . . . . . . . . . . . . . . . . 435
Andrés Carrillo, Antonia Lopez, and Pablo Bayoumy
54 Noninvasive Ventilation in Cord Paralysis Diseases:
Is It a Possible Safe Indication? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Sven Stieglitz
55 Noninvasive Mechanical Ventilation in Older Patients . . . . . . . . . . . . 451
Cuneyt Salturk, Zuhal Karakurt, and Huriye Berk Takir
56 Role of Noninvasive Mechanical Ventilation in Difficult Weaning . . . 457
Inderpaul Singh Sehgal, Sahajal Dhooria,
Ashutosh N. Aggarwal, and Ritesh Agarwal
xiv Contents

57 Psychological Factors as Determinants of Noninvasive

Continuous Positive Airway Pressure Response:
Key Practical Aspects and Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473
Alex H. Gifford

Part VI Hospital Critical Care Applications: Critical Care Postoperative

58 Preoperative Noninvasive Ventilation: Key Practical

Recommendations and Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
R. Zaimi, J. Bardet, and Patrick Bagan
59 Intraoperative Noninvasive Ventilation: Key Technical
and Practical Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489
Luca Cabrini, Giovanni Landoni, and Alberto Zangrillo
60 Use of NIMV in the Early Postoperative Period:
Key Practical Aspects and Clinical Evidence . . . . . . . . . . . . . . . . . . . . 495
Emre Erbabacan
61 Noninvasive Mechanical Ventilation After Cardiac Surgery . . . . . . . 501
Gökhan İnangil and Ahmet Ertürk Yedekçi
62 Noninvasive Ventilation in the Post-extubation Period:
What Have We Learned? Evidence and Key Practical
Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
Christophe Girault, Gaëtan Beduneau, and Dorothée Carpentier
63 Perioperative Adverse Events in Obstructive Sleep
Apnea and Use of Noninvasive Mechanical Ventilation:
Key Topics and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . 519
C. Gregoretti, A. Braghiroli, G. Insalaco, A. Cortegiani, and R. Corso

Part VII Hospital Critical Care Applications: Non Invasive Ventilation

in Critically Cancer

64 Respiratory Failure and Noninvasive Mechanical Ventilation

in Cancer Patients: Global Overview . . . . . . . . . . . . . . . . . . . . . . . . . . 539
S. Egbert Pravinkumar and Antonio M. Esquinas
65 Noninvasive Versus Invasive Ventilation in Patients
with Hematological Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547
Massimo Antonelli, Giorgio Conti, and Giuseppe R. Gristina
66 Noninvasive Mechanical Ventilation in Critically Ill Patients
with Hematological Malignancy: Flow Chart, Evidence,
and Key Practical Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . 555
Pieter Depuydt
Contents xv

67 Noninvasive Ventilation in Patients with Solid Malignancies . . . . . . . 563

Pascal Kingah and Ayman O. Soubani

Part VIII Hospital Critical Care Applications: Non Invasive Ventilation

in Upper Airways, Endoscopy Procedures
and Sedation

68 Noninvasive Ventilation in Difficult Endotracheal Intubation . . . . . . 577

Igor Barjaktarevic, Jeffrey Albores, and David Berlin
69 Lung Ultrasound and Noninvasive Ventilation . . . . . . . . . . . . . . . . . . 591
Giovanni Ferrari, Alberto Milan, and Giovanni Volpicelli
70 Noninvasive Ventilation in Cardiac Procedures:
Key Technical and Practical Implications . . . . . . . . . . . . . . . . . . . . . . 599
Francesco Sbrana, Bruno Formichi, and Antonio Pisano
71 Noninvasive Mechanical Ventilation During Bronchoscopy:
Key Technical and Clinical Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . 607
Raffaele Scala
72 Sedation and Analgesia for Noninvasive Ventilation
in Intensive Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621
Yalim Dikmen
73 Use of Noninvasive Ventilation in the Course of Extracorporeal
Membrane Oxygenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 627
Adriano Peris, Maria Cristina Cozzolino, and Morena Ferraro
74 Noninvasive Ventilation Outside the ICU . . . . . . . . . . . . . . . . . . . . . . . 633
Laura Pasin, Pasquale Nardelli, and Alessandro Belletti

Part IX Non Invasive Ventilation in Sleep Medicine

75 Anatomical, Physical, and Psychological Factors

of NIV Interfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 641
Zoltan Tomori, Viliam Donic, Pavol Torok, and Josef Firment
76 Identification of Therapeutic CPAP for the Treatment
of Obstructive Sleep Apnea: Key Major Topics
and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649
Oreste Marrone, Adriana Salvaggio, Anna Lo Bue,
and Giuseppe Insalaco
77 Dual-Mode Noninvasive Mechanical Ventilation:
Key Technical and Practical Applications . . . . . . . . . . . . . . . . . . . . . . 657
Grazia Crescimanno, Andrea Vianello, and Oreste Marrone
xvi Contents

78 Results of Servo-ventilation and Other Ventilatory

Modes in Sleep Apnea Syndrome: Key Topics
and Practical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667
Dominic Dellweg, Markus Wenzel, and Jens Kerl
79 Contribution of Back-Up Respiratory Rate Setting
in Noninvasive Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
Jean-Paul Janssens, Dan Adler, Patrick Pasquina, and Olivier Contal
80 Nasal High Flow: Novel Approach for Ventilatory
Assist During Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681
Hartmut Schneider and Jason P. Kirkness
81 NIV Adaptation Process: Implications of Team:
Key Practical Recommendations and Evidence . . . . . . . . . . . . . . . . . . 691
Pawel J. Kuca and Witold Z. Tomkowski
82 Adherence to and Complications of CPAP in Obstructive
Sleep Apnea: Key Determinants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 703
Ahmed S. BaHammam, Aisha Hussain, and Mohammad Al-Asmri
83 “Deventilation Syndrome” in CPAP Users with Obstructive
Sleep Apnea: Clinical Impact and Solutions . . . . . . . . . . . . . . . . . . . . 717
Çiğdem Akyol Beyoğlu, Aylin Özdilek, and Emre Erbabacan
84 Psychological Factors in Noninvasive Home Ventilation Users . . . . . 725
Alicia Carissimi, Denis Martinez, and Cintia Zappe Fiori
85 Ambulatory Model of Noninvasive Ventilation Adaptation:
Implications for Health Care, Organization, and Outcome . . . . . . . . 731
Alessio Mattei, Cinzia Ferrero, and Giuseppe Tabbia
86 Chronic Obstructive Pulmonary Disease and Obstructive
Sleep Apnea, Known as the Overlap Syndrome:
Indications for CPAP and BiPAP. Evidence and Key Practical
Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
Philippe Jaoude and Ali A. El Solh
87 Continuous Positive Airway Pressure in Nonapneic Asthma . . . . . . . 747
J. Navarro-Esteva and G. Juliá-Serdá
88 Chronic Heart Failure and Sleep-Disordered Breathing:
Evidence for the Effect of Continuous Positive Airway
Pressure and Key Practical Implications . . . . . . . . . . . . . . . . . . . . . . . 753
Takatoshi Kasai

Part X Non Invasive Ventilation in Long-Term Applications

89 Long-Term Noninvasive Ventilation Application

in COPD: Determinants and Lessons Learned . . . . . . . . . . . . . . . . . . 767
Nicolino Ambrosino
Contents xvii

90 Long-Term Noninvasive Ventilation Among Chronic

Respiratory Failure Diseases (Cystic Fibrosis
and Other Diseases) Awaiting Lung Transplantation:
Key Determinants and Practical Implications . . . . . . . . . . . . . . . . . . . 771
Ana Souto Alonso, Pedro Jorge Marcos Rodriguez,
and Carlos J. Egea Santaolalla
91 Home Mechanical Ventilation and Quality of Life
in Neuromuscular Patients During Noninvasive Mechanical
Ventilation: New Trends and Key Practical Topics . . . . . . . . . . . . . . . 781
Catarina Ferreira and Joaquim Moita
92 European Models of Home Noninvasive Mechanical
Ventilation: What Have We Learned? Evidence
and Key Determinants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
Francisco J. Ribas-Solís, Julia A. Garcia-Fuertes, and Carlos J.
Egea-Santaolalla
93 Telemonitoring of CPAP Compliance: Key Technical
Topics and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 799
Sevinc Sarinc Ulasli and Aylin Ozsancak Ugurlu
94 Psychological Factors as a Determinant of Noninvasive
Ventilation Compliance: Key Practical Aspects and Topics . . . . . . . . 807
Marie-Christine Rousseau and Stéphane Pietra

Part XI Non Invasive Ventilation Pediatric

95 Interfaces for Acute and Long-Term Noninvasive Positive

Pressure Ventilation in Children: Key Technical Elements
and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
Brigitte Fauroux, Adriana Ramirez, and Alessandro Amaddeo

Part XII Non Invasive Ventilation, Epidemiology,

Health Care Organization, Education and Ethics

96 Epidemiology, Practice and New Trends in Noninvasive

Mechanical Ventilation: What Are We Learning?. . . . . . . . . . . . . . . . 829
Claudia Crimi and Annalisa Carlucci
97 Determinants of Utilization of Noninvasive Mechanical Ventilation
in Hospitals: Key Technical and Nontechnical Issues . . . . . . . . . . . . . 839
Guy W. Soo Hoo
98 Influence of Staff Training on the Outcome of Noninvasive
Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 851
Bárbara M.E.M.A. Seabra
xviii Contents

99 Quality of Life during Long-Term Mechanical

Ventilation in Hypercapnic Respiratory Failure:
Main Determinants and Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . 859
Graham T. Atkins and Alex H. Gifford
100 Ethics: Decision Making in Noninvasive Ventilation . . . . . . . . . . . . . 867
Andrea Purro

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 873
 Part I
Rational, Interface, Equipment
and Ventilatory Modes of Non Invasive
Mechanical Ventilation
Rationale of Noninvasive Ventilation
1
Nicolino Ambrosino

Contents
1.1 Stable Hypercapnic Chronic Obstructive
Pulmonary Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1.1 Correction of Hypoventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.1.2 Respiratory Muscle Unloading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.1.3 Reset of the Respiratory Centers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.1.4 Cardiovascular Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2 Acute COPD Exacerbations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 How Does NPPV Work in Acute Exacerbations of COPD? . . . . . . . . . . . . . . . . . . . . . . 5
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

1.1 Stable Hypercapnic Chronic Obstructive

Pulmonary Disease

The hypothesized but not proven mechanisms of action of long-term noninvasive

positive pressure ventilation (NPPV) in stable hypercapnic patients with chronic
obstructive pulmonary disease (COPD) are

1. Reverting hypoventilation
2. Respiratory muscle unloading
3. Respiratory center reset
4. Cardiovascular effects

These mechanisms may work alone or in synergy.

N. Ambrosino
Pulmonary Rehabilitation and Weaning Unit, Auxilium Vitae, Volterra, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 3

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_1
4 N. Ambrosino

1.1.1 Correction of Hypoventilation

Physiological studies have shown that, in stable hypercapnic COPD patients, NPPV
in pressure support mode is able to improve alveolar ventilation by increasing the
tidal volume and reducing the respiratory rate [1].

1.1.2 Respiratory Muscle Unloading

There is evidence that noninvasive inspiratory pressure is able to unload the inspira-
tory muscles, whereas the application of positive end-expiratory pressure (PEEP)
counteracts the intrinsic PEEP (PEEPi) associated with hyperinflation in these
patients [2], an effect more evident in acute exacerbations.

1.1.3 Reset of the Respiratory Centers

There is evidence that, compared with long-term oxygen therapy (LTOT) alone,
addition of NPPV at night resulted in significant improvements in daytime arterial
oxygen (PaO2) and carbon dioxide (PaCO2) tension, total sleep time, sleep effi-
ciency, and overnight PaCO2. Quality of life with LTOT plus NPPV was signifi-
cantly better than with LTOT alone. The degree of improvement in daytime PaCO2
was significantly correlated with an improvement in mean overnight PaCO2 [3].

1.1.4 Cardiovascular Effects

Night-time NPPV applied over 3 months may improve heart rate variability, reduce
circulating natriuretic peptide levels, and enhance the functional performance of
patients with advanced but stable COPD, suggesting that nocturnal NPPV may
reduce the impact of cardiac comorbidities in COPD patients [4].

1.2 Acute COPD Exacerbations

In acute exacerbations of COPD leading to acute respiratory failure (ARF), the work
of breathing (WOB is) increased as a result of the increase in airway resistances.
Because of lung hyperinflation, the respiratory muscles are less effective and, if the
underlying pathology does not reverse in a relatively short time, they are at risk of
failure and fatigue. Despite an increase in respiratory drive, rapid shallow breathing
may lead to reduction in alveolar ventilation, even when minute ventilation is normal
or even increased. Respiratory muscles progressively become unable to maintain
1 Rationale of Noninvasive Ventilation 5

adequate alveolar ventilation, resulting in an increase of PaCO2. When PaCO2 is

severely increased for a prolonged time, the level of consciousness is generally
impaired.

1.3 How Does NPPV Work in Acute Exacerbations of COPD?

When the cause of ARF is reversible, medical treatment works to maximize lung
function and reverse the precipitating cause, whereas the aim of ventilatory support
is [5]

• To buy time for the treatment of the cause of ARF to work

• To decrease the work of breathing (WOB)
• To reverse life-threatening hypoxemia and respiratory acidosis

In these circumstances, inspiratory support works to increase alveolar ventilation

by increasing tidal volume and to unload inspiratory muscles by decreasing
WOB. The addition of an external PEEP may further reduce WOB by counterbal-
ancing the PEEPi.
Such patients may require intubation for airway protection in addition to ventila-
tory assistance, unless the hypercapnia can be reversed within minutes. It has been
shown that NPPV may avoid most of the complications associated with invasive
mechanical ventilation, ensuring at the same time a similar degree of efficacy [6].
The early use of NPPV in COPD patients may prevent further deterioration and thus
avoid endotracheal intubation, improving survival compared with standard medical
therapy. As a consequence, NPPV is considered as the first-line treatment of acute
exacerbations of COPD.
The early use of NPPV is mandatory because success rate decreases with dis-
ease progression. On the other hand, NPPV may be useless or even a problem for
the patient when applied in mild exacerbations that can be treated only by medi-
cal therapy [7]. In other words, as in other fields of medicine, this therapeutic
tool should be applied during a therapeutic window: not too early, not too late. In
practice, arterial blood gases, and signs (tachypnea or increased accessory mus-
cle use) and symptoms (dyspnea) of increased WOB should be used as markers
to start NPPV in these conditions [8]. When NPPV is started early, those patients
not in danger (pH not lower than 7.30) can be managed outside of the intensive
care unit (ICU), eventually even in a ward with an adequately skilled team [9]. In
addition, dedicated units such as high-dependency respiratory intensive care
should be encouraged to deliver NPPV to most but not all patients. For these
patients, these units may offer noninvasive monitoring systems and higher nurse-
to-patient ratios than in general wards with less burden but similar success rates
as in ICUs [10].
6 N. Ambrosino

Key Points
• Possible mechanisms of action of long-term NPPV in stable hypercapnic
COPD patients are correction of hypoventilation, respiratory muscle
unloading, reset of the respiratory centers, and inducing positive cardio-
vascular effects.
• The goals of ventilatory support in ARF are to buy time for the treatment
of the cause of ARF to work, to decrease the WOB, and to reverse life-
threatening hypoxemia and respiratory acidosis.
• NPPV may avoid most of complications associated with invasive mechani-
cal ventilation, ensuring at the same time a similar degree of efficacy.
• NPPV in acute COPD exacerbation must be applied during an appropriate
therapeutic window.
• The location of NPPV must be related to timing and severity of disease.

References
1. Ambrosino N, Nava S, Bertone P, et al. Physiologic evaluation of pressure support ventilation
by nasal mask in patients with stable COPD. Chest. 1992;101:385–91.
2. Nava S, Ambrosino N, Rubini F, et al. Effect of nasal pressure support ventilation and external
PEEP on diaphragmatic activity in patients with severe stable COPD. Chest. 1993;103:
143–50.
3. Meecham Jones DJ, Paul EA, Jones PW, et al. Nasal pressure support ventilation plus oxygen
compared with oxygen therapy alone in hypercapnic COPD. Am J Respir Crit Care Med.
1995;152:538–44.
4. Sin DD, Wong E, Mayers I, et al. Effects of nocturnal noninvasive mechanical ventilation on
heart rate variability of patients with advanced COPD. Chest. 2007;131:156–63.
5. Tobin MJ. Advances in mechanical ventilation. N Engl J Med. 2001;344:1986–96.
6. Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care set-
ting: where are we? Eur Respir J. 2008;31:874–86.
7. Barbè F, Togores B, Rubi M, et al. Noninvasive ventilator support does not facilitate recovery
from acute respiratory failure in chronic obstructive pulmonary disease. Eur Respir J. 1996;9:
1240–5.
8. Keenan SP, Powers CE, McCormack DG. Noninvasive positive-pressure ventilation in patients
with milder chronic obstructive pulmonary disease exacerbations: a randomized controlled
trial. Respir Care. 2005;50:610–6.
9. Plant PK, Owen JL, Elliott MW. A multicenter randomized controlled trial of the early use of
non-invasive ventilation in acute exacerbation of chronic obstructive pulmonary disease on
general respiratory wards. Lancet. 2000;355:1931–5.
10. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009;374:
250–9.
Cardiopulmonary Function Interactions
during Noninvasive Mechanical 2
Ventilation: Key Topics and Clinical
Implications

Angelo Petroianni

Contents
2.1 Introduction ................................................................................................................... 8
2.1.1 Basic Physiological Concepts in Cardiopulmonary Interactions ...................... 8
2.1.2 Cardiopulmonary Interaction During Spontaneous Breathing.......................... 11
2.2 Interactions on Cardiopulmonary Function in NIV ...................................................... 12
2.2.1 NIV and Clinical Implications in Respiratory and Cardiovascular Diseases ... 14
Conclusions ............................................................................................................................ 17
References .............................................................................................................................. 19

Abbreviations

CO Cardiac output
COPD Chronic obstructive pulmonary disease
FRC Functional residual volume
ITP Intrathoracic pressure
LV Left ventricle
MV Mechanical ventilation
NIV Noninvasive ventilation
PA Alveolar pressure
Pa Arterial pressure
PEEP Positive end-expiratory pressure
PH Pulmonary hypertension
Ppl Pleural pressure

A. Petroianni, MD, PhD, FCCP

Respiratory Diseases Unit, Department of Cardiovascular and Respiratory Diseases,
Polyclinic Umberto I, Sapienza University of Rome, Viale del Policlinico 155,
Rome 00100, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 7

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_2
8 A. Petroianni

PPV Positive pressure ventilation

Ptm Transmural pressure
Pv Venous pressure
PVR Pulmonary vascular resistance
RV Right ventricle
TLC Total lung capacity
V/Q Ventilation/perfusion ratio
VI Ventricular interdependence
WOB Work of breathing

2.1 Introduction

The thoracic cavity contains the lungs, with pulmonary vasculature divided
into intra- and extra-alveolar vessels, and the heart, with the great veins and
thoracic aorta. The dynamic mechanical properties of the thoracic organs are
variable and conditioned by their volume and elasticity. Changes in lung vol-
ume and pleural pressure (Ppl) influence cardiac function even during sponta-
neous breathing.
The intrathoracic cardiovascular system is described as two pumps (right and left
ventricles) connected in series and separated from each other by the pulmonary and
systemic circulation. Output of the right ventricle (RV) provides the input (venous
return) for the left ventricle (LV) through the pulmonary circulation with a lag time
of two beats [1].
Cardiopulmonary interactions can be substantially understood on the basis of the
effects of changes in intrathoracic pressure (ITP) and lung volume on the determi-
nants of cardiovascular performance: atrial preload, ventricular afterload, myocar-
dial contractility, and heart rate. Changes in ITP are transmitted to the intrathoracic
structures: the heart and pericardium, the great arteries and veins [2]. These interac-
tions are observable in health and can be increased or modified in the presence of
diseases or mechanical ventilation (MV).
The effects of spontaneous ventilation on the circulation were first documented
in 1733 by Stephen Hales, showing that the blood pressure of healthy people fell
during spontaneous inspiration. Over a century later, Kussmaul described the pulsus
paradoxus (inspiratory absence of the radial pulse) in patients with tuberculous
pericarditis [3].

2.1.1 Basic Physiological Concepts in Cardiopulmonary

Interactions

A brief definition of some basic physiological concepts involved in cardiopulmo-

nary interactions is essential before illustrating their effects during noninvasive
ventilation (NIV).
2 Cardiopulmonary Function Interactions during Noninvasive Mechanical Ventilation 9

• Pulmonary compliance defines the change in lung volume due to changes in

transpulmonary pressure applied to the lung (ΔV/ΔP). It is a measure of the abil-
ity of the lungs to be stretched and expanded. The transpulmonary pressure is
determined by the difference between pleural pressure (Ppl) or ITP and alveolar
pressure (PA). Ppl is normally a subatmospheric pressure (−5 cmH2O) and PA
(force of airflow into and out of the lungs) is <0 cmH2O in inspiration and >0 in
expiration. The compliance is highest at moderate lung volumes, near functional
residual capacity (FRC), with a normal value of 200 ml/cmH2O, and much lower
at very low volumes (toward residual volume) or very high volumes (toward total
lung capacity). However, if the lung is more rigid (as in restrictive diseases),
pulmonary compliance decreases, moving the pressure-volume curve to the
right, whereas increases in conditions with less rigidity (emphysema) move the
pressure-volume curve to the left. This concept is important when NIV is applied.
Lung and chest wall compliance constitutes the total compliance of the system.
In the supine position, the pressure-volume curve of the lung does not change
compared with the orthostatic position, but the curve of the chest wall moves to
the right because it is more difficult to stretch the chest [4].
• Transmural pressure (Ptm), also called distending pressure, is the difference
between the pressure within a chamber or vessel (intramural stress or Pin) and the
pressure around it (extramural stress or Pex). The Ptm (= Pin–Pex) describes the
complex effects of changes in ITP or blood volume on the cardiac chambers.
Respiration induces phasic fluctuations in cardiac Ptm, and inspiratory Ppl is low-
ered by the respiratory muscles during spontaneous breathing and is increased
during the application of positive pressure ventilation (PPV). The resultant varia-
tion of Ppl determines a change in Pex in the heart with a direct influence on LV
and RV volume and function. The rise in Ptm, consequent to a fall in Ppl, promotes
ventricular filling and impedes ejection [4].
• Ventricular interdependence (VI) is the influence of the RV on the
LV. Anatomically, the LV and RV share a common pericardial sac, with limited
volume and compliance, and a common interventricular septum [4]. The filling
of one ventricle can directly influence the function of the other: an increase in RV
volume during spontaneous inspiration leads to a reduction in LV compliance
and, hence, LV filling. VI is considered the major cause of pulsus paradoxus in
patients with a restrictive pericardium as a result of tamponade. This effect
becomes greater as Ppl becomes more negative or with a fluid bolus that acutely
fills the RV. The application of positive end-expiratory pressure (PEEP) can be
beneficial in these conditions [4].
• Cardiac output (CO) is the volume of blood pumped by the LV or RV in
1 min. An average resting CO is 5.6 l/min for a male and 4.9 l/min for a
female [5]. Respiration with its ITP variations influences diastolic heart fill-
ing and, hence, CO. During NIV, these respiratory changes are particularly
important. CO is measured at a defined phase of the respiratory cycle, usually
at end-expiration [5].
• Ventilation/perfusion ratio (V/Q) is not uniform in all the zones of the lung. V/Q
inequalities in the lung were proposed by Permutt in 1962 and 2 years later by
10 A. Petroianni

West et al. [6]. In the erect position, the perfusion increases from the top to the
bottom of the lung. This is a result of hydrostatic forces combined with the dif-
ferent effect of airway pressure. In theory, the lung is divided into three vertical
regions, based on the relationship between the pressure in the alveoli (PA), in the
arteries (Pa), and the veins (Pv). Zone 1 (PA > Pa > Pv) is a region at the top of the
lung in which Pa falls below PA. It is not observed in the normal healthy human
lung, because Pa exceeds PA in all parts of the lung. This is generally observed in
marked hypotension or during NIV. In these circumstances, capillaries remain
collapsed and low perfusion occurs (dead space). In zone 1, V/Q is the highest.
Zone 2 (Pa > PA > Pv) is the part of the lung about 3 cm above the heart, where
pulmonary Pa is greater than PA, but Pv remains below PA. In this region, blood
flows in pulses. Zone 3 (Pa > Pv > PA) includes the majority of the lung in health.
In this zone, both Pa and Pv exceed PA, producing continuous blood flow through-
out the cardiac cycle.
• Pulmonary vascular resistance (PVR) is the flow resistance that must be over-
come to push blood through the vasculature of the lungs. The total resistance of
the pulmonary circulation depends on the balance in the vascular tone of its two
components: the alveolar vessels and the extra-alveolar or parenchymal vessels.
PVR is closely related to lung volume, rising at both extremes of lung volume
variations (Fig. 2.1). PVR is minimal at FRC. When the lungs are inflated above
FRC toward total lung capacity (TLC), alveolar vessels become compressed as a
result of alveolar distension or hyperinflation. As lung volume falls from FRC
toward residual volume, extra-alveolar vessels become progressively more tortu-
ous and tend to collapse and terminal airway collapse at low volumes causing

Fig. 2.1 Schematic representation of the relation between lung volumes and pulmonary vascular
resistance (PVR). Alveolar and extra-alveolar resistance determine the PVR. As lung volume
increase from residual volume (RV) to total lung capacity (TLC), the alveolar vessels become
compressed by distending alveoli and their resistance increases, whereas the extra-alveolar vessels
become less tortuous with a fall of their resistance. At functional residual capacity (FRC) PVR is
lowest
2 Cardiopulmonary Function Interactions during Noninvasive Mechanical Ventilation 11

alveolar hypoxia. Hypoxic pulmonary vasoconstriction independently increases

PVR. In addition, lower pH leads to increased pulmonary vasoconstriction.
Hereafter, these concepts will be applied to the interactions in cardiopulmo-
nary function in spontaneous breathing, during NIV, and in the presence of respi-
ratory and cardiac diseases.

2.1.2 Cardiopulmonary Interaction During Spontaneous

Breathing

In spontaneous breathing, the contractions of the diaphragm and intercostal muscles

reduce ITP, leading to a greater pressure gradient according to the values of atmo-
spheric and airway pressure. The decrease in ITP is transmitted to the intrathoracic
organs, resulting in a fall in cardiac Pex and a rise in Ptm. The increase in Ptm pro-
motes RV diastolic filling. Consequently, RV increases stroke volume via the Frank-
Starling mechanism [5]. The subsequent rise in pulmonary flow increases LV
pressure load and its end-diastolic volume. Also, LV Pex falls and Ptm rises during
inspiration, increasing LV afterload during the systole. As a result, LV stroke vol-
ume and systolic blood pressure fall and LV end-systolic volume rises [5]. Thus, the
main consequences of the decrease in ITP during spontaneous breathing are an
increase in LV afterload and an increase in RV preload (Table 2.1).
In healthy subjects, spontaneous inspiration is usually associated with a slight
fall in systolic blood pressure (<10 mmHg). During spontaneous inspiration, both
Ppl and intravascular aortic pressure fall, but the fall in Ppl is relatively greater than
the fall in aortic pressure, increasing Ptm and resulting in an increased LV afterload
and a reduction in LV stroke volume.

Table 2.1 Different effects on lung and heart function

Spontaneous breathing Noninvasive ventilation
↓ ITP (negative) ↑↑ ITP (positive)
↓ Blood systemic pressure inspiration ↓↓ Blood systemic pressure inspiration
÷ PVR ↑ PVR
↑ Ptm ↓ Ptm
↑ Venous return RA ↓↓ Venous return RA
↑ RA preload ↓ RA preload
↑ RV afterload ↑ RV afterload
↑ RV cardiac output ↓ RV cardiac output
↑ LV afterload ↓ LV afterload
↓ LV cardiac output ↑ LV cardiac output
↑ Myocardial O2 consumption RV
↓ Myocardial O2 consumption LV
ITP intrathoracic pressure, PVR pulmonary vascular resistance, Ptm transmural pressure, RA right
atrium, RV right ventricle, LV left ventricle
12 A. Petroianni

Increased respiratory efforts with a greater variation of Ppl and Ptm, as in asthma
and pulmonary edema, or increased sensitivity to changes in Ptm in the heart, as in
hypovolemia and congestive cardiac failure, leads to a decrease in systolic blood
pressure during inspiration more than 10 mmHg, creating pulsus paradoxus [3].
The effect of spontaneous breathing on pulmonary blood vessels is generally
irrelevant and hardly ever causes a significant drop in systolic pressure. In addition,
changes in lung volumes during spontaneous ventilation rarely determine an
increase in PVR.
Neurohumoral processes probably play a primary role in the long-term effects of
ventilation on the cardiovascular system. However, most of the immediate effects of
ventilation on the heart are secondary to changes in autonomic tone. The lungs are
richly enervated with somatic and autonomic fibers that mediate different homeo-
static processes and instantaneously alter the cardiovascular function. The most
common of these are the vagally mediated heart rate changes during ventilation [7].
Inflation of the lung to normal tidal volumes (<10 ml/kg) induces vagal-tone with-
drawal, accelerating heart rate. This phenomenon is known as respiratory sinus
arrhythmia and can be used to document normal autonomic control, especially in
patients with diabetes who are at risk for peripheral neuropathy [7]. Inflation to
larger tidal volumes (>15 ml/kg) decreases heart rate by a combination of both
increased vagal tone and sympathetic withdrawal. Sympathetic withdrawal also
determines arterial vasodilation. This inflation/vasodilation response can reduce LV
contractility in healthy subjects and, as reported below, in ventilator-dependent
patients with the initiation of high-frequency ventilation or hyperinflation [7].

2.2 Interactions on Cardiopulmonary Function in NIV

Mechanical ventilation, applying a positive pressure on inspiration and increasing

ITP, produces physiological effects that are directly opposite from normal spontane-
ous ventilation. The positive ITP is transmitted to the alveoli and the interstitial
tissues. Intrapulmonary and interstitial pressures remain positive in inspiration and
return toward atmospheric pressure on expiration. If a PEEP is added, ITP remains
positive even in expiration. As in spontaneous breathing, MV is associated with an
inspiratory fall in aortic flow and systolic blood pressure, but the mechanism is
considerably different [8].
In the 1940, Cournand et al. [9] studied the physiological effects of a PPV on
cardiac function, demonstrating a variable reduction in CO in healthy subjects
receiving PPV. Cournand showed that RV filling was inversely related to ITP, and as
this became more positive the RV preload fell, producing an evident fall in CO.
PPV determines a simultaneous rise in ITP and in lung volumes. The increase in
lung volume plays a significant role in the hemodynamic changes during NIV: tidal
volumes are often higher than those in spontaneous breathing.
The interactions with cardiopulmonary function during NIV are complex and
may depend on baseline cardiopulmonary function and, in a certain way, differences
in the mode of ventilation.
2 Cardiopulmonary Function Interactions during Noninvasive Mechanical Ventilation 13

The main hemodynamic effects of PPV include a decrease in venous return of

RV and LV, an increase in VI, an increase in PVR, an increase in central venous
pressure, and a decrease in LV afterload (Table 2.1).
The positive ITP decreases venous return and alters RV and LV ejection.
Increased lung volume enlarges RV size by raising PVR, causing intraventricular
cardiac septum shift and decreasing LV filling. In addition, augmented ITP
reduces LV afterload, increasing ejection of blood from LV. These effects are
proportional to the amount of positive pressure, inspiratory volume, and value of
PEEP [4].
The decrease in preload and blood pressure essentially depends on the volume
status of the patient and is more pronounced in conditions of reduced venous return
(hypovolemia and vasodilation). This is primarily due to the influence of ITP on
venous return of RV, leading to a fall in left heart output. Considering ventilation
modalities, the decrease in preload and blood pressure can be greater with con-
trolled modes of MV with high tidal volume and high airway pressure. Thus, the
application of assisted MV modalities (CPAP, BiPAP, PSV), maintaining a sponta-
neous inspiratory effort, is favored in these cases [10].
Conversely, patients with fluid overload and congestive heart failure consider-
ably benefit from PEEP or PPV and may radically improve after its application.
Because ITP is higher during NIV, volume infusion stabilizes the relationship
between venous return and CO.
The intrathoracic cardiovascular system is often described as two sections (RV
and LV) connected in series. Therefore, it is clinically more practical to consider the
effects of NIV on right and left heart (Table 2.1).

• Effects of NIV on right heart: the effects on right heart are mainly characterized
by a decrease in venous return (RA preload), an increase of RV afterload, and a
decrease in RV coronary flow. PVR is the main determinant of RV afterload and
is directly affected by changes in lung volume (Fig. 2.1). PVR rises during NIV,
determining increased work for the right heart and decreased filling for the left
heart.
The decrease of venous return, especially in patients with hypovolemia (real
or relative), determines a complex compensatory sympathetic response with
tachycardia, vasoconstriction, oliguria, and retention of water and NaCl [4].
Increased RV afterload, especially when using high tidal volumes, results in an
increase of RV work and O2 consumption. For this reason, the use of low tidal
volumes is preferable in patients with acute cor pulmonale.
• Effects of NIV on left heart: the effects on the left heart include a decrease in LA
preload, the reduction of LV afterload, an increase in stroke volume, decrease in
O2 consumption, and increase of CO. The reduction of LV afterload is the most
relevant effect during NIV, restoring the hemodynamics to a more favorable
position on the Starling curve: Ptm (distending pressure) decreases with a high
ITP (Ptm = Pin – ITP). Therefore, patients with left heart failure show a functional
improvement during NIV, even if limited by the decrease in venous return for
high levels of PEEP.
14 A. Petroianni

Extrinsic PEEP (PEEPe), increasing mean PA and also Ppl, is commonly used to
recruit alveoli, defend end-expiratory lung volume, and improve oxygenation dur-
ing MV. Some data support the neurohumoral-mediated effects of PEEP on cardiac
function in addition to its mechanical effects [10]. The achievement of the best
value of PEEP is based on the balance between the respiratory benefits of PEEP and
its adverse cardiovascular and respiratory effects.
Physiologically, V/Q inequalities coexist in the different zones of the lung.
Alveolar recruitment is essential for the efficacy of NIV. The state of the airways,
their resistance, and the alveolar compliance determine the effect of the pressure
in different regions of the lung. These factors define the individual time constant
of the different regions. Positive pressure preferentially aerates high compliance
areas at the expense of lower compliance areas, whereas collapsed alveoli may
require higher constant pressure to be opened. The variation in time constants
between alveoli and lung regions precludes a single pressure as suitable for all
lung regions [11].
Dyspnea is the imbalance between breathing effort and chest displacement. The
patient’s strategy to maintain alveolar ventilation that minimizes the work of breath-
ing (WOB) is the breathing pattern balancing the elastic and resistive ventilation
forces. Increased inspiratory effort produces a large negative Ppl that increases LV
afterload and may lead to respiratory muscle fatigue and respiratory acidosis. A
positive inspiratory pressure-assist favors the reduction of patient’s WOB, inspira-
tory effort, and dyspnea [11].
NIV does not directly depress cardiac contractility. The presence of PEEP pro-
motes the release of cardiodepressive humoral factors. Furthermore, the alteration
between O2 demand and supply for increased RV afterload can justify a reduction in
contractility, rather than the LV, where the decrease in preload and afterload reduces
wall stress and O2 demand.
In summary, conditions that can accentuate the hemodynamic effects of MV
include hypovolemia and venodilation (decrease in venous return), use of large tidal
volume or high PEEPe (increase in mean ITP), and anesthesia and sedatives (reduc-
tion of compensatory sympathetic reflexes). The use of volume expansion to restore
LV preload, assisted modes of ventilation to reduce Ppl, and the avoidance of high
ITP occurring with a high minute volume, high inspiratory flow, or PEEPe are effi-
cient strategies to minimize these effects.

2.2.1 NIV and Clinical Implications in Respiratory

and Cardiovascular Diseases

In patients with cardiovascular or pulmonary diseases, the application of NIV

requires special consideration.

• Cardiac diseases are frequent in patients requiring MV. These have important
hemodynamic effects during NIV depending on the type and severity of the dis-
ease. As described above, the main physiological determinants of CO are preload,
2 Cardiopulmonary Function Interactions during Noninvasive Mechanical Ventilation 15

contractility, afterload, and heart rate. Changes in CO are the result of the increase
in ITP, which causes a decrease in preload and afterload [11].
In cases of hypovolemia, restrictive cardiomyopathy, tamponade, or valvular
stenosis, where CO is dependent on venous return, PPV can cause a further
reduction in CO. In coronary heart disease, heart diseases with fibrosis, or hyper-
trophy, characterized by reduced ventricular compliance, increased ITP during
NIV reduces LV afterload and increases CO.
In ischemic diastolic LV dysfunction with pulmonary edema, characterized
by the increase in preload and afterload, increased intrathoracic blood volume,
a positive ITP, or simply the use of PEEP can improve CO by limiting venous
return and lowering LV afterload. In addition, PEEP helps to maintain alveolar
patency and lung volume in these patients at risk of secondary atelectasis as a
result of edema. In cases of coronary artery disease and impaired LV contractil-
ity, the heart is not able to compensate for the increased O2 need and increased
effort for breathing, which can increase up to 20 times and can sometimes result
in cardiorespiratory arrest [2]. In LV failure, an increase in preload and afterload
also increases O2 demand of the myocardium, leading to a negative myocardial
O2 balance. The application of MV may have a favorable effect on preload and
afterload reduction of LV, and reduces the need for O2 with the correction of
hypoxia and metabolic acidosis. PEEP determines improvements in oxygenation
and in lung volume toward FRC and can also have a beneficial effect on RV
afterload.
The effect of PPV on the RV is not so favorable. The increase in ITP and
PEEP increases PVR and impairs RV function by reducing preload and
increasing afterload. In subjects with pulmonary hypertension (PH), acute
pulmonary embolism, COPD, or RV infarction, characterized by afterload-
induced RV dysfunction, MV may affect the balance of RV supply and demand
of oxygen. The treatment of reversible pulmonary vasoconstriction by hypoxia
or acidosis and the defense of coronary perfusion pressure with pressor agents
can be beneficial [8].
In heart failure secondary to RA stretch, circulating levels of natriuretic pep-
tides increase. These hormones promote sodium and water diuresis. PPV and
persistent hyperinflation decrease RA stretch mimicking hypovolemia. During
PPV, plasma norepinephrine and rennin increase, whereas atrial natriuretic pep-
tide decreases [4].
• Pulmonary diseases determine pathological changes in lung mechanics affecting
lung volume and elasticity, airflow resistance, WOB, and RV impedance [10].
Conditions altering lung volume, with a reduction in lung compliance and
volume, are the result of bronchial obstruction (inflammation, secretions), an
increase in lung elastance (pulmonary edema, pneumonia, acute respiratory dis-
tress syndrome (ARDS)), a reduction in FRC (anesthesia, supine posture,
abdominal and thoracic trauma), or an increase in closing volume.
Any variation in lung volume increases PVR (Fig. 2.1) and increases RV load.
A reduction in lung volume increases the resistance in extra-alveolar pulmo-
nary vessels due to hypoxic vasoconstriction, structural distortion, and
16 A. Petroianni

vasoconstrictor mediators (thromboxanes). This condition also increases the

dependence and interaction of LV function on the RV.
The prevention of acute right heart failure due to excessive increase in PVR
can be achieved by avoiding NIV with large volumes and high pressure. Alveolar
recruitment and reversal of hypoxia and acidosis are important efforts to reduce
PVR. After the initiation of MV in patients with severe lung diseases, assisted
ventilation modes are recommended utilizing fluid therapy to improve LV pre-
load and inotropic agents to support CO.
Pulmonary diseases with increased airway resistance (asthma, COPD) pro-
long the expiratory time and oppose alveolar deflation resulting in dynamic
hyperinflation and creating intrinsic PEEP (PEEPi). PEEPi is the lowest PA that
must be overcome by the inspiratory muscles to initiate inspiratory gas flow. As
already mentioned, increased lung volume reduces venous return of RV and
LV. Dynamic hyperinflation and inspiratory airflow limitation both increase the
inspiratory effort to maintain alveolar ventilation. Consequently, the increased
ITP at expiration increases LV afterload and reduces venous return, producing a
greater fall in systolic blood pressure and increasing the possibility of paradoxi-
cal pulse. Extreme expiratory effort with increase in WOB can cause respiratory
arrest and sudden death in severe bronchospasm [2]. Hence, MV may further
increase dynamic hyperinflation and Ppl in presence of severe airflow limitation.
Ventilatory settings must carefully avoid further air trapping, using a long expira-
tory time and avoiding large tidal volume, high frequency, and prolonged inspi-
ratory time. In these patients, assisted modes of ventilation, reducing the
threshold work and inspiratory effort and improving minute volume, minimize
the hemodynamic effects of MV. Although PEEPe reduces WOB, it is recom-
mended to avoid PEEPe in excess of PEEPi [11].
Most pulmonary diseases are associated with an increase in minute volume
and an increase in respiratory effort per breath (WOB). High minute volume
demand may result from an elevation in metabolic rate or deterioration in gas
exchange. The metabolic cost of breathing, normally only 1–2 % of total body O2
consumption, may rise to as much as 20 % in acute respiratory failure. MV has
therapeutically beneficial effects on WOB by reducing O2 consumption and pre-
serving cardiac function. Significant negative deflections in both esophageal and
transdiaphragmatic pressure characterize chronic lung diseases with elevated
spontaneous WOB. Applying a PEEP, NIV reduces WOB by counterbalancing
PEEPi, reducing the threshold load to inspiration, and by increasing respiratory-
system compliance, reducing the elastic load to inspiration. In general, an inspi-
ratory pressure-support level of 15 cmH2O and a PEEP of 5 cmH2O reduce most
measures of WOB and inspiratory effort toward normal [11].
In pulmonary diseases with increased RV impedance (afterload), increase in
lung volume progressively increases alveolar vessel resistance. Hyperinflation
can cause considerable hemodynamic compromise and create significant PH and
precipitate acute cor pulmonale and RV ischemia. PH is a frequent complication
of pulmonary embolism, acute exacerbation of chronic lung disease, ARDS, and
chronic pulmonary disease. PH increases RV afterload and induces acute RV
2 Cardiopulmonary Function Interactions during Noninvasive Mechanical Ventilation 17

dilatation and progressive RV failure. This may significantly reduce pulmonary

flow and LV preload and precipitate systemic hypotension. The combination of
systemic hypotension and PH has an unfavorable effect on RV myocardial O2
supply and demand. In addition, most inotropic agents have pulmonary vasocon-
strictor properties. In these cases, noradrenaline appears to have the best profile
by producing less pulmonary vasoconstriction for comparable levels of inotropic
effect and support of myocardial perfusion [4]. Appropriate ventilatory manage-
ment in PH aims at avoiding factors that exacerbate pulmonary vasoconstriction:
hypoxia, hypercapnia or acidosis, atelectasis, and excessive changes in lung vol-
ume. MV reduces pulmonary vasomotor tone by counteracting hypoxic pulmo-
nary vasoconstriction, increasing O2 alveolar partial pressure, PEEP recruitment
of collapsed alveoli, and small lung volume toward FRC, and reducing respira-
tory acidosis and central sympathetic output, which decreases the stress of
breathing.
ARDS is characterized by markedly increased lung elastance, alveolar col-
lapse, airflow limitation, pulmonary hypertension, and elevated metabolic rate
and WOB. Humoral inflammatory mediators can produce pulmonary vasocon-
striction, myocardial depression, and systemic hypotension. During MV in
ARDS, a greater inspiratory airway pressure is required to maintain adequate
alveolar ventilation, and high levels of PEEP are often utilized to prevent airway
collapse and aid recruitment of alveoli. Moreover, RV dysfunction during MV is
due to the combined effects of positive ITP and presence of elevated PVR. In
ARDS, maintenance of RV preload (volume loading), RV contractility (inotropic
agents), and systemic blood pressure (pressor agents) with clinical and hemody-
namic assessment is essential. The requirement for an ideal MV mode in ARDS,
without adverse respiratory and cardiac side effects, has lead to the proposal of
the use of high-frequency ventilation, inverse ratio ventilation, extracorporeal
oxygenation, inhaled pulmonary vasodilators, and prone ventilation [4].
Finally, the evaluation of fluid status during the initiation of PPV is crucial.
An acute reduction in systemic venous return is one of the most commonly
observed cardiopulmonary interactions. The inflation-vasodilatation response
due to vagal overstimulation can further aggravate it. This can be particularly
dramatic in hypovolemic patients and in vasodilated patients with systemic sep-
sis. The respiratory variation in arterial pressure induced by MV, initially
described as reversed pulsus paradoxus, is currently considered a predictor of
fluid responsiveness and not an indicator of blood volume [10].

Conclusions
Respiration and circulation are complementary physiological processes that
interact with each other during spontaneous breathing. The introduction of MV
and the presence of pulmonary and cardiac diseases increase the complexity of
this interaction. ITP decreases during spontaneous inspiration and increases dur-
ing PPV. Thus, the different hemodynamic responses during spontaneous and
positive-pressure breathing are related to the changes in ITP and the energy
18 A. Petroianni

necessary to produce these changes. Spontaneous inspiration increases RV pre-

load and LV afterload. MV with a positive pressure decreases RV preload and
reduces LV preload and afterload. Therefore, NIV can alter the cardiovascular
function by altering lung volume and ITP and increasing metabolic demands.
Preexisting cardiac and respiratory conditions and the mode of ventilation modu-
late the influence of MV on the cardiopulmonary system. Mechanisms involved
in these interactions include mechanical (pressure and volume), neural, and
humoral processes.
In a normal heart, CO is principally preload dependent. The application of PEEP
typically causes a reduction in CO by the Frank-Starling mechanism through a decrease
in venous return and LV filling. This is particularly true in hypovolemic patients.
In cardiac failure, CO is more responsive to changes in afterload than preload. In
MV, LV function improves for the better LV filling and the reduction of afterload
and O2 consumption.
In addition, NIV reduces WOB in direct proportion to the level of inspiratory
pressure-assist and also by the ability of applied PEEP to counter PEEPi. Modes and
parameters of ventilation to minimize cardiovascular effects depend upon the pul-
monary pathophysiological status and may change over time in the same subject.
An accurate consideration of cardiopulmonary interactions in NIV helps to treat
appropriately the different pathological conditions.

Key Recommendations
• Spontaneous breathing with a negative ITP leads to increased venous
return (RV preload) and a rise in LV afterload. Conversely, PPV increases
ITP and lung volume leading to a reduction in venous return (RV preload)
and a decrease of LV afterload.
• NIV determines cardiopulmonary effects through mechanical, neural, and
humoral mechanisms. The increase in ITP and lung volume affect venous
return, RV and LV filling and afterload, and heart rate. Consequently, CO
is reduced by increase of PVR, reduced preload, VI, and changes in
contractility.
• In presence of LV or RV dysfunctions, MV determines different effects on
CO and O2 consumption: functional improvement in left heart failure or
impaired RV function in cor pulmonale.
• Pulmonary diseases with different lung volume and elasticity, airflow
resistance, WOB, and RV impedance may require appropriate modes of
ventilation to reduce the negative cardiopulmonary effects of NIV.
• An adequate blood volume minimizes the negative effects of PPV on
venous return. A significant decrease in venous return is observed in hypo-
volemic status, whereas an improved LV ejection, increased CO, and
reduced myocardial O2 demand can result in patients with hypervolemic
heart failure.
2 Cardiopulmonary Function Interactions during Noninvasive Mechanical Ventilation 19

References
1. Pinsky MR. Clinical applications of cardiopulmonary interactions. J Physiol Pharmacol.
1997;48:587–603.
2. Shekerdemian L, Bohn D. Cardiovascular effects of mechanical ventilation. Arch Dis Child.
1999;80:475–80.
3. Wise RA, Robotham JL, Summer WR. Effects of spontaneous ventilation on the circulation.
Lung. 1981;159:175–86.
4. Gomez H, Pinsky MR. Effect of mechanical ventilation on heart-lung interactions. In:
Principles and practice of mechanical ventilation. 3rd ed. New York: MacGrawHill; 2012.
p. 821–49.
5. Guyton AC, John E. Textbook of medical physiology. 11th ed. Philadelphia: Elsevier Inc;
2006. p. 161–80; 471–90.
6. West J, Dollery C, Naimark A. Distribution of blood flow in isolated lung; relation to vascular
and alveolar pressures. J Appl Physiol. 1964;19:713–24.
7. Pinsky MR. Recent advances in the clinical application of heart-lung interactions. Curr Opin
Crit Care. 2002;8:26–31.
8. Pinsky MR. The hemodynamic consequences of mechanical ventilation: an evolving story.
Intensive Care Med. 1997;23:493–503.
9. Cournand A, Motley HL, Werko L et al. Physiological studies of the effects of intermittent
positive pressure breathing on cardiac output in man. Am J Physiol. 1948;152:162–74.
10. Duke JG. Cardiovascular effects of mechanical ventilation. Crit Care Resusc. 1999;1:388–99.
11. Kallet RH, Diaz JV. The physiologic effects of noninvasive ventilation. Respir Care.
2009;54(1):102–14.
Noninvasive Ventilation with Oral Mask:
Key Determinants and Clinical Evidence 3
Dilek Ozcengiz and Ersel Gulec

Contents
3.1 Introduction ................................................................................................................... 21
3.2 Discussion ..................................................................................................................... 24
Conclusion ............................................................................................................................. 25
References .............................................................................................................................. 26

Abbreviations

ARF Acute respiratory failure

EPAP Expiratory positive airway pressure
IPPV Intermittent positive-pressure ventilation
NIV Noninvasive ventilation
PEEP Positive end-expiratory pressure

3.1 Introduction

In 1953, Dr. John Affeldt was the first to use intermittent positive noninvasive ven-
tilation (NIV) via mouthpiece. In 1968, the Bennett lip seal, which fixes the mouth-
piece in the mouth for sleep and seals the lips to prevent air leakage out of the
mouth, entered the American market [1]. NIV has a considerable impact on the

D. Ozcengiz, MD () • E. Gulec, MD

Department of Anesthesiology, Cukurova University Faculty of Medicine, Adana, Turkey
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 21

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_3
22 D. Ozcengiz and E. Gulec

treatment of acute respiratory failure (ARF). Proper interface selection is a major

determinant in achieving successful NIV because they are associated with adverse
events such as air leakage, claustrophobic reaction, facial erythema, acneiform
eruptions, and skin or eye injuries [2].
Patients have reported mouthpiece NIV to be easy to use during daily activi-
ties such as eating and speaking [1]. However, the use of this technology is not
common and it is utilized in only a few centers. Currently, there are no evi-
dence-based guidelines for this application. A small, angled mouthpiece or
straw-type mouthpiece with volume-controlled ventilators can be used in
patients with neuromuscular disease. An intermittent positive-pressure ventila-
tion (IPPV) technique was used in one study [3]. This study included 257 ven-
tilator users. Mouth IPPV was performed using commercially available
mouthpieces for support during daytime and a mouthpiece with lip seal or cus-
tom orthodontic interfaces for nocturnal ventilator support. Mouth IPPV alone
or other noninvasive ventilatory supports were reviewed for these 257 patients.
Mouth IPPV was used during nocturnal support by 163 individuals, 61 of whom
had little or no measurable vital capacity or significant ventilator-free breathing
time.
In terms of a patient’s ability to use the mouthpiece, NIV can be more reliably
performed via a Lipseal (Philips-Respironics Inc., Murrysville, PA, USA) or
Oracle (Fisher & Paykel Healthcare Inc., Auckland, New Zealand) mouthpiece
interface if sedation is required. This kind of oral interface is designed to reduce
air leakage. Nose plugs may be required if nasal air leak occurs in the patient
(Figs. 3.1 and 3.2).
One study reported that mouthpiece ventilation was used by patients undergoing
bronchoscopy [4]. Physiologic parameters consisting of ventilatory parameters,
indexes of patients’ respiratory effort, gas exchange, leaks and asynchrony, and
comfort were evaluated in another study. The study suggested that a mouthpiece is
as effective as a full-face mask in reducing inspiratory effort in both hypoxemic
ARF and hypercapnic ARF.
A leak is a significant complication during the mouthpiece ventilation. Levels of
leaks were relatively moderate and were lower with the largest mask, being present
in 36 % of cases with oronasal masks and 60 % with mouthpiece [5]. A mouthpiece
is probably more appropriate for patients with chronic conditions than for patients
in respiratory failure.
Mouthpiece ventilation increased pH and lowered paCO2 and prevented endotra-
cheal intubation requirements in patients with respiratory failure due to chronic
obstructive respiratory diseases and cardiac insufficiency. Mouthpiece ventilation
has also been recommended for the treatment of severe sleep-related breathing dis-
orders [1]. A lip seal or custom orthodontic interface has been used for nocturnal
mouthpiece noninvasive positive pressure ventilation.
3 Noninvasive Ventilation with Oral Mask: Key Determinants and Clinical Evidence 23

Fig. 3.1 Oracle Fisher

oral mask
24 D. Ozcengiz and E. Gulec

Fig. 3.2 Mouthpiece

ventilation. Respironics
Mouthpiece Ventilation
(MPV) Support System

3.2 Discussion

The most significant benefits of a mouthpiece to support ventilation are less interfer-
ence with speech, little dead space, better appearance, no necessity of headgear,
and, therefore, no possibility of claustrophobia.
The greatest disadvantage is that it is useful predominantly during the daytime
except when retained by a lip-covering interface such as Lipseal or Oracle at night
[2, 3]. Another disadvantage limiting its use in ARF is nasal leakage, however,
mouth air leaks can be controlled with a tight-fitting lip seal and nasal plugs or nose
clips can be used to prevent air leak via the nares [3, 6].
Vomit aspiration is a potential complication. In addition, air may be swallowed
and cause gastric distention. The advantages and disadvantages of mouthpiece use
are summarized in Table 3.1.
3 Noninvasive Ventilation with Oral Mask: Key Determinants and Clinical Evidence 25

Table 3.1 Advantages and disadvantages of mouthpiece use

Advantages Disadvantages
Mouthpiece Lower interference with speech Less effective if patient cannot maintain
Very little dead space mouth seal
No requirement for headgear Usually requires nasal or oronasal
Eliminates any possibility of interface at night
claustrophobia Nasal air leakage
Better appearance Mouthpieces can cause gag reflex,
salivation, or vomiting
Long-term use can cause orthodontic
deformities

Mouthpiece ventilation can be obtained with positive expiratory pressure (expi-

ratory positive airway pressure (EPAP) or positive end-expiratory pressure (PEEP))
but it cannot be maintained for patients using open systems of NIV. Obstructive
apneas are relieved by sufficient positive inspiratory pressure delivery. Apnea
alarms, when present, should be set at the highest threshold to avoid unnecessary
activation and nuisance.
The most common ventilator mode used is assist volume-controlled with tidal
volume between 0.7 and 1.5 l with no PEEP (EPAP), low pressure alarm set at
the minimum, and maximum apnea duration. Although volume cycling permits
air stacking, when gastric inflation is severe, volume cycling is discontinued in
favor of pressure cycling. A gastrostomy is needed in some patients so that air
insufflated into the stomach can be “burped out” during sleep. Mouthpiece NIV
is not successful when patients are uncooperative, cannot access the interface, or
when a severe bulbar dysfunction causes aspiration of saliva such that the O2
saturation baseline remains below 95 %. It can cause or exacerbate dry mouth.
Heated humidification or switching to oronasal interfaces may beneficial in such
patients. Mouthpiece NIV can reduce risk of pneumonias and other respiratory
complications. Its use improves cough, speech, and pulmonary compliance.
These improvements can obtain high life quality for patients with neuromuscular
diseases.

Conclusion
In conclusion, oral masks can delay invasive ventilation and improve the life
quality for patients with neuromuscular diseases, sleep apnea, and chronic respi-
ratory failure. The limitation is necessity of high cooperation ability.

Recommendations
• An oral mask can be the first choice for the patient requiring NIV.
• The mask can be helpful for the patient who has a claustrophobia.
• Further study should be recommended to spread use of oral masks.
26 D. Ozcengiz and E. Gulec

References
1. Garuti G, Nicolini A, Grecchi B, et al. Open circuit mouthpiece ventilation: concise clinical
review. Rev Port Pneumol. 2014;20(4):211–8.
2. Nava S, Navalesi P, Gregoretti C. Interfaces and humidification for noninvasive mechanical
ventilation. Respir Care. 2009;54:71–84.
3. Bach JR, Alba AS, Saporito LR. Intermittent positive pressure ventilation via the mouth as an
alternative to tracheostomy for 257 ventilator users. Chest. 1993;103:174–82.
4. Tran J, Bach JR, Gonçalves MR. Alternatives to mouthpiece noninvasive ventilatory support to
permit dental care. Am J Phys Med Rehabil. 2014;93:182–5.
5. Fraticelli AT, Lellouche F, L’her E, Taillé S, Mancebo J, Brochard L. Physiological effects of
different interfaces during noninvasive ventilation for acute respiratory failure. Crit Care Med.
2009;37(3):939–45.
6. Gonzales J, Sharshar T, Hart N, et al. Air leaks during mechanical ventilation as a cause of
persistent hypercapnia in neuromuscular disorders. Intensive Care Med. 2003;29:596–602.
Nasal Pillow for Sleep Apnea Syndrome:
Key Technical Determinants and Clinical 4
Evidence

Yoshinori Matsuoka

Contents
4.1 Introduction ................................................................................................................. 28
4.1.1 Although Nasal Masks Are Effective for the Management
of Obstructive Sleep Apnea Syndrome, They Have Many
Side Effects.................................................................................................... 28
4.1.2 Appearance of Nasal Pillows on the Market ................................................. 28
4.2 Discussion and Analysis Main Topic .......................................................................... 28
4.2.1 Clinical Evidence for the Effects of Nasal Pillows ....................................... 28
4.2.2 Nasal Pillows Can Become a First-Choice Option
for CPAP Therapy ......................................................................................... 28
4.2.3 Nasal Pillows Can Be Used for Patients Requiring
High CPAP Pressures .................................................................................... 29
4.2.4 A Weakness Peculiar to Nasal Pillow Use .................................................... 29
4.2.5 What Disease Is Most Suitable for Nasal Pillows? ....................................... 29
Conclusion ............................................................................................................................. 30
References .............................................................................................................................. 30

Y. Matsuoka, MD, PhD

Department of Emergency Medicine, Kagoshima Minami Kyushu City, Japan
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 27

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_4
28 Y. Matsuoka

4.1 Introduction

4.1.1 Although Nasal Masks Are Effective for the Management

of Obstructive Sleep Apnea Syndrome, They Have Many
Side Effects

Continuous positive airway pressure (CPAP) therapy is the most effective treatment
for patients with obstructive sleep apnea syndrome (OSAS), particularly those with
moderate and severe disease [1]. However, the device is cumbersome and compli-
ance rates are only moderately satisfactory [2]. In particular, local side effects directly
related to the nasal mask are common, with up to 50 % of patients complaining of
pressure sores or ulceration, air leaks, allergic reactions on the face, claustrophobia,
or mask dislodgement [3]. Therefore, proper mask fitting and patient education are
important for reducing air leaks, ensuring optimal mask adjustment, and improving
adherence to treatment [4]. However, despite our best efforts, a significant proportion
of patients continue to experience nasal mask-related side effects.

4.1.2 Appearance of Nasal Pillows on the Market

To circumvent nasal mask-related side effects, different interfaces have been intro-
duced to the market. One such interface is the nasal pillow, as developed by
Mallinckrodt Corporation [5], Fisher and Paykel, and ResMed. Nasal pillows fit
into the nostrils, thereby allowing breathing to be more natural, reducing nasal pres-
sure on the nose, and preventing air leaks. Moreover, the device is less intrusive and
can reduce the sense of claustrophobia.

4.2 Discussion and Analysis Main Topic

4.2.1 Clinical Evidence for the Effects of Nasal Pillows

Ryan et al. [6] argue that patients with OSAS find the use of nasal pillows more com-
fortable than standard nasal masks during CPAP therapy, thereby resulting in improved
satisfaction. However, despite these assertions, the compliance rates, objective and
subjective effectiveness, and side-effect profile remain unaltered. Although the overall
SF-36® quality of life scores were comparable for both devices, the use of nasal pil-
lows resulted in a significant improvement in the “change of health” domain.

4.2.2 Nasal Pillows Can Become a First-Choice Option for CPAP

Therapy

In a recent study, the mask type was found to affect adherence to CPAP therapy.
Specifically, oronasal masks were found to have a negative impact on CPAP
4 Nasal Pillow for Sleep Apnea Syndrome 29

adherence, with the authors suggesting that nasal masks should be the preferred
first-choice option [7]. In addition, Ryan et al. [6] confirmed the comparable effec-
tiveness of the nasal pillow to the nasal mask. They observed that both the apnea-
hypopnea index and the Epworth sleepiness scale were similarly reduced by both
devices, suggesting that the nasal pillow could be the initial choice for CPAP titra-
tion in certain patients, particularly when proper mask fitting cannot be achieved
with a nasal mask at the initial mask-fitting session.

4.2.3 Nasal Pillows Can Be Used for Patients Requiring High

CPAP Pressures

Mask selection is known to affect a patient’s experience of CPAP. However, nasal

pillows are infrequently used on patients requiring high CPAP pressures, and their
performance at these pressures has not been evaluated systematically. Zhu et al. [8]
examined the treatment efficacy and user satisfaction of nasal pillows compared
with those of nasal masks at CPAP pressures ≥12 cm H2O. They found that nasal
pillows were at least as efficacious and subjectively acceptable as nasal masks
when treating patients with OSAS at high CPAP pressures. Their study suggests
that clinical practice can be amended to allow patients with CPAP the option to
choose the most suitable mask type for themselves, regardless of their pressure
requirements.

4.2.4 A Weakness Peculiar to Nasal Pillow Use

Belge et al. [9] have reported that the flexibility of nasal pillows can lead them to
collapse against the skin, thereby abolishing the therapeutic effect of CPAP. Moreover,
because this can occur without inducing leaks that would otherwise awaken patients,
it can persist for prolonged periods. This important observation demonstrates that
not every nasal pillow type fits every nose. Medical and paramedical personnel
working with CPAP machines and interfaces need to be aware of this particular
characteristic of soft nasal pillows so that they can remain vigilant for poor thera-
peutic response and inform patients of the risk.

4.2.5 What Disease Is Most Suitable for Nasal Pillows?

Porszasz et al. [10] evaluated a novel noninvasive open ventilator system that was
designed for use by hypoxemic patients with chronic obstructive pulmonary disease
(COPD) and intended to be practical to facilitate activities of everyday living. The
device was well tolerated by patients in their laboratory study, markedly increasing
exercise tolerance and substantially reducing dyspnea. The mechanism of improve-
ment appeared to be through a combination of unloading of the respiratory muscles
and improved oxygenation.
30 Y. Matsuoka

Conclusion
The use of a nasal pillow rather than a standard nasal mask for CPAP therapy in
patients with OSAS may result in improved comfort and therefore satisfaction.
The equivalent effectiveness of the nasal pillow to the nasal mask suggests that
nasal pillows can at least be considered a first-choice option for CPAP. Because
nasal pillows can be used for patients requiring high CPAP pressures, the adapta-
tion of nasal pillows will be extended to patients with severe OSAS. In addition,
nasal pillows have been successfully adapted for patients with COPD and OSAS,
effectively facilitating activities of daily living.

Key Major Recommendations

• Nasal pillows should be considered a first-choice option for CPAP.
• Nasal pillows are safe and effective for patients requiring high CPAP
pressures.
• Professionals should be vigilant for the risk of collapse peculiar to nasal
pillows.
• Nasal pillow appear suitable for patients with comorbid COPD and OSAS.

References
1. Gay P, Weaver T, Loube D, et al. Evaluation of positive airway pressure treatment for sleep
related breathing disorders in adults. Sleep. 2006;29:381–401.
2. Reeves-Hoche MK, Meck R, Zwillich CW. Nasal CPAP: an objective evaluation of patient
compliance. Am J Respir Crit Care Med. 1994;149:149–54.
3. Pepin JL, Leger P, Veale D, et al. Side effects of nasal continuous positive airway pressure in sleep
apnea syndrome. Study of 193 patients in two French sleep centers. Chest. 1995;107:375–81.
4. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the
challenge to effective treatment. Proc Am Thorac Soc. 2008;5:173–8.
5. Massie CA, Hart RW. Clinical outcomes related to interface type in patients with obstructive
sleep apnea/hypopnea syndrome who are using continuous positive airway pressure. Chest.
2003;123:1112–8.
6. Ryan S, Garvey JF, Swan V, et al. Nasal pillows as an alternative interface in patients with
obstructive sleep apnea syndrome initiating continuous positive airway pressure therapy.
J Sleep Res. 2011;20:367–73.
7. Borel JC, Tamisier R, Dias-Domingos S, et al. Type of mask may impact on continuous posi-
tive airway pressure adherence in apneic patients. PLoS One. 2013;8:e64382.
8. Zhu X, Wimms AJ, Benjafield AV. Assessment of the performance of nasal pillows at high
CPAP pressures. J Clin Sleep Med. 2013;9:873–7.
9. Belge C, Delguste P, Mouchart F, et al. Obstructive apneas during continuous positive airway
pressure: unexpected finding with nasal pillow interface. Am J Respir Crit Care Med.
2012;185:112–4.
10. Porszasz J, Cao R, Morishige R, et al. Physiologic effects of an ambulatory ventilation system
in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:334–42.
ICU Ventilators Versus BiPAP Ventilators
in Noninvasive Ventilation 5
Tamer Fahmy and Sameh Salim

Contents
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
5.2 Leaks and Ventilator Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
5.2.1 Leak Estimation and Compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
5.3 Comparison Between Ventilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
5.4 Variation with Different Modes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
5.4.1 Volume (Average Volume) Assured Pressure Support . . . . . . . . . . . . . . . . . 37
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

5.1 Introduction

In contrast to the closed-circuit ventilation of invasive ventilation, noninvasive ven-

tilation (NIV) is an open-circuit ventilation where leaks are inherent and, paradoxi-
cally, essential to its success. The success of NIV, whether in the acute setting,
weaning, or long-term therapy is dependent on all three aspects for its use, appropri-
ate patient selection, suitably fitting interface, and a specifically designed machine.
The choice of a ventilator may be crucial for the success of NIV in the acute setting,
because intolerance and excessive air leaks are significantly correlated with NIV
failure [1].

T. Fahmy, MD, PhD (*) • S. Salim, MD

Critical Care Medicine, Cairo University Hospitals, Giza, Egypt
e-mail: [email protected], [email protected]

© Springer International Publishing Switzerland 2016 31

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_5
32 T. Fahmy and S. Salim

5.2 Leaks and Ventilator Performance

In contrast to unintentional leaks creating difficulties with ventilation, intentional

leaks are “venting leaks.” They should be created in the system in two instances.
The first is to prevent the accumulation of CO2 and rebreathing due to the dead
space present in the interface, which may reach up to 800 ml in total face masks [2].
This accumulated air should be vented via exhalation ports in the interface. In the
second instance, single-limb circuits should contain either a port for continuous
intentional leaks or an exhalation valve. The intentional leaks are constant and con-
trollable. Other sites of leaks, including that between the interface and the patient’s
face and mouth leaks with nasal masks, are sudden, variable, and unpredictable.
Leaks are less marked during expiration than during inspiration, because upper
airway pressure decreases markedly when mechanical insufflation switches off to
permit expiration. However, positive end-expiratory pressure (PEEP) may still pro-
mote expiratory leaks, where its level is proportional to the occurrence of leaks.
Such leaks interfere with proper ventilation by affecting the trigger, pressurization
during insufflations, and cycling off to exhalation. This ultimately leads to poor
ventilation, lack of patient compliance, and prolongation or failure of NIV. Expiratory
leaks can mimic an inspiratory effort for the ventilator, leading to auto-triggering,
and inspiratory leaks can mimic a sustained inspiration, leading to delayed cycling
[3].
If leak flow reaches the trigger threshold, auto-triggering occurs. Because of this,
the frequency of auto-triggering does not depend on the magnitude of the increase
in leak. On the other hand, if the leak is large enough, the ventilator may not detect
respiratory efforts, leading to miss-triggering [3]. Vignaux et al. [4] demonstrated
that auto-triggering was present in 13 % of patients, and delayed cycling in 23 % of
patients during NIV. Auto-triggering per se may also induce miss-triggering if
inspiratory time is prolonged, because of auto-triggering overlapping the patient’s
next inspiratory effort. In other words, cycle asynchrony can produce trigger asyn-
chrony. Additionally, leaks can lead to aerophagia, odynophagia, dry mouth, eye
irritation, and nasal symptoms, and noise may result, all of which reduce therapeutic
compliance [5].
Ventilators used in NIV must be capable of detecting and properly estimating
leaks and compensating for such leaks. Indeed, the response of these ventilators will
vary according to the degree of leak, their capability to compensate, ventilation
target (pressure vs volume targeted ventilation), and the type of intrinsic lung dis-
ease (obstructive vs restrictive pattern).

5.2.1 Leak Estimation and Compensation

The leak volume, as estimated from the difference in inspiratory and expiratory
volumes, occurs during both inspiration and expiration. In the past, tidal volume has
been estimated from the expiratory volume. However, given the observation that
volume is also lost during expiration, tidal volume (Vt) can be underestimated from
5 ICU Ventilators Versus BiPAP Ventilators in Noninvasive Ventilation 33

expiratory volume, and, consequently, crucial inspiratory leakage might be overes-

timated [6, 7]. Conceivably, the expired-volume method for measuring Vt might
underestimate the Vt if leaks occur during expiration and therefore may induce
overcompensation.
The simplest way to estimate the patient’s Vt during leaks is to measure expira-
tory Vt and to consider that Vt is underestimated in case of expiratory leakage [7].
Ventilators with an expiratory valve have no expiratory circuit and no pneumotacho-
graph connected to the patient interface. Consequently, these ventilators cannot
measure expiratory Vt and, therefore, the patient’s real Vt during leaks [7]. By mea-
suring pressure and flow inside the ventilator, while taking into account the ventila-
tor turbine speed throughout the entire respiratory cycle and detecting the beginning
and end of inspiration, the ventilators with single-limb circuits with intentional leak
are able to rebuild the patient’s flow pattern and to establish a “baseline” breathing
pattern corresponding to the patient’s zero flow [7].
Khairani et al. [7] evaluating the ability of home ventilators to maintain the mini-
mum Vt in volume-targeted pressure support ventilation (VT-PSV) in seven differ-
ent NIV ventilators using different circuits. They concluded that ventilators that can
be used with a single-limb circuit with intentional leak outperform devices that use
double circuits or expiratory valves, where the latter could even paradoxically exac-
erbate the Vt drop during unintentional leak when used in VT-PSV mode. All but
one of the studied ventilators with a double-limb circuit and all studied ventilators
with an expiratory valve misinterpreted leaks as an increase in Vt and therefore
decreased their inspiratory pressure to the minimal preset level, thereby paradoxi-
cally exaggerating the fall in Vt.

5.3 Comparison Between Ventilators

Three major types of ventilators have been commonly used for NIV over the past
two decades: regular intensive care unit (ICU) ventilator (with no NIV capabilities
or algorithm), ICU ventilator with NIV algorithm, and dedicated NIV ventilators. In
general, in ICU ventilators without algorithms for leak compensation, a minimal
amount of leak can be attained because the ventilator can only minimally compen-
sate for the decline in pressure. If leaks are greater, the ventilator leak alarm will be
activated, and the leaks will abort the breath due to disconnection. The failure to
operate alarm is activated at higher levels. In the latter case, the system alarm for
disconnection may be modified to a higher level, however, this still cannot be com-
pensated for. ICU ventilators are more powerful and have more adjustable features
(trigger type and sensitivity, slope of pressurization, cycling criteria) and monitor-
ing capabilities. Their downside is cost, size, and the knowledge required for their
safe use.
NIV ventilators, on the other hand, are portable devices with a turbine-type blower
capable of delivering a high inspiratory flow rate (>100 l/min), are easier to use, and
are less costly [8]. Most of the first generation bi-level ventilators, however, had
important technical limitations, including limited pressure-generation ability, poor
34 T. Fahmy and S. Salim

performance if respiratory-system load increased, risk of CO2 rebreathing, and lack

of ventilatory monitoring, alarms, or battery [1]. Although there have been many
updates, NIV ventilators still cannot administer high inspired O2 concentrations, nor
can they reliably provide high (>20 cmH2O) levels of pressure support. These two
factors could prove to be a limitation in patients with hypoxemic respiratory failure,
in whom high levels of FiO2 and PEEP are required. In addition, CO2 rebreathing can
occur with some circuits, and they often lack monitoring capability [8].
Several bench and clinical studies have compared ventilator operability as well
as patients’ synchrony with different ICU ventilators (with and without leak com-
pensation algorithms) and dedicated NIV ventilators (portable and ICU ventilators).
In a randomized, crossover clinical study, Lofaso et al. [8] compared a home device
to a device specially designed for intensive care use in seven intubated patients dur-
ing weaning from mechanical ventilation. The main differences between the two
devices were trigger sensitivity and initial flow acceleration. For the same level of
pressure support, there were no significant differences in arterial PCO2, Vt, respira-
tory rate, or minute ventilation between these two devices. However, the esophageal
pressure-time product was 30 % higher with the home device. They concluded that
differences exist between devices in terms of occurrence of rebreathing, speed of
attainment of stable pressure support level, and expiratory resistance. These differ-
ences characterizing the delivery of pressure support may have clinical impact on
the inspiratory effort of patients.
Didier et al. (2002) compared an NIV ventilator with three different ICU ventila-
tors in a bench study they found its inspiratory trigger responded as quickly as the
ICU ventilators tested, while its speed of pressurization was equal to some ICU
ventilators, even at high inspiratory demand, provided the level of pressure support
was kept below 20 cmH2O. At higher levels, the proportional solenoid valve of the
ICU machines was clearly at an advantage over the turbine-type blower of the home
device [8].
In a bench study, Ferreira et al. (2009) [9] evaluated the ability of nine different
ICU ventilators to function in the presence of leaks compared with NIV ventilators.
They found that as the leak was sequentially increased, all ventilators, except for
one dedicated NIV and another ICU ventilator, needed adjustment of sensitivity
and/or inspiratory termination criteria to maintain synchrony, and some ventilators
transitioned to backup ventilation. They found that only those two ventilators were
able to synchronize with the lung simulator at all leak levels without adjustment.
However, the dedicated NIV ventilator outperformed the ICU ventilator.
In a bench and a clinical study, Carteaux et al. (2012) [3] compared 19 different
ICU ventilators with dedicated NIV ventilators. They found that in NIV conditions,
most dedicated NIV ventilators allowed better patient-ventilator synchronization
than ICU ventilators, even when the NIV algorithm was engaged, especially regard-
ing the risk of auto-triggering. Most dedicated NIV ventilators exhibited a synchro-
nization performance in the presence of leaks equivalent to ICU ventilators in the
absence of leaks. Moreover, the NIV algorithm usually improved, at least slightly,
the triggering and/or cycling synchronization of ICU and transport ventilators in the
presence of leaks. The authors suggested that each ICU ventilator should be
5 ICU Ventilators Versus BiPAP Ventilators in Noninvasive Ventilation 35

examined individually regarding its ability to manage NIV conditions. In contrast,

dedicated NIV ventilators exhibited more homogeneous behavior during our bench
evaluation, with an ability to avoid auto-triggering or delayed cycling while keeping
a short triggering delay despite leaks.
Miyoshi et al. (2005) [10] evaluated the effects of gas leak on triggering function
during NIV with dedicated NIV and ICU ventilators using a lung simulator. They
found that the dedicated NIV ventilators triggered properly at several levels of leak
(up to 44.2 l/min at 5 cmH2O of PEEP) and that triggering was more effective than
with the ICU ventilators (but not in NIV mode).
Oto et al. (2013) [11], in a lung model of chronic obstructive pulmonary disease
(COPD) and acute respiratory distress syndrome (ARDS) evaluated seven different
ICU and NIV ventilators at different levels of leaks up to 36 l/min. They found that
ventilators performed better during decreasing than increasing leak, and that venti-
lators performed better with lower than with higher PEEP. Moreover, miss-triggering
occurred more frequently and longer times were required to stabilize Vts in the
COPD model than in the ARDS model. On the other hand, auto-triggering occurred
more frequently in the ARDS model than in the COPD model. The ventilators may
automatically decrease trigger sensitivity according to the level of leak to avoid
auto-triggering, but as the leak decreases, the trigger sensitivity increases. This can
lead to miss-triggering, particularly if the change is larger than the inspiratory effort.
If the change in leak is smaller than the inspiratory effort, miss-triggering is unlikely,
though higher patient effort is required to reach this threshold. The authors further
added that because all the ventilators measure one or several cycles and adjust trig-
ger/cycling for the subsequent cycles following a leak level change, it is not possible
to synchronize on the exact breath that the leak changes. Due to this technical con-
straint, leak compensation on current acute care ventilators is limited in its ability to
provide synchrony.
Nakamura et al. (2014) [2] found that only one of eight tested ICU ventilators
was suitable for NIV using a total face mask with large leaks. Four were considered
totally nonoperational due to inappropriate turning-off (misinterpretation of discon-
nection) or auto-triggering, whereas three of the remaining four had problems com-
pensating for the large leaks through the exhalation ports, resulting in inability to
keep PEEP and inspiratory pressure, delayed inspiratory triggering, or delayed
cycling to expiration.
To increase safety, various manufacturers have limited the leak compensation for
ICU ventilators to values equal to or lower than 30 l/min (or 0.5 l/s), values above
which the disconnection alarm of the ventilator goes off [13]. However, the authors
mentioned in the limitations of their study that some of the failed ICU ventilators
upgraded their NIV software to a higher level of leak compensation after the com-
mencement of their study.
To conclude, in different comparative studies:

• There is a wide range of heterogeneity among ICU ventilators in the leak com-
pensation algorithms, while dedicated NIV ventilators are more homogenous.
Because the manufacturers have not revealed the exact triggering and cycling
36 T. Fahmy and S. Salim

algorithms used during system leak, it is difficult to explain the discrepancies

among the different studies.
• Dedicated NIV ventilators outperform ICU ventilators in NIV, especially in
patient–ventilator synchrony.
• NIV algorithms mostly improve ICU ventilator performance in NIV, however,
modifications still have to be carried out to prevent triggering and cycling
asynchrony.

5.4 Variation with Different Modes

In addition to the inherent characteristic of the device, the mode and setting also
affect the leak compensation mechanisms within the same ventilator. Three differ-
ent controls are being used in NIV: volume-targeted, pressure-targeted, and volume
(average) assured pressure support. The response to different degrees of leak widely
differs among these modes/controls.
When a leak is introduced, the peak inspiratory pressure decreases in the system
and delivered Vt decreases. In volume-targeted ventilation, compensation is far less
effective than in pressure-targeted ventilation [12]. This is expected with most
volume-targeted ventilators, where the inspiratory flow is fixed and cannot increase,
accounting for its poor leak compensation capabilities [12]. This cannot be over-
come by increasing the inspiratory time, as this would also increase the duration of
leak at higher pressures. Although increasing the Vt could partially compensate for
leaks, this strategy for leak compensation is less effective than using pressure-tar-
geted ventilators. Thus, volume-targeted ventilators would not be the first choice for
noninvasive positive-pressure ventilation in patients with substantial air leakage.
On the other hand, when leak occurs in pressure-targeted ventilation, inspiratory
flow will increase to maintain system pressurization for an extended time, increasing
the inspiratory time. However, this compensatory effect depends on the rate of lung
filling and emptying and the absolute inspiratory duration. Prolonging the inspiratory
time to the point of inverting the inspiratory-expiratory ratio is counterproductive at
higher rates (e.g., 30/min) because of incomplete emptying of the lung, resulting in
higher end-expiratory pressure and therefore lower differential pressure [12].
Two counterproductive mechanisms occur. First, increasing pressure also
increases leakage further, and the patient may not tolerate it, or it may further lead
to aerophagia. Second, increasing the inspiratory time, especially with high rates,
leads to expiratory asynchrony, requiring the patient to use the expiratory muscles
to cycle off. Hence, this compensatory mechanism leads to increasing the inspira-
tory time, and at high rates would lead to air trapping, cycling off expiratory asyn-
chrony, and intolerance to NIV [12]. Additionally, if pressure increases, in
NIV-dedicated ventilators, inspiratory oxygen fraction obtained in these cases
depends on factors such as the mixing of air supplied by the system and the oxygen
in the circuit. If greater flow is needed to pressurize the circuit, high oxygen concen-
trations are harder to reach, even with high flow supplements [5].
This patient response varies among different ventilators and modes. If the patient-
ventilator interface develops a large air leak during the attempted delivery of a
5 ICU Ventilators Versus BiPAP Ventilators in Noninvasive Ventilation 37

pressure-targeted, flow-cycled breath, the ventilator will prolong inspiration because

it does not sense the drop in flow required to terminate inspiration [13]. The ventila-
tor may not be able to generate enough flow to maintain adequate inspiratory pres-
sure. The patient will then “pull” against the ventilator circuitry, increasing the work
of breathing. In contrast, a subset of patients may experience discomfort when
exposed to an inspiratory flow exceeding demand [13].
The mechanism of expiratory asynchrony is terminated by a decrease in inspira-
tory flow up to a maximum duration of 3 s. Therefore, inspiratory time increases
during leak because inspiratory flow fails to drop sufficiently to cycle the ventilator
[12]. If airway resistance or lung elastance increases, normally Vt can be delivered
only in volume targeted ventilation, and decreases in pressure controlled.

5.4.1 Volume (Average Volume) Assured Pressure Support

These devices increase the delivered Vt by increasing inspiratory flow during inspi-
ration. However, when working within a single-circuit configuration without moni-
toring of the expiratory volume, it may expose to inefficient compensation especially
when inspiratory leaks are present [14]. Some have used a proprietary system to
adjust their leak compensation, which uses pressure-targeted ventilation to obtain
optimal control of both inspiratory positive airway pressure (IPAP) and inspiratory
time (Ti) to determine which of these adjustments is most effective for leak compen-
sation [14]. The original feature of their leak compensation mode is that a Ti increase
is combined with an IPAP increase to maintain sufficient minute ventilation based
on monitoring of the patient’s exhaled Vt. The ventilator takes the amount of leak-
age into account, cycle by cycle, and increases inhaled Vt to obtain an exhaled Vt
value as close as possible to the set security Vt [14]. One important limitation of this
system is that expiratory leaks may lead to errors by decreasing the exhaled Vt
detected by the ventilator. The result may be inappropriately large increases in Ti,
inspiratory flow, and IPAP, possibly producing lung overinflation [14]. They con-
cluded that their leak-compensation system is probably less effective in compensat-
ing for expiratory leaks than inspiratory leaks and may be ineffective when the
entire exhaled Vt leaks around the interface [14, 15].
In the presence of a mild leak during NIV, whether with an ICU ventilator or a
dedicated NIV ventilator, either volume-controlled or volume-assured ventilation
can be used. However, as the leak increases, pressure-targeted ventilation may be
preferred to compensate for the leaks, as long as the pressure still allows (less than
20–25 cmH2O) and the inspiratory time can still be increased. To best compensate
for air leaks, pressure-targeted ventilators should have high and sustained maximal
inspiratory flow capabilities.

Conclusion
Because leakage is a prerequisite in the application of NIV, ventilators used for
NIV should be specifically designed to overcome this leak. The degree of leak
compensation should be enough to build-up the baseline pressure set on the ven-
tilator. ICU ventilators with NIV capabilities or bi-level positive airway pressure
38 T. Fahmy and S. Salim

units usually have leak compensation between 30 and 60 l/min. Some ICU ven-
tilators may have higher compensation, reaching more than 100 l/min. The set
baseline expiratory pressure must not be less than 4 to allow for continuous vent-
ing of CO2 and to prevent rebreathing; therefore, leak compensation must be
capable of maintaining that minimum pressure during expiration.
In order for a ventilator to maintain synchrony in the presence of leak, the
ventilator must automatically adjust the trigger sensitivity and/or cycling time
[11]. Furthermore, in any mode the ventilator should have an algorithm for dif-
ferentiating the leak from the decrease in base flow for triggering to prevent trig-
gering dyssynchrony (missed efforts and auto-triggering). Similarly, in case of
pressure support mode, the ventilator should also be able to discriminate between
the leak and the expiratory trigger criteria (cycling) to allow for inspiratory syn-
chrony and the following breath trigger level. In addition, the ventilator should be
designed to have a secondary cycling mechanism in case of failure to sense the
expiratory trigger level, so that the inspiratory time is not unduly prolonged (i.e.,
longer than 1.5 s). In such cases, the ventilator will switch from pressure-support
mode to pressure control (time cycled). In order for a ventilator to maintain syn-
chrony in the presence of increasing leaks, the ventilator must be able to acclimate
by adjustment of both triggering and cycling, ideally automatically [9].

References
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2014;40(3):294–303.
3. Carteaux G, Lyazidi A, Cordoba-Izquierdo A, Vignaux L, Jolliet P, Thille AW, Richard JC,
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invasive ventilation. Respir Med. 2009;103(10):1477–83.
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2009;136(2):448–56.
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10. Miyoshi E, Fujino Y, Uchiyama A, Mashimo T, Nishimura M. Effects of gas leak on triggering
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Ventilators for Noninvasive Mechanical
Ventilation: Theory and Technology 6
Raffaele Scala

Contents
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
6.2 Classification of Ventilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
6.3 Technological Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.3.1 Source of Gas and Oxygen Supply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.3.2 Circuit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.3.3 Inspiratory Trigger and Expiratory Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
6.3.4 Inspiratory Flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
6.3.5 Back-up Respiratory Rate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6.3.6 Air Leak Compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6.3.7 Battery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
6.3.8 Alarm and Monitoring System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
6.4 Controversial Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

Abbreviations

ARF Acute respiratory failure

CPAP Continuous positive airway pressure
CRF Chronic respiratory failure
EPAP Expiratory positive airway pressure

R. Scala, MD
Pulmonology and Respiratory Intensive Care Unit,
AUSL8, S. Donato Hospital,
Via Nenni, 20, Arezzo 52100, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 41

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_6
42 R. Scala

f Respiratory rate
FiO2 Inspiratory fraction of O2
IPAP Inspiratory positive airway pressure
NPPV Noninvasive positive pressure ventilation
PAV Proportional assist ventilation
PCV Pressure-controlled ventilation
PEEP Positive end-expiratory pressure
PSV Pressure support ventilation
Ti Inspiratory time
VAPS Volume-assured pressure support ventilation
VCV Volume-controlled ventilation
Vt Tidal volume

6.1 Introduction

The use of noninvasive positive pressure ventilation (NPPV) to treat both acute
respiratory failure (ARF) and chronic respiratory failure (CRF) has been tremen-
dously expanded in the last two decades in terms of spectrum of diseases to be suc-
cessfully managed, settings of application/adaptation, and achievable goals [1–3].
The choice of a ventilator may be crucial for the outcome of NPPV in the acute and
chronic setting as poor tolerance and excessive air leaks are significantly correlated
with the failure of this ventilatory technique [3, 4]. Patient-ventilator dyssynchrony
and discomfort may occur when the clinician fails to adequately set NPPV in
response to the patient’s ventilatory demands during acute distress, wakefulness,
and sleep [3–5]. Technical properties of the ventilator (i.e., type of circuit, efficiency
of trigger and cycling systems, speed of pressurization, air leak compensation, CO2-
rebreathing, blender for O2, monitoring accuracy, transportability) play a key role in
helping NPPV to achieve the goals of mechanical ventilation in ARF (unloading
respiratory muscles, improved gas exchange) and CRF (improved gas exchange,
sleep quality, quality of life, survival) [3, 4].
With the growing implementation of NPPV, a wide range of ventilators have
been produced to deliver noninvasive support, both in randomized controlled trials
and in “real-life scenarios.” This chapter examines the key points concerning the
technology of ventilators for NPPV and their main impact in clinical practice.
Because of constraints in length, ventilators for negative pressure ventilation (i.e.,
iron lung, cuirass, poncho-wrap) are not covered.

6.2 Classification of Ventilators

Even if any ventilator can be theoretically used to start NPPV both in ARF and in
CRF, success is more likely if the ventilator is able to (a) adequately compensate for
leaks; (b) let clinician continuously monitor patient-ventilator synchrony and venti-
latory parameters due to a display of pressure-flow-volume waveforms and a
6 Ventilators for Noninvasive Mechanical Ventilation: Theory and Technology 43

double-limb circuit; (c) adjust the fraction of inspired oxygen (FiO2) with a blender
to assure stable oxygenation; and (d) adjust inspiratory trigger sensitivity and expi-
ratory cycling as an aid to manage patient-ventilator asynchronies [3, 4].
Ventilators may be classified in four categories, whose features are briefly sum-
marized below and in Table 6.1 [3]:

1. Volume-controlled home ventilators were the first machines used to deliver

NPPV, mostly for a domiciliary care. Even if well equipped with alarms, moni-
toring system, and inner battery, their usefulness to apply NPPV is largely lim-
ited by their inability to compensate for air leaks. Consequently, their NPPV
application is today restricted to home-based selected cases of neuromuscular
disorders, although they still play a role in the safe invasive support of ventilatory-
dependent tracheostomized patients [3].
2. Bi-level ventilators are the evolution of home-based continuous positive airway
pressure (CPAP) devices and derive their name from their capability of support-
ing spontaneous breathing with two different pressures: an inspiratory positive
airway pressure (IPAP) and a lower expiratory positive airway pressure (EPAP)
or positive end-expiratory pressure (PEEP). These machines were specifically
designed to deliver NPPV, thanks to their efficiency in compensating air leaks.
Because of their easy handling, transportability, lack of alarms and monitoring
system, and low costs, the first generation of bi-level ventilators matches the
needs for nocturnal NPPV in chronic patients with a large ventilatory autonomy.
However, traditional bi-level ventilators showed important technical limitations
(risk of CO2 rebreathing due to their single-limb circuit in non-vented masks;
inadequate monitoring; lack of alarms and O2 blending; limited generating pres-
sures; poor performance to face the increase in respiratory system load, lack of
battery), which have been largely overcome by more sophisticated machines.
The newer generations of bi-level ventilators have gained popularity in clinical
practice to apply acute NPPV, especially in higher levels of care settings, as well
as to invasively support ventilatory-dependent chronic patients at home. These
new devices are capable of delivering a large extent of more advanced presso-
metric modalities of ventilation, with the inclusion of “hybrids modes” such as
volume-target pressure-preset ventilation (i.e., volume-assured pressure support
ventilation, or VAPS), which can dynamically change the level of pressure assis-
tance depending on the measured tidal volume according to different algorithms.
Despite their physiological benefits, the real clinical advantages of these “hybrids
modes” have yet to be demonstrated compared with the traditional pressometric
modalities [3, 4].
3. ICU ventilators were initially designed to deliver invasive ventilation via a cuffed
endotracheal tube or tracheal cannula to either sick patients in the intensive care
unit (ICU) or to allow surgical procedures in the theatre room. Despite good mon-
itoring of ventilatory parameters and of flow-pressure-volume waves, as well as a
satisfactory setting of FiO2 and of ventilation, performance of conventional ICU
ventilators in delivering NPPV is poor because they are not able to cope with
leaks. Thus, a new generation of ICU ventilators has been developed to efficiently
 44

Table 6.1 Characteristics of the four categories of ventilators for NPPV

Adjustment
CO2- Blender of trigger Modality of Air leak com
rebreathing O2 and cycling NPPV Monitoring compensation Alarms Battery Transportability Costs
Volume-target − No + Volumetric + − ++ Yes ++ ++
ventilators
Older Bi-level +++ No − Pressometric − +++ − No +++ +
ventilators
Newer Bi-level ± No +++ Pressometric, ++ +++ ++ Yes +++ ++
ventilators Volumetric,
Hybrids
Intermediate ± Some ++ Pressometric, ++ ++ +++ Yes ++ ++
ventilators Volumetric,
Hybrids
Conventional − Yes ++ Pressometric +++ − +++ Yes ± +++
ICU ventilators and Volumetric
New ICU − Yes +++ Pressometric +++ +++ +++ Yes ± +++
ventilators and Volumetric
R. Scala
6 Ventilators for Noninvasive Mechanical Ventilation: Theory and Technology 45

assist acute patients with NPPV with to the option of leak compensation (i.e.,
“NPPV mode”), which allows a partial or total correction of air leak-induced
patient-ventilator asynchrony, even with large intermachine variability [5].
4. Intermediate ventilators combine some features of bi-level, volume-cycled, and
ICU ventilators (dual-limb circuit, sophisticated alarm and monitoring systems,
inner battery, both volumetric and pressometric modes, wide setting of inspira-
tory and expiratory parameters). “Hybrid modes” of ventilation, such as VAPS,
are available with the great majority of newer intermediate ventilators. These
new machines are designed to meet the patients’ needs, both at home and in the
hospital, and for the safe transport of critically ill patients [3, 4].

6.3 Technological Issues (Table 6.2)

6.3.1 Source of Gas and Oxygen Supply

ICU ventilators are equipped with high pressure air sources and with a blender in
which O2 from high-pressure sources and room air are variably mixed, making the
FiO2 controlled and stable. Conversely, bi-level and several intermediate ventilators
are provided with either a compressor or an electrically supplied turbine pump to
pressurize the room air. which may not assure constant stability in the pressuriza-
tion. Moreover, these machines do not have a blender, so O2 is delivered from low
pressure sources and the FiO2 during NPPV is not easily predictable because it is
dependent on several variables: site of O2 enrichment, type of exhalation port, ven-
tilator setting, O2 flow, breathing pattern, and amount of leakage [3]. It was calcu-
lated that the highest FiO2 is achieved with the leak port in the circuit and O2 added
into the mask using low IPAP levels [6]. Assuring a preset precise FiO2 is a great
help in managing acute hospitalized patients suffering from either severe hypox-
emia (i.e., requirement of high O2 inhaled gas) or hypercapnic decompensated CRF
(i.e., avoidance of CO2 rebound due to inappropriately high O2 delivery).

6.3.2 Circuit

With ventilators having a single-limb circuit there are two possibilities, depending
on the type of exhalation system: (1) intentional leak or “vented circuit” and (2)
anti-rebreathing expiratory valve or “non-vented circuit” [7]. The original
Respironics BiPAP, like most of the first-generation bi-level ventilators, was pro-
vided with a vented single-limb circuit. With this device, the exhalation of the
expired air occurs through the whisper swivel, a fixed resistance, variable flow, leak
port situated either in the circuit proximal to the interface or within the interface
itself. According to physiologic bench studies, this type of equipment may theoreti-
cally expose the patient to the risk of CO2 rebreathing, which may be detrimental
when treating hypercapnic patients [3]. The CO2 rebreathing is also influenced by
46 R. Scala

Table 6.2 Key points of the Source of gases

performance of ventilators for
Compressed medical gases
NPPV [3]
Compressor or electrically supplied turbine pump
Oxygen supply
High-pressure sources with a blender
Low-pressure sources with connection at the: ventilator,
circuit, mask
Circuit
Single-limb circuit with: non-rebreathing valve, plateau
exhalation valve or whisper
Double-limb circuit
Inspiratory trigger with sensitivity changeable or not
Flow, Pressure, Volume, Mixed
Expiratory cycle
Flow-dependent (with threshold changeable or not),
Time-dependent, Auto-function
Inspiratory flow changeable or not
Back-up respiratory rate
Air leak compensation
Humidification
Heated humidifiers, Heat-moisture exchangers
Battery
Internal, Additional external
Alarms
Lack or minimal
Sophisticated
Monitoring systems
Only some inspiratory parameters
Inspiratory and expiratory parameters
Flow, volume, pressure curves
Mode of ventilation
Only spontaneous modes without (PSV, PAV) or with a
guaranteed Vt (VAPS)
Both spontaneous (PSV, PAV) and mandatory modes
(VCV, PCV)
Interface
Nasal mask, full-face mask, total-face mask, helmet,
mouthpiece
PSV pressure support ventilation, PAV proportional assist ventila-
tion, VAPS volume-assured pressure support ventilation, VCV vol-
ume controlled ventilation, PCV pressure controlled ventilation

the site of the exhalation port, being significantly lower by using a facial mask with
the exhalation port inside compared with a facial mask with the exhalation port in
the circuit and a total face mask with the exhalation port inside [8]. The options that
6 Ventilators for Noninvasive Mechanical Ventilation: Theory and Technology 47

the clinician has to prevent this risk are (a) to keep the conventional whisper swivel
and apply high EPAP levels, such as 8 cm H2O, which may be, therefore, poorly
tolerated or (b) to use specific devices such as the plateau exhalation valve, which
has a diaphragm that limits air leaks during inspiration and allows a unidirectional
air flow during expiration [3]. However, it should be noted that the clinical impact
of the potential risk of CO2 rebreathing using ventilators equipped with a vented
single-limb circuit is probably overestimated.
Ventilators with a non-vented single-limb circuit are provided with a non-
rebreathing valve (mushroom, diaphragm, or balloon valve), which works a true
valve. During inspiration, the diaphragm or its balloon is inflated, with full occlu-
sion of the expiratory circuit limb, whereas during expiration, as the valve is
deflated, air is allowed to be exhaled throughout it [7]. According to physiological
bench studies, even with large variability, these valves may interfere with resistance
and expiratory work and, therefore, may increase lung hyperinflation (i.e., intrinsic
PEEP) [3, 4]. However, the clinical significance of these physiological findings is
unknown.
With ventilators having a dual-limb circuit in which a complete separation exists
between inspiratory and expiratory lines (i.e., ICU, last generation bi-level, and
intermediate ventilators) there is no risk of rebreathing. Conversely, dual-limb cir-
cuit ventilators are less user friendly and more cumbersome compared with single-
limb circuit devices. The latter may be preferable for home-based noninvasive
ventilatory treatment of the clinical patterns of CRF patients [3].

6.3.3 Inspiratory Trigger and Expiratory Cycle

The optimization of patient-ventilator interaction during NPPV is essentially based

on the technological efficiency of the machine in detecting the patient’s minimum
inspiratory effort as quickly as possible (i.e., inspiratory trigger) and in ending the
delivery of mechanical support as close as possible to the beginning of the patient’s
expiration (i.e., expiratory cycling), independent from respiratory system imped-
ance and air leaks [3, 4]. Ideally, the inspiratory trigger should be set at a higher
sensitivity capable of reducing the patient’s effort required to activate the mechani-
cal support. Bi-level ventilators equipped with flow triggers are associated with
lower work of breathing and shorter triggering delay time compared with those
equipped with pressure triggers [9]. As a matter of a fact, the chance of patient-
ventilator dyssynchrony due to “wasted efforts” for a too “tough trigger” is likely
to be lower with the former devices. On the other hand, a too sensitive trigger,
especially if flow-based, may induce auto-triggering during NPPV with substantial
air leaks, and, consequently, ventilator dyssynchrony due to “unwanted efforts”
[5]. Inspiratory trigger function may significantly differ, not only among the differ-
ent categories of ventilators but also within the same category, because of the struc-
tural features of the circuit (i.e., single-limb circuit with high resistive valves,
“incomplete dual-limb circuit” and a PEEP valve in the short expiratory limb) and
the heterogeneity in their performance (pressure-time and flow-time waveforms,
48 R. Scala

trigger delay, leak-induced auto-triggering during NPPV with flow-triggered

ventilators) [3].
The cycling to expiration optimizes the synchrony between the inspiratory time
(Ti) of the patient and that of the machine. During pressure support ventilation (PSV),
cycling to expiration is flow-dependent and occurs at a threshold, which is the
decrease in flow either to a default or changeable percentage (usually 25 %) of inspi-
ratory peak flow or to an absolute flow [3, 4]. Patient-ventilator dyssynchrony with
expiratory muscle activation and “wasted efforts” due to incomplete lung emptying
may happen under NPPV in the case of excessive air leaks that delay or prevent the
inspiratory flow from reaching the threshold (i.e., “inspiratory hang-up”) [5].
Successful strategies for preventing inspiratory hang-up that may be applied with
some ventilators include (a) setting a suitable threshold and/or a maximum Ti; (b)
use of special algorithms (i.e., “auto-track system”); and (c) switching to pressure
control ventilation (PCV) mode, in which expiratory cycling is time-dependent [3].
The opportunity to finely set the threshold for expiratory cycling because of the dis-
play of mechanics waveforms available in some newer ventilators may be helpful in
improving patient-ventilator synchrony during NPPV, as well as comfort and the
possibility of success [4, 10].
As observed with the inspiratory trigger, the behavior of different ventilators var-
ies in terms of cycling to expiration, and a marked heterogeneity is reported for a
given ventilator in response to various conditions of respiratory mechanics and air
leaks. Generally speaking, most of the bi-level ventilators use a cut-off at a higher
fraction of inspiratory flow than most of the ICU ventilators to avoid the mask leak-
induced deleterious prolongation of Ti. Newer bi-level ventilators tend to prema-
turely cycle to expiration under normal respiratory system mechanics, and this
tendency is exaggerated in restrictive conditions. Conversely, under obstructive
conditions, most of the older bi-level ventilators show a delayed cycling, and this
behavior is greatly exaggerated by the presence of air leaks. Consequently, at their
default setting, bi-level ventilators seem to be better adapted for supporting
obstructed patients [3]. Opposite to bi-level ventilators, in the absence of leaks and
at their default setting, newer ICU ventilators present some degree of delay in
cycling to expiration that is worsened by obstructive conditions, whereas restrictive
mechanics lead to premature cycling. The addition of leaks increases the delayed
cycling in normal and obstructive conditions and partially corrects premature
cycling in restrictive status. This dyssynchrony in expiratory cycling may be pre-
vented by using NPPV modes in normal and obstructive mechanics [3–5].

6.3.4 Inspiratory Flow

It is known that severely dyspneic patients with chronic obstructive pulmonary dis-
ease (COPD) cope better with higher inspiratory flow and neuromuscular patients do
better with lower inspiratory flow (i.e., pressure rise times of 0.05–0.1 and 0.3–0.4 s,
respectively) [3]. In most bi-level ventilators, this parameter is unchangeable; con-
versely, in more advanced bi-level ventilators, as well as in most intermediate and
6 Ventilators for Noninvasive Mechanical Ventilation: Theory and Technology 49

ICU ventilators, the rise time may be set with a potential profound effect on unload-
ing of respiratory muscles, tolerance, and leaks. In a physiologic study, the highest
pressurization rate was associated with an increased air leakage and poorer NPPV
tolerance, even though the diaphragmatic effort was reduced more compared with
lower speeds without significant differences in blood gases or breathing pattern. As
patient comfort was not different at the lower pressurization speeds, the authors sug-
gested that the individual titration should be targeted to achieve a good tolerance and
to minimize air leaks, keeping a relatively high pressurization rate [11].

6.3.5 Back-up Respiratory Rate

Some bi-level ventilators do not have the option of setting a back-up respiratory rate
(f), which raises the costs. Conversely, the majority of newer bi-level ventilators and
all intermediate and ICU ventilators are equipped with a back-up f. This option is
particularly advantageous in sicker patients with instability of their respiratory drive
because it prevents the phenomena of apneas and of periodic breathing, such as
Cheyne-Stokes in chronic heart failure. Back-up f may also be useful when a cau-
tious sedation is administered to improve patient compliance to NPPV in expert
intensive acute care settings [3].

6.3.6 Air Leak Compensation

Because of the kind of interface used, air leak is almost a constant feature of NPPV
and may interfere with patient comfort, patient-ventilator synchrony and, eventu-
ally, the likelihood of success both in acute and chronic patients [1, 5, 10]. During
NPPV delivered by ventilators equipped with a vented single-limb circuit, one must
consider both intentional (due to the presence of the exhalation system) and unin-
tentional leaks (throughout the mouth during nasal ventilation and/or between the
interface and the face with both nasal and oronasal masks) [7]. Excessive uninten-
tional leaks are strongly correlated with NPPV failure as a consequence of alveolar
hypoventilation, discomfort, patient-ventilator asynchronies, and sleep fragmenta-
tion. On the other hand, attempting to tightly fit the straps of headgear to reduce air
leaks should be avoided, because thus may reduce the patient’s tolerance and pre-
dispose to skin damage [3, 4]. Consequently, it is important to have a ventilator
capable of well compensating air leaks during NPPV. Air leak compensation is
greater using bi-level than volume-target home ventilators, with the fall in tidal
volume (Vt) >50 % with the latter. Conversely, the fall in Vt is <10 % and in IPAP
<8 % with bi-level ventilators in case of leaks because of an adequate increase in the
inspiratory flow and in the Ti. However, the effects of air leaks during NPPV are
more complex than the simple fall in IPAP and Vt, due to the role played by further
variables such as Ti, expiratory cycling and inspiratory trigger sensitivity.
Mathematical models that analyze the complex interaction between air leaks and
PSV in the obstructive conditions and their potential clinical implications have been
50 R. Scala

recently implemented. Even though all bi-level ventilators and most intermediate
and newer ICU ventilators equipped with NPPV modes were able to compensate air
leaks, their performance was not uniform [3, 4].

6.3.7 Battery

For both acute and chronic patients with a high level of dependency on NPPV, a
battery power source is mandatory in case of electricity supply failure at home and
in case of the need to transport the patient within the hospital or to another hospital.
However, clinician must be aware that battery duration differs greatly among the
different portable ventilators and may be shorter than that reported in the operator's
manual. Moreover, portable ventilator battery duration is affected by the setting, the
lung impedance characteristics, and the ventilator features [3].
As an alternative or in addition to internal batteries for NPPV ventilators, it is
also possible to use external batteries that guarantee a prolonged autonomy of the
ventilator in case of loss of electricity. It has to be considered that external batteries
may make the ventilator too heavy when it is to be transported.

6.3.8 Alarm and Monitoring System

The need for sophisticated alarms and monitoring systems during NPPV is based on
clinical practice because, to date, there is no scientific evidence of their clinical util-
ity. This is especially true for patients on home ventilation. Care must be taken when
setting the alarms on the ventilator to ensure that they will only function when a
genuine need arises, as frequent, often spurious alarms can significantly disturb the
sleep of the patient. The prototype of Respironics BiPAP did not have either alarm
or monitoring features, with an advantage in cost and transportability in the home
care setting. In the acute setting, the availability of newer bi-level, intermediate, and
ICU ventilators with more sophisticated alarms (i.e., low and high pressure, Vt, f,
FiO2, leaks) and monitoring graph (i.e., flow, Vt, and pressure curves) may be useful
in terms of safety and in improving patient-ventilator interaction [4, 5]. Conversely,
too elaborate alarms may be counter-productive in the clinical practice because they
frequently indicate minor air leaks during NPPV [3].
In the context of patient-ventilator interaction, even if some asynchronies may be
suspected at bedside by a careful observation of chest and abdomen movements
during NPPV, the interpretation of ventilator curves is helpful to noninvasively
assess patient-ventilator interaction [7] (Fig. 6.1). The correct identification of the
type of asynchrony during NPPV is helpful in choosing the best strategy to improve
the degree of patient-ventilator interaction (e.g., choosing a different interface to
reduce leaks and/or changing the setting of the ventilator). A randomized controlled
trial clearly demonstrated that a curve-driven setting of the ventilator is capable of
achieving a correction of acidosis in a shorter time compared with traditional
settings in severe COPD exacerbations [10].
6 Ventilators for Noninvasive Mechanical Ventilation: Theory and Technology 51

Flow

Pressure

Fig. 6.1 A typical patient-ventilator asynchrony pattern resulting from ineffective efforts during
noninvasive ventilation that may be easily suspected by looking at the flow-pressure curves of
sophisticated more advanced ventilators

The keys parameters to be monitor during NPPV are expiratory Vt and f, the
determinants of the breathing pattern. Concerning the former, the excessive air
leaks may cause a significant discrepancy between inspiratory and expiratory Vt.
Expiratory Vt assessment is feasible only with ventilators equipped with a dual-
limb circuit where expiratory Vt is obtained by subtracting leaks from inspira-
tory Vt. With these ventilators, monitoring of expiratory Vt is more reliable with
machines that take the measurement at the level of the expiratory branch of the
Y-tube than with those that take the measurement at the inlet of the expiratory
tube into the ventilator [3]. With ventilators having a single-limb circuit there are
two possibilities, depending on the type of exhalation system. In presence of a
non-vented circuit, the ventilator gives a inspiratory Vt value that is always an
actual measurement of volume delivered by the ventilator. The values are com-
puted at the beginning of inspiration, so that, in the presence of leaks, the leaks
are considered as part of the delivered inspiratory Vt. In this case, the ventilator
is not able to measure and provide an estimation of leaks and of expiratory Vt as
well. In presence of a vented circuit, the ventilator provides an estimation (and
not a measure) of expiratory Vt that should be the real volume inspired by the
patient without the intentional leaks. In this case, the ventilator is able to provide
an estimation of leaks. The leak value displayed may be the total value of leak
(intentional + unintentional) or only the unintentional leaks according to the
algorithm used by the ventilator. Unfortunately, for a very large leak, its estima-
tion, as well as the estimation of expiratory Vt, may become unreliable [7]
(Fig. 6.2).
Concerning f assessment during NPPV, there may be a gap between the rate of
ventilator-assisted and patient-triggered breaths. Looking at the ventilator-f, inef-
fective efforts and auto-triggering may cause, respectively, underestimation and
overestimation of the effective patient’s f [7].
52 R. Scala

a Vt monitoring
Ventilator with dual-limb circuit
Nonintentional
leak

From the patient Expiratory-Vt

Ventilation generated
by the
ventilator

To the patient Inspiratory-Vt Nonintentional

leak

Inspiratory-Vt = Ventilation generated by the ventilator + Nonintentional leak

Expiratory-Vt = Inspiratory-Vt – Nonintentional leak

b Vt monitoring
Ventilator with single-limb “non-vented” circuit
Nonintentional
leak

Non-rebreathing valve

Expiratory-Vt
Ventilation generated
by the
ventilator

Nonintentional
Inspiratory-Vt
leak

Inspiratory-Vt = Ventilation generated by the ventilator + Nonintentional leak

Expiratory-Vt = ???

c Vt monitoring
Ventilator with single-limb “vented” circuit
Nonintentional
leak

Intentional leaks

Estimated
Expiratory-Vt?
Ventilation generated
by the
ventilator

Nonintentional
Inspiratory-Vt
leak

Inspiratory-Vt = Ventilation generated by the ventilator + Intentional leaks + Nonintentional leak

Expiratory-Vt = Inspiratory-Vt – Intentional leaks

Fig. 6.2 Differences in Vt monitoring during noninvasive ventilation delivered by means of ven-
tilators equipped with double (a) or single-limb circuit provided with a non-vented (b) or vented
(c) exhalation system with permission from reference [7]
6 Ventilators for Noninvasive Mechanical Ventilation: Theory and Technology 53

6.4 Controversial Issues

Because of the huge gap between the increasing number of newer ventilators that
are commercially available and their physiologic and clinical careful evaluation,
there is no published data about several sophisticated ventilators routinely used in
the clinical practice. With few in vivo investigations, the majority of data about the
performance of the different available ventilators comes from in vitro studies con-
ducted on lung models. Therefore, some doubts remain about the real clinical sig-
nificance of the technical differences observed in the bench studies among the vary
types of ventilators. Consequently, every extrapolation of these experimental data to
the clinical setting must be done cautiously because no lung model can simulate the
ventilatory variability observed in patients. This is particularly true when the find-
ings of in vitro studies have to be applied to acute patients under NPPV in the pres-
ence of leaks.
Based on the published data of the literature, despite a wide heterogeneity found
in each category of machines, several bi-level ventilators demonstrated a better per-
formance than several ICU ventilators [3, 4]. However, no study has shown greater
NPPV clinical success for one type of ventilator than another both in the acute and
chronic settings. Nevertheless, some points should be clear when the clinician must
choose a ventilator [3].

Key Major Recommendations

• As excessive air leaks are correlated with treatment failure, the clinician
should choose ventilators designed for NPPV with leak compensation
capability (i.e., bi-level, some intermediate and new ICU ventilators).
Moreover, the capability of setting several parameters and looking at flow-
volume-pressure waveforms with newer ventilators may be helpful in
improving patient-ventilator synchrony, comfort, gas exchange and, hope-
fully, clinical outcome.
• The choice of ventilator should be tailored to the pathophysiology and the
severity of ARF and CRF. In the acute setting, for hypoxemic patients,
ventilators with an O2 blender are recommended, whereas in those with
hypercapnia, ventilators with a dual-limb circuit have an advantage in low-
ering PaCO2. In patients with mild COPD exacerbation, the use of home
ventilators may be appropriate, particularly if the patient is already on
home NPPV. In contrast, patients with life-threatening ARF at risk of intu-
bation should be treated with more sophisticated machines. In the chronic
setting, conditions where respiratory drive is good (e.g., COPD) could use
a simple ventilator that works in a spontaneous mode, whereas those in
whom respiratory drive is impaired must have a mandatory back-up rate.
Conversely, in case of fast-progressing neuromuscular diseases, a more
sophisticated ventilator with adequate monitoring equipment and an inner
battery is recommended. The clinical superiority of new hybrid modes of
54 R. Scala

NPPV (e.g., VAPS) over the traditional pressometric modes has yet to be
demonstrated in both the acute and chronic settings.
• The selection of a ventilator should also take into account costs and staff
experience. The more sophisticated a ventilator is, the longer the training
for clinicians is required. With the tremendous growth of the ventilator
market in terms of complexity, some of the new bi-level ventilators are not
user-friendly even for trained ICU clinicians. The smaller the variety of
devices used, the greater the likelihood that all team members will acquire
enough experience in NPPV set-up, with positive repercussions in costs
and workload.
• The clinician should be aware of the multiple interferences of the accessories
for NPPV (interfaces, exhalation systems, pressure settings, and humidifica-
tion devices) with the performance of the different categories of ventilators.
For example, concerning humidification during NPPV, heated humidifiers
show great clinical and physiological advantages compared with heat-mois-
ture exchangers, even though the former is more time-consuming.

References
1. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009;374(9685):
250–9.
2. Ozsancak A, D’Ambrosio C, Hill NS. Nocturnal noninvasive ventilation. Chest. 2008;133(5):
1275–86.
3. Scala R, Naldi M. Ventilators for noninvasive ventilation to treat acute respiratory failure.
Respir Care. 2008;53(8):1054–80.
4. Gregoretti C, Navalesi P, Ghannadian S, et al. Choosing a ventilator for home mechanical
ventilation. Breathe. 2013;9:394–408.
5. Vignaux L, Vargas F, Roeseler J, et al. Patient-ventilator asynchrony during non-invasive ven-
tilation for acute respiratory failure: a multicenter study. Intensive Care Med. 2009;35(5):
840–6.
6. Schwartz AR, Kacmarek RM, Hess DR. Factors affecting oxygen delivery with bi-level posi-
tive airway pressure. Respir Care. 2004;49(3):270–5.
7. Scala R. Monitoring choices in acute NIV. In: Simonds AK, ed. ERS Practical Handbook of
Noninvasive Ventilation. Sheffield, European Respiratory Society. 2015; pp. 93–101.
8. Schettino GP, Chatmongkolchart S, Hess DR, et al. Position of exhalation port and mask
design affect CO2 rebreathing during noninvasive positive pressure ventilation. Crit Care Med.
2003;31(8):2178–82.
9. Nava S, Ambrosino N, Bruschi C, et al. Physiological effects of flow and pressure triggering
during non-invasive mechanical ventilation in patients with chronic obstructive pulmonary
disease. Thorax. 1997;52(3):249–54.
10. Di Marco F, Centanni S, Bellone A, et al. Optimization of ventilator setting by flow and pres-
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Ventilatory Modes and Settings During
Noninvasive Ventilation 7
Claudio Rabec and Daniel Rodenstein

Contents
7.1 NIV: A Short Story. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
7.2 Issues of Particular Importance During NIV: Leaks,
Upper Airway Resistance, the Type of Exhalation Port,
and NIV Ventilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7.2.1 Influence of Unintentional Leaks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7.2.2 Influence of the Upper Airways:
A to Component Variable Resistor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
7.2.3 Influence of Type of Exhalation Device
and Connecting Circuits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
7.2.4 Influence of the Ventilator: Intensive-Care
(ICU) Versus Home Devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
7.3 Patient Ventilator Synchrony: One Goal, Two Pumps . . . . . . . . . . . . . . . . . . . . . . . . . . 60
7.3.1 How Do Inspiration and Expiration Start and Stop?. . . . . . . . . . . . . . . . . . . . 61
7.3.2 How a Ventilator Acts and How Patient
Ventilator Synchrony Is Achieved:
The Ventilatory Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
7.4 Modes of Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
7.4.1 Volume-Targeted Mode. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
7.4.2 Pressure-Targeted Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
7.4.3 NIV: Volume or Pressure Targeted? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
7.4.4 Volume Targeting Pressure Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
7.5 Combined or Dual Ventilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
7.6 Choice of Ventilator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
References ............................................................. 77

C. Rabec, MD (*)
Service de Pneumologie et Réanimation Respiratoire, Centre Hospitalier et Universitaire de
Dijon, 2 Bd Maréchal de Lattre de Tassigny, Dijon 21079, France
e-mail: [email protected]
D. Rodenstein, MD, PhD
Service de Pneumologie, Cliniques Universitaires Saint Luc, Université Catholique de
Louvain, Bruxelles, Belgium

© Springer International Publishing Switzerland 2016 55

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_7
56 C. Rabec and D. Rodenstein

Since the early 1980s, when noninvasive ventilation (NIV) showed efficacy in the
management of some forms of respiratory failure [1–3], the number of patients
receiving this treatment both in the acute setting and at home has steadily increased.
This is explained by a growing number of indications in which the effectiveness of
NIV has been proven, and also by major technological advances that led to the avail-
ability of high-performance portable ventilators and the development of a technical
support infrastructure [4]. In the particular case of chronic respiratory failure
patients, NIV applications were extended from conventional indications in chest
wall and neuromuscular diseases to other more frequent conditions such as obesity
hypoventilation and chronic obstructive pulmonary disease (COPD), although, in
the latter, the role of NIV is still controversial [5–7].
NIV is predominantly applied at night. Sleep is a unique state that induces pro-
found ventilatory changes, including modifications in ventilatory control, upper air-
way patency, and respiratory muscle recruitment. These sleep-related physiological
changes, although without clinical consequences in healthy subjects, may represent
an additional challenge when the respiratory system is in a disease state, exceeding
the response capabilities of the system and leading to failure [8]. Furthermore, it has
been well demonstrated that sleep-related hypoventilation is the first sign of ventila-
tory failure preceding daytime chronic respiratory failure [9].
Nocturnal NIV can have sustained effects in correcting arterial blood gases dur-
ing the day. It has been hypothesized that this improvement is mediated by a number
of possible mechanisms: (1) improving ventilatory mechanics, (2) resting fatigued
respiratory muscles, or (3) enhancing ventilatory sensitivity to CO2 [10]. In addi-
tion, improvement in sleep stage distribution may increase chemosensitivity and
enhance sleep quality [11].
This chapter deals with the equipment and mechanisms for NIV and, in particu-
lar, the major ventilator modes and settings.

7.1 NIV: A Short Story

From an historical point of view, negative pressure ventilation (NPV) was the first
mode applied to long-term mechanical ventilation. In NPV, a perithoracic subatmo-
spheric pressure is applied to generate inspiration by using body ventilators
(e.g., tank or cuirasses). Apart from some specialized centers, this treatment has
been almost completely substituted for positive pressure ventilation. The main rea-
sons for this trend were cumbersome NPV devices, the lack of accessibility by the
patient, and the danger of inducing upper airway obstruction [12].
The first positive pressure ventilators were powered by a piston chamber, a rotary
piston, or a standard compressor. They were large, encumbering, and not versatile
and had limited capabilities to modify airflow. Most of them provided only a
volume-targeted mode. In the mid-1990s, the development of blower-driven con-
tinuous positive airway pressure (CPAP) devices to treat obstructive sleep apnea
(OSA) and the growing popularity of NIV influenced the evolution toward the first
7 Ventilatory Modes and Settings During Noninvasive Ventilation 57

blower-driven devices providing bi-level positive pressure. These devices were

originally conceived to improve the tolerance of patients with OSA and consisted of
a CPAP blower modified with a magnetic valve to cycle between two different pres-
sure levels, hence the name bi-level devices [13]. Since then, NIV devices have
rapidly evolved with the development of microprocessor-controlled, high-
performance, blower-driven micro ventilators. These new technology devices have
some advantages, such as flexibility and variability in gas-delivery patterns, high
leak compensation capabilities, and “intelligent” inspiratory and expiratory trigger
mechanisms. Some of them also have the capability of interfacing with computer
systems and built-in monitoring modules that can assess ventilatory parameters and
store the data in memory for subsequent analysis.

7.2 Issues of Particular Importance During NIV: Leaks,

Upper Airway Resistance, the Type of Exhalation Port,
and NIV Ventilators

Compared with invasive ventilation, NIV has two unique characteristics: the non-
airtight nature of the system that poses the potential risk of unintentional leaks, and
the fact that the ventilator-lung assembly cannot be considered as a single-
compartment model because of the presence of a variable resistance represented by
the upper airway (UA). Both situations may compromise the delivery of an effective
tidal volume. As a consequence, during NIV, increasing the delivered volume or the
delivered inspiratory pressure do not necessarily result in increased effective venti-
lation reaching the lungs [14].

7.2.1 Influence of Unintentional Leaks

Unintentional leaks are very common in NIV [11, 15]. Leakage may be absent or
minimal when the patient is awake but may worsen during sleep as a result of the
loss of voluntary control and decreased muscle tone. Leaks can take place at the
mouth, between the skin and the mask but an amount of air can also be deposited at
the oropharyngeal reservoir and even pass to the digestive tract (“internal” leaks)
[16]. After having ruled out poor adaptation of the interface, leaks can be classified
according to causal factor: as primary or “passive”, resulting from hypotonic mas-
seter muscles and/or inability of the soft palate and the oral muscles to counterbal-
ance the high inspiratory pressure insufflated by the ventilator, or secondary to
closure of the upper airways occurring at the level of the oropharynx or the glottis
[14, 16, 17].
Leaks can impair quality of both ventilation and sleep. They can largely affect
ventilator triggering, pressurization, volume delivered, rate of inspiratory pressur-
ing and cycling function and induce sleep fragmentation. A detail of leak-induced
abnormalities can be seen in Table 7.1.
58 C. Rabec and D. Rodenstein

Table 7.1 NIV: impact of Impact of unintentional leaks depends on:

unintentional leaks (see text
Ventilatory mode (volume or pressure controlled)
for details)
Management of expiration (valve or leak outlet)
Unintentional leaks may affect:
Patient-ventilator synchrony and level of ventilatory
assistance by affecting
Inspiratory triggering
Auto-triggering
Ineffective inspiratory efforts
I to E cycling [35, 38]
Rise time
Pressurization
Maintain of desired PEEP level
Tolerance of ventilation
Quality of sleep by inducing frequent arousals and sleep
fragmentation
The consequences of leaks on the quality of NIV will depend on:
The ventilatory cycle phase during which the leak occurs
The magnitude of the leak
The continuous or intermittent nature of the leak
The ability of the ventilator to compensate for leaks

7.2.2 Influence of the Upper Airways: A to Component

Variable Resistor

During NIV, a variable resistance constituted by the upper airway (UA) is inter-
posed between the ventilator and the lung. This explains why a reduction of air-
way patency may occur, compromising delivery of an effective tidal volume.
Intermittent obstruction of the UA is common during NIV and may be related to
two mechanisms. The first corresponds to obstructive events at the oropharyngeal
level because of UA collapse, as a result of insufficient expiratory positive airway
pressure (EPAP). This mechanism may be present in patients with an unstable
UA, such as patients with OSA [7, 18]. Another mechanism corresponds to epi-
sodes of intermittent obstruction at the glottal level, reflecting cyclic glottal clo-
sure induced by hyperventilation, a type of “ventilation resistance” reflex
[19–22].

7.2.3 Influence of Type of Exhalation Device and Connecting

Circuits

Whereas intensive care unit (ICU) ventilators classically use a double circuit with
an integrated expiratory valve, two different types of circuits can be used to provide
7 Ventilatory Modes and Settings During Noninvasive Ventilation 59

NIV. The first uses a similar assembly to those used in ICU devices and includes
either single or double tubing, in which inspiration and expiration are separated and
a true expiratory valve is present so that CO2 rebreathing is not a significant problem
(Fig. 7.1a). The other type of ventilators, like the CPAP devices that they were
derived from, do not have a true exhalation valve and often use a single-limb circuit
with a risk of rebreathing. To avoid rebreathing, this system includes a calibrated
leak (called intentional leak) either at the mask level or in the circuit (Fig. 7.1b).
Single-circuit pressure-targeted ventilators, provided with a calibrated leak (called
bi-level ventilators), are most commonly used for NIV today. These devices cycle
between a higher inspiratory positive airway pressure (IPAP) and a lower EPAP that
can be independently adjusted. With these devices, a minimum mandatory EPAP
level of 4 cm H2O is needed to ensure an effective washout of CO2, [23]. The use of
specific “anti-rebreathing” valves may also diminish rebreathing, although their
clinical relevance remains uncertain. Moreover, some of these devices increase
expiratory work of breathing and may potentially lead to dynamic hyperinflation
and patient discomfort [23, 24]. Interestingly, one study showed that the exhalation
port position influences CO2 rebreathing with a more efficient CO2 washout when
the leak is positioned within the mask [25].

a
Insuflation

Ventilator Patient

Expiration

Ventilator
Patient

Pressure

Airflow

Thoracic
belt
Abdominal
belt

SpO2
1 2

Expiratory valve

Fig. 7.1 Type of circuits used in non-invasive ventilation (NIV) with (a) an expiratory valve and
(b) intentional leak,Note that when a simple circuit with an intentional leak is used, the leak may
be interposed in the circuit or incorporated at the mask
60 C. Rabec and D. Rodenstein

b Insuflation

Ventilator Patient

Expiration

Ventilator Patient

Pressure

Airflow

Thoracic
belt

Abdominal
belt

SpO2

Intentional
leak
d

Fig. 7.1 (continued)

7.2.4 Influence of the Ventilator: Intensive-Care (ICU) Versus

Home Devices

Both ICU and home ventilators can be used to deliver NIV. The main technical
characteristic differentiating them is that, for the former, the driving pressure is
supplied by compressed gas, whereas the latter incorporate their own pressure
source. Nevertheless, the type of ventilatory support that they provide is
similar

7.3 Patient Ventilator Synchrony: One Goal, Two Pumps

When delivering mechanical ventilation, there are two ventilatory pumps acting
together: the ventilator, on the one hand, and the patient’s own respiratory muscles,
on the other hand. These two pumps may work in harmony, but, in fact, they can
interact in any number of ways, many of which will create problems rather than
solving them. Hence, patient ventilator asynchrony is quite common in patients
during NIV [26, 27]. Asynchronies may occur at two levels: during inspiratory
7 Ventilatory Modes and Settings During Noninvasive Ventilation 61

triggering, in situations in which there is a mismatch between patient inspiratory

effort and ventilator triggering (i.e., ineffective inspiratory effort, double trigger-
ing, or auto-triggering) or during cycling from inspiration to expiration, when ven-
tilator cycling does not coincide with the end of patient effort (premature or delayed
cycling) [27].
We will begin this section by reviewing the triggering and cycling modes.

7.3.1 How Do Inspiration and Expiration Start and Stop?

The patient can control the initiation (triggering) and the end (cycling) of inspiration
or, on the contrary, neither of them, in which case the ventilator controls both the
initiation and the end of inspiration.

7.3.1.1 Spontaneous Mode (S)

In this mode, the patient controls the beginning and end of inspiration. Inspiration
starts when the ventilator is triggered by the patient. During the low-level expiratory
pressure (EPAP), the patient’s inspiratory effort modifies the pressure and flow into
the circuit, starting the change to the higher inspiratory pressure (IPAP). The pres-
sure is maintained as long as a minimal preset inspiratory flow is occurring. The end
of inspiratory assistance (cycling from inspiration to expiration) occurs when the
declining inspiratory flow reaches a predetermined percentage of peak inspiratory
flow and the pressure in the circuit reverses to EPAP. In this mode, a targeted inspi-
ratory pressure, an inspiratory trigger sensitivity, and a percentage threshold of peak
flow for cycling to expiration (see below) must be selected. In some ventilators,
these can all be set by the clinician, whereas in others, only the inspiratory pressure
can be set. Trigger sensitivity, peak flow, and the level of ventilatory support (IPAP –
EPAP) are the main variables that determine the patient’s work of breathing Because
each cycle is terminated by a flow criterion rather than by volume or time, the
patient retains control of cycle length as well as its depth and flow profile. This
mode is also called pressure support ventilation (PSV).

7.3.1.2 Assist Mode (A)

In A mode, the patient controls the onset of inspiration but the inspiratory length is
regulated by the operator. In this mode, the clinician must select a targeted volume
or pressure, an inspiratory-expiratory (I:E) ratio, or an inspiratory time and an inspi-
ratory trigger sensitivity

7.3.1.3 Assist-Control Mode (A/C)

As in assist mode, in A/C mode the patient controls onset of inspiration but end of
inspiration is time triggered and determined by the operator. As this mode also
allows presetting a backup respiratory rate (RR), if patient RR is lower than the
preset ventilator backup RR, the system moves to control mode. Then, this mode
allows the patient to trigger the ventilator but also tries to grant a minimum minute
62 C. Rabec and D. Rodenstein

ventilation by allowing a backup rate. In this mode, the clinician must select a
backup rate, a targeted volume or pressure, an expiratory pressure, an I:E ratio, and
inspiratory trigger sensitivity. Trigger sensitivity and peak flow are the main vari-
ables that determine the patient’s work of breathing.

7.3.1.4 Control Mode (C)

In the control mode, there is a preset automatic cycle based on time. The ventilator
controls the beginning and end of inspiration and thus the RR. Therefore, one
expects the ventilator to capture and inhibit the patient’s respiratory center and the
patient to follow the settings imposed by the ventilator. In this mode, the clinician
must select a targeted volume or pressure, a fixed RR, and an I:E ratio or inspiratory
and expiratory durations. With this mode, the entire work of breathing is supposed
to be performed by the ventilator. In some ventilators, this mode is also called timed
(T) mode, but it is rarely used.
A particular combination of these modes is available in some NIV ventilators.
This mode, called S/T is basically a PSV that provides a backup rate. In this particu-
lar mode, cycling from inspiration to expiration is flow limited in patient-triggered
cycles and switched to time limited when the patient’s spontaneous RR falls below
the backup rate. It also happens when, during S cycles, inspiratory time exceeds a
predetermined maximal length (see below). A patient-triggered cycle can be seen in
curves of ventilation as a negative inspiratory deflection in pressure and flow curves
(see trace no 2 in both Fig. 7.2b, c).

7.3.2 How a Ventilator Acts and How Patient Ventilator

Synchrony Is Achieved: The Ventilatory Cycle

Inadequate patient cooperation, mask intolerance, and patient selection criteria have
been advocated as frequent causes of NIV failure, but little attention has been paid
to settings and type of ventilator. However, appropriate settings are essential to
obtain optimal patient-ventilator synchrony, a main condition to ensure a good qual-
ity of ventilation and a proper tolerance by the patient [28]. The most logical
approach to explain how a ventilator acts and how patient ventilator synchrony is
achieved is to analyze the different phases of a typical positive pressure ventilatory
cycle (Fig. 7.3).

7.3.2.1 Triggering
As described above, the beginning of inspiration can be triggered by time or patient
effort. In the A and AC mode, the ventilator must recognize the patients’ inspiratory
effort. This is called triggering function. Classically, NIV devices propose two types
of triggers. The first, called a pressure-based trigger, present in older NIV ventila-
tors, is based on a drop in proximal airway pressure and requires a closed circuit.
The amplitude of this drop is a function of preset sensitivity and also of patient
respiratory drive. A second, called a flow-based trigger, present in almost all newer
NIV devices, is based on detection of an inspiratory flow in the presence of a con-
tinuous flow washing out the circuit during expiration.
7 Ventilatory Modes and Settings During Noninvasive Ventilation 63

a
PAW 0
(cmH20)

-10

100
(I.min-1)

INSP
0
EXP
FLOW

100

b
30
Paw (cmH2O)

20

10
1 2
sec
0

Paw {{Trigger threshold}}

during SB

Inspiratory flow
Flow (l.min-1)
40 during SB

sec
20

20

40

Fig. 7.2 Flow and Paw dynamics during (a) spontaneous breathing, (b) pressure-targeted
ventilation, (c) volume-targeted ventilation. 1 Controlled cycle, 2 assisted cycle. Dashed lines
represent simultaneous theoretical spontaneous breathing kinetics. Note that, during PTM, flow
contour remains close to physiological flow dynamics, facilitating a better adaptation to patient
ventilatory needs and patient-ventilator synchrony (for details, see text)
64 C. Rabec and D. Rodenstein

c
Paw (cmH2O)
30

20

PEEP level
10 1 2

5
sec
0
Paw {{Trigger threshold}}
during SB

Inspiratory flow
40
during SB Flow (l.min-1)

20
sec
0

20

40

Fig. 7.2 (continued)

Inspiratory plateau
level
Pressure
I to E cycling

PEEP level

Pressurisation

Time

Inspiratory
triggering

Fig. 7.3 The ventilatory cycle

Patient ventilatory synchrony during the triggering phase needs a match between
the three physiological variables characterizing spontaneous breathing (ventilatory
drive, ventilatory requirements, and Ti/Tot, which is the ratio of inspiratory time/total
time) and the three technological variables characterizing ventilator function (trigger
function, gas delivery algorithm, and cycling criteria). Asynchrony during the
7 Ventilatory Modes and Settings During Noninvasive Ventilation 65

inspiratory phase is quite common during sleep in patients under NIV, may compro-
mise ventilatory efficacy and sleep quality, and is mainly influenced by the delay
duration, trigger sensitivity, and amount of pre-inspiratory effort (which depends itself
on respiratory drive and muscle strength) [26]. Therefore, the inspiratory trigger
should have a short delay of response (i.e., a short time between onset of inspiratory
effort and pressurization) and be sensitive enough to allow the patient to trigger easily
without auto-triggering, even in the presence of leaks. It ideally should be <100 ms,
inasmuch as higher values can increase work of breathing and lead to asynchrony or
discomfort [29]. As opening a demand valve during pressure triggering can impose
substantial effort [29], ventilators that use flow triggering have, in general, shorter
trigger delays [30]. However, these triggers expose the patient to greater occurrence of
auto-triggering [31, 32]. Other than intrinsic performance of the trigger system, trig-
gering depends on type of circuit used (simple or double), the patient profile, the level
of auto-positive end expiratory pressure (auto-PEEP), and the presence of leaks [33].
Leaks may greatly affect trigger function, either by precluding detection of patient
inspiratory effort (leading to ineffective inspiratory effort) or by mimicking an “inspi-
ratory flow” (when using flow triggering) or dragging EPAP level below trigger
threshold (when using pressure triggering), with both of the latter situations possibly
leading to autocycling. Finally, other frequent causes of asynchrony during the trig-
gering phase are excessive pressure assistance (as high pressure generates dynamic
hyperinflation due to larger tidal volume and shorter expiratory time, contributing to a
new inspiratory effort occurring before an incomplete exhalation), additional resis-
tance in the circuit, and dynamic hyperinflation [27, 33].
The newer technologies (microprocessors, servo valves, and fast blowers) have sub-
stantially improved trigger response. Moreover, an adjustable inspiratory trigger is an
option presently available in most home ventilators. Automated complex trigger algo-
rithms, are available, in which a flow-time waveform is used to trigger the ventilator.
With these systems, triggering arises when patient inspiratory effort distorts the expira-
tory flow waveform and this signal crosses the flow shape signal. This method is said to
be more sensitive than classical flow triggering, allows adjusting trigger sensitivity in
presence of leaks, and can help to reduce ineffective efforts and autocycling. However,
the respective advantages of this sophisticated trigger system have not been assessed in
rigorous studies. It should be emphasized that some adjustable-trigger devices are scaled
in arbitrary units (1–5 or even 1–10), which makes them difficult to use in real life

7.3.2.2 Pressurization
As the correct pressurization is essential to decrease inspiratory effort and improve
synchronization, during this phase, inspiratory flow should be sufficient to match
inspiratory demand [34]. Circumstances influencing pressurization are the level of
ventilatory support, the amount of time required to reach the target pressure (pres-
surization slope, also called rise time), compliance and resistance of the respiratory
system, and patient inspiratory effort. Studies comparing different ventilators also
emphasize the influence of the type of device on pressurization, in particular in situ-
ations of high inspiratory demand [35].
A faster rise time has been shown to better unload the respiratory muscles [34].
As the slope becomes flatter, the machine delivers lower flow rates and the patient’s
66 C. Rabec and D. Rodenstein

work of breathing increases [34]. In these situations, the device acts by creating an
increasing hindrance to airflow, simulating a condition in which the patient breathes
through a narrow circuit. However, it must be emphasized that if a slow pressuriza-
tion can increase inspiratory work, an excessive peak flow can also have adverse
effects as it may increase the sensation of dyspnea [36], induce double triggering
[27], and lead to high peak mask pressure, which favors leaks. Moreover, leaks can
themselves impair pressurization [35].
Some new ventilators offer an adjustable rise time, allowing an individual
titration that can profoundly affect patient comfort and synchrony. In this con-
text, it must be emphasized that even if the data published show that the steepest
pressure ramp slope induced the lowest work of breathing in both obstructed and
restricted patients [34], COPD patients tend to prefer relatively rapid rise time
(0.05–0.1 s) whereas patients with neuromuscular diseases prefer a slower one
(0.3–0.4 s)
Whereas the pressurization capacity of recent bi-level ventilators have shown
improvements, NIV blower-powered devices are, in this aspect, clearly at a disad-
vantage when compared with proportional valve-powered ICU ventilators [35].
Moreover, studies comparing different home ventilators found major differences in
terms of pressurization, even when tested at similar rise times, in particular in situ-
ations of high inspiratory demand [35]. Regardless, when considering long-term
ventilation, this concern is probably not as important as it is in the acute setting
because most patients do not have high inspiratory demands

7.3.2.3 Sustainment of Inspiratory Plateau

Inspiratory pressure level is one of the main determinants of efficacy of
NIV. Determination of the optimal level can be the result of balancing two opposing
aims: the desire to provide effective minute ventilation and the need to minimize
leaks and discomfort caused by excessive inspiratory pressure. It must be empha-
sized that, even if newer ventilatory devices have great capabilities to compensate
mild to moderate leaks, greater leaks may compromise the ability of the device to
attain a desired level of inspiratory pressure. Because very high IPAP levels may
favor leaks and the ability of these devices to compensate for them is limited, these
two conditions will determine whether inspiratory pressure level remains stable or
decreases. Even if there is no recognized gold standard for the level at which venti-
latory support must be set, high IPAP levels must be avoided because, in addition to
favoring leaks and discomfort, they can induce central apneas during sleep, leading
to arousals and sleep fragmentation [37], and can also cause patient ventilatory
asynchrony [27].

7.3.2.4 Cycling from Inspiration to Expiration

Switching from inspiration to expiration can be time cycled or flow cycled. In the
time-cycled mode, ventilators use a time criteria chosen by the clinician. In the
flow-cycled mode, cycling occurs as inspiratory flow decreases to a preadjusted
percentage of the peak inspiratory flow, which is supposed to indicate the end of
inspiratory effort. The criteria used to end inspiration may have a clinically relevant
7 Ventilatory Modes and Settings During Noninvasive Ventilation 67

impact on quality of ventilation. Ideally, cycling should coincide with the end of
patient effort. However, synchronization between end of neural inspiration and ven-
tilator expiratory triggering is mainly determined by respiratory mechanics moving
from a premature cycling in restrictive patients to a late cycling in obstructive ones
[35, 38]. Moreover, when flow cycling is used, leaks may also delay switching to
expiration because flow rate is maintained, in an attempt to maintain pressure, above
the level at which cycling into expiration occurs (Fig. 7.4). Both these conditions
may lead to patient ventilator expiratory asynchrony, a common condition in patients
with COPD [38]. Moreover, this late cycling may aggravate auto-PEEP, also leading
to ineffective inspiratory triggering [38]. As with other components of the ventila-
tory cycle, leaks may profoundly modify I to E cycling, either by advancing or
delaying expiratory triggering. In the latter case, increasing the ventilator flow for
leak compensation may counterbalance the decrease of inspiratory flow under the
preadjusted threshold level, thus impeding recognition of the end of inspiration.
This results in abnormal prolongation of inspiratory time that may lead to asyn-
chrony, as patients exhale against the machine (aggravating auto-PEEP, in particu-
lar, in obstructive patients) or even inhale without receiving any ventilatory support
(inspiratory hang-up) [38].
In older ventilators, expiratory trigger is fixed at 25 % of peak flow, but newer
ventilators offer adjustable expiratory triggers. Some of them use arbitrary units, but
others allow defining a known percentage of peak flow. These adjustable expiratory
triggers may allow tailoring settings to the patient’s underlying condition. For
instance, Tassaux et al. [39] demonstrate in a COPD population under invasive ven-
tilation that increasing the expiratory trigger from 10 to 70 % of peak flow (this
means shortening inspiration to allow a greater expiratory time) was associated with
a marked reduction in delayed cycling and intrinsic PEEP. Whether the same is true
in patients under NIV remains to be elucidated.
To improve patient ventilator expiratory synchrony, some bi-level ventilators
provide intelligent flow-based algorithms that, by “copying” previous ventilatory
cycle patterns and by using moving signals, are able to modify cycle thresholds to
automatically adjust breath-to-breath inspiratory time. These algorithms are sup-
posed to be useful, in particular to adjust inspiratory time during leaks.
Finally, additional mechanisms proposed by some ventilators can improve
cycling to prevent undesired inspiratory time prolongation. Sudden increases in
pressure (that can be assumed as secondary to an active expiratory effort) produce,
in almost all the devices, early cycling to expiration. Another mechanism is to limit
maximal inspiratory time. This maximal inspiratory time (called also Timax) is gen-
erally fixed at 3 s but may be adjustable for some devices. The aim of Timax is to
switch to a time criterion to terminate the breath to prevent an unsuitable lengthen-
ing of inspiratory time (in particular when leaks are present).

7.3.2.5 PEEP Level

PEEP is an above-atmospheric (positive) pressure applied during expiration.
When positive pressure is applied during machine breaths, the term PEEP is main-
tained but when applied during spontaneous breathing the term CPAP is used.
68 C. Rabec and D. Rodenstein

Paw

Time

{{Trigger threshold}}

Flow V’ peak
(V’)
Insp.
V’
insp.
0
V’exp.
Time
Exp. Flow criterion
(variable) Cycling from I to E
without leaks:
{{expiratory trigger}}
flow-limited
Ti max
b
Paw

Time

{{ Trigger threshold}}
Flow increase
V’peak to compensate
Flow leaks
(V’)
Insp.
V’insp.
Time
0 V’exp.
Cycling from I to E
Exp. during leaks:
{{expiratory trigger}}
Switch from flow-limited
to time-limited

Fig. 7.4 Impact of leaks on I to E cycling during PSV (S in bi-level devices) mode. (a) Pressure sup-
port ventilation without leaks. (b) With leaks. Note that during leaks, the cycle switches to a time mode
7 Ventilatory Modes and Settings During Noninvasive Ventilation 69

With both, the positive pressure is maintained throughout the entire cycle.
Providing an external PEEP (called EPAP in bi-level devices) during NIV has
many theoretical advantages. Other than flushing dead space CO2 and preventing
rebreathing, EPAP can, in some obstructive patients, reduce dynamic hyperinfla-
tion by offsetting intrinsic PEEP [40], thereby reducing inspiratory work required
to trigger assisted inspiration. Moreover, an optimal PEEP level can preserve the
airway patency in patients with unstable upper airway during sleep. Additional
advantages are alveolar recruitment, which increases functional residual capacity
and decreases the tendency to microatelectasis. In the three latter situations,
higher levels of EPAP (>6 cm) may be needed [41]. Unnecessary increases in
EPAP levels should be avoided because inspiratory pressure must be increased in
parallel if inspiratory assistance is to be maintained, which can lead to intolerance
and favor leaks. As a result and regarding the ventilator category (ICU or home
ventilator), the PEEP setting may interfere with either pressure support or IPAP
levels. In fact, ICU ventilators propose PEEP and pressure support settings, how-
ever, PEEP and IPAP settings are usually associated with home ventilators. Thus,
PEEP setting increases IPAP level on ICU ventilators, and PEEP setting decreases
pressure support level on home ventilators. Moreover, high EPAP levels may, in
some cases, increase work of breathing if lung volume increases to a point where
EPAP induces overdistension and increases elastic impedance [42]. A further con-
cern is that the application of a high level of EPAP can result in hemodynamic
impairment.
Leaks, if significant, may make it impossible to maintain the set EPAP level. If
the device uses a pressure-based inspiratory trigger, this may lead to autocycling
because the EPAP levels fall below the trigger threshold.
Measures aimed at improving patient-ventilator synchrony under NIV are
detailed in Table 7.2.

7.4 Modes of Ventilation

When NIV was introduced, there were a limited number of modalities and types
of ventilators with only a few possible settings. We now have more than 30 brands
offering numerous options for settings [43]. Moreover, ventilators are not submit-
ted to stringent medical regulations. This leaves manufacturers free to give differ-
ent names to the same ventilator modalities and settings and even to “create” new
modalities that correspond frequently only to small modifications of a known
class. This explains the wide variety of existing terminology describing NIV
modalities.
Theoretically, NIV can be delivered using all the modalities used in invasive
ventilation. In practice, this is not the case, because the circumstances of ventilation
and target population are different but also because available equipment is often
limited. Because most ventilators used for NIV deliver either volume- or pressure-
targeted modes, and the place of other anecdotally proposed modes for some NIV
devices, such as synchronized intermittent mandatory ventilation (SIMV),
70 C. Rabec and D. Rodenstein

Table 7.2 Measures aiming to improve patient-ventilator synchrony under NIV

Component of ventilatory cycle Measure
Inspiratory trigger Avoid excessive inspiratory pressure or volume
Control unintentional leaks
Use device with short response time (ideally <100 ms)
Set trigger (if adjustable) sensitive enough to allow easy
triggering without auto-triggering, even in the presence
of leaks
Reduce additional resistance
Avoid dynamic hyperinflation
Use respiratory backup rate in patients with muscular
weakness
Use flow-triggered devices (or, better yet, a device with
“flow waveform method of triggering”)
Set EPAP level to counteract intrinsic PEEP (avoiding high
EPAP levels)
Pressurization Control unintentional leaks
Use bi-level ventilators offering an adjustable rise time
Set “tailored” rise time (faster slope while avoiding
excessive peak flow)
Maintain targeted pressure/ Control unintentional leaks
volume Avoid excessive inspiratory pressure or volume
Use devices with acceptable capabilities of leak
compensation
Cycling from I to E Control unintentional leaks
Reduce IPAP level
Tailor flow threshold
Set Timax (if available)
Avoid high backup RR (in particular in obstructive patients)
Use adjustable expiratory triggers or “flow waveform
method” of triggering
Sustaining EPAP level Control unintentional leaks
Avoid high EPAP levels

proportional assisted ventilation (PAV) or other “hybrid” modalities, is not yet clear,
this chapter focuses only on the former two modes.

7.4.1 Volume-Targeted Mode

In the volume-targeted mode (VTM), also called the flow-limited mode, the ventila-
tor delivers a fixed volume during a given time and with whatever pressure is neces-
sary to achieve this. Pressure in the airways (Paw) results from the interaction
between ventilatory settings, compliance and resistance of the respiratory system,
and spontaneous inspiratory efforts (Fig. 7.2b). It should be emphasized that any
inspiratory effort will not lead to changes in delivered volumes or flows but will
only result in a decrease in Paw.
7 Ventilatory Modes and Settings During Noninvasive Ventilation 71

Because each breath is delivered with the same predetermined flow time pro-
file and the area under the flow time curve defines volume, the advantage of this
mode is the strict delivery, in the absence of leaks, of the preset volume, what-
ever the values of C and R. A major disadvantage is, precisely, that delivery of
this fixed ventilatory assistance does not allow taking into account the patient’s
varying requirements. Another inconvenience is that, if there is a leak, there will
be no increase in flow rate to compensate and the generated pressure will be
lower, so that the effectively delivered volume will be reduced proportionally.
Ventilators that deliver VTM use a simple or double circuit with an integrated
expiratory valve. Nevertheless, a new ventilator (Trilogy, Philips, Koninklijken
Netherlands) incorporates a volume mode using a simple circuit with intentional
leak. To ensure tidal volume, this device includes a complex algorithm to compen-
sate for total leaks. Most older ventilators delivering this mode deliver volumes via
a piston or bellows, however, newer devices are blower driven and capable of pro-
viding internal PEEP adjustment.

7.4.2 Pressure-Targeted Mode

In the pressure-targeted mode (PTM), also called the pressure-limited mode, the
ventilator is set to deliver airflow by generating a predefined positive pressure in
the airways for a given time. Therefore, airflow is adjusted so as to establish and
maintain a constant Paw according to the preset pressure. Constant analysis of
the flow rate and airway pressure determines the flow variations necessary to
maintain a flat or “square wave” pressure. Flow is brisk at the beginning of
inspiration when the gradient between the circuit pressure and pressure target is
large (Fig. 7.2c). As this gradient narrows, flow decelerates until driving flow no
longer exists and flow ceases. Thus, for a given patient, the volume delivered is
not fixed and will depend on the interaction between the preset pressure, patient
inspiratory effort, the physical characteristics of the respiratory system (R and
C), and inspiratory time. PTM ventilators can use circuits with or without an
expiratory valve. An important advantage of PTM is the ability to compensate
for mild to moderate leaks. Simple-circuit PTM ventilators without an expira-
tory valve (called bi-level ventilators) are used the most for NIV. These devices
are provided with a calibrated leak and cycle between IPAP and EPAP. The
mathematical difference between both pressures corresponds to a pressure sup-
port in S mode or a pressure control in T mode. With these devices, the patient’s
effort determines flow and, when switching to EPAP, the device delivers a lower
positive pressure that splints and maintains a positive alveolar pressure.
Therefore, IPAP and EPAP level can be independently adjusted both to augment
alveolar ventilation and maintain upper airway patency during sleep. In S mode
(and in ST mode above backup RR), the patient can control inspiratory and
expiratory time, inspiratory flow, tidal volume, and respiratory rate, with th the
ventilator providing only a preset pressure. Therefore, this mode is comfortable
and provides a suitable patient ventilator synchrony.
72 C. Rabec and D. Rodenstein

7.4.3 NIV: Volume or Pressure Targeted?

Most of the initial studies concerning NIV used VTM ventilators [1, 44]. However,
PTM ventilators were increasingly prescribed and surpassed VTM ventilators at the
end of the 1990s. Although studies published showed no significant differences in
terms of clinical efficacy or arterial blood gas results [45, 46], a European survey
showed that more than 75 % of home-ventilated patients use PTM ventilators and
that, in fact, VTM indications were restricted to patients with neuromuscular dis-
ease [47]. There are several technological and financial reasons for this trend.
Ventilators providing PTM, in particular those of the bi-level type, are smaller, qui-
eter, lighter, more compact, cheaper, and easier to adjust. Moreover, PTM provides
better synchronization because this mode (and, in particular, PSV) was primarily
designed to facilitate the patient’s effort to breathe and flow contour and volume can
be varied on a breath-by-breath basis. In addition, as a consequence of the deceler-
ated flow rate, PTM can provide the same delivered tidal volumes by generating
lower mean and peak airway pressures [48, 49], allowing less mask tightness and
reducing the likelihood of leaks and side effects. An additional benefit of PTM is a
better compensation for mild-to-moderate unintentional leaks because the capabili-
ties of these devices to increase inspiratory flow to compensate for a leak-induced
pressure drop [50].
A characteristic of NIV is that the magnitude of leaks changes continuously with
movement, posture, and sleep stages changes and with the amount of pressure,
which may provide a more stable ventilatory support. In fact, some of the modern
home PTM devices can achieve peak inspiratory flow rates up to 180 l·min–1. A
further advantage of small, portable PTV ventilators is the absence of unnecessary
alarms, which controls costs and maximizes portability. Finally, a further advantage
of PTM concerns the situations in which O2 must be added. As most of the available
portable ventilators do not have an O2 blender, supplemental O2 is provided by an
additional admission in the ventilator tube. When VTM is used, this flow is added
to minute volume delivered to the patient. Therefore, tidal volume needs to be pro-
portionally reduced to impede overventilation. On the contrary, as in PTM, the ven-
tilator targets a preset pressure, the addition of an external flow will not modify tidal
volume and then no additional adjustments are needed.
On the other hand, PTM ventilators are less able to compensate for changes in
compliance and resistance and the blowers powering most bi-level devices have
limited maximal pressure-generation capacities. This may lead to insufficient venti-
lation. Therefore, PTM ventilators are less reliable than piston-driven volume ven-
tilators when higher insufflation pressures are needed. Moreover, during PTM,
delivered tidal volume differs substantially among different pathological entities
and also between ventilators, despite similar settings, even in the absence of leaks.
This is related to differences in inspiratory flow, rates, inspiratory duration, and even
actual pressure delivered [50]. For that, VTM may be preferred in patients with
changing respiratory impedance to ensure a given tidal volume and for some situa-
tions characterized by reduced thoraco-pulmonary compliance. An additional
7 Ventilatory Modes and Settings During Noninvasive Ventilation 73

advantage of VTM is to provide the possibility of air stacking for assisted coughing
and increasing the voice volume during NIV. Finally, VTM has been shown to pro-
duce more complete offloading of respiratory muscles, but at the expense of comfort
[51]. Therefore, as has been suggested, VTM may offer advantages in patients with
some conditions, such obesity hypoventilation, chest wall restriction, and neuro-
muscular disease, who may require high insufflation pressure or in those in whom
adequate control is not achieved with PTM [52, 53]. Also, VTM is suitable in more
dependent patients needing alarms (as VTM ventilators have better alarm capabili-
ties than simple bi-level ventilators) or built-in battery backup systems (because
blower-based technology used by bi-level devices consumes considerably more
energy than piston-powered devices, large internal batteries are needed that counter-
balance the benefits of light weight and compact size).
A comparative analysis of the two modalities and of corresponding flow and
pressure patterns is summarized in Table 7.3.

7.4.4 Volume Targeting Pressure Mode

A limitation of pressure ventilation is that it cannot guarantee a tidal volume

delivered to the patient. Volume targeting is a feature available in some bi-level
ventilators that can allow overweighting of this limitation. In this hybrid mode,
which combines the advantages of the pressure and volume modes, the ventila-
tor estimates the delivered tidal volume and adjusts parameters to achieve a
target tidal volume (Vt). Some of them adjust a target volume intracycle (each
breath starts as a pressure-limited breath and if the set Vt is not reached, the
breath converts to a flow-cycled mode by prolonging the inspiratory time), but
most progressively adjust the pressure support level along several cycles within
a preset range to provide a Vt as close as possible to the target volume set by the
clinician. Whether this feature can improve ventilation effectiveness is not yet
clear; as has been demonstrated, a higher level of pressure support is not neces-
sarily associated with a decrease in diaphragmatic energy expenditure because
wasted efforts were more common [54]. Interestingly, two studies using of this
mode in patients with obesity hypoventilation syndrome (OHS) showed a sig-
nificant improvement in nocturnal and daytime PaCO2 compared with usual bi-
level ventilation, but at the expense of impaired objective quality of sleep [55,
56]. Moreover, there are no differences between the two modes in terms of
health-related quality of life.
There are two possible explanations for these findings. One is that pressure varia-
tions may induce sleep stages changes and/or arousals. But it is also possible that this
altered sleep quality is a consequence of an impairment in patient ventilator syn-
chrony secondary to glottic apneas triggered by increasing inspiratory pressure [21].
Interestingly, one study shows that the respiratory disturbance index was greater
when patients were ventilated with volume-targeted mode, supporting the latter
hypothesis [56].
74 C. Rabec and D. Rodenstein

Table 7.3 Comparison between pressure- and volume-targeted ventilators

Volume targeted Pressure targeted
Type of ventilatory Fixed volume in spite of changing Fixed pressure
assistance delivered resistance and compliance Tidal volume may vary with
changes in C and R
Controlled variable Maintains a constant inspiratory Maintains a constant
preset flow inspiratory preset pressure
Breath-to-breath Not possible. Ventilator delivers a Possible. Flow and volume
adjustments fixed assistance can be varied on a breath-to-
breath basis.
Possibility to guarantee Yes (if no leaks) No
a fixed tidal volume
Peak airway pressure Not limited Limited (useful in patients at
risk of barotraumas or gastric
distension)
Size Tend to be of larger size Smaller
Powered by Piston, compressor, blower Blower
Alarms Wide range of alarms Limited alarms (or none)
Breath stacking Possible Not possible
Peak airway pressure Not limited Limited (useful in patients at
risk of barotraumas or gastric
distension)
Rebreathing Minimal Possible
Leak compensation Poor, leaks may significantly Good, for mild to moderate
reduce delivered volume and leaks
induce hypoventilation
PEEP Internal PEEP generally not Internal PEEP available
available. External PEEP can be
addeda
Digestive insufflation Frequent Infrequent
Comfort Lower Higher
Need to adjust settings Yes No
when oxygen is added
a
More recent blower-driven volume-targeted ventilation may provide internal PEEP

7.5 Combined or Dual Ventilators

Some manufacturers of home ventilators have developed a category of ventilators

that combine some features of bi-level, home VTM, and ICU ventilators. These
high-performance micro blower-driven devices, called intermediate ventilators, can
provide PTM, VTM, and hybrid modes (such as volume targeting) and have been
designed to bridge the gap between bi-level devices, volume-targeted home ventila-
tors, and ICU ventilators. They can guarantee high inspiratory pressures (up to
40 cmH2O), have adjustable pressure rise time and maximum inspiratory time, and
some also have minimal inspiratory time and sophisticated monitoring systems.
7 Ventilatory Modes and Settings During Noninvasive Ventilation 75

Table 7.4 Summary of Ventilatory modes

technical characteristics of
Pressure targeted
NIV ventilators
Volume targeted
Hybrids
Circuit type
Single or double limb with expiratory valve
Single limb with calibrated leak
Triggering modes
Assisted
Controlled
Assisted-controlled
Inspiratory trigger function
Timed
Adjustable
Pressure triggered
Flow triggered
Automatic flow-based triggering “flow waveform”
I to E cycling
Timed based
Flow based
Fixed
Adjustable (% of peak flow)
“Intelligent” algorithms
Rise time
Fixed
Adjustable
PEEP
Internal
External
Options
Batteries
Alarms
Oxygen blender
Monitoring modules

Some of these devices offer the possibility to choose between either a single-limb
circuit with calibrated leak or a single or double limb with expiratory valve and are
able to automatically detect the type of circuit. The role of these hybrid ventilators
has not yet been sufficiently explored. Their attraction is the availability of different
modes in the same ventilator and the possibility to ensure the best tailored settings
for each patient using only one device.
A summary of technical characteristics of NIV ventilators is provided in
Table 7.4.
76 C. Rabec and D. Rodenstein

7.6 Choice of Ventilator

In spite of the increasing sophistication and wide difference in available options

present in commercial home ventilators, there are, to date, no formal recom-
mendations concerning preference of one particular ventilator. Moreover, tech-
nical issues determining the actual quality of devices are neither standardized
nor regulated by guidelines. Both ventilator choice and optimal settings are
poorly defined and selection is left to the perceptions of the clinician and patient.
This underlines the importance of patient-tailored prescription and emphasizes
the need for nocturnal monitoring of NIV efficacy. The choice of NIV ventilator
should depend on both patient condition and device characteristics, including
(1) clinical situation and underlying diagnosis (in particular, the degree of ven-
tilator dependency and mobility); (2) patient comfort; (3) versatility and, if
needed, availability of different ventilatory modes; (4) device performance; (5)
mechanisms of leak compensation; (6) quality and accuracy of monitoring
(asynchronies and unintentional leak detection); and (7) experience of the clini-
cal team. At the same time, as those ventilators can be used regularly and long
term at home, devices should be simple and easy to handle. Therefore, the ergo-
nomics of home ventilators must be taken into account as benefits derived from
good performance can sometimes be outweighed by a confusing user interface.
In a trial evaluating user friendliness of home ventilators frequently used in
clinical practice, Gonzalez et al. [57] tested the capacity of physicians experi-
enced in mechanical ventilation to perform a series of standardized usual tasks.
They showed major differences in accessibility of settings between the different
devices with potentially dangerous delays necessary to accomplish even the
simplest maneuver.
In general, patients eligible for home ventilation are in a stable condition.
Therefore, in contrast to invasive mechanical ventilation or acute NIV, patients
under long-term NIV were not threatened by temporary disruption of ventilation.
Consequently, with the exception of patients with little autonomy, home ventilators
may not need sophisticated technical systems such as external batteries, supplemen-
tal O2, pressure or volume monitoring, or surveillance devices or alarms that are
more of an annoyance than a necessity and must be optional rather than imperative.
Moreover, as NIV is generally used at night, these alarms when activated may dis-
rupt sleep quality.
Finally, mechanisms of leak detection and leak compensation capabilities are
critical issues that dictate ventilator choice because they determine how well a NIV
device performs. Moreover, because knowing the actual Vt is essential to providing
the desired ventilatory support, another important aspect is how the device estimates
Vt. In a system characterized by leaks, measuring effective ventilation is impossi-
ble, thus, Vt can only be estimated from appropriate mathematic algorithms inte-
grating flow and pressure. These algorithms, usually not disclosed by manufacturers,
are crucial in determining the quality of a given ventilator as they determine not
only the ability of the device to guarantee the prescribed ventilatory support but also
because they serve to adjust inspiratory and expiratory triggers. Fortunately, nearly
7 Ventilatory Modes and Settings During Noninvasive Ventilation 77

Table 7.5 The ideal ventilator

User friendly and ergonomic
Portable and quiet
Easy to adjust
Operates in assist and control modes
Pressure targeted (may offer volume-targeted ventilation as an option)
Simple circuit with intentional leak (may offer double circuit with expiratory valve as an
option)
May provide high pressure level (up to 40 cm H2O)
Detects the inspiratory effort as quickly as possible
Sensitive flow-based inspiratory trigger
Not influenced by mild to moderate leaks (preferably of the “flow waveform method” type)
Ending inspiration as close as possible to beginning of patient expiration
Adjustable expiratory trigger
Independent of respiratory impedance
With algorithm compensating for mild to moderate leak
With Timax
Can apply PEEP
Adjustable rise time with possibility of fast pressurization
Basic alarms (may be deactivated)
Low pressure
High pressure
Massive leaks
Power failure
Versatile
Dual voltage
Reliable and robust
Low-cost maintenance
Provides and stores accurate, user-friendly monitoring data
May provide as option
Batteries
Oxygen blender

all newer home ventilators perform as least as well as ICU ventilators and are capa-
ble of meeting high ventilatory demands [52]. Conditions to be met by an “ideal”
ventilator are listed in Table 7.5

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47. Lloyd-Owen SJ, Donaldson GC, Ambrosino N, Escarabill J, Farre R, Fauroux B, Robert D,
Schoenhofer B, Simonds AK, Wedzicha JA. Patterns of home mechanical ventilation use in
Europe: results from the Eurovent survey. Eur Respir J. 2005;25:1025–31.
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Respir Care. 2009;54:85–101.
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50. Mehta S, McCool F, Hill N. Leak compensation in positive pressure ventilators: a lung model
study. Eur Respir J. 2001;17:259–67.
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physiologic effects of noninvasive assist-control and pressure support ventilation in acute
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Respir J. 2002;20:1029–36.
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Software for Home Ventilators and Leak
Compensation: Key Technical 8
and Practical Applications

Patrick Pasquina, Jean-Paul Janssens, Olivier Contal,

and Dan Adler

Contents
8.1 Introduction ..................................................................................................................... 82
8.2 Compliance ..................................................................................................................... 82
8.3 VT and Minute Ventilation ............................................................................................. 83
8.4 Leaks ............................................................................................................................... 85
8.5 Respiratory Rate and Percentage of Respiratory Cycles Triggered by the Patient ......... 85
8.6 Apnea-Hypopnea Index .................................................................................................. 87
Conclusion ............................................................................................................................... 87
References ................................................................................................................................ 88

Abbreviations

%Trigg Percentage of respiratory cycles triggered by the patient

ABG Arterial blood gases
AHI Apnea-hypopnea index
COPD Chronic obstructive pulmonary disease
NIV Noninvasive ventilation
OHS Obesity hypoventilation syndrome

P. Pasquina • J.-P. Janssens, MD (*) • D. Adler, MD

Division of Pulmonary Diseases, Geneva University Hospitals,
4-6 rue Gabrielle-Perret-Gentil, Geneva 1211, Switzerland
e-mail: [email protected]; [email protected]; [email protected]
O. Contal, PhD
University of Health Sciences (HESAV), Lausanne, Switzerland
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 81

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_8
82 P. Pasquina et al.

RR Respiratory rate
VE Minute volume
VT Tidal volume

8.1 Introduction

During the past 20 years, long-term noninvasive ventilation (NIV) has become the
key treatment for chronic hypercapnic respiratory failure. Technical advances, in
particular in bi-level pressure-cycled ventilators, have been tremendous over the
years in terms of pressurization, compensation for leaks, size, noise, and improve-
ment of patient-ventilator synchronization through adjustable inspiratory and expi-
ratory triggers. Many newer bi-level ventilators designed for home care are provided
with built-in software that supplies detailed information about compliance, tidal
volume (VT), minute ventilation (VE), respiratory rate (RR), estimated leaks, respi-
ratory cycles triggered by the patient (%Trigg), and apnea-hypopnea index (AHI)
[1, 2]. This chapter discusses the reliability of data recorded by software for home
ventilators and highlights their clinical utility based on the published evidence.

8.2 Compliance

Data recorded by ventilator software are extremely useful for assessing compliance
and pattern of ventilator use. The pattern of ventilation is an indirect indicator of toler-
ance of NIV and comfort. For example, multiple interruptions during the night after
short periods of NIV or an erratic pattern of use over several days is suggestive of poor
adaptation to NIV and patient discomfort (Fig. 8.1). Conversely, a rapid increase in
NIV use may suggest imminent exacerbation in patients who are not ventilator depen-
dent (Fig. 8.2). A study by Borel et al. [3] assessed whether data retrieved from a NIV
device could be used to predict the risk of exacerbation in patients with chronic
obstructive pulmonary disease (COPD) treated by home NIV. In this selected popula-
tion, some patients increased their adherence to NIV prior to exacerbations (because
NIV alleviates dyspnea), whereas other patients reduced its use (reflecting intolerance
and/or inadequacy of ventilator settings during exacerbations). As reported by our
group, compliance may also be related to the underlying chronic respiratory condi-
tion. For instance, neuromuscular patients, especially those suffering from progres-
sive disease, tend to increase their use of NIV over time compared with patients
treated for obesity hypoventilation syndrome (OHS) [2]. Monitoring of daily use of
NIV may also detect progression of highly dependent patients who need a second
ventilator with an internal battery for security reasons.
A detailed report on compliance is important for deciding whether or not to pur-
sue ventilatory support, discussing alternate patterns of daily use of NIV in case of
poor tolerance during the night (i.e., daytime sessions), and understanding insuffi-
cient impact of NIV on arterial blood gases (ABG) or clinical symptoms.
8 Software for Home Ventilators and Leak Compensation 83

a
10:00
07:00

04:00
01:00
22:00
19:00

16:00

12:00
6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

b
12:00
09:00
06:00
03:00
00:00
21:00
18:00
15:00

12:00
25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 23 14 15

Fig. 8.1 (a) Graphic transcription of daily compliance and pattern of use of a ventilator provided
by ventilator software in a patient who is well adapted to his ventilator, with excellent compliance.
Use of the ventilator during the night is continuous, without interruption, suggesting acceptable
quality of sleep. (b) Graphic transcription of daily compliance and pattern of use of ventilator
provided by ventilator software in a patient who tolerates his treatment poorly, revealing multiple
interruptions during the night, and days without ventilator use (Adapted from Ref. [2])

8.3 VT and Minute Ventilation

Although leaks have traditionally been a problem in volume-cycled NIV, pressure

cycling and advances in blower technology now allow a certain amount of uninten-
tional leakage without affecting pressurization capabilities and efficient delivery of
VT, at least in some ventilators [4]. This is of major importance because uninten-
tional leaks are a clinical reality in unsupervised patients treated by domiciliary NIV.
In single-limb circuits with a vented mask, the built-in flow sensor monitors total
gas flow, that is, the sum of respiratory flow and unintentional and intentional leaks
(Fig. 8.3). Because there is no direct measurement of expiratory flow in a single-limb
84 P. Pasquina et al.

Utilisation

10:00
07:00
04:00
01:00
22:00
19:00
16:00

12:00
20 21 22 23 24 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
m j v s d l m m j v s d l m m j v s d l m m j v s d l m m j v s d l m m j v

août 2014 septembre 2014

Utilisation totale

11.0
9.5
8.0
6.5
5.0
3.5
2.0

0.0
20 21 22 23 24 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
m j v s d l m m j v s d l m m j v s d l m m j v s d l m m j v s d l m m j v

août 2014 septembre 2014

Fig. 8.2 Upper graph: pattern of use; Lower graph: total daily use. Graphic illustration of pattern
of use and total daily use in a COPD patient with poor adaptation to NIV. Note frequent interrup-
tion during treatment, days with no treatment, and daily use <4 h. Six days before admission to the
respiratory ward for acute exacerbations of COPD, the patient complained of shortness of breath
that was alleviated by NIV, as evidenced by a rapid increase in daily use

Fig. 8.3 Flow and leaks

during NIV with a bi-level
pressure support ventilator Patient
(single-tube system and Mask leak flow
nasal mask vented) Mask
flow

Vent flow

Mouth
Total flow leak
from
Respiratory flow
ventilator

circuit, VT can only be estimated by taking into account changes in flow and unin-
tentional leaks (from the mask or from the mouth), assuming that the intentional leak
is known. For most ventilators, built-in software underestimates VT and this under-
estimation is little affected by leaks. Conversely, higher pressure support increases
underestimation of VT [5, 6]. Sogo et al. [7] developed a bench model presented as
8 Software for Home Ventilators and Leak Compensation 85

more representative of clinical leaks by inducing random dynamic leaks during

inspiratory or expiratory phases. Unlike previous studies, the authors found that the
four ventilators tested significantly overestimated VT (with differences ranging from
18 % ± 7 % to 36 % ± 18 %) suggesting that a portion of the identified leak was erro-
neously considered by the software as volume delivered to the patient. The inaccu-
racy in VT estimation has direct clinical implications: commercial software can
unpredictably either underestimate or overestimate VT. For these reasons, clinicians
should minimize unintentional leaks by adjusting mask fit or changing mask type or
ventilator settings. Once leaks have been corrected, clinicians must remain aware of
differences in estimation of VT between ventilators and not rely only on information
provided by ventilator software to monitor efficacy of NIV.

8.4 Leaks

Unintentional leaks are major contributors to NIV intolerance, patient-ventilator

asynchrony, suboptimal correction of ABGs, and nocturnal hypoventilation.
Estimation of leaks by the ventilator – if reliable – is a useful contribution to NIV
monitoring.
Rabec et al. [8] showed that leaks assessed by built-in software of the VPAPTM
III-ResLinkTM (ResMed, North Ryde, Australia) ventilators were highly correlated
with bench test measurements. These results cannot, however, be extrapolated to all
home bi-level ventilators because bench testing of different commercially available
home ventilators has demonstrated important discrepancies in leak estimation
between devices [5–7]. One important caveat is that devices do not all report estima-
tions of leaks in the same way. For instance, leaks are reported either as an estima-
tion of unintentional leaks or as an estimation of total leaks (i.e., leaks through mask
exhalation valves plus unintentional leaks) (Fig. 8.3). Physicians monitoring patients
on home NIV should therefore be aware of these differences. Manufacturers have
determined an arbitrary threshold for leaks below which pressurization is consid-
ered effective. In case of major leaks, the leak compensation may be insufficient and
impair efficacy of ventilation, as shown in Fig. 8.4 [8]. Conversely, thresholds
reported by manufacturers are not necessarily relevant, inasmuch as recent home
ventilators have a high capacity for leak compensation.

8.5 Respiratory Rate and Percentage of Respiratory Cycles

Triggered by the Patient

Most ventilator softwares provide information about spontaneous RR and %Trigg.

This information must be interpreted with caution according to the clinical scenar-
ios. For instance, a low %Trigg may occur when the patient has a backup RR above
his or her spontaneous RR. In this situation, the patient is assumed to be treated with
a “controlled ventilation mode.” However, in conditions in which inspiratory efforts
are potentially not detected by the ventilator (major leaks, patients with severe
86 P. Pasquina et al.

Fig. 8.4 VPAP-Reslink™ characteristic tracing showing – from top to bottom – respiratory rate,
leaks (unintentional leaks in liters/second), minute ventilation, and SpO2. Important unintentional
leaks (>0.4 l/s) are associated with a prolonged decrease in SpO2 directly measured by the device’s
pulse oximetry module (Adapted from Ref. [8])

neuromuscular disease and low inspiratory muscle strength, intrinsic positive end-
expiratory pressure in severe COPD, upper airway closure), a low %Trigg may in
fact reflect the inability of the ventilator to respond to the patient’s inspiratory
efforts, leading to patient-ventilator asynchrony. Conversely, a high value of RR
above backup rate and a high %Trigg can represent appropriate detection of trigger-
ing efforts in a “spontaneous mode” as well as auto-triggering in case of important
unintentional leaks or clinical conditions with low respiratory drive.
Whether it is preferable to use a high or a low backup rate for home NIV is still
a matter of debate. It has been a long tradition to “capture” the patient with a backup
rate in neuromuscular diseases. In OHS, evidence suggests that using a backup rate
may prevent central and obstructive respiratory events [9]. In COPD, evidence as to
increasing backup rate is scarce: high-intensity NIV with high inspiratory pressures
and a high backup rate improves physiological endpoints [10]; however, a recent
randomized controlled trial demonstrated no advantage of associating a high backup
rate to high pressure support in night-time ventilator adherence or any of the other
measured physiological parameters (including PaCO2) [11]. These data suggest that
it is the high-pressure component of the high-intensity NIV approach that plays the
therapeutic role in the management of hypercapnic respiratory failure, at least in the
COPD population. Using a telemetry approach, Borel et al. [3] recently demon-
strated that daily variations in RR and %Trigg are predictors of acute exacerbations
in patients with COPD. This “proof of concept” study provides a potentially simple
8 Software for Home Ventilators and Leak Compensation 87

predictive approach through telemonitoring, which requires neither the patient’s

active involvement nor additional sensors in their environment.

8.6 Apnea-Hypopnea Index

To our knowledge, the validity and accuracy of AHI provided by home ventilators
has not been thoroughly studied. The lack of standardized definitions for respiratory
events occurring under positive-pressure ventilation and their mode of detection is
problematic. In an observational study of OHS patients under NIV, the correlation
between AHI provided by the ventilator software and AHI measured simultane-
ously by polysomnography was high, with a low bias. An arbitrary threshold value
of 10 for AHI proved to be sensitive and specific for discriminating between patients
appropriately ventilated versus those requiring further adjustment of ventilator set-
tings [12]. This study had, however, a few limitations and should be repeated in
other patient groups with different NIV devices before one can determine whether
it is possible to rely on AHI indices provided by ventilator software.

Conclusion
Home ventilators with built-in software provide substantial information for mon-
itoring home NIV, such as compliance, pattern of ventilator use, leaks, RR,
%Trigg, and AHI. This information may be used to adapt ventilator settings and
can have a direct impact on patient management. However, reliability of data is
not equivalent between all ventilators. The NIV physician therefore should not
completely rely on these data to adapt ventilator settings. Presently, data pro-
vided by ventilator software are a useful adjunct to recommended tools for basic
monitoring of NIV, such as ABG analysis, nocturnal pulse oximetry, nocturnal
capnography, and polygraphy.

Key Points
• A detailed report on compliance is important for deciding whether or not
to pursue ventilatory support, discussing alternate patterns of daily use of
NIV in case of poor tolerance during the night (i.e., daytime sessions), and
understanding insufficient impact of NIV on ABG or clinical symptoms.
• Clinicians monitoring patients on home NIV should be aware of differ-
ences in the estimation of leaks between ventilators. They should aim to
maintain the 95th percentile of leak values at the lowest possible level by
adjusting interface and ventilator settings.
• Home ventilator softwares (see above) does not provide accurate and reli-
able values of VT and VE. Discrepancies exist between home ventilators
and are influenced by leaks. Clinicians should thus not rely only on these
data for adjusting ventilator settings.
• RR and %Trigg can help the clinician to better set the backup RR on the
home ventilator.
88 P. Pasquina et al.

References
1. Janssens JP, Borel JC, Pépin JL. Nocturnal monitoring of home non-invasive ventilation: the
contribution of simple tools such as pulse oximetry, capnography, built-in ventilator software
and automatic markers of sleep fragmentation. Thorax. 2011;66:438–45.
2. Pasquina P, Adler D, Farr P, Bourqui P, Bridevaux PO, Janssens JP. What does built-in software
of home ventilators tell us? An observational study of 150 patients on home ventilation.
Respiration. 2012;83:293–9.
3. Borel JC, Pelletier J, Taleux N, Briault A, Arnol N, Pison C, Tamisier R, Timsit JF, Pepin
JL. Parameters recorded by software of non-invasive ventilators predict COPD exacerbation:
a proof-of-concept study. Thorax. 2015;70:284–5.
4. Battisti A, Tassaux D, Janssens JP, Michotte JB, Jaber S, Jolliet P. Performance characteristics
of 10 home mechanical ventilators in pressure-support mode: a comparative bench study.
Chest. 2005;127:1784–92.
5. Contal O, Vignaux L, Combescure C, Pepin JL, Jolliet P, Janssens JP. Monitoring of noninva-
sive ventilation by built-in software of home bilevel ventilators: a bench study. Chest.
2012;141:469–76.
6. Luján M, Sogo A, Pomares X, Monsó E, Sales B, Blanch L. Effect of leak and breathing pat-
tern on the accuracy of tidal volume estimation by commercial home ventilators: a bench
study. Respir Care. 2013;58:770–7.
7. Sogo A, Montanyà J, Monsó E, Blanch L, Pomares X, Lujàn M. Effect of dynamic random
leaks on the monitoring accuracy of home mechanical ventilators: a bench study. BMC Pulm
Med. 2013;13:75.
8. Rabec C, Georges M, Kabeya NK, Baudouin N, Massin F, Reybet-Degat O, Camus P.
Evaluating noninvasive ventilation using a monitoring system coupled to a ventilator: a bench-
to-bedside study. Eur Respir J. 2009;34:902–13.
9. Contal O, Adler D, Borel JC, Espa F, Perrig S, Rodenstein D, Pépin JL, Janssens JP. Impact of
different back up respiratory rates on the efficacy of noninvasive positive pressure ventilation
in obesity hypoventilation syndrome: a randomized trial. Chest. 2013;143:37–46.
10. Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-
invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial.
Thorax. 2010;65:303–8.
11. Murphy P, Brignall K, Moxham J, Polkey M, Davidson C, Hart N. High pressure versus high
intensity noninvasive ventilation in stable hypercapnic chronic obstructive pulmonary disease:
a randomized crossover trial. Int J Chron Obstruct Pulmon Dis. 2012;7:811–8.
12. Georges M, Adler D, Contal O, Espa F, Perrig S, Pépin JL, Janssens JP. Reliability of apnea-
hypopnea index measured by a home bi-level pressure support ventilator versus a polysomno-
graphic assessment. Respir Care. 2015;60(7):1051–6.
Maintenance Protocol for Home
Ventilation Circuits 9
Michel Toussaint and Gregory Reychler

Contents
9.1 Introduction .................................................................................................................... 90
9.1.1 Equipment for Home Mechanical Ventilation ................................................... 90
9.1.2 Dirtiness and Contamination.............................................................................. 90
9.1.3 Maintenance Is Empirically Driven ................................................................... 90
9.1.4 A European Survey on Maintenance.................................................................. 91
9.1.5 Patients Do Not Clean Their Equipment............................................................ 91
9.1.6 Sensitivity to Infections ..................................................................................... 91
9.2 Analysis and Discussion ................................................................................................ 92
9.2.1 Restrictive Disorders .......................................................................................... 92
9.2.2 Obstructive Disorders......................................................................................... 93
References ............................................................................................................................... 95

Abbreviations

CF Cystic fibrosis
COPD Chronic obstructive pulmonary disease
HVC Home ventilation circuits
MRSA Methicillin-resistant Staphylococcus aureus
PPO Potentially pathogenic organism

M. Toussaint, PhD (*)

Centre for Neuromuscular Disease and Centre for Home Mechanical Ventilation
UZ-VUB-Inkendaal, Rehabilitation Hospital Inkendaal, Inkendaalstraat, 1,
Vlezenbeek 1602, Belgium
e-mail: [email protected]
G. Reychler, PhD
Pulmonology Unit and the Department of Physical Medicine and Rehabilitation,
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Avenue Hippocrate 10,
Brussels 1200, Belgium
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 89

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_9
90 M. Toussaint and G. Reychler

9.1 Introduction

Home mechanical ventilation has become a standard of care to effectively treat

chronic respiratory failure, both in patients with restrictive diseases such as neuro-
muscular and thorax cage disorders and in patients with obstructive diseases such as
selected cases of lung and airways disorders. Depending on the group of patients,
home ventilation may improve survival and quality of life in the long term and may
decrease the rate of lower respiratory tract infections [1].

9.1.1 Equipment for Home Mechanical Ventilation

Home mechanical ventilation requires equipment consisting of a generator of pres-

sure (volume- or pressure-cycled ventilator), a circuit with tubing (with or without
expiratory valve), and an interface to deliver air to the patient. In the majority of
patients, a nasal mask is the most appropriate interface for nocturnal use. Total face
masks may be used in the rare cases where nasal masks are useless. Finally, mouth-
pieces are preferentially used in waking patients for daytime noninvasive ventila-
tion. Invasive ventilation via tracheostomy may be required when noninvasive
ventilation is no longer possible.

9.1.2 Dirtiness and Contamination

Contamination of circuits infers the transient presence of bacteria in the circuits

and/or in the airways, whereas colonization infers the multiplication of the germs in
the airways of patients that may lead to chronic respiratory infection. In contrast
with the hospital setting, transmission of infection by cross contamination is rare in
the home setting because patients receiving home mechanical ventilation use their
own equipment and have no direct or indirect contact with other patients. The pos-
sible causes of contamination are inappropriate maintenance or manipulation of the
equipment with contaminated hands. In home use, the question is to what extent
home ventilation circuits (HVC) must be disinfected. Is dirtiness of HVC a risk fac-
tor for HVC contamination and the patient’s self-colonization? What is the best
protocol for cleaning? Is disinfection needed and how often is it recommended? The
aim of this chapter is to answer these questions and to suggest an adequate protocol
for maintenance of HVC.

9.1.3 Maintenance Is Empirically Driven

Although home ventilation is widely used around the world, maintenance of HVC
is empirically driven. Instructions given before discharging patients home are
mostly taken from the recommended guidelines from other areas such as lung func-
tion tests, nebulization techniques, or respiratory monitoring. These instructions are
9 Maintenance Protocol for Home Ventilation Circuits 91

generally based on tradition rather than scientific evidence and vary depending on
the country and center. Instructions are often too elaborate and not specifically
adapted for patients receiving home ventilation. Current instructions often include
the use of a disinfectant solution, vinegar mixed with water or a quaternary ammo-
nium compound, but generally fail to explain how basic maintenance may be
achieved by simple cleaning with soap and hot water or with the dishwasher.

9.1.4 A European Survey on Maintenance

In a European survey including more than 20,000 patients receiving home ventila-
tion (two-thirds of patients with restrictive disorders, one-third with obstructive),
only 60 % of the participating centers provided written instructions on the cleaning
and maintenance of the equipment 2]. There was a significant positive correlation
between the size of the center and the proportion of written instructions (p < 0.001).
On average, only 56 % of the centers had protocols for correct cleaning and main-
tenance of circuits and interfaces. These findings clearly demonstrate that a greater
effort is needed to improve communication to patients regarding adequate rules of
maintenance before home discharge.

9.1.5 Patients Do Not Clean Their Equipment

In one study, two-thirds patients who were given cleaning instructions prior to dis-
charge did not adequately clean their equipment at home [3]. Tubing and masks
were most commonly found as “unacceptably” dirty. It was hypothesized that dirti-
ness of equipment exposes circuits and masks to a higher risk of contamination.
Indeed, the dirtiest circuits were found to be significantly more contaminated than
the cleanest ones [3, 4]. Dirtiness and contamination could potentially expose
patients to a higher risk of airway colonization, which in turn could cause respira-
tory infections. However, this relationship has not yet been demonstrated with
evidence.

9.1.6 Sensitivity to Infections

Clearly, regular cleaning appears to be the most important instruction that needs to
be followed by all patients for the maintenance of HVC. As previously seen, how-
ever, there needs to be a considerable effort to target and institute this basic effective
cleaning. By contrast with cleaning rules, the instructions for post-cleaning disin-
fection depend upon the relative sensitivity of patients to respiratory tract infections
and the related risks for bacterial colonization of the airways. Two groups of patients
need to be considered here: restrictive and obstructive disease patients. Clearly, both
groups are not equally sensitive to infections and, as a consequence, should not
require a similarly elaborate disinfection level.
92 M. Toussaint and G. Reychler

9.2 Analysis and Discussion

9.2.1 Restrictive Disorders

By contrast with patients affected by obstructive respiratory diseases, patients

affected by restrictive respiratory diseases or hypoventilation syndrome are a priori
at low risk for bacterial colonization of airways.
In an uncontrolled study with stable patients receiving written and verbal infor-
mation on maintenance of HVC (the recommendation was for daily cleaning with
soap and water), a Spanish group questioned patients regarding their cleaning habits
[3]. They conducted both visual inspection of HVC and sampling of masks (con-
tamination) plus nostrils (colonization) in each patient. As a result, the frequency of
cleaning was found as follows: 47 % cleaned their HVC once a week, 23 % cleaned
once a month, 15 % cleaned sporadically, and 15 % never cleaned their equipment.
In total, 67 % of HVC were deemed as very dirty and a positive relationship between
circuit contamination and nostril colonization was highlighted. Bacterial coloniza-
tion was more important in those patients where HVC were dirtier. The authors
could not conclude whether colonization preceded or followed contamination.
However, they suggested that adequate cleaning decisively decreased the rate of
contamination. However, these authors did not provide a protocol for adequate
maintenance of HVC.
In another study, visual and bacterial inspection of HVC was assessed before and
after cleaning in a first experiment [4]. In a second experiment, the authors ran-
domly compared cleaning either with a household dishwasher or low-level disinfec-
tion with an ammonium-chlorhexidine complex. Their findings were in agreement
with the findings of Rodriguez et al. [3]. Prior to cleaning, circuits were found to be
dirty in 69 % of the cases. HVC were dirtier in invasive ventilation. There was a
significant positive correlation between the level of visual dirtiness and bacterio-
logic contamination of HVC (p = 0.56; p < 0.001). Bacteriologic contamination
reached 22 % of noninvasive HVC with little presence of fungi. Nevertheless, by
contrast with invasive HVC, contamination of noninvasive HVC did not include
potentially pathogenic organisms (PPO) such as Serratia marcescens, methicillin-
resistant Staphylococcus aureus (MRSA), or Pseudomonas aeruginosa. In invasive
HVC, contamination affected 81 % of HVC and included the important presence of
fungi; 19 % of HVC were PPO including S. marcescens in two cases, and MRSA in
one case, but no P. aeruginosa contaminated HVC in this group. In the second
experiment of this study, cleaning in the dishwasher was shown to be superior to the
chemical compounds for both cleaning and disinfecting HVC. In addition, Gram-
negative bacteria and fungi survived in the chemical complex but not in the
dishwasher.
In accordance with the findings of Ebner et al. [5], we suggest using either a
dishwasher at 65 °C or basic soap and hot water as the best means of cleaning HVC
used by restrictive patients (Table 9.1). Nevertheless, a disinfectant agent may be
recommended (1) in the very dirty HVC, (2) in circuits from invasive ventilation,
and (3) in HVC from patients known for their high sensitivity to respiratory
9 Maintenance Protocol for Home Ventilation Circuits 93

Table 9.1 Maintenance protocol for home mechanical ventilation circuits

Dirty circuits of home mechanical ventilation

Cleaning:
- 65° dishwasher or
- Brush, detergent and hot water

Rinsing
drying

Restrictive patient Diagnosis ? Obstructive patient

Very dirty circuits

or
invasive ventilation?

Yes
No

Disinfection:
- Hypochlorite solution (20
minutes of soaking in a
No disinfection
concentration of 0.5 %)
- High temperature
disinfection (>75º c)

Regular control :
Sporadic control : - Cleaning
- Cleaning - Bacteriologic sampling
in case of doubt

infections, such as obstructive patients. Effective cleaning must always precede any
disinfection. It is important to be sure that a thermo-stable HVC is used before
cleaning or disinfecting at temperatures >60 °C. Effective disinfection is described
below.

9.2.2 Obstructive Disorders

The situation regarding hygiene of HVC is slightly different in obstructive respira-

tory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease
(COPD) compared with restrictive respiratory diseases. The major reason for this
94 M. Toussaint and G. Reychler

difference is a higher sensitivity to bacterial colonization of the airways in these

patient populations. The rate of airway colonization often correlates with the sever-
ity and/or speed of obstructive disease progression. In addition, there is evidence
that the need for noninvasive ventilation becomes more frequent after airway colo-
nization in these patients.
Ventilator-associated pneumonia is well documented. In intensive care units, the
use of mechanical ventilation is an important risk factor for the development of
nosocomial pneumonia. Moreover, current risk is greater with the use of invasive
mechanical ventilation compared with noninvasive ventilation. Unfortunately, the
relationship between the use of noninvasive ventilation and an increased risk for
nosocomial pneumonia is not demonstrated.
The greater number of manipulations and the presence of an endotracheal tube
associated with invasive ventilation contribute to HVC contamination. It can be
hypothesized that manipulations related to noninvasive ventilation also represent a
potential risk for contamination. This implies a rigorous implementation of classical
nonspecific rules of hygiene, including hand washing. Nevertheless, the ventilator, the
circuit, and the interface do not represent major risk factors for contamination and
colonization, but monitoring potential bacterial contamination of devices and paying
attention to the basic rules of hygiene probably remain important challenges.
There is little published research to support the relationship between hygiene and
noninvasive ventilation devices in obstructive diseases. In a small study on cystic
fibrosis patients (particularly at risk of cross contamination), no evidence was found
of pathogenic microbial contamination of NIV devices [6]. However, we can extrapo-
late findings from therapies such as respiratory physiotherapy devices to patients with
obstructive disorders receiving long-term noninvasive ventilation. Indeed, the mate-
rial involved in noninvasive ventilation is part of the semi-critical devices that are in
contact with mucus membranes as defined by the Centers for Disease Control and
Prevention. Fortunately, recommendations on hygiene of these devices are available.
In patients affected by CF and other chronic respiratory diseases, nebulizers are
considered potential vectors of bacterial infection of airways. Notably, studies
showed that nebulizers of CF patients are frequently contaminated [7]. Similarly, it
was suggested that nebulizers can lead to nosocomial disease in COPD patients [8].
The bacterial contamination of HVC is related to the duration of its use and the
airway colonization of the patient.
Based on this evidence, several recommendations were proposed and could be
applied to the pieces of the circuit involved in noninvasive ventilation in obstructive
diseases. As shown in Table 9.1, regular cleaning of HVC and masks is mandatory, at
least as a basic hygiene procedure and, more specifically, to eliminate the biofilm
deposited on the surfaces that further decreases the efficacy of disinfectants [9]. The
necessary frequency of cleaning is still being debated. Based on the results of studies
on nebulizers, a daily cleaning could theoretically be the recommended timing.
However, a less regular cleaning, for instance, once a week, could be acceptable in the
practice. The possibility of using tap water for cleaning must be taken into account
whether HVC are contaminated by S. marcescens and Stenotrophomonas maltophila.
9 Maintenance Protocol for Home Ventilation Circuits 95

When considering disinfection, different methods may be proposed. The choice

of the optimal method largely depends on the material chosen to disinfect. A ther-
mal disinfection (e.g., sterilizer, boiling water) may be not suitable for some non-
thermo-stable pieces of HVC even though its efficacy is evident with all germs.
There are a number of chemical methods and each one has its own characteristics.
The duration of soaking and the concentration of the chemical depend on the par-
ticular substance used, and the guidelines for each must be followed carefully.
Acetic acid is not recommended due to its inefficacy on gram-positive and gram-
negative bacteria [10, 11]. In contrast with acid acetic, hypochlorite solution (20 min
of soaking in a concentration of 0.5 %) may be the best alternative of those readily
available chemical solutions.
After disinfection, rinsing and drying is the last part of the cleaning and disinfec-
tion sequence. Drying seems important as a higher contamination rate was related
to non-dried nebulizers in CF patients. Because there is a paucity of specific data
related to noninvasive ventilation, precise recommendations can not be made.
However, it could justify more studies on this topic. Finally, it appears critically
important to investigate the relative effectiveness of the different established proto-
cols for cleaning and disinfecting of HVC to maintain their integrity.

Key Major Recommendations

• Cleaning the ventilator, circuits, and interfaces is required 2–4 times per
month in all patients receiving mechanical ventilation at home.
• Written instructions on how to clean the equipment for home ventilation
are useful. Regular assessment of whether or not circuits and interfaces are
correctly cleaned and maintained is mandatory.
• In patients with restrictive disorders, cleaning in the dishwasher is effective
and sufficient for thermo-stable circuits and interfaces. Cleaning with soap
and hot water may be sufficient for all pieces. Disinfection is not mandatory.
• In patients with obstructive disorders, cleaning must be more frequent than
for restrictive disorders. Cleaning always precedes disinfection. After
cleaning, rinsing and drying are important. An effective weekly disinfec-
tion may be achieved by using a hypochlorite solution (20 min of soaking
in a concentration of 0.5 %).
• The expiratory valve must be washed specifically, with care taken so that
the balloon is not held underwater.

References
1. Dohna-Schwake C, Podiewski P, Voit T, et al. Non-invasive ventilation reduces respiratory
tract infections in children with neuromuscular disorders. Pediatr Pulmonol. 2008;43:67–71.
2. Farre R, Loyd-Owen SJ, Ambrosino N, et al. Quality control of equipment in home mechani-
cal ventilation: a European survey. Eur Respir J. 2005;26:86–94.
96 M. Toussaint and G. Reychler

3. Rodriguez Gonzalez-Moro JM, Andrade Vivero G, de Miguel Diez J, et al. Bacterial coloniza-
tion and home mechanical ventilation: prevalence and risk factors. Arch Bronconeumol.
2004;40:392–6.
4. Toussaint M, Steens M, Van Zeebroeck A, et al. Is disinfection of mechanical ventilation
needed at home? Int J Hyg Environ Health. 2006;209:183–90.
5. Ebner W, Eitel A, Scherrer M, et al. Can household dishwashers be used to disinfect medical
equipment? J Hosp Infect. 2000;45:155–9.
6. Mutagi A, Nash EF, Cameron S, Abbott G, Agostini P, Whitehouse JL, Honeybourne D,
Boxall E. Microbial contamination of non-invasive ventilation devices used by adults with
cystic fibrosis. J Hosp Infect. 2012;81(2):104–8.
7. Vassal S, Taamma R, Marty N, et al. Microbiologic contamination study of nebulizers after
aerosol therapy in patients with cystic fibrosis. Am J Infect Control. 2000;28:347–51.
8. Mastro TD, Fields BS, Breiman RF, et al. Nosocomial Legionnaires' disease and use of medi-
cation nebulizers. J Infect Dis. 1991;163:667–71.
9. Merritt K, Hitchins VM, Brown SA, et al. Safety and cleaning of medical materials and
devices. J Biomed Mater Res. 2000;53:131–6.
10. Karapinar M, Gonul SA. Effects of sodium bicarbonate, vinegar, acetic and citric acids on
growth and survival of Yersinia enterocolitica. Int J Food Microbiol. 1992;16:343–7.
11. Reychler G, Aarab K, Van Ossel C, et al. In vitro evaluation of efficacy of 5 methods of disin-
fection on mouthpieces and facemasks contaminated by strains of cystic fibrosis patients. J
Cyst Fibros. 2005;4:183–7.
Noninvasive Open Ventilation (NIOV™)
Therapy: Clinical Implications 10
Heidi A. Pelchat, Patrick L. Williams, and Alex H. Gifford

Contents
10.1 Introduction ................................................................................................................. 98
10.2 Overview of NIOV Technology .................................................................................. 98
10.3 Testing of the NIOV System Using a Lung Simulator ............................................... 100
10.4 Clinical Efficacy of the NIOV System ........................................................................ 101
10.5 Institutional Experience with NIOV at Dartmouth-Hitchcock Medical Center ......... 102
Conclusion ............................................................................................................................. 103
References .............................................................................................................................. 103

Abbreviations

COPD Chronic obstructive pulmonary disease

CF Cystic fibrosis
EMG Electromyography
EPAP Expiratory positive airway pressure

H.A. Pelchat, BS, RRT

Department of Medicine, Section of Cardiology, Cardiac and Pulmonary Rehabilitation,
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
P.L. Williams, BA, RRT
Department of Respiratory Care, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
A.H. Gifford, MD (*)
Department of Medicine, Section of Pulmonary and Critical Care Medicine, Dartmouth-
Hitchcock Medical Center, Lebanon, NH, USA
Section of Pulmonary and Critical Care Medicine, 5C, New Hampshire Cystic Fibrosis
Center, Dartmouth-Hitchcock Medical Center, One Medical Center Drive,
Lebanon, NH, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 97

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_10
98 H.A. Pelchat et al.

FEV1 Forced expiratory volume in one second

FiO2 Fraction of inspired oxygen
HFT High-flow therapy
ILD Interstitial lung disease
IPAP Inspiratory positive airway pressure
LPM Liters per minute
NIPPV Noninvasive positive pressure ventilation
PEEP Positive end-expiratory pressure
PTP Peak-to-peak
VT Tidal volume
VE Minute ventilation
SpO2 Oxyhemoglobin saturation

10.1 Introduction

The convention of using trademark only at first mention of product is fine. is a novel
portable system for delivering inspiratory positive pressure and supplemental oxy-
gen through a specially designed nasal pillows interface during ambulation. The
NIOV system augments tidal volume (VT), minute ventilation (VE), and oxyhemo-
globin saturation (SpO2), which in total has beneficial effects on respiratory mechan-
ics, exercise capacity, and symptom burden in chronic obstructive pulmonary
disease (COPD), as discussed later in this chapter. Patients and their respiratory care
providers can adjust a number of settings on the device to optimize its performance.
In this chapter, we describe how NIOV functions, review several studies of its clini-
cal utility, and share some of our experiences with the device in our pulmonary
rehabilitation and cystic fibrosis programs.

10.2 Overview of NIOV Technology

The NIOV system consists of a unique nasal pillows interface and a sophisticated
microprocessor-controlled ventilator that can be programmed by the clinician to
deliver inspiratory pressure in synchrony with the patient’s breathing pattern
(Fig. 10.1). It requires a compressed gas source for operation. The amount of pres-
sure and volume delivered are determined by the patient’s inspiratory effort and
respiratory system mechanics. The microprocessor housing is small, lightweight,
and designed to be worn at the waist or mounted on a pole. Buttons on the front of
the device allow the patient to choose settings that are appropriate for recumbent
and sitting positions and ambulation. A large liquid-crystal touch screen display
(LCD) depicts the target inspiratory volume, activity setting, current respiratory
rate, oxygen flow rate in liters per minute (LPM), and remaining battery life. A
speaker for audible alarm output is located in the face of the housing.
Sensing ports located in the nasal pillows interface (Fig. 10.2) detect spontane-
ous respirations. The system can provide a mean fraction of inspired oxygen (FiO2)
10 Noninvasive Open Ventilation (NIOV™) Therapy: Clinical Implications 99

Fig. 10.1 NIOV™

apparatus (compressed
oxygen source not shown)

NIOV provides
positive pressure
NIOV delivers O2

NIOV entrains AIR

Entrainment
ports Sense ports

Fig. 10.2 The NIOV™ nasal pillows interface blends oxygen with air entrained through ports in
the side of the interface, an application of the Venturi effect. Centrally located sense ports detect
patient inspiratory effort, triggering the device to delivery positive pressure through nasal pillows
that conform to the patient’s nares
100 H.A. Pelchat et al.

of 0.43 [1] by entraining air through two ports and blending it with supplemental
oxygen (Venturi principle). Two molded nasal pillows form a seal at the nares to
ensure positive pressure delivery. The maximum attainable inspiratory pressure and
VT are 18 cm H2O and 1150 ml, respectively [1]. Other technical specifications of
the device are listed in Table 10.1.

10.3 Testing of the NIOV System Using a Lung Simulator

Several abstracts and white papers have described the performance of the NIOV
system using a lung simulator. McCoy and Diesem [2] equipped a breathing simula-
tor (Hans Rudolph, Series 1101, Shawnee, KS, USA) with a simulated nose to

Table 10.1 Technical specifications of the NIOV™ system

Physical
Weight 1.0 lb (0.5 kg)
Height 3.1 in (7.9 cm)
Width 7.5 in (19.1 cm)
Depth 1.3 in (3.2 cm)
Mounting Belt clip or pole mount
Features
Delivered gas Oxygen with entrained air
Flow delivery Closed-loop proportional valve
Breath sensing Proximal in patient interface
Rate (breaths/min) 2–40, based on patient’s spontaneous
breathing
Internal battery duration 4 h with nominal use
Internal battery charge time 90 % recharged within 2.5 h
Alarm types Audible and vibrating
User interfaces Push buttons, LEDs, color LCD touch screen
Patient accessible settings
Power On, off
Volume delivery settings Low, medium, high
Trigger sensitivity 0–9 (−0.01 to −0.34 cm H2O)
Alarm loudness 1–5
Vibrating alarm On, off
LCD brightness 1–5
Clinician programmable settings
Breath timeout 12 breaths/min or 3 LPM
Volume delivery 50–250 ml in 10 ml increments
Inspiratory delivery time 10–40 % of breath period
Clinician programmable alarms
Breath timeout period 20 or 60 s
High breath rate 5–120 breaths/min
Low breath rate 0–119 breaths/min
10 Noninvasive Open Ventilation (NIOV™) Therapy: Clinical Implications 101

accommodate nasal cannulae. They compared NIOV to high-flow therapy (HFT) on

the basis of delivered VT and peak-to-peak (PTP) pressure differentials over a range
of values for resistance (5, 10, and 20 cm H2O/l/s) and compliance (70, 100, and
120 ml/cm H2O). For all combinations of these parameters, the lung simulator was
set to breathe at a rate of 12 breaths per minute with VT of 500 ml and an inspiratory-
to-expiratory time ratio of 1:2. The NIOV was set to 250 ml and 21 % delivery time,
defined as the time during which the selected target volume is delivered as a fraction
of the patient’s spontaneous breath period. HFT was modeled using the AIRVO™
system (Fisher & Paykel Healthcare, Auckland, New Zealand) set to the maximum
45 LPM setting. VT and PTP pressure differentials were uniformly higher for NIOV
than HFT. Importantly, NIOV but not HFT provided inspiratory pressure support,
while HFT but not NIOV provided positive end-expiratory pressure (PEEP). This
finding highlights different capabilities of the two systems.
In a parallel study using the same lung model and resistance and compliance
values, McCoy and Diesem [3] compared NIOV to the LTV® 1100 (CareFusion,
San Diego, CA, USA) and VPAP Tx™ (ResMed Corporation, San Diego, CA,
USA) on the basis of inspiratory positive airway pressure (IPAP) and expiratory
positive airway pressure (EPAP). The NIOV and LTV 1100 devices intrinsically had
0 cm H2O of EPAP, and the VPAP Tx was set to its minimum EPAP of 3 cm H2O for
testing. Observed mean VT and pressure support values were statistically similar
among all three devices, suggesting that NIOV could generate comparable ventila-
tory support.
Blakeman and Branson [4] also tested the NIOV apparatus using a bench model
of human ventilation. These investigators devised a nasopharynx and trachea in
which the resistance to airflow and anatomic dead space were comparable to the
human respiratory tract. They employed an ASL 5000 computerized test lung
(IngMar Medical, Pittsburgh, PA, USA) to mimic the physiology of a normal human,
a human with COPD, and a human with interstitial lung disease (ILD). The NIOV
was programmed for VT of 100, 150, 200, and 250 ml. The device was observed to
deliver augmented simulated patient VT ranging between 362 and 828 ml, increasing
the spontaneous VT by up to 459 ml depending on ventilator settings and type of lung
disease the ASL 5000 was supposed to approximate. The delivered FiO2 was 0.36–
0.45, again depending on conditions. Auto-triggering was not observed during any
aspect of the study. Using available data, the researchers were able to quantify VT
under normal, COPD, and ILD conditions by a linear regression equation. This
important study proved that the NIOV system could theoretically augment VT and
supplement FiO2 in patients with obstructive and restrictive physiology.

10.4 Clinical Efficacy of the NIOV System

NIOV has mostly been studied in patients with COPD. Porszasz et al. [5] have pub-
lished the most detailed assessment to date of how the device influences dyspnea,
respiratory muscle activation, and pulmonary gas exchange efficiency in COPD
patients during constant work rate exercise on the cycle ergometer. The 15 patients
were all men with mean percent-predicted forced expiratory volume in 1 s
102 H.A. Pelchat et al.

(FEV1) = 32.2 ± 12.0 % and exercise-induced oxyhemoglobin desaturation (mean

SpO2 = 86.5 ± 2.9 %) on FiO2 = 0.21. The mean age of study participants was
65.5 ± 9.1 years, and 53 % of them had class IV disease according to the Global
Initiative for Chronic Obstructive Lung Disease (GOLD) classification system. For
each patient, peak work rate was identified by incremental cycle ergometry, and
NIOV testing was performed at 80 % of this value.
There were four permutations for exercise testing: unencumbered, NIOV plus
air, NIOV plus oxygen, and unencumbered plus oxygen through a nasal cannula.
Exercise tolerance was reduced during incremental testing, and patients had ventila-
tory limitation to exercise by multiple lines of evidence. The authors [5] found that
endurance time was significantly longer and Borg dyspnea scores were significantly
lower when patients exercised with NIOV plus oxygen compared with all other
permutations. Isotime SpO2 was significantly higher for NIOV plus oxygen, and
electromyography (EMG) of respiratory muscles revealed mechanical unloading
under these conditions. Moreover, a positive correlation (r = 0.42, p = 0.0053) was
identified between isotime Borg dyspnea score reduction and isotime EMG signal
reduction. In total, this important study provides a sophisticated mechanistic under-
standing of the benefits of NIOV to COPD patients.

10.5 Institutional Experience with NIOV at Dartmouth-

Hitchcock Medical Center

We have utilized NIOV in our outpatient pulmonary rehabilitation program for indi-
viduals who require more than 4 LPM of supplemental oxygen during exercise,
those who are unable to maintain SpO2 ≥90 %, and those who rate their dyspnea
severity as ≥3 points on a Borg scale during exercise. The NIOV device has allowed
our participants with COPD and ILD to increase exercise workload and duration
with decreased dyspnea ratings and improved SpO2 levels. These individuals have
also noted that their portable oxygen tanks were lasting longer because their con-
sumption through the NIOV decreased significantly (i.e., 6–8 LPM continuous flow
vs 3–4 LPM via the NIOV). Interestingly, our patients have observed improved
SpO2 levels on their usual supplemental oxygen flow rate after using the NIOV. We
have had individuals use the NIOV for exercise training only and others who utilize
it as their primary oxygen source during the day. With the increase in VT, individuals
who have significant airway mucus production may note increased mucus clearance
and overall improvement in aeration and SpO2 levels.
Our patients’ responses to NIOV have been quite positive. One patient
reported, “I can breathe without having to work at it!” Most of these individuals
are highly aware of their work of breathing, and the effects of mitigating that
perception have been no less than remarkable. Patients have also noticed that
their skin tone has gone from dusky to pink, while others have commented on
how good they look.
We have also brought the NIOV device to bear on the case of a young woman
with advanced cystic fibrosis (CF) during a hospital stay for treatment of acute pul-
monary exacerbation. She had a percent-predicted FEV1 of 36 %, was active on the
10 Noninvasive Open Ventilation (NIOV™) Therapy: Clinical Implications 103

list for lung transplantation at the time, and required supplemental oxygen by nasal
cannula at a flow rate of 6–8 LPM and nocturnal noninvasive positive pressure ven-
tilation (NIPPV). During a 6-min walk test, we observed a reduction in Borg dys-
pnea score with the introduction of NIOV and reduced work of breathing when she
was at rest. Responding to our inquiry a few weeks later about her NIOV experi-
ence, she stated that the device reduced air hunger during ambulation and the extent
to which she became tachycardic in this setting. She did not sleep well with the
NIOV system and instead used her other NIPPV apparatus. Finally, she observed
shorter daytime longevity of her compressed oxygen tanks with the NIOV system,
but this may have been related to an increased level of physical activity.

Conclusion
NIPPV can clearly improve quality of life and mitigate the distressing symptom
of dyspnea in many patients with chronic respiratory insufficiency, including
those with COPD and progressive neuromuscular dysfunction. Challenges to the
delivery of this important therapy have included unwieldy size and weight of the
apparatus and a lack of technical sophistication of the apparatus sufficient enough
to allow straightforward and customizable use. The NIOV system appears to
have overcome these challenges and, as such, represents an innovative and effec-
tive treatment option. Further study is needed, however, in patients with ILD, CF,
and partially reversible airflow obstruction.

Key Recommendations
• The NIOV system should be considered as a means of supporting ventila-
tion and oxygenation and mitigating dyspnea in patients with COPD.
• Because the NIOV device allows for customization of numerous parame-
ters, the settings should be defined, adjusted, and monitored for efficacy by
specialists in respiratory care.
• Although most of the preclinical and clinical research involving the NIOV
system has focused on obstructive lung disease, the system could reason-
ably be applied to patients with restrictive lung diseases such as ILD.

References
1. Device Technical Specifications: Breathe Technologies, Incorporated, 2013. http://www.
breathetechnologies.com/clinician/NIOV/system
2. McCoy R, Diesem R. Bench comparison of non-invasive open ventilation to high flow therapy
in various test scenarios. COPD8USA. Chicago; 2013.
3. McCoy R, Diesem R. Bench comparison of non-invasive open ventilation to home and bilevel
ventilation in non-invasive conditions. COPD8USA. Chicago; 2013.
4. Blakeman T, Branson R. Evaluation of a volume targeted NIV device: bench evaluation of the
breathe technologies Non-Invasive Open Ventilation system (NIOV). COPD. 2014;11:568–74.
5. Porszasz J, Cao R, Morishige R, et al. Physiologic effects of an ambulatory ventilation system
in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:334–42.
Transnasal Insufflation: A New Approach
in the Treatment of Obstructive Sleep 11
Apnea Syndrome?

Giuseppe Fiorentino, Antonio Pisano,

and Daniela G. Giordano

Contents
11.1 Introduction ................................................................................................................. 106
11.2 Discussion and Analysis ............................................................................................. 106
11.2.1 Mechanisms of OSA ..................................................................................... 106
11.2.2 Effect of TNI ................................................................................................. 107
11.2.3 TNI in Children with OSA ............................................................................ 108
11.2.4 TNI in Adults with OSA................................................................................ 109
11.2.5 TNI in Adults with OSA and Stroke ............................................................. 109
Conclusions ............................................................................................................................ 110
References .............................................................................................................................. 111

Abbreviations

AHI Apnea-hypopnea index

CPAP Continuous positive airway pressure
LV Left ventricle
OSA Obstructive sleep apnea
PEEP Positive end-expiratory pressure
RDI Respiratory disturbance index
REM Rapid eye movement

G. Fiorentino, MD (*)
Division of Respiratory Physiopathology and Rehabilitation, A.O.R.N. “Dei Colli” – Monaldi
Hospital, Naples, Italy
e-mail: [email protected]
A. Pisano, MD • D.G. Giordano, MD
Cardiac Anesthesia and Intensive Care Unit, A.O.R.N. “Dei Colli” – Monaldi Hospital,
Naples, Italy
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 105

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_11
106 G. Fiorentino et al.

SDB Sleep-disordered breathing

TNI Transnasal insufflation
WOB Work of breathing

11.1 Introduction

Obstructive sleep apnea (OSA) is a condition of cyclic or repetitive obstruction of

the upper airway during sleep, with micro-arousals occurring at the end of a respira-
tory event. OSA is thought to affect 2 % of female and 4 % of male adults, whereas
its prevalence is higher than 8 % among men aged 40–59 years [1]. Continuous
positive airway pressure (CPAP), usually applied nasally, is the established treat-
ment for moderate-to-severe OSA. However, although CPAP is an effective treat-
ment for OSA, it is widely acknowledged that significant limitations to its actual use
by patients exist. In fact, adherence to nasal CPAP is substantially low. It has been
shown that only 46 % of patients used nasal CPAP for at least 4 h during 70 % of
the observed nights [1]. Nonadherence to CPAP generally occurs early during the
first week of therapy, usually by the second to fourth day, primarily because of the
mask and head gear required for maintaining positive pressure during sleep [2].
Transnasal insufflation (TNI) has been introduced as an alternative method for
improving respiration during sleep.

11.2 Discussion and Analysis

11.2.1 Mechanisms of OSA

During wakefulness, tonic and phasic output to the respiratory muscles of the upper
airway is similar (and proportional) to that of the thoracic pump: throughout each
breath, the upper airway is stiffened, thus preventing lumen closure during the gen-
eration of a subatmospheric intraluminal pressure. During sleep, however, the uni-
formity of motor output is lost and the airway becomes more compliant and
vulnerable to collapse. If the stiffness of the soft tissues in the narrowest segments
of the passive airway is inadequate to counteract the negative intraluminal pressure
that is generated during inspiration, airway obstruction occurs. As a result, the cen-
tral nervous system adjusts sleep to a lighter level to increase muscle tone and, thus,
allow opening of the airway and resumption of the breathing cycle. In patients with
OSA, there is a reduction in the expansion forces of the pharyngeal dilator muscles,
as in the case of genioglossus muscle dysfunction, and a lack of coordination
between the inspiratory activity of this muscle and respiratory effort. Additional
factors that may contribute to OSA are excessive or elongated tissues of the soft
palate, macroglossia, tonsillar hypertrophy, and a redundant pharyngeal mucosa [3].
The therapeutic mechanism of ventilatory treatment of OSA involves the cre-
ation of a “pneumatic splint” by an effective positive pressure applied to the
11 Transnasal Insufflation for Obstructive Sleep Apnea Syndrome 107

pharynx, which provides immediate relief from obstruction, thus allowing sleep
continuity and preservation of sleep architecture.

11.2.2 Effect of TNI

The use of TNI, consisting of high flow rates of room air or room air/oxygen mix-
tures delivered to the patient via a nasal cannula (Fig. 11.1), has been suggested for
the treatment of respiratory diseases such as OSA and for respiratory failure. These
high flow rates (ranging from 16 to 40 l/min) are tolerable because the air is warmed
and humidified and because nasal cannulas are designed not to create a jet directed
to mucosal surfaces.
Several studies have shown that TNI improves oxygenation, increases end-
inspiratory lung volume, reduces airway resistance, increases functional resid-
ual capacity, and flushes nasopharyngeal dead space (thus reducing CO2
rebreathing) [4].
The nasopharynx facilitates the humidification and warming of inspired gases
through contact with its large surface, but this generates an appreciable resistance to
the gas flow. However, TNI minimizes the inspiratory resistance of the nasopharynx
by providing a nasopharyngeal gas flow that matches or exceeds the patient’s peak
inspiratory flow. The resulting change in resistance translates into a decrease in
resistive work of breathing (WOB) [4].
Parke et al. [5] measured airway pressure during TNI at 30, 40, and 50 l/min in
healthy individuals with both open and closed mouth. They found a positive linear
relationship between the flow imposed and airway pressure. In patients recovering

Fig. 11.1 A patient

treated with transnasal
insufflation (TNI)
108 G. Fiorentino et al.

from cardiac surgery, a mean positive airway pressure of 2.7 cmH2O was measured
with a flow of 35 l/min with the mouth closed. In healthy individuals, TNI generated a
flow-dependent median positive expiratory pressure of 7.4 cmH2O at 60 l/min with the
mouth closed [6]. However, a large interpatient variability was reported, probably due
to differences in air leak around the outer part of the nasal cannula and the wide vari-
ability in the size of the nostrils. A smaller leak may create an increased resistance to
expiration, resulting in higher nasopharyngeal pressure and, therefore, in an increased
positive end-expiratory pressure (PEEP) effect [5]. Although this mechanism is par-
ticularly effective in neonates, it could also be potentially useful in adult patients.
Moreover, by delivering humidified air, TNI may prevent drying of the airway,
thus avoiding the consequent inflammatory response and improving mucociliary
function, and could facilitate the clearance of secretions and reduce the formation of
atelectasis. Finally, conditioning (warming) of the gas mixture administered can
also minimize airway constriction, resulting in a reduction of WOB, which may
help to maintain effective delivery of oxygen to the lungs [4].

11.2.3 TNI in Children with OSA

CPAP is the most effective treatment option for children with OSA who are not
eligible for surgical interventions (adenotonsillectomy is the treatment of choice
when there is adenoid or tonsil hypertrophy), whose parents refuse adenotonsil-
lectomy, or who have residual OSA after surgery. However, as mentioned, adher-
ence to CPAP is relatively low. Accordingly, a large number of children remain
untreated [4].
The use of TNI in children with OSA may offer several advantages. First, the
patient interface is a nasal cannula, which is less bulky than a nasal mask and avoids
facial compression. Accordingly, it might be better tolerated by children during
sleep. Moreover, TNI could represent a therapeutic option even more effective than
CPAP in children who showed a suboptimal response to the latter. McGinley et al.
[7] assessed the effect of TNI (20 l/min of air), compared with CPAP, on upper air-
way obstruction in 12 children, aged 10 ± 1 years, with mild to severe OSA (2–36
events/hour), by measuring the inspiratory duty cycle and the apnea-hypopnea
index (AHI) (namely, the rate of obstructive events per hour of sleep) during both
rapid eye movement (REM) and non-REM sleep. They found that the improve-
ments in AHI with TNI were similar to those with CPAP in most of the children.
These results appear to be better than those previously shown in adult OSA patients
[5]. A possible explanation is that TNI may be generally more effective in increas-
ing pharyngeal pressure in children than in adults because of the relatively larger
size of the nasal cannula as compared with the size of the nostrils. Alternatively, the
slight increase in pharyngeal pressure might increase lung volume to a greater
extent in children than in adults because of higher chest wall and lung compliance,
particularly during REM sleep (when the chest wall musculature is hypotonic).
The improvement in AHI in children receiving TNI suggests that the increases in
inspiratory airflow and tidal volumes provided by this technique may be sufficient
11 Transnasal Insufflation for Obstructive Sleep Apnea Syndrome 109

to prevent hypoxia and/or arousals. If these data are confirmed by larger investiga-
tions, the implications for the management of sleep-disordered breathing in children
could be significant.

11.2.4 TNI in Adults with OSA

TNI has also been used in adult patients with OSA (see Fig. 11.1). McGinley et al. [8]
assessed its efficacy in 11 patients with mild-to-severe obstructive apnea–hypopnea
syndrome. TNI reduced the overall AHI by 63.2 % (from 28 ± 5 to 10 ± 3 per hour,
p < 0.01), and some improvement in the AHI was observed in each subject. In a
larger study, TNI was shown to reduce the respiratory disturbance index (RDI),
namely the mean number of episodes of apnea, hypopnea, and respiratory event-
related arousal per hour of sleep, below a clinically acceptable threshold (10 events/
hour) in approximately one-quarter of the 56 patients who required CPAP. Overall,
RDI decreased by 31 % (from 22.6 ± 15.6 to 17.2 ± 13.2 events/hour, p < 0.01) [3].
Nilius and colleagues [3] also investigated the predictors for treatment responses
with TNI and found that they were independent from the severity of the sleep apnea
disease and the level of prescribed CPAP. Also, anthropometric characteristics did
not predict treatment responses. However, the success rate was markedly increased
in patients who predominantly had hypopneas and in patients with mild upper air-
way obstruction. Conversely, the presence of >10 % central apneas predicted poor
response to TNI. In other words, TNI therapeutic responses probably depend on the
severity of upper airway obstruction but not on its frequency (i.e., the severity of the
OSA disease). It is possible that insufflation of air into the nose, by washing out
the anatomic dead space, leads to a reduction in CO2 rebreathing, thereby contribut-
ing to the occurrence of central apneas.
As highlighted in the aforementioned investigation, the main mechanism by
which TNI reduces the RDI seems to be the increase in pharyngeal pressure that is
associated with a rise in the inspiratory airflow. At a rate of 20 l/min, in fact, TNI
increases nasal pressure by about 2 cmH2O and inspiratory airflow by about
100 ml/s. Because the mean peak inspiratory airflow for hypopneas and flow-limited
breaths ranges from approximately 150 to 200 ml/s, the additional flow provided by
TNI will develop an inspiratory airflow of 250–300 ml/s, a level previously associ-
ated with stabilization of breathing patterns [8].
Finally, the results of the study by Nilius et al. [3] also suggest that response rates
to TNI would be higher in adults with a predominance of REM-sleep-disordered
breathing events, as compared with non-REM sleep associated events.

11.2.5 TNI in Adults with OSA and Stroke

In a 10-year follow-up study on stroke patients, the presence of OSA (with AHI >15
events/hour) was shown to increase the risk of death by 75 %, mostly due to cardiac
complications [9]. In fact, futile inspiratory effort against a closed glottis, as occurs
110 G. Fiorentino et al.

in OSA, leads to the generation of negative intrathoracic pressure and increases

venous return to the right heart. As a result, right ventricle distention and diastolic
leftward shift of the interventricular septum occur. This adversely affects left ven-
tricle (LV) filling and causes reduced stroke volume and delayed LV relaxation.
Haba-Rubio et al. [10] examined both tolerability and efficacy of treatment with
TNI in patients with acute stroke and sleep-disordered breathing (SDB). To ensure
maximum comfort, they used a slightly lower flow rate (18 l/min) compared with
the above-mentioned studies (20 l/min). TNI was shown to be well accepted, and no
significant side effects were reported. Globally, TNI significantly lowered both the
AHI (by 23.8 %) and the oxygen desaturation index (ODI, i.e., the number of times
per hour of sleep that arterial oxygen saturation drops by 3 % or more from base-
line). TNI also improved sleep stage distribution, with an increase in slow-wave
sleep. However, the magnitude of such improvement was rather modest. Moreover,
the response to TNI was heterogeneous, with only modest effects on respiratory
events in most patients. Indeed, it is likely that nasal CPAP is more effective than
TNI in reducing AHI in these patients. Nevertheless, as CPAP is often poorly toler-
ated, especially in the acute phase of stroke, TNI offers a simplified nasal interface
for delivering relatively low levels of pharyngeal pressure and it does not require
titration. Accordingly, it could be an alternative option for the treatment of SDB
when CPAP is not feasible.

Conclusions
In children, the effects of TNI on SDB suggest that it might provide an alterna-
tive to surgery and, compared with CPAP, might be a more readily accepted
treatment option. The minimally intrusive nasal interface of TNI may improve
adherence to treatment in children and, ultimately, may prove to be more effec-
tive in managing the long-term morbidity and mortality of OSA. In adults, TNI
offers an alternative to the standard CPAP therapy, especially in patients who
predominantly have obstructive hypopnea.

Key Major Recommendations

• TNI could be an alternative treatment for OSA in patients who are poorly
adherent to CPAP.
• In adults, TNI seems to be as effective as CPAP in only some subgroups of
OSA patients (prevailing hypopneas, mild upper airway obstruction),
whereas it is poorly successful in others (e.g., frequent central apneas).
• TNI seems to be particularly effective in children with OSA and may rep-
resent a valid alternative to surgery and, compared with CPAP, a more
readily accepted treatment option.
• In stroke patients with SDB, TNI should be considered only when nasal
CPAP is unfeasible.
11 Transnasal Insufflation for Obstructive Sleep Apnea Syndrome 111

References
1. Lee W, Nagubadi S, Kryger MH, et al. Epidemiology of obstructive sleep apnea: a population-
based perspective. Expert Rev Respir Med. 2008;2(3):349–64.
2. Weawer TE, Grustein RR. Adherence to continuous positive airway pressure therapy: the chal-
lenge to effective treatment. Proc Am Thorac Soc. 2008;5:173–8.
3. Nilius G, Wessendorf T, Maurer J, et al. Predictors for treating obstructive sleep apnea with an
open nasal cannula system (transnasal insufflation). Chest. 2010;137:521–8.
4. Dysart K, Miller TL, Wolfson MR, et al. Research in high flow therapy: mechanisms of action.
Respir Med. 2009;103:1400–5.
5. Parke RL, McGuinness SP. Pressures delivered by nasal high flow oxygen during all phases of
the respiratory cycle. Respir Care. 2013;58(10):1621–4.
6. Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volun-
teers. Aust Crit Care. 2007;20:126–31.
7. McGinley B, Halbower A, Schwartz AR, et al. Effect of a high-flow open nasal cannula system
on obstructive sleep apnea in children. Pediatrics. 2009;124:179–88.
8. McGinley BM, Patil SP, Kirkness JP, et al. A nasal cannula can be used to treat obstructive
sleep apnea. Am J Respir Crit Care Med. 2007;176:194–200.
9. Sahlin C, Sandberg O, Gustafson Y, et al. Obstructive sleep apnea is a risk factor for death in
patients with stroke: a 10-year follow-up. Arch Intern Med. 2008;168(3):297–301.
10. Haba-Rubio J, Andries D, Rey-Bataillard V, et al. Effect of transnasal insufflation on sleep-
disordered breathing in acute stroke: a preliminary study. Sleep Breath. 2012;16(3):759–64.
Exhalation Ports and Interface: Key
Technical Determinants and Clinical 12
Implications

Henry K.H. Kwok

Contents
12.1 Introduction ................................................................................................................. 114
12.2 Different Types of Exhalation Devices on the Effects of CO2 Elimination ................ 114
12.2.1 Product Information from the Manufacturer ................................................. 115
12.2.2 Laboratory and Clinical Investigations on CO2
Elimination Performance............................................................................... 117
12.3 Position of the Exhalation Port on the Removal of CO2
from the Breathing Circuit .......................................................................................... 118
12.4 Effects of Different Types of Exhalation Devices on the Dispersion
of Aerosols to the Surroundings.................................................................................. 119
Conclusion ............................................................................................................................. 120
References .............................................................................................................................. 120

Abbreviations

CO2 Carbon dioxide

COPD Chronic obstructive pulmonary disease
EPAP Expiratory positive airway pressure
ICU Intensive care unit
NIV Noninvasive positive pressure ventilation
PEEP Positive end-expiratory pressure
RVEA Resident volume of expired air
SARS Severe Acute Respiratory Syndrome

H.K.H. Kwok, MBBS(HK), MPH, MRCP(UK), FCCP, FHKAM

Respiratory Medicine, Private Practice, Hong Kong, SAR, China
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 113

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_12
114 H.K.H. Kwok

12.1 Introduction

Noninvasive positive pressure ventilation (NIV) is the delivery of mechanical ven-

tilation without endotracheal intubation and has been established as the treatment of
choice for various causes of respiratory failure, one of which is hypercapnic respira-
tory failure [1]. Although traditional intensive care unit (ICU)-type ventilators can
be used, NIV is more commonly delivered through the more portable NIV or so-
called “bi-level” devices, which are able to alternate between a high inspiratory and
a low expiratory pressure. In contrast with the ICU types of ventilators, which usu-
ally have separate inhalation and exhalation arms of a circle system design, the
usual NIV setup involves a single ventilator tube, an exhalation device for the escape
of carbon dioxide (CO2), and the user interface, which can be any type of nasal, oro-
nasal, or full face mask. The single ventilator tube is a concern because of the pos-
sibility of CO2 rebreathing [2].
Because of the setup of the breathing circuit, CO2 can escape from the breathing
system either through the exhalation device or other leaks from the mask–patient
interface. Such exhalation devices that facilitate the escape of CO2 are theoretically
important in the determination of the overall performance of a NIV breathing circuit
and, therefore, the overall success of the NIV therapy. It should be noted that other
ways of CO2 escape are inevitably present, such as through the leaks from the
incomplete seal between the face and the mask. Such leaks are usually minimized
to allow the delivery of a desired pressure support to the patient.
Several issues arise that could affect the performance of the NIV breathing cir-
cuits. These include (1) whether different types of exhalation devices would make a
difference in the CO2 elimination, (2) effects of different position of exhalation
devices on the removal of CO2, and (3) effects of different types of exhalation
devices on the dispersion of aerosols into the surroundings.

12.2 Different Types of Exhalation Devices on the Effects

of CO2 Elimination

Various types of exhalation devices are available for use in the NIV circuit. These
devices can either be (1) built in on the air hose or on the mask or (2) separate and
connectable devices on the circuit. The built-in devices usually take the form of a
series of small holes, either in the mask itself or on the elbow connector on the
mask. For those separate devices not built in on the mask, various forms are avail-
able, ranging from a single hole on the connector (Disposable Exhalation Port,
Respironics Inc., Murrysville, PA, USA), a fixed valve connector with several nar-
row slits (Whisper Swivel, Respironics Inc., Murrysville, PA, USA), a connector
with a circumferential leak design that allows the gas to escape along the direction
of the air hose (Whisper Swivel II, Respironics Inc., Murrysville, PA, USA), or to a
specially designed valve with a variable resistor that minimizes rebreathing (Plateau
Valve, Respironics Inc., Murrysville, PA, USA) (Fig. 12.1).
12 Exhalation Ports and Interface: Key Technical Determinants and Clinical Implications 115

Fig. 12.1 Different types of connectable exhalation ports. From left to right: Disposable
Exhalation Port, Whisper Swivel, Whisper Swivel II, and Plateau Valve (Respironics Inc.,
Murrysville, PA, USA)

The built-in exhalation ports have the advantage of being a built-in device
without the need to worry about an additional connector on the circuit, whereas
the connectable devices have the advantage of being a separate piece of equip-
ment that can be replaced more easily and also allow easier disinfection after
use. The question is whether there are any differences in the performance of
these different devices in CO2 exhalation. Additional factors, such as the size of
the dead space in using the different types of built-in or connectable devices that
could affect the performance of CO2 exhalation, will not be addressed in this
chapter.

12.2.1 Product Information from the Manufacturer

Laboratory studies have been performed to compare the CO2 elimination of these
different types of exhalation devices. The product specification leaflet from the
manufacturer of the masks or exhalation ports provides information about the
leak rate at different pressure levels used in treatment, an example of which is
found from Philips Respironics Inc. [3]. It appears that the newly designed masks
commonly have built-in exhalation ports rather than using the conventional
detachable exhalation ports. As listed by the manufacturer, the intentional leak is
increased with increasing level of applied pressure, and the leaks are usually
similar between the different masks and are within a narrow range for different
types of masks with different exhalation devices, except for a specific model
(Small Child Profile Lite), which has a higher levels of leaks compared with
other models (Table 12.1).
 116

Table 12.1 Intentional leak rates for masks and exhalation ports
ComfortGel ComfortLite2
ComfortFusion ComfortGel Small ComfortLite Pillows Simplicity
ComfortGel ComfortSelect Full OptiLife Child 2 cushion with
Whisper Blue ComfortClassic ComfortFull all Profile Simple Direct seal 15 mm
Mask Swivel 2 EasyLife ProfileLite 2 FullLife FitLife cushions Lite cushion Cushion elbow
Pressure 2.5 11 12 13 12 13 8 11 20 13 14 11
(cmH2) 5 17 18 18 19 19 13 16 31 19 20 16
10 26 26 26 28 26 20 23 45 27 29 22
15 33 32 31 34 32 26 29 57 33 35 28
20 40 37 37 40 37 31 34 68 38 41 32
25 45 42 41 44 42 35 38 74 43 46 36
30 50 46 45 48 46 40 42 82 47 51 39
35 55 50 49 52 50 43 45 89 51 55 42
40 59 54 52 56 53 47 49 96 55 59 45
Adapted from Respironics [3]
H.K.H. Kwok
12 Exhalation Ports and Interface: Key Technical Determinants and Clinical Implications 117

12.2.2 Laboratory and Clinical Investigations on CO2 Elimination

Performance

Clinical investigators have also performed studies on the performance of different

exhalation devices. In a lung model study, Lofaso et al. [4] demonstrated that when
the usual type of exhalation port (Whisper Swivel) was used, significant CO2
rebreathing occurred with resident volume of expired air (RVEA) of up to 55 % of
tidal volume detected at a positive end-expiratory pressure (PEEP) level of
1.3 cmH2O and an inspiratory pressure of 9.4 cmH2O. When a non-rebreathing
valve (Sanders NRV-2 Non-Rebreathing Valve, Respironics Inc., Murrysville, PA,
USA) was used to replace the usual type of exhalation port, an auto-PEEP effect
was noted, raising the level of PEEP to 2.4 cmH2O, and at the same time, the RVEA
was eliminated.
In a small-scale clinical study of seven critical care patients, Lofaso et al. [4]
compared the effect in blood gas and ventilator changes when using conventional
intensive care ventilators, NIV with usual type of exhalation port (Whisper Swivel),
and NIV with a non-rebreathing exhalation port (Sanders NRV-2 Non-Rebreathing
Valve). The authors found that there were no significant effect on PaCO2 and respi-
ratory rate, although a small nonsignificant rise in PaO2 for the NIV with usual type
of exhalation port was observed.
In another clinical study of chronic stable chronic obstructive pulmonary disease
(COPD) and normal volunteers, Ferguson and Gilmartin [5] evaluated the effects of
different exhalation devices on the PaCO2 levels, CO2 rebreathing, and other respi-
ratory parameters under different NIV pressure settings. The authors found that
significant CO2 rebreathing could occur at low expiratory pressure levels
(≤4 cmH2O), and they also found that CO2 rebreathing could be eliminated at an
expiratory positive airway pressure (EPAP) of 8 cmH2O. Such CO2 rebreathing
could be effectively eliminated by the use of the Plateau Valve, which was designed
to minimize rebreathing by a variable resistor that permits more air to escape at low
expiratory pressures than the traditional type of exhalation devices.
On the other hand, Hill et al. [6] directly compared the effectiveness of the tradi-
tional exhalation valve with a three-slit design (Whisper Swivel) to the Plateau
Valve in the blood gas and respiratory outcomes among patients receiving long-term
nocturnal nasal ventilation for various causes and using low expiratory pressure of
≤4 cmH2O. The authors found that the use of the Plateau Valve did not improve
daytime or nocturnal gas exchange or symptoms in patients receiving long-term
nasal NIV. The authors attributed the lack of differences to the presence of air leak-
age from other routes (e.g., through the mouth or under the mask) during nocturnal
ventilation.
In summary, exhalation ports are usually built in on the masks, or the ports can
be available in the form of a detachable device. Most of the masks with built-in
exhalation ports have similar performance in leaks when compared with the com-
monly used detachable exhalation port, with very few exceptions. Laboratory stud-
ies have shown that different detachable exhalation devices have different CO2
elimination efficacy, with the non-rebreathing valve being more effective in CO2
118 H.K.H. Kwok

elimination. In small-scale clinical studies, however, studies on different patient

groups have shown different performance of various exhalation devices. Specific
types of exhalation valves, such as the Plateau Valve, have shown different results
when assessed in different studies, with a favorable result in the study by Ferguson
and Gilmartin [5] and a neutral result in the study by Hill et al. [6]. Other factors,
such as the level of PEEP or the dead space of the mask, might have a role in influ-
encing the efficiency of the CO2 elimination.

12.3 Position of the Exhalation Port on the Removal of CO2

from the Breathing Circuit

As the exhalation port serves to eliminate CO2 from the breathing circuit, its posi-
tion should be placed as near the patient as possible to more effectively capture the
CO2 exhaled by the patient and to decrease the chance of CO2 being washed up into
the breathing circuit. With reference to the different designs of the interface and the
circuits, the position of the exhalation port can either be placed on the ventilator
tubing or on the mask itself. Studies have been conducted to evaluate whether there
are any differences in the CO2 efficacy if the exhalation port is positioned
differently.
Lofaso et al. [7], in a bench study of different types of NIV ventilators, tried plac-
ing side holes in the inspiratory circuit of a NIV device to allow venting of expira-
tory gas to the atmosphere, but found that these side holes on the circuit were not
effective.
In a laboratory study, Schettino et al. [8] evaluated CO2 rebreathing in three dif-
ferent types of interface setting: (1) the full face mask with a exhalation port on the
mask over the nasal bridge, (2) a facial mask using the Whisper Swivel exhalation
port on the circuit connected to the mask, and (3) the Total Face Mask (Respironics
Inc., Murrysville, PA, USA) with the exhalation port within the mask. The authors
found that the facial mask with built-in exhalation port could more effectively clear
CO2 from the mask and circuit, whereas the facial mask with an in-circuit Whisper
Swivel exhalation port performed similarly to the Total Face Mask, which had a
much larger dead space. The authors also found that increasing the EPAP level from
4 cmH2O to 8 cmH2O had only a small effect in decreasing the CO2 rebreathing
when masks with exhalation ports within the mask were tested.
In a study by Chen et al. [10], seven patients with COPD were treated with NIV
with the path of exhalation connected to the side hole on the mask. The authors
found that CO2 rebreathing could be minimized with such a setup modification
when compared with the usual setup of placing the exhalation port on the circuit [9].
This study led some investigators to suggest that exhalation ports over the nasal
bridge should become the “standard” in NIV.
In summary, position of the exhalation port may impact the performance of the
CO2 elimination, as shown in different laboratory and small-scale human studies,
with some suggestion that CO2 elimination is most favorable when the exhalation
port is placed on the top of the mask near the nasal bridge. Because of the small
12 Exhalation Ports and Interface: Key Technical Determinants and Clinical Implications 119

number of studies having been conducted, and also because of the involvement of
other factors such as air pressures, types of patients, and the size of the dead space
of different masks, further studies are needed to confirm such observations.

12.4 Effects of Different Types of Exhalation Devices

on the Dispersion of Aerosols to the Surroundings

A more contemporary issue related to exhalation is the dispersion of bioaerosols

from the port. This issue stems from the epidemic of the severe acute respiratory
syndrome (SARS) in 2003, when 8,098 patients were infected, resulting in the death
of 774 people, with a case fatality rate of 9.6 % [11], including a significant propor-
tion of health-care workers [12]. The question of whether NIV could cause disper-
sion of infectious bioaerosols become a heated debate, and many pulmonologists
and professional societies have issued precautionary statements and guidelines on
the use of NIV for patients with pulmonary infections [13]. Since then, studies have
been conducted on the dispersion of bioaerosols from NIV both in laboratory set-
tings and in human studies.
In a laboratory study by Hui et al. [14], oil-based smoke particulates were used
to assess the dispersion distances of bioaerosols from two different combinations of
mask and exhalation device (Respironics Inc. ComfortFull 2 full face mask with
built-in exhalation diffusers vs Image 3 full face mask with an external Whisper
Swivel exhalation port). It was found that the Image 3–Whisper Swivel exhalation
port had a higher maximal dispersion distance at all the tested IPAP pressures:
0.95 m at IPAP 10 cmH2O, >0.95 m at IPAP 14 and 18 cmH2O. This was compared
with dispersion distances of 0.65, 0.65, and 0.85 m at IPAP 10, 14, and 18 cmH2O
for the ComfortFull 2 mask. The diffusion from the Image 3-Whisper Swivel com-
bination was also more diffuse and extensive. The difference in dispersion distance
could be related to the design of the mask and the exhalation port.
In another setting using human subjects, Simmonds et al. [15] recruited three
groups of participants (normal subjects, subjects with coryzal symptoms, and sub-
jects with chronic lung disease exacerbations) and gave them a series of respiratory
therapies, including chest physiotherapy, oxygen therapy, neubilized medications,
and NIV. NIV was delivered either through a vented full face mask or using a modi-
fied circuit with a non-vented full face mask coupled with a viral/bacterial filter
placed between the mask and the expiratory leak. Measurements of aerosol sizes
and number were made at two positions, one immediately adjacent to the partici-
pants (D1) and from a second position at 1 m from the participants (D2). The authors
found that, after treatment with NIV using standard circuits with vented full face
mask, a significant increase in amount of aerosols larger than 10 μm was found at
position D1 for subjects with chronic lung diseases and for coryzal subjects. At
position D2, coryzal subjects were also found to generate significantly more aero-
sols of sizes 3–5 μm and 5–10 μm and a borderline significant increase in aerosols
at >10 μm size range. Although this study has not compared the propensity for dif-
ferent exhalation ports to generate bioaerosols, it illustrates that in a real-life
120 H.K.H. Kwok

situation, bioaerosols generated from NIV through the exhalation port can be mini-
mized by the installation of a bacterial/viral filter placed between the patient inter-
face and the exhalation port.

Conclusion
Different types of exhalation devices are available for use in NIV, from the con-
ventional detachable types of exhalation ports to the built-in exhalation ports on
the NIV mask, which are increasingly popular. Performance in CO2 elimination
among the different exhalation devices varies, but the difference tends to be
small, with some advantages in certain non-rebreathing devices. It appears from
a few small-scale studies that the position of the exhalation port is best placed
near the top of the NIV mask near the nasal bridge for the most efficient CO2
elimination performance. That being said, confounding variables such as the
level of EPAP and the dead space of the mask itself should be noted in the overall
evaluation of the exhalation port effectiveness. A more contemporary issue
relates to the dispersion of bioaerosols through the exhalation port, highlighting
the importance of infection control when using NIV for patients with pulmonary
infections.

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dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest
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other airborne infections. Health Technol Assess. 2010;14(46):131–72 [Research Support,
Non-U.S. Gov’t].
Technological Aspects and Safe Use
of Noninvasive Mechanical Ventilation 13
Devices: Key Technical and Practical
Recommendations

Sven Stieglitz

Contents
13.1 Introduction .................................................................................................................... 124
13.2 Discussion and Analysis ................................................................................................ 125
13.2.1 Choice of Ventilator ........................................................................................... 125
13.2.2 Oxygenation ....................................................................................................... 125
13.2.3 Misconnections of Invasive and Noninvasive Ventilation .................................. 126
13.2.4 Pressure Constancy ............................................................................................ 127
13.2.5 Manipulation of Interfaces ................................................................................. 127
13.2.6 Rapid Eye Movement Rebound ......................................................................... 128
13.2.7 Importance of the Interface ................................................................................ 128
Conclusion .............................................................................................................................. 128
References ............................................................................................................................... 129

Abbreviations

CO2 Carbon dioxide

FFM Full face mask
ICU Intensive care unit
NIV Noninvasive ventilation
NM Nasal mask

S. Stieglitz, MD
Department of Pneumology and Cardiology,
Petrus Hospital Wuppertal, Academic Teaching Hospital of the University of Duesseldorf,
Carnaper Str. 48, 42283 Wuppertal, Germany
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 123

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_13
124 S. Stieglitz

13.1 Introduction

The first patients to be ventilated were patients in Denmark with poliomyelitis.

Before the 1950s, the iron lung (negative pressure tank) was the only available ven-
tilator and, from some points of view, these ventilators may be regarded as noninva-
sive. Negative pressure tanks were able to treat hypercapnic failure but were not a
good solution for treating severe hypoxemic failure.
The next stage in the development of ventilators was the introduction of positive-
pressure ventilators, which worked by a simple push-pull bellows pump that venti-
lated patients via an endotracheal tube and a breathing circuit. The smaller proportions
of these ventilators led to a worldwide distribution of ventilators in intensive care
units (ICUs), which now is considered a key technology in the ICU [1]. The main
technical features of ICU ventilators are the different modes and a variety of ventila-
tor settings, the use of a breathing circuit with low or even very low leakage, a reli-
able oxygen supply, a high level of safety with a maximum of alarming, some tools
for ventilator settings (e.g., for determining upper and lower inflection points), and a
large display indicating parameters and curves. There are two different pneumatic
principles of ICU ventilators. The one drive system operates with compressed gas
sources that are dispensed and mixed by high-precision valves. The other drive sys-
tem works independently of a central compressed air supply by sucking in ambient
air via a turbine and mixing additional oxygen from a gas source. Most modern ICU
ventilators operate by high-precision valves that require central gas sources. Because
they are dependent on a gas source, this type of ventilator is immobile. Compared
with invasive ventilation, the distinguishing features of noninvasive ventilation (NIV)
are the non-hermetic nature of the system, with intended and unintended leaks, and
the presence of variable resistance resulting from the upper airway [2]. This explains
a major disadvantages of ICU ventilators driven by a central gas source: they are not
suitable for handling leakage. This makes them inappropriate for NIV, despite the
fact that an increasing number of ICU ventilators offer a NIV mode.
The history of NIV ventilators is exciting because the development was driven in
two different ways. Some ventilators were engineered as portable ventilators with a
bellows pump. The first ventilators specifically designed for long-term home
mechanical ventilation were the volume-controlled PLV 100 (Philips Respironics,
Amsterdam, Netherlands), followed by the pressure-controlled PV 401 (Breas
Medical, Herrsching, Germany). These portable ventilators were lightweight and
economical compared with ICU ventilators. At the time, NIV was also applied as
volume-controlled ventilation, like the ventilators that operated only in this mode.
Other ventilators were developed from continuous positive airway pressure (CPAP)
machines that were designed to pump a flow of air into the nasal passages to keep the
airway open in sleep apnea. These devices, used in sleep medicine, were driven by a
turbine. Modification of these devices led to ventilators that had an inspiratory pres-
sure of 20 mbar and a simple S-mode (spontaneous), which corresponds to the pres-
sure support ventilation (PSV) of ICU ventilators. Later, ST and T (timed) modes
were developed. Today, both types of ventilators are turbine driven. Most NIV venti-
lators operate as pressure-controlled ventilators and are turbine driven. An increasing
13 Technological Aspects and Safe Use of Noninvasive Mechanical Ventilation Devices 125

number of features of ICU ventilators, such as configuring the inspiratory trigger-

threshold or displaying ventilator curves are transferred to portable NIV ventilators.
This brief history of the development of ventilators explains the confusing diversity
of nomenclature of modes in NIV. Nevertheless, one may recognize the different
types of NIV ventilators. One type works with a breathing circuit with an integrated
expiratory valve (either active or passive) and the other requires a mask with a pre-
defined leakage that works as a passive expiratory “valve” (vented mask).
Three different types of ventilators can be found in a hospital or even within a
single ICU:

1. Dedicated ICU ventilators working with gas sources and high-precision valves
2. Dedicated NIV ventilators that are turbine-driven and approved for NIV only
3. Portable turbine-driven ventilators that are approved for invasive (either for
breathing support or for life-sustaining ventilation) as well for noninvasive
ventilation

13.2 Discussion and Analysis

13.2.1 Choice of Ventilator

Dedicated ICU ventilators that operate with compressed gas sources are limited
regarding the maximum of possible flow that they might deliver by the central gas
source. They usually achieve a maximum of flow about 120 l/min, although some
manufacturers find technical solutions by a built-in tank working as a reservoir that
allows generation of flows of about 180 l/min. Turbine-driven portable ventilators
are able to achieve flow rates above >200 l/min. Today, the highest possible flow is
generated by turbine-driven ICU ventilators with flow rates of 260–300 l/min. When
ventilating patients noninvasively, it is important to employ ventilators that generate
high flow rates. The flow is necessary to compensate for the leakage at the mask, to
avoid CO2 rebreathing (especially in single circuits and passive expiratory valves),
and to handle the high flow that may be generated by spontaneously breathing
patients, especially in case of acute respiratory failure. As shown above, for techni-
cal reasons the small portable turbine-driven ventilators are superior in NIV com-
pared with dedicated ICU ventilators that operate with valves and central gas
sources. The latter are not recommended in NIV, even when the manufacturers of
the ventilator offer a “NIV” mode.

13.2.2 Oxygenation

ICU ventilators are able to ensure an adequate oxygen delivery, which is sometimes
less well balanced in dedicated NIV ventilators. In NIV, the oxygen is usually deliv-
ered by a constant flow. Nevertheless, the delivery of oxygen varies because the
concentration of oxygen that reaches the patient depends on the pressure (which is
126 S. Stieglitz

generated by the flow of the turbine), the flow of the spontaneously breathing
patient, and the leakage within the breathing circuit or mask (which again will
increase the flow to compensate for the leakage). Particularly large leakage may
reduce the concentration of inspired oxygen. There is another observation that can
be made: patients sometimes require a higher oxygen delivery when they are venti-
lated with NIV compared with spontaneous breathing. This happen when the flow
of the spontaneous breathing is lower than the flow generated by NIV. In this case,
the oxygen is diluted by the ambient air, which may reduce the hemoglobin oxygen
saturation and require an increase of the oxygen flow during NIV. Therefore,
patients with severe hypoxemia who are ventilated with NIV require an optimal
medical surveillance.
When NIV is started, it is important to begin the ventilation first and to connect
the oxygen afterwards. This prevents the oxygen from getting into the ventilator,
which generates a fire hazard. Many manufacturers also require the use of a pressure
valve to avoid oxygen intrusion into the ventilator.
There are only few ventilators approved for NIV that have a separate input for
oxygen. In general, the oxygen may be introduced either near the mask or near the
ventilator. These two possibilities seem to be equal with regard to the oxygenation
of the patient.

13.2.3 Misconnections of Invasive and Noninvasive Ventilation

Whereas mechanical ventilation in the ICU is performed within a limited area by a

defined team that is well trained and ventilates patients only in the ICU, performing
NIV in conventional medical wards not only extends the location where NIV is
performed but also increases the group of people faced with NIV and the problems
of the patients who use NIV. Performing NIV out-of-hospital further increases this
group and adds the patients themselves (and their relatives) who must utilize the
NIV correctly and the employees of the home-care provider. As shown above, the
situation is complicated by the three categories of ventilators: dedicated ICU venti-
lators, dedicated NIV ventilators, and portable turbine-driven ventilators that are
approved for invasive and noninvasive ventilation.
NIV is usually used with a single-circuit ventilation system. The advantage of
single circuits is their lower weight compared with double-circuit systems of invasive
ventilation, which is important considering the fitting of the mask. The handling is
simpler, which is particularly important in the use of NIV outside of the hospital.
The situation is further complicated by two competing systems: one using a
breathing circuit with an integrated expiratory valve (active or passive), which
requires a non-vented mask, and the other using a breathing circuit without an expi-
ratory valve but requiring a vented mask. The most common misconnections in NIV
seems to be the misconnection of a breathing circuit with an expiratory valve inte-
grated with a vented mask, leading to an abnormal leakage that impairs an adequate
increase of the pressure, and the misconnection of a breathing system without an
expiratory valve with a non-vented mask, which leads to a failure of CO2
13 Technological Aspects and Safe Use of Noninvasive Mechanical Ventilation Devices 127

elimination. This is especially dangerous because it might be overlooked in the

clinical routine. Even marked hypercapnia can be associated with normal oxygen
saturation when additional oxygen is administered. In fact, hemoglobin oxygen
saturation is only a marker for ventilation when patients are breathing room air.
Therefore, we recommend routine measurement of CO2 by blood gas analysis or by
transcutaneous measurement (end-tidal measurement of CO2 works only in invasive
ventilation). Regrettably, there is no solution for this problem, although the connec-
tion between the mask and tubing (the elbow piece) of vented and non-vented masks
is sometimes designed in different colors. Because the elbow piece fits both types of
masks, the error still has the potential to occur, especially after removing this piece
to clean the mask [3].
Another type of misconnection applies to the use of ventilators that offer both
invasive and noninvasive modes. Although these ventilators are approved for both
modes, the setting of the mode is done manually. It is possible to connect a ventila-
tor that operates with a simple single circuit (without expiratory valve) in a NIV
mode to a breathing tube, leading to severe hypercapnia. There is no technical solu-
tion to avoid this. Therefore, we recommend a clear separation between invasive
and noninvasive ventilators and, in our clinical routine, ventilators that are approved
for both modes are used exclusively for either invasive or noninvasive ventilation.
The incorrect use of the ventilator equipment and, therefore, the human factor
are the main reasons for critical incidents in respiratory medicine. Thus, continued
training of doctors, nursing staff, respiratory therapists, and caregivers is required.
One should always also take into account that misuse occurs by the patients, their
relatives, and employees of home-care provider.

13.2.4 Pressure Constancy

The pressure constancy of portable turbine-driven ventilators varies ±2.5 mbar

(sometimes even higher) for most portable ventilators. This explains the observation
that many patients remark on a difference after exchange of the ventilator even if the
ventilator settings remain unchanged. Therefore, an exchange of the ventilator
always requires a clinical control (e.g., blood gas analysis). This is especially impor-
tant in home mechanical ventilation and chronic hypercapnic failure.

13.2.5 Manipulation of Interfaces

NIV is often underestimated with regard to its effectiveness and its complexity.
Additionally, as mentioned above, the group of people helping to provide NIV is
larger than the small, specialized teams who care for invasive ventilation in an
ICU. This might explain why manipulation of the NIV may sometimes be observed,
with the potential risk of harm to the patient. We recommend appointing one nurse
(or a team) or respiratory therapist who controls the NIV in daily routine and checks
the ventilator equipment.
128 S. Stieglitz

13.2.6 Rapid Eye Movement Rebound

Rapid eye movement (REM) rebound occurs after initiation of CPAP and may also
play a role in NIV. In clinical studies, the increase of REM after one night of CPAP
amounts to 20 % [4], but in single cases REM may increase to more than 70 % after
initiation of CPAP [5]. In REM, the CO2- and O2-threshold for ventilation are
changed and the stimulation of breathing due to hypoxemia or hypercapnia is mark-
edly reduced. Additionally, the threshold for awakening is reduced in REM. This all
together contributes to a challenging situation that requires clinical care of the
patient and an optimal control of the ventilator equipment in the first few nights
after initiation of NIV. Special attention should be given to the displacement of the
mask and disconnection of the breathing tube in this situation.

13.2.7 Importance of the Interface

The most commonly used interfaces in NIV are the full face (FFM) and the nasal
mask (NM) [6]. There seems to be a trend toward the FFM, especially when high-
pressure (>25 cmH2O) NIV is performed [7]. In this regard, it is important to recog-
nize that NIV failure may occur not only because of the chosen ventilation strategy
(invasive vs noninvasive) or the ventilator setting (pressure difference, frequency,
triggering, ramp, etc.) [2] but also as a result of the chosen interface. Furthermore,
also sedation affects the effectiveness of NIV and the interaction of interface and
ventilation [8]. The study of Oto et al. [8] showed that the NM is superior to the
FFM in unconscious patients. For these reasons, changing of the interface
(e.g., from NM to FFM) requires a medical control of the ventilation.

Conclusion
The use of turbine-driven NIV ventilators allows ventilation of patients outside
the ICU and even at home. However, a specialized team is required to care for the
NIV equipment and for the patients. The presence of vented and non-vented
systems is a pitfall that requires good care of all the equipment used. The flow of
the NIV ventilator reduces the hemoglobin oxygen saturation in the case of addi-
tional oxygen supply. REM rebound may occur after initiation of NIV, which
may potentially harm patients because of the reduced hypercapnic and hypox-
emic stimulation of ventilation in REM. Therefore, good medical care is required
after initiation of NIV.

Key Major Recommendations

• Turbine-driven ventilators are recommended for NIV.
• Because a higher oxygen delivery may be necessary with NIV compared
with spontaneous breathing due to dilution with ambient air, optimal medi-
cal surveillance is necessary when patients are hypoxemic.
13 Technological Aspects and Safe Use of Noninvasive Mechanical Ventilation Devices 129

• To avoid misconnections of vented and non-vented systems and any

manipulation of the interfaces, the foundation of a specialized “NIV team”
who cares for all ventilator equipment is strongly recommended.
• Clinical care of the patient and optimal control of the ventilator equipment
in the first few nights after initiation of NIV are required to avoid critical
incidents resulting from REM rebound, with special attention paid to the
displacement of the mask and disconnection of the breathing tube in this
situation.

References
1. Marini J. Mechanical ventilation: past lessons and near future. Crit Care. 2013;17 Suppl 1:51.
2. Rabec C, Rodenstein D, Leger P, et al. Ventilator modes and settings during non-invasive ventilation:
effects on respiratory events and implications for their identification. Thorax. 2011;66(2):170–8.
3. Stieglitz S, George S, Priegnitz C, et al. Life-threatening events in respiratory medicine: mis-
connections of invasive and non-invasive ventilators and interfaces. Pneumologie. 2013;67(4):
228–32.
4. Brillante R, Cossa G, Liu PY, et al. Rapid eye movement and slow-wave sleep rebound after
one night of continuous positive airway pressure for obstructive sleep apnea. Respirology.
2012;17:547–53.
5. Bue AL, Salvaggio A, Insalaco G, et al. Extreme REM rebound during continuous positive
airway pressure titration for obstructive sleep apnea in a depressed patient. Case Rep Med.
2014;2014:292181.
6. Silva RM, Timenetsky KT, Neves RC, et al. Adaptation to different noninvasive ventilation
masks in critically ill patients. J Bras Pneumol. 2013;39(4):469–75.
7. Murphy PB, Brignall K, Moxham J, et al. High pressure versus high intensity noninvasive
ventilation in stable hypercapnic chronic obstructive pulmonary disease: a randomized cross-
over trial. Int J Chron Obstruct Pulmon Dis. 2012;7:811–8.
8. Oto J, Li Q, Kimball WR, et al. Continuous positive airway pressure and ventilation are more
effective with a nasal mask than a full face mask in unconscious subjects: a randomized con-
trolled trial. Crit Care. 2013;17:R300.
CPAP Device Therapy for Noninvasive
Mechanical Ventilation in Hypoxemic 14
Respiratory Failure: Key Technical
Topics and Clinical Implications

Rodolfo Ferrari

Contents
14.1 Introduction ................................................................................................................. 132
14.2 Background ................................................................................................................. 133
14.3 Technical Topics: Devices and Interfaces ................................................................... 133
14.4 Main Clinical Indications............................................................................................ 134
14.5 Indications and Contraindications, Criteria for Inclusion or Exclusion ..................... 138
14.6 Predictors for Success or Failure ................................................................................ 139
14.7 New Perspectives and Future Development................................................................ 139
References .............................................................................................................................. 142

Abbreviations

AA Acute asthma
ABG Arterial blood gas analysis
ACPE Acute cardiogenic pulmonary edema
AHRF Acute hypoxemic respiratory failure
ARDS Acute respiratory distress syndrome
ARF Acute respiratory failure
CHF Chronic heart failure
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
DNI Do not intubate
ED Emergency department

R. Ferrari, MD
Medicina d’Urgenza e Pronto Soccorso, Policlinico Sant’Orsola – Malpighi, Dipartimento
dell’Emergenza – Urgenza, Azienda Ospedaliero – Universitaria di Bologna,
Via Albertoni, 10, Bologna 40138, Italy
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 131

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_14
132 R. Ferrari

FEV1 Forced expiratory volume in 1 second

FiO2 Fraction of inspired oxygen
FRC Functional residual capacity
HMDU High medical dependency unit
ICU Intensive care unit
IMV Invasive mechanical ventilation
NCPAP Noninvasive continuous positive airway pressure
NIMV Noninvasive mechanical ventilation
NPPV Noninvasive double-level positive pressure ventilation
OOH Out of hospital
OSAS Obstructive sleep apnea syndrome
PaO2 Arterial oxygen pressure
PEEP Positive end-expiratory pressure
RCCT Randomized controlled clinical trial
RR Respiratory rate
SO2T Standard oxygen therapy
SpO2 Oxygen saturation
TI Tracheal intubation
VPM Ventilation / perfusion mismatch
WB Work of breathing

14.1 Introduction

Continuous positive airway pressure (CPAP) entails delivering to the opening of the
airways, by an external interface or an endotracheal tube, a positive (over-
atmospheric) pressure, continuously, during both expiration and inspiration.
Although CPAP cannot literally be defined as a noninvasive mechanical ventilation
(NIMV) technique: it is often, but not always, noninvasive; it is sometimes mechan-
ically generated, but there are many simpler ways to perform it; and it cannot strictly
be considered “ventilation,” because, even if in specific cases CPAP is able to
increase alveolar ventilation, it cannot perform any work of breathing (WB).
Today, CPAP is universally accepted and included in the field of NIMV, because, as
opposed to the “mandatory controlled” way of ventilating, it represents the “spontane-
ous” way: the patient is in charge of the whole WB and must be able to individually
manage each period of the inhalation phase (triggering, limiting, and cycling). In the
last two decades, NIMV demonstrated its main role in the treatment of acute respira-
tory failure (ARF). It is safe and effective when delivered early to carefully selected
patients who do not meet the criteria for tracheal intubation (TI), because of its ability
to reduce morbidity and mortality related to invasive mechanical ventilation (IMV) [1].
The use of noninvasive CPAP (NCPAP) in treating acute hypoxemic respiratory
failure (AHRF) has spread in the everyday real world of clinical practice in emer-
gency care, coming out of the intensive care units (ICUs) to reach the high-dependency
medical units (HMDUs), the emergency department (ED), and the out-of-hospital
14 CPAP in Hypoxemic Respiratory Failure 133

(OOH) setting. NCPAP is also the cornerstone for treating, even at home, such chronic
condition as chronic heart failure (CHF) and obstructive sleep apnea syndrome
(OSAS). With the spread of NCPAP, today, even in the scientific medical literature,
the term CPAP has become synonymous with NCPAP. Similarly, the acronym PEEP
(positive end-expiratory pressure) is often used with the same meaning as CPAP.
Nevertheless, we can never forget that NIMV and NCPAP are not actually a real
“therapy,” as they are not able to resolve by themselves the cause of the ARF. They
are a “bridge” we use to support the WB while therapy is ongoing to confront and
resolve the acutely decompensated basic pathological condition. Drugs remain the
mainstay of medical etiopathogenetic treatment.

14.2 Background

NCPAP, versus standard oxygen therapy (SO2T), has proven its efficacy in reducing
the rate of TI and hospital mortality in ARF resulting from acute cardiogenic pulmo-
nary edema (ACPE) [2]. Its success is mainly due to the increase in intrathoracic
pressure and its subsequent hemodynamic cardiovascular and respiratory effects. In
many other clinical conditions, unresponsive to SO2T alone, NCPAP showed lower
levels of evidence and strength of recommendation [3]. The pathophysiological
rationale is often in the increased ventilation/perfusion mismatch (VPM) compli-
cated by AHRF, and the capability of interfering with atelectasis and the shunt effect.
Key determinants for the success of the technique include the right selection of
patients, an early intervention, the choice of a comfortable and well-fitting interface,
careful monitoring, and a skilled team [4, 5]. Once NCPAP is established as part of
the treatment for ARF in a particular patient, some further choices are then pivotal:

• Which positive pressure level must be set (usually expressed as cmH2O), depend-
ing on the underlying clinical condition and the hemodynamic state of the
patient?
• Which fraction of inspired oxygen (FiO2, expressed as a percentage) to start
with, depending on the ideal target in oxygen saturation (SpO2)?
• Which interface to choose?
• Where to perform the treatment, and which kind of monitoring is needed?
• How to prepare in case of NIMV failure?

One must always keep in mind that any unnecessary delay in recognizing the
need for IMV, and its dramatic consequences, should be avoided.

14.3 Technical Topics: Devices and Interfaces

CPAP can be provided in many different ways, by many different devices and sys-
tems. For the treatment of ARF in the acute care setting, NCPAP is usually provided
by simple high-flow generators needing only an oxygen source (standalone systems,
134 R. Ferrari

Table 14.1 NCPAP: high-flow generators versus ventilators

High-flow generators Ventilators
Pros Pros
Simpler, less parameters needed to set No limits in high flow versus high FiO2
Cheaper Leak compensation, more stable pressure
No triggering system Waveforms, alarms, monitoring
Easier and lighter for transport or OOH use Known FiO2
Cons Cons
Compromise between high flow and/or high More complex, more parameters to set
FiO2
Less stable positive pressure Expensive
No alarms, no monitoring Need for synchronization and triggering
Inaccurate FiO2 Need for batteries or electricity
Lower performances Need for specific NIV module

Venturi-like, Boussignac®-like, etc.) or by turbine- or piston-driven ventilators

(with a NIMV module). The main pros and cons are listed in Table 14.1.
Today there is no reason to strongly recommend a specific device over another. A
pivotal factor in the approach and the choice is the need to provide a high flow, high
enough to meet the needs of a patient with ARF, mainly in the very early phase of
inhalation. Some other simpler devices, with or without oxygen supply, are particu-
larly tailored for home treatment of chronic conditions. On the other hand, patient
comfort and tolerance of the interface are probably the crucial factors for successful
NIMV [6]. Oro-nasal masks, full or total face masks, and helmets can be used to pro-
vide NCPAP in treating ARF. The pros and cons are listed in Table 14.2. Nasal masks,
nasal prongs, and mouthpieces are used outside of the acute care setting; interfaces
covering both the mouth and the nose are the first choice for acute NIMV. The ideal
mask does not exist and cannot be expected a priori for an individual patient.
In an ideal situation, even in the emergency setting, it is useful to be able to
change the size or rotate different interfaces to reduce the rate of complications
(Table 14.3) and increase patient comfort during NCPAP. The most common com-
plications associated with interfaces for NCPAP can be, at least in part, prevented,
treated, and resolved [3, 7]. The contribution provided by the nursing staff in the
management of the interface can make the difference in the success of the treatment.
Training, experience, skills, and motivation are vital factors, primarily in the early
phases of treating ARF by NIMV, for a successful outcome [4].

14.4 Main Clinical Indications

The efficacy of NIMV on patient outcome predominantly depends on the underly-

ing pathology. ACPE provides the best evidence for efficacy of NCPAP in ARF [8].
By reducing WB and improving gas exchanges, lung and thorax mechanics (com-
pliance, functional residual capacity (FRC)), right ventricular preload, and left
14 CPAP in Hypoxemic Respiratory Failure 135

Table 14.2 NCPAP interface characteristics

Oro-nasal Mask Full/total face mask Helmet
Pros Pros Pros
Few air leaks Scarce air leaks Minimum air leaks
Stable airway pressure Easy fitting Neither nasal nor facial skin damage
Easy application Stable airway pressure No problem in facial trauma, burns,
edentulism
Less cooperation No nasal bridge skin lesions Less flow resistance
required
Cheaper Less noisy Easier speaking
Panoramic view
Possible drinking
Enteral nutrition allowed
Easier coughing and expectoration
More suitable for long-lasting
treatments
Cons Cons Cons
Nasal skin decubitus Facial skin lesions Very high gas flow required
Vomiting Vomiting Noisy
Claustrophobia Claustrophobia High dead space
Eyes irritation Eyes irritation Risk for CO2 rebreathing
Difficult seeing Difficult speaking Less stable airway pressure
Difficult speaking Ophthalmopathies Axillae or neck skin lesions
Neither eating nor Expensive Longer time for application
drinking Difficult humidification
Expensive

ventricular afterload, it demonstrates the power to reduce mortality and rate of TI

versus SO2T.
In 2008, a famous randomized controlled clinical trial (RCCT), which confirmed
how NIMV can induce a quicker improvement in respiratory distress and metabolic
disturbances versus SO2T, raised uncertainty about the ability of NIMV to reduce the
rate of TI and mortality [9]. The paper was widely and harshly criticized for its meth-
ods and the structure of the study protocol [10, 11], but, even today, its consequences,
when defining the grade of recommendation for NIMV in ACPE, endure [2].
In the field of NIMV, there is no recommendation to date that favors NCPAP over
noninvasive double-level positive pressure ventilation (NPPV) for treating ACPE,
even though the published data are slightly stronger for NCPAP [8]. Because it is
easier and cheaper, NCPAP is considered by many authors as the first-line treatment
in ACPE. Moreover, the presence of hypercapnia during an episode of ARF due to
ACPE does not represent an indication to prefer NPPV over NCPAP; they are com-
parable in efficacy, even in this subgroup of cases. This confirms (and is a conse-
quence of the fact) that hypercarbia, in the context of ACPE, is not mainly due to
pump failure but has a multidimensional pathophysiological explanation [12].
136 R. Ferrari

Table 14.3 Most common Leaks

complications due to NCPAP
Pressure sores and ulcers
interfaces
Discomfort
Soft skin tissue damage
Claustrophobia
Aspiration
Mucous plugging
Conjunctivitis
Keratitis
Eye irritation
Oral and nasal dryness
Nasal congestion
Vomiting
Gastric distention
Aerophagia
Difficult speaking
Difficult eating
Difficult hearing
Noise
Allergy

NCPAP has demonstrated different, lower levels of evidence versus SO2T in the
early treatment of other different causes of AHRF in the acute care setting. The
pathophysiological background for NCPAP in these conditions is, most likely, one
of the following reasons:

• To reduce atelectasis
• To regain and recover (“recruit”) flooded alveoli to ventilation (to open and keep open)
• To increase compliance and FRC
• To decrease WB
• To unload respiratory muscles
• To increase tidal volume
• To decrease VPM
• To improve oxygenation and correct gas exchange abnormalities

Many promising experiences have been reported in the literature regarding

NCPAP for the treatment of AHRF resulting from blunt chest trauma, pneumo-
nia (with or without chronic obstructive pulmonary disease (COPD)), peri- and
postoperatively (for both prevention and treatment), mild acute respiratory dis-
tress syndrome (ARDS), pandemics, aspiration, pleural effusion, restrictive
conditions, facilitation of weaning/extubation, and prevention of extubation
failure [1, 3, 13, 14].
Acute asthma (AA) is worthy of special mention. Currently, in the field of
chronic obstructive pulmonary diseases, AA is a peculiar entity and one of the most
14 CPAP in Hypoxemic Respiratory Failure 137

common reasons for NIMV application in EDs in the United States [15]. For AA,
NCPAP showed positive results in early prevention of AHRF, and less strong data in
the treatment of AHRF itself, even with a convincing pathophysiological back-
ground (Table 14.4).
NCPAP also has pathophysiological significance for ARF resulting from acute
exacerbations of COPD, overcoming intrinsic PEEP and acting as a kind of mechan-
ical bronchodilator, and reducing both dyspnea and WB. In this area, the efficacy of
NPPV versus SO2T, and also versus CPAP, is evident [16].
NCPAP is used to treat AHRF in chronic conditions such as OSAS [17] and CHF,
and also in some carefully selected patients, often overlapping, with neuromuscular
diseases, obesity hypoventilation syndrome, restrictive pulmonary diseases, thoracic
cage deformities, partial upper airway obstruction, sleep disorders, idiopathic pulmo-
nary fibrosis, and so on. In these chronic conditions, the purpose for NCPAP is to
achieve physiologic benefits, palliate symptoms, improve quality of life, decrease pul-
monary morbidity, reverse reversible superimposed conditions responsible for acute
deterioration, prevent hospitalizations, and, in some cases, extend survival.
Regardless of the specific causes of AHRF, there is a high grade of recommenda-
tion for NIMV and NCPAP in immunocompromised patients [3]. This is mainly due
to the high rate of infectious complications during IMV and its consequences in
terms of hospital mortality. The subgroup of immunosuppressed patients features
one of the most striking and strong indications for NIMV and NCPAP, in terms of
efficacy and outcome, for the treatment of various forms of ARF [18, 19].
In summary, each unusual or off-label application of NCPAP for AHRF has
lights and shadows, and, even in cases of promising preliminary results, remains
controversial. Large, prospective, multicenter RCCTs are needed. Out of shared
indications, NCPAP should be provided early, cautiously, safely and carefully, dur-
ing the proper “window of opportunity,” by an experienced team, in an appropriate
setting (ICU or HMDU), with a quick access to facilities for TI and IMV [1, 3, 4].

Table 14.4 Pathophysiological rationale for NCPAP in AA

Increased bronchodilation (mechanically, equal pressure point, alveolar patency at end
expiration), decreased airway resistance, re-expanded atelectasis (collateral reinflation),
promoted removal of secretions, enhanced bronchial clearance, influencing medical treatment
Increased functional residual capacity, raised minimal pleural pressure, decreased swing in
transdiaphragmatic pressure, decreased adverse hemodynamic effects
Reduction of respiratory muscles load, accessory recruitment and work: reduced
transdiaphragmatic pressure, pressure time product for the inspiratory muscles and diaphragm,
and fractional inspiratory time (endurance); reduction of elastic work (due to intrinsic PEEP);
offset intrinsic PEEP and rest respiratory muscles;
Reduction of dyspnea, respiratory rate, pulse rate
Improvement in arterial blood gas exchanges, reduced inspiratory work (improved efficiency
and decreased energy cost), increased FEV1
Need of lower inspiratory pressures versus IMV
Reduced side effects and avoided complications versus TI, reduced need for sedation versus
TI; decreased adverse hemodynamic effects of large negative peak and mean inspiratory
pleural pressures; reduced need/frequency/duration of hospital admission
138 R. Ferrari

14.5 Indications and Contraindications, Criteria for Inclusion

or Exclusion

A proper selection process to identify the right candidates to NCPAP for AHRF is
the mainstay of the clinical management for critical cases. In the acute care setting
characterized by AHRF, it is not easy to fix strict criteria for beginning NCPAP,
particularly in the ED. The first decision is based exclusively on clinical grounds,
when deeper diagnostic assessment is yet to be started, and only a little help from
limited “point of care” imaging data or laboratory information is available. In this
situation, the good candidate for NCPAP is the patient, suffering from severe acute
respiratory distress, who we clinically consider will not be able to resolve AHRF by
SO2T and, at the same time, is not showing indications for TI and IMV.
In the early clinical decision phase, the first point to set, and the first question to
answer, in an emergency situation is, is the patient really able to “spontaneously”
breath and perform the needed amount of WB by him or herself, protecting his or
her airways? The main indications to start NCPAP are listed in Table 14.5.
Special attention must be paid to cooperation and sensorium disturbances. Even
though, in conditions such as ACPE, a neurologic status score such as a Kelly-
Matthay grade 4 [20] can be considered a “relative” contraindication for NCPAP, in
different situations (such as AA) any slight worsening in alertness should be consid-
ered, evaluated and treated as a “red flag” to move toward IMV. Contraindications
for NCPAP are described in Table 14.6.
Many conditions previously considered as absolute contraindications have
become relative contraindications or are no longer contraindications:

• NCPAP use after thoracic or major abdominal surgery (also facial, upper airway,
or gastroesophageal tract) showed a good outcome both in preventing and treat-
ing ARF.
• New interfaces have overcome problems related to peculiar craniofacial shapes
or skin damage such as burns or decubitus.
• The presence of a pneumothorax, if narrow or after drainage, does not adversely
condition noninvasive treatment of blunt chest trauma.
• The use of light sedation or analgesia showed some benefit for reducing intoler-
ance to the interface in properly selected cases.

In the recent past, when approaching ARF, the failure of a SO2T “trial” was con-
sidered an indication for NIMV. Today, when identifying early indications for

Table 14.5 Criteria to start Moderate to severe respiratory distress

NCPAP in AHRF
RR >30 breaths per minute
Increased WB
Ventilatory accessory muscles recruited
Impaired sensorium
PaO2/FiO2 <200 mmHg
14 CPAP in Hypoxemic Respiratory Failure 139

Table 14.6 Contraindications for Cardiac arrest

NCPAP in AHRF
Respiratory arrest
Gasping
Coma (Kelly-Matthay grade ≥4)
Multiorgan failure
Shock
Upper gastrointestinal bleeding
Respiratory fatigue
Ventilatory muscle pump exhaustion
Inability to protect the airway
High aspiration risk
Inability to clear secretions
Inability to fit the noninvasive interface
Swallowing impairment
Major tachyarrhythmias
Bradycardia < 50 pulse per minute
Systolic blood pressure <70 mmHg
Agitation, confusion, encephalopathy
Inability to cooperate
Seizures
pH <7.10

NCPAP, any delay in starting NIMV has to be considered as deleterious as a delay

in TI and IMV [21] and, similarly, must be avoided. NIMV and NCPAP should no
longer be considered as merely “alternatives” to IMV or SO2T; NIMV has gained its
own significant role with its own specific indications.

14.6 Predictors for Success or Failure

Once an indication to start NCPAP in a patient with AHRF has been assessed, it is
necessary to perform an early risk stratification to identify cases that are likely to
fail or succeed. This decision-making process has an impact on clinical outcome. It
is necessary to recognize predictive signs of failure early, choosing the right setting
for the right patient, primarily concerning monitoring, access and availability of TI
and IMV, and also of NPPV, especially in off-label cases [4, 22]. The most signifi-
cant predictors of outcome are listed in Tables 14.7 and 14.8.

14.7 New Perspectives and Future Development

Many promising improvements in NCPAP for AHRF are possible. RCCTs in the
acute care setting are needed to define and enlighten efficacy in applications such as
AA, mild ARDS, pneumonia, and blunt chest trauma. Studies of NCPAP are needed,
140 R. Ferrari

Table 14.7 NCPAP in Preserved sensorium, better neurologic score

AHRF: predictors for success
Airways protection
Good tolerance to the interface
Few air leaking
Low acuity of illness, low physiologic score
ACPO
Mild hypoxaemia
Mild pH abnormality
Few secretions
Younger age (<45 years old)
Intact dentition
Improvement in RR and ABG after 1 and 2 h

Table 14.8 NCPAP in Poor nutritional status

AHRF: predictors of failure
Multiple comorbidities
Diabetes
Obesity
Severe hypoxemia (PaO2/FiO2 <60 mmHg)
RR >38 breaths per minute
Sensorium disturbances (Kelly-Matthay grade ≥4)
Impaired mental status
Agitation
Uncooperative
Inability to correctly protect the airway
Inability to control the entire inhalation phase
Excessive secretions
Nasal breathing
Edentulism
Inability to fit the interface
Inability to tolerate the interface
High physiologic status
ARF “de novo”
ARDS
Clinical worsening
Worsening symptoms
New complications
Failure to improve RR, heart rate, blood pressure, ABG
after 1 and 2 h

focusing on “special” cohorts of patients (more than specific diseases) with AHRF,
patients with DNI (do-not-intubate) orders, and those for whom NCPAP can be
considered a ceiling treatment or palliation, near the end of life, for symptomatic or
ethical reasons, to treat acute and reversible causes of ARF and respiratory distress,
with no impact on medium-term survival. RCCTs are not easy to carry out [23] in
14 CPAP in Hypoxemic Respiratory Failure 141

Table 14.9 Criteria to stop RR <25 breaths per minute during NCPAP
NCPAP in case of success
SpO2 >94 % during NCPAP with FiO2 <40 %
PaO2 >75 mmHg in SO2T with FiO2 <50 %

these cases (DNI most of all) [24], which are often managed in the ED without
subsequent admission to ICUs [25].
New devices and systems for NCPAP need to be developed to ensure high
flows, stable pressures, and known precise FiO2, even in difficult settings such
as OOH or during transport. It is not clear how to noninvasively set the proper
pressure level from the start. We know that 7.5–10 cmH2O is usually needed to
offset atelectasis; it is also commonly accepted to set lower PEEP in COPD
patients (to avoid undue expiratory resistances and subsequent air trapping) or
in hypotensive or hypovolemic cases (due to the reduction in gradient of sys-
temic venous return and then in right ventricular preload). In some other condi-
tions (ARDS, restrictive disorders, etc.), a higher PEEP may be advisable. To
date, arterial blood gas analysis (ABG) and hemodynamic parameters have been
the mainstay of the decision-making process to set PEEP. Point of care ultra-
sound has shown promises in this field [26]. FiO2 is usually set referring to a
target SpO2 (≥94 % in critical patients with AHRF, SpO2 between 88 and 92 %
in COPD cases) [27], but these criteria are not universally specifically validated
for NIMV and NCPAP patients.
Even the best way to deliver inhalation therapy is under debate [28, 29]. Are
nebulizers or pressurized metered dose inhalers better? And is it better to treat dur-
ing NCPAP or during intervals? The use of NIMV for treating ARF, since the last
decades, has grown continuously and spread outside the ICUs.
In the future for NCPAP, location, setting, environment, and welfare will be
important topics in ARF patient care [1]. Adequate staffing, 24 h a day and 7 days a
week, is mandatory. After pioneering trials, HMDUs and step-down units, mainly
inside the ED, strictly linked to the emergency room, were shown to have every
necessary characteristic to successfully deliver NIMV [12, 30]. Some general ward,
OOH, and even long-term acute care facilities show promise in delivering NCPAP
in AHRF [30]. Culture, education, training, technical and nontechnical skills, and
enthusiasm always make the difference in terms of efficacy, efficiency, and outcome
[4, 31, 32].
It is unlikely that shared criteria will be defined or that a consensus will be
reached regarding strong recommendations, but studies are needed to try to
standardize a “weaning” strategy from NCPAP to SO2T, referring, for example,
to ABG (improvement in pH and gas exchange), severity of respiratory distress,
trends of RR and SpO2, and so on (Table 14.9). Different hypotheses and trials
have been described toward the discontinuance of NCPAP for AHRF. Some
authors have suggested a gradational decrease of PEEP, others in FiO2, and still
others a reduction in time length of NCPAP, always with careful monitoring dur-
ing intervals. At present, there is no consensus about the way to end NCPAP,
and, even in the real-life world of emergency medicine, most frequently, the
142 R. Ferrari

Table 14.10 Criteria to stop Inability to correctly protect the airway

NCPAP in case of failure
Excessive secretions
Coma
Agitation
Sensorium worsening
Seizures
Hemodynamic instability
Electrocardiographic instability
Hypotension not responding in 1 h to fluid resuscitation
Inability to tolerate the interface
Inability to control leaks
Worsening (or inability to improve) dyspnea
Worsening (or inability to improve) respiratory distress
Signs of fatigue
PaO2 <65 mmHg with FiO2 ≥60 %

right time is often recognized by patients who independently decide to stop [1].
On the other hand, it is much clearer when to stop NCPAP in case of failure,
switching to IMV (Table 14.10).

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8. Masip J, Roque M, Sànchez B, et al. Noninvasive ventilation in acute cardiogenic pulmonary
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13. Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care set-
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Noninvasive Neurally Adjusted
Ventilatory Assist (NIV-NAVA) in Children 15
and Adults

Jennifer Beck, Yun Liu, and Christer Sinderby

Contents
15.1 Introduction .................................................................................................................... 146
15.2 Discussion and Analysis of NIV-NAVA ......................................................................... 146
15.2.1 Equipment and Theory ....................................................................................... 146
15.2.2 Ventilator Control............................................................................................... 147
15.2.3 Neural Integration with Respiratory Reflexes .................................................... 149
15.2.4 Recent Publications About NIV-NAVA.............................................................. 149
Conclusion .............................................................................................................................. 150
References ............................................................................................................................... 151

J. Beck, PhD (*)

Department of Pediatrics, University of Toronto, Toronto, ON, Canada
Keenan Research Centre for Biomedical Science, St. Michael’s Hospital,
Toronto, ON, Canada
e-mail: [email protected]
Y. Liu, MD
Department of Critical Care Medicine, Jiangsu Province Hospital,
Nanjing Medical University, Nanjing, Jiangsu Province, China
e-mail: [email protected]
C. Sinderby, PhD
Keenan Research Centre for Biomedical Science, St. Michael’s Hospital,
Toronto, ON, Canada
Department of Critical Care Medicine, St. Michael’s Hospital, Toronto, ON, Canada
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 145

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_15
146 J. Beck et al.

Abbreviations

Edi Electrical activity of the diaphragm

FRC Functional residual capacity
NAVA Neurally Adjusted Ventilatory Assist
NIV-NAVA Noninvasive Neurally Adjusted Ventilatory Assist
PEEP Positive end-expiratory pressure

15.1 Introduction

Neurally Adjusted Ventilatory Assist (NAVA) is a mode of ventilation controlled by

the electrical activity of the diaphragm (Edi) and can be delivered invasively (NAVA)
or noninvasively with different interfaces (NIV-NAVA). NAVA was US Food and
Drug Administration approved and has been commercially available since 2007.
More than 28 peer-reviewed studies in adults and infants (n = 376 patients) have
demonstrated unequivocally that, compared with conventional (pneumatically con-
trolled) modes of ventilation, patient-ventilator interaction – both in terms of timing
and proportionality – is much improved with NAVA and NIV-NAVA. For those
studies (n = 261 patients) reporting an Asynchrony Index (AI), NAVA has a signifi-
cantly lower AI (4.7 %) compared with pneumatically controlled mechanical venti-
lation (25.6 %).
The improvement in synchrony observed with NAVA and NIV-NAVA is achieved
by the use of a neural signal (the Edi), which is independent of pneumatics for the
purpose of controlling the ventilator. Often neglected, but equally important in the
evaluation of respiratory effort and respiratory metrics, is the additional benefit of
using the Edi signal as a monitoring tool. The Edi signal represents the final output
of the respiratory centers, after receiving multiple afferent inputs about lung stretch,
diaphragm force, arterial blood gases, and voluntary influences (Fig. 15.1).
Furthermore, the natural coordination of the upper airway (dilator) muscles with the
neural activation of the diaphragm allows efficient delivery of assist during NIV-
NAVA, without opposition from the upper airway constrictor muscles. The inter-
ested reader is referred to several detailed descriptions about NAVA, NIV-NAVA,
and the Edi signal [1–3]. This chapter provides an update of the clinical and experi-
mental findings of the use of NIV-NAVA since the 2013 Minerva publication [2].

15.2 Discussion and Analysis of NIV-NAVA

15.2.1 Equipment and Theory

The most important feature when using NIV-NAVA pertains to the Edi catheter
(a routinely used naso- or orogastric feeding tube with miniaturized sensors embed-
ded to record Edi), available in sizes suitable for adults and children (Fig. 15.2). The
15 Noninvasive Neurally Adjusted Ventilatory Assist (NIV-NAVA) in Children and Adults 147

Fig. 15.1 Multiple Upper

afferent signals Lung airways
Sedation
continuously meet and stretch
integrate in the respiratory
centers. The electrical CO2
Muscle Voluntary
activity of the diaphragm
force activation
(Edi) is the final neural
output from the respiratory
centers (efferent
stimulation of the
Respiratory
diaphragm) but contains Centers
the afferent information
about lung stretch, PaCO2,
and muscle force

Phrenic nerve

Edi

Edi catheter is connected to a SERVO-i or SERVO-U or SERVO-n ventilator

(Maquet Critical Care, AB, Solna, Sweden). The catheter is well tolerated and easy
to place, as described in the literature. During NIV-NAVA, any interface can be used
(e.g., face mask, helmet, nasal prongs) with maintained synchrony, because the con-
trol of the ventilator is not affected by leaks.

15.2.2 Ventilator Control

To initiate a ventilator breath, the Edi signal triggers inspiration once a threshold
change in Edi has been exceeded. The pressure delivered after triggering increases
during inspiration in proportion to the Edi, until neural exhalation begins, and the
ventilator cycles off (70 % of the peak Edi). The NIV-NAVA level determines the
proportionality between the Edi and the ventilator pressure. After cycling off,
the assist returns to a user-defined positive end-expiratory pressure (PEEP) level. In
this fashion, the patient is in control of their own ventilator rate and level of assist,
which can vary on a breath-by-breath basis. Figure 15.3 demonstrates Edi and ven-
tilator pressure tracings for an infant patient breathing on NIV-NAVA, and demon-
strates the synchrony between the Edi (patient) and airway pressure (ventilator),
both in terms of timing and proportionality. As in any another mode of mechanical
148 J. Beck et al.

Fig. 15.2 Example of an Edi catheter (8 F size shown), used for feeding and measuring of dia-
phragm electrical activity (Maquet, Solna, Sweden)

Fig. 15.3 Example of time tracings for ventilator pressure (top, yellow), flow (green), volume
(blue), and Edi (bottom, magenta). Note the synchrony and proportionality between Edi and ven-
tilator pressure, despite a leak (18 %)
15 Noninvasive Neurally Adjusted Ventilatory Assist (NIV-NAVA) in Children and Adults 149

ventilation, upper pressure limits can be set. Backup ventilation is provided in the
case of apnea or accidental catheter removal.

15.2.3 Neural Integration with Respiratory Reflexes

The neural drive to breathe during NIV-NAVA is controlled by multiple afferent

inputs originating in the lungs (stretch receptors), the central and peripheral chemo-
receptors (CO2 and pH sensitive), the respiratory muscles (muscle tension recep-
tors), and the upper airway muscles (chemical and pressure receptors). Depending
on clinical practice, a further influence on respiratory drive is sedation and analge-
sia. These multiple afferent inputs are continuously being “centralized” and “inte-
grated” in the respiratory centers of the brainstem, with the resultant package of
respiratory-related information being sent out via the phrenic nerves to electrically
activate the diaphragm (i.e., the Edi) and other respiratory muscles (Fig. 15.1).
Therefore, the physiological responses driving the patient’s diaphragm are also
simultaneously driving the ventilator throughout each breath during NIV-NAVA.

15.2.4 Recent Publications About NIV-NAVA

A total of 21 papers appear on PUBMED with the topic of NIV-NAVA since its
release in 2008. Since the update in Minerva in 2013 [3], five clinical NIV-NAVA
studies and one experimental study have been published [4–9]. Three of these arti-
cles were accompanied by editorials [10–12].
In 12 adult patients with COPD, Doorduin et al. [4] performed automated patient-
ventilator interaction analysis during NIV-pressure support ventilation (PSV)
(delivered with two separate ventilators, Maquet’s SERVO-i and Respironics’
Vision) and NIV-NAVA. Synchrony was superior (the Neurosync index was low,
5 %) during NIV-NAVA compared with NIV-PSV (24 % Vision, 21 % SERVO-i).
The improvement in synchrony was mainly due to reduced triggering and cycling-
off delays. The authors also found that there was a progressive number of wasted
efforts as the triggering and cycling-off delays got worse.
In pediatrics, three studies have all shown feasibility and tolerance of NIV-
NAVA, as well as insertion of the Edi catheter [5–8].
Vignaux et al. [5] demonstrated in six children (interquartile range 5–27 months)
requiring NIV for respiratory failure after surgery, that NIV-NAVA improved
patient-ventilator interaction (asynchrony index 2.3 %) compared to NIV-PSV
(asynchrony index 40 %), even with optimization of expiratory trigger setting in
PSV with Edi feedback. The improvement in synchrony was mainly due to reduced
trigger delays and a reduction in ineffective efforts.
In younger children receiving NIV for respiratory support following cardiac sur-
gery, Houtekie et al. [6] performed a cross-over study by randomizing babies
(age range 1–22 weeks and weight <5 kg) to either nasal continuous positive airway
pressure (CPAP) or NIV-NAVA immediately after extubation. The peak Edi values
150 J. Beck et al.

during NIV-NAVA were significantly lower, indicating more diaphragm unloading

compared with nasal CPAP. Synchrony analysis was reported for NIV-NAVA and
showed (despite average leakage of 70 %) 99 % neural triggering (compared with
95 % in the Vignaux et al. [5] study), with a low inspiratory trigger delay.
More recently, in another physiological cross-over study, NIV-NAVA was com-
pared with conventional NIV in 13 children admitted to the pediatric intensive care
unit for respiratory failure (interquartile age range 2–109 months), 8 of whom had
pneumonia or bronchiolitis [7]. The authors found that during conventional NIV,
patients spent between 27 and 32 % of the time in asynchrony, whereas it was only
8 % of the time in NIV-NAVA. This was mainly a result of reduced trigger delay,
cycling-off delay, and ineffective efforts. These same authors also described the
clinical importance of monitoring the Edi signal during all NIV modes after extuba-
tion in a recent review [13].
In 11 children with viral bronchiolitis who were failing nasal CPAP (aged on
average 35 days), Baudin et al. [8] studied patient-ventilator interaction during nasal
pressure assist control (settings determined clinically) versus NIV-NAVA (2 h each).
With matching peak pressures in both modes, breath-by-breath analysis revealed a
lower asynchrony index during NIV-NAVA, mainly due to less trigger delays.
Ineffective efforts were extremely prevalent during nasal pressure assist control
(~22 events per minute), and did not occur during NIV-NAVA. The number of auto-
triggering events was higher in assist control (8 per minute) compared with NIV-
NAVA. The neural respiratory rate and ventilator rate were comparable for
NIV-NAVA; however, in pressure assist control, neural respiratory rate was higher
than the ventilator rate.
In animals with early experimental injury, Mirabella et al. [9] examined lung
injury markers after 6 h of volume control ventilation with a lung protective strategy
(6 ml/kg with PEEP), compared with 6 h of NIV-NAVA and spontaneous breathing
and no PEEP, and found a lower lung injury score and plasma interleukin (IL)-8 for
the NIV-NAVA group. Interestingly, despite no PEEP being applied during NIV-
NAVA, the upper airways were able to aid in the maintenance of functional residual
capacity (FRC).

Conclusion
NAVA is a promising technique for NIV because it is able to provide synchro-
nized and proportional assist, even in the presence of large leakage. In light of
studies demonstrating the role of asynchrony on intensive care unit length of
stay, duration of mechanical ventilation, and mortality [14], it would seem that
improving synchrony should be a priority. NIV-NAVA allows the patient the
freedom to choose their own breathing pattern, and to recruit the lung when
needed with large inspirations (sighs) or maintenance of FRC with tonic activa-
tion of the diaphragm. The upper airway dilator muscles are coordinated with the
onset of diaphragm activation, and therefore, the risk of gastric insufflation may
be reduced with NIV-NAVA. We acknowledge that, in the presence of large
leaks, pressure delivery may be underestimated, and it is possible that the NAVA
level should be increased to compensate. The Edi signal offers the tool for this
15 Noninvasive Neurally Adjusted Ventilatory Assist (NIV-NAVA) in Children and Adults 151

evaluation, as increasing the NAVA level – if resulting in unloading of the dia-

phragm – could be monitored. In addition, if respiratory rate is an important
clinical metric, the neural frequency (which is unaffected by leaks) offers a reli-
able measurement, restoring confidence in decision support.

Key Major Recommendations

• Use NIV-NAVA to improve synchrony.
• Use Edi during NIV to obtain a reliable measure of neural respiratory
drive.
• Use Edi during NIV to obtain a reliable measure of respiratory rate.

Disclosure Drs. Beck and Sinderby have made inventions related to neural control of mechanical
ventilation that are patented. The patents are assigned to the academic institution(s) where the
inventions were made. The license for these patents belongs to Maquet Critical Care. Future com-
mercial uses of this technology may provide financial benefit to Drs. Beck and Sinderby through
royalties. Dr. Beck and Dr. Sinderby each own 50 % of Neurovent Research Inc. (NVR). NVR is
a research and development company that builds the equipment and catheters for research studies.
NVR has a consulting agreement with Maquet Critical Care.

References
1. Sinderby C, Beck J. Neurally adjusted ventilatory assist. In: Tobin MJ, editor. Principles and
practice of mechanical ventilation. 3rd ed. New York: McGraw Hill; 2012.
2. Sinderby C, Beck J. Neurally adjusted ventilatory assist in non-invasive ventilation. Minerva
Anestesiol. 2013;79(8):915–25.
3. Oppersma E, Doorduin J, van der Heijden EH, et al. Noninvasive ventilation and the upper
airway: should we pay more attention? Crit Care. 2013;17(6):245.
4. Doorduin J, Sinderby CA, Beck J, et al. Automated patient-ventilator interaction analysis dur-
ing neurally adjusted non-invasive ventilation and pressure support ventilation in chronic
obstructive pulmonary disease. Crit Care. 2014;18(5):550.
5. Vignaux L, Grazioli S, Piquilloud L, et al. Patient-ventilator asynchrony during noninvasive
pressure support ventilation and neurally adjusted ventilatory assist in infants and children.
Pediatr Crit Care Med. 2013;14(8):e357–64.
6. Houtekie L, Moerman D, Bourleau A, et al. Feasibility study on neurally adjusted ventilatory assist
in noninvasive ventilation after cardiac surgery in infants. Respir Care. 2015;60(7):1007–14.
7. Ducharme-Crevier L, Beck J, Essouri S, et al. Neurally adjusted ventilatory assist (NAVA)
allows patient-ventilator synchrony during pediatric noninvasive ventilation: a crossover phys-
iological study. Crit Care. 2015;19:44.
8. Baudin F, Pouyau R, Cour-Andlauer F, et al. Neurally adjusted ventilator assist (NAVA)
reduces asynchrony during non-invasive ventilation for severe bronchiolitis. Pediatr Pulmonol.
2014. doi:10.1002/ppul.23139.
9. Mirabella L, Grasselli G, Haitsma JJ, et al. Lung protection during non-invasive synchronized
assist versus volume control in rabbits. Crit Care. 2014;18(1):R22.
10. Quintel M, Moerer O. Another brick in the wall of needs for invasive ventilation? Crit Care.
2014;18(2):122.
11. Ramet J, De Dooy J. Patient-ventilator asynchrony during noninvasive pressure support venti-
lation and neurally adjusted ventilatory assist in infants and children. Pediatr Crit Care Med.
2013;14(7):728–9.
152 J. Beck et al.

12. Nava S, Pisani L. Neurally adjusted non-invasive ventilation in patients with chronic obstruc-
tive pulmonary disease: does patient-ventilator synchrony matter? Crit Care. 2014;18(6):670.
13. Ducharme-Crevier L, Du Pont-Thibodeau G, Emeriaud G. Interest of monitoring diaphrag-
matic electrical activity in the pediatric intensive care unit. Crit Care Res Pract. 2013;2013:
384210.
14. Blanch L, Villagra A, Sales B, et al. Asynchronies during mechanical ventilation are associated
with mortality. Intensive Care Med. 2015;41(4):633–41.
Off-Cycling During NIV in Chronic
Obstructive Pulmonary Disease: Clinical 16
Implications

Lars-Olav Harnisch and Onnen Moerer

Contents
16.1 Introduction ................................................................................................................. 153
16.2 Discussion and Analysis ............................................................................................. 154
16.2.1 Lung Mechanics in COPD ............................................................................ 154
16.2.2 Flow and Pressure Curves and Ventilator Performance ................................ 155
16.2.3 Patient-Ventilator Interaction ........................................................................ 156
16.2.4 Premature Off-Cycling .................................................................................. 156
16.2.5 Delayed Off-Cycling ..................................................................................... 156
Conclusion ............................................................................................................................. 158
References .............................................................................................................................. 159

16.1 Introduction

Noninvasive mechanical ventilation (NIV) has evolved to be part of the current

standard therapy for patients suffering from acute exacerbation of chronic obstruc-
tive pulmonary disease (aeCOPD) [1]. Using noninvasive ventilation in this condi-
tion helps to avoid the common complications of invasive ventilation, such as
ventilator-associated pneumonia, and has been shown to substantially improve the
course of the disease and decrease length of hospital stay [2].
Although NIV is widely used with great benefit in aeCOPD, there are patients for
whom and situations where NIV does not provide satisfactory support or even adds
further stress and increases the patient’s work of breathing. A main cause is poor
patient-ventilator interaction attributed to patient-ventilator asynchrony, which is
reported to be common in NIV [3]. Additionally, the characteristics of the chosen

L.-O. Harnisch • O. Moerer (*)

Department of Anesthesiology, Emergency- and Intensive Care Medicine, University of
Goettingen Medical School, Robert-Koch-Str. 40, Goettingen 37099, Germany
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 153

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_16
154 L.-O. Harnisch and O. Moerer

interface, individual patient characteristics, and suboptimal ventilator settings have

been found to be a major source of this asynchrony. During pressure support venti-
lation (PSV) - the ventilator mode of assisted mechanical ventilation mainly used
for NIV at present - patient ventilator interaction is of major importance.
Delayed recognition of the patient’s inspiratory effort (inspiratory trigger delay)
by the ventilator at the beginning of the inspiration, and especially a prolonged
inspiratory phase at the end of the patient’s inspiratory phase (expiratory trigger
delay or off-cycling delay), lead to considerable asynchrony between the patient’s
and the ventilator’s inspiratory and expiratory phases. The transition from inspira-
tion to expiration, known as ventilator (off-)cycling, occurs when inspiratory flow
provided by the ventilator decreases to a predetermined fraction of peak inspiratory
flow [4]. Prolonged pressurization by the machine into the patient’s expiratory
phase can lead to expiratory asynchrony and increased work of breathing [2].
Ideally, cycling should coincide with the end of the patient’s inspiratory effort
and no delay or premature termination should be observed. However, clinically,
untimely off-cycling is always present but can be small or large in value and, there-
fore, varies in relevance for the individual patient.
Delayed off-cycling is a crucial determinant for patient-ventilator synchrony and
most likely occurs in the presence of COPD [4, 5] if a low and fixed value for expira-
tory triggering and off-cycling is used, as is the case with many mechanical ventila-
tors. Adjusting the off-cycling criterion should improve patient-ventilator synchrony
(Moerer O et al., unpublished data). To reduce asynchrony, fitting the ventilator well
to the patient, lung mechanics in COPD, pressure and flow curves, ventilator perfor-
mance, and patient-ventilator interaction have to be thoroughly understood.

16.2 Discussion and Analysis

16.2.1 Lung Mechanics in COPD

In comparison with respiration in a healthy person, COPD is characterized by a

profound change in respiratory mechanics and respiratory muscle function [6]. The
pathophysiological hallmark of COPD is an expiratory flow limitation. In flow-
limited patients, expiratory time is often too short to allow lung volume to decline
to its physiological functional residual capacity. Dynamic hyperinflation occurs in
flow-limited patients when the inspired tidal volume increases and/or the expiratory
time decreases, resulting in variable increases of end-expiratory lung volume. Acute
exacerbations of COPD are marked by an abrupt increase in airway resistance,
worsening expiratory flow limitation and consequently increasing end-expiratory
lung volume. Because of the failure of the muscle pump, patients are not able to
maintain a sufficient tidal volume and often adopt a rapid, shallow breathing pattern
that further limits expiratory time [7].
Viewed from a pressure point of view, dynamic hyperinflation can be defined as
intrinsic positive end-expiratory pressure (PEEPi). The additional remaining vol-
ume in the lung increases airway pressure at the end of expiration. This pressure has
16 Off-Cycling During NIV in Chronic Obstructive Pulmonary Disease 155

to be overcome at the beginning of the next inspiration, which takes more work than
without PEEPi because the compliance curve of the lung is sigmoid and more pres-
sure is therefore needed to inflate the lung sufficiently.

16.2.2 Flow and Pressure Curves and Ventilator Performance

A normal breath starts with contractions of the diaphragm, creating a negative pres-
sure in the respiration system that can be measured at mouth level. This value is
known as p0.1, and it is measured by a short inspiratory occlusion maneuver and depic-
tures strength of inspiration force. In unassisted spontaneous breathing, inspiration
goes on as long as there is a pressure difference between the pressures inside the lung
and the surrounding atmosphere, that is, until they are equaled. At the end of inspira-
tion, the diaphragm relaxes and expiration is said to happen passively, meaning that
there is normally no active contraction of muscles involved. Nevertheless, there is an
active recoil of stretched elastic structures such as thorax and lung tissue. In flow-
limited patients, the active recoil of elastic structures often lacks force to overcome the
increased airway resistance, and these patients additionally use muscles (intercostal
and abdominal) that reduce the size of the thoracic cavity to increase expiration force.
Because of the increased airway resistance, it takes longer for these patients to exhale
their tidal volume, which can clinically be seen as a prolonged expiration time.
PSV is mainly used for NIV at present. In this ventilation mode, start and stop of
the patient’s inspiration are marked by pressure changes in the ventilation system
(patient, ventilator, connecting tubes, etc.) detected by the ventilator. Modern venti-
lators use either a pressure or a flow trigger for cycling; in some machines, the trig-
ger can be chosen.
If a pressure trigger is used, the ventilator measures p0.1 directly and cycles when
a certain (preset) value appears. In flow triggering, the ventilator tries to hold the
pressure in the ventilation system steady. When the patient initiates inspiration, a
flow directed away from the ventilator occurs that is measured as pressure drop
within the ventilator or deflection of a membrane in the breathing stream. This is
what causes the ventilator to cycle when, again, a preset value is reached. Knowing
this, a pressure curve of noninvasive ventilation can be viewed as follows: Starting at
PEEP-level, first a pressure drop appears. When the ventilator starts pressure sup-
port, this pressure drop is equaled to PEEP-level and then turned into a positive pres-
sure with preset variables. This pressure will be held until the off-cycling criterion is
reached; after this point, expiration is “allowed” by the ventilator. During expiration,
airway pressure decreases back to PEEP-level with its own time constant. A flow
curve of noninvasive ventilation might be described like this: From a constant (bias-)
flow, flow increases up to a maximum (FMAX) and decreases a little, but continuously,
from that point on. This decreasing flow goes on up to the off-cycling criterion where
flow is stopped, returns to bias flow, and expiration is therefore facilitated.
The majority of modern ventilators allow for an individual adjustment of off-
cycling criteria. The main challenge is, by and large, the decision of when and how
to sufficiently adjust this parameter.
156 L.-O. Harnisch and O. Moerer

16.2.3 Patient-Ventilator Interaction

The impaired lung mechanics in COPD and knowledge of ventilator performance

and its limits are the basis for optimizing patient-ventilator interaction. Although
the latter is usually the case with COPD patients, impaired off-cycling of the venti-
lator to herald the expiratory phase can either be too early or too late.

16.2.4 Premature Off-Cycling

Having set the off-cycling criterion to high values of about 60 and 70 % peak flow,
double triggering can be observed regularly as a specificity of asynchrony. At these
high off-cycling values, pressure support appears only for a short duration of time in
the breathing cycle. In these cases, pressure support stops when the patient has not yet
stopped the inspirational effort. As a consequence, problems occur when the ventila-
tor is ready for on-cycling again while inspiration effort is still going on. In these
cases, the ventilator misinterprets ongoing inspiration as another inspiration and will
administer pressure support. This extra pressure support leads to overinflation of the
lungs; it adds expiratory pressure load and, therefore, even more expirational work of
breathing to the already impaired expirational flow, and, last but not least, PEEPi is
increased. All of these are unfavorable effects. As a side note, these effects seem to be
less frequent when using a ventilation helmet compared with a nose-and-mouth-ven-
tilation mask because flow and pressure transmissions from patient to ventilator are
somewhat impaired due to the internal volume of the helmet [8].

16.2.5 Delayed Off-Cycling

Setting the off-cycling criterion to very low values of about 10 and 20 %, nonsup-
ported inspirational effort is likely to appear. With the ventilator “waiting” for flow to
decrease to 10 % or even 20 % of peak inspiratory flow, pressure support often goes
on into the next breathing cycle, and sometimes flow does not even reach these low
flow values. In these cases, the ventilator still facilitates expiration while the patient
already wants to have another inspiration. Therefore, obviously, no inspirational pres-
sure support can be given and work of breathing or tidal hyperinflation increases for
that breath. Again, these effects seem to be related to the ventilation device used.
Nonsupported inspirational effort seems to be more likely to occur using a nose-and-
mouth ventilation mask than using a ventilation helmet. Once again, impaired trans-
missions resulting from internal helmet volume seems to be liable.
16 Off-Cycling During NIV in Chronic Obstructive Pulmonary Disease 157

Taking a stepwise approach to understanding the effects of adjustment of the off-

cycling criterion, a mode result would most likely look like this: Setting the off-
cycling criterion to low values about every second inspirational effort will not be
supported by the ventilator. Raising the off-cycling criterion nonsupported inspira-
tional effort will disappear, but the PEEPi measured by the ventilator will still be
large. Raising off-cycling further, PEEPi will diminish further. Raising off-cycling
further still, suddenly double triggering will be present in high off-cycling criteria.
Because this model seems to be common in COPD, the off-cycling criterion that
allows the best synchrony was found to be 50 % peak inspiratory flow on average
(Moerer O et al., 2014, unpublished data) (Figs. 16.1 and 16.2). However, this value
should not be set blindly. There are a large variety of influencing and biasing factors
that have an impact on synchrony and asynchrony. As mentioned before, the con-
necting ventilation device has its specific characteristic influence, but there are other
factors such as respiration frequency, height of pressure support, and, of course, the
ventilator itself with its specific mechanical and software characteristics. The prime
influencing factor, however, is the patient him or herself. Lung mechanics such as
compliance, resistance, mucus production, and airway smooth muscle tone, just to
mention a few, change on a breath-to-breath basis, throughout an exacerbation and
throughout the course of the disease as a whole. This makes it pretty clear that no
single off-cycling criterion can be recommended generally. Rather, finding the per-
fect off-cycling criterion for the aeCOPD patient is an ongoing trial-and-error bed-
side process that needs to be reviewed and adjusted over and over again, throughout
the day if needed, that is, when asynchrony is present.

Expiratory delay dependence on setting

Severe delay of ventilator off-cycling criterion
600
Expiratory delays [%]

Full synchonization
0 Full synchonization

10 %
20 %
30 %
40 %
50 % −600
Premature cycling
60 %
70 %
Off-cycling criterion [%]

Fig. 16.1 Influence of ventilator off-cycling on patient-ventilator synchronization in

COPD. Symbolized presentation of the findings from several studies and data from the authors’
own investigations [3, 4] (Moerer O et al., 2014, unpublished)
158 L.-O. Harnisch and O. Moerer

PEEPI dependence on setting of

ventilator off-cycling criterion
High intrinsic PEEP
0.5

PEEP-

PEEP [cmH2O]
Setting Low intrinsic PEEP
(8 cmH20) 0

10 % 20 %
30 %
40 %
50 % - 0.5
60 %
70 %
Off-cycling criterion [%]

Fig. 16.2 Influence of set ventilator off-cycling on the development of intrinsic PEEPi (symbol-
ized presentation of the findings from several studies and data from the authors’ own investigations
[4, 5] (Moerer O et al., 2014, unpublished). Obviously, the lowest PEEPi values appear at an off-
cycling criterion of 40–50 %. Negative values are very small and therefore negligible; they are due
to the inability of many ventilators to maintain PEEP in the face of leakage. Because the default
value in ventilators is often 25 % peak flow, this setting needs to be adjusted in COPD patients

Conclusion
The off-cycling criterion needs to be adjusted very precisely, but there is not one
single value that can be recommended. Nevertheless, some assistance can be
granted as to how to find the optimal setting for the individual patient.
The existence of high PEEPi, prolonged inspiratory plateau phase and
mechanical inspiration time, an end-inspiratory increase in pressure, or nonsup-
ported inspirational effort suggest a belated off-cycling. In their presence, off-
cycling criteria should be raised as long as the measured values are not satisfactory
or until nonsupported inspirational effort disappears. As an indicator of accuracy
of the off-cycling criterion setting, the value may very well be larger than 30 %
peak flow in COPD patients.
On the other hand, when double triggering or decreased tidal volume are pres-
ent, which can be detected easily in clinical practice, they are likely to depicture
premature off-cycling. Here, off-cycling criteria should be decreased until dou-
ble triggering disappears and tidal volume increases to a maximum. Furthermore,
curve-tracings can be easily done inasmuch as any ventilator displays the venti-
lation curves. In doing so, dissenting characteristics, such as convexity in an
expiratory flow curve or concavity of an expiratory pressure curve, depicturing
expiratory flow limitation may be found.
As has been said before, setting the off-cycling criterion cannot be done in a
“drive-by” mode, but one has to take the time to assess the parameters and curves
described to adjust the ventilator to the patient. Once the optimal setting has been
found, one has to go over the process just described again and again to readjust
the off-cycling criterion because lung mechanics as well as human afflictions are
dynamic processes.
16 Off-Cycling During NIV in Chronic Obstructive Pulmonary Disease 159

After all, to be honest, good patient-ventilator synchrony has not been shown
to be of benefit. But bad synchrony has been shown to produce bad comfort for
the patient [3], can be responsible for prolonged mechanical ventilation and NIV
failure [9], and is clearly associated with increased morbidity and mortality [10].
Thus, finding the optimal setting regarding off-cycling seems not to be an auxil-
iary task but rather a conditio sine qua non!

Recommendations
• Reevaluation and adjustments of off-cycling criteria must not be viewed as
auxiliary but rather mandatory, especially in patients suffering from COPD,
and should be part of the daily routine.
• Detect patient-ventilator asynchrony by clinical events or tracing of flow-
and pressure curves and values measured by the ventilator.
• Raise the off-cycling criterion as long as nonsupported inspiratory effort,
prolonged inspiratory time, or high PEEPi persists.
• Decrease the off-cycling criterion as long as double triggering or low tidal
volumes due to asynchrony persist.

References
1. Crimi C, Noto A, Princi P, et al. A European survey of noninvasive ventilation practices. Eur
Respir J. 2010;36:362–9.
2. Burns KE, Adhikari NK, Meade MO. A meta-analysis of noninvasive weaning to facilitate
liberation from mechanical ventilation. Can J Anaesth. 2006;53:305–15.
3. Vignaux L, Vargas F, Roeseler J, et al. Patient-ventilator asynchrony during non-invasive ven-
tilation for acute respiratory failure: a multicenter study. Intensive Care Med. 2009;35:840–6.
4. Gentile MA. Cycling of the mechanical ventilator breath. Respir Care. 2011;56:52–60.
5. Jubran A, Van de Graaff WB, Tobin MJ. Variability of patient-ventilator interaction with pres-
sure support ventilation in patients with chronic obstructive pulmonary disease. Am J Respir
Crit Care Med. 1995;152:129–36.
6. Bergmann N. Intrapulmonary gas trapping during mechanical ventilation at rapid frequencies.
Anesthesiology. 1972;37:626–33.
7. O’Donnell DE, Parker CM. COPD exacerbations. 3: pathophysiology. Thorax.
2006;61:354–61.
8. Moerer O, Fischer S, Hartelt M, et al. Influence of two different interfaces for noninvasive
ventilation compared to invasive ventilation on the mechanical properties and performance of
a respiratory system: a lung model study. Chest. 2006;129:1424–31.
9. Thille AW, Rodriguez P, Cabello B, et al. Patient-ventilator asynchrony during assisted
mechanical ventilation. Intensive Care Med. 2006;32:1515–22.
10. Chao DC, Scheinhorn DJ, Stearn-Hassenpflug M. Patient-ventilator trigger asynchrony in pro-
longed mechanical ventilation. Chest. 1997;112:1592–9.
 Part II
Monitoring Respiratory Care,
Phisiotherapy and Rehabilitation
Monitoring Patients During Noninvasive
Ventilation: The Clinical Point of View 17
G. Caironi, G. Gadda, R. Rossi, and Andrea Bellone

Contents
17.1 Introduction ................................................................................................................. 164
17.2 Discussion ................................................................................................................... 164
17.2.1 Time: Start – Patient Positioning, Information, and First Care ..................... 164
17.2.2 Time: First 15 Min – Selection and Management of Interface Device,
Patient-Ventilator Interaction, and Reduction of Major Adverse
Effects............................................................................................................ 165
17.2.3 Time: After the First 15 Min – Monitoring Vital Signs
and Blood Gas Analysis ................................................................................ 169
Conclusions ............................................................................................................................ 171
References .............................................................................................................................. 172

G. Caironi, RN
Emergency Department, A.O. Sant’Anna (Presidio di Como), Como 22100, Italy
e-mail: [email protected]
G. Gadda, LN
Emergency Unit, A.O. Guido Salvini (Presidio di Rho), Como 22100, Italy
e-mail: [email protected]
R. Rossi, LN
Emergency Unit, A.O. Sant’Anna (Presidio di Cantù), Como 22100, Italy
e-mail: [email protected]
A. Bellone, MD (*)
Emergency Department, UOC di PS-OSA, Via Ravona 1, San Fermo della Battaglia,
Como 22100, Italy
Emergency Department, A.O. Sant’Anna (Presidio di Como), Como 22100, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 163

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_17
164 G. Caironi et al.

17.1 Introduction

Noninvasive ventilation (NIV) has proved to be an excellent technique in selected

critical patients with acute respiratory failure due to different causes. Careful patient
selection is imperative for successful outcomes, and a number of predictors have
been identified to maximize success on NIV [1, 2].
Equally important, however, is the monitoring, because only careful and continu-
ous patient care may prematurely detect improvements or worsening of the clinical
condition. Monitoring is the set of actions that confirms the correct choice of venti-
lation, analyzes the patient’s condition, guides all adjustments of the ventilator set-
tings, and assesses the patient-ventilator interaction. Monitoring includes five
different levels: (1) information about the patient and positioning; (2) choice of
interface and reduction of the main adverse effects (leaks, patient-ventilator missed
interaction); (3) patient observation, assessment of vital signs, evaluation of clinical
condition (state of consciousness, anxiety level, and characteristics of breathing);
(4) evaluation of laboratory data (arterial blood gas); and (5) continuous checking
of ventilation parameters on the basis of clinical response. The combination of these
different aspects, integrated in a continuous development of events, comprises
monitoring.
Finally, the objective is to assess the patient-ventilator interaction, making sure
that the ventilator “has to adapt” to the patient, and not patient to ventilator, improv-
ing patient outcome. Clinical observations provide measures for objective progress
evaluation and assessing the opportunity for weaning.

17.2 Discussion

17.2.1 Time: Start – Patient Positioning, Information,

and First Care

Nurses must communicate care, composure, and competence, as dyspneic patients

are distressed, often fearing the worst. Confident and professional care may ease
the patient’s distress, gaining cooperation and motivating the patient to adapt to
NIV [3].
Generally, the sitting position is preferred by patients with respiratory distress. In
case of an overweight patient with a protuberant abdomen, the semi-sitting or supine
position for ventilating is sometimes preferable, if possible. Sitting upright with the
head well supported, or in a more advanced position with upper body forward and
elbows resting on a support, promotes better recruitment of respiratory muscles and
better diaphragmatic excursion. The patient should be placed in stable, comfortable,
and convenient position, using supports and pillows to maintain the correct
position.
Assess the patient’s consciousness level with the Glasgow Coma Scale or, better,
the Kelly scale. Assess that the patient’s airways are not obstructed and that patient
is able to cough and expectorate. Examine the abdomen for distension, air
17 Monitoring Patients During Noninvasive Ventilation: The Clinical Point of View 165

swallowing, and nausea as possible immediate complications in NIV. These inspec-

tions must be ensured at the beginning and also throughout the entire ventilation
treatment [4].
Before treatment begins, it is appropriate to provide information about and
explain the purpose and potential benefits of NIV, obtaining verbal consent and
screening the bed to protect patient privacy and dignity.
Encouraging patients to hold the mask to their face while the ventilator is on and
asking them to breathe is a good way for begin. Patients can also be shown how to
release the mask quickly so they feel they have some control over the system [3].

17.2.2 Time: First 15 Min – Selection and Management

of Interface Device, Patient-Ventilator Interaction,
and Reduction of Major Adverse Effects

17.2.2.1 Interface Device

Choice of interface is an important determinant of NIV success or failure and the
goal is to maximize patient comfort, minimizing leaks and allowing patient-
ventilator synchrony [5]. This chapter will not discuss whether it is preferable to use
a facial mask or a helmet. Many studies show the effectiveness of both devices,
identifying their advantages and disadvantages. A helmet ensures better tolerability
but allows CO2 rebreathing and potential patient asynchrony. Masks are sometimes
poorly tolerated and may result in skin lesions.
Recently, preliminary data showed that an optimized setup for helmet bi-level
positive airway pressure (PAP), which limits device compliance and ventilator cir-
cuit resistance as much as possible, might be highly effective in improving pressure
support delivery and patient-ventilator interaction [7]. Simultaneously, it is widely
accepted that a helmet is the best interface with a very high tolerability when pro-
longed and continuous assistance is needed, for instance, in an intensive care unit or
during pre-hospital treatment. On the other hand, in the emergency department,
where the ventilation time is short and patients are often older with high comorbidi-
ties, including chronic obstructive pulmonary disease (COPD), the best interface for
delivering bi-level PAP seems to be the face mask. However, as for the comparison
between continuous positive airway pressure (CPAP) and bi-level PAP modalities
of NIV, the choice of ventilator interfaces should be based on factors such as staff
experience, habit, and individual patient’s choice [3, 4].
In choosing a mask, the appropriate mask size, the correct size of headgear, the
presence of a mask cushion, and the size of the dead space (to minimize CO2
rebreathing) are important [6]. A full face mask is recommended for the initial 24 h
and is better for patients with COPD, who tend to mouth breathe [7].
It is important to have a different kind of interfaces available (helmet, oro-nasal
mask, total face mask) with different sizes because a variety of interfaces for NIV
can be used in the acute care setting. Prevention and monitoring of side effects
related to interfaces and evaluation of patient tolerance are crucial to avoiding NIV
failure as protocols shared by the whole team [3].
166 G. Caironi et al.

Table 17.1 Causes of leaks Descriptor % of nonadaptation

Face format 30.5
Discomfort 28.8
Air leaking 27.7
Claustrophobia 18.6
Uncooperative patient 10.1
Patient agitation 6.7
Other causes

17.2.2.2 Leaks and Adjusting Interface Devices

The first step in monitoring is to observe and assess the leaks of air around the
interface device. The primary cause of leaks is a poor fit between mask and skin
caused by several factors (Table 17.1) [8]. Position the interface device comfort-
ably, avoiding making it too tight. Keep the device adherent to the patient’s face
manually for some minutes, allowing the patient to become familiar with the cho-
sen interface device. This procedure also allows checking to see whether the
device choice is the correct shape and size and if it fits the patient's face. Then, the
mask should be secured in place with straps and/or headgear and reassessed after
few minutes.
There are many possible side effects and adverse events. If the mask causes dis-
comfort, it is possible to check the fit, adjust the straps, or choose another mask
type. Masks can cause erythema or nasal bridge ulceration and it is appropriate to
apply artificial skin (hydrocolloid dressing) to prevent this. In prolonged treatment,
nasal or oral dryness may occur and the recommendation is to use nasal saline/
emollient. To prevent leaks, an oro-nasal mask is sometimes preferred or pressures
can be reduced slightly. Check for air leaks into the eyes (which can lead to conjunc-
tivitis), around the nose, and at the side of the interface.
High-performing ventilators show leaks through a numerical estimate expressed
as a percentage and compensate for them. In the first 10–15 min of treatment, the
percentage of acceptable leaks is not more than 20 %. A successful patient adapta-
tion and a patient-ventilator interaction should then progress to a reduction in the
percentage of leaks from the system.
The effectiveness of treatment is achieved by obtaining the right balance between
high leaks and excessive intolerance of the interface device. Remember that when
positive pressure (inspiratory positive airway pressure, or IPAP) reaches more than
20 cmH2O, it may cause a marked increase in leaks.

17.2.2.3 Patient-Ventilator Interaction and Pressure-Flow Graph

Interpretation
Especially in the first 10–15 min of ventilation, it is crucial to monitor the adapta-
tion of the patient to the ventilator and whether the ventilator is really assisting with
the patient’s respiratory efforts. One hand should be positioned on the abdomen of
the patient, feeling breaths and then comparing them with those reported in the
graphs of flow and pressure (Fig. 17.1). Each inspiration by the patient should match
17 Monitoring Patients During Noninvasive Ventilation: The Clinical Point of View 167

Onset of Support End of Support

Mechanical Inspiration

Support
E

A C

Peep
B

Flow

Patient Inspiration

By Guido Caironi

Fig. 17.1 Matching patient effort and ventilator assistance

the curve of respiratory support delivered by the ventilator and shown on the graph.
The assessment of inspiratory function includes evaluation of synchronization
between inspiratory effort and the onset of ventilation assistance and trigger sensi-
tivity. Synchronization is evaluated by assessing the time lag between the onset of
effort and the initial delivery of flow.
In Fig. 17.1, the interval A-B on the x-axis (time) represents the trigger delay,
corresponding to trigger sensitivity. Inadequate matching between ventilator and
patient could be to the result of a delay of ventilation assistance exceeding 360 ms
[9] (too hard a trigger, inadequate circuit connections).
Ineffective efforts (muscle contractions not able to trigger the ventilator) are the
most frequent problems in patients with obstruction and ventilated with high inspi-
ratory pressures and high tidal volumes that avoid complete exhalation of the accu-
mulated air. Therefore, the patient tries to start a new breath (Fig. 17.2, part a) when
168 G. Caironi et al.

0,4
Flow
(L/s)

−0,4
Ineffective efforts
24
Airways Pressure
(Cm/H20)

16

Leak during
b inspiration

0,4
Flow
(L/s)

−0,4
Airways Pressure

24
(Cm/H20)

16

8 Hung Up

By Guido Caironi

Fig. 17.2 Ineffective efforts (part a) and “hung up” phenomenon (part b)

the degree of hyperinflation is too high to allow him or her to return to the equilib-
rium point of the respiratory system and then to trigger the ventilator. The analysis
of the parameters of flow and airway pressure shows a few small “ bumps” that are
not followed, or are contemporaneous, to an inspiratory support by the ventilator.
The patient is unsuccessfully attempting to trigger the machine.
An assisted inspiration followed quickly by another one (or three, in “triple trig-
gering”) is another problem. It can be explained by setting a flow too high, or a too
sensitive expiratory trigger, that requires a modest flow fall to switch from the
17 Monitoring Patients During Noninvasive Ventilation: The Clinical Point of View 169

inspiratory phase to the expiratory phase. Figure 17.2 part b shows a prolonged
inspiratory act, and the graph of flow shows a fall, followed by a plateau; this is the
“hung up” phenomenon. The patient does not appear to reach a predetermined drop-
ping flow level to switch to the expiratory phase. The problem is usually caused by
circuit or interface device leaks that interfere with the ventilator algorithm, increas-
ing the inspiratory time over the maximum established [9]. If the patient is not able
to adapt, it is appropriate to ensure that he or she is not muscularly exhausted, that
there is no airway obstruction, and that the circuit does not suffer from leaks or
disconnections.

17.2.3 Time: After the First 15 Min – Monitoring Vital Signs

and Blood Gas Analysis

17.2.3.1 Vital Signs and Clinical Status

The patient treated with NIV should be located in a special area, with an available
cohort of staff with adequate experience, equipped with a multi-parameter monitor
and devices for emergency management. Primarily, and in the first minutes, it is
necessary to assess the work of breathing through the observation of accessory mus-
cle recruitment (such as sternocleidomastoid muscle activity) and respiratory rate.
Lack of reduction in respiratory frequency indicates that alveolar ventilation is not
obtained because of a wasted ventilation. Causes include inappropriate ventilation
setting leading to patient intolerance, leaks, and missed coordination with the ven-
tilator [3, 10].
Improvement in dyspnea is usually seen within 15 min to 1 or 2 h and is usually
accompanied by an improvement of the neurological state [3]. Therefore, the
evaluation of tidal volume is crucial, expecting a value of 8 ml/kg (better the expi-
ratory tidal volume, shown by the ventilator monitor, because it is less influenced
by leaks).
In the published papers about NIV ventilation, there are few data on oxygen satu-
ration or transcutaneous CO2. However, several studies have shown that oxygen
levels improve early with NIV: SpO2 monitoring is likely helpful, although does not
replace the need for measurements of arterial blood gas tensions in the early stages
of treatment. Oxygen saturation should be monitored continuously for at least 24 h
after beginning NIV and supplementary oxygen administered to maintain saturation
between 85 and 90 %. Transcutaneous CO2 monitoring can also be used when it is
available because it provides a more complete picture of alveolar ventilation as an
integration of arterial blood gas analysis.
Monitoring of the vital signs must be done through a multi-parametric monitor,
which is capable of showing the electrocardiographic trace, heart rate, and hemo-
globin saturation. Our purpose is a standard protocol, with clinical observation and
collection of vital signs at fixed times: every 15 min in the first hour; every 30 min
in the next 3 h; then hourly for the next 8 h. Clinical observation should include
comfort, mental status, verbal and nonverbal cues, airway patency, nasal conges-
tion, dryness, gastric insufflation, conjunctiva irritations, inability to sleep and,
170 G. Caironi et al.

importantly, patient-ventilator synchrony. Vital signs should include respiratory rate

(observing chest-wall movement and use of accessory respiratory muscles), satura-
tion, pulse rate, rhythm, blood pressure (noninvasive), evaluation of skin, and diure-
sis characteristics. Obviously, observation and collection of vital signs can be
repeated as needed regardless of proposed standards.

17.2.3.2 Arterial Blood Gas Analysis

Arterial or arterialized capillary blood gas analysis of pH, PaCO2, PaO2, and rela-
tionship between PaO2 and fraction of inspired oxygen (P/F) are important in the
assessment of patients on NIV. Timing of arterial blood gas measurement will
depend on the patient’s condition, but we propose to consider fixed intervals
(Table 17.2), and to carry out these measurements rather than relying on the duty
doctor. During the first 24 h, the use of an indwelling arterial line should be consid-
ered to reduce patient’s discomfort and pain [3, 4].
Frequency will depend on the patient’s progress and the different etiologies of
respiratory failure. Where the patient’s condition is rapidly improved, blood sam-
ples should not be taken frequently as these patients are often sleep deprived and
need to sleep and relax. When there is no improvement or it is very slow, assess-
ments should be more frequent to guide ventilator setting or interface adjustments,
or to consider invasive ventilation. We propose a standard, based on fixed times, for
taking samples of arterial blood: after 30 min, then at 120 and 240 min.
It is important to realize that failure of improvement in arterial blood gas tensions
is not a criterion for simply increasing the FiO2 but for clinical re-evaluation. Any
changes in oxygenation cannot be assessed in the absence of inspired oxygen con-
centration information; the metered flow rate and the mode of supplementation
should always be clearly recorded.

Table 17.2 Vital signs and arterial blood gases monitoring

Hour Time Vital signs, comfort, and clinical observation Arterial blood gas analysis
1 0 Yes Yes
15 Yes Not routinely
30 Yes Yes
45 Yes Not routinely
60 Yes Yes
2 90 Yes Not routinely
120 Yes Yes
3 150 Yes Not routinely
180 Yes Not routinely
4 240 Yes Yes
5 300 Yes If necessary
Etc. Etc. – –
17 Monitoring Patients During Noninvasive Ventilation: The Clinical Point of View 171

17.2.3.3 Alarms
Alarms are based on flow, pressure, or volume. A low-pressure alarm detects discon-
nection or excessive leakage, but alarms based on flow are more informative and can
warn of changing leakage, worsening airflow obstruction, or partially occluded tub-
ing. By measuring flow and leaks, some ventilators compute tidal volume and, hence,
minute volume, with greater monitoring potential with settings such as a larger or
smaller tidal volume or low or too high respiratory rate. Alarms for a multi-parametric
monitor should be set to warn about a too high heart rate or hypotension.

Conclusions
Patients undergoing NIV require a complex service and high-quality and global
care. In many cases, the patient can be ventilated for 24 consecutive hours.
Remember that breaks in NIV should be made for drugs, physiotherapy, and meals.
It is important to ensure the most appropriate nursing care and the correct clinical
and instrumental observation for these patients. Monitoring and continuous care
are the key to success of the treatment and to guarantee a good outcome.
Here, we have divided the monitoring actions into sections: observing clinical
conditions and care, control of laboratory tests, and examination of flow and
pressure charts. However, monitoring is a set of coordinated and continuing
actions, divided into distinct phases to make it easier.
Using a standard assessment as well as the one proposed here may help pro-
fessionals in the management of these complex patients. It allows a rational use
of resources, avoiding abuse of diagnostic procedures that are often painful and
unnecessary for the patient. Finally, a high level of professionalism is expressed
through continuous updating and training of the team caring for these patients,
mainly in an emergency department.

Key Major Recommendation

• Give information to the patients about NIV and ensure the correct patient
position and comfort.
• Select an interface device. If it is a mask (oro-nasal or total face), hold it in
place for the first few minutes to help familiarize the patient with it, then
secure with straps, checking for leaks.
• Set up the ventilator and use a multi-parametric monitor and pulse oximeter.
• Check the patient-ventilator interaction.
• Observe clinical status, arterial blood samples, and vital signs as indicated
at fixed times or when needed.
172 G. Caironi et al.

References
1. Vital FMR, Ladeira MT, Atallah AN. Non-invasive positive pressure ventilation (CPAP or bilevel
NPPV) for cardiogenic pulmonary edema. Cochrane Database Syst Rev. 2013;5:CD005351.
2. Hess DR. The evidence for noninvasive positive-pressure ventilation in the care of patients in
acute respiratory failure: a systematic review of the literature. Respir Care. 2004;49(7):810–29.
3. BTS Standards of Care Committee. Non-invasive ventilation in acute respiratory failure.
Thorax. 2002;57(3):192–211.
4. Keenan SP, et al. Clinical practice guidelines for the use of noninvasive positive-pressure ven-
tilation and noninvasive continuous positive airway pressure in the acute care setting. Can Med
Assoc J. 2011;183(3):195–214.
5. Nava S, Navalesi P, Gregoretti C. Interfaces humidification for noninvasive mechanical venti-
lation. Respir Care. 2009;54(1):71–84.
6. Mojoli F, Iotti GA, Currò I, et al. An optimized set-up for helmet noninvasive ventilation
improves pressure support delivery and patient-ventilator interaction. Intensive Care Med.
2013;39:38–44.
7. Elliott MW. The interface: crucial for successful noninvasive ventilation. Eur Respir J.
2004;23:7–8.
8. Silva RMD, et al. Adaptation analysis of different noninvasive ventilation interfaces in criti-
cally ill patients. Crit Care. 2011;15 Suppl 2:1.
9. Nava S, Fanfulla F. Ventilazione meccanica non invasiva. Milan: Springer; 2010.
10. Hill NS. Noninvasive ventilation for chronic obstructive pulmonary disease. Respir Care.
2004;49(1):72–87.
Monitoring Accuracy of Home
Mechanical Ventilators: Key Technical 18
Elements and Clinical Implications

Manel Luján, Xavier Pomares, and Ana Sogo

Contents
18.1 Introduction ................................................................................................................. 173
18.2 Discussion and Analysis ............................................................................................. 174
18.2.1 Morphology and Characteristic of the Native Graphics ................................ 174
18.2.2 Physical Phenomena...................................................................................... 176
18.3 Conclusions and Clinical Implications ....................................................................... 178
References .............................................................................................................................. 178

Abbreviations

CPAP Continuous positive airway pressure

ICU Intensive care unit
IPAP Inspiratory positive airway pressure
NIV Noninvasive ventilation.

18.1 Introduction

The interest in monitoring home noninvasive ventilation (NIV) has increased in the
last 10 years. In this setting, NIV manufacturers have introduced some improve-
ments in their ventilators that allow the clinician to obtain information about

M. Luján, MD, PhD (*) • X. Pomares, MD • A. Sogo, MD

Pneumology Service, Hospital de Sabadell Corporació Parc Taulí,
Universtat Autònoma de Barcelona, Sabadell, Spain
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 173

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_18
174 M. Luján et al.

patient-ventilator interactions during the use of the device. This information is

sometimes available in real time, but also it can be downloaded from the internal
memory of the ventilators and displayed, often breath to breath, by means of the
pressure-time and flow-time graphics through specific software (the so-called built-
in software). Then, in the daily practice, the clinician has, at least in theory, two
devices (ventilator and monitor) in a single machine.
However, one of the main drawbacks of the “monitorization” of home mechani-
cal ventilators is the important differences found in comparative bench studies in the
estimated leak and delivered tidal volume values by built-in software of ventilators
from different manufacturers (in pressure-limited modes) [1]. The differences in
estimated delivered tidal volume ranged from −50 to + 450 ml when the ventilators
were submitted to different levels of external controlled continuous leakage in a
bench design with single limb and leak port. One of the consequences of these
deviations is that a European expert committee in NIV (the Somno-NIV group),
although recognizing some clinical value, attributed to the built-in software a low
level of evidence in their recommendations for monitoring and titrating NIV home
ventilators [2].
The main function of the built-in software should be to display accurately in the
device screen the amount of gas entering into the patient’s upper respiratory airway.
This simple point, easy to understand, can certainly be complicated to apply in the
practice, because the ventilator monitors the pressure and flow inside the device and
there are several physical phenomena, for example, related to the controlled leak
port or to the presence of unintentional leaks by a poorly fitted interface, that might
occur between the ventilator’s exit and the patient’s upper respiratory airway. In this
setting, the signal obtained inside the ventilator should be modified through math-
ematical algorithms, trying to reflect the true gas entering into the patient. In our
opinion, one of the most important conclusions of the above-mentioned study that
can explain their findings is that manufacturers apply different modifying algo-
rithms of the native signal in their built-in software [1].
In this chapter, we review the basis for monitorization of NIV and how the exter-
nal factors usually present in its clinical application can interfere with the reliability
of this monitorization. Nearly all concepts are based on the findings in pressure-
limited modes (the most used in clinical practice), but the conclusions can be also
easily applied to volume-limited modes.

18.2 Discussion and Analysis

18.2.1 Morphology and Characteristic of the Native Graphics

The use of mechanical ventilators at home has resulted in a simplification, not only
of the ventilators (smaller, portable) but also of the tubing used for delivering the
gas into the patient’s airway. The use of a double-limb system, however (as in inten-
sive care units (ICUs) or anesthesia), can add a significant complication for the
management at home, and systems with single limb are preferred for home
18 Monitoring Accuracy of Home Mechanical Ventilators 175

Pressure

Native (uncorrected) flow

Native (uncorrected) volume

Estimated leaks

Corrected flow

Corrected volume

Fig. 18.1 Reproduction of the correction for the intentional estimated leaks in native flow-time
graphics (see text for more details) in the laboratory with the help of a simulator. The abrupt “drop”
in the uncorrected volume-time graphic (Channel 3) is related to the reset in the integral of the
flow-time graphic (in the transition negative-positive of the flow-time graphic – Channel 2-).
Usually, built-in software displaying volume-time graphics can present this drop in the presence of
leaks

ventilation today. But the use of single-limb systems is also associated with the
mandatory use of an alternative expiratory system (intentional leak port or active
valve). In both systems, there are important differences in the flow and pressure
graphics monitored inside the ventilator compared with those at the patient’s
airway.
From a generic point of view, it can be considered that the total gas exiting the
ventilator should be considered as a sum of the gas entering the patient (tidal vol-
ume) plus the intentional (if a system with leak port and single limb is used) and
unintentional (attributable to a suboptimal fitting of the mask) leaks. Finally, the
compressible volume (CV) remaining in the limb(s) should also be considered
(Eq. 18.1):

Totalgas Flow = VT + V ( IL ) + V ( NIL ) + CV (18.1)

where VT = tidal volume, V (IL) corresponds to the flow or volume exiting through
the leak port, V (NIL) is the flow/volume of unintentional leaks, and CV is the com-
pressible volume.
In the laboratory environment, and with the help of a simulator, the morphology
of the native graphics can be reproduced, placing a pneumotachograph at the exit of
the ventilator. For example, in a system with single limb and leak port, and without
unintentional leaks, the morphology can be similar to that represented in Fig. 18.1.
In fact, the native flow-time graphic contains, in the inspiratory phase (Fig. 18.1,
Channel 2) the amount of gas delivered to the patient plus the gas escaping through
the valve (calculated from the pressure-leak equation in Channel 4). When the
176 M. Luján et al.

estimated leaks are subtracted from native flow graphs, the typical morphology with
equal positive and negative phases is obtained (Channel 5). Conversely, the expira-
tory phase in the native flow-time graph is smaller than the true exhaled tidal vol-
ume because there is an amount of gas escaping through the leak port and not
directly monitored by the pneumotachograph inside the ventilator.
This is only an example of how distorted the flow signal monitored inside the
ventilator can be. The function of mathematical algorithms applied to this signal
should be to provide true information about the gas entering the patient, and the
algorithms should take into account some physical phenomena that may occur dur-
ing noninvasive home ventilation in the clinical practice.

18.2.2 Physical Phenomena

18.2.2.1 The Expiratory System

Today, due to its simplicity, not only for the patient but also for caregivers, the single
limb with an expiratory leak port embedded in the mask or as an independent piece
between the mask and the tubing is probably the preferred configuration in home
noninvasive ventilation. This expiratory leak port acts as a continuous leak, with a
higher resistance than the tubing itself. The behavior of this continuous leak can be
easily determined in the laboratory by means of the so-called “leak test”: with the
distal end of the mask or tubing occluded, the system is submitted to increasing
pressure levels (e.g., in continuous positive airway pressure (CPAP) mode) and a
pneumotachograph inside the ventilator captures only the flow leaks. Finally, the
data are plotted on an X-Y graph and a second-degree equation can approximate
with reasonable accuracy the amount of intentional leak for each level of pressure.
These values can be subtracted from the native graphics to obtain the true gas flow
entering and exiting from the patient.
This approach has two drawbacks, however. First, it is not always easy to perform
a leak test when the port is built into the mask because the seal of the distal end might
be incomplete. The second drawback appears in the presence of leaks. In this setting,
and explained by Poiseuille’s law regarding the flow of fluids, with a higher flow exit-
ing from the ventilator, the pressure difference between the true monitoring point
(inside the ventilator) and the expiratory leak port also increases. This phenomenon
can lead to an overestimation of leaks and progressive underestimation of tidal vol-
ume at increasing leak values [3]. The latter phenomenon, however, can be overcome
by the introduction of a correction factor based on the resistance of the tubing and
following Poiseuille’s law. This factor attempts to calculate the distal (in the leak port)
pressure as a function of exiting flow, resistance, and proximal pressure values.
On the other hand, if an active valve is used, there are also some drawbacks asso-
ciated with the monitoring. The most important is that, although there is not an
intentional leakage during the inspiratory phase, the built-in software “misses” the
signal corresponding to the expiratory phase because the expired gas is exhaled
through the valve. In this setting, the only technical solution is to place a pneumo-
tachograph between the valve and the interface.
18 Monitoring Accuracy of Home Mechanical Ventilators 177

18.2.2.2 The Unintentional Leak

Classically, the influence of the leaks in monitoring in the laboratory has been per-
formed with models of continuous leakage. Even in a review focused on bench
studies, leaks are “standardized” as holes of different diameter [4]. However, the
behavior of leaks in clinical practice might not correspond to this pattern. In fact, a
poorly fitted mask can generate leaks only during inspiration, or inversely, a patient
wearing a nasal mask can theoretically exhale through the mouth. In both cases, the
relationship of proportionality between inspiratory and expiratory phases of the
respiratory cycle disappears.
For these reasons, the unintentional leak should be considered in a different way,
with a “nonlinear “or “dynamic random” approach [5]. In fact, in one study, four
home ventilators from different companies were tested in a bench environment in
conditions of random or nonlinear leak. The results obtained in this study (overesti-
mation of tidal volume in a model of inspiratory leaks and underestimation in expi-
ratory leaks) reinforced the hypothesis that the approach of considering unintentional
leaks as a linear parameter can lead to significant misestimation of tidal volume. In
the same study, an algorithm based on the assumption of lack of proportionality
between inspiratory and expiratory phases showed minimal deviations in the esti-
mation of tidal volume and unintentional leaks.
But the drawbacks of this misestimation can go beyond wrong information for
the clinician. It should be highlighted that, in some new modes of noninvasive ven-
tilation (the dual-control or volume-targeted pressure support modes), the ventilator
makes its own decisions based on target tidal volume estimation. If random leaks
appear, as demonstrated in a recent study, the ventilator can modify its pressure sup-
port level in a different way than expected [6]. In this setting, it seems reasonable to
recommend setting in the ventilator a safety lower level of pressure support.

18.2.2.3 The Compressible Volume

The compressible volume refers to the excess of volume contained in the tubing
between both phases of the respiratory cycle. From a mathematical perspective, it
can be quantified as follows:
VC = PIP − PEEP / C
where VC is the compressible volume, PIP is the peak inspiratory pressure (in pres-
sure support modes it can be considered as an equivalent of IPAP), and C is the
compliance of the tubing (ml/cmH2O/m).
Being that the compressible volume is a parameter directly related to the length
of the tubing, it is easy to understand that, in the configuration with double tubing,
the amount of compressible gas can be twice that in comparison with single tubing.
In the same way, the use of extremely compliant tubing can increase the compress-
ible volume.
The effects of compressible volume depend on the use of pressure- or volume-
limited modes. In fact, if pressure-limited modes are used, the monitored tidal vol-
ume can be overestimated in the presence of compressible volume. When
volume-limited modes are used, the delivered tidal volume can be less than that set
178 M. Luján et al.

in the ventilator. Under normal circumstances, the compressible volume is not

higher than 10 % of the delivered gas, and many companies introduced in their
ventilators a compensation factor for this phenomenon [7].

18.3 Conclusions and Clinical Implications

The built-in software for different ventilators shows important variability, suggest-
ing that each manufacturer has its own algorithm in the management of native
graphics. An effort should be made to standardize the treatment of pressure and flow
native graphics, considering all the physical phenomena and clinical scenarios that
may distort the native graphics.

Key Major Recommendations

• The clinician should consider that the graphics displayed by the built-in
software of the ventilators are usually treated by mathematical
algorithms.
• Manufacturers can use different algorithms to treat native graphics. This
fact can explain some differences between the devices from different
companies.
• Configuration of the limbs (single or double) and expiratory system (leak
port, active valve) plays an important role in the monitoring of home
ventilators.

References
1. Contal O, Vignaux L, Combescure C, Pepin JL, Jolliet P, Janssens JP. Monitoring of non-
invasive ventilation by built-in software of home bi-level ventilators: a bench study. Chest.
2012;141:469–76.
2. Janssens JP, Borel JC, Pepin JL, SomnoNIV Group. Nocturnal monitoring of home noninva-
sive ventilation: the contribution of simple tools such as pulse oximetry, capnography, built-in
ventilator software and autonomic markers of sleep fragmentation. Thorax. 2011;66:438–45.
3. Luján M, Sogo A, Pomares X, Monsó E, Sales B, Blanch L. Effect of leak and breathing pattern
on the accuracy of tidal volume estimation. Respir Care. 2013;58(5):770–7.
4. Oliveri C, Costa R, Conti G, Navalesi P. Bench studies evaluating devices for non-invasive
ventilation: critical analysis and future perspectives. Intensive Care Med. 2012;38:160–7.
5. Sogo A, Montanyà J, Monsó E, Blanch L, Pomares X, Lujàn M. Effect of dynamic random
leaks on the monitoring accuracy of home mechanical ventilators: a bench study. BMC Pulm
Med. 2013;13:75.
6. Luján M, Sogo A, Grimau C, Pomares X, Blanch L, Monsó E. Influence of dynamic leaks in
volume-targeted pressure support noninvasive ventilation: a bench study. Respir Care. 2015;60(2):
191–200.
7. Bachiller PR, McDonough JM, Feldman JM. Do new anesthesia ventilators deliver small tidal
volumes accurately during volume-controlled ventilation? Anesth Analg. 2008;106:1392–400.
Capnography as a Tool to Improve
Noninvasive Ventilation: Technical Key 19
Topics and Clinical Implications

Eren Fatma Akcil, Ozlem Korkmaz Dilmen,

and Yusuf Tunali

Contents
19.1 Introduction .................................................................................................................... 179
19.2 Discussion ...................................................................................................................... 180
Conclusions ............................................................................................................................. 181
References ............................................................................................................................... 181

19.1 Introduction

Noninvasive ventilation (NIV) is a mechanical ventilation method frequently used

in the treatment of acute and chronic respiratory failure. As it is a noninvasive
method, it prevents complications related to intubation and invasive mechanical
ventilation and thus decreases morbidity and mortality. The clinical conditions that
benefit most from NIV are acute exacerbation of chronic obstructive pulmonary
disease (COPD) and cardiogenic pulmonary edema. Its application in pneumonia
and acute respiratory distress syndrome (ARDS) is limited; however, it is beneficial
in thoracic trauma and postoperative mild hypoxic respiratory failure [1]. Monitoring
of respiration during NIV enables the evaluation of its effectiveness and prevents
delays in the initiation of invasive mechanical ventilation and also prevents compli-
cations. For this purpose, respiratory rate, pulse oximetry, arterial blood gas analy-
sis (ABG), and capnography are frequently used. This section provides an overview
of the importance and contributions of capnography in NIV.

E.F. Akcil, MD (*) • O.K. Dilmen, MD • Y. Tunali, MD

Department of Anaesthesiology and Intensive Care Medicine,
Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 179

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_19
180 E.F. Akcil et al.

19.2 Discussion

Capnography was first used in the Central Military Hospital in Holland in 1962 by
Professor Bob Smalhout. Since 1988, it has been used in operating rooms as a part of
routine clinical practice. Accompanied by technological developments, capnography
has been recommended in many practice fields for patient safety, not only in intu-
bated patients, but also in nonintubated patients (Table 19.1) [2]. The primary goal of
anesthesiologists is to prevent hypoxia, and capnography helps identify situations
that can lead to hypoxia, such as disconnection of the circuit and hypoventilation. It
also prevents undesirable results of hypoxia, among which irreversible brain damage
is the most important. Because of these advantages, the utility of capnography has
recently been extended outside the operating room to emergency rooms, endoscopic
suites, X-ray rooms, and even on-site emergency and trauma fields.
Although there is an opportunity for end-tidal CO2 (etCO2) monitoring in nonin-
tubated patients with the developing technology in mainstream and sidestream
capnographies, false results can be obtained as a result of obstruction due to water
and secretion. Microstream (MST) is a new method developed for CO2 measure-
ment, based on molecular correlation spectroscopy. In this method, a specific infra-
red radiation wavelength is used to detect CO2, which is not affected by the other
gases (i.e., O2, N2O, He, inhaled anesthetics). In the MST procedure, a low sample
flow rate (50 ml/min) is adequate, which makes the procedure useful in different
types of patients, such as neonates. MST can be used in intubated and nonintubated
patients, and it is widely available for monitoring etCO2 during NIV [3].
In nonintubated patients, capnography provides information about the respira-
tory rate, airway obstruction (bronchospasm), apnea, hypoventilation/hyperventila-
tion, and dead space ventilation. During NIV, these features of capnography are
employed. While capnography is used in the evaluation of the effectiveness of NIV
on ventilation and CO2 elimination, it also provides information about CO2
rebreathing [4]. In the monitoring of end-tidal CO2 pressure (PetCO2) during NIV,
the type and size of the mask, the sampling site, and the localization of the exhala-
tion port are important. Nuccio et al. [4] applied continuous positive airway pres-
sure (CPAP) and bi-level positive airway pressure (BIPAP) at two different pressure
levels in three groups and obtained etCO2 samples from three locations, including

Table 19.1 Recommendations for capnography

OR ICU Recovery Sedation CPR ED
NAP4 2011 2011 2011 2011
ASA 1987 2011
AAGBI 1988 2009 2009 2009 2009 2009
Resusc. Council 2010
ICS 2011
NAP4 National Audit Project 4, ASA American Society of Anesthesiologists, AAGBI The
Association of Anesthetists of Great Britain and Ireland, Resusc. Council Resuscitation Council,
ICS Intensive Care Society, OR operating room, ICU intensive care unit, CPR cardiopulmonary
resuscitation, ED emergency department
19 Capnography as a Tool to Improve Noninvasive Ventilation 181

the nasal/oral cannula, mask sample port, and ventilator circuit connector. They
found that the best measurement could be obtained with different minute ventila-
tions and different amounts of leakage in nasal/oral cannula applications. It has
been demonstrated that in sampling from the nasal/oral cannula, etCO2 levels are
not affected by the mask type but are correlated with baseline values in different
ventilation parameters, and the wave form in the capnogram is not disturbed.
Therefore, nasal/oral cannulas are preferred for etCO2 monitoring in NIV.
CO2 rebreathing in NIV is an important problem, as it decreases CO2 elimination
and increases work of breathing. Increasing positive end-expiratory pressure (PEEP)
and CPAP levels and the addition of non rebreathing valves to the breathing circuits
decrease rebreathing [5]. However, in NIV applications in which the exhalation port
is located in the breathing circuit instead of the mask, and in which high volume
masks are used, increasing PEEP and CPAP does not sufficiently decrease rebreath-
ing. It has been demonstrated that the systems in which the exhalation port is pres-
ent in the mask and in which low volume masks are used decrease rebreathing [6].
Another problem that influences capnography in NIV is leakage. In most of the
ventilators used in NIV, there is leakage compensation, and a small amount of leak-
age is tolerated to prevent the firm placement of the mask on the face of the patients.
Increasing this amount causes a disruption in ventilation, a decrease in CO2 elimina-
tion, and a decrease in etCO2 levels in capnography.

Conclusions
Capnography is essential for monitoring of the respiration system. MST is a new
technique of capnography. NIV and MST are both noninvasive methods, and
their synergy provides for the safe management of respiratory failure.

Key Recommendations
• Nasal/oral cannula should be the preferred tool for capnography during
NIV.
• Leaks must be minimized for accurate measurement.
• More experience is required with MST and NIV.

References
1. Ferrer M, Torres A. Noninvasive ventilation for acute respiratory failure. Curr Opin Crit Care.
2015;21:1–6.
2. Whitaker DK. Time for capnography - everywhere. Anaesthesia. 2011;66:539–49.
3. www.capnography.com/new/technology/microstream. Bhavani-Shankar Kodali copyright©2013.
4. Nuccio P, Hochstetler G, Jackson M. End-tidal CO2 measurements with noninvasive ventila-
tion. Anesth Analg. 2007;105(S 6):111.
5. Lofaso F, Brochard L, Touchard D, et al. Evaluation of carbon dioxide rebreathing during pressure
support ventilation with airway management system (BIPAP) devices. Chest. 1995;108:772–8.
6. Schettino G, Chatmongkolchart S, Hess D, et al. Position of exhalation port and mask design
affect CO2 rebreathing during noninvasive positive pressure ventilation. Crit Care Med. 2003;
31:2178–82.
Humidification for Noninvasive
Ventilation: Key Technical Determinants 20
and Clinical Evidence

Aylin Ugurlu Ozsancak and Antonio M. Esquinas

Contents
20.1 Introduction .................................................................................................................... 184
20.2 Discussion and Analysis ................................................................................................ 184
20.2.1 Effects of Inefficient Gas Conditioning During NIV
and Contributing Factors .................................................................................... 184
20.2.2 Effects of Humidifiers During NIV Use ............................................................ 186
20.2.3 Recommendations About Humidifier Use for NIV............................................ 186
20.2.4 Types of Humidifiers .......................................................................................... 186
20.2.5 Humidifier Settings ............................................................................................ 188
Conclusion .............................................................................................................................. 189
References ............................................................................................................................... 189

Abbreviations

AH Absolute humidity
ARF Acute respiratory failure
CPAP Continuous positive airway pressure
FiO2 Fractional inspired oxygen
HH Heated humidifiers
HME Heat-and-moisture exchangers
IMV Invasive mechanical ventilation
IPAP Inspiratory positive airway pressure

A.U. Ozsancak, MD (*)

Department of Pulmonary Medicine, Baskent University Hospital, Istanbul, Turkey
e-mail: [email protected]
A.M. Esquinas, MD, PhD, FCCP
Intensive Care and Non Invasive Ventilatory Unit, Hospital Morales Meseguer, Murcia, Spain
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 183

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_20
184 A.U. Ozsancak and A.M. Esquinas

NAWR Nasal airway resistance

NIV Noninvasive ventilation
SRBD Sleep-related breathing disorders
WOB Work of breathing

20.1 Introduction

During spontaneous breathing, inhaled air conditioning (i.e., heating and humidifi-
cation of air) is provided by the upper airways. Artificial humidification is recom-
mended when the upper airway is bypassed, such as during invasive mechanical
ventilation (IMV), to prevent hypothermia, disruption of the airway epithelium,
bronchospasm, atelectasis, and airway obstruction [1].
Noninvasive ventilation (NIV) has been increasingly used at hospitals for acute
respiratory failure (ARF) [2]. It is also used at home for chronic respiratory failure
and sleep-related breathing disorders (SRBD). Unfortunately, it might lead to com-
plications, including nasal congestion and/or upper airway dryness (especially when
there is air leakage), which might in turn result in intolerance or decrease in patient’s
compliance and subsequently in NIV failure. Gas conditioning can prevent these
adverse effects. It can be either done actively by heated humidifiers (HH) or pas-
sively by heat-and-moisture exchangers (HME). Currently, active humidification by
HH is suggested for NIV by the American Association of Respiratory Care, as it
may improve adherence and comfort [1].
In this chapter, we summarize the effects of inefficient gas conditioning during
NIV, factors worsening these effects, types of humidifiers and their properties, and
current recommendations for humidification.

20.2 Discussion and Analysis

20.2.1 Effects of Inefficient Gas Conditioning During NIV

and Contributing Factors

During normal breathing, the upper airway heats and humidifies inhaled air so that
the gas entering the alveoli reaches body temperature and is fully saturated with
water vapor [3]. The upper airway recovers added inspiratory heat and moisture
partially during exhalation. During IMV, when the upper airway is bypassed by an
endotracheal tube or tracheostomy, inadequately humidified dry gases were shown
to cause changes of respiratory tract structure and function (including inflammation,
necrosis, and squamous metaplasia), deterioration in lung function, and increase in
tenacity of sputum leading to airway/endotracheal tube occlusion [4].
During NIV, the inspired gas is conditioned by the upper airways. However it can
be overwhelmed in case of inhalation of cool, dry gas with high flow, especially
during utilization of intensive care ventilators (using anhydrous wall air or oxygen)
20 Humidification for Noninvasive Ventilation 185

Table 20.1 Effects of inadequate humidification during NIV and factors affecting
humidification
Effects of inadequate humidification Factors affecting humidification
Anatomical and functional changes of nasal mucosa Presence of leak
Nasal dryness and/or congestion Type of mask
Increased NAWR and WOB Type of ventilator
Mucus plugs, secretion retention, atelectasis, airway Level of FiO2 and airflow
obstruction, difficult intubation in case of NIV failure Level of IPAP
Symptoms (mouth dryness, discomfort) leading to Temperature of the environment
decrease in tolerance or compliance and inhaled gas
Abbreviations: FiO2 fraction of inspired oxygen, IPAP inspiratory positive airway pressure, NAWR
nasal airway resistance, NIV noninvasive ventilation, WOB work of breathing

or during leak compensation. A clinical review examined the effects of inappropri-

ate gas conditioning during NIV [5] (Table 20.1). Structural and functional deterio-
ration of nasal mucosa was reported, including metaplastic changes and
keratinization of the nasal epithelium and submucosa, both for acute and chronic
NIV use, and change in ciliary activity, mucus secretion, and local blood flow.
Unidirectional inspiratory nasal airflow, worsened by mouth air-leaks, can lead to
nasal dryness, which would decrease the capacity of gas conditioning of upper air-
ways and stimulate release of inflammatory mediators leading to nasal congestion,
increased nasal airway resistance (NAWR), and work of breathing (WOB). The
secretions can become tenacious and result in mucus plugs, atelectasis, and life-
threatening airway obstruction. Additionally, difficult intubation can be another
consequence of non-humidified dry air during NIV use. Up to 50–60 % of patients
using continuous positive airway pressure (CPAP) (especially with nasal mask) for
management of ARF or SRBD experience nasal dryness or congestion. Because of
nasal or mouth dryness, dry/sore throat, cough, reduced sense of smell, or discom-
fort, compliance with NIV or tolerance can be adversely affected for chronic or
acute use of NIV, leading to NIV failure.
Some conditions can worsen gas conditioning during NIV (Table 20.1). Presence of
leaks, type of interface and ventilator, level of fractional inspired oxygen (FiO2), and
inspiratory positive airway pressure (IPAP) are the major contributors. Unintentional
leaks through mouth or at the periphery of the mask can cause unidirectional airflow,
resulting in continuous decrease in absolute humidity (AH) (i.e., the total water present
in the gas) of air in airways with increased nasal airway resistance, as explained above
[5]. This risk is increased with use of nasal masks rather than oro-nasal masks. Some
physicians prefer a helmet, especially for ARF. When inspiratory flow is medium or
low (FiO2 of 0.21), humidification during delivery by helmet may be less necessary
than during other modes, because of mixture of inspired ambient air with expired
humidified gas in a relatively larger inner space [6]. However, with higher FiO2 (≥0.50),
AH drops by half to an unacceptable level (9.7 mg H2O/l), because of the greater pro-
portion of anhydrous dry medical gas in inspired air. Increased IPAP as well as high
flow rates (up to 90 l/min) can lead to inadequate humidification even with humidifiers.
Ventilator type is another crucial factor, as intensive care unit (ICU) ventilators,
186 A.U. Ozsancak and A.M. Esquinas

obtaining dry medical gas from pipes, provide lower levels of humidity than home
ventilators, using compressed room air. Therefore, the clinician should carefully adjust
humidification level taking these factors into account.

20.2.2 Effects of Humidifiers During NIV Use

Humidification through artificial humidifiers can prevent these adverse effects of

inadequately humidified air inhalation during NIV. Decrease in WOB, nasal airway
resistance, and symptoms (such as dry throat) with improved comfort have been
shown by utilization of humidifiers in short-term users [5, 7, 8]. In long-term NIV
use, especially for SRBD, although there is an improvement in nasopharyngeal
symptoms (such as dryness) with humidification during NIV, there are conflicting
data that humidification increases patient adherence to and tolerance of CPAP [5].

20.2.3 Recommendations About Humidifier Use for NIV

There are actually no large epidemiological studies to determine whether or not

humidification is routinely required for every patient for short- or long-term use.
However, the guideline by the American Association of Respiratory Care published
in 2012 suggested use of humidification for NIV with possibility of improvement in
adherence and comfort [1]. However, in real life, the surveys of physicians manifest
that a quarter to nearly half of physicians did not employ humidification during NIV
use in acute settings [9, 10]. On the other hand, the American Association of Sleep
Medicine also recommended its use as a practice parameter in 2006 to improve
CPAP utilization in management of SRBD in adults [11]. Accordingly, some insur-
ance companies (along with the Medicare and Medicaid programs in the United
States) pay for it [3]. Unfortunately, this is not possible in every country (such as in
Turkey), possibly due to socioeconomic restrictions.

20.2.4 Types of Humidifiers

There are two main types of humidification devices: HH and HME, used for both
short- and long-term NIV [4]. By use of HH, gases may be actively warmed and
moistened by passing air over the surface of a heated water reservoir attached to the
ventilator. The system may have a heated wire in the inspiratory limb of the ventila-
tor circuit to prevent cooling and condensation of the air. On the other hand, HME,
usually placed between the Y-piece and the interface, passively humidifies air by
recovering patient’s expired heat and moisture and returning them to the patient dur-
ing inhalation.
Both types of humidifiers can result in some complications [1, 4]. HH may lead
to electrical shock, thermal injury, hypo/hyperthermia, inadvertent overfilling or
pooled condensate with risk of improper ventilator performance and nosocomial
20 Humidification for Noninvasive Ventilation 187

Table 20.2 Pros and cons of humidification systems during NIV

Pros Cons
HH Smaller or no addition of dead space More expensive
with less CO2 retentiona More difficult to use
Less WOBa “Condensation fog” formation, fever and
Provides effective humidification for discomfort with increasing heat (helmet)
clinical use in hypercapnic ARF Needs electricity
HME Easier to use Bigger internal volume
Cheaper Increased dead space
No need for electricity CO2 retentiona
Extensively used during IMV Increased NAWR (especially with leaks)
Condensation prevention Increased WOBa
Better preservation of humidity during Decreased performance in case of leaks
low ambient temperature and at high
flow
Abbreviations: ARF acute respiratory failure, CO2 carbon dioxide, IMV invasive mechanical ven-
tilation, NAWR nasal airway resistance, NIV noninvasive ventilation, WOB work of breathing
a
Recent studies reported no difference for work of breathing with similar CO2 elimination by using
positive end-expiratory pressure or HME with smaller dead space

infection, and patient-ventilator asynchrony. HME can increase dead space, leading
to hypoventilation due to hypercapnia. There is also a potential increased risk for
airway occlusion with HME due to impaction of mucus secretions compared with
HH. Both can cause under-hydration and mucus plugs (<26 mg H2O/l) with
hypoventilation and/or alveolar gas trapping.
Although humidifiers have demonstrated beneficial therapeutic effects during
NIV, there is still controversy over the selection of the best humidifier to obtain the
best outcomes, such as improved compliance and/or gas exchange, or decreased
intubation [5]. Both humidifiers have some pros and cons (Table 20.2). In a long-
term (12-month) randomized crossover pilot study, HH were found to result in no
differences for NIV compliance, tolerance, rate of hospitalization, or for most of the
complications related to dry gases (except for dry throat) when compared with
HME during NIV use for chronic respiratory failure [8]. However, at the end of the
study, a higher number of patients (10/14) preferred to continue with HH for home
use.
In short-term studies, HH were reported to deliver gases with higher water con-
tent than HME during NIV, especially in case of leaks [7]. This is probably because
of the inability of HME to recover heat and moisture due to unidirectional flow dur-
ing leaks. Therefore, it is crucial to consider the presence of mouth or mask leaks
when choosing the humidifier type. HH were also shown to improve alveolar venti-
lation and CO2 elimination and decreased WOB at zero end-expiratory pressure
when compared with HME [12], which could be related to substantial dead space
added to the ventilator circuit by HME. The lack of improvement in gas exchange
with CO2 retention is an important factor predisposing NIV failure. Therefore,
based on these data, the current recommendations were made by the American
Association of Respiratory Care favoring the use of HH over HME during NIV [1].
188 A.U. Ozsancak and A.M. Esquinas

Fig. 20.1 Types of humidifiers: (from left to right) Heat-and-moisture exchanger (HME electro-
static filter, Covidien Inc., Boulder, CO, USA), a built-in heated humidifier in A-flex Auto CPAP
(Philips Respironics, Murrysville, PA, USA), and heated humidifier (MR 850; Fisher & Paykel
Healthcare Limited, Panmure, Auckland)

However, HME with small dead space were recently reported to have similar
effects on respiratory parameters (such as respiratory rate, minute ventilation, end-
tidal CO2, oxygen saturation, etc.) and comfort perception as HH [13]. Additionally,
a multicenter randomized controlled study declared that the short-term physiologic
benefits of HH in comparison with HME during NIV with ICU ventilators were not
observed [14]. The authors explained that this lack of difference could be the result
of use of positive end-expiratory pressure during real-life NIV application, reducing
the impact of the difference in dead space between humidification systems.
Intubation rate and long-term outcomes (including NIV duration, length of stay, and
mortality) were also reported to be similar. Based on these results, the recommenda-
tion of HH as a first-line treatment in all patients with ARF should be revisited
(Fig. 20.1).

20.2.5 Humidifier Settings

Humidifiers can be used in critical care, acute care in-patient, operating room, home
care, extended nursing facilities, and transport settings [1]. There is no clear recom-
mendation regarding its settings. Exposure to humidity below 25 mg H2O/l for 1 h
or 30 mg H2O/l for ≥24 h was shown to be associated with mucosal dysfunction [1].
Lellouche et al. [7] measured water content during NIV without humidification or
with HME or HH (10 min of each period) in healthy subjects and reported these
results based on type of ventilator used (turbine or ICU ventilator) and level of FiO2.
There was a dramatic decrease in AH, down to 5 mg H2O/l, during NIV when an
ICU ventilator was used; but gas humidity was equivalent to ambient air hygrome-
try with a turbine ventilator at minimal FiO2 (12.5 H2O/l). Humidifiers (HME and
HH) had comparable performances (25–30 mg H2O/l), which is adequate for the
20 Humidification for Noninvasive Ventilation 189

physiologic functioning of the upper airway. Based on ratings of respiratory dis-

comfort, it was suggested that the minimal level of AH required during NIV was
15 mg H2O/l. Gas temperatures during NIV were also suggested to be set based on
patient comfort/tolerance, adherence, and underlying pulmonary condition [1].
Comfort measures can vary, especially in patients with ARF using a longer duration
of NIV; however, this is the only available data at this time.

Conclusion
The utilization of NIV can lead to detrimental effects on airway mucosa, espe-
cially in patients with mouth leaks, receiving dry gases by ICU ventilators, high
FiO2, or high inspiratory flows. Although there is no recommendation for routine
use of supplemental humidification in all patients receiving NIV, its use in symp-
tomatic patients (such as nasal congestion or thick or tenacious secretions) with
the above risk factors may be helpful to prevent deleterious effects of NIV and
improve compliance and adherence. The choice of humidifier type will depend
on ventilator and mask type, humidifier availability, and patient’s clinical condi-
tion. Heated humidifiers are recommended over HME by current guidelines,
inasmuch as HME may increase WOB and circuit dead space leading to hyper-
capnia. However, based on latest literature, the use of HME (ideally with a low
dead space) seems to be acceptable.

Key Major Recommendations

• Humidification during NIV can be helpful in preventing symptoms such as
dryness of upper airways due to dry gas inhalation, and therefore may
improve tolerance and adherence.
• Supplemental humidification would better be applied in symptomatic
patients with risk factors for increased moisture loss (e.g., dry gas inhala-
tion by ICU ventilators, nasal mask use, mouth leaks, high IPAP or FiO2)
• The type of humidifier should be chosen based on properties of ventilator
and mask, availability of the humidifier, and the patient’s clinical
condition.
• Although current guidelines recommend use of HH over HME due to
increased WOB and circuit dead space with HME, the latest literature
manifested no differences between the two.

References
1. Restrepo RD, Walsh BK, AARC Practice Guideline. Humidification during invasive and non-
invasive mechanical ventilation: 2012. Respir Care. 2012;57(5):782–8.
2. Schnell D, Timsit JF, Darmon M, et al. Noninvasive mechanical ventilation in acute respiratory
failure: trends in use and outcomes. Intensive Care Med. 2014;40(4):582–91.
3. Branson RD, Gentile MA. Is humidification always necessary during noninvasive ventilation
in the hospital? Respir Care. 2010;55(2):209–16.
190 A.U. Ozsancak and A.M. Esquinas

4. Kelly M, Gillies D, Todd DA, et al. Heated humidification versus heat and moisture exchang-
ers for ventilated adults and children. Cochrane Database Syst Rev. 2010;4:CD004711.
5. Esquinas AM, Scala R, Soroksky A, et al. Clinical review: humidifiers during non-invasive
ventilation - key topics and practical implications. Crit Care. 2012;16:203–9.
6. Ueta K, Tomita T, Uchiyama A, et al. Influence of humidification on comfort during noninvasive
ventilation with a helmet. Respir Care. 2013;58(5):798–804.
7. Lellouche F, Maggiore SM, Lyazidi A, et al. Water content of delivered gases during non-invasive
ventilation in healthy subjects. Intensive Care Med. 2009;35:987–95.
8. Nava S, Cirio S, Fanfulla F, et al. Comparison of two humidification systems for long-term
noninvasive mechanical ventilation. Eur Respir J. 2008;32:460–4.
9. Chanques G, Jaber S, Delay JM, et al. Phoning study about postoperative practice and application
of noninvasive ventilation. Ann Fr Anesth Reanim. 2003;22:879–85.
10. Crimi C, Noto A, Princi P, et al. A European survey of noninvasive ventilation practices.
Eur Respir J. 2010;36:362–9.
11. Kushida CA, Littner MR, Hirschkowitz M, et al. American Academy of Sleep Medicine:
practice parameters for the use of continuous and bilevel positive airway pressure devices to
treat adult patients with sleep-related breathing disorders. Sleep. 2006;29:375–80.
12. Lellouche F, Maggiore SM, Deye N, et al. Effect of humidification device on the work of
breathing during noninvasive ventilation. Intensive Care Med. 2002;28:1582–9.
13. Boyer A, Vargas F, Hilbert G, et al. Small dead space heat and moisture exchangers do not
impede gas exchange during noninvasive ventilation: a comparison with heated humidifier.
Intensive Care Med. 2010;36:1348–54.
14. Lelouche F, L’Her E, Abroug F, et al. Impact of humidification device on intubation rate during
noninvasive ventilation with ICU ventilators: results of a multicenter randomized controlled
trial. Intensive Care Med. 2014;40:211–9.
NIV Aerosol Therapy: Key Technical
Determinants and Clinical Evidence 21
Serpil Ocal and Arzu Topeli

Contents
21.1 Introduction ................................................................................................................. 192
21.2 Discussion and Analysis ............................................................................................. 193
21.2.1 Ventilator-Related Factors ............................................................................. 193
21.2.2 Circuit-Related Factors ................................................................................. 194
21.2.3 Type of Interface ........................................................................................... 194
21.2.4 Type of Aerosol-Generating Device and Its Configuration........................... 195
21.2.5 Drug-Related Factors .................................................................................... 196
21.2.6 Patient-Related Factors.................................................................................. 196
21.3 Administration Techniques ......................................................................................... 196
Conclusion ............................................................................................................................. 197
References .............................................................................................................................. 197

Abbreviations

BIPAP Bi-level positive airway pressure

CPAP Continue positive airway pressure
DPI Dry powder inhaler
EPAP Expiratory positive airway pressure
IMV Invasive mechanical ventilation
IPAP Inspiratory positive airway pressure
MV Mechanical ventilation
NIV Noninvasive mechanical ventilation
pMDI Pressurized metered-dose inhaler

S. Ocal, MD (*) • A. Topeli, MD

Medical Intensive Care Unit, Hacettepe University, Faculty of Medicine,
Sihhiye, Ankara 06100, Turkey
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 191

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_21
192 S. Ocal and A. Topeli

21.1 Introduction

Aerosol therapy during noninvasive mechanical ventilation (NIV) is commonly

used in critically ill patients. Bronchodilators, steroids, prostanoids, surfactants,
mucolytics, and antibiotics are the best major aerosol drugs and can be administered
to mechanically ventilated patients by the inhalation route. Interestingly, the use of
drugs such as atropine, furosemide, heparin, terlipressin, and milrinone by the inha-
lation route has also been reported [1]. Treatment of pulmonary diseases such as
chronic obstructive pulmonary disease, asthma, cystic fibrosis, and pneumonia with
aerosol drugs offers advantages over oral and parenteral drugs. The use of aerosol
drugs allows selective treatment of the lungs, directly achieving more rapid onset of
action and high drug concentrations while using lower doses and, therefore, reduc-
ing systemic adverse effects by minimizing systemic drug levels. Inhaled β2 agonist
bronchodilators especially produce a more rapid onset of action through the inhala-
tion route than through oral delivery. Some drugs are only active with aerosol deliv-
ery, such as cromolyn and ciclesonide for patients with asthma and dornase alfa for
patients with cystic fibrosis. Bronchodilators and steroids are the most frequently
used aerosol drugs during NIV [2]. Some studies have been carried out on inhaled
bronchodilator therapy in NIV, but issues related to optimum aerosol delivery dur-
ing NIV are unexplored [3–7].
Moreover, the physiology of aerosol delivery during NIV is not same as the
physiology of aerosol delivery during invasive mechanical ventilation (IMV).
Patients undergoing NIV can receive aerosol drugs in two different ways: (1) If
the patient can tolerate brief periods of discontinuation, NIV can be removed and
aerosol drugs can be administered by a nebulizer or a pressurized metered-dose
inhaler (pMDI) in the standard manner. (2) In patients for whom NIV should be
applied without interruption due to severe hypoxemia or dyspnea, aerosol drugs
should then be administered by pMDI with a spacer or nebulizer. Aerosol deliv-
ery has been shown to be better when applied during NIV in the emergency
department or the intensive care unit. Pollack et al. [3] found that albuterol deliv-
ery by a nebulizer during bi-level positive airway pressure (BIPAP) applied with
a nasal interface resulted in a greater increase in peak expiratory flow in patients
with acute asthma compared with when it is applied with a nebulizer alone.
Furthermore, Fauroux et al. [4] reported better aerosol deposition in children
with cystic fibrosis when a nebulizer was used with pressure support ventilation
of 8–10 cm H2O with positive end-expiratory pressure. Salbutamol delivery by
pMDI with a spacer during NIV is feasible and has been shown to result in sig-
nificant bronchodilation [5].
Successful aerosol therapy depends on adequate drug deposition and penetration
at the intended site of action in the lung. Both in vitro and in vivo studies have con-
tributed to our understanding of the complex factors governing aerosol delivery
during mechanical ventilation. The heterogeneity between the in vivo and in vitro
data might have been caused by several factors such as the circuit or the humidity,
and aerosol losses during exhalation were not taken into account in vitro studies.
21 NIV Aerosol Therapy: Key Technical Determinants and Clinical Evidence 193

Hence, in vitro data should be confirmed clinically. Factors related to pulmonary

deposition of aerosol in patients with IMV also differ from those in spontaneously
breathing patients.

21.2 Discussion and Analysis

Factors influencing aerosol delivery during NIV are not completely understood.
Multiple factors, including the mechanical effect of the applied pressure itself, inde-
pendent of the drug delivered, as well as penetration, positive pressure applied to
recruit collapsed alveoli, increase in tidal volume and functional residual capacity,
and decrease in respiratory rate and inspiratory flow rate might have roles in improv-
ing ventilation-perfusion mismatch and therefore aerosol delivery. Unfortunately,
aerosol drug losses in the ventilator circuit, interfaces, and upper airways reduce the
efficiency of drug delivery during NIV. Moreover, outflow of aerosol to the environ-
ment due to mask leak creates health risks to patients and health-care providers.
Aerosol delivery during NIV depends on several factors.

21.2.1 Ventilator-Related Factors

Critical care ventilators, bi-level ventilators, and home care ventilators can be used
to provide NIV. The characteristics of these ventilators may significantly influence
the aerosol delivery into the lungs during NIV. Critical care ventilators have the
advantages of capability of precise control of fraction of inspired oxygen, presence
of various modes and inspiratory flow patterns, and capability of separating inspi-
ratory and expiratory flow to limit rebreathing. Bi-level ventilators are available
specifically to provide NIV. Unlike critical care ventilators, they use a single-limb
circuit and function well in the presence of leaks. However, aerosol delivery with a
bi-level ventilator is more complex because of single-circuit design and the pres-
ence of a leak port.
Ventilator mode significantly influences aerosol delivery into the lung. Fink et al.
[6] showed that continuous positive airway pressure (CPAP) increased albuterol
delivery from a pMDI with a spacer compared with controlled mechanical ventila-
tion, assist-control ventilation, and pressure support ventilation at similar tidal vol-
umes. CPAP delivers positive airway pressure at a level that remains constant
through the respiratory cycle (inspiration and expiration). This keeps the upper air-
way open, thus preventing upper airway collapse or narrowing during sleep.
Additionally, increased functional residual capacity and improvement in lung com-
pliance allow a higher volume change per unit of pressure change and, therefore,
lead to potentially better aerosol distribution.
BIPAP with a higher inspiratory positive airway pressure (IPAP) and lower expi-
ratory positive airway pressure (EPAP) settings produces better tidal volume, result-
ing in more retrograde flow into the ventilator circuit. Therefore, the aerosol
194 S. Ocal and A. Topeli

concentrations in the circuit at the end of the expiratory phase and the aerosol deliv-
ery in the next inspiratory phase with a jet nebulizer placed between the patient and
leak port during NIV with single limb circuit increase [7]. Moreover, higher IPAP is
also associated with longer inspiratory time, which allows more time for the aerosol
to reach to the circuit outlet. On the other hand, with higher EPAP, increased flow
during the expiratory phase results in increased clearance of the aerosol from the
BIPAP device circuit through the leak port and, hence, a decreased aerosol delivery.
Inspiratory flow rate significantly influences aerosol delivery into the lung. High
inspiratory flow rates increase turbulent flow and produce stronger inertial forces,
leading to impaction of particles in the oropharynx and proximal airways [8]. Lower
inspiratory flow rates may be used to improve drug delivery during NIV as long as
this is tolerated by the patient. Aerosol delivery can be influenced by the respiratory
rate, pressure settings, and breath-triggering mechanism.

21.2.2 Circuit-Related Factors

The gas in the ventilator circuit is heated and humidified to prevent drying of the
airway mucosa, but humidification increases loss of aerosol drugs in the ventilator
circuit [6]. During NIV, unlike IMV, air is heated and humidified during its passage
through the nose. The humidification capacity of the nose may be overwhelmed by
the sustained high airflow rates employed during NIV. Although the optimum
method of humidification for patients with acute respiratory failure has not been
established, the intensivist may prefer heated humidification for patients with acute
respiratory failure as it decreases the work of breathing and increases CO2 clear-
ance. A heat and moisture exchanger is not recommended for NIV.
The dual-limb circuit is the most common circuit used with general-purpose
critical care ventilators. However, home-care and BIPAP ventilators can be used
with single-limb circuits. There are two types of single-limb circuits: (1) those with
built-in expiratory valves and (2) those with a leakage-type exhaust valve. Branconier
and Hess [9] evaluated different positions of the leak port in BIPAP devices with a
single-limb circuit and detected higher aerosol delivery when the leak port was in
the circuit rather than the mask.

21.2.3 Type of Interface

The most commonly used interface for NIV in the intensive care unit is an oronasal
mask. Other interfaces include nasal, total face masks, helmets, mouthpieces, and nasal
pillows. A variety of sizes and designs are commercially available. Unsuccessful
aerosol therapy can occur more often in the nasal mask or poorly fitted oronasal mask
at particularly setting higher positive pressure due to major leaks. Anisocoria can
develop in patients undergoing NIV who receive ipratropium via a poorly fitting
oronasal mask. Total face masks and helmets should not be used for aerosol delivery.
21 NIV Aerosol Therapy: Key Technical Determinants and Clinical Evidence 195

21.2.4 Type of Aerosol-Generating Device and Its Configuration

Bronchodilators are among the most commonly used aerosol drugs in the inten-
sive care unit. These drugs are available in the three principal types of inhaler
devices, which include pMDI, dry powder inhaler (DPI), and nebulizers. Only
pMDIs and nebulizers have been adapted for clinical use during NIV. The effi-
ciency of aerosol delivery with a DPI in this setting is likely to be low because of
the known effect of humidity in reducing aerosol delivery from such devices.
Nebulizers or pMDIs with in-line spacers are used to administer inhaled medica-
tions during NIV.
Nebulizers: The three basic types of nebulizer devices are jet, ultrasonic, and
mesh nebulizers. Nebulizers are connected in the single-limb circuit between the
leak port and interface [10], but the optimum position of nebulizer in the dual-
limb circuit is yet to be determined. Nebulizer performance is affected by both
technical and patient-related factors. Mesh nebulizers are lighter and more por-
table than jet and ultrasonic nebulizers. Moreover, mesh nebulizers usually
deliver the medication dose more quickly and lead to higher aerosol delivery
than jet nebulizers. To avoid infection, nebulizers should be cared for appropri-
ately because of the risk of contamination. Additionally, when jet and ultrasonic
nebulizers are used, aerosol deposition occurs in the nebulizer cup, which causes
ineffective aerosol therapy.
pMDIs: The pMDI is the most commonly used aerosol device for inhalation
therapy worldwide. The drug is released from the canister through a metering
valve and stem that fits into an actuator boot designed and extensively tested by
the manufacturer to work with that specific formulation. A spacer is needed to
adapt the pMDI into the ventilator circuit, and a variety of spacers are used for
aerosol drug delivery in mechanically ventilated patients. Types of spacers include
inline devices (unidirectional and bidirectional) and chamber. These are placed in
the inspiratory limb of the dual-limb circuit. The spacer type influences the effi-
ciency of aerosol delivery during mechanical ventilation. Whereas a bidirectional
spacer is superior to a unidirectional spacer in dose delivery, a chamber spacer
with pMDI is more efficient for aerosol drug delivery compared with a bidirec-
tional or a unidirectional spacer. With a chamber spacer, the aerosol particle has
an opportunity to slow and propellant evaporation decreases the size of aerosol
particles. Both of these phenomena reduce aerosol drug losses caused by particle
impaction on the walls of the ventilator circuits and interface. The aerosolized
bronchodilator delivery is also significantly reduced when the pMDI is actuated
during the expiratory phase, hence it is important that it is actuated at the initia-
tion of the inspiratory phase.
If a dose counter is not used with a pMDI, it becomes difficult to determine
the dose left in the pMDI. The dose counters, which are attached to the top or
boot of the pMDI, are manufactured by different companies. Several commer-
cially adapters or actuators are used to connect the pMDI canister to the ventila-
tor circuit.
196 S. Ocal and A. Topeli

21.2.5 Drug-Related Factors

Ideally, the majority of the drug particles in pMDI and nebulizer aerosols should be
in the range 1–5 μm. While smaller aerosol particles will likely be quickly exhaled
before reaching the lung tissue, larger aerosol particles are trapped in the ventilator
circuit and on the interface and deposited in the proximal airways during
NIV. Additionally, aerosol delivery could be influenced by the drug dose and formu-
lation and duration of action.

21.2.6 Patient-Related Factors

During NIV, tidal volume is variable depending on the compliance of the lung and
the chest wall and the resistance of the airways. Accordingly, higher lung compli-
ance and lower airway resistance provide better distal deposition of aerosol drug.
Successful therapy is influenced by several additional variables, such as the pres-
ence and severity of airway diseases, presence of mucus, counter-regulatory effects
of inflammation and other drugs, and patient’s response. The best way to deliver
aerosol drugs to a patient is in the sitting position. However, if the patient cannot sit
in the bed during inhalation therapy, the head of the bed should be elevated at least
20–30° above for better aerosol administration during NIV.

21.3 Administration Techniques

Successful aerosol therapy for inhaled bronchodilator drugs in patients undergoing

NIV requires careful attention to the administration technique. When these tech-
niques are employed, adequate pulmonary drug deposition is achieved and a signifi-
cant response to bronchodilators is observed (Tables 21.1 and 21.2).

Table 21.1 Optimal 1. Review order, identify patient, and asses the need for
technique for drug bronchodilator therapy
delivery by pMDI in
2. Minimize leaks in the mask and/or circuit
patients undergoing NIV
3. Shake pMDI and warm it to hand temperature
4. Be sure that the dose counter is attached to the pMDI
5. Place the pMDI with chamber spacer
(a) Near the “Y” adapter in inspiratory limb for
dual-limb circuit
(b) Between the leak port and mask for single-limb
circuit
6. Coordinate pMDI action with beginning of inspiration
7. Wait at least 15 s between actuations, and administer the
total dose
8. Remove pMDI with spacer from circuit
9. Monitor for adverse effects
21 NIV Aerosol Therapy: Key Technical Determinants and Clinical Evidence 197

Table 21.2 Optimal 1. Review order, identify patient, and asses the need for a
technique for drug delivery bronchodilator therapy
by a nebulizer in patients
2. Minimize leaks in the mask and/or circuit
undergoing NIV
3. Place mesh/jet nebulizer
(a) Between the leak port and mask in a single-limb
circuit
(b) Near the “Y” adapter in the inspiratory limb of a
dual-limb circuit
4. Pour the recommended drug volume into the nebulizer
5. Set the gas flow to nebulizer at 2–10 l/min, based on the
manufacturer label
6. Run until the nebulizer begins to sputter
7. Remove the nebulizer from the circuit, rinse with sterile
water, run dry
8. Monitor for adverse effects

Conclusion
Despite the common use of aerosol drugs during NIV, it is still unclear which
technique should be used for aerosol delivery. In recent decades, a number
of bench model studies during NIV and in vitro studies during IMV have
defined some settings allowing successful aerosol therapy. Unfortunately, only
a few investigators have studied aerosol delivery in patients undergoing
NIV. Aerosolized bronchodilator therapy is effective albeit complex during NIV
and more studies are needed for optimum aerosol delivery.

Key Major Recommendations

• Both the nebulizer and the pMDI with spacer are appropriate for delivery
of bronchodilators during NIV.
• Proper technique when using a pMDI with spacer, or nebulizer during NIV
should be applied.
• Precautions to decrease contamination and to avoid aerosol particles depo-
sitions should be in place.

References
1. Ehrmann S, Roche-Campo F, Sferrazza Papa GF, et al. Aerosol therapy during mechanical
ventilation: an international survey. Intensive Care Med. 2013;39(6):1048–56.
2. Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and outcomes of aerosol therapy:
evidence-based guidelines: American College of Chest Physicians/American College of
Asthma, Allergy, and Immunology. Chest. 2005;127(1):335–71.
198 S. Ocal and A. Topeli

3. Pollack Jr CV, Fleisch KB, Dowsey K. Treatment of acute bronchospasm with beta-adrenergic
agonist aerosols delivered by a nasal bilevel positive airway pressure circuit. Ann Emerg Med.
1995;26(5):552–7.
4. Fauroux B, Itti E, Pigeot J, Isabey D, et al. Optimization of aerosol deposition by pressure sup-
port in children with cystic fibrosis: an experimental and clinical study. Am J Respir Crit Care
Med. 2000;162(6):2265–71.
5. Nava S, Karakurt S, Rampulla C, et al. Salbutamol delivery during non-invasive mechanical
ventilation in patients with chronic obstructive pulmonary disease: a randomized, controlled
study. Intensive Care Med. 2001;27:1627–35.
6. Fink JB, Dhand R, Duarte AG, et al. Aerosol delivery from a metered-dose inhaler during
mechanical ventilation. An in vitro model. Am J Respir Crit Care Med. 1996;154:382–7.
7. Calvert LD, Jackson JM, White JM, et al. Enhanced delivery of nebulized salbutamol during
non-invasive ventilation. J Pharm Pharmacol. 2006;58(11):1553–7.
8. Dolovich M. Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized
drug delivery to the lung. Respir Care. 2000;45:597–608.
9. Branconier MP, Hess DR. Albuterol delivery during noninvasive ventilation. Respir Care.
2005;50(12):1649–53.
10. Chatmongkolchart S, Schettino GP, Dilman C, et al. In vitro evaluation of aerosol bronchodila-
tor delivery during noninvasive positive pressure ventilation: effect of ventilator settings and
nebulizer position. Crit Care Med. 2002;30:2515–9.
Skin Breakdown in Patients with Acute
Respiratory Failure Undergoing 22
Noninvasive Ventilation: Key Topics

Samantha Torres Grams and Wellington Pereira Yamaguti

Contents
22.1 Introduction ................................................................................................................. 199
22.2 SB Classification ......................................................................................................... 200
22.3 Frequency of SB ......................................................................................................... 200
22.4 Treatment-Related Risk Factors for SB ...................................................................... 201
References .............................................................................................................................. 202

Abbreviations

ARF Acute respiratory failure

NIV Noninvasive ventilation
SB Skin breakdown

22.1 Introduction

Noninvasive ventilation (NIV) has been recognized as an effective treatment to

avoid the need for invasive mechanical ventilation and its associated complications
in patients with acute respiratory failure (ARF). Compared with invasive mechani-
cal ventilation, the use of NIV has the advantage of decreasing the risk of ventilator-
associated pneumonia, as well as a reduction in the hospital stay and mortality.
NIV has particularly been indicated to treat patients with chronic obstructive
pulmonary disease exacerbation, acute cardiogenic pulmonary edema, hypercapnic

S.T. Grams, MSc • W.P. Yamaguti, PhD (*)

Rehabilitation Service, Hospital Sírio-Libanês, Centro de Reabilitação, São Paulo, SP, Brazil
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 199

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_22
200 S.T. Grams and W.P. Yamaguti

respiratory failure secondary to chest wall deformity or neuromuscular diseases,

pulmonary infection in immunosuppressed subjects, acute pancreatitis, and in
weaning from tracheal intubation. However, some complications and injurious
effects with the use of NIV have also been identified, such as aerophagia, ineffi-
ciency to handle copious secretions, bronchoaspiration, hemodynamic instability,
and patient-ventilator asynchrony. Other factors that may limit the use of NIV are
interface-related problems such as air leaks and mask intolerance due to claustro-
phobia and anxiety. The development of facial skin breakdown (SB) in the zones of
greatest contact pressure between the mask and the patient’s skin has also been
recognized as one of the most serious complications related to the use of an inter-
face in patients with ARF because it can increase the discomfort reported by the
patient, resulting in interface intolerance and, consequently, in NIV failure [1].
Therefore, this chapter reviews the classification, frequency, and potential treatment-
related risk factors for SB. Early identification of these factors is fundamental to
preventing the development of SB, thus providing the best quality of care to patients.

22.2 SB Classification

Constant pressure during a critical 1–2-h interval increases the risk of SB develop-
ment due to the production of microscopic pathologic tissue changes [2]. According
to the European Pressure Ulcer Advisory Panel and the American National Pressure
Ulcer Advisory Panel [3], SB may be classified as:

• Stage I: when intact skin has non-blanchable redness of a localized area, usually
over a bony prominence (may indicate “at risk” persons);
• Stage II: when there is partial thickness loss of dermis presented as a shallow
open ulcer with a red-pink wound bed;
• Stage III: when there is full thickness tissue loss;
• Stage IV: when there is exposed bone, tendon, or muscle. Serious complications
such as osteomyelitis (infection of the bone) or sepsis (infection carried through
the blood) can occur.

22.3 Frequency of SB

Few studies have investigated the frequency of SB in patients undergoing NIV. In a

multicenter randomized study, the frequency of SB was evaluated when comparing
a prototype oronasal mask and a conventional oronasal mask in adult patients with
ARF [4]. The results showed that the patients who used the prototype oronasal
mask, specifically designed to allow a more comfortable patient-mask interface, had
significantly lower frequency of SB (43 %) compared with the conventional orona-
sal mask (100 %). In a more recent study [5], the frequency of SB was lower in a
similar population after the use of NIV with oronasal mask (14.4 %). It was
22 Skin Breakdown in Patients with Acute Respiratory Failure 201

demonstrated that 13.1 % of patients showed SB at Stage I, 1.3 % had SB at Stage

II, and no patient developed skin necrosis (Stage III). The authors explained that
these differences in results, among other factors, may be due to the use of a protec-
tive dermal sheet applied over the nasal bridge during NIV. This study also evalu-
ated the frequency of SB in patients who used NIV with total face mask, and the
results showed that the use of this type of interface avoided SB development (only
1.6 % of patients had SB).
In children, the frequency of SB was observed in 48 % of the patients with
obstructive sleep apnea, neuromuscular disorders, and cystic fibrosis undergoing
NIV via nasal mask [6]. Among the patients, 18 % showed transient erythema
(Stage I), 23 % had prolonged erythema (Stage II), and 8 % developed skin necrosis
(Stage III).

22.4 Treatment-Related Risk Factors for SB

It has been demonstrated that the total duration of NIV and the use of oronasal mask
were considered independent risk factors for the development of SB in patients with
ARF:

• Total duration of NIV use: 24–26 h of NIV use is associated with increased risk
of skin injury [4, 5]. Longer periods of NIV use are associated with a higher risk
of SB: in a previous study, 70 % of patients who continuously used NIV for 48 h
presented skin injury [7]. These findings reinforce the hypothesis that the risk of
development of SB in subjects undergoing NIV is time dependent. Although
longer periods of NIV are more associated with SB, it is important to note that
constant pressure for 1–2 h is sufficient to cause tissue damage and cell death [2]
and, therefore, even short periods of NIV deserve attention.
• Type of interface: previous studies showed that an oronasal mask may also be
considered an independent risk factor for the development of SB in adult patients
[4, 5]. The use of other types of interface that produce less pressure against the
face, such as total face mask and helmet, has been proposed as an alternative to
treat ARF, with better tolerance, comfort, and less risk of SB than oronasal mask
[5, 8, 9]. Another recommendation to prevent SB in patients who need prolonged
NIV is to use different types of mask periodically, changing the zones of pressure
on the face [10].

Higher levels of respiratory pressures and the ventilatory modes could be consid-
ered other treatment-related risk factors for the development of SB. During NIV
with high levels of respiratory pressures, the interface is usually tightly sealed to the
skin to reduce possible air leaks. If this mask pressure against the face exceeds the
skin capillary pressure, the tissue perfusion is impaired and, consequently, the risk
of SB development could be higher in this condition [9]. During the application of
CPAP, air leaks are less problematic because the pressure is constant and does not
require a very tight-fitting mask adjustment. On the other hand, as bi-level positive
202 S.T. Grams and W.P. Yamaguti

airway pressure ventilation involves oscillation of high level to lower level pres-
sures, the mask adjustment should be tighter. For these reasons, it could be expected
that ventilatory modes and higher levels of respiratory pressures would be associ-
ated with greater risk of developing skin lesions. However, this relation was not
found in a previous study [5]. The authors explained that the ventilatory mode and
its level of pressure applied did not seem to influence the occurrence of SB in their
population because the mask was properly fitted.

Key Recommendations
• Total face mask and helmet may be considered in patients who need pro-
longed NIV to prevent SB.
• Different types of masks could be used periodically, changing the zones of
pressure on the face.

References
1. American Thoracic Society, European Respiratory Society, European Society of Intensive
Care Medicine, Société de Réanimation de Langue Française. International Consensus
Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute
respiratory failure. Am J Respir Crit Care Med. 2001;163(1):283–91.
2. Breuls RG, Bouten CV, Oomens CW, et al. Compression induced cell damage in engineered
muscle tissue: an in vitro model to study pressure ulcer aetiology. Ann Biomed Eng.
2003;31(11):1357–64.
3. European Pressure Ulcer Advisory Panel, National Pressure Ulcer Advisory Panel. Prevention
and treatment of pressure ulcers: quick reference guide. 2009. http://www.epuap.org/guide-
lines/Final_Quick_Prevention.pdf. Accessed 08 Mar 2015.
4. Gregoretti C, Confalonieri M, Navalesi P, et al. Evaluation of patient skin breakdown and
comfort with a new face mask for non-invasive ventilation: a multi-center study. Intensive Care
Med. 2002;28(3):278–84.
5. Yamaguti WP, Moderno EV, Yamashita SY, et al. Treatment-related risk factors for develop-
ment of skin breakdown in subjects with acute respiratory failure undergoing noninvasive ven-
tilation or CPAP. Respir Care. 2014;59(10):1530–6.
6. Fauroux B, Lavis JF, Nicot F, et al. Facial side effects during noninvasive positive pressure
ventilation in children. Intensive Care Med. 2005;31(7):965–9.
7. Beltrame F, Lucangelo U, Gregori D, et al. Noninvasive positive pressure ventilation in trauma
subjects with acute respiratory failure. Monaldi Arch Chest Dis. 1999;54(2):109–14.
8. Chacur FH, Vilella Felipe LM, Fernandes CG, et al. The total face mask is more comfortable
than the oronasal mask in noninvasive ventilation but is not associated with improved outcome.
Respiration. 2011;82(5):426–30.
9. Nava S, Navalesi P, Gregoretti C. Interfaces and humidification for noninvasive mechanical
ventilation. Respir Care. 2009;54(1):71–84.
10. Fraticelli AT, Lellouche F, L’her E, et al. Physiological effects of different interfaces during
noninvasive ventilation for acute respiratory failure. Crit Care Med. 2009;37(3):939–45.
Nutrition During Noninvasive
Ventilation: Clinical Determinants 23
and Key Practical Recommendations

Anneli Reeves, Khoa Tran, and Peter Collins

Contents
23.1 Introduction .................................................................................................................. 204
23.2 Nutritional Depletion and Respiratory Disease ........................................................... 204
23.3 Nutritional Intervention in Respiratory Disease .......................................................... 205
23.4 Composition of Nutritional Support ............................................................................ 205
Conclusion .............................................................................................................................. 206
References ............................................................................................................................... 207

Abbreviations

COPD Chronic obstructive pulmonary disease

ETF Enteral tube feeding
NIV Noninvasive ventilation
ONS Oral nutrition support

A. Reeves, BSc Grad Dip Nut & Diet, Adv APD (*)
Nutrition Services Department, Logan Hospital, Meadowbrook, QLD, 4131, Australia
e-mail: [email protected]; [email protected]
K. Tran, MBBS, FRACP, FCICM
Respiratory Medicine, Logan Hospital, Meadowbrook, QLD, 4131, Australia
e-mail: [email protected]
P. Collins, PhD, APD
Nutrition and Dietetics, School of Exercise and Nutrition Sciences, Faculty of Health,
Queensland University of Technology, Kelvin Grove, QLD, 4059, Australia
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 203

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_23
204 A. Reeves et al.

23.1 Introduction

Malnutrition is a common problem affecting between 25 and 40 % of individuals

with advanced chronic obstructive pulmonary disease (COPD) [1]. As COPD
patients have some of the highest incidences of repeat hospital admissions [2] and
with malnutrition in COPD associated with a prolonged length of hospital stay, the
optimization of nutritional intake during these periods is important. Despite malnu-
trition being highly prevalent and associated with poor clinical outcomes, recent sys-
tematic reviews and meta-analyses have shown that, if it is identified, it is treatable
[3, 4]. Nutritional support was found to not only significantly improve nutritional
intake and nutritional status [3] but also to translate to improvements in respiratory
muscle strength, functional capacity, and quality of life [4]. However, only two stud-
ies included in the reviews targeted inpatients, and these were in non-acute, stable
COPD patients with no reported use of noninvasive ventilation (NIV) [3].

23.2 Nutritional Depletion and Respiratory Disease

The association between nutritional depletion and chronic respiratory disease is

well known. During exacerbations of respiratory disease, pulmonary function can
be impaired to a level that negatively impacts an individual’s ability to achieve their
nutritional requirements [5]. The etiology of nutritional depletion in this instance is
multifactorial and a combination of an inability to achieve altered nutritional
requirements against a background of elevated systemic inflammation, impaired
functional capacity, and medication side effects [5]. Although medical interventions
such as NIV can serve as an additional physical barrier to the intake of food, NIV
has been shown to be associated with an improvement in nutritional status in those
previously identified as at nutritional risk [6]. Budweiser and colleagues [6]
acknowledged the complexity of weight loss in COPD and speculated that NIV
could assist in producing a positive nutritional balance required for weight gain
through reducing the work associated with breathing. Similar improvements in
body weight have also been reported following lung volume reduction surgery [5,
6]. It is also feasible that NIV results in improved nutritional status through other
mechanisms such as improvement of hypercapnia and acidosis, which are known to
negatively impact protein synthesis [6]. Elevated systemic inflammation, particu-
larly during acute episodes of the disease, is known to negatively impact on appe-
tite, nutrition intake, and protein synthesis and breakdown [5, 6]. As NIV assists in
reducing episodes of respiratory failure, hypoxia, and elevated inflammation, this
may reduce periods of negative energy balance and catabolism [6]. Acute exacerba-
tions that did not involve the use of NIV have been associated with reduced nutri-
tional intake and increased energy expenditure in COPD patients [7]. There is
limited research describing nutritional intake of hospitalized patients receiving NIV,
with no protocols currently available to guide health-care professionals in the nutri-
tional management of this patient group. One prospective study of 36 hospitalized
patients receiving NIV showed that more than 75 % of the patients had inadequate
23 Nutrition During Noninvasive Ventilation: Clinical Determinants 205

intake [8]. Intake was lower with increasing time on NIV, and earlier during their
hospital admission. Patients who were enterally fed received significantly more
energy and protein than those who were receiving oral nutrition only [8].

23.3 Nutritional Intervention in Respiratory Disease

As malnutrition in respiratory disease is a significant clinical problem leading to

increased mortality risk, patients at risk of malnutrition need to be identified and to
receive prompt appropriate nutrition support. This requires routine nutritional
screening followed by appropriate nutritional intervention (such as nutritional sup-
plements or enteral feeds) for patients identified as malnourished or at risk of mal-
nutrition. Malnutrition assessment includes consideration of low body mass index
(<20 %), low fat free mass (<17 % for males and <15 % for females), and involun-
tary weight loss of 5 % or more during the last 6 months [5]. Oral nutritional support
is the preferred method of management of malnutrition with high-energy, high-
protein foods offered. Texture-modified foods or minced and moist foods might be
used as they require less chewing in a breathless patient and are easily swallowed.
High-energy, high-protein, liquid multi-nutrient oral nutritional supplements (ONS)
are also used and can be divided into doses throughout the day to assist with toler-
ance [9]. Where patients are unable to achieve 75 % of their estimated nutritional
requirements despite these oral nutritional support strategies, a period of enteral
tube feeding (ETF) is indicated [10]. Although there is robust evidence for the clini-
cal effectiveness of ONS in stable COPD [3, 4], only one randomized placebo-
controlled trial to date has used nocturnal ETF in a small sample of stable,
malnourished COPD patients [10]. Despite ETF only being provided for 16 days,
the intervention group gained a significant amount of weight (3 kg) and experienced
significant improvements in respiratory muscle function.

23.4 Composition of Nutritional Support

It has long been known that nutrition and ventilation are linked with oxygen needed
for energy production, and it was thought that a lower carbohydrate and higher fat
intake in patients requiring ventilation would be beneficial in optimizing oxygen
utilization while minimizing carbon dioxide production [1]. Clinical evidence sup-
porting this practice is limited and, more recently, it has been recognized that
avoiding overfeeding and providing excessive substrate that needs to be oxidized is
more critical [1]. In addition, the delayed gastric emptying with aggressive feeding
and the potential negative impact on breathing mechanics will further increase the
burden on the respiratory system [1]. In fact, there is data showing patients experi-
ence less dyspnea after a carbohydrate-rich liquid ONS than after an isocaloric
fat-rich ONS that would have a longer gastric transit time [7]. However, oral nutri-
tion support achieves best results not by manipulating macronutrient composition
but by being given in small, frequent doses, thereby avoiding complications and
206 A. Reeves et al.

improving compliance [1, 9]. There remains interest in how nutrition can be
manipulated to provide better care for respiratory patients, and one such study
investigated the effect of ETF enriched with eicosapentaenoic and gamma-linoleic
acid versus a high-fat ETF in ventilated patients [11]. Those ventilated patients
who received the omega-3 fatty acid–enriched ETF had significantly improved
oxygenation by day 4, a shorter requirement for ventilation, and significantly
reduced mortality at 28 days [11]. These extremely promising results demonstrat-
ing the benefits of nutritional support and its potential immunomodulatory effects
indicate further exploration in other respiratory groups is warranted. This is par-
ticularly the case in patient groups where malnutrition and elevated systemic
inflammatory markers are hallmarks.

Conclusion
The etiology of malnutrition in respiratory disease and those requiring NIV is
complex, but the result is poor clinical and economic outcomes and poorer qual-
ity of life for the patient. However, in conditions such as stable COPD, malnu-
trition is treatable and can be prevented. This results in improvements in
nutritional status, functional capacity, and quality of life. To maximize the
effectiveness of nutritional support, the nutritional management of patients
requires a coordinated approach and consideration of care in the acute and sta-
ble phases of the disease. Routine nutritional screening and assessment are
needed to promptly identify malnourished individuals and those at risk of mal-
nutrition, with the initiation of nutritional support ideally overseen by a
dietitian.

Key Points
• COPD patients receiving NIV should be routinely screened for malnutri-
tion, and nutritional intake should be monitored for adequacy.
• Early referral to a dietitian and/or commencement of nutrition support is
recommended for patients identified as at nutritional risk.
• Ventilated patients have a great variation in nutritional needs depending on
whether they are hypometabolic, normometabolic, or hypermetabolic.
Regular nutritional assessment of ventilated patients is required.
• Although there are some promising results around the manipulation of
nutrition and the use of specialist enteral feeds in critically ill patients,
more evidence is needed before they can be recommended over standard
enteral formulas.
• Current evidence recommends use of high-energy, high-protein, and low-
volume oral nutritional supplements in addition to maximizing oral intake.
If nutrition support cannot be managed orally, enteral tube feeding is indi-
cated and should be considered.
23 Nutrition During Noninvasive Ventilation: Clinical Determinants 207

References
1. Anker SD, John M, Pedersen PU, Raguso C, Cicoira M, Dardai E, Laviano A, Ponikowski P,
Schols AM, DGEM (German Society for Nutritional Medicine), Becker HF, Böhm M,
Brunkhorst FM, Vogelmeier C, ESPEN (European Society for Parenteral and Enteral
Nutrition). ESPEN guidelines on enteral nutrition: cardiology and pulmonology. Clin Nutr.
2006;25(2):311–8.
2. Porter J, Herring J, Lacroix J, Levinton C. CIHI survey: avoidable admissions and repeat
admissions: what do they tell us? Healthc Q. 2007;10(1):26–8.
3. Collins P, Stratton R, Elia M. Nutritional support in chronic obstructive pulmonary disease: a
systematic review and meta-analysis. Am J Clin Nutr. 2012;95:1385–95.
4. Collins P, Elia M, Stratton R. Nutritional support and functional capacity in chronic obstructive
pulmonary disease: a systematic review and meta-analysis. Respirology. 2013;18(4):616–29.
5. Schols A, Ferreira I, Franssen F, Gosker H, Janssens W, Muscaritoli M, Pison C, Rutten-van
M, Slinde F, Steiner M, Tkacova R, Singh S. Nutritional assessment and therapy in COPD:
Metabolism and nutrition: shifting paradigms in COPD management. http://ow.ly/As0xh 201
from http://www.ciro-horn.nl/en/publications-2014/An official systematic review of the
European Respiratory Society. European Respiratory Society statement from ERS Publications
Taskforce Report.
6. Budweiser S, Heinemann F, Meyer K, Wild P, Pfeifer M. Weight gain in cachectic COPD
patients receiving noninvasive positive-pressure ventilation. Respir Care. 2006;51(2):126–32.
7. Vermeeren MA, Wouters EF, Nelissen LH, van Lier A, Hofman Z, Schols AM. Acute effects
of different nutritional supplements on symptoms and functional capacity in patients with
chronic obstructive pulmonary disease. Am J Clin Nutr. 2001;73(2):295–301.
8. Reeves A, White H, Sosnowski K, Tran K, Jones M, Palmer M. Energy and protein intakes of
hospitalised patients with acute respiratory failure receiving non-invasive ventilation. Clin
Nutr. 2014;33(6):1068–73.
9. Broekhuizen R, Creutzberg EC, Weling-Scheepers CA, Wouters EFM, Schols AMWJ.
Optimizing oral nutritional drink supplementation in patients with chronic obstructive pulmo-
nary disease. Br J Nutr. 2005;93(6):965–71.
10. Whittaker JS, Ryan CF, Buckley PA, Road JD. The effects of refeeding on peripheral and
respiratory muscle function in malnourished chronic obstructive pulmonary disease patients.
Am Rev Respir Dis. 1990;142:283–8.
11. Singer P, Theilla M, Fisher M, Gibstein L, Grozovski E, Cohen J. Benefit of an enteral diet
enriched with eicosapentaenoic acid and gamma-linoleic acid in ventilated patients with acute
lung injury. Crit Care Med. 2006;34(4):1033–8.
Mechanical Insufflation-Exsufflation
as Adjunctive Therapy During 24
Noninvasive Ventilation with Airways
Encumbrance: Key Technical Topics
and Clinical Indications in Critical Care

Andrea Vianello, Oreste Marrone, and Grazia Crescimanno

Contents
24.1 Introduction .................................................................................................................. 209
24.2 Mechanically Assisted Coughing in the Critical Care Setting .................................... 210
References ............................................................................................................................... 213

24.1 Introduction

Patients undergoing noninvasive positive pressure ventilation (NPPV) for acute

respiratory failure (ARF) may experience retained secretions from several causes,
including reduced mucociliary clearance, increased mucus volume and consistency,
and an inability to cough effectively as a result of weakened respiratory and/or bul-
bar muscles. A noninvasive approach to the management of tracheobronchial secre-
tions, based on the combination of NPPV and expiratory muscle aid, may result in
a reduced need of nasal suctioning and conventional endotracheal intubation (ETI)
and/or tracheostomy. In addition, preventive application of assisted coughing tech-
niques after extubation may provide a clinically important advantage to patients
with neuromuscular disorders (NMDs) by averting the need for reintubation and
shortening their stay in the intensive care unit (ICU).

A. Vianello, MD (*)
Respiratory Pathophyisology Division, University-City Hospital of Padova, Padova, Italy
e-mail: [email protected]
O. Marrone, MD • G. Crescimanno, MD
Institute of Biomedicine and Molecular Immunology, CNR, Palermo, Italy
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 209

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_24
210 A. Vianello et al.

24.2 Mechanically Assisted Coughing

in the Critical Care Setting

Airway clearance techniques have the potential to improve mucociliary clearance dur-
ing NPPV therapy or immediately after extubation by reducing mucus plugging and
enhancing the removal of secretions. It is important to distinguish between secretion
mobilization techniques (clearance of peripheral airways), including postural drain-
age, chest wall vibration, positive expiratory pressure therapy, high-frequency chest
compression, and high-frequency chest wall oscillation, and cough augmentation
techniques (clearance of central and upper airways), including manually and mechan-
ically assisted coughing. Among cough augmentation aids, mechanically assisted
coughing (MAC) can be delivered by a device consisting of a two-stage axial com-
pressor that provides positive pressure to the airway, then rapidly shifts to negative
pressure, thereby generating a forced expiration. It is usually applied via a facemask.
It commonly produces a decrease in pressure by approximately 80 cm H2O in 0.2 s;
the insufflation and exsufflation pressure and time are independently adjustable. The
device can deliver maximum positive and negative pressures of about 60 cm H2O.
The use of mechanical insufflation-exsufflation (MI-E) devices for MAC has
been proposed as a complement to NPPV in patients with NMD with an inability to
generate an effective cough who develop an intercurrent respiratory tract infection,
with the goal to expel secretions, allay secretion-associated dyspnea, and increase
oxyhemoglobin saturation and pulmonary parameters.
Ability to effectively cough can be evaluated by measuring peak cough flow
(PCF), the maximum airflow generated by the patient during cough, which is depen-
dent on lung volume, airway caliber, compliance of the respiratory system, and
inspiratory and expiratory muscle strength. Normal individuals may produce a PCF
as great as 720 l/min (occasionally higher in healthy individuals). The minimum
effective PCF was inferred from patients who were being weaned from mechanical
ventilation, showing that successful extubation requires at least 160 l/min (2.7 l/s).
Bach and Saporito [1], in fact, conducted a mixed-population study in 49 patients
that found that those with PCF below 160 l/min, irrespective of the ability to breathe,
failed extubation or decannulation. On this basis, indications for the use of MI-E in
the acute setting have been considered as the following:

• An established diagnosis of paralytic/restrictive disorder

• Patient unable to cough or clear secretions effectively with a PCF less than 160 l/
min using lung volume recruitment (LVR) with bag or volume ventilator
• Patient overly fatigued when performing LVR with the resuscitation bag or vol-
ume ventilator [2]

The following contraindications should be carefully considered before using

MI-E:

• A patient with a history of bullous emphysema

• Susceptibility to pneumothorax or pnuemomediastinum
• Recent barotraumas
24 Mechanical Insufflation-Exsufflation in the Critical Care Setting 211

Because MI-E releases positive pressure, the following precautions should also
be considered before its use: facial fractures; recent esophageal, pulmonary, or
anti-reflux surgery; gastric distention; cardiovascular system instability (hypoten-
sion and arrhythmias); raised intracranial pressure; pain; nausea; bronchospasm;
pulmonary edema; extreme tachypnea; large airway carcinoma; and unexplained
hemoptysis [3].
Physiologically, MI-E has been shown to increase PCF in patients with NMD [3,
4]; an increase in PCF is thought to improve the efficacy of cough and thus assist in
secretion removal. A study performed in individuals with amyotrophic lateral scle-
rosis demonstrated significant increases in PCF from baseline unassisted coughs, in
patients both with and without bulbar muscle weakness, when using either exsuffla-
tion alone, or MI-E. In those without bulbar muscle involvement, the weakest
patients (Vital Capacity < 50 %) demonstrated the largest increases in PCF [4].
In the acute setting, MAC has been utilized in combination with NPPV to avoid
ETI and tracheotomy, to facilitate extubation and decannulation, and to prevent
post-extubation failure in patients with NMD [5–9]. Servera et al. [5] conducted a
prospective cohort study in the respiratory medicine ward of a university hospital to
study the success rate of the use of continuous NPPV and manually and mechani-
cally assisted coughing to avert ETI in 24 consecutive episodes of ARF for 17
patients with NMD. NPPV and coughing aids were used to reverse decreases in
oxyhemoglobin saturation and relieve respiratory distress that occurred despite oxy-
gen therapy and appropriate medication. Noninvasive management was successful
in averting death and ETI in 79.2 % of the acute episodes, with bulbar dysfunction
resulting the only independent risk factor for failure of the noninvasive approach.
In our experience, we compared 11 NMD patients who received a mean ± SD
2.7 ± 0.9 MI-E sessions per day to 16 historical matched controls who were treated
with postural drainage, and suction when required. The results of the retrospective
study showed that patients who received MI-E had a lower treatment failure rate
(defined by the need to insert a mini-tracheostomy or the need to intubate; 2/11 vs
10/16; p = 0.047). There was no significant difference between the groups in the
duration of NPPV (p = 0.93) or in the proportion of patients requiring bronchoscopy
(p = 0.71). In addition, MI-E did not produce serious side effects and was well toler-
ated by all subjects [6]. On this basis, MI-E in combination with NPPV can be sug-
gested as an effective alternative to ETI in managing ARF in NMD patients with
mucous encumbrance.
Extubation failure is an outcome to be avoided because it is independently associ-
ated with increased hospital mortality, prolonged ICU and hospital stay, higher costs,
and greater need for tracheotomy [10]; therefore, strategies preventing this occur-
rence are required. To avert extubation failure in patients at high risk, recent studies
have evaluated the effectiveness of NPPV as a preventive strategy, concluding that its
application can reduce the need for reintubation and mortality rate in the ICU in
individuals with chronic respiratory disorders (including chronic obstructive pulmo-
nary disease, obesity hypoventilation, sequelae of tuberculosis, chest wall deformity,
and chronic persistent asthma), congestive heart failure, and/or hypercapnia of differ-
ent etiologies [11, 12]. Unfortunately, poor cough strength and inability of patients to
protect their upper airway, with the need for airway suctioning and an increased risk
212 A. Vianello et al.

of aspiration and pneumonia, are a common occurrence among patients with NMD,
leading to extubation intolerance and, finally, failure, regardless of the use of inspira-
tory aids. As a consequence, the combination of NPPV and cough assistance may
become essential to prevent extubation failure in neuromyopathic patients. Bach
et al. [8] reported data collected on 152 consecutive unweanable patients who could
not pass a spontaneous breathing trial (SBT) before or after extubation. They were
administered a protocol including extubation once SpO2 was maintained ≥95 % in
ambient air to full NPPV support and aggressive manually assisted cough-
ing. Extubation success was defined as not requiring reintubation during the hospi-
talization. The first attempt protocol extubation success rate was 95 % (144 patients).
All 96 extubation attempts on patients with assisted PCF ≥ 160 l/m were successful.
Six of 7 patients who initially failed extubation succeeded on subsequent attempts,
so only one with no measurable assisted PCF underwent tracheotomy. The author
concluded that the standardized use of NPPV and cough assist can lead to effective
extubation of almost all “unweanable” patients with NMD who could not pass an
SBT, supporting the argument that timely provision of inspiratory and expiratory
aids allows for virtual elimination of post-extubation failure in patients with NMD.
In our experience, we reported the prospective analysis of the short-term out-
comes of 10 patients with NMD who were treated by NPPV and assisted coughing
immediately after extubation, comparing them with the outcomes of a population of
10 historical control patients who received standard medical therapy (SMT) alone
[13]. Need for reintubation despite treatment was evaluated. Significantly fewer
patients who received the treatment protocol required reintubation and tracheos-
tomy compared with those who received SMT (reintubation, 3 vs 10; tracheostomy,
3 vs 9; p = .002 and .01, respectively). Mortality did not differ significantly between
the two groups. Patients undergoing the weaning protocol remained for a shorter
time in the respiratory ICU compared with historical controls (7.8 ± 3.9 vs
23.8 ± 15.8 days; p = .006).
Finally, MI-E has also been successfully used in the acute setting in the treatment
of postoperative sputum retention following major surgery in patients with NMD,
permitting quick extubation of subjects with profuse airway secretions. In particu-
lar, a case has been reported demonstrating the successful postoperative manage-
ment of a child with spinal muscular atrophy undergoing a single-stage posterior
spinal fusion procedure. An MI-E device was used to successfully treat bronchial
mucous encumbrance and avoid a tracheotomy [14].
According to these results, we conclude that MI-E combined with NPPV pro-
vides greater success in weaning patients with NMDs from invasive mechanical
ventilation than do conventional methods.

Key Major Recommendations

• Ineffective cough with mucous encumbrance is a major cause of mortality
and morbidity in patients with NMD who develop ARF.
• A normal cough requires the ability to generate transient PCFs of at least
160 l/min.
24 Mechanical Insufflation-Exsufflation in the Critical Care Setting 213

• The use of MI-E in combination with NPPV should be considered in the

management of mucous retention in patients with NMD developing ARF.
• Preventive application of assisted coughing techniques combined with
NPPV after extubation may avert the need for reintubation or tracheostomy.

References
1. Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with
ventilatory failure. A different approach to weaning. Chest. 1996;110:1566–71.
2. Toussaint M, Boitano LJ, Gathot V, et al. Limits of effective cough-augmentation techniques
in patients with neuromuscular disease. Respir Care. 2009;54:359–66.
3. Chatwin M, Ross E, Hart N, Nickol AH, Polkey MI, Simonds AK. Cough augmentation with
mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J.
2003;21:502–8.
4. Mustfa N, Aiello M, Lyall RA, et al. Cough augmentation in amyotrophic lateral sclerosis.
Neurology. 2003;61:1285–7.
5. Servera E, Sancho J, Zafra MJ, et al. Alternatives to endotracheal intubation for patients with
neuromuscular diseases. Am J Phys Med Rehabil. 2005;84:851–7.
6. Vianello A, Corrado A, Arcaro G, et al. Mechanical insufflation-exsufflation improves out-
comes for neuromuscular disease patients with respiratory tract infections. Am J Phys Med
Rehabil. 2005;84:83–8.
7. Bach JR, Gonçalves M. Ventilator weaning by lung expansion and decannulation. Am J Phys
Med Rehabil. 2004;83:560–8.
8. Bach JR, Gonçalves MR, Hamdani I, Winck JC. Extubation of patients with neuromuscular
weakness: a new management paradigm. Chest. 2010;137:1033–9.
9. Gonçalves MR, Honrado T, Winck JC, Paiva JA. Effects of mechanical insufflation-exsufflation
in preventing respiratory failure after extubation: a randomized controlled trial. Crit Care.
2012;16(2):R48.
10. Epstein SK. Extubation failure: an outcome to be avoided. Crit Care. 2004;8:310–2.
11. Ferrer M, Valencia M, Nicolas JM, et al. Early noninvasive ventilation averts extubation failure
in patients at high risk: a randomized trial. Am J Respir Crit Care Med. 2006;173:164–70.
12. Ferrer M, Sellarés J, Valencia M, et al. Non-invasive ventilation after extubation in hypercap-
nic patients with chronic respiratory disorders: randomised controlled trial. Lancet. 2009;374:
1082–8.
13. Vianello A, Arcaro G, Braccioni F, Gallan F, et al. Prevention of extubation failure in high-risk
patients with neuromuscular disease. J Crit Care. 2011;26:517–24.
14. Marchant WA, Fox R. Postoperative use of a cough-assist device in avoiding prolonged intuba-
tion. Br J Anaesth. 2002;89:644–7.
Role of Complementary Chest
Physiotherapy Techniques: Strategies 25
to Prevent Failure During Noninvasive
Mechanical Ventilation

Sergio R.M. Mateus

Contents
25.1 Introduction ................................................................................................................. 215
25.2 Airway Clearance Techniques .................................................................................... 216
25.2.1 Manual Techniques ....................................................................................... 216
25.2.2 Cough ............................................................................................................ 217
25.2.3 Intrapulmonary Percussive Ventilation ......................................................... 218
25.2.4 Orotracheal and Nasotracheal Aspiration ..................................................... 219
Conclusion ............................................................................................................................. 220
References .............................................................................................................................. 220

Abbreviations

IPPB Intermittent positive pressure breathing

IPV Intrapulmonary percussive ventilation

25.1 Introduction

Use of noninvasive ventilation in many clinical scenarios, including those with a

strong evidence such as in the exacerbation of chronic obstructive pulmonary dis-
ease and in cardiogenic pulmonary edemas is agreed upon [1]. However, results
noninvasive ventilation can be optimized through the identification of the cause and,
consequently, type of respiratory failure, the patient’s state of consciousness,

S.R.M. Mateus, PT, MSc, PhD

Assistant Professor, Physical Therapy, Post Graduate Program in
Biomedical Engineering, University of Brasília – UnB, Brasília, Brazil
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 215

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_25
216 S.R.M. Mateus

collaboration, and understanding of the procedure, and the adaptation of the inter-
face and the ventilator equipment [2]. Respiratory monitoring during noninvasive
ventilatory assistance, along with early identification of the clinical alterations that
may occur, can result in an immediate therapeutic intervention.
There are two types of respiratory failure. Type I is characterized by a deficit of
oxygenation, that is, hypoxemia, caused by a reduction of regional ventilation and
of airway clearance, ineffective coughing, disturbance of the patient’s diffusion
capacity, and change in ventilation and perfusion. Such alterations take place due to
pulmonary parenchyma dysfunction. Type II appears as the ventilatory pump failure
allowing ventilation and respiratory disorders, that is, hypercapnia and hypoxemia,
to be observed. Alterations in the respiratory drive or respiratory mechanics and
neuromuscular disorders can also be noted. It is important to identify the type and
cause of the respiratory failure so that the correct physiotherapy technique can be
prescribed and the results of the noninvasive ventilation optimized [3]. Independent
of the type of respiratory failure, there is frequently an increase in bronchial secre-
tions, either due to an increase in production, as occurs in an infectious process, or
to the patient’s inability to cough [4]. Such a condition constitutes a risk factor for
failure of the noninvasive ventilation [5], and chest physiotherapy techniques may
constitute a strategy that can be used in this case [6].
The failure of noninvasive ventilation can be divided into three periods: immediate
(<1 h), early (1–48 h), and late (>48 h) [5]. Fifteen percent of failures occur in the
immediate period, 68 % in the early period, and 17 % in the late period. The clinical
condition that contributes most to failure during the immediate period is a weak cough
reflex and/or excessive secretions [5]. Nevertheless, chest physiotherapy measures can
effectively contribute to the success of noninvasive ventilation [6]. For a chest physio-
therapy technique to be selected, it is necessary to consider the patient’s age, severity
of disease, the viability of the procedure in terms of practicality and ease of use, patient
comfort [4], execution time, and the patient’s level of dependency on noninvasive ven-
tilation. The aims of physiotherapy in respiratory dysfunction are to improve global
and/or regional ventilation and lung compliance, reduce airway resistance and the work
of breathing, and clear airway secretions, consequently oxygenation is optimize by
improving ventilation possible to optimize oxygenation by improving ventilation.

25.2 Airway Clearance Techniques

25.2.1 Manual Techniques

25.2.1.1 Percussion, Vibration, and Shaking

Despite the lack of evidence of the effectiveness of manual techniques, we empha-
size that these maneuvers depend on the operator, whose must reach a specific fre-
quency and rhythm necessary for the secretion to be dislocated toward a more
central airway [7].
Percussion involves rhythmical beating, at a frequency of 3–6 Hz, with properly
shaped hands on the chest wall over specific regions of the lungs to remove the
25 Role of Complementary Chest Physiotherapy Techniques 217

mucus. Manual vibration of the chest wall can be performed by placing both hands
firmly on the chest wall over the treated region of the lungs and making fast and
continuous pressing movements during both inspiration and expiration. Shaking of
the chest wall is performed by pressing the sides of the chest wall with flatly placed
hands [7]. We suggest that it begin after inspiration. It can be associated with postural
drainage for the improvement of the dislocation of secretions. Both percussion and
vibration cause air oscillations inside the airway, facilitating mucus transport [7].
These techniques should take into consideration the time of execution in the indi-
vidual with noninvasive ventilation, due to the risk that the reduction of oxygen may
lead to discomfort. Furthermore, to be considered efficient, it must be finished with
measures to induce spontaneous coughing, manually assisted coughing, huffing, or
aspiration. The technique is contraindicated in cases where the patient has coagula-
tion disorders. With respect to the lack of evidence, it is possible that the clinical
outcomes investigated in the studies were not sensitive enough for any clinical differ-
ence to be detected [8]. After the performance of manual techniques, assisted or
voluntary coughing, huffing, or tracheal aspiration should be induced for the elimina-
tion of bronchial secretions.

25.2.2 Cough

25.2.2.1 Cough Evaluation

Coughing has three phases. In the inspiratory phase, it is necessary to maintain the
integrity of the inspiratory musculature, pulmonary and thoracic complacency, and
the maximum inspiratory effort, which increases the pulmonary volume until it
draws near the total pulmonary capacity. The second phase is characterized by the
closure of the glottis and a rise in the intrathoracic pressure, which occurs due to the
action of bulbar muscles, following the reopening of the glottis in 0.2 s. Finally,
there is the expulsion phase, which consists of the liberation of the respiratory flow
through the contraction of the expiratory muscles, especially the abdominal muscles
[9]. If the patient presents any alterations in any of these phases, it will directly
affect the peak flow of the cough. Thus, the peak flow of the cough should be evalu-
ated considering that, below 160 l/min, the cough is ineffective and may predict the
failure of noninvasive ventilation; between 160 and 270 l/min, it represents a mod-
erate risk of complication. However, cough assistance measures are effective in the
latter context [10]. At this point, strategies for bronchial hygiene can be defined.

25.2.2.2 Cough Assistance

There are three kinds of cough assistance: manual, mechanical, and functional elec-
trical stimulation. In patients receiving noninvasive ventilation, only the manual and
mechanical options are used.

25.2.2.3 Manual Assistance

The manually assisted cough consists of the manual compression of the abdomen’s
epigastric region, which must be synchronized with the moment in which the glottis
218 S.R.M. Mateus

is opened. It can be performed by the placement of both hands on the abdomen or

with one hand on the thoracic region and the other on the abdomen. This technique
increases the cough’s peak flow [11]; however, it depends on the integrity of the
inspiratory musculature or on techniques of maximum insufflation capacity, which
ensures the first phase of the cough, inspiratory volume. In addition, the integrity of
the bulbar musculature is also required, because it is responsible for glottal control
and, consequently, compression of gas. The abdominal compression increases the
intra-abdominal pressure, which is transmitted to the thoracic pressure with the dis-
location of the diaphragm and the rise in the expiratory flow.

25.2.2.4 Mechanical Assistance or Cough Machine

Cough assist equipment promotes positive pressure during inspiration, assisting the
first phase of cough. With the increase in the inspiratory volume, a thoracic expan-
sion can be observed, and, after a few seconds (2–3), the patient is asked to cough.
With the glottis open, a negative pressure is applied to promote a suction of the
secretion. This system is also known as mechanical insufflation-exsufflation, and
the pressure is applied by a mask or mouthpiece. It is important to always begin and
end with the inspiratory pressure, thus expanding the lungs before moving to the
suction phase of negative pressure. It is also relevant to repeat some of the phases
only with inspiration, which is similar to the technique of intermittent positive pres-
sure breathing (IPPB). After the patient is fully adapted and understands the pro-
cess, the complete cycle may be utilized, that is, positive pressure, insufflation, and
negative pressure. Although there is no consensus on the subject, we suggest that
the pressure to be applied is around +40 cmH2O to –60 cmH2O. It is important to
adjust this pressure to the thoracic and pulmonary complacency so that the expan-
sion is adequate to enhance the inspiratory volume and, consequently, the efficiency
of the cough. This technique is able to ensure the inspiratory pulmonary volume. In
addition, it can be executed quickly and efficiently to eliminate bronchial secretions.
The method is applicable to patients using noninvasive ventilation assistance and
contributes to the success of the treatment.
Complications such as pneumothorax due to barotrauma, aerophagia, and
abdominal distension can occur.

25.2.3 Intrapulmonary Percussive Ventilation

Intrapulmonary percussive ventilation (IPV) equipment provides a pulsatile air flow

during inspiration. Based on a method modified from IPPB, IPV generates mini
bursts of air with frequencies ranging from 100 to 300 cycles per minute, oscilla-
tions from 1.7 to 5 Hz, and pressures from 5 to 35 cm H2O. The system produces a
shock wave from the airways, then the vibration dislocates the secretions, which are
conducted by the airflow to the central region. The equipment may be associated
with postural drainage [12]. Presenting evidence of level 1, it has also proven to be
effective when used in patients with exacerbated chronic obstructive pulmonary
diseases, acute respiratory failure, atelectasis [13], and cystic fibrosis [12]. The
25 Role of Complementary Chest Physiotherapy Techniques 219

cooperation of the patient is essential, and during the performance of this technique,
the individual will be disconnected from noninvasive ventilation. IPV is also used in
cases of noninvasive ventilation though a helmet [14].

25.2.4 Orotracheal and Nasotracheal Aspiration

Aspiration must be carried out when secretions cannot be eliminated. This procedure
is, thus, an option for bronchial hygiene. It is executed by the introduction of a suc-
tion catheter in the trachea, either orally (orotracheal suctioning) or nasally (nasotra-
cheal suctioning). This technique is not always easy to execute because it is performed
blindly, that is, the operator does not have sight of the end of the catheter. We suggest
lubricating the nostrils with gel and careful introducing the aspiration catheter,
because, when it approaches the epiglottis, the patient’s coughing reflex is frequently
activated, usually followed by inspiration. At this moment, the catheter is introduced
and aims at the trachea, where the suctioning of the secretion is carried out. To opti-
mize the technique and direct the catheter toward the trachea, an oropharyngeal
(Fig. 25.1) or a nasopharyngeal (Fig. 25.2) tube may be used. The nasopharyngeal

Fig. 25.1 Position of an

oropharyngeal tube in the
airway

Fig. 25.2 Position of a

nasopharyngeal tube in the
airway
220 S.R.M. Mateus

tube is indicated for hypersecretion, due to the necessity of a higher frequency of

aspiration, reducing traumas on the nasal mucosa and on the superior airway. Some
measures must be taken before initiating this procedure, including raising the inspired
fraction of oxygen. During the performance of suctioning, the patient’s oxygenation,
cardiovascular function, and perfusion should be monitored [15]. There are many
complications associated with this procedure, including bleeding, vomiting, arrhyth-
mia, tachycardia, bradycardia, and cardiac arrest due to vagal stimulation [15].
Hence, this technique should only be utilized as a last resort for bronchial
clearance.

Conclusion
An objective of chest physiotherapy techniques is to promote bronchial hygiene to
make sure that the patient’s airways remain pervious. Therefore, the methods
described here contribute to decreasing resistance in the airways and, consequently,
respiratory effort, preventing atelectasis and other respiratory complications. In the
case of the noninvasive ventilation, tracheal intubation is avoided, leading to more
favorable prognoses. There are numerous chest physiotherapy measures that can
contribute to the success of noninvasive ventilation. Decisions to undertake such
measures are based on scientific evidence, clinical scenario, available material
resources, time required for execution of the technique, and experience of the oper-
ators. Patients should be kept under clinical bedside monitoring to allow early
detection of the necessity for the most appropriate intervention.

Key Major Recommendations

• Evaluate the cough through its peak flow, remembering that an index of
<160 l/min indicates failure of the noninvasive ventilation.
• Manual techniques require skill and take a longer period of time to per-
form. In patients who are unable to cough, cough assistance measures
should be added.
• Mechanically assisted coughing should be encouraged as a measure for
bronchial clearance because it is useful in two important phases of cough –
inspiration and expiration – and can be quickly executed.
• In cases of hypersecretion requiring nasotracheal suctioning, the usage of
a nasopharyngeal tube is advisable.

References
1. Berg KM, Clardy P, Donnino MW. Noninvasive ventilation for acute respiratory failure: a
review of the literature and current guidelines. Intern Emerg Med. 2012;7:539–45.
2. Penuelas O, Frutos-Vivar F, Esteban A. Noninvasive positive-pressure ventilation in acute
respiratory failure. CMAJ. 2007;177:1211–8.
3. Gosselink R, Bott J, Johnson M, et al. Physiotherapy for adult patients with critical illness:
recommendations of the European Respiratory Society and European Society of Intensive
25 Role of Complementary Chest Physiotherapy Techniques 221

Care Medicine Task Force on Physiotherapy for Critically Ill Patients. Intensive Care Med.
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4. Volsko TA. Airway clearance therapy: finding the evidence. Respir Care. 2013;58:1669–78.
5. Ozyilmaz E, Ugurlu AO, Nava S. Timing of noninvasive ventilation failure: causes, risk fac-
tors, and potential remedies. BMC Pulm Med. 2014;14:19.
6. British Thoracic Society Standards of Care C. Non-invasive ventilation in acute respiratory
failure. Thorax. 2002;57:192–211.
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transport. Eur Respir J. 1999;13:1477–86.
8. Rubin BK. Designing clinical trials to evaluate mucus clearance therapy. Respir Care.
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9. Flume PA. Airway clearance techniques. Semin Respir Crit Care Med. 2003;24:727–36.
10. Kang SW, Bach JR. Maximum insufflation capacity: vital capacity and cough flows in neuro-
muscular disease. Am J Phys Med Rehabil. 2000;79:222–7.
11. Bach JR. Mechanical insufflation-exsufflation. Comparison of peak expiratory flows with
manually assisted and unassisted coughing techniques. Chest. 1993;104:1553–62.
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adult, medical, spontaneously breathing patient. Thorax. 2009;64 Suppl 1:i1–51.
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tional chest physiotherapy for the treatment of atelectasis in the pediatric patient. Respir Care.
2002;47:1162–7.
14. Antonaglia V, Lucangelo U, Zin WA, et al. Intrapulmonary percussive ventilation improves the
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15. AARC Clinical Practice Guideline. Nasotracheal suctioning—2004 revision & update. Respir
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Noninvasive Ventilation
in Cardiovascular Rehabilitation 26
Vinicius Zacarias Maldaner da Silva, Gerson Cipriano Jr.,
and Graziela Franca Bernadelli Cipriano

Contents
26.1 Introduction .................................................................................................................. 224
26.2 Discussion and Analysis .............................................................................................. 224
26.2.1 Effect of NIV on Hemodynamic Parameters ................................................. 224
26.2.2 Effects of NIV on Functional Performance.................................................... 225
26.2.3 NIV for Dynamic Hyperinflation ................................................................... 225
26.2.4 Level of Evidence ........................................................................................... 226
Conclusion .............................................................................................................................. 227
References ............................................................................................................................... 227

Abbreviations

BPAP Bi-level positive airway pressure

COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
DH Dynamic hyperinflation
EPAP End positive airway pressure
HF Heart failure
LV Left ventricular

V.Z.M. da Silva, PT, PhD (*)

Hospital de Base do Distrito Federal, Brasilia, Brazil
Division of Physical Therapy, University of Brasilia, SQS 215 Bloco A apto 305 ASA SUL,
70294–010, Brasília, DF, Brazil
e-mail: [email protected]
G. Cipriano Jr., PT, PhD • G.F.B. Cipriano
Division of Physical Therapy, University of Brasilia, SQS 215 Bloco A apto 305 ASA SUL,
70294–010, Brasília, DF, Brazil

© Springer International Publishing Switzerland 2016 223

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_26
224 V.Z.M. da Silva et al.

NIV Noninvasive ventilation

PT Peak torque
Pw Peak work
TW Total work

26.1 Introduction

Patients with heart failure (HF) are often prematurely functionally limited as a result
of excessive fatigue, dyspnea, or a combination of both, independent of etiology.
Pathophysiological abnormalities specific to HF, such as metabolic derangements in
skeletal muscle, peripheral blood flow reduction, and excessive ventilator require-
ments (leading to inspiratory muscle fatigue and increased muscle metaboreflex)
have been documented [1–4] and are related to exercise intolerance and respiratory
muscle weakness. These abnormalities may limit these patients in performing at
moderate-to-high intensity or for an adequate time during an exercise training reha-
bilitation protocol, which can reduce the beneficial physiological effects [5]. The
use of noninvasive ventilation (NIV) support during rehabilitation sessions has been
proposed as an alternative to improve exercise tolerance and cardiopulmonary per-
formance. This chapter discusses the major concepts regarding use of NIV during
cardiopulmonary rehabilitation and its level of evidence.

26.2 Discussion and Analysis

26.2.1 Effect of NIV on Hemodynamic Parameters

Positive airway pressure appears to enhance cardiac function in patients with HF

[6]. During a regular cardiac rehabilitation program, acute cardiovascular adjust-
ments are required to maintain an adequate blood flow supply to activated muscles.
During resistance exercise training, ventilatory effort rises and greater inspiratory
pleural pressure is required to maintain ventilation in pace with metabolic demands.
Therefore, an increase in negative pleural pressure would increase both the left ven-
tricular (LV) transmural pressure gradient and LV afterload [4]. Previous studies
have demonstrated that positive airway pressure decreases the large variations in
pleural pressure during the effort and, consequently, reduces LV afterload, thereby
improving contractile performance of the heart during exercise [7, 8].
Another mechanism that may be involved with changes in hemodynamic behav-
ior during NIV is the decrease in LV preload. During a regular ventilation cycle,
within two pressure levels, the increase in intrathoracic pressure elevates right
atrial pressure, which results in decreased venous return, followed by a reduction
in LV filling. This results in enhanced LV performance in patients with HF [9].
Therefore, it is suggested that improvements in cardiac function with the applica-
tion of positive airway pressure is the result of augmented LV filling and decreased
LV afterload [10].
26 Noninvasive Ventilation in Cardiovascular Rehabilitation 225

During a submaximal evaluation (6-min walk test), Chermont et al. [11] and Lima
Eda et al. [12] did not report significant modifications in systolic blood pressure and
heart rate in patients with HF when continuous positive airway pressure (CPAP) was
applied before the exercise. However, in agreement with our study [13], which dem-
onstrated a cardiorespiratory improvement during a resistance protocol when bi-level
positive airway pressure (BPAP) was applied during the exercise, O’Donnell et al.
[14] has also demonstrated that BPAP improves cardiorespiratory responses during a
maximum cardiopulmonary test in the same population. These differences in
responses between CPAP and BPAP may reflect additional beneficial effects of
BPAP and the application during exercise, which can produce a lower pulmonary
capillary wedge pressure and expiratory flow limitation during exercise.

26.2.2 Effects of NIV on Functional Performance

Silva et al. [13] demonstrated that NIV reduces quadriceps fatigability (lower Δ
peak torque (PT), Δ total work (TW), and Δ peak work (Pw), p < 0.05) during an
isokinetic resistance exercise protocol. Bhorgi-Silva et al. [15] previously demon-
strated similar results in fatigability reduction in patients with chronic obstructive
pulmonary disease (COPD) utilizing the same ventilatory strategy.
This improvement could be explained by the increase in perfusion to working
skeletal muscle during ventilatory unloading. Previous studies have shown augmen-
tation of total respiratory work increases noradrenaline levels and reduces leg blood
flow during exercise [16]. Moreover, other studies have demonstrated an increase in
blood flow to active skeletal muscle during diaphragm muscle unloading [17]. As an
example, Harms et al. [18] previously demonstrated ventilatory muscle unloading
with a different NIV approach (proportional assisted ventilation that increased leg
blood flow).
In addition, increased metabolic stimulation of small afferent fibers (types III
and IV) from the respiratory musculature, especially from the diaphragm [19], may
contribute to physical activity limitations in this patient population. Activation of
this mechanism during exercise seems to induce inspiratory muscle fatigue and may
also contribute to the reduction in blood flow to the active skeletal muscle [20].
Therefore, the application of NIV during exercise could possibly attenuate the
inspiratory metaboreflex impact on physical performance, but this hypothesis
requires further investigation.

26.2.3 NIV for Dynamic Hyperinflation

The dynamic hyperinflation (DH) observed in patients with COPD leads to dyspnea
and limits the capacity to perform exercise training. The use of NIV to decrease DH
during exercise has been documented [21]. The mechanism thought to promote this
attenuation in exercise DH is the reduction of expiratory dynamic airway compres-
sion. Application of expiratory positive airway pressure (EPAP) may increase
226 V.Z.M. da Silva et al.

bronchial pressure and consequently transmural pressure, leading to a diminution of

airway collapse [22]. Additionally, EPAP should reduce the inspiratory threshold
load on the inspiratory muscles of patients with COPD with hyperinflation and
enhance neuromuscular coupling [22]

26.2.4 Level of Evidence

Two recent meta-analyses demonstrated that NIV increases functional capacity

(evaluated by a 6-min walk test, Figs. 26.1 and 26.2) and quality of life in patients
with HF and also those with COPD [23, 24]. However, the methodological quality
and sample size is low and new studies should be encouraged to investigate

NIV Control Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI IV, Fixed, 95% CI
1.3.1 Percentage change peak work rate
Hawkins 2002 32.9 17.4 10 14.5 10.1 9 64.8% 18.40 [5.76, 31.04]
Johnson 2002 50 35.4 11 38 35 11 12.0% 12.00 [-17.42, 41.42]
Reuxeny 2005 24.5 20.7 9 8.8 26.2 10 23.2% 15.70 [-5.43, 36.83]
Subtotal (95% CI) 30 30 100.0% 17.01 [6.83, 27.19]
2 2
Heterogeneity: Chi = 0.17, df = 2 (P = 0.92); I = 0%
Test for overall effect: Z = 3.27 (P = 0.001)

1.3.2 Percentage change constant work rate endurance time

Hawkins 2002 123 97.2 10 74 50.1 9 64.2% 49.00 [-19.56, 117.56]
xan’t Hul 2006 164 124 15 88 128 14 35.8% 76.00 [-15.83, 167.83]
Subtotal (95% CI) 25 23 100.0% 58.66 [3.72, 113.60]
Heterogeneity: Chi2 = 0.21, df = 1 (P = 0.64); I2 = 0%
Test for overall effect: Z = 2.09 (P = 0.04)

- 200 - 100 0 100 200

Higher with control Higher with NIV

Fig. 26.1 Forest plot comparing exercise capacity in protocols with NIV during exercise training
versus exercise training in patients with COPD (Withdraw from Ricci et al. [23])

CPAP Control/Sham
Study or Mean SD Total Mean SD Total Weig Mean difference IV, Mean difference
subgroup Fixed, 95% CI IV, Fixed, 95% CI

Chermont et
507 33 12 446 36 12 91.9% 61.00 [33.37, 88.63]
al.4 2009

Lima et al.5
534 89.9 6 420 73.8 6 8.1% 114.00 [20.93, 207.07]
2011

Total (95% CI) 18 18 100% 65.29 [38.80, 91.78]

2
Heterogeneity: Chi2 = 1.14, df = 1 (P = 0.28): I = 13%;
Test for overall effect: Z = 4.83 (P < 0.00001)
−220 −110 0 110 220
Favors Control/Sham Favors CPAP

Fig. 26.2 Forest plot comparing 6-min walk test in two different protocols: CPAP × control/sham
group in patients with HF (Withdraw from: Bundchen et al. [24])
26 Noninvasive Ventilation in Cardiovascular Rehabilitation 227

physiological effects, best parameters, and NIV modalities to allow successful use
of NIV during exercise.

Conclusion
NIV has emerged as a complementary therapy during cardiovascular rehabilita-
tion programs to improve exercise tolerance and possibly optimize skeletal mus-
cle and cardiopulmonary benefits during cardiovascular rehabilitation.

Key Major Recommendations

• Despite the growing body of the literature about NIV during cardiac reha-
bilitation protocols, the actual available evidence supports this application
to improve exercise tolerance and walking distance.
• Clinicians must have expertise in the implementation NIV during exercise
to choose the best NIV modality, pressure level, and application to achieve
better responses in patients with HF and also those with COPD.

The authors have no conflicts of interest to disclose.

References
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related to the aetiology of heart disease. Heart. 1997;78:569–71.
2. Harrington D, Coats AJ. Skeletal muscle abnormalities and evidence for their role in symptom
generation in chronic heart failure. Eur Heart J. 1997;18:1865–72.
3. Harrington D, Clark AL, Chua TP, Anker SD, Poole-Wilson PA, Coats AJ. Effect of reduced
muscle bulk on the ventilatory response to exercise in chronic congestive heart failure second-
ary to idiopathic dilated and ischemic cardiomyopathy. Am J Cardiol. 1997;80:90–3.
4. Yan AT, Bradley TD, Liu PP. The role of continuous positive airway pressure in the treatment
of congestive heart failure. Chest. 2001;120:1675–85.
5. Guazzi M, Adams V, Conraads V, Halle M, Mezzani A, Vanhees L, Arena R, Fletcher GF,
Forman DE, Kitzman DW, Lavie CJ, Myers J, EACPR, AHA. EACPR/AHA Joint Scientific
Statement. Clinical recommendations for cardiopulmonary exercise testing data assessment in
specific patient populations. Eur Heart J. 2012;33:2917–27.
6. Naughton MT, Rahman MA, Hara K, Floras JS, Bradley TD. Effect of continuous positive
airway pressure on intrathoracic and left ventricular transmural pressures in patients with con-
gestive heart failure. Circulation. 1995;91:1725–31.
7. Lalande S, Luoma CE, Miller AD, Johnson BD. Effect of changes in intrathoracic pressure on
cardiac function at rest and during moderate exercise in health and heart failure. Exp Physiol.
2012;97:248–56.
8. Lalande S, Johnson BD. Breathing strategy to preserve exercising cardiac function in patients
with heart failure. Med Hypotheses. 2010;74:416–21.
9. Grace MP, Greenbaum DM. Cardiac performance in response to PEEP in patients with cardiac
dysfunction. Crit Care Med. 1982;10:358–60.
10. Pinsky MR, Matuschak GM, Klain M. Determinants of cardiac augmentation by elevations in
intrathoracic pressure. J Appl Physiol. 1985;58:1189–98.
11. Chermont S, Quintao MM, Mesquita ET, Rocha NN, Nobrega AC. Noninvasive ventilation
with continuous positive airway pressure acutely improves 6-minute walk distance in chronic
heart failure. J Cardiopulm Rehabil Prev. 2009;29:44–8.
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12. Lima Eda S, Cruz CG, Santos FC, Gomes-Neto M, Bittencourt HS, Reis FJ, Aras R, Guimaraes
AC, Rodrigues-Junior ES. Effect of ventilatory support on functional capacity in patients with
heart failure: a pilot study. Arq Bras Cardiol. 2011;96:227–32.
13. da Silva VZ, Lima A, Cipriano GB, da Silva ML, Campos FV, Arena R, Martins WR, Chiappa
G, Bottaro M, Cipriano G. Noninvasive ventilation improves the cardiovascular response and
fatigability during resistance exercise in patients with heart failure. J Cardiopulm Rehabil Prev.
2013;33:378–84.
14. O’Donnell DE, D’Arsigny C, Raj S, Abdollah H, Webb KA. Ventilatory assistance improves
exercise endurance in stable congestive heart failure. Am J Respir Crit Care Med.
1999;160:1804–11.
15. Borghi-Silva A, Di Thommazo L, Pantoni CB, Mendes RG, Salvini Tde F, Costa D. Non-
invasive ventilation improves peripheral oxygen saturation and reduces fatigability of quadri-
ceps in patients with COPD. Respirology. 2009;14:537–44.
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exercise limitation in heart failure: pathophysiological mechanisms. Rev Bras Fisioter.
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Dempsey JA. Effects of respiratory muscle work on cardiac output and its distribution during
maximal exercise. J Appl Physiol. 1998;85:609–18.
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JA. Respiratory muscle work compromises leg blood flow during maximal exercise. J Appl
Physiol. 1997;82:1573–83.
19. Hill JM. Discharge of group IV phrenic afferent fibers increases during diaphragmatic fatigue.
Brain Res. 2000;856:240–4.
20. Callegaro CC, Ribeiro JP, Tan CO, Taylor JA. Attenuated inspiratory muscle metaboreflex in
endurance-trained individuals. Respir Physiol Neurobiol. 2011;177:24–9.
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2005;9:581–7.
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ventilation on dynamic hyperinflation of patients with COPD during activities of daily living
with upper limbs. Rev Bras Fisioter. 2012;16:61–7.
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Noninvasive Ventilation: Factors
Influencing Carbon Dioxide 27
Rebreathing – Key Practical Implications

Jacek Nasiłowski

Contents
27.1 Introduction .................................................................................................................. 230
27.2 Mask Ventilation .......................................................................................................... 231
27.2.1 Dual-Limb Circuit .......................................................................................... 231
27.2.2 Single-Limb Circuit with Exhalation Valve ................................................... 231
27.2.3 Single-Limb Circuit with Exhalation Port (Leak Port) .................................. 231
27.3 Helmet Ventilation ....................................................................................................... 233
References ............................................................................................................................... 234

Abbreviations

CO2 Carbon dioxide

EPAP Expiratory positive airway pressure
FiCO2 Fraction of inspiratory CO2
ICU Intensive care unit
NIV Noninvasive ventilation
Vte Exhaled tidal volume
Vti Inspiratory tidal volume

J. Nasiłowski, MD, PhD

Department of Internal Medicine, Pneumology and Allergology,
Medical University of Warsaw, ul. Banacha 1a, Warsaw 02-097, Poland
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 229

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_27
230 J. Nasiłowski

27.1 Introduction

Noninvasive ventilation (NIV) may increase the risk of carbon dioxide (CO2)
rebreathing for two reasons: firstly, the single-limb circuit that is preferentially used
for NIV causes patients to exhale into the same space from which they inhale, and,
secondly, the interfaces used for NIV increase dead space.
As the main indication for NIV is hypoventilation resulting in hypercapnia
[1], whether the side effects of ventilation will overcome the aim of the therapy
seems to be a crucial issue. This question is particularly important in the treat-
ment of the acute episodes of chronic disease, when hypercapnia is usually much
greater and can cause life-threatening respiratory acidosis. Moreover, in the
acute setting, interfaces covering the nose and mouth with a larger volume of
dead space (oronasal masks, total face masks, and helmets) are the interfaces of
choice [2].
There are a few issues concerning CO2 rebreathing. Firstly, it is not clear
whether CO2 rebreathing is only a theoretical problem or if it has an important
clinical significance, translating into failure of NIV. There is no conclusive proof,
for example, reported cases, that CO2 rebreathing during NIV caused a need of
intubation. However, as a potential drawback of NIV, it must be always a concern
of the physician. Secondly, the assessment of fraction of inspiratory CO2 (FiCO2)
is not technically an easy procedure and physicians are not able to measure it dur-
ing everyday practice. Thirdly, there are only a few studies that have evaluated
this issue, and most of them were carried out in lung models [3–6] or healthy
volunteers [4, 7], which cannot perfectly imitate in vivo conditions. The most
informative study on patients was that of Szkulmowski et al. [8]. They evaluated
FiCO2 in patients with respiratory failure hospitalized in an intensive care unit
(ICU). Seven subjects were ventilated noninvasively with oronasal mask and 11
invasively. All of them used a single-limb circuit with a leak port and pressure
support mode of ventilation (mean inspiratory positive airway pressure (IPAP)
23.9 ± 6.0 mmHg; mean expiratory positive airway pressure (EPAP)
7.3 ± 1.8 mmHg). The authors found that only 19 % of all inhaled breaths had
FiCO2 > 0.1 %. The mean FiCO2 of those breaths was 0.27 ± 0.33 %, whereas the
average FiCO2 of all breaths was 0.072 ± 0.17 %, which is close to the concentra-
tion of CO2 in the air (0.03 %). Four factors were significantly correlated with
higher FiCO2:

1. High level of end tidal CO2

2. Low EPAP
3. High respiratory rate
4. And, surprisingly, invasive versus noninvasive ventilation

NIV should provoke higher CO2 rebreathing due to larger dead space, caused by
an interface comparable to an endotracheal tube, which reduces dead space.
However, lower FiCO2 may be easily explained by the presence of unintentional
leaks during NIV. And it seems to be a self-correcting mechanism, which can protect
against CO2 rebreathing [9].
27 Noninvasive Ventilation 231

27.2 Mask Ventilation

Treatment with NIV can be performed by three different circuit systems: dual-limb
circuit, single-limb circuit with exhalation valve, and single-limb circuit with exha-
lation port (leak port).

27.2.1 Dual-Limb Circuit

A dual-limb circuit is a traditional ventilator system used broadly in ICUs with inva-
sive ventilation. It consists of one inhalation limb that introduces air into the patient’s
airways and one exhalation limb that leads exhaled gas outside of the airways. This
system prevents the mixing of exhaled gas with inhalation gas. The risk of rebreath-
ing of exhaled CO2 comes from the enlarged dead space created by an interface and
the part of the circuit situated distally from Y-piece valve. To prevent CO2 rebreath-
ing, one must take care to increase the exhaled tidal volume (Vte) by the amount of
the volume of additional dead space. Increasing only an inspiratory tidal volume
(Vti) may not effectively reduce the risk of reinhalation due to an unknown volume
of inhaled gases escaping with unintentional leaks, which to a larger or smaller extent
are always present between the mask and the skin of the patient’s face.

27.2.2 Single-Limb Circuit with Exhalation Valve

A single-limb circuit with an exhalation valve is rarely used in acute settings but is
quite popular in chronic ventilation. A unidirectional valve is located in the patient’s
end of a limb. The valve is closed on inspiration and opens on expiration, allowing
the exhaled gas to leave the respiratory circuit. A unidirectional valve system pre-
vents mixing of inhaled and exhaled gases and prevents CO2 rebreathing [10]. As in
a double-limb circuit, this circuit enlarges dead space by the volume of interface and
the distal part of the circuit situated between the valve and interface. The clinician
must be aware of the additional volume and increase Vte accordingly.

27.2.3 Single-Limb Circuit with Exhalation Port (Leak Port)

A single-limb circuit with an exhalation port is most frequently used at home and in
the hospital. The exhalation port located within an interface or in a distal part of a
tube is open throughout the entire respiratory cycle. In this scenario, inhaled and
exhaled gases mix easily during every breath in the inner space of the interface and
the risk of CO2 rebreathing has to be taken into consideration. The empting of the
exhaled gas from the interface space depends on

1. The expiratory flow

2. The distance between the exhalation port and nose and/or mouth (dynamic dead
space)
232 J. Nasiłowski

Table 27.1 Factors Domain Factor

increasing the risk of CO2
Ventilatory settings Low CPAP
rebreathing during mask
ventilation with a single-limb Low inspiratory:exspiratory ratio
circuit with exhalation port Short inspiratory time
High respiratory rate
Interface High inner volume
Exhalation port Large distance from nose and mouth
High resistance of the holes
Patient High PaCO2
Rapid pattern of breathing

3. The volume of the interface (static dead space)

4. The patient’s breathing pattern (the time of expiration)

In practice, unintentional leaks also play a role, but they cannot be taken into
consideration, although the aim is to reduce them as much as possible. To clear the
mask space of exhaled CO2, it is necessary to set the EPAP to provide an intentional
leak that exceeds patient expiratory flow. In the mid-1990s, Lofaso et al. [11] stud-
ied the flow-though Whisper Swivel connector, which is located between a mask
and the distal end of a circuit. They found that, at the level of EPAP 5 cmH2O, the
intentional leak was 200 ml/s, which means that during respiration with higher tidal
volume (e.g., 500 ml) or shorter expiratory time (e.g., 1 s), expiratory gas cannot be
fully washed out at this setting. EPAP had to be increased in such a respiratory pat-
tern scenario. The higher the EPAP level, the faster the venting of the interface
space and the lower the risk of CO2 rebreathing. Ferguson et al. [10] proved that
EPAP below 4–6 cmH2O markedly increased CO2 rebreathing. The EPAP level is
the factor that can most easily be corrected by a physician, and it should be adjusted
according to the static and dynamic dead space, breathing pattern, and actual level
of PaCO2.
The second relatively easily modifiable element of mask ventilation is the loca-
tion of the leak port. Saatci et al. [12] proved that an exhalation port over the nasal
bridge reduces dynamic (effective) dead space to a higher extent than ports posi-
tioned elsewhere within the mask. The dynamic dead space was the largest when the
port was situated between the mask and circuit. Moreover, the relationship between
static dead space (inner volume of the interface) and dynamic dead space is quite
poor. This means that even an interface with a larger volume, for example, a total
face mask, can have small dynamic dead space if the flow of gas through the mask
is effective. Table 27.1 lists the factors that increase the risk of CO2 rebreathing.
Up-to-date ventilators and interfaces strive to protect against rebreathing. The pres-
sure support ventilation setting and circuits with an exhalation port do not allow
reduction of EPAP below a certain level (2–4 cmH2O), and an alarm sounds if too
little leakage occurs. Masks have a leak port located close to the nose to reduce
effective dead space.
27 Noninvasive Ventilation 233

27.3 Helmet Ventilation

A helmet is an interface that has an extremely large internal volume, up to 10 l,

which constitutes a huge dead space, promoting CO2 rebreathing [4, 13]. In fact,
a helmet cannot be considered as an interface sensu stricto. It is rather a kind of
hermetic tent over the patient’s head, with the aim of creating a high-pressure
environment for the respiratory system. The pressure is maintained by the con-
stant flow of gas that enters by the inspiratory limb and exits by the exhalation
limb. The internal volume of a helmet is much larger than the patient’s tidal
volume. The patient takes a breath from the gas located under the helmet and
then exhales into this specific semi-closed atmosphere. However, the volume of
a helmet does not correspond to effective dead space. Fodil et al. [14], using a
mathematical model, estimated the effective dead space of a helmet by analyzing
the pressure field/flow pattern. They found that effective dead space consists of
only 4 % of helmet gas volume due to the streaming effect. Exhaled CO2 is
diluted in internal gas volume and inhaled gas may be only slightly enriched with
CO2. To correctly perform NIV with a helmet, sufficient gas flow has to be pro-
vided. The flow is aimed not only to maintain adequate expiratory and inspira-
tory pressures but also to constantly extract CO2 from the inner space. The
concentration of CO2 in the helmet gas is dependent on PaCO2 [6]. Thereupon,
the flow must be adjusted according to the level of patient’s hypercapnia and
generally should exceed 30 l/min.
Antonelli et al. [15] published one of the first studies comparing efficacy of
helmet NIV and NIV with mask in hypercapnic respiratory failure. In this
matched case control study, the efficacy of helmet NIV was worse in terms of
reducing PaCO2, which may confirm the important role of CO2 rebreathing in the
treatment effects. However, lesser efficacy of ventilation could partly be attrib-
uted to worse patient-ventilator synchronization in comparison with mask venti-
lation. In a randomized study published in 2015 by Pisani et al. [16], a new
model of helmet, specifically designed to improve performance in hypercapnic
patients, was tested in comparison with oronasal mask. The novel helmet (CaStar
R Next, StarMed, Mirandola, Italy) has less internal volume than standard ones.
Moreover, the authors used ventilator settings specifically focused on optimiza-
tion of patient-ventilator synchronization: fast rate of pressurization and a
cycling-off threshold between 25 and 50 % of maximal inspiratory flow. The
pressures were titrated to provide a flow inside the helmet >30 l/min. The mean
inspiratory and expiratory pressures were 19.6 ± 5.7 cmH2O and 7.7 ± 1.9 cmH2O,
respectively, which was ~30 % higher than in mask ventilation. The results
showed the same efficacy in improving hypercapnia and respiratory acidosis in
both groups.
Current evidence authorizes the use of helmet ventilation in hypercapnic respira-
tory failure. However, a physician must take into account the higher risk of CO2
rebreathing than with ventilation with a mask. Higher pressures, proportionally to
PaCO2 of the patient, are needed and close monitoring should be applied.
234 J. Nasiłowski

Key Recommendations
• CO2 rebreathing occurs during mask ventilation with a single-limb circuit
with exhalation port and during helmet ventilation.
• In spite of a lack of convincing evidence, CO2 rebreathing must be treated
as a potential risk factor of NIV failure.
• To avoid CO2 rebreathing, adequate EPAP (mask ventilation) and flow-by
(helmet ventilation) must be provided, adjusted to PaCO2, respiratory rate,
and effective dead space of the interface.

References
1. Muir J-F, Molano C, Cuvelier A. NIV and obstructive lung diseases. Eur Respir Mon. 2008;41:
203–23.
2. Crimi C, Noto A, Princi P, et al. A European survey of noninvasive ventilation practices. Eur
Respir J. 2010;36:362–9.
3. Loeppky JA, Icenogle MV, Caprihan A, et al. CO2 rebreathing model in COPD: blood-to-gas
equilibration. Eur J Appl Physiol. 2006;98:450–60.
4. Taccone P, Hess D, Caironi P, et al. Continuous positive airway pressure delivered with a
“helmet”: effects on carbon dioxide rebreathing. Crit Care Med. 2004;32:2090–6.
5. Schettino GP, Chatmongkolchart S, Hess DR, et al. Position of exhalation port and mask
design affect CO2 rebreathing during noninvasive positive pressure ventilation. Crit Care Med.
2003;31:2178–82.
6. Mojoli F, Iotti GA, Gerletti M, et al. Carbon dioxide rebreathing during non-invasive ventila-
tion delivered by helmet: a bench study. Intensive Care Med. 2008;34:1454–60.
7. Samolski D, Calaf N, Güell R, et al. Carbon dioxide rebreathing in non-invasive ventilation.
Analysis of masks, expiratory ports and ventilatory modes. Monaldi Arch Chest Dis. 2008;69:
114–8.
8. Szkulmowski Z, Belkhouja K, Le QH, et al. Bilevel positive airway pressure ventilation: fac-
tors influencing carbon dioxide rebreathing. Intensive Care Med. 2010;36:688–91.
9. Hill NS, Carlisle C, Kramer NR. Effect of a nonrebreathing exhalation valve on long-term
nasal ventilation using a bilevel device. Chest. 2002;122:84–91.
10. Ferguson GT, Gilmartin M. CO2 rebreathing during BiPAP ventilatory assistance. Am J Respir
Crit Care Med. 1995;151:1126–35.
11. Lofaso F, Brochard L, Hang T, et al. Home versus intensive care pressure support devices.
Experimental and clinical comparison. Am J Respir Crit Care Med. 1996;153:1591–9.
12. Saatci E, Miller DM, Stell IM, et al. Dynamic dead space in face masks used with noninvasive
ventilators: a lung model study. Eur Respir J. 2004;23:129–35.
13. Esquinas AM, Papadakos PJ, Carron M, et al. Clinical review: helmet and non-invasive
mechanical ventilation in critically ill patients. Crit Care. 2013;17:223.
14. Fodil R, Lellouche F, Mancebo J, et al. Comparison of patient–ventilator interfaces based on
their computerized effective dead space. Intensive Care Med. 2011;37:257–62.
15. Antonelli M, Pennisi MA, Pelosi P, et al. Noninvasive positive pressure ventilation using a
helmet in patients with acute exacerbation of chronic obstructive pulmonary disease: a feasi-
bility study. Anesthesiology. 2004;100:16–24.
16. Pisani L, Mega C, Vaschetto R, et al. Oronasal mask versus helmet in acute hypercapnic respi-
ratory failure. Eur Respir J. 2015;45:691–9.
 Part III
Clinical Applications: Pre and Intra Hospital
Noninvasive Mechanical Ventilation
in Hypoxemic Respiratory Failure: 28
Determinants of Response and Patients’
Flow Chart Recommendations – Key
Topics and Clinical Implications

Roberto Cosentini and Tommaso Maraffi

Contents
28.1 Introduction .................................................................................................................. 238
28.2 Acute Cardiogenic Pulmonary Edema ......................................................................... 238
28.2.1 Bi-level NPPV Versus CPAP: Are Two Better than One? ............................. 238
28.2.2 Hypertensive Versus Nonhypertensive ACPE:
Blood Pressure Matters .................................................................................. 239
28.2.3 NIV for ACPE in Practice .............................................................................. 239
28.3 Acute Respiratory Distress Syndrome ......................................................................... 240
28.4 Pneumonia ................................................................................................................... 242
28.4.1 NPPV for Pneumonia in Practice ................................................................... 243
28.5 Blunt Chest Trauma and Atelectasis ............................................................................ 244
28.6 Acute Respiratory Failure After Drowning ................................................................. 244
References ............................................................................................................................... 247

Abbreviations

ACPE Acute cardiogenic pulmonary edema

DNI Do not intubate
ETI Endotracheal intubation
IBW Ideal body weight

R. Cosentini, MD (*)
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
Pronto Soccorso e Medicina d’Urgenza, Milan, Italy
Gruppo NIV_UOC Pronto Soccorso e Pronto Soccorso e Medicina d’Urgenza, Milan, Italy
e-mail: [email protected]
T. Maraffi, MD
Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti,
Universita’ degli Studi di Milano, Milan, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 237

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_28
238 R. Cosentini and T. Maraffi

NPPV Non-invasive positive pressure ventilation

NPPV Noninvasive positive pressure ventilation
PEEP Positive end-expiratory pressure
PS Pressure support
Vt Tidal volume

28.1 Introduction

Acute hypoxemic respiratory failure (AHRF) is one of the most common conditions
of severe dyspnea seen in the emergency department. This chapter summarizes the
main indications for noninvasive positive pressure ventilation (NPPV) in AHRF,
with a focus on evidence, clinical recommendations, and practical points.

28.2 Acute Cardiogenic Pulmonary Edema

The literature and rationale for noninvasive ventilation (NIV) use in acute cardio-
genic pulmonary edema (ACPE) are discussed in detail in Chap. 27 of this book; we
summarize it briefly here:

• NIV treatment in ACPE significantly reduces endotracheal intubation (ETI) and

mortality, as evidenced by several systematic reviews and a meta-analysis.
• The number needed to treat (NNT) for ETI is 8 and is 13 for mortality. Therefore,
there is a strong recommendation for NIV in ACPE, based on a high level of
evidence.
• ACPE is also effectively treated with NIV in the prehospital setting.

When treating a patient with ACPE in the emergency department, two main clin-
ical questions must be answered:

1. Should the patient with hypercapnia be treated with bi-level NPPV rather than
CPAP?
2. Does the patient with hypertensive ACPE have a different prognosis compared
with a patient who is nonhypertensive?

28.2.1 Bi-level NPPV Versus CPAP: Are Two Better than One?

As many as 50 % of patients treated with NIV for ACPE present with acute respira-
tory failure. This is due to muscle fatigue induced by a remarkable decrease of
compliance resulting from sudden alveolar flooding. The theoretical advantage for
muscle workload of the addition of pressure support (PS) to positive end-expiratory
pressure (PEEP) versus continuous positive airway pressure (CPAP) is not demon-
strated in the literature. Several randomized studies and a meta-analysis showed
28 Noninvasive Mechanical Ventilation in Hypoxemic Respiratory Failure 239

faster relief of respiratory acidosis; however, neither ETI nor mortality differed sig-
nificantly between the two modalities. The Cochrane Review on NPPV efficacy in
ACPE concludes, “CPAP may be considered the first option in selection of NPPV
due to more robust evidence for its effectiveness and safety and lower cost com-
pared with bilevel NPPV” [1]. This may be explained by the rapid favorable effects
of PEEP application on both respiration (alveolar recruitment + compliance increase)
and circulation (venous return decrease + left ventricle transmural pressure
decrease). In summary, in patients with ACPE who have acute respiratory acidosis,
NIV and CPAP are equivalent; hence, our advice is to use the treatment that you
prefer and are most familiar with.

28.2.2 Hypertensive Versus Nonhypertensive ACPE:

Blood Pressure Matters

As many as 50 % of patients treated with NIV for ACPE present with hypertensive
crisis, that is, arterial blood pressure ≥140/90 mmHg. Cardiogenic shock associated
with ACPE has a much greater mortality. The question is whether nonhypertensive
ACPE patients have a worse prognosis than those with hypertensive ACPE. Several
studies observed that mortality significantly increases in patients presenting to the
emergency department with blood pressure <140/90 mmHg when treated either
with NIV or standard therapy. This means that, especially in these patients, the
search for a possibly reversible cause of ACPE is mandatory [2]. The comprehen-
sive approach to patients with ACPE should include the assessment of lung involve-
ment, volemia, and heart dysfunction to identify reversible causes such arrhythmias,
myocardial ischemia, or valvular dysfunction with bedside ultrasound.

Summary
1. NIV is effective in the treatment of ACPE (Evidence A; NNT = 8 for ETI,
NNT = 13 for mortality).
2. NIV can be started effectively in the prehospital setting.
3. Patients with acute respiratory acidosis can be treated with either CPAP or NPPV,
provided that the patient does not have any preexisting respiratory muscle
overload.
4. Reversible causes (e.g., ischemia, arrhythmias, valvular disease) should be
identified.
5. Patients without hypertensive response have a worse prognosis.

28.2.3 NIV for ACPE in Practice

• An initial PEEP level of 10 cmH2O is probably the best choice.

• If CPAP is used, high-flow stand-alone devices are preferred.
• If bi-level NPPV is used, apply a PS of 10–15 cmH2O on top of PEEP 8–10
cmH2O, closely monitoring patient-ventilator interaction, respiratory rate (RR),
and tidal volume (Vt).
240 R. Cosentini and T. Maraffi

• Titrate FiO2 to a SpO2 >94 %.

• Titrate PS level to obtain a Vt ≤6 ml/kg ideal body weight (IBW) and a RR
<25 bpm.
• Increase PEEP up to 12–15 cmH2O if necessary.
• Set the minimal inspiratory trigger to avoid auto-triggering.
• Set a short rise time according to RR.
• Set a late expiratory trigger (e.g., 20–40 %).
• After 30 min of NIV, reassess arterial blood gases to evaluate both oxygenation
and ventilation.

During NIV, serial monitoring of clinical and laboratory values is mandatory:

• Search for any reversible cause (e.g., ischemia, arrhythmias, valvular

disease).
• Chose a mask or helmet according to patient preference.
– Assess patient comfort and leaks.
– Assess patient-ventilator interaction and synchrony (ineffective efforts, dou-
ble triggering, auto-triggering).
– Measure RR and adjust ventilator settings, aiming for a RR ≤25 bpm.
– Monitor Vt, aiming for ≤6 ml/kg IBW.
– Repeat arterial blood gas tests for oxygenation and CO2 monitoring.

28.3 Acute Respiratory Distress Syndrome

Evidence for the use of NPPV in acute respiratory distress syndrome (ARDS) is
scant and heterogeneous, however sound knowledge of the pathophysiology of
ARDS and ventilator-induced lung injury (VILI) may guide clinicians in deciding
whether to apply NIV. The literature and the rationale for NIV use in ARDS are
discussed in detail in Chap. 50 of this book, but we summarize it briefly below:

1. In the case of NIV in AHRF, patients with ARDS have worse outcomes [7, 8].
2. NIV in ARDS is accompanied by a high failure rate (up to 70 % [6]), and NIV
failure is associated with increased mortality [10].
3. Patients with successful NIV have a low mortality rate (around 20 %) [10], but
this may be due to selection of less severe patients.

The main clinical goals for the use of NIV in ARDS should be the following:

• Reversal of hypoxemia
• Prevention of muscle fatigue and severe hypercapnia
• Attenuation of dyspnea and respiratory distress
• Prevention of VILI
28 Noninvasive Mechanical Ventilation in Hypoxemic Respiratory Failure 241

Table 28.1 Berlin definition of ARDS from Ferguson et al. [10]

Acute respiratory distress syndrome
Timing Within 1 week of a known clinical insult or new/worsening respiratory
symptoms
Chest imaginga Bilateral opacities—not fully explained by effusions, lobar/lung collapse,
or nodules
Origin of edema Respiratory failure not fully explained by cardiac failure or fluid
overload; need objective assessment (e.g., echocardiography) to exclude
hydrostatic edema if no risk factor present
Mild Moderate Severe
Oxygenationb 200< PaO2/FiO2 ≤300 100< PaO2/FiO2 ≤200 PaO2/FiO2 ≤100 with
with PEEP or CPAP with PEEP ≥5 PEEP ≥5 cmH2O
≥5 cmH2Oc cmH2O
ARDS acute respiratory distress syndrome, PaO2 partial pressure of arterial oxygen, FiO2 fraction
of inspired oxygen, PEEP positive end-expiratory pressure, CPAP continuous positive airway
pressure, N/A not applicable
a
Chest X-ray or CT scan
b
If altitude is higher than 1000 m, a correction factor should be applied as follows: PaO2/
FiO2 × (barometric pressure/760)
c
This may be delivered noninvasively in the mild ARDS group

According to the Berlin definition of ARDS [9], patients can be stratified into
three different categories based on their initial PaO2/FiO2 ratio while on at least 5
cmH2O of PEEP (see Table 28.1). Given the above considerations, we recommend
considering NIV only in patients not requiring immediate intubation (approximately
15 % of ARDS patients) [10] and those without significant hemodynamic impair-
ment or severe metabolic acidosis [6].
In patients considered for a NPPV trial:

• Ensure the appropriate environment for NPPV delivery (intensive care unit or
high dependency unit) and appropriate ventilator availability (no home
ventilators).
• Use an oronasal mask as interface to minimize leaks.
• NIV is preferred over CPAP use, especially in patients with marked distress
and hypercapnia. ARDS is generally accompanied by an increased respiratory
drive and places great stress on the respiratory muscles. Attenuation of inspira-
tory effort with PS is advisable. Another important advantage of NIV over
CPAP is the ability to closely monitor Vt, which must be maintained below
6 ml/kg IBW.
• Start with a low PEEP level: 5 cmH2O is probably the best choice, as it allows for
subsequent reassessment of the degree of hypoxemia and appears to improve
patient stratification [11].
• Apply a PS of 10–15 cmH2O, closely monitoring patient-ventilator interaction,
RR, and Vt.
• Titrate FiO2 to a SpO2 >94 %.
242 R. Cosentini and T. Maraffi

• After 30 min of NIV, reassess arterial blood gases.

– If PaO2/FiO2 ratio is <200, the patient has moderate to severe ARDS. Invasive
mechanical ventilation is indicated [11].
– If PaO2/FiO2 ratio is >200, the patient has mild ARDS and may be treated with
NIV in this phase.
– If hypercapnia with respiratory acidosis has developed or worsened (i.e., pH
<7.3 with PaCO2 >50 mmHg), consider invasive mechanical ventilation.

Once it has been established that a patient has mild ARDS on NIV with 5 cmH2O
of PEEP and does not have significant or worsening respiratory acidosis:

1. Titrate PS level to obtain a Vt ≤6 ml/kg IBW and a RR <25.

2. Titrate FiO2 to maintain a SpO2 ≥94 %.
3. Increase PEEP up to 10 cmH2O if necessary.

During NIV, serial monitoring of clinical and laboratory values is mandatory:

• Assess patient comfort and leaks.

• Assess patient-ventilator interaction and synchrony (ineffective efforts, double
triggering, auto-triggering).
• Measure respiratory rate and adjust ventilator settings, aiming for a RR ≤25 bpm.
• Monitor Vt, aiming for ≤6 ml/kg IBW.
• Repeat arterial blood gases for oxygenation and CO2 monitoring.

Maintain a low threshold for ETI and invasive mechanical ventilation in ARDS
patients. Delaying a necessary intubation may harm patients and increase mortality [10].

28.4 Pneumonia

The scant literature on randomized and observational studies in the immunocompetent

population does not allow for a strong recommendation for NIV for the treatment of
acute respiratory failure in the course of pneumonia. The explanation for the difference
of success in comparison with ACPE is twofold: (1) the effects of medical treatment on
pneumonia takes much longer; and (2) the favorable effect of PEEP on oxygenation
depends on the pattern of lung involvement (greater recruitment in interstitial than in
consolidation), and its cardiovascular effects may be remarkably deleterious.
The results of randomized and observational trials in the immunocompromised
population are more encouraging, because ETI – the alternative to NIV for severe
acute respiratory failure – is frequently complicated by severe infections and a high
mortality. Hence, NIV use in the immunocompromised population may decrease
intubation rate and improve outcome.
According to the literature, the following suggestions can be made on the proba-
bility of NIV success in pneumonia in the immunocompetent population. The out-
come is significantly better in patients with preexisting chronic cardiocirculatory or
28 Noninvasive Mechanical Ventilation in Hypoxemic Respiratory Failure 243

obstructive lung disease than in those with de novo acute respiratory failure [3].
Finally, early treatment of severe hypoxemic pneumonia with helmet CPAP may
effectively reduce the risk of meeting ETI criteria compared with oxygen therapy [4].

Summary
1. NIV is effective in the immunocompromised population.
2. NIV is more effective in acute-on-chronic versus de novo respiratory failure.
3. In immunocompetent patients without a do not intubate (DNI) order, a cautious
early NIV trial may be attempted (the interface is a key factor).
4. In immunocompetent patients with a DNI order, NIV is a possible ceiling treat-
ment (the interface is a key factor).

28.4.1 NPPV for Pneumonia in Practice

• An initial PEEP level of 5–8 cmH2O is probably the best choice.

• If your choice is CPAP, high-flow stand-alone devices are preferred.
• The interface is crucial; helmet CPAP may be better tolerated because treatment
is generally longer than two days.
• If your choice is bi-level NPPV, apply a PS of 10–15 cmH2O on top of PEEP 5–8
cmH2O, closely monitoring patient-ventilator interaction, RR, and Vt.
• Titrate FiO2 and PEEP to a SpO2 >94 %.
• Test the best PEEP, according to PaO2/FiO2 ratio, pCO2, and vital signs responses.
• Titrate PS level to obtain a Vt ≤6 ml/kg IBW and a RR <25 bpm.
• Increase PEEP up to 10–12 cmH2O if necessary, according to PEEP test.
• Set the minimal inspiratory trigger to avoid auto-triggering.
• Set a short rise time according to respiratory rate.
• Set a late expiratory trigger (e.g., 20–40 %).
• After 30 min of NIV, reassess arterial blood gases to evaluate both oxygenation
and ventilation.

During NIV, serial monitoring of clinical and laboratory values is mandatory:

• Treat and monitor clinical response to sepsis (antibiotics, fluids, lactate clear-
ance, etc.).
• Chose the interface according to patient preference; a long NIV course is
expected, therefore, a helmet might be preferable.
– Assess patient comfort and leaks.
– Assess patient-ventilator interaction and synchrony (ineffective efforts, dou-
ble triggering, auto-triggering).
– Measure RR and adjust ventilator settings, aiming for a RR ≤25 bpm.
– Monitor Vt, aiming for ≤6 ml/kg IBW.
– Repeat arterial blood gases for oxygenation and CO2 monitoring

Maintain a low threshold for ETI and invasive mechanical ventilation.

244 R. Cosentini and T. Maraffi

28.5 Blunt Chest Trauma and Atelectasis

NIV in atelectasis is reviewed in detail elsewhere in this book. Trauma patients

frequently develop acute respiratory failure resulting from ventilation perfusion
mismatching and shunt because of lung contusion, atelectasis, inability to clear
secretions, or pneumothorax and/or hemothorax. The rationale for NIV is alveolar
recruitment and chest stabilization to prevent ETI and its complications that may
lead to adverse outcomes. Randomized trial excluded patients with either severe
hypoxemia (PaO2/FiO2 <200), respiratory acidosis, or multiorgan dysfunction
because they are usually unable to cooperate or protect the airway or clear secre-
tions [5]. Time is a key factor, inasmuch as early treatment is associated with better
outcome; further, a lack of response at 1–4 h should promptly lead to intubation and
invasive mechanical ventilation. Patient selection seems to be the most important
prognostic factor for improved outcome of NPPV treatment of acute respiratory
failure due to blunt chest trauma.

Summary
• NIV may decrease both ETI and mortality provided that:
Patients are treated during early acute respiratory failure
• NIV is used only in hypoxemic non-hypercapnic patients
• NIV is used only in patients without other organ failures
• Other medical and surgical treatments are added to NIV

28.6 Acute Respiratory Failure After Drowning

Acute respiratory failure after drowning is a common event, but its severity spans
from rapidly reversible mild hypoxemia to full-blown ARDS. For an in-depth
review of the pathophysiology of drowning and the applications of NIV, see
Chap. 50 in this book.
Drowning involves aspiration of water into the airways, which directly damages
alveolar surface, washes surfactant, and increases lung weight determining atelecta-
sis. Additionally, reflex bronchospasm contributes to hypoxia and respiratory dis-
tress while increased permeability in the lung induces pulmonary edema (Szpilman
D Drowning NEJM 2012). Interestingly, drowning appears to be associated with
rapidly reversible respiratory failure [14], thus often requiring short-term ventila-
tory support. After rescue from water, patients may present with cardiac arrest, gen-
erally associated with pulseless electrical activity. Cardiac arrest in this situation is
generally hypoxic in nature (especially in the young population) and thus mandates
rapid administration of oxygen and ventilatory assistance as well as reversal of
hypothermia.
In hemodynamically stable patients, respiratory symptoms may vary from
cough and rales (presentation associated with low mortality rates) to severe
hypoxemia, cough, and foamy secretions (mortality around 20 % [13]).
28 Noninvasive Mechanical Ventilation in Hypoxemic Respiratory Failure 245

Administration of oxygen and SpO2 monitoring for at least 8 h are advisable in

all patients, but those presenting SpO2 <94 % and signs of respiratory distress
may deserve treatment with NIV before considering ETI [15]. NIV may be
applied in the prehospital period if indications for emergency ETI are not met.
The main concerns with NIV use in drowned patients are the inability to fully
protect the airway and sudden vomiting and aspiration. Given the pathophysiology
of drowning, it seems logical to start with noninvasive CPAP, which is usually
more widely available and easier to manage. Helmet or full face mask may be used
according to availability and staff experience. We recommend starting CPAP with
a continuous high-flow delivery system (Venturi system) to avoid CO2 rebreathing
and maximize oxygen delivery to the patient, starting with a PEEP of 10 cmH2O
and titrating FiO2 to achieve a SpO2 >94 %. Alternatively, NIV can be started with
a PEEP of 10 cmH2O and a PS level titrated to the patient’s need, aiming for a Vt
of 6–8 ml/kg IBW (usually around 10 cmH2O). NIV may be better than CPAP in
patients presenting with hypoxic-hypercapnic respiratory failure, provided no
alterations in neurologic status exist. Foamy secretions certainly represent a chal-
lenge, but clinicians must remember that they are the result of increased permeabil-
ity in the lung and may thus be controlled or reduced with positive airway
pressure.
After NIV or CPAP initiation, neurologic status, RR, blood pressure, and
SpO2 should be closely monitored during the first 1–2 h. Arterial blood gas tests
should then be performed. If oxygenation is improving after 60–120 min of
CPAP or NIV and no hypercapnia has developed, patients may continue treat-
ment. However, if oxygenation fails to improve or signs of respiratory muscle
fatigue are present (including respiratory acidosis), ETI must be performed and
invasive mechanical ventilation started. Prognostic factors associated with favor-
able outcome after drowning are short submersion time and symptom severity
after rescue, with worse prognosis in case of cardiac arrest (up to 90 %
mortality).

Key Major Recommendations (Fig. 28.1)

• Patients with ACPE should be treated with either CPAP or NIV (strong
recommendation).
• In patients with ARDS, NIV is preferred over CPAP. If a cautious trial fails
within 1 h, prompt intubation is required.
• In immunocompromised patients with pneumonia, early treatment with
NIV may avoid the need for intubation.
• In immunocompetent patients with pneumonia, early treatment is recom-
mended with NIV. The interface is crucial (a helmet is better tolerated).
Test a short trial. Pay attention to sepsis.
• In patients with blunt chest trauma: start early, only in hypoxaemic patients
and those without other organ failures.
246 R. Cosentini and T. Maraffi

AHRF

DEFINE
ETIOLOGY

ACPE ARDS PNEUMONIA TRAUNMA

DROWNING
ATELECTASIS

HYPOXIC HYPOXIC
± ±
HYPERCAPNIC HYPERCAPNIC

!
HYPERCAPNIA = NO HYPERCAPNIA = YES

PaO2 /FiO2
≥200 ONLY CPAP NPPV
(mild ARDS)

CPAP
consider
NIPPV
!
SEPSIS

NO ↑ P/F 1h
LOW THRESHOLD
Assess BP: ↑GCS
FOR INTUBATION
≥140/90: If:
continue treatment 1. Tv > 6ml/kg
2. RR > 30
<140/90:
consider IPPV 3. Distress
4. PaO2 /FiO2 ↓ consider
<90/60: IPPV 5. Kelly ↑ IPPV

Fig. 28.1 Algorithm for initial management of acute hypoxaemic respiratory failure with NIPPV
28 Noninvasive Mechanical Ventilation in Hypoxemic Respiratory Failure 247

References

ACPE

1. Vital FMR, Ladeira MT, Atallah AN. Non-invasive positive pressure ventilation (CPAP or
bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev.
2013;5:CD005351. doi:10.1002/14651858.CD005351.pub3.
2. McMurray JJV, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treat-
ment of acute and chronic heart failure 2012. Eur Heart J. 2013;33:1787–847.

Pneumonia

3. Carrillo A, Gonzalez-Diaz G, Ferrer M, Martinez-Quintana ME, Lopez-Martinez A, Llamas

N, et al. Non-invasive ventilation in community-acquired pneumonia and severe acute respira-
tory failure. Intensive Care Med. 2012. doi:10.1007/s00134-012-2475-6.
4. Brambilla AM, Aliberti S, Prina E, et al. Helmet CPAP vs. oxygen therapy in severe hypox-
emic respiratory failure due to pneumonia. Intensive Care Med. 2014;40:942–9. doi:10.1007/
s00134-014-3325-5.

Trauma

5. Karcz MK, Papadakos PJ. Noninvasive ventilation in trauma. World J Crit Care Med.
2015;4(1):47–54.

ARDS

6. Rana S, Jenad H, Gay PC, et al. Failure of noninvasive ventilation in patients with acute lung
injury: observational cohort study. Crit Care. 2006;10:R79.
7. Ferrer M, Esquinas A, Leon M, et al. Noninvasive ventilation in severe hypoxemic respiratory
failure: a randomized clinical trial. Am J Respir Crit Care Med. 2003;168:1438–44.
8. Agarwal R, Agarwal AN, Gupta D. Role of noninvasive ventilation in acute lung injury/acute
respiratory distress syndrome: a proportion meta-analysis. Respir Care. 2010;55:1653–60.
9. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition.
JAMA. 2012;307:2526–33.
10. Antonelli M, Conti G, Esquinas A, et al. A multiple-center survey on the use in clinical prac-
tice of noninvasive ventilation as a first-line intervention for acute respiratory distress syn-
drome. Crit Care Med. 2007;35:18–25.
11. Ferguson N, Fan E, Camporota L, et al. The Berlin definition of ARDS: an expanded rationale,
justification, and supplementary material. Intensive Care Med. 2012;38:1573–82.
12. Caironi P, Carlesso E, Cressoni M, et al. Lung recruitability is better estimated according to the
Berlin definition of acute respiratory distress syndrome at standard 5 cm H2O rather than
higher positive end-expiratory pressure: a retrospective cohort study. Crit Care Med.
2015;43:781–90.
248 R. Cosentini and T. Maraffi

Drowning
13. Szpilman D. Near-drowning and drowning classification: a proposal to stratify mortality based
on the analysis of 1831 cases. Chest. 1997;112(3):660–5.
14. Gregorakos L, Markou N, Psalida V, et al. Near-drowning: clinical course of lung injury in
adults. Lung. 2009;187(2):93–7.
15. Dottorini M, Eslami A, Baglioni S, et al. Nasal-continuous positive airway pressure in the
treatment of near-drowning in freshwater. Chest. 1996;110(4):1122–4.
Noninvasive Mechanical Ventilation
in Acute Exacerbations of Chronic 29
Obstructive Pulmonary Disease: Key
Determinants of Early and Late Failure

Oya Baydar and Ezgi Ozyilmaz

Contents
29.1 Introduction ................................................................................................................. 250
29.2 Discussion and Analysis ............................................................................................. 250
29.2.1 Patient-Related Risk Factors ......................................................................... 252
29.2.2 Immediate NIV Failure ................................................................................. 252
29.2.3 Early NIV Failure .......................................................................................... 253
Conclusion ............................................................................................................................. 256
References .............................................................................................................................. 257

Abbreviations

ABG Arterial blood gas

ARF Acute respiratory failure
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
ETI Endotracheal intubation
FiO2 Fraction of inspired oxygen
HES Hypercapnic encephalopathy
ICU Intensive care unit
IMV Invasive mechanical ventilation
IPV Intrapulmonary percussive ventilation
NIV Noninvasive ventilation
NNT Number needed to treat
OR Odds ratio
RCTs Randomized controlled trials
UMC Usual medical care

O. Baydar, MD (*) • E. Ozyilmaz, MD

Department of Chest Diseases, Cukurova University Faculty of Medicine, Adana, Turkey
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 249

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_29
250 O. Baydar and E. Ozyilmaz

29.1 Introduction

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a fre-

quent cause of admission to the hospital and the intensive care unit (ICU). During
these episodes, a major deterioration in gas exchange is accompanied by a worsen-
ing in the clinical condition of the patient, characterized by a rapid and shallow
breathing pattern, severe dyspnea, right ventricular failure, and encephalopathy. The
pathophysiological pathway of all these features is the inability of the respiratory
system to maintain adequate alveolar ventilation in the presence of major abnor-
malities in respiratory mechanics. Hypercapnia, acidosis, and hypoxemia all ensue,
leading to clinical deterioration in cardiovascular and neurological functions [1].
Estimates of inpatient mortality range from 4 to 30 %, but patients admitted due to
acute respiratory failure (ARF) experience a higher rate, in particular elderly
patients with comorbidities (up to 50 %) and those requiring ICU admission (11–
26 %) [2].
What triggers the abnormal breathing pattern of the patient remains unclear [1].
The key element during decompensation seems to be the shortening of the inspira-
tory time, inducing both a decrease in tidal volume and an increase in respiratory
frequency. Because this is associated with, or is secondary to, excessive respiratory
loads, treatment should be directed at reducing the loads imposed on the respiratory
muscles. Unfortunately, the ability of medical treatment to reverse severe respira-
tory failure in these patients is limited. When hypoventilation becomes so severe
that several organ dysfunctions occur, there is no choice other than to provide “arti-
ficial” ventilation to avoid a fatal outcome [1]. The traditional manner of artificial
ventilation was invasive mechanical ventilation (IMV), but today the role of nonin-
vasive ventilation (NIV) in the management of acute hypercapnic respiratory failure
secondary to COPD is well established [3]. Several randomized controlled trials
(RCTs) have demonstrated that adding NIV to standard medical therapy improves
dyspnea as well as reduces mortality, intubation rate, and hospital length of stay [3,
4]. A previous study using NIV in respiratory failure secondary to exacerbations of
COPD demonstrated reductions in respiratory rate and transdiaphragmatic activity
with increases in tidal volume and minute ventilation. Thus, NIV not only rapidly
improves gas exchange but also allows respiratory muscle rest, reducing respiratory
muscle work in respiratory failure [5].

29.2 Discussion and Analysis

How does NIV work? There are three important characteristics of NIV in this
setting that must be understood to answer this question. The first concerns ven-
tilation itself. The success of the technique is based on the ability of assisted
ventilation (or synchronized ventilation) to improve alveolar ventilation by
increasing tidal volume. The widely accepted pressure-targeted modes deliver
support in synchrony with the patient’s inspiratory effort, which usually results
in an increase in tidal volume, subsequently associated with a reduction in the
29 Noninvasive Mechanical Ventilation in Acute Exacerbations of Chronic 251

amount of effort performed by the patient [6]. The ability of these modes to
improve the volume delivered to the lung explains the ability of NIV to reverse
other clinical and gas exchange abnormalities. The second characteristic of NIV
is that it is an intermittent mode of support. NIV is usually delivered for only a
few hours during a 24-h period (usually 6–12 h) and is rarely delivered as a
continuous support. These patients have a highly stimulated and active respira-
tory drive and can therefore sustain prolonged periods of spontaneous breath-
ing. However, the treatment should provide a reduction in the amount of effort
needed and intermittent support seems to be adequate. When the need for venti-
latory support becomes permanent, tolerance of the mask becomes a limitation
and is frequently a cause of failure. The third characteristic of NIV is the use of
a face mask in place of an endotracheal tube. Although the use of these masks
is associated with specific problems such as leaks and limited clinical tolerance,
they have been shown to replace endotracheal intubation (ETI) advantageously
as a first-line treatment [1].
Chandra et al. [7] reported outcome data over a 10-year period, from 1998 to
2008, including more than 7.5 million COPD admissions from a database of 1,000
hospitals in the United States. These data demonstrated a four-fold increase in the
use of NIV, which represented an increase from 1.0 to 4.5 % of all admissions.
There was a corresponding 42 % decrease in invasively ventilated patients, from 6.5
to 3.5 % of all admissions.
Lindanauer reported a retrospective cohort study of 25,628 patients hospital-
ized for exacerbation of COPD who received mechanical ventilation on the first
or second hospital day. Those initially treated with NIV had a lower risk of death
or of developing pneumonia during the hospitalization, a shorter length of stay,
and lower costs compared with those who initially underwent invasive ventila-
tion. The relative advantage of NIV was attenuated among patients with higher
comorbidity burden and in the subgroup of patients who had pneumonia present
at the time of hospital admission [8]. NIV has been shown to improve acute
respiratory acidosis (increases pH and decreases PaCO2) and decrease respira-
tory rate, work of breathing, severity of breathlessness, complications such as
ventilator-associated pneumonia, and length of hospital stay (evidence level A).
More importantly, mortality and intubation rates are reduced by this intervention
(evidence level A) [9].
However, NIV is not successful in all cases of acute or chronic respiratory failure
due to COPD when compared with usual medical care, with reported failure rates of
between 9 and 50 %. There has also been concern that NIV may delay ETI and
mechanical ventilation, resulting in a worse outcome [10].
Prediction of outcomes, specifically negative predictors, following acute NIV is
essential to assisting the physician with decisions regarding the use of NIV in the
acute setting. Patient selection is the cornerstone of NIV. Among the patient-related
predictors of NIV failure, based on data from RCTs, three temporal moments were
identified: (1) immediate failure (within minutes to <1 h), (2) early failure (1–48 h),
and (3) late failure (after 48 h); these three types of failures were associated with 15,
68, and 17 % of failures, respectively.
252 O. Baydar and E. Ozyilmaz

29.2.1 Patient-Related Risk Factors

Immediate Risk Factors

1. Weak cough reflex and/or excessive secretions
2. Hypercapnic encephalopathy and coma
3. Intolerance and psychomotor agitation
4. “Fighting with the machine”: patient-ventilator asynchrony

Early Risk Factors: Hypoxemic ARF

1. Baseline arterial blood gas (ABG) and inability to correct gas exchange
(pH < 7.25)
2. Increased severity of disease
3. Increased respiratory rate (>35 breaths/min)
4. Miscellaneous: poor nutritional status, increased heart rate, higher baseline
C-reactive protein/white blood cell count, lower serum potassium, airway colo-
nization by nonfermenting gram-negative bacilli

Late Risk Factors

1. Sleep disturbance
2. Functional limitation
3. Possible initial improvement in pH
4. Hyperglycemia

29.2.2 Immediate NIV Failure

Immediate NIV failure refers to failure within minutes and not beyond the first hour
of treatment. About 15 % of all NIV failures were defined as “immediate” in RCTs,
irrespective of the underlying causes of respiratory failure.

29.2.2.1 Weak Cough Reflex and/or Excessive Secretions

NIV does not allow direct access to the airways. A weak cough reflex leading to
inefficient clearance of excessive secretions from airways is a common cause of
immediate NIV failure. The inability to spontaneously remove secretions is consid-
ered a relative contraindication for NIV, especially in patients with impaired con-
sciousness and depressed cough. Some data indicate that specific “manual” or
“mechanical” physiotherapeutic techniques may improve mucociliary clearance
during NIV, and NIV can still be used in these circumstances. Intrapulmonary per-
cussive ventilation (IPV) is a technique that delivers small bursts of high-flow respi-
ratory gas at high rates for mobilization of secretions. Two clinical studies
demonstrated that IMV used before or in combination with NIV may reduce the risk
of ETI in COPD patients with difficulties removing secretions. Early fiber-optic
bronchoscopy is another potential intervention that can be used to minimize the
burden of respiratory secretions [11].
29 Noninvasive Mechanical Ventilation in Acute Exacerbations of Chronic 253

29.2.2.2 Hypercapnic Encephalopathy and Coma

Hypercapnic encephalopathy (HES) is often considered a cause of immediate NIV
failure because of poor compliance due to confusion and/or agitation. Additionally,
it is viewed as a relative contraindication because of the increased risk of aspiration.
The risk of aspiration has been shown to be minimized by the rapid improvement of
neurological status under NIV, and NIV failure rates were reported to be compara-
ble among patients with and without HES. The use of a relatively high back-up rate
and/or pressure control ventilation may also help to “capture” the patient better.
Another key factor in patients with HES is the rebound effect of fraction of inspired
oxygen (FiO2) on the PaCO2 and pH, known as the “Haldane effect.” This effect can
be prevented by a simple intervention: decreasing the FiO2 level [11].

29.2.2.3 Intolerance and Psychomotor Agitation

Patient tolerance has been shown to be critical for NIV success, especially in the
first few minutes while the patient adapts to this “new mode” of breathing. The use
of judicious sedation may be valuable to achieve a sedation level that keeps the
patient awake, easily arousable, and comfortable. Ideal sedatives should be short
acting and have no significant effects on respiratory drive and hemodynamics. It has
to be kept in mind that oversedation during NIV can be potentially dangerous. Thus,
close monitoring with evaluation of ABG, cardiopulmonary and ventilator param-
eters, adverse events, and the level of sedation is mandatory [11].

29.2.2.4 Patient-Ventilator Asynchrony

Asynchrony has rarely been cited as a direct cause of NIV immediate failure.
Asynchrony can easily be detected by a physical examination (e.g., number of spon-
taneous breaths vs ventilator-delivered breaths, accessory muscle use) of the patient
and symptoms (e.g., dyspnea). Two main causes of asynchrony are a high level of
ventilator support and an increased number of leaks. A number of strategies can be
implemented to avoid “gross asynchronies,” such as optimization of ventilator set-
tings using the screen ventilator waveforms, adjusting trigger sensitivity, increasing
positive end-expiratory pressure, minimizing leaks, and using different modes or
more sophisticated ventilators. New modes of ventilation, such as neutrally adjusted
ventilator assist, have been documented to reduce asynchrony [11].

29.2.3 Early NIV Failure

Nearly 65 % of NIV failures occur within 1–48 h of NIV use. This time interval has
received more attention in assessments of predictors of failure. It has two main sub-
types, hypoxemic and hypercapnic respiratory failure, and we will discuss hyper-
capnic failure in detail, as it is our main concern.
Although hypercapnic ARF includes ARF due to neurological disorders (such as
neuromuscular disorders) and other acute or chronic lung disorders (such as restric-
tive lung disease), most of the studies done in this field have involved patients with
COPD exacerbations [11].
254 O. Baydar and E. Ozyilmaz

29.2.3.1 Baseline ABG and Inability to Correct Gas Exchange

The pH level, which is an indicator of the severity of hypercapnia, has been reported
to be a critical factor in determining the success of NIV. Although some reports
failed to show any relationship between baseline ABGs and the success of NIV, a
large body of evidence clearly indicated that a lower baseline pH is a risk factor for
NIV failure in COPD patients. In nearly 50–60 % of patients with a baseline pH of
<7.25, NIV was unsuccessful. A subgroup analysis of COPD patients with mild to
moderate acidosis revealed that NIV improved patient outcomes only if the baseline
pH was ≥7.30. Three studies with 320 patients were included in the 7.35–7.30 sub-
group and five studies with 221 patients in the <7.30 subgroup. Studies in both pH
subgroups showed treatment failure to be significantly less with NIV (RR 0.63;
95 % CI 0.43, 0.95 and RR 0.37; 95 % CI 0.25, 0.54, respectively). There were no
significant differences between the two pH subgroups [5].
In addition to baseline levels, pH values 1 h after the application of NIV were
shown to be strong predictors of the success of NIV, with high sensitivity and good
specificity (93 and 82 %, respectively) [9]. In a study of more than 1,000 COPD
patients, Confalonieri et al. pointed out that a pH <7.25 after 1 h of NIV use was
associated with an increased risk of failure and that the risk of failure was even
greater than when the pH levels were <7.25 at admission [12]. For the above-men-
tioned reasons, we do not recommend routine use of NIV in patients with a pH
<7.25 outside a “protected” environment [11].

29.2.3.2 Increased Severity of Disease

The relationship between NIV failure and the severity scores, including Acute
Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute
Physiology Score II (SAP II), has been documented in a number of reports. Several
researchers found an association, whereas others failed to find any association.

29.2.3.3 Increased Respiratory Rate

An initial high respiratory rate and its reduction after 1 h of NIV have been shown
to be associated with successful NIV outcomes in COPD patients. A respiratory rate
of 30–34 and ≥35 breaths/min at admission were demonstrated to lead to NIV fail-
ure, with an OR of 1.83 and 2.66, respectively, whereas the ratios increased to 2.67
and 4.95, respectively, for the same breathing frequency after 2 h of NIV [11].

29.2.3.4 Miscellaneous Risk Factors of NIV Failure

Miscellaneous risk factors for NIV failure in hypercapnic ARF are poor nutritional
status, a high white blood cell count, low serum potassium, and an increased heart
rate. Two additional issues may merit specific consideration. Old age has never been
shown to be a “negative” variable in determining NIV outcomes, and older patients
with hypercapnic ARF may respond even better than younger ones to NIV [11].

29.2.3.5 Late NIV Failure

Although the definition of late NIV failure has not been standardized, it is usually
defined as failure that occurs 48 h after initiation of NIV, following an initial
29 Noninvasive Mechanical Ventilation in Acute Exacerbations of Chronic 255

successful response. It occurs in a considerable subset of patients (about 15 % of

NIV failures).
The occurrence of late failure in COPD patients admitted with hypercapnic ARF
to ICUs when NIV was used >24 h was found to be associated with functional limi-
tation before admission, the presence of hyperglycemia, and a lower pH at admis-
sion. PaCO2 and pH values improved gradually and similarly within the first 24 h in
both success and late failure groups. This is of particular importance because initial
good responses to NIV may decrease attention and monitoring by clinicians in the
following hours. During a hospital stay, pneumonia was more frequently observed
as a complication in a late failure group compared with a success group (12.9 % vs
0 %). The mortality of a late failure group was extremely high compared with a suc-
cessful group in another study (68 % vs 0 %). In a recent study, sleep disturbance
(classified as an abnormal electroencephalographic pattern, greater circadian sleep-
cycle disruption, and less nocturnal rapid eye movement sleep) and increased delir-
ium during an ICU stay were also associated with late NIV failure in hypercapnic
patients. NIV patients should be continuously monitored (including their sleep pat-
terns and state of delirium), even if their initial clinical and ABG responses are
good, because late NIV failure can lead to high mortality [11].
The global rise in obesity has impacted on the COPD population. Of further
interest, obese COPD patients were protected from adverse outcomes and were less
likely to develop late NIV failure or require hospital readmission at 1 year. Patients
with COPD and obesity are also more likely to receive long-term ventilatory sup-
port in the form of either NIV or continuous positive airway pressure (CPAP) to
treat COPD–obstructive sleep apnea overlap syndrome. It is unclear from the data
whether the improved outcomes in obese patients with COPD are a reflection of
enhanced interaction between opposing pulmonary mechanics or whether it simply
reflects the higher incidence of home NIV and CPAP as a treatment, which increases
overall health-care support.
Concerning the efficiency of NIV in COPD patients with severe community
acquired pneumonia, one randomized study including COPD patients with hyper-
capnic ARF and pneumonia reported by Confalonieri et al. showed that NIV may
reduce the rate of intubation and complications in comparison with medical therapy.
The same advantages were not achieved when NIV was compared with conven-
tional mechanical ventilation [13].
We have discussed the patient-related risk factors of NIV failure; there are also
some non-patient-related risk factors, too. The timing of the application of NIV is a
critical factor. A longer delay between admission and NIV use was shown to be an
independent risk factor for NIV failure, probably due to the progression of the
underlying disease. Therefore, early use of NIV is recommended. It is also critical
not to unduly delay the decision to intubate a patient with failed NIV, because the
risk of unanticipated respiratory or cardiac arrest could lead to increased morbidity
and mortality [5, 11].
The location of the NIV therapy is another important determinant in the success
of NIV. The decision about where to perform NIV should be based on matching the
capabilities of the units and teams with the patient’s clinical severity and the need
256 O. Baydar and E. Ozyilmaz

for monitoring. Five studies with 414 patients were conducted outside the ICU and
three studies with 127 patients in the ICU. Both subgroups showed significant
improvements in treatment failure with NIV, with the results being slightly better in
the ICU subgroup. However, the difference did not reach statistical significance, as
can be seen with the overlapping 95 % CIs for the two point estimates [5].
The experience and the skills of the staff are other key components of NIV suc-
cess. Training in NIV implementation is an important factor in reducing nosocomial
infections and improving survival in critically ill patients with COPD [11].
Although much attention has been paid to the development of new interfaces to
increase tolerance and patient comfort, mask intolerance remains a major cause of
NIV failure. An oronasal mask is generally the most commonly preferred one in
ARF, followed by nasal masks, helmets, and mouthpieces [11].
How to withdraw the patient from NIV is also critical. A pilot prospective,
single-center, open-labeled randomized study comparing stepwise versus immedi-
ate withdrawal of NIV in patients with COPD exacerbation recovering from acute
hypercapnic respiratory failure revealed no statistically significant difference in the
success rate, with NIV successfully stopped in 74.3 % and 56 % in the stepwise and
immediate withdrawal groups, respectively (p = 0.139).

Conclusion
In summary, a review of 14 RCTs with 758 patients shows clear benefit of NIV
as an adjunct therapy to usual medical care (UMC) (compared with UMC alone)
in the management of patients admitted to hospital with respiratory failure sec-
ondary to an acute exacerbation of COPD. NIV compared with UMC showed
significant improvements in pH, PaCO2, respiratory rate, treatment failure, mor-
tality, intubation rate, complications, and length of hospital stay. Studies con-
ducted in the ICU or outside the ICU were also not significantly different. With
NIV, the risk of treatment failure was reduced by more than 50 % and the number
needed to treat was 5. Therefore, for every five patients treated with NIV, we
would avoid one patient failing treatment. Treatment failure was significantly
reduced, whether the study was conducted in the ICU or the wards. However, as
with the pH subgroups, greater reduction in the risk of treatment failure was seen
with studies in ICUs (risk reduction of 71 %) than in studies conducted in the
ward (risk reduction of 39 %). There was a significant reduction in risk of mor-
tality with NIV of 48 % compared with UMC. For every 10 patients treated with
NIV, we would avoid one death. There has been debate as to whether NIV would
delay ETI, leading to an increase in mortality. It is shown that mortality is signifi-
cantly decreased with NIV use. With admission pH less than 7.30, risk reduction
was 49 %; with admission pH between 7.35 and 7.30, risk reduction was 55 %.
With NIV, the risk of ETI was more than halved (59 %), and by treating four
patients with NIV we would avoid one patient being intubated. Length of hospi-
tal stay was significantly reduced by more than 3 days with NIV. Acidosis has
been shown to be an important prognostic factor in survival from respiratory
failure in COPD, and thus early correction of acidosis is an essential goal of
therapy [5].
29 Noninvasive Mechanical Ventilation in Acute Exacerbations of Chronic 257

Recommendations
Studies show that NIV offers better outcomes to patients admitted with acute
exacerbations of COPD than either medical treatment alone or ICU manage-
ment with ETI as second-line treatment (approximately 75 % of patients).
Three complementary interventions can therefore now be proposed in a step-
wise approach to these patients, and their combination should become a new
standard of care. The first step is based on drug treatment and appropriate
management of oxygen. The second step is the early use of NIV to prevent
further worsening and clinical deterioration. How soon this treatment should
be applied is still a matter of debate and may be difficult to base solely on
objectively quantified criteria. The final treatment step is ETI and mechanical
ventilation. This should be reserved for patients in whom NIV is contraindi-
cated, for those meeting intubation criteria despite NIV, or those requiring
immediate ETI on admission.

References
1. Brochard L. Non-invasive ventilation for acute exacerbations of COPD: a new standard of
care. Thorax. 2000;55:817–8.
2. American Thoracic Society. Standards for the diagnosis and care of patients with chronic
obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152:77–120.
3. Plant PK, Owen JL, Elliott MW. Early use of noninvasive ventilation for acute exacerbations
of chronic obstructive pulmonary disease on general respiratory wards: a multicentre ran-
domised controlled trial. Lancet. 2000;355:1931–5.
4. Conti G, Antonelli M, Navalesi P, et al. Noninvasive vs. conventional mechanical ventilation
in patients with chronic obstructive pulmonary disease after failure of medical treatment in the
ward: a randomized trial. Intensive Care Med. 2002;28:1701–7.
5. Ram FSF, Picot J, Lightowler J, Wedzicha JA. Non-invasive positive pressure ventilation for
treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease
(Review). Cochrane Database Syst Rev. 2003;326:185–190.
6. Brochard L, Isabey D, Piquet J, et al. Reversal of acute exacerbations of chronic obstructive
lung disease by inspiratory assistance with a face mask. N Engl J Med. 1990;323:1523–30.
7. Chandra D, Stamm JA, Taylor B, et al. Outcomes of noninvasive ventilation for acute exacer-
bations of chronic obstructive pulmonary disease in the United States, 1998–2008. Am J
Respir Crit Care Med. 2012;185:152–9.
8. Lindenauer PK, Stefan MS, Shieh MS, et al. Outcomes associated with invasive and non-
invasive vertilation among patients hospitalized with exacerbations of chronic obstructive pul-
monary disease. JAMA Intern Med. 2014;174(12):1982–93.
9. Global Intiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis,
management, and prevention of Chronic Obstructive lung disease. Updated 2014. Global ini-
tiative for chronic obstructive lung disease, Inc. Available from: http://www.goldcopd.org/
uploads/users/files/GOLD_Report2014_Feb07.pdf. Accessed July 12, 2015.
10. Ambrosino N, Foglio K, Rubini F, Clini E, Nava S, Vitacca M. Non-invasive mechanical ven-
tilation in acute respiratory failure due to chronic obstructive pulmonary disease: correlates for
success. Thorax. 1995;50:755–7.
11. Ozyilmaz E, et al. Timing of noninvasive ventilation failure: causes, risk factors, and potential
remedies. BMC Pulm Med. 2014;14:19.
12. Confalonieri M, Garuti G, Cattaruzza MS, et al. A chart of failure risk for non-invasive ventila-
tion in patients with COPD exacerbation. Eur Respir J. 2005;25(2):348–55.
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community-acquired pneumonia. Am J Respir Crit Care Med. 1999;160:1585–91.
Noninvasive Ventilation
in the Prehospital Setting: Key 30
Applications

Patrick Chaftari, Maria Teresa Cruz Carreras,

and Jayne Viets-Upchurch

Contents
30.1 Respiratory Emergencies ............................................................................................ 259
30.2 Noninvasive Ventilation Techniques and Mechanisms ............................................... 260
30.3 Indications ................................................................................................................... 261
30.3.1 Hospital Setting ............................................................................................. 261
30.3.2 Prehospital Setting......................................................................................... 262
30.4 Outcomes .................................................................................................................... 262
30.5 Contraindications and Complications ......................................................................... 262
Conclusions ............................................................................................................................ 263
References .............................................................................................................................. 264

Abbreviations

ACPE Acute cardiogenic pulmonary edema

COPD Chronic obstructive pulmonary disease
NIV Noninvasive ventilation

30.1 Respiratory Emergencies

In normal respiration, the contraction of external intercostal muscles and the dia-
phragm increases the lung volume, creating negative pressure that results in the
movement of air to the alveoli. The relaxation of the external intercostal muscles

P. Chaftari, MD (*) • M.T.C. Carreras, MD • J. Viets-Upchurch, MD

Emergency Medicine, The University of Texas MD Anderson Cancer Center,
Houston, TX, USA
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 259

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_30
260 P. Chaftari et al.

and diaphragm restores the thoracic cavity to preinspiratory volume, increasing

pressure in the lungs and generating exhalation. This movement of air in and out of
the lungs, known as pulmonary ventilation, provides the necessary oxygen to the
alveoli and eliminates carbon dioxide. Pulmonary ventilation maintains optimal
partial pressure of each gas, allowing gas exchange at the level of the alveoli and
pulmonary capillaries.
Some of the most common calls to emergency medical services are associated
with respiratory complaints [1–4]. Differential diagnosis includes neurological
issues (e.g., head trauma, drugs, and cerebrovascular accidents), upper airways
(e.g., swelling, blockage by a foreign body, and trauma), lower airways (e.g., asthma
and chronic obstructive pulmonary disease (COPD)), alveoli, and possible impair-
ment in pulmonary circulation resulting from pulmonary embolism. Congestive
heart failure and COPD make up the largest percentage of respiratory emergencies.
In the United States, approximately one million patients per year are treated by
paramedics for acute congestive heart failure [5].
Dyspnea, or shortness of breath, accounts for 10–13 % of emergency medical
service calls [6]. Standard care for dyspnea in the prehospital setting typically
involves supplemental oxygen and beta agonist nebulizer therapy. Vasopressors and
diuretics may also be employed, depending on the emergency medical service pro-
tocol and responder skill level.
Respiratory failure occurs when the lungs can no longer provide adequate oxy-
genation, generally resulting in tachypnea, hypoxemia, hypercapnia, and perceived
dyspnea. Severe respiratory failure has been managed in the prehospital setting by
endotracheal intubation, an invasive procedure that requires sedation and advanced
skills. Endotracheal intubation may be difficult and dangerous because of the pres-
ence of contact-protective airway reflexes [7] and is associated with multiple com-
plications, such as oral lacerations, aspiration, tube malposition, barotrauma, and
ventilator-associated pneumonia. The poorly controlled environment of the prehos-
pital setting increases the likelihood of these complications.
Trauma and pneumothorax may present with the symptom of dyspnea. The pres-
ence of trauma is generally easily discerned, and presentation of significant pneu-
mothorax typically involves tracheal deviation and unilateral loss of breath sounds.
More perplexing are the life-threatening medical causes of dyspnea, such as exacer-
bations of COPD, asthma, pneumonia, pulmonary embolism, cardiac ischemia, and
acute cardiogenic pulmonary edema (ACPE) (COPD and ACPE are the most com-
mon). The uncertain etiology of medically induced dyspnea complicates its man-
agement in the prehospital setting.

30.2 Noninvasive Ventilation Techniques and Mechanisms

Improving alveolar ventilation is a critical step for delivering oxygenated blood to the
tissue. Different techniques for accomplishing this have been introduced over the
years, ranging from provision of supplemental oxygen to endotracheal intubation.
With recent advances, noninvasive positive-pressure ventilation (NIV), a technique
30 Noninvasive Ventilation in the Prehospital Setting: Key Applications 261

introduced in 1981 by Sullivan and colleagues to provide alveolar ventilation without

creation of an invasive airway, has emerged as an efficient alternative to endotracheal
intubation with mechanical ventilation; NIV also has a lower rate of complications
such as pneumonia, vocal injury, and tracheal stenosis than invasive techniques [8].
Unlike bag valve mask ventilation, the most basic form of NIV, which is typi-
cally used for pre-oxygenation of a patient prior to endotracheal intubation, two
types of NIV are used in lieu of endotracheal intubation. The first type, continuous
positive airway pressure, applies supportive pressure in a uniform fashion during
both the inspiratory phase and the expiratory phase. The second type, bi-level posi-
tive airway pressure, alternates different levels of inspiratory and expiratory pres-
sure. Both types typically provide pressure support of 4–20 cmH2O, usually via a
face mask, although helmets and nasal cannulas can also be used [9]. Because BiPaP
matches the patient’s spontaneous respiratory drive, in certain patients NIV may be
more efficient than endotracheal intubation and controlled mechanical ventilation
[10]. In addition, the training required to deliver NIV is less extensive than the train-
ing required for endotracheal intubation.
Over the past several years, NIV modalities have proven to be effective in man-
agement of acute respiratory failure. NIV decreases the effort required for breathing
through several mechanisms. It improves pulmonary compliance and reduces the
ventilation/perfusion mismatch. Smaller, pliable airways are stented open. This
allows for recruitment and ventilation of atelectatic alveoli. The increased intratho-
racic pressure decreases venous return, transmural pressure, and afterload, which
improves cardiac function. Edema is shifted back into the vascular system [10].

30.3 Indications

30.3.1 Hospital Setting

Common indications for NIV in hospital patients include COPD exacerbation,

ACPE, acute respiratory failure in immunosuppressed patients, post-intubation
weaning, and post-extubation support in patients at high risk for reintubation [9].
Patients with nontraumatic chest wall deformity, neuromuscular disease, obstructive
sleep apnea, cystic fibrosis, or pneumonia may benefit as well [11]. The evidence
supporting routine use of NIV for asthma is limited, although small studies indicate
that NIV may be of value [2, 9, 11]. The British Thoracic Society recommends NIV
for chest trauma if analgesia and high-flow oxygen fail to maintain adequate oxygen-
ation; in such cases, patients should be monitored closely for pneumothorax [11].
NIV may obviate the need for endotracheal intubation [12]. Recent reviews and
guidelines have suggested that NIV be considered the first option for ventilatory
support in patients with COPD or ACPE, citing decreased mortality and shorter
hospital stays [9, 12–14]. Evidence supporting the use of continuous positive airway
pressure is more robust than that supporting the use of bi-level positive airway pres-
sure [15]. Because NIV does not require sedation, it provides the advantage of keep-
ing the patient alert and capable of making health-care decisions.
262 P. Chaftari et al.

30.3.2 Prehospital Setting

Although there is now compelling evidence of the benefits of the early initiation of
NIV as an adjunct to medication for COPD and ACPE, the use of NIV for respira-
tory failure in the prehospital setting remains limited [16]. Paramedics in the field
can improve the effectiveness of their treatment of respiratory failure by becoming
more familiar with the indications for and methods of NIV so that NIV can be used
appropriately and in all cases that warrant it.
NIV should be carefully considered in patients with respiratory failure. The best
candidate for NIV is an awake patient in respiratory distress who is alert and coop-
erative and has an intact gag reflex [17]. It is appropriate to consider NIV in patients
with respiratory failure with oxygen saturation less than 90 % despite oxygen deliv-
ery at 15 l/m. It is also appropriate to use NIV in patients with do-not-intubate
orders or when the patient’s wishes regarding advanced life support are unknown
and cannot be discussed on the scene.

30.4 Outcomes

Acute respiratory failure must be treated promptly for optimal outcome. Given the
positive results for NIV in inpatients, it follows that administering NIV to patients
in the field would also improve outcomes. Inpatient studies suggest that COPD and
ACPE patients are the most likely to benefit from prehospital NIV.
Several studies and meta-analyses have attempted to clarify the value of NIV in
the prehospital setting [2, 3, 15, 18–21]. Most of these studies have focused on
ACPE. Primary endpoints included mortality, need for subsequent intubation,
length of hospital stay, length of intensive care unit stay, vital sign stability, and
patients’ subjective assessment of symptom control. Studies like this are fraught
with challenges. Because double-blind studies are impractical, the potential for
treatment bias is high. Ethically, the care of a patient experiencing respiratory fail-
ure should not be delayed for the purpose of obtaining consent for treatment.
Compared with standard medical care, prehospital NIV is generally associated with
lower mortality and lower rates of intubation [2, 3, 15, 19–21]. Patients treated with NIV
reported symptomatic relief [18, 19]. Whereas some studies reported clear improvement
in vital signs [19, 20], others did not find this to be the case [18]. Improvements were
most pronounced with regard to the heart rate and respiratory rate, not oxygen saturation
[22]. Despite such improvements, most studies did not show a decrease in the length of
stay in the intensive care unit or in the length of hospitalization [2, 19].

30.5 Contraindications and Complications

NIV is contraindicated in comatose patients. Patients with hemodynamic instability,

decreased respiratory drive, or severe respiratory distress mandate immediate endo-
tracheal intubation to secure the airway. As with endotracheal intubation,
30 Noninvasive Ventilation in the Prehospital Setting: Key Applications 263

pneumothorax should be treated prior to initiation of NIV therapy. Structural facial

abnormalities, trauma, and burns can hinder mask-to-face sealing and preclude the
use of NIV. Patients with fixed upper airway obstructions do not respond to
NIV. Altered mentation, agitation, or somnolence can decrease a patient’s ability to
cooperate with NIV therapy. Decreased gag reflexes put patients at a higher risk of
aspiration of digestive tract contents through NIV. Gastrointestinal contraindica-
tions include active vomiting, distention, and bowel obstruction, which also increase
the risk of aspiration. Patients with recent facial or upper gastrointestinal tract sur-
gery should not receive NIV [10, 11].
Patients should be monitored for response to NIV. As a patient’s subjective com-
fort level improves, objective findings such as oxygenation, vital signs, and work of
breathing should stabilize. Successfully treated patients should continue to receive
therapy. Treatment should be coordinated with the receiving emergency department
so that the treatment is not interrupted. Progressive deterioration, intolerance to
therapy, or development of treatment-related complications mandate an alternative
strategy (e.g., intubation or construction of a surgical airway).
NIV is generally well tolerated, but in the prehospital setting, emesis and claus-
trophobia are frequent complications of NIV [2, 23]. Other NIV-associated compli-
cations include nasal abrasion, rhinitis, nose pain, gastric distention, and poor sleep
[24]. There are also challenges when it comes to mask leakage and poor mask fit.
One study suggested an increase in mortality from acute myocardial infarction in
hospital patients treated with NIV [25]. Subsequent meta-analyses have not sup-
ported this finding [13, 26]. In cases of trauma, there is a risk for pneumocephalus,
subcutaneous emphysema, pneumothorax, hypotension, and infection [10].
Oxygen toxicity has been cited as detrimental in critically ill patients, particu-
larly in patients with myocardial infarction and cerebrovascular disease. NIV has
traditionally been used with high oxygen concentrations, but a recent study has
shown low oxygen concentrations to be effective in patients with these condi-
tions [23].

Conclusions
Acute respiratory distress is a common diagnostic dilemma for paramedics and
can be due to various conditions. The goals of care include identifying the cause,
promptly initiating targeted management, stabilizing the airway, and observing
for ventilatory improvement or deterioration. When advanced directives are not
clear and the patient has an advanced illness or a poor prognosis, administering
noninvasive ventilation to a patient in respiratory distress provides the time
needed to explore the patient’s wishes by communicating directly with the
patient, family members, or medical personnel who might be familiar with the
patient, while en route to the hospital.
In the prehospital setting, diagnostic testing is challenging and transport times
can be long. Prior to arrival at a hospital, options are limited for patients whose
condition is rapidly deteriorating. In patients with severe respiratory distress,
prehospital NIV has been shown to reduce the need for intubation or mechanical
ventilation upon admission to a hospital as well as in-hospital mortality in
264 P. Chaftari et al.

several randomized controlled trials reviewed by Mal and colleagues [2]. NIV is
generally safe, especially when the provider is knowledgeable of the contraindi-
cations for prolonged NIV such as excessive somnolence, respiratory fatigue,
agitation, or facial anomalies.

Key Recommendations
• The best candidates for NIV are patients in respiratory distress who are
awake and cooperative. It is appropriate to consider NIV in patients with
respiratory failure with oxygen saturation less than 90 % despite oxygen
delivery at 15 l/m.
• NIV can be administered by means of continuous positive airway pressure
or bi-level positive airway pressure via a ventilator, at the discretion of the
emergency medical service personnel at the scene or of a physician [27].
• Consider NIV and early initiation of ventilation for COPD and ACPE as an
adjunct to medication.
• Progressive deterioration, intolerance to therapy, or development of
treatment-related complications mandates intubation or construction of a
surgical airway.
• Patients with facial abnormalities, decreased respiratory drive, or evidence
of cognitive impairment should not be treated with NIV.

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Equipment Technology for Noninvasive
Ventilation in the Pre-hospital Setting 31
Steven C. LeCroy

Contents
31.1 Important Components of a Pre-hospital NIV Device ................................................ 268
31.2 Types of Pre-hospital NIPPV Systems ....................................................................... 270
31.2.1 Conventional External Pressure Regulator NIPPV Systems ........................... 270
31.2.2 Disposable CPAP Devices ............................................................................... 271
31.2.3 Demand Flow .................................................................................................. 274
31.2.4 Transport Ventilators with NIV Functionality................................................. 275
Work Cited ............................................................................................................................. 276
Resources..................................................................................................................... 276

Noninvasive ventilation (NIV) is the delivery of ventilatory support without the

need for an artificial airway. NIV is provided using either positive or negative pres-
sure. However, since the early 1980s, noninvasive positive pressure ventilation
(NIPPV) has emerged as an important advance in respiratory care. In 2000, the
National Association of EMS Physicians (NAEMSP) issued a position statement on
pre-hospital NIPPV: “Non-invasive positive pressure ventilation is a viable pre-
hospital therapeutic option for acute dyspnea” [1]. The NAEMSP position state-
ment was based on the work of Kosowsky [2], titled “Pre-hospital use of continuous
positive airway pressure (CPAP) for presumed pulmonary edema: a preliminary
case series,” also published in 2000.
NIPPV has proved effective in the pre-hospital setting for a variety of cardio-
pulmonary conditions, from congestive heart failure (CHF) to chronic obstruc-
tive pulmonary disease (COPD). In fact, it is not uncommon to see pre-hospital
medical protocols directing emergency medical services (EMS) clinicians to

S.C. LeCroy, MA, CRTT, EMTP

Emergency Medical Services, St. Petersburg College, St. Petersburg, FL, USA
Hillsborough Community College, Plant City, FL, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 267

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_31
268 S.C. LeCroy

consider NIPPV for any patient in respiratory distress regardless of underlying

pathology. A common technique for NIPPV pre-hospital is continuous positive
airway pressure (CPAP). Another option can be the use of bi-level positive air-
way pressure (BiPAP). Of the two, CPAP has a proven track record when used
pre-hospital; support for BiPAP is still lacking. In addition, current technology
for providing BiPAP requires a more complex device or ventilator; neither is well
suited for prehospital use. In contrast, simple disposable and non-disposable
CPAP devices designed specifically for pre-hospital are available, as well as a
variety of transport ventilators with NIV capabilities. This chapter will cover the
current technology and equipment to provide NIPPV in the out-of-hospital emer-
gency environment.
Historically, NIPPV use in the field was limited by the available technology.
Limitations of using hospital NIV devices included size, cost, durability, and oxy-
gen consumption. Over time and with feedback from the field, each of these limita-
tions has been addressed with new and innovative technology. Before looking at
current devices available for use in the pre-hospital setting and to help determine the
appropriate device for a particular agency, there are a few fundamental questions
that providers should ask before selecting a device: First, what constitutes a good
pre-hospital NIPPV device? Second, what capabilities are required to meet the
needs of a particular agency? EMS agencies share some basic fundamental proto-
cols and equipment types, but, if you have seen one EMS agency then you have seen
one EMS agency; no two are alike.
There are a variety of devices available for clinicians to choose from when
providing NIPPV, from fully disposable to capital equipment. All medical
devices have variations in performance and design. Providers of NIPPV should
be aware of these differences and the effect the differences may have on the care
provided.

31.1 Important Components of a Pre-hospital NIV Device

Patient Interface NIPPV is only effective if the patient is compliant with the
treatment; patient comfort is key, as a patient is rarely compliant when not
comfortable. The choice of interface is a crucial issue in NIV. Available inter-
faces include nasal, oronasal, and facial masks, mouthpieces, and helmets,
with full face mask being common. Interfaces come in different sizes, and hav-
ing the correct size makes the device more comfortable and improves the seal,
requiring less pressure from the head strap or harness. Another option to
improve comfort is to have some mechanism to take pressure off the bridge of
the nose, reducing the incidence of pressure sores, a common complaint of
patients receiving NIV.
Manometer Applying positive pressure to the airway is not without risk and may
lead to a wide range of problems, including pneumothorax, reduced cardiac output,
and even death. As with every therapy, keeping a balance between risk and reward
31 Equipment Technology for Noninvasive Ventilation in the Pre-hospital Setting 269

is important. To help manage the risk, it is recommended that all patients receiving
NIPPV should have the pressure continuously monitored. A manometer also allows
the clinician to document pressures used, information that will be valuable in the
event of a bad outcome.
Few Parts/Compact EMS units have limited, space not only in their vehicles but
in the equipment bags/cases taken to the patient. It is imperative that any equipment
designed for EMS be compact and simple, with minimal parts. Historically, EMS
providers have an aversion to any equipment with lots of parts that require assembly
before use. Because the number of parts increases confusion, application error and
reduction in use increases.
Oxygen Consumption Unlike a hospital, EMS crews or ambulances have a lim-
ited supply of oxygen. Many agencies have converted to D cylinders because of
their size and weight as a trade-off for less oxygen. Those agencies with longer
transport times have to be concerned with oxygen consumption rates.
Nebulizer Capable With the expanded use of NIV for patients in respiratory dis-
tress, including COPD and asthma, the ability to provide nebulized medications is
no longer an option but a necessity.
Capnography/Capnometry Capable The measuring of end tidal CO2 (EtCO2)
should be a standard for any patient in respiratory distress or failure. With current
EtCO2 technology, all critical patients should be continuously monitored.
Anti-asphyxia Capabilities With EMS’s limited oxygen carrying capabilities
and potential long transport times or delays, a NIV device should have anti-
asphyxia capabilities. Anti-asphyxia or anti-suffocation protection is commonly
provided by an anti-asphyxia valve if the device is of a closed design. Open
systems do not require an anti-asphyxia valve because the device is open to
room air.
Adequate Inspiratory Flow Rates Patients in respiratory distress often require
the air/oxygen to be provided at a fast enough speed to meet their demand. It is often
not the volume of air/oxygen that is the problem, but the velocity at which it arrives.
Inadequate inspiratory flow rates will cause shortness of breath, difficulty breathing,
and an increase in work of breathing. Patients in respiratory distress may need flow
rates as high as 65 l/min or greater.
Fraction of Inspired Oxygen (FiO2) The administration of high oxygen con-
centrations has been the subject of great debate for several years. The outdated
theory that oxygen administration is risk free has been shown to be false.
However, at this time the only way to treat hypoxia is with oxygen. A NIV device
with low oxygen concentration capabilities is limited when treating hypoxic
patients. Clinicians are left with few options when a device has a maximum FiO2
of 30 % and the patient is still hypoxic but needs the positive pressure to reduce
the work of breathing.
Pressure Pop-Off or Relief Because high airway pressures are dangerous, a NIV
device should incorporate a mechanism to relieve excessive pressure. Common
causes of excessive pressure are blocked exhalation valves or blocked exhalation
openings, commonly found with open systems.
270 S.C. LeCroy

31.2 Types of Pre-hospital NIPPV Systems

Commercially available systems provide portable NIPPV through either a conven-

tional external pressure regulator, disposable CPAP system, demand-flow, or a
transport ventilator. All four designs contain key features that influence selection
and implementation.
Regulator-based portable NIPPV systems generate continuous pressure from
oxygen flow, directly controlling inspiratory and expiratory pressure. Regulator-
based NIPPV systems allow different inhaled oxygen fractions with reduced oxy-
gen consumption.
Some disposable devices are open systems and use a different NIPPV approach,
accelerating oxygen flow through a series of channels to create turbulence. The
turbulence acts as a virtual valve, generating positive airway pressure.
Demand-flow devices have a variety of pressure levels and built-in manometers.
Transport ventilators may be designed to provide NIPPV. Depending on the indi-
vidual brand and model, the process can be somewhat complicated and beyond
standard EMS training.

31.2.1 Conventional External Pressure Regulator NIPPV Systems

Regulator-based portable NIPPV systems generate continuous pressure from oxy-

gen flow, directly controlling inspiratory and expiratory pressure. Regulator-based
NIPPV systems allow different inhaled oxygen fractions with reduced oxygen con-
sumption. In 1981, J.B. Downs invented a new Venturi device called the Downs
Flow Generator. The flow generators were the first pre-hospital devices used on a
large scale and come in two types, adjustable flow and fixed flow. Devices using the
Downs Flow Generator design incorporate controls to adjust flow rates as well as
the inspired oxygen percentage (FiO2). Positive end-expiratory pressure (PEEP) is
determined by a PEEP valve found in the mask.

31.2.1.1 WhisperFlow® and Vital Signs CPAP Systems

The first Downs Flow Generator devices were the WhisperFlow (Philips
Respironics; http://whisperflow.respironics.com/) and the Vital Signs (http://www.
obex.co.nz/Product/Index/137) CPAP systems. Both devices are reuseable flow
generators with disposable circuits that attach to the high-pressure side of a flow
meter or regulator. These devices are solely powered by gas flow and entrain room
air through a Venturi device. Each produces high gas flow rates ranging from 100
to 140 l/min. The gas flow leaves the device and enters a breathing circuit, exiting
through a spring-loaded valve; all pressure adjustments are made by changing
valves. Neither unit incorporates a pressure manometer, and they both have high
oxygen consumption rates [3].
31 Equipment Technology for Noninvasive Ventilation in the Pre-hospital Setting 271

Variable flow Whisperflow, Photograph by Steve LeCroy

31.2.2 Disposable CPAP Devices

Disposable devices attach to the low-pressure side of the regulator or flow meter
(Boussignac®, Flow-Safe®, O-Two Controlled Ventilation™, and Rescuer®
Emergency CPAP System) or to the high-pressure side (O2-RESQ™).

31.2.2.1 Boussignac
The disposable Boussignac CPAP device (Vygon; https://www.vygon.com/cata-
log/vygon-boussignac-cpap_572_00557013), first described by Dr. George
Boussignac in 1989, was the first completely disposable CPAP devices. The prin-
ciple behind the Boussignac valve is to increase the forward velocity of a gas by
narrowing the flow through a cylinder. By increasing the velocity, turbulence is
created within the device. It is the turbulence and friction within the cylinder that
creates the resistance the patient must breathe against. All pressure adjustments are
made by adjusting the flow rate to either increase or decrease the turbulence. This
process eliminates the need for valves or moving parts. The valve is open, meaning
that it is open to the atmosphere, allowing the patient to breath in room air as
needed. The device incorporates a measuring port to add a manometer if needed.
The manufacturer reports that CPAP of 10 cmH2O can be achieved with approxi-
mately 25 l/min of oxygen flow.
272 S.C. LeCroy

31.2.2.2 Flow-Safe

Photograph courtesy of Mercury Medical

Flow-Safe (Mercury Medical; http://mercurymed.com/home/) is a completely dis-

posable CPAP device featuring a built-in manometer to monitor airway pressure and
a pressure relief valve for patient safety. There are three versions of Flow-Safe: the
original Flow-Safe, Flow-Safe II, and Flow-Safe II EZ. Each device uses the same
principle to create pressure. Similar to the Boussignac, the Flow-Safe device
changes the velocity of the gas by narrowing the flow. The increased gas flow cre-
ates the inspiratory pressure to assist the patient to inhale and also provides the
PEEP during exhalation. Pressure adjustments are made by increasing or decreasing
the gas flow rate from the flow meter or regulator and monitoring the built-in
manometer. According to the manufacturer, the original Flow-Safe achieves pres-
sures from 1.5 to 10 cmH2O with oxygen flow rates of 10–25 l/min. Flow-Safe II
achieves the same pressures as the original Flow-Safe using lower flow rates, how-
ever, the trade-off is a slightly lower FiO2. Flow-Safe II EZ incorporates a built-in
nebulizer, allowing both the valve and the nebulizer to be powered from a single gas
source.

31.2.2.3 O-Two Controlled Ventilation

The O-Two Single-Use CPAP device (O-Two Medical Technologies; http://otwo.
com/emergency-cpap/o_two-single-use-cpap/) is completely disposable.
Adjustment of pressure levels occurs by adjusting the flow rate from the flow meter
or regulator. Pressure and flow rate settings are found on the body of device.
31 Equipment Technology for Noninvasive Ventilation in the Pre-hospital Setting 273

According to the manufacturer, the CPAP range is between 5 and 20 cmH2O at flow
rates of 8–25 l/min.

Photograph by Steve LeCroy

31.2.2.4 O2-RESQ
The O2-RESQ (Pulmodyne; http://www.pulmodyne.com/products/pre-hospital-
and-emergency-medicine/o2-resq-product-information/) is an expansion chamber
with a Venturi air entrainment port. The basic unit provides approximately 30 %
FiO2 at a continuous flow up to 140 l/min to meet patient demand. CPAP valves are
available from 2.5 to 20 cmH2O and provide constant pressures at any flow rate.
With the addition of the O2-MAX™ Trio adaptor, FiO2 can be adjusted from 30% to
60% or 90%. CPAP valves, snapped onto the anti-asphyxia housing end of the cir-
cuit, are used to maintain PEEP pressures.

31.2.2.5 Rescuer Emergency CPAP System

Rescuer Emergency CPAP (BLS Systems; http://blssystemsltd.com/cpap_em.html)
incorporates an oxygen reservoir that, according to the manufacturer, allows higher
FiO2 levels with low flow rates, saving oxygen. The device also has filters on both
the inhalation and exhalation side to reduce exposure to airborne pathogens. With
the addition of the Rescuer II compact, a smaller version than the original BLS
Rescuer, BLS Systems now offers a version with a built-in manometer. The device
can also be configured to power a small volume nebulizer directly off the CPAP
device.

31.2.2.6 Smith Oxy-PEEP™

Oxy-PEEP (Smiths Medical; http://www.smiths-medical.com/catalog/oxygen-
medication-delivery/oxygen-delivery/oxygen-masks/oxy-peep.html) is a high-
concentration, high-flow oxygen diluter with adjustable PEEP. However, the device
should not be considered a CPAP or BiPAP device inasmuch as there is no inspira-
tory pressure. Only when the patient attempts to breathe out is there any pressure
274 S.C. LeCroy

within the circuit. This device allows for variable flows, variable O2 concentrations,
and variable PEEP.

31.2.3 Demand Flow

31.2.3.1 PortO2Vent™
The PortO2Vent Oxygen Delivery System (Emergent Respiratory Products; http://
www.eresp.com/products/porto2vent/) is a gas-powered device that delivers nonin-
vasive positive pressure to spontaneously breathing patients. The device features a
nondisposable demand valve that delivers oxygen during inhalation through a dis-
posable circuit at a flow rate determined by the patient’s inspiratory effort. A spe-
cially designed expiratory valve is pressure balanced to precisely maintain pressure
levels and reduce patient effort to open and exhale through the valve.

31.2.3.2 MACS CPAP System

The MACS CPAP System (Airon; http://aironusa.com/macs-cpap-system/)provides
infinitely variable PEEP, a built-in pressure gauge, and only flows oxygen during
inspiration, for reduced oxygen consumption and easier patient monitoring. The
device is non-disposable and uses a disposable circuit. It also incorporates a calibrated
knob that sets the CPAP level and a switch selects either 65 % or 100 % oxygen.

Photograph Courtesy of Airon Corporation

31 Equipment Technology for Noninvasive Ventilation in the Pre-hospital Setting 275

31.2.4 Transport Ventilators with NIV Functionality

Most transport ventilators are complex mechanical ventilation devices and provide
most forms of ventilation, including both CPAP and BiPAP. However, many were
not designed to provide facemask NIV; the CPAP/BiPAP modes are for patients
with protected airways. Transport ventilators that do provide NIV have capabilities
well beyond those found on other types of pre-hospital NIV devices and are consid-
ered capital equipment, with an average starting price of approximately $5,000 per
unit with a disposable circuit and mask. The following is a noninclusive list of
transport ventilators that offer NIV capabilities:

CAREvent® ALS+ CPAP (O-Two TM Medical Technologies; http://otwo.com/wp-

content/uploads/O-Two_CAREvent-ALS-CPAP_2012.pdf)
Flight 60 (Flight Medical®; http://www.flight-medical.com/flight-60-3)

Photograph Courtesy of Mercury Medical

LSP AutoVentTM 4000 CPAP (Allied Healthcare Products Inc.; http://www.alliedhpi.

com/images/z90-00-0008.pdf)
Newport HT70® Ventilator (CovidienTM; http://www.covidien.com/rms/products/
portable-ventilation/newport-ht70-plus)
Pneupac® paraPAC plus™ (Smiths Medical; http://www.smiths-medical.com/cata-
log/mechanical-ventilation/pneupac/para-pac/pneupac-parapac-mri-p200d.
html)
pNeuton® Model S Ventilator (Airon; http://aironusa.com/ems-products/ems-pneuton-
model-s/)
276 S.C. LeCroy

Photograph Courtesy of Airon Corporation

Oxylog® 3000 Plus (Drager Medical; http://www.draeger.com/sites/en_aunz/

Pages/Hospital/Oxylog-3000-plus.aspx)
Uni-Vent® 731 Series Model EMV + ® and AEV® (Zoll®; http://www.impactii.
com/Vents.html)
ReVel® Portable Critical Care Ventilator (CareFusion; http://www.carefusion.com/
medical-products/respiratory/ventilation/revel-ventilator-system/)

Work Cited
1. Daily J, Wang H. Noninvasive positive pressure ventilation: resource document for the National
Association of EMS Physicians position statement. Prehosp Emerg Care. 2011;15(3):432–8.
2. Kosowsky J, Stephanides S, Branson R, Sayre M. Prehospital use of continuous positive airway
pressure (CPAP) for presumed pulmonary edema: a preliminary case series. Prehosp Emerg
Care. 2001;5(2):190–6.
3. Glover GW, Fletcher SJ. Assessing the performance of the Whisperflow continuous positive
airway pressure generator: a bench study. Br J Anaesth. 2009;102(6):875–81.

Resources

Branson R, Johannigman J. Pre-hospital oxygen therapy. Respir Care. 2013;58(1):86–97.

Eisenman A, Rusetski V, Sharivker D, Avital RN. Role of the Boussignac continuous positive pres-
sure mask in the emergency department. Israeli J Emerg Med. 2008;8(2):6–11.
Fisher GC. The Downs’ adjustable flow generator. Anaesthesia. 1988;43:766–9. The Association
of Anaesthetists of Gt Britain and Ireland.
Hubble M, Richards M, Jarvis R, Millikan T, Young D. Effectiveness of prehospital continuous
positive airway pressure in the management of acute pulmonary edema. Prehosp Emerg Care.
2006;10(4):430–9.
Mosesso V, Dunford J, Blackwell T, Griswell J. Prehospital therapy for acute congestive heart
failure: state of the art. Prehosp Emerg Care. 2003;7(1):13–23.
Simpson PM, Bendall JC. Prehospital non-invasive ventilation for acute cardiogenic pulmonary
oedema: an evidence-based review. Emerg Med J. 2011;28(7):609–12.
Templier F, Dolveck F, Baer M, Chauvin M, Fletcher D. ‘Boussignac’ continuous positive airway
pressure system: practical use in a prehospital medical care unit. Eur J Emerg Med.
2003;10:87–93.
Intra-hospital Transport of Patients
during Noninvasive Ventilatory Support: 32
Key Topics

Antonio Javier Domínguez Petit and Antonio M. Esquinas

Contents
32.1 Introduction ................................................................................................................. 278
32.2 Discussion and Analysis ............................................................................................. 278
Appendix 1: Inter-hospital Transport of Patients Receiving NIV Algorithm ........................ 282
References .............................................................................................................................. 283

Abbreviations

ECG Electrocardiography
ED Emergency department
ICU Intensive care unit
IMV Invasive mechanical ventilation
NIV Noninvasive mechanical ventilation

A.J. Domínguez Petit, MD, Ph (*)

Emergency Department of the General Hospital, Hospital Universitario Virgen del Rocío,
Seville, Spain
e-mail: [email protected]
A.M. Esquinas, MD, PhD, FCCP
Intensive Care and Non Invasive Ventilatory Unit, Hospital Morales Meseguer, Murcia, Spain
International School of Non-invasive mechanical Ventilation, Murcia, Spain
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 277

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_32
278 A.J.D. Petit and A.M. Esquinas

32.1 Introduction

Noninvasive mechanical ventilation (NIV) has proven to be effective in patients

with acute respiratory failure of various etiologies. Its application in both the
pre-hospital and hospital settings decreases the need for invasive mechanical
ventilation (IMV) and admission to the intensive care unit (ICU), especially in
selected cases of acute cardiogenic pulmonary edema or chronic obstructive
pulmonary disease exacerbations [1, 2], but evidence is growing regarding its
efficacy in different conditions, such as pulmonary contusion, pneumonia, and
near-fatal drowning [3]. In recent years, NIV has gained a growing role in emer-
gency departments (EDs) and their acute care areas, as there is a greater under-
standing of the practice and evidence of its benefits in selected groups of
patients.
Intra-hospital transports of noninvasively ventilated patients usually are made (1)
from the ED to the ICU or other hospital wards with experience in handling NIV
(e.g., the respiratory intermediate care unit), (2) between the ED and the radiology
facilities, and (3) between different areas of these unit [4, 5]

32.2 Discussion and Analysis

The architecture of hospitals and the location of the different destinations signifi-
cantly affect the time spent in performing such movements and exposure to
potential adverse effects during treatment [5–7]. Ideally, the transfer of a patient
on NIV to another hospital area should not exceed 10–15 min once the circuit
transfer is activated. Some recommendations on some specific points may be
useful.

Staff All patients on NIV should be accompanied by at least one physician and
one nurse, well trained in airways management and cardiopulmonary resuscitation,
and one technician or medical transport guard. It is, of course, of pivotal impor-
tance that the personnel involved in the transfer are competent with noninvasive
ventilatory support modalities, accessories, and interfaces and will recognize any
problems and act accordingly. The team receiving the patient should be warned in
advance, to allow sufficient staff available to implement the transfer to bed, prepare
the NIV system change (if necessary), and minimize the occurrence of complica-
tions. On arrival at the receiving unit, there must be a direct communication
between the accompanying team and the one expected to assume responsibility for
the patient’s care after the transport is complete. A specifically dedicated record
reporting the patient’s medical history, treatment initiated, ventilator settings, vital
signs, and major events suffered during transport should be part of the entire medi-
cal file. The authors strongly suggest the implementation of a clear clinical flow-
chart, readily accessible to all staff members involved, reflecting their role in the
transfer process.
32 Intra-hospital Transport of Patients during Noninvasive Ventilatory Support 279

Equipment Equipment should be light, strong, and able to be easily transported

through corridors and lifts. A wide range of devices capable of administering NIV
is available. We recommend devices specifically designed for NIV because there
is less trouble in administering noninvasive support. To minimize the problems
related to the transfer of devices, it is important to use dedicated equipment, even-
tually placed on stands with wheels or directly attached to the bed for easy
movement.

Should the duration of the transport be extended, as in the case of multiple

imaging evaluation, a key consideration is the provision of adequate battery and
oxygen supply. It is therefore crucial to check the status of the battery and the
oxygen cylinders before moving the patient. It is also necessary to carry the elec-
trical connections of the devices and appropriate extensions to connect the venti-
lator to the wall oxygen jacks. NIV and transport ventilators generally have an
internal battery life of 5 h or longer. The authors strongly recommend that the
operators involved in the transfer know in-depth the functions and settings of the
ventilator in use.
Masks and interfaces deserve separate consideration. Different types of inter-
faces have been validated for NIV. While ventilator modalities are set to a specific
clinical goal, the choice of a particular interface affects prevention of leaks and
patient comfort and is closely related to the success of the technique [8]. Therefore,
in the absence of specific evidence on this subject, it seems logical that a patient
who is well adapted on a particular interface before being transferred should con-
tinue on NIV with the same interface during the transfer, which could also reduce
hospital costs. This peculiar requirement must be matched to the features of the
ventilator system adopted for the transport. In any case, it is important to ensure a
proper fit of the mask before the transfer and to check it continuously during the
transfer because accidental displacements and air leaks frequently occur in this
setting.
Although a discussion of ventilator modalities is beyond the scope of this chap-
ter, during the transport it is important to maintain the patient on the same parame-
ters that he or she is well adapted to. This may require a correction of the settings
when switching a patient from a different ventilatory algorithm so that the same
level of ventilatory support is maintained. For this and the aforementioned reasons,
as a general rule, one should avoid replacing a NIV system, as this may result in the
loss of the benefit obtained.
Finally, although thorough stabilization of the patient must precede the decision
to transfer (see below), one must be prepared for the eventuality of an abrupt wors-
ening of the patient’s clinical condition during the transfer. Therefore, adequate
instrumentation and medications for advanced airways control and cardiopulmo-
nary resuscitation must be part of the equipment for intra-hospital transports.

Monitoring Patient monitoring during transfers should address the main potential
complications described for this condition (Table 32.1) [9, 10]. During the transport,
280 A.J.D. Petit and A.M. Esquinas

Table 32.1 Major complications and contraindications during intra-hospital transport

Major complications:
1. The loss of PEEP/CPAP can lead to hypoxemia
2. The changes in the patient’s position may involve hypotension and hypoxemia
3. Arrhythmias associated with transporting critically ill
4. Malfunction of the equipment used, which can result in loss of patient monitoring or
collecting of incorrect variables
5. The movement can cause the disconnection of ventilatory support and compromise the
patient’s respiratory function
6. The movement may cause the accidental withdrawal of catheters and intravenous
administration interruption medications which the patient is receiving
Major contraindications for transferring patients on NIV:
1. Inability to provide adequate oxygenation and ventilation during transport through the
chosen NIV system
2. Inability to maintain adequate hemodynamics during transport (hemodynamic instability,
shock, unstable ischemic heart disease, arrhythmias, poorly controlled)
3. Inability to monitor the patient’s cardiopulmonary status during transfer
4. Inability to maintain control of the airway during transport (respiratory arrest, upper
gastrointestinal bleeding, excessive secretions, airway obstruction, increased risk of
pulmonary aspiration, severe encephalopathy with GCS <10 points, burn, trauma, or facial
surgery)
5. Shortage of staff to perform the transfer under optimal conditions
6. Insufficient knowledge in the transfer of critically ill members appointed to do
7. Lack of communication and coordination between the various departments involved

NIV should be monitored objectively and subjectively (improvement of dyspnea and

comfort). Consequently, the authors recommend the provision of the following points:
1. Continuous electrocardiography (ECG) tracing
2. Intermittent noninvasive blood pressure
3. Continuous oxygen saturation
4. Respiratory rate and exhaled tidal volumes
5. Patient-ventilator synchrony (physical signs or pressure and flow curves)
6. Clincal surveillance for the entire duration of the transfer, with particular atten-
tion to the level of consciousness, auscultation, inspection, and detection of dis-
placement of the mask and air leaks

Selection of Patients to be Transported on NIV Hemodynamic stability, sponta-

neous breathing, and the ability to protect the airways are definite requirements for the
application of NIV. Patients who have only a partial response to the technique or those
in whom the indication for a NIV approach is debatable, are poor candidates to be
transferred on NIV. Patients who display poor synchronization with the system or
continue to be severely dyspneic despite efforts to optimize ventilator settings, along
with those who are agitated and uncooperative or have severe and difficult-to-handle
bronchorrhea, require further evaluation and to be stabilized before transfer. Table 32.2
summarized the key major elements of intra-hospital transport of patients on NIV.
32 Intra-hospital Transport of Patients during Noninvasive Ventilatory Support 281

Table 32.2 Key major elements and equipment to intra-hospital transport

1. Ensure proper indication of NIV
2. Assess the risks and benefits to the patient of alternatives (high-flow oxygen therapy, IMV)
3. Decide whether or not to maintain NIV
4. Equipment and practical checking:
(a) Before starting the transfer, verify the availability and correct functioning of intubation,
ventilation bag, and proper equipment to perform intubation if the patient’s respiratory
status deteriorates
(b) Presence of a source of oxygen with sufficient volume for the secured transfer
(c) Presence of a portable monitor that provides ECG monitoring and heart rate and allows
measurement of arterial pressure
(d) Capacity to perform pulse oximetry (always) and capnography (desirable)
(e) If a non-mechanical NIV device is used (continuous positive airway pressure (CPAP)
high-flow devices):
(i) Check the correct operation of the manometer to maintain desired level of CPAP:
1. Checking that the flowmeter is suitable, that is, can provide 30 l/min instead of
15 l/min to get the virtual CPAP valve effect
2. Evaluating and adjusting the position of the interface and the correct connection of
the hose, filter, and oxygen source
(ii) If a mechanical NIV device is used:
1. Check the battery charge status
2. Monitor tidal volume, respiratory rate, level of positive end-expiratory pressure,
leaks, and the FiO2 system provided
3. Set system alarms
4. Evaluate the tightness of interfaces and the correct connection between the different
parts
(f) Appropriate medication (sedatives, opioids, nitrites, etc.)

Key Major Recommendations

• Conduct a comprehensive assessment of the patient and proceed to stabi-
lize the patient prior to transfer, assuring perfect coordination between the
various teams participating in the transfer, avoiding delays and limiting the
exposure of the patient to the possibility of adverse events.
• Provide a clear flowchart (printed or digital), readily accessible to all staff,
reflecting the role of every member of the transport team.
• Define the monitoring equipment necessary to carry out the transport.
• Know in-depth the characteristics and functioning of the devices in use
during transport, providing an adequate training of staff on NIV, airways
management, and cardiopulmonary resuscitation.
• Review the problems encountered during transport to avoid their repetition
in the future (production of records and audits), and establish periodical
retraining programs on NIV for staff.
282 A.J.D. Petit and A.M. Esquinas

Appendix 1: Inter-hospital Transport of Patients Receiving NIV

Algorithm

Decission to Transfer patient on NIV to another hospital

Contrast the risks and benefits of transfer

Assessing patient's condition. Is it stable?

Yes No

· Choose receiver hospital, assess and consider: Assess and provide care measures to ensure:
a) Distance to receiver hospital. a) Airway safe
b) Available Resources (staff, equipment). b) Endovenous access
c) Bed availability. c) Appropriate fluid resuscitation
.
d) Patient choice. d) Appraisal: Laboratory findings, Xray.
· Get on to the physician receiving the patient. e) Keep on treatment.
· Does the transfer has been accepted? f) To consider any other mode of
ventilatory support.

No
Yes

· Keep on provenance
· Obtain informed consent of the family. hospital management.
· Select transfer way: overland or overhead. · Optimize current plan.
a) Costs
b) Patient severity
c) Distance
d) Environmental conditions (weather)
· Mobilising necessary staff, equipment and drugs.
· Nurse to nurse report to expedite reception.
· Photocopy medical records to expedite reception.

· Start transport:
o Sedate patient if required.
o Fasten if required
· Start NIV support protocol.
· Clinical record during transport.
· Start monitoring during transport.
· Follow performance protocols depending on events.
· Contact medical head if necessary.
32 Intra-hospital Transport of Patients during Noninvasive Ventilatory Support 283

References
1. Esquinas RAM. Desarrollo de la VMNI: del reto clínico a la evidencia científica. In: Esquinas
RA, editor. Tratado de ventilación mecánica no invasiva. Madrid: Grupo Aula Médica SL;
2006. p. 3–5.
2. Esquinas R, et al. Guía Esencial de Metodología en Ventilación no Invasiva. Editorial Médica
Panamericana; 2010.
3. Carrillo A, Gonzalez-Diaz G, Ferrer M, Martinez-Quintana ME, Lopez-Martinez A, Llamas
N, Alcazar M, Torres A. Non-invasive ventilation in community-acquired pneumonia and
severe acute respiratory failure. Intensive Care Med. 2012;38(3):458–66.
4. Fanara B, Manzon C, Barbot O, Desmettre T, Capellier G. Recommendations for the intra-
hospital transport of critically ill patients. Crit Care. 2010;14:R87.
5. European Society of Intensive Care Medicine. Update patient transport skills and techniques.
2011. Available at: http://pact.esicm.org/media/Patient%20transportation%201Feb2011%20
final.pdf. Consultado el 10.06.2011.
6. Warren J, Fromm R, Orr R, Rotello L, Horst M. Guidelines for the inter- and intrahospital
transport of critically ill patients. Crit Care Med. 2004;32:256–62.
7. Schwebel C, Clec’h C, Magne S, et al. Safety of intrahospital transport in ventilated critically
ill patients: a multicenter cohort study*. Crit Care Med. 2013;41:1919–28.
8. Storre JH, Bohm P, Dreher M, Windisch W. Clinical impact of leak compensation during non-
invasive ventilation. Respir Med. 2009;103:1477–83.
9. Gillman L, Leslie G, Williams T, et al. Adverse events experienced while transferring the criti-
cally ill patient from the emergency department to the intensive care unit. Emerg Med J.
2006;23:858–61.
10. Papson JPN, Russell KL, Taylor D. Unexpected events during the intrahospital transport of
critically ill patients. Acad Emerg Med. 2007;14:544–7.
 Part IV
Hospital Critical Care Applications:
Acute Chronic Exacerbations
Respiratory Mechanics in COPD Patients
Who Failed Noninvasive Ventilation 33
Vittorio Antonaglia, Massimo Ferluga,
and Umberto Lucangelo

Contents
33.1 Introduction ................................................................................................................. 287
33.2 Discussion ................................................................................................................... 288
Conclusions ............................................................................................................................ 291
References .............................................................................................................................. 292

33.1 Introduction

First-line intervention with noninvasive positive pressure ventilation (NPPV) can ade-
quately treat acute respiratory failure in a significant number of patients, in particular
those with an acute exacerbation of chronic obstructive pulmonary disease (COPD),
but in some instances NPPV treatment fails [1, 2]. These patients failed NPPV essen-
tially for respiratory reasons or, after an initial rapid improvement of blood pH and gas
exchange, they may require tracheal intubation and sedation for intolerance of the face
mask or claustrophobia, due to the almost continuous application of NPPV. The latter
can be considered as responders to NPPV in terms of improvement in gas exchange
and reduction of respiratory rate and dyspnea. In these patients, the main cause of
subsequent intubation is increased ventilation/perfusion mismatching, which is ampli-
fied by the decrease in mixed venous partial pressure of oxygen resulting from greater
oxygen consumption due to the increased work of the respiratory muscles subsequent
to lung dynamic hyperinflation. The partial dissipation of inspiratory pressure in the
NPPV device, which thwarts the patient-machine synchrony, a delay in pressurization

V. Antonaglia, MD (*) • M. Ferluga, MD • U. Lucangelo, MD, PhD

Laboratory of Respiratory Biomechanics, Department of Anesthesia and Intensive Care,
Cattinara Hospital, University of Trieste, Strada di Fiume 447, Trieste I-34139, Italy
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 287

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_33
288 V. Antonaglia et al.

of the interface that is incompatible with the high inspiratory drive, and difficulties in
managing copious tracheal secretions can prevent NPPV from effectively increasing
alveolar ventilation and improving gas exchange.
The elevated mechanical load and, particularly, the high intrinsic positive end-
expiratory pressure (PEEPi) were found to be the major determinants of COPD
patients’ ventilator dependence [3]. In this line, a correlation between the severity of
COPD and the ratio between dynamic and static intrinsic positive end-expiratory
pressure (PEEPi,dyn/PEEPi,stat) has been reported in mechanically ventilated
patients [4]. PEEPi,stat represents the average PEEPi of the pulmonary regions with
different time constants reached after a sufficient equilibration time between
regional alveolar and airway opening pressure has elapsed. PEEPi,dyn corresponds
to the lowest PEEPi resulting from the lung region with the shortest time constant,
and will underestimate PEEPi,stat in the presence of significant time constant
inequalities [4]. As a result, the discrepancy between PEEPi,dyn and PEEPi,stat has
been introduced as an index of pulmonary mechanical inequality, reflecting an inho-
mogeneous time constant distribution and/or viscoelastic behavior [5].

33.2 Discussion

PEEPi,dyn is believed to represent the “best” mechanical condition in a sick inhomo-

geneous lung in relation to an imposed ventilatory pattern; the static intrinsic PEEP
reflects the mean time constant of the system [4]. During artificial ventilation, the
values of PEEPi must be taken into account; naturally, they should tend to decrease
with the improvement in respiratory mechanics. In patients who failed NPVV for
respiratory causes, the trend to find higher values of PEEPi,stat at zero end-expiratory
pressure (ZEEP) reflects a more important lung hyperinflation, and the lower value
of PEEPi,dyn/PEEPi,stat represents a potential increase in the inhomogeneous time
constant distribution and/or viscoelastic behavior [5]. Indeed, a small value of
PEEPi,dyn/PEEPi,stat indicates an inhomogeneous system [4], whereas the closer
the ratio is to unity, a more homogeneous gas distribution is obtained.
In a group of COPD patients with acute exacerbation, a mean value of PEEPi,dyn
of 5.3 cmH2O during noninvasive pressure support ventilation was reported [3]. In a
recent investigation, lower values of PEEPi,dyn under zero end-expiratory pressure
(ZEEP) were found, but this difference can be attributed to the technique of measure-
ment used during mechanical ventilation [6]. Moreover, Appendini et al. [3] found
that the diaphragmatic effort was reduced by the use of low-level external PEEP (80–
90 % of PEEPi,dyn). During noninvasive ventilation, Rossi et al. [7] used similar
values of external PEEP, obtaining an improvement in gas exchange without either
changes in mechanical load or hemodynamic effects. In the study of Antonaglia et al.
[6], PEEPi,dyn/PEEPi,stat increased after external PEEP application in line with the
improvement in PaO2/FiO2 in both groups of patients, but the difference between them
remained significant. Thus, external PEEP improved gas exchange, reducing the
inequalities between the time constants present in each group of patients [7], but it was
not able to reduce the differences between the groups. In fact, in the presence of
33 Respiratory Mechanics in COPD Patients Who Failed Noninvasive Ventilation 289

external PEEP, PEEPi,stat remained substantially unchanged, reflecting potential flow

limitation, whereas the PEEPi,dyn increased in both groups, indicating a reduction in
inhomogeneous time constant distribution and/or viscoelastic behavior.
Many methods have approached gas distribution during invasive mechanical
ventilation in heterogeneous lung using static and dynamic computed tomography
scanning and different experimental lung injury models, but the respiratory mechan-
ical modifications induced by NPPV have been scantly studied. Diaz et al. [8], using
the multiple inert gas elimination technique, found that the improvement in respira-
tory blood gases during NPPV was essentially caused by a higher alveolar ventila-
tion and not an improvement in the ventilation/perfusion relationship. In the study
of Antonaglia et al. [6], the patients who failed NPPV for respiratory causes or
intolerance presented similar elastic and resistive loads, and intolerant patients can
be considered as responders to NPPV in terms of improvement in gas exchange and
reduction in respiratory rate and dyspnea. It follows that the less important lung
mechanical inhomogeneities in the latter, as reflected by a higher PEEPi,dyn/
PEEPi,stat, can be considered responsible for the improvement in arterial blood
gases. In this group of patients, pH and PaCO2 presented a remarkable trend of
improvement with respect to the start values, whereas, in the group of patients who
failed NPPV for respiratory reasons, the pH remained unchanged and the reduction
in PaCO2 was slight. Before intubation, only pH was different between the two
groups. PaCO2 levels were also different, but the sample size was probably not large
enough to make this difference statistically significant.
Moreover, in the group of patients who responded to NPPV but failed because
of intolerance, PEEPi,dyn/PEEPi,stat was lower when the use of NPPV was shorter
and increased nonlinearly when the duration of NPPV was augmented (Fig. 33.1).
After a limited period of continuous use of NPPV, a sequential use of NPPV was
applied with different modalities. In a clinical trial where NPPV was proposed as
an alternative to invasive mechanical ventilation (in patients with similar clinical
characteristics to those of Antonaglia et al. [6]), the patients successfully treated
with NPPV received it continuously for at least 18 h/day during the first 48 h [2].
In another study, the control group treated with mask NPPV received a mean value
of 30 h of NPPV before allowing sequential use [9]. According to Fig. 33.1,
PEEPi,dyn/PEEPi,stat increased and become stable after about 30 h of continuous
NPPV. Thus, a potential relationship between the improvement in PEEPi,dyn/
PEEPi,stat and the duration of NPPV, applied as first-line intervention in patients
with acute severe COPD exacerbation, is conceivable. In similar clinical condi-
tions, the application of NPPV beyond 30 h should not promote further decrease in
pulmonary mechanical inequality, essentially inducing intolerance and potential
NPPV failure. In the study of Antonaglia et al. [6], 35 % of intolerant patients
failed NPPV after 30 h. Therefore, after this period it can be useful for the clinician
to implement short periods of NPPV with other strategies like oxygen therapy and
chest physiotherapy.
Another important finding in the latter study was that the time dependency disap-
peared after the measurements were made at PEEP, which was able to reduce the
differences in time constants of lung districts. External PEEP changed the value of
290 V. Antonaglia et al.

0.5

0.4
PEEPi, dyn/PEEPi,stat

0.3

0.2

0.1

0 10 20 30 40 50
Time (hours)

Fig. 33.1 Relationship between duration of NPPV and the ratio between dynamic and static mea-
surements of intrinsic PEEP (PEEPi,dyn/PEEPi,stat) at ZEEP (●) and PEEP (Δ) in patients who
failed NPPV because of intolerance

PEEPi,dyn in both groups in comparison to ZEEP, while the PEEPi,stat remained

substantially unchanged. The small difference between dynamic and static PEEP
did not permit assessment of the relationship between duration of NPPV and
PEEPi,dyn/PEEPi,stat.
In the first day of treatment of patients with severe exacerbation of COPD it may
be necessary to apply NPPV continuously, and intolerance to the interface may be a
complication. A subgroup of patients, after an initial rapid improvement in blood
pH and gas exchange, may require tracheal intubation and sedation owing to intoler-
ance to the face mask. Conti et al. [1] reported a percentage of success of NPPV by
facial mask of 38 %, similar to those found by Squadrone et al. [2]. Among the
patients who failed NPPV, 46 % failed due to intolerance [9].
In the study of Antonaglia et al. [6], respiratory mechanical parameters were
assessed within 6 h of invasive mechanical ventilation under the same conditions,
that is, they were sedated, paralyzed, and ventilated with a similar ventilatory set-
ting and PEEP was used during NPPV. The mechanical parameters were measured
again after a short period of stabilization at ZEEP and were within the range reported
in the literature pertaining to COPD patients [7].
Peak tracheal pressure (Ptr,max) was followed by a rapid initial drop in Ptr (Pi)
and by a slow decay of Ptr to an apparent plateau value. This plateau pressure,
recorded 5 s after the occlusion, was taken to represent the static end-inspiratory
elastic recoil pressure of the respiratory system (Pst). By dividing (Ptr,max – Pi) by
the flow (V’) immediately preceding the occlusion, the Newtonian resistance of the
33 Respiratory Mechanics in COPD Patients Who Failed Noninvasive Ventilation 291

respiratory system (Rint) was obtained. The static elastance of the respiratory system
(Est) was computed by dividing the corresponding values of (Pst – PEEPi,stat – PEEP)
by tidal volume (VT). ∆P was calculated as (Pi – Pst) and represents the pressure dis-
sipated against viscoelastic properties and mechanical inhomogeneities in the respi-
ratory system. We considered the change in end-expiratory lung volume (ΔEELV)
relative to the relaxation volume of the respiratory system [6].
ΔP is an indicator of the degree of inhomogeneous time constant distribution
and/or viscoelastic behavior within the respiratory system, and it also encompasses
the pressure used to overcome the viscoelastic properties of the system. In this line,
ΔP tended to be lower in patients intubated owing to intolerance to NPPV than in
those who failed due to respiratory causes. In the study of Antonaglia et al. [6],
PEEPi,dyn/PEEPi,stat was found to be inversely correlated with ΔP, thus support-
ing the aforementioned notion of the existence of more important mechanical
inequalities in the lungs of these patients.
The methods for approaching gas distribution during noninvasive mechanical
ventilation present some limitations. Firstly, the measurements were usually
made in sedated, paralyzed patients and the results, therefore, must be cau-
tiously extended to spontaneously breathing patients. Secondly, the increase in
PEEPi,dyn with external PEEP reflects the mode of measurement of dynamic
PEEPi (value of tracheal pressure at zero flow). If the measurement of
dynamic PEEPi were made using esophageal pressure, this increase could pos-
sibly be smaller. Moreover, the data obtained by partitioning the respiratory
mechanics by esophageal pressure would be useful for accurate interpretation of
our data. If the measures were performed in paralyzed patients and no signifi-
cant pleural effusions or parietal abnormalities were found in chest X-rays and
no obese patients were studied, we believe that the analysis could be sufficiently
appropriate.

Conclusions
The patients who failed NPPV owing to intolerance had a smaller amount of
inhomogeneous time constant distribution and/or viscoelastic behavior, but simi-
lar impairment of the mechanical properties as the subjects requiring invasive
ventilation due to respiratory reasons. In the former patients, the degree of pul-
monary mechanical inequality was correlated with the duration of NPPV, provid-
ing a hypothetical explanation for the effects of NPPV on the lungs of patients
with COPD.

Key Major Recommendations

• NPPV can fail for different reasons related to gas exchange impairment or
intolerance.
• The patients who failed NPPV because of intolerance present a smaller
mechanical inequality, expressed as PEEPi,dyn/PEEPi,stat.
• PEEPi,dyn/PEEPi,stat is correlated with the duration of NPPV.
292 V. Antonaglia et al.

References
1. Conti G, Antonelli M, Navalesi P, et al. Noninvasive vs. conventional mechanical ventilation in
patients with chronic obstructive pulmonary disease after failure of medical treatment in the
ward: a randomized trial. Intensive Care Med. 2002;28:1701–7.
2. Squadrone E, Frigerio P, Fogliati C, Gregoretti C, Conti G, Antonelli M, Costa R, Baiardi P,
Navalesi P. Noninvasive vs invasive ventilation in COPD patients with severe acute respiratory
failure deemed to require ventilatory assistance. Intensive Care Med. 2004;30:1303–10.
3. Appendini L, Purro A, Patessio A, Zanaboni S, Carone M, Spada E, Donner CF, Rossi
A. Partitioning of inspiratory muscle workload and pressure in ventilator-dependent COPD
patients. Am J Respir Crit Care Med. 1996;154:1301–9.
4. Maltais F, Reissmann H, Navalesi P, Hernandez P, Gursahaney A, Ranieri VM, Sovilj M,
Gottfried SB. Comparison of static and dynamic measurements of intrinsic PEEP in mechani-
cally ventilated patients. Am J Respir Crit Care Med. 1994;150:1318–24.
5. Koutsoukou A, Bekos B, Sotiropoulou C, Koulouris NG, Roussos C, Milic-Emili J. Effects of
positive end-expiratory pressure on gas exchange and expiratory flow limitation in adult respi-
ratory distress syndrome. Crit Care Med. 2002;30:1941–9.
6. Antonaglia V, Ferluga M, Capitanio G, et al. Respiratory mechanics in COPD patients who
failed non-invasive ventilation: role of intrinsic PEEP. Respir Physiol Neurobiol.
2012;184:35–40.
7. Rossi A, Santos C, Roca J, Torres A, Felez MA, Rodriguez-Roisin R. Effects of PEEP on VA/Q
mismatching in ventilated patients with chronic airflow obstruction. Am J Respir Crit Care
Med. 1994;149:1077–84.
8. Diaz O, Iglesia R, Ferrer M, Zavala E, Santos C, Wagner PD, Roca J, Rodriguez-Roisin
R. Effects of noninvasive ventilation on pulmonary gas exchange and hemodynamics during
acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit
Care Med. 1997;156:1840–5.
9. Antonelli M, Pennisi MA, Pelosi P, Gregoretti C, Squadrone V, Rocco M, Cecchini L,
Chiumello D, Severgnini P, Proietti R, Navalesi P, Conti G. Noninvasive positive pressure ven-
tilation using a helmet in patients with acute exacerbation of chronic obstructive pulmonary
disease. Anesthesiology. 2004;100:16–24.
Impact of Comorbidities on Noninvasive
Mechanical Ventilation Response: Key 34
Practical Implications

Szymon Skoczyński

Contents
34.1 Introduction ................................................................................................................. 294
34.2 Discussion and Analysis ............................................................................................. 295
34.2.1 Chronic Respiratory Failure .......................................................................... 295
34.2.2 Acute Respiratory Failure ............................................................................. 296
34.2.3 Comorbidities and Age Groups ..................................................................... 297
34.2.4 Facial Oronasal Comorbidities and Airway Clearance ................................. 298
34.2.5 Metabolic Comorbidities and Obesity........................................................... 299
Conclusion ............................................................................................................................. 299
References .............................................................................................................................. 300

Abbreviations

ALS Amyotrophic lateral sclerosis

ARF Acute respiratory failure
CAP Community-acquired pneumonia
CHS Central hypoventilation syndromes
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
CRF Chronic respiratory failure
DNI Do not intubate

S. Skoczyński, MD, PhD

Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia,
Medyków 14 Street, Katowice 40-752, Poland
Institute of Occupational Medicine and Environmental Health, Kościelna 13 Street,
Sosnowiec 41-200, Poland
e-mail: [email protected], [email protected]

© Springer International Publishing Switzerland 2016 293

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_34
294 S. Skoczyński

EPAP Expiratory positive airway pressure

FEV1 Forced expiratory volume in 1 second
FiO2 Fraction of inspired oxygen
ICU Intensive care unit
IPAP Inspiratory positive airway pressure
NIV Noninvasive mechanical ventilation
OHS Obesity hypoventilation syndrome
OSA Obstructive sleep apnea
PaO2/FiO2 Ratio of arterial oxygen partial pressure to fractional inspired oxygen
PCF Peak cough flow
PCO2 Partial pressure of carbon dioxide
PEEP Positive end-expiratory pressure
PS Pressure support
PVT Peak velocity time
RF Respiratory failure
RR Respiratory rate
S/T Spontaneous over timed mode
SCI Spinal cord injuries
T Timed mode
TV Tidal volume

34.1 Introduction

Noninvasive mechanical ventilation (NIV) is a universally recognized, effective

method for type-2 respiratory failure (RF) treatment. Ventilator settings and treat-
ment success rates vary, depending on machine configuration, provider experience,
patient compliance, and, last but not least, the underlying condition and/or overlap-
ping diseases. NIV is accepted by evidence-based medicine as a good treatment
option for the following chronic diseases: amyotrophic lateral sclerosis (ALS), cen-
tral hypoventilation syndromes (CHS), chronic obstructive pulmonary disease
(COPD), kyphoscoliosis, obesity hypoventilation syndrome (OHS), Duchenne
muscular dystrophy, and other muscular dystrophies and myopathies, as well as for
patients with post-polio syndrome [1] and after spinal cord injuries (SCI) (usually
level A of evidence). In acute respiratory failure (ARF), NIV is indicated in COPD
exacerbations with pH < 7.35 (acute or acute-on-chronic respiratory failure), pneu-
monia in immunocompromised patients, cardiogenic pulmonary edema disqualified
from interventional treatment, high-risk recurrent ARF after planned extubation or
weaning from mechanical ventilation, ARF in declared “do not intubate” patients,
and in acute respiratory deteriorations of patients on NIV due to chronic conditions
(usually level A of evidence) [2].
Along with increasing knowledge and NIV development, the number of clinical
indications proved by guidelines is constantly rising. On the other hand, interna-
tional guidelines are usually disease specific; therefore, in clinical practice, it may
be difficult to apply disease-specific ventilator settings and choose patients ade-
quately. Recently, especially in aging Western populations, overlapping of frequent
34 Impact of Comorbidities on Noninvasive Mechanical Ventilation Response 295

diseases, such as COPD, obstructive sleep apnea (OSA), OHS, and/or CHS second-
ary to cardiovascular complications, is often observed, but there is still insufficient
high-level evidence on precise NIV applications and settings. Therefore, in overlap-
ping diseases, the most important advice is watchful observation of the patient’s
respiratory pattern, including rate and depth of use of additional respiratory mus-
cles, as well as careful monitoring of measured variables such as minute ventilation,
respiratory rate (RR), tidal volume (TV), and arterial blood gases in case of hospi-
talized patients. If possible, it is recommended to preset TV at 6-8 ml/kg (ideal body
weight) in all adult patients, if different values are not indicated on the basis of
pulmonary functional tests (spirometry and/or body plethysmography). As stated
above, it is important to remember that overlapping is poorly addressed in the litera-
ture but may be frequently observed in real life, such as in the case of COPD and
OSA/OHS overlapping, in which, if it is well tolerated by the patient and not previ-
ously determined by other anatomical and/or pathophysiological factors, pressure
support (PS) should be primarily set on the basis of COPD guidelines, and expira-
tory positive airway pressure (EPAP) set on the basis of previous continuous posi-
tive airway pressure (CPAP) titration.

34.2 Discussion and Analysis

34.2.1 Chronic Respiratory Failure

Pure COPD has been accepted as one of the leading indications for home NIV [3].
With aging, a substantial number of patients with COPD may suffer from stroke or
other cardiovascular complications. In these patients, there is a great likelihood of
clinically significant bulbar syndrome. Therefore, it must be emphasized that,
besides COPD-typical NIV settings, cough-assist devices may have to be imple-
mented, which is not routinely done in patients with COPD. In these patients, maxi-
mal inspiratory positive airway pressure (IPAP) may be limited by the risk secondary
to air-trapping gastric extension, which, if not considered in ventilator settings, can
lead to increased risk for regurgitation and aspiration.
Another important comorbidity that may increase risk of death in patients with
COPD is lower respiratory tract infections such as severe COPD exacerbation and/
or pneumonia. Although these clinical situations are accepted as NIV susceptible,
the increased risk might be caused by delay in medical consultation and antibiotic
administration, resulting from the patient’s self-assurance. Another possible sce-
nario, which should also be taken into account, is chest injury complicated by pneu-
mothorax or spontaneous pneumothorax. In such situations, NIV application
without chest tube insertion, even in a minor lung injury, may result in tension
pneumothorax and death.
Chest deformation, such as scoliosis in the course of neuromuscular diseases, is not
a real overlapping disease but rather a disease manifestation or complication, which
should be taken into account in home treatment. In these patients, TV should be accord-
ingly adjusted, from volumes calculated initially on the basis of ideal body weight, to
smaller values adjusted according to slowly decreasing total lung capacity.
296 S. Skoczyński

34.2.2 Acute Respiratory Failure

In most clinical guidelines, NIV patients undergoing acute and chronic respira-
tory failure are subject to single organ failure (lung/skeletal frame/respiratory
muscle/ventilatory central drive). Those disease-related groups are well defined
and should be treated according to disease-specific guidelines. In the course of
these chronic conditions, overlapping diseases are primarily lower respiratory
tract infections. The additional NIV settings are not yet sufficiently described in
the literature, but it is usually underlined that NIV is effective and provides sur-
vival benefit. To deal with this problem, it is recommended that NIV settings be
adjusted according to the severity of clinical disease condition (basic indication or
overlapping disease). In case of lobar pneumonia or pulmonary cardiogenic
edema, to improve alveolar recruitment and, therefore, oxygenation, it is sug-
gested to increase positive end-expiratory pressure/ expiratory positive airway
pressure (PEEP/EPAP) above standard COPD/OHS overlapping baseline (5–10
cmH2O), with or without inspiratory time prolongation. In patients with bronchial
pneumonia or bronchial obstruction, such as in cases of acute bronchitis or COPD
acute exacerbation, it is recommended to increase the driving pressure, which
means increasing PS or IPAP above baseline value. In acute-on-chronic and, more
importantly, in ARF, close patient monitoring is vital. In case of observed NIV
therapy ineffectiveness 4 h after treatment onset, urgent intubation and transfer to
the intensive care department/intermediate care department should be undertaken,
especially because intubation after initial NIV failure is a greater risk factor for
death than direct intubation without a preceding NIV trial [4]. This might be even
of greater importance in patients with overlapping diseases, and, therefore, it
should be taken under consideration for appropriate patient selection when con-
sidering NIV treatment.
A large group of “good candidates” in acute setting are patients with “do not
intubate” (DNI) orders, however, in this group the most common clinical indication
is severe COPD complicated by disease exacerbation or overlapping diseases such
cancer (particularly lung cancer) and advanced heart failure. Therefore, in most
cases, the NIV device can be set according to standard NIV disease-specific guide-
lines, with the main difference being that the major treatment goal should be achiev-
ing patient comfort and dyspnea relief rather than pushing treatment efficacy in
terms of partial pressure of carbon dioxide (PCO2) reduction by high-intensity
NIV. In this group, it is more likely that there will be consciousness problems requir-
ing more nursing stuff assistance, airway clearance, and physiotherapy maneuvers.
NIV in patients with DNI orders is accepted as cost effective, especially when there
are intensive care bed shortages.
Contrary to the above-mentioned standard ARF NIV indications, sepsis, acute
respiratory distress syndrome, and other non-pulmonary systemic inflammatory
response syndromes generally represent multiorgan failure caused by systemic cap-
illary leak syndrome, which results in hypoperfusion, increased oxygen consump-
tion, and CO2 and lactate accumulation, indicating probable (≈50 %) NIV failure
34 Impact of Comorbidities on Noninvasive Mechanical Ventilation Response 297

[5]. Another important but frequently forgotten concomitant disease that should be
taken into account while applying NIV is anemia. In both acute and chronic RF, in
cases of patient’s paleness and/or difficult-to-explain tachycardia, tissue hypoxemia
mirrored by hemoglobin lactate level should be assessed. If confirmed and indi-
cated, red cell transfusion should be considered rather than increasing positive end-
expiratory pressure (PEEP) and/or fraction of inspired oxygen (FiO2) to the limit. If
NIV is applied in immunocompromised patients suffering from ARF, it is most
effective if the underlying cause is a hematological condition, even though high
Acute Physiology and Chronic Health Evaluation (APACHE) II score, need for cat-
echolamine administration, and low ratio of arterial oxygen partial pressure to frac-
tional inspired oxygen (PaO2/FiO2) ratio at admission are known as independent
risk factors for NIV failure [5].
In community-acquired pneumonia (CAP), NIV is known to be beneficial; how-
ever, in patients with large secretion volume, the application may be difficult.
Nevertheless, patients with CAP and hypercapnia benefit more than those with pure
hypoxemia. Interestingly, NIV administered in patients with overlapping COPD is
more effective in terms of the intubation rate and mortality decrease [6].
Another frequently observed “comorbidity situation” is encountered in a wide
group of patients with a few mild, underlining medical conditions such as COPD,
OSA, and heart failure. These patients often undergo various surgical procedures
that are not necessarily related to the above-mentioned impairing respiratory condi-
tions. In this group, risk of postoperative hypoxemia resulting from atelectasis or
pulmonary edema is especially high. The risk is especially high after pulmonary,
cardiac, or abdominal procedures or surgeries.
It was found that not only NIV but also CPAP treatment at a level from 7.5 to 10
cmH2O may decrease pneumonia morbidity, intubation rates, and days in intensive
care unit (ICU) [7].

34.2.3 Comorbidities and Age Groups

Coexistence of the most common NIV indication, hypercapnic respiratory failure in

COPD with mild airflow obstruction (FEV1 > 40%N), is frequently caused by over-
lapping OSA and/or OHS. These patients should be assessed with polysomnogra-
phy, and their treatment should start with CPAP titration along with oxygen therapy.
The number of elderly patients with multiple comorbidities and consciousness dis-
turbances is increasing, especially in the inpatient setting. Consequently, agitation
or confusion may lead to difficulties with mask administration and secretion man-
agement, resulting in significant risk for aspiration pneumonia.
On the other hand, in elderly patients with muscle wasting, there is a consider-
able risk for weaning problems and MV complications. Bearing in mind the signifi-
cantly higher risk for endotracheal intubation, cautious NIV initiation may be
considered by experienced caregivers in a closely monitored setting with an ICU
backup [8].
298 S. Skoczyński

34.2.4 Facial Oronasal Comorbidities and Airway Clearance

Facial oronasal comorbidities are especially important in home NIV treatment.

Patients with a dental prosthesis qualified for home NIV program in hospital set-
tings should be informed that, during home treatment, the denture should be used
the same as at the time of qualification and hospital treatment. Denture removal may
cause excessive leakage due to secondary facial softening and mask-induced facial
deformation. To prevent such situations, the patient should be informed that, during
NIV therapy, dentures should not be removed, or, if effective and well tolerated, it
may be reasonable to supply the patient with different types of masks, such as nasal
prongs which are tolerated and effective when IPAPmax settings are < 20 cmH2O.
In contrary to nasal and oro-nasal masks nasal prongs do not require facial
bone support.
Another significant and often observed comorbidity is chronic and/or acute
sinusitis. In chronic conditions, positive airway pressure application may lead to
secondary nasal congestion and upper airway disease exacerbation. In these cases,
nasal congestion should be proactively treated, for example, with nasal glucocorti-
costeroids, as in atopic rhinitis. Poor compliance due to nasal congestion is likely to
stop patients NIV treatment. To facilitate NIV continuation, an oronasal mask
should be preferred over nasal masks in patients with nasal congestion and sinusitis.
In those patients with Chronic respiratory failure (CRF), humidification in NIV may
greatly improve patient compliance as a result of a decrease in nasal congestion.
With bacterial sinusitis, the patient should be informed that positive airway treat-
ment may aggravate the disease and cause potential purulent complications.
Therefore, in cases of acute sinusitis, the patient should be advised to seek help
from the home-care provider and/or their general practitioner, depending on the
local NIV system.
ALS and lower respiratory tract infection overlapping in a patient already treated
with NIV may cause problems with effective airway clearance leading to NIV inef-
fectiveness, respiratory failure exacerbation, and potential complications such as
pneumonia. To prevent such situations, patients with stable disease should be
assessed with the Norris bulbar scale (<29; 39 = normal value), peak cough flow
(PCF) (<4.25 l/s), or peak cough flow/peak velocity time (PCF/PVT < 28.88 l/s). If
at least one borderline point is met, assisted airway clearance techniques should be
introduced [9]. In ALS, congestive heart failure (periodic breathing), or COPD/
OHS overlapping, there is a significant probability of the co-presence of central
apneas and hypopneas; therefore, the spontaneous over timed (S/T) ventilation
mode is recommended. Similarly, patients on chronic NIV after SCI have signifi-
cant risk of respiratory complications such as atelectasis, difficulties in secretion
clearance, and higher pneumonia morbidity. Lifelong maneuvers dedicated to main-
taining airway clearance are recommended to prevent complications that are
accepted as leading causes of death in patients with high-level tetraplegia. Patients
presenting with SCI are usually young and therefore initially do not have significant
overlapping diseases. Chest deformities predisposing to progressive respiratory
impairment are frequently observed after longer treatment.
34 Impact of Comorbidities on Noninvasive Mechanical Ventilation Response 299

Mask-related complications such as facial bruises are accepted as some of the

most important NIV contraindications and side effects, and proactive screening
should be implemented. To avoid this complication, patients and their families
should be well trained and informed of the need to change the interface or even
obtain a mask customized to the patient. This applies to selected cases of home-
treated patients, especiallychildren with neuromuscular diseases.

34.2.5 Metabolic Comorbidities and Obesity

Type-2 diabetes is often observed in patients with OHS/OSA and obese patients
with COPD. It should be taken into consideration that NIV may promote weight
loss and decrease insulin resistance. This may result in glycemia level reduction,
which is, from a long-term perspective, beneficial for the patient. On the other hand,
an uninformed patient, especially on insulin treatment, may suffer potentially life-
threatening hypoglycemia episodes. Therefore, patients with diabetes should be
advised that more attentive glucose control and potential anti-diabetic drug dosage
modification may be necessary.
Accordingly, in patients with poorly controlled hypertension, effective NIV
treatment may lead to secondary blood pressure decrease and hypotonia related
complications such as fainting. In both clinical conditions, hypoglycemia and hypo-
tension are clinically positive features, but caution is needed to adjust the patient’s
drug dosages accordingly. Moreover, significant weight loss in patients with over-
lapping OSA/OHS may allow for a decrease in treatment intensity from NIV to
CPAP. Therefore, a ventilation program in obese patients should always be enhanced
by weight loss consulting and/or a treatment program.

Conclusion
There is a deficit of prospective randomized studies that assess the impact of
comorbidities on noninvasive mechanical ventilation response. Moreover, cur-
rently, even in single-disease guidelines, there are huge gaps in knowledge, even
in basic recommendations such as ventilation mode, triggering, interface, and
humidification [10]. Therefore, more random controlled trials are needed in
basic diseases in most fields of NIV. Patients with overlapping diseases may
undergo NIV treatment, but they require carefully monitoring and alternative
treatment options, such intubation and mechanical ventilation, should be readily
available. In these situations, the staff should have significant experience, as
treatment outcomes rely significantly on personal experience and watchful
patient observation.
Generally it is easier and more feasible to treat obese patients with a slow
respiratory rate than lean patients with fast shallow breathing. In cases where a
few diseases overlap, the presence of COPD should be considered a positive
prognostic factor. Standard NIV contraindications seem to have a stronger impact
on treatment results than in single-disease scenarios, with exception of patients
with DNI orders, where the treatment is dedicated to comfort than effectiveness.
300 S. Skoczyński

The role of comorbidities may be crucial but different in acute and in chronic
settings. The role of diseases not directly correlated with ventilation should be
taken into account when applying NIV. Most importantly, the patient and the
patient’s family should be involved in the process of therapeutic decision mak-
ing. The most important factors influencing RF treatment efficacy are precise
understanding of overlapping disease pathophysiology, medical team dedication,
and an ethics-based approach. Currently, it seems impossible to create a univer-
sal flowchart or table to guide the treatment protocol in all patients with RF
caused by overlapping diseases. Therefore, clinicians are encouraged to publish
their own observations in this important area of clinical research.

Key Major Recommendations

• NIV should be attempted in all patients (without absolute NIV contraindi-
cations) with type-2 chronic respiratory failure, even in cases with signifi-
cant overlapping diseases.
• NIV should be attempted in most patients with type-2 acute or acute-on-
chronic respiratory failure, even in cases of significant overlapping
diseases.
• NIV settings should be always adjusted on the basis of combined patho-
physiology of overlapping diseases and the patient’s treatment tolerance.
• In overlapping diseases, the final result of the treatment is more dependent
on the combination of contraindications than the treatment indications.
• In overlapping diseases, the presence of COPD, especially in patients with
decreased respiratory drive, should be considered as a positive prognostic
factor.

References
1. McKim DA, Road J, Avendano M, et al. Canadian Thoracic Society Home Mechanical
Ventilation Committee, Canadian Thoracic Society Home Mechanical Ventilation Committee.
Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline. Can
Respir J. 2011;18:197–215.
2. Non-invasive ventilation guidelines for adult patients with acute respiratory failure. Available
at: http://www.aci.health.nsw.gov.au/. Downloaded on 20 Mar 2015.
3. Köhnlein T, Windisch W, Köhler D, et al. Non-invasive positive pressure ventilation for the
treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre,
randomised, controlled clinical trial. Lancet Respir Med. 2014;2:698–705.
4. Walkey AJ, Wiener RS. Use of noninvasive ventilation in patients with acute respiratory fail-
ure, 2000–2009: a population-based study. Ann Am Thorac Soc. 2013;10:10–7.
5. Razlaf P, Pabst D, Mohr M, et al. Non-invasive ventilation in immunosuppressed patients with
pneumonia and extrapulmonary sepsis. Respir Med. 2012;106:1509–16.
34 Impact of Comorbidities on Noninvasive Mechanical Ventilation Response 301

6. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/
American Thoracic Society consensus guidelines on the management of community-acquired
pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27–72.
7. Squadrone V, Coha M, Cerutti E, et al. Continuous positive airway pressure for treatment of
postoperative hypoxemia: a randomized controlled trial. JAMA. 2005;293:589–95.
8. Scala R. Non-invasive ventilation in acute respiratory failure with altered consciousness syn-
drome: a bargain or an hazard? Minerva Anestesiol. 2013;79:1291–9.
9. Sancho J, Servera E, Díaz J, Marín J. Predictors of ineffective cough during a chest infection
in patients with stable amyotrophic lateral sclerosis. Am J Respir Crit Care Med. 2007;175:
1266–71.
10. Keenan SP, Sinuff T, Burns KE, et al.; Canadian Critical Care Trials Group/Canadian Critical
Care Society Noninvasive Ventilation Guidelines Group. Clinical practice guidelines for the
use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway
pressure in the acute care setting. CMAJ. 2011;183:E195-214.
Noninvasive Continuous Positive Airway
Pressure Response in Bronchiectasis 35
Exacerbations: Key Practical Aspects
and Topics

Annia Schreiber, Andrea Antonelli, and Cesare Gregoretti

Contents
35.1 Introduction ................................................................................................................. 304
35.2 Discussion and Analysis ............................................................................................. 305
35.2.1 CPAP in Acute Respiratory Failure............................................................... 306
35.2.2 CPAP in Promoting Airway Clearance and During Chest Physiotherapy .... 307
35.2.3 CPAP During Exercise .................................................................................. 309
Conclusion ............................................................................................................................. 309
References .............................................................................................................................. 310

Abbreviations

CF Cystic fibrosis
CPAP Continuous positive airway pressure
COPD Chronic obstructive pulmonary disease
FEV1 Forced expiratory volume in one second
FRC Functional residual capacity
FVC Forced vital capacity

A. Schreiber, MD (*)
Terapia Subintensiva Respiratoria e Pneumologia Riabilitativa, IRCCS Fondazione Salvatore
Maugeri, Pavia, Italy
e-mail: [email protected]
A. Antonelli, MD
Allergologia e Fisiopatologia Respiratoria, ASO Santa Croce e Carle, Cuneo, Italy
e-mail: [email protected]
C. Gregoretti, MD
Dipartimento di Anestesia, Città della Salute e della Scienza, Torino, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 303

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_35
304 A. Schreiber et al.

FiO2 Fraction of inspired oxygen

HFNC High-flow nasal cannula oxygen
NIV Noninvasive ventilation
NPPV Noninvasive positive pressure ventilation
PaCO2 Partial pressure of carbon dioxide
PaO2 Partial pressure of oxygen
PEEPi Intrinsic positive end-expiratory pressure
PEP Positive expiratory pressure
Pdi Transdiaphragmatic pressure
Pes Esophageal pressure
PTPes/b Pressure time product of the esophageal pressure per breath
PTPes/min Pressure time product of the esophageal pressure per minute
RV Residual volume
TPEP Temporary positive expiratory pressure
VO2 Oxygen consumption
WOB Work of breathing

35.1 Introduction

Non-cystic fibrosis bronchiectasis is a chronic, debilitating condition characterized

by persistent cough and chronic excessive sputum production. This term refers to the
permanent abnormal dilatation of the airways associated with parenchymal destruc-
tion [1]. The precise prevalence of bronchiectasis is unknown due to a lack of cross-
sectional community surveys. In addition, different diseases causing bronchiectasis
vary across different countries and different historical periods, and the techniques
used to diagnose and define this condition have changed over the years. It has been
estimated that in 2005 in the United States it affected at least 110,000 adults [2], but
it is likely to be underdiagnosed. As a matter of fact, many of the affected patients are
misdiagnosed, suffering from other conditions, particularly chronic obstructive pul-
monary disease (COPD) or asthma. However, there is an overlap with COPD, with a
reported incidence of bronchiectasis in COPD of between 29 and 50 % [3].
Bronchiectasis is typically complicated by poor mucus clearance, resulting in bacte-
rial colonization with recurrent infections and excessive airway inflammation in
response to the infection. An ongoing cycle of infection and inflammation may then
be established and contribute to lung damage [4]. The natural history is a progressive
lung disease with parenchymal destruction, resulting in poor gas exchange and pro-
gressive respiratory failure. Infective exacerbations are a significant cause of morbid-
ity in non-cystic fibrosis bronchiectasis and often necessitate utilization of health-care
resources including in-patient admissions for intravenous antibiotic therapy and for
the management of the consequent respiratory failure [5]. Respiratory failure is the
cause of death in more than 90 % of patients with cystic fibrosis (CF) and it also
represents the leading cause of death in diffuse bronchiectasis [6, 7].
In the initial stages of the disease or in case of localized disease, patients with
bronchiectasis may be characterized by a preserved pulmonary function. As the
35 Noninvasive Continuous Positive Airway Pressure Response in Bronchiectasis 305

disease evolves, spirometry usually shows some degree of airway obstruction with
a high prevalence of bronchial hyperreactivity [8]. Obstruction is mainly related to
thickening of the bronchial wall due to infiltration of the airway walls by inflamma-
tory cells [9]. The inflammation within the bronchial walls causes structural damage
and airways dilatation with lack of structural support, which determines distal air-
way collapse during expiratory maneuvers. The peculiar accumulation of mucus
plugging also contributes to the obstructive pattern; large airways plugging was
found to be most closely associated with alterations in the forced expiratory volume
in one second (FEV1) and partial pressure of oxygen (PaO2), whereas changes in
small airways plugging were shown to be most strongly associated with a decrease
in forced vital capacity (FVC) [9, 10]. The association with a restrictive disease,
related to the presence of small atelectasis, may configure a mainly restrictive lung
disease or a mixed obstructive and restrictive clinical condition [11].
Acute respiratory failure commonly arises because of alveolar flooding caused by
new infections or exacerbations of previous colonizations. Also, an acute event such
as abdominal surgery or chest trauma, causing pain, could impair cough and expec-
toration and worsen atelectasis and consequently hypoxemia [12]. The final result is
an increase in the ventilation-perfusion mismatch, a fall in FEV1, a decrease in func-
tional residual capacity (FRC) and lung compliance, with a consequent increase in
the work of breathing (WOB) [12]. Progressive hypoxemia with the establishment of
chronic respiratory failure can be a consequence of a chronic progression of the lung
disease. At a later stage of the disease, beyond a worsening of ventilation-perfusion
mismatch, alveolar hypoventilation and hypercapnia may occur.
Similarly to what happens in CF, hypoxemia and hypercapnia first become clini-
cally significant during sleep and during situations that require an increase in alveolar
ventilation such as during the exercise, chest physiotherapy, and exacerbations.
Hypercapnia could eventually become diurnal as disease progresses over time [13, 14].
Bronchiectasis treatment and management guidelines are still not clearly defined.
Initial ventilatory strategies should aim to decrease ventilation-perfusion mismatch,
correct hypoxemia, improve lung function, increase compliance, and limit atelecta-
sis formation. In the more advanced stages, when the respiratory load is increased
due to progressive airflow, obstruction and hypoventilation occur, and an additional
goal is to correct hypercapnia.
Studies of bronchiectasis have generally included fewer than 20 patients and few
of them have been randomized or blinded. Furthermore, the vast majority of recom-
mendations existing were based on the management of the microbiological aspect,
on infection control, and on the treatment of pulmonary exacerbations with medical
therapies, prevalently antibiotics [15].

35.2 Discussion and Analysis

Continuous positive airway pressure (CPAP) consists of the application of positive

airway pressure throughout the entire respiratory cycle in a spontaneously breathing
subject. This distinguishes CPAP from noninvasive positive pressure ventilation
(NPPV), which supplies real ventilatory support and allows an increase in effective
306 A. Schreiber et al.

alveolar ventilation with a consequent decrease in partial pressure of carbon dioxide

(PaCO2). NPPV is generally considered part of the treatment of advanced disease,
sometimes at the end-stage and as a bridge to transplant. When alveolar hypoventi-
lation occurs and a progressive hypercapnic respiratory failure is established, NPPV
is able to unload the respiratory muscles, thereby improving alveolar ventilation and
gas exchange. Little is known about the role of CPAP in bronchiectasis, and the
limited knowledge available is based on evidence from studies in CF. CPAP has
been used in exacerbations of bronchiectasis with the aim of improving ventilation-
perfusion mismatch [16], promoting airway clearance as a part of chest physio-
therapy [17] or assisting chest physiotherapy [18]. Both during and after
exacerbations, there may be value for CPAP use during exercise, as has been shown
in other conditions [19].

35.2.1 CPAP in Acute Respiratory Failure

The primary indication for CPAP should be severe hypoxemia (type I respiratory
failure), when the patient is refractory to high-concentration oxygen therapy. In fact,
CPAP may deliver a constant fraction of inspired oxygen (FiO2) in comparison with
conventional supplementary oxygen, when used with dedicated devices.
In bronchiectasis, it may promote recruitment of the flooded alveoli, increasing
the number of functioning units and re-expanding dependent areas of the lung in
which airway opening occurs late in inspiration or does not occur at all. In the
prevalent restrictive pattern, CPAP may lead to an increase in FRC and residual
volume (RV), thereby improving respiratory mechanics [16]. The increase in RV
also contributes to more effective clearance of bronchial secretions.
By reversing hypoxemia and reducing respiratory rate together with improved
respiratory mechanics, CPAP will contribute to decrease the ventilation-perfusion
mismatch and relief of dyspnea. Last but not least, by countering intrinsic positive
end-expiratory pressure (PEEPi), particularly in case of airways obstruction, as dur-
ing acute exacerbations of chronic obstructive pulmonary disease (COPD) patients,
CPAP may also reduce the WOB [20–23].
A novel way to supply a continuous positive pressure is the humidified high-flow
nasal cannula oxygen (HFNC). HFNC is a technique that can deliver heated and
humidified gas, up to 100 % oxygen, at a maximum flow of 60 l/min of gas via nasal
cannula [24, 25]. Previous studies have demonstrated that this method of supplying
high-flow humidified oxygen is associated with the generation of a low level of
CPAP. It has also been shown that the degree of CPAP is flow dependent and also
reliant on the way of breathing (the higher the leak from an open mouth, the lower
the pressure) [26, 27]. A study by Vargas and coworkers [28] evaluated the effects
of HFNC compared with CPAP and oxygen therapy delivered via facemask in
patients with acute hypoxemic respiratory failure. Compared with the conventional
oxygen therapy device and similarly to CPAP, HFNC resulted in less inspiratory
effort, as indicated by a significant reduction in esophageal pressure (Pes), pressure
time product of the esophageal pressure per breath and per minute (PTPes/b and
35 Noninvasive Continuous Positive Airway Pressure Response in Bronchiectasis 307

PTPes/min), and in a slight but significant increase in the PaO2/FIO2 ratio. In addi-
tion, HFNC led to a significant reduction in median respiratory rate compared with
standard oxygen therapy, without a significant difference compared with CPAP. Both
HFNC and CPAP decreased dyspnea, although not significantly. Tolerance was
similar for both methods.
Besides the effect of generating a CPAP, HFNC delivers heated and humidified
gas, which per se appears to play a role in bronchiectasis. Inspired air humidifica-
tion has, in fact, been reported to show some benefit in bronchiectasic patients.
Hasani and coworkers [29] used a radioaerosol technique to measure lung mucocili-
ary clearance before and after 7 days of domiciliary humidification. They found that
following warm air humidification, lung mucociliary clearance significantly
improved compared with baseline assessment. This appears to be of a crucial rele-
vance in bronchiectasis, especially during an exacerbation.
A preliminary study by Storgaard and coworkers [30] showed that, in patients
affected by COPD and chronic respiratory failure who were receiving long-term
oxygen therapy, HFNC reduced the number of acute exacerbations in comparison
with controls. Furthermore, patients treated with HFNC had fewer hospital admis-
sions than the control patients. This could be partly due to the effect of promoting
mucus clearance and it seems reasonable to surmise that this result could be repli-
cated in bronchiectasis. Further studies are needed to demonstrate this theory. The
use of HFNC may also play a role in preserving lung function, as we know that secre-
tions and the vicious cycle of inflammation and infection contribute to the functional
decline. Hasani and coworkers found that all lung function indices slightly improved
following a short period of HFNC therapy, even if not significantly. We could hypoth-
esize that these data could become significant in the long term.

35.2.2 CPAP in Promoting Airway Clearance and During Chest

Physiotherapy

Despite the lack of physiotherapy guidelines advocating specific techniques and

outcome measures [31], bronchiectasic patients, except those with virtually no spu-
tum, appear to benefit from airway clearance strategies and should therefore under-
take regular chest physiotherapy, particularly during exacerbations. In fact, effective
clearance of excessive mucus from the airways appears to be important as it can
potentially break the vicious cycle of the disease by minimizing the stagnation of
mucus, mucus plug formation, bacterial load, inflammation, and recurrent infec-
tions. Treatment methods that improve mucus clearance are therefore considered
essential in optimizing respiratory function and reducing the progression of the dis-
ease. Moreover, recent studies have provided evidence that regular physiotherapy
improves quality of life [32]. This is particularly true during pulmonary exacerba-
tions when the amount of sputum is typically increased and sputum clearance may
be further impaired by more severe airway inflammation and obstruction and by the
greater viscosity of secretions [33]. Chest physiotherapy has been used for many
years with the aim of promoting lung re-expansion, improving clearance of mucus,
308 A. Schreiber et al.

and facilitating its expectoration. Several techniques that involve positive pressure
are available, such as positive expiratory pressure (PEP) and oscillatory PEP devices
(e.g., the so-called flutter device), but few controlled studies have documented a
clinical benefit in bronchiectasis [34]. PEP consists of cycles of active expiration
against a variable expiratory orifice flow-resistor. It is usually applied via a face
mask or mouthpiece. The mucus clearing effect is thought to be due to the widening
of the airways because of the increased expiratory pressure [17].
A new modality to deliver a low positive pressure level during spontaneous
breathing for a fraction of the expiratory phase is now available. Called temporary
positive expiratory pressure (TPEP), this technique was developed to assist patients
with chronic mucus hypersecretion, such as patients with bronchiectasis. Preliminary
studies have shown that, in the long term, a low positive pressure (less than or equal
to 1 cmH2O) applied for a fraction of the expiratory phase may improve the distribu-
tion of alveolar ventilation, symptoms, and lung volumes [35]. A more recent study
[36] demonstrated that, in the short-term (after 10 days of treatment), there were
significant increases in FEV1, FVC, tidal volume, and inspiratory capacity in com-
parison with a control group treated by manually assisted breathing techniques. The
effect on inspiratory capacity appears to be correlated with the concomitant reduc-
tion in airways obstruction and the recruitment of collapsed lung parenchyma.
TPEP was also associated with an improvement in both the perceived bronchial
encumbrance and the effective reduction of expectoration, as well as with an
improvement in secretion density and purulence, compared with the control group.
The effect on lung function appears to be common to other types of positive expira-
tory pressure-based techniques. The benefit of all these techniques is in their ability
to enhance mucus clearance by stenting the airways and preventing airway collapse,
or increasing intrathoracic pressure and collateral ventilation distal to retained
secretions, or decreasing functional residual capacity [37].
The continuous administration of positive airway pressure (i.e., CPAP) has been
evaluated in promoting mucus clearance, and its effect has been compared with PEP
delivered via a face mask (PEP mask) and to NPPV [17]. Placidi and coworkers [17]
compared the short-term effects of these three techniques in 17 patients with CF and
severe airway obstruction admitted for pulmonary exacerbation. There were no sta-
tistically significant differences in sputum clearance and the dry weight of sputum
collected between CPAP, mask PEP, and NPPV. At the same time, they did not find
any differences in terms of pulmonary-function measures, pulse-oximetry values,
and patients’ subjective efficacy scores. Less fatigue was reported after CPAP and
NPPV than after mask PEP. The authors concluded that CPAP and NPPV could be
considered as an alternative airway-clearance regimen that might be clinically rel-
evant in patients who feel tired and uncomfortable using conventional airway-
clearance techniques during a lung-disease exacerbation.
Although chest physiotherapy is a critical component of the care of patients with
bronchiectasis, especially during exacerbations, it should be remembered that it
may increase energy expenditure and cause oxygen desaturation, respiratory muscle
fatigue, and dyspnea [38]. This could occur particularly when there is a greater need
to promote airway clearance, such as during exacerbations.
35 Noninvasive Continuous Positive Airway Pressure Response in Bronchiectasis 309

In this context, NPPV has been shown to decrease respiratory muscle work and
improve oxygenation, thereby decreasing the occurrence of respiratory failure and
dyspnea [18]. We can postulate that CPAP may play a role similar to that of NIV, at
least in preventing or limiting desaturations, improving oxygenation, and in allevi-
ating dyspnea during chest physiotherapy [16]. It has, in fact, been demonstrated
that both CPAP and NPPV could decrease inspiratory muscle WOB [39]. An alter-
nating application of CPAP and chest physiotherapy could therefore be hypothe-
sized with the purpose of optimizing the duration and effectiveness of physiotherapy
sessions.

35.2.3 CPAP During Exercise

A relevant proportion of patients with CF have a marked decrease in exercise toler-

ance, which can be mainly related to lung disease, as well as to impaired muscle
function and decreased physical activity levels in daily life [40]. Preliminary find-
ings suggest that patients with non-CF bronchiectasis face the same problems and
share the same mechanisms [41].
Previous studies have evaluated the role of CPAP during exercise in chronic
obstructive lung diseases. In these patients, the sensation of dyspnea is mostly
related to the increased WOB, a consequence of an increased resistive load, hyper-
inflation, and of the deleterious effect of intrinsic positive end-expiratory pressure
(PEEPi) [40]. As previously mentioned, the administration of low-level CPAP pro-
vides a means of counteracting the effect of PEEPi in patients with severe hyperin-
flation [20–22, 42].
CPAP has been associated with an improvement in exercise tolerance in CF
patients, particularly in those with more severe lung disease [43]. Indeed, in these
patients, CPAP seemed to significantly reduce oxygen consumption (VO2), the
respiratory effort assessed by the transdiaphragmatic pressure (Pdi) and dyspnea;
these values tended to increase only slightly in patients with mild lung disease [43].
The decreases in VO2, Pdi, and dyspnea score suggest that CPAP can reduce the
work of breathing and increase exercise tolerance [19]. The beneficial effects during
exercise were more important in the patients with severe lung disease because, in
these patients, the presence of PEEPi may be favorably counteracted by
CPAP. However, because upper airway loading with complete or partial obstruction
and PEEPi are not the sole mechanisms of hypoventilation, CPAP alone may be
insufficient in patients with significant respiratory function abnormalities. In this
case, NPPV should be used.

Conclusion
In conclusion, there is a physiologic rationale for the use of CPAP in bronchiec-
tasis exacerbations and as an airway clearance technique. However, CPAP is not
a true ventilator mode and therefore is not suitable for the treatment of hypercap-
nic respiratory failure. Close monitoring of patients treated with CPAP for a
hypoxemic episode is to be recommended to switch to true ventilatory support in
310 A. Schreiber et al.

the occurrence of hypercapnia. Further studies are needed to define the most
pertinent criteria to propose CPAP in patients with bronchiectasis as well as the
best ventilatory regimens for each situation.

Key Recommendations
In patients affected by bronchiectasis:
CPAP should be recommended in patients with acute exacerbation of hypox-
emic respiratory failure, unless there are contraindications.
CPAP may promote lung recruitment, reverse hypoxemia, improve respira-
tory mechanics, reduce the WOB, and alleviate dyspnea.
CPAP could play a role in promoting airway clearance, limiting desaturations
during chest physiotherapy, and increasing tolerance during exercise.

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Noninvasive Mechanical Ventilation
in Asthma Exacerbation: Key Practical 36
Aspects and Clinical Evidence

Guniz M. Koksal and Emre Erbabacan

Contents
36.1 Introduction ................................................................................................................. 314
36.2 Criteria for Defining Severe Acute Asthma ................................................................ 314
36.2.1 Clinical Signs ................................................................................................ 314
36.2.2 Physiologic Signs .......................................................................................... 314
36.3 Discussion and Analysis ............................................................................................. 315
Conclusion ............................................................................................................................. 317
References .............................................................................................................................. 317

Abbreviations

BiPAP Bi-level positive airway pressure

COPD Chronic obstructive pulmonary disease
CPAP Continuous Positive Airway Pressure
FEV1 Forced expiratory volume in 1 s
GINA Global initiative for asthma
NIV Noninvasive mechanical ventilation
PEEP Positive end-expiratory pressure

G.M. Koksal, MD (*) • E. Erbabacan, MD

Department of Anesthesiology and Reanimation, Cerrahpasa Medical School, Istanbul
University, Istanbul, Turkey
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 313

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_36
314 G.M. Koksal and E. Erbabacan

36.1 Introduction

Asthma is highly prevalent worldwide (estimated to account for 1 in every 250

deaths) and its exacerbations can lead to acute respiratory failure. A mortality rate
of 27 % has been reported in invasively ventilated patients. Approximately 5–10 %
of asthmatic patients experience at least one severe acute asthma episode in a given
year, and there are approximately 2 million emergency department visits and
500,000 hospital admissions annually worldwide [1].
The major physiological changes in severe acute asthma are associated with the
onset or worsening of limitation of the air flow as a result of bronchospasm, muco-
sal edema, and mucus hyperproduction, which are triggered by bronchial flogosis
and hyperresponsiveness. Like in COPD exacerbations, the increase in airway resis-
tance prolongs the exhalation time required to empty the lung, producing air trap-
ping (dynamic hyperinflation with increased auto-positive end-expiratory pressure
(PEEP)), reduced FEV1 (<60 %), and reduced lung elastic recoil [2].
The severity assessment of an asthma attack has been suggested by the Global
Initiative for Asthma (GINA) [3]

36.2 Criteria for Defining Severe Acute Asthma

36.2.1 Clinical Signs

Clinical signs include the following: breathlessness at rest; wheezing (life-

threatening respiratory arrest is imminent if the chest is silent); use of accessory
respiratory muscles (life-threatening respiratory arrest is imminent if paradoxical
thoracoabdominal movement is present); limited ability to talk; and agitation (life-
threatening respiratory arrest is imminent if confusion or coma are present).

36.2.2 Physiologic Signs

Physiologic signs include the following: respiratory rate > 30 breaths/min; heart
rate > 120 beats/min (life-threatening respiratory arrest is imminent if bradycardia is
present); pulsus paradoxus >25 mmHg (life-threatening respiratory arrest is immi-
nent if pulsus paradoxus is present); post-bronchodilator peak expiratory flow <60 %
of patient’s best or predicted, or <100 l/m; FEV1 < 30 % of patient’s best or predicted
Level; and SpO2 < 90 %, PaO2 < 60 mmHg, and PaCO2 > 45 mmHg on room air.
The NIV therapy is used routinely in the acute exacerbations of COPD, and its
efficiency has been proved. It is known that the efficacy of bronchodilator therapy
also increases as the airways and alveoli open during NIV application [4]. It is curi-
ous that even the physiopathologies of COPD and asthma exacerbations are so
alike; NIV therapy is not used routinely during the asthma attacks. A reason for this
is the lack of strong prospective, randomized clinical studies with large number of
patients that suggest the use of NIV in asthma exacerbations. Although all clinical
36 Noninvasive Mechanical Ventilation in Asthma Exacerbation 315

studies show that administration of NIV during asthma exacerbations increases

FEV1, PaO2, and peripheral oxygen saturation values and decreases the work of
breathing, none of those studies recommend use of NIV during exacerbations
strictly [5–9].
Gupta et al. [5] randomized 53 patients hospitalized in an intensive care unit with
severe acute asthma attacks into two groups. Twenty-five of the patients received
only medical therapy whereas 28 patients received NIV with oronasal mask in addi-
tion to medical therapy. NIV therapy was started with inspiration/expiration pres-
sures values of 8/4 cmH2O and they were increased 2 cmH2O according to peripheral
oxygen saturation and arterial blood gas sample follow-ups. Maximum pressure
values administered were 20/10 cmH2O. Bronchodilator therapy was given via
T-piece with ultrasonic nebulizer. They found that NIV was of similar efficacy to
standard medical treatment in improving respiratory rate, FEV1, pH, PaO2/FiO2, and
PaCO2 in every acute asthma. A limitation of their study was the small number of
patients included in the study.
Soma et al. [6] prospectively randomized 44 patients with acute mild and moder-
ate asthma suffering an attack into two main groups: (a) a group receiving NIV
(bi-level positive airway pressure (BiPAP)) therapy via a nasal or face mask (n =
30), which was divided into two subgroups, receiving high (8/6) and low pressure
(6/4), or (b) a control group (n = 14). They suggested that NIV, even if delivered at
lower pressures than are usually recommended to support acute respiratory failure
patients, might help acute asthma attacks, even without inhaled bronchodilators.
Brandao et al. [7] evaluated the effects of bronchodilators administered via jet
nebulization during either spontaneous breathing or NIV with inspiratory/expira-
tory pressures of 15/5 or 15/10 cmH2O and showed an improvement in peak expira-
tory flow, FEV1, and forced vital capacity in comparison with the control group.
They speculated that this synergic effect of NIV in adjunct to the nebulized bron-
chodilator might be due to a better drug penetration into the peripheral airways.
Soroksky et al. [8] reported a pilot study where they applied BiPAP to severely
asthmatic patients who were refractory to standard medical treatment. BiPAP was
applied for 3 h in the emergency ward. They found that use of BiPAP significantly
improved lung function tests in 80 % of the patients in the BiPAP group who reached
the predetermined primary endpoints (an increase of at least 50 % in FEV1 com-
pared with baseline) versus 20 % in control group. However, a major limitation of
the study was its small sample size.
Tokioka et al. [9] showed that application of pressure support may decrease auto-
PEEP and work of breathing in asthmatic patients. This may unload inspiratory
muscles and decrease muscle fatigue.

36.3 Discussion and Analysis

When studies of asthma attacks were considered, different understandings and

approaches were found. Exact information on the timing and duration for NIV
application is absent. For example, should NIV be delivered in the beginning of the
316 G.M. Koksal and E. Erbabacan

attack when the steroid dose is increased as the patients are unresponsive to steroid
therapy (prophylactic), delivered when hypoxia emerges, or even only when silent
lung is observed and just before intubation? NIV administration should possibly be
started when respiratory rate increases and when drug doses need to be increased.
By this means, the airways and alveoli will stay open and the bronchodilator therapy
will be able to reach to the terminal points where its efficiency will be secured. Most
of the patients with asthma diagnosis are not hypoxic or hypercarbic except during
the attacks. In this sense, it is important to differentiate COPD with asthma. Patients
with COPD are resistant to hypoxia and hypercarbia and hence they have longer
time for NIV application [10]. In an asthma attack, as the arterial blood gas samples
start to deteriorate in the later periods, using them as a predictor for NIV might be
erroneous. As the occurrence of hypoxia and hypercarbia will worsen the clinical
state of the patient, administration of NIV could be slow and patients’ synchroniza-
tion could be more difficult. Accordingly, by delivering NIV at the beginning of the
attack, we may increase our chance of success [1].
It is important to clarify the parameters that will be used during asthma attacks, as
these are directly related to the success of NIV administration. In an asthma attack,
inspiratory flow and airway resistance increases, expiration time decreases, air trap-
ping occurs, and these increase auto-PEEP, which results with an increase in the
work of breathing. The patient needs to make more effort to start the inspiration. To
reduce all these pathologies and thereby work of breathing, external PEEP should be
applied via NIV and auto-PEEP can be offset. The type of ventilation mode that can
be used is not clarified in these studies. Although recovery was faster and FEV1 val-
ues increased in patients receiving CPAP, it might be inappropriate to use the same
airway pressures during inspiration and expiration to overcome inspiratory flow
increase and airway resistance during an asthma attack. The main issue that increases
the work of breathing during an asthma attack is increase in the inspiratory flow and
airway resistance, and, hence, higher pressure support levels are needed during inspi-
ration compared with expiration [7, 8]. Using the same levels during expiration and
inspiration can cause overdistention, as the emptying of the alveoli can be even less
sufficient with the already shortened expiration time. For that matter, it might be
more appropriate to use BiPAP that has two different pressure support parameters or
pressure support modes that use decelerating flow in patients with asthma attacks.
Patients synchronized with NIV will not be in need of sedation [8].
NIV administration during asthma attacks can be done via nasal mask, oronasal
mask, or full face mask. These options can be chosen according to the facial features
of the patients or to availability. In patients with excessive secretions who cannot
excrete them successfully, or in agitated patients with coughing attacks, synchroni-
zation with ventilation fails, causing failure in NIV therapy. Humidification of the
air given during NIV administration can be problematic and needs extra consider-
ation [10].
Patients with acute asthma attacks should be monitored and must be followed
closely. Although this follow-up is most efficient in intensive care units, NIV ther-
apy can be applied in emergency departments by experienced health-care workers.
36 Noninvasive Mechanical Ventilation in Asthma Exacerbation 317

NIV therapy should never delay intubation. NIV is never an alternative to intuba-
tion. NIV prevents the occurrence of the factors that lead to intubation and avoid
intubation [10].

Conclusion
During asthma attacks, administration of NIV with the appropriate parameters
and modes at the right time can increase efficacy of the medical therapy, result-
ing in a shorter hospital stay and positive effects on mortality. Prospective, ran-
domized clinical trials with larger numbers of patients are needed to determine
these effects.

Key Major Recommendations

• An acute asthma attack is pathophysiologically similar to COPD. NIV can
be used during asthma attacks.
• Choosing the appropriate patient and time to start to NIV therapy affects
the success of the therapy. NIV can be started with the first signs of an
asthma attack.
• Two different levels of pressure support can increase patient synchroniza-
tion and NIV success.

References
1. Scala R. Noninvasive ventilation in severe acute asthma? Still far from the truth. Respir Care.
2010;55(5):630–7.
2. Brenner B, Corbridge T, Kazzi A. Intubation and mechanical ventilation of the asthmatic
patient in respiratory failure. J Allergy Clin Immunol. 2009;124(2 Suppl):S19–28.
3. Global Initiative for Asthma. Global strategy for asthma management and prevention. NIH
publication 02–3659. Revised 2007. http://www.ginasthma.com/guidelineItem.asp?intid=1389.
Accessed 5 Mar 2010.
4. Nowak R, Corbrigde T, Brenner B. Noninvasive ventilation. J Allergy Clin Immunol.
2009;124(2 Suppl):S15–8.
5. Gupta D, Nath A, Ritesh A, Behera D. A prospective randomized controlled trial on the effi-
cacy of noninvasive ventilation in severe acute asthma. Respir Care. 2010;55(5):536–43.
6. Soma T, Hino M, Kida K, Kudoh S. A prospective and randomized study for improvement of
acute asthma by non-invasive positive pressure ventilation. Intern Med. 2008;47(6):493–501.
7. Brandao DC, Lima VM, Filho VG. Reversal of bronchial obstruction with bi-level positive
airway pressure and nebulization in patients with acute asthma. J Asthma.
2009;46(4):356–61.
8. Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of
bilevel positive airway pressure in acute asthmatic attack. Chest. 2003;123:1018–25.
9. Tokioka H, Saito S, Saeki S, et al. The effect of pressure support ventilation on auto-PEEP in
a patients with asthma. Chest. 1992;101:285–6.
10. Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of
chronic obstructive pulmonary disease. N Engl J Med. 1995;333:817–22.
Acute Applications of Noninvasive
Ventilation in Obesity Hypoventilation 37
Syndrome: Evidence and Key Practical
Recommendations

Malcolm Lemyze

Contents
37.1 Introduction ................................................................................................................. 319
37.2 Discussion ................................................................................................................... 320
37.2.1 Main Indications for NIV .............................................................................. 320
37.2.2 Positioning Morbidly Obese Patients for NIV .............................................. 321
37.2.3 Ventilator Settings ......................................................................................... 321
Conclusion ............................................................................................................................. 322
References .............................................................................................................................. 322

Abbreviations

ARF Acute respiratory failure

BMI Body mass index
EPAP Expiratory positive airway pressure
IPAP Inspiratory positive airway pressure
NIV Noninvasive ventilation
OHS Obesity hypoventilation syndrome
OSAS Obstructive sleep apnea syndrome

37.1 Introduction

Obesity hypoventilation syndrome (OHS) refers to the form of chronic respiratory

failure specifically resulting from obesity. The diagnostic criteria include obesity
(body mass index (BMI) > 30 kg/m2), alveolar hypoventilation (PaCO2 > 45 mmHg),

M. Lemyze, MD
Department of Respiratory and Critical Care Medicine, Schaffner Hospital, Lens, France
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 319

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_37
320 M. Lemyze

and sleep-disordered breathing, without any common cause of respiratory failure

(e.g., chronic obstructive pulmonary disease (COPD), chest wall deformity, or neu-
romuscular disease) [1]. Given the current epidemic of obesity, OHS is expected to
become the second leading cause of chronic respiratory failure worldwide [2, 3].
The higher the BMI, the higher the incidence of OHS [2]. The diagnosis is usually
made during an episode of acute respiratory failure (ARF), which is the most com-
mon life-threatening complication of OHS. Over the last two decades, noninvasive
ventilation (NIV) has emerged as the most effective treatment for ARF in obese
patients [1].

37.2 Discussion

37.2.1 Main Indications for NIV

37.2.1.1 Type 2 (Hypercapnic) Respiratory Failure

Hypercapnic ARF is the most meaningful indication for NIV especially in morbidly
obese patients. During a 13-year study period, Carillo et al. [4] have prospectively
evaluated the benefit of NIV in 173 patients with OHS versus 543 patients with
COPD in hypercapnic ARF. NIV was more effective in preventing intubation in
decompensated OHS than in COPD (NIV failure 7 % vs 13 %, p = 0.037), resulting
in a lower in-hospital mortality in the OHS group compared with COPD patients
(6 % vs 18 %, p < 0.001). In our prospective study including 76 morbidly obese
patients weakened by malignant OHS and admitted to the intensive care unit (ICU)
for ARF, NIV was constantly successful in patients with idiopathic hypercapnic
ARF [5]. The severity of respiratory acidosis, the level of hypercapnia, and the
depth of encephalopathy were not reliable criteria for predicting NIV failure. Along
the same lines, Dias et al. [6] clearly demonstrated that NIV is safe and successful
in reversing hypercapnic coma in patients in acute-on-chronic respiratory failure. In
this series, the success rate reached 80 % in comatose patients (Glasgow Coma
Score <7, n = 95) as compared with 70 % in non-comatose patients (Glasgow Coma
Score >8, n = 863, p = 0.04). Response to NIV may be delayed, especially in hyper-
capnic obese patients on respiratory depressant drugs or diuretics promoting alveo-
lar hypoventilation [5].

37.2.1.2 Type 1 (Hypoxemic) Respiratory Failure

If the use of NIV for patients in hypoxemic ARF is still questionable, at best it
avoids intubation and at worst it can be used for patient preoxygenation because it
has been demonstrated effective in the preoperative management of morbidly obese
patients before abdominal surgery [7]. In all cases, NIV must be initiated in a suit-
able environment (an emergency room, ICU, or at least a respiratory step-down
unit) with a large, well-trained team capable of providing close monitoring and
quick intubation if the patient’s condition worsens. In cases of persistent refractory
hypoxemia (PaO2/FiO2 < 200) after a 1–2 h NIV trial, escalation to intubation should
37 Acute Applications of Noninvasive Ventilation in Obesity Hypoventilation 321

be immediately discussed, especially when the cause of ARF is not easily and rap-
idly reversible (e.g., pneumonia, ARDS, or gravitational atelectasis).

37.2.1.3 Preoxygenation Before Intubation

A combination of preoxygenation with NIV before intubation and a lung recruit-
ment maneuver, consisting of applying CPAP at 40 cmH2O for 40 s immediately
after intubation, reduces the risk of desaturation and improves lung volume during
and after intubation [7].

37.2.1.4 Post-extubation Respiratory Distress

Morbidly obese patients are usually difficult to wean from mechanical ventilation
and are prone to post-extubation ARF. In a randomized controlled study, El-Solh
et al. [8] demonstrated that the systematic use of prophylactic NIV immediately
after extubation can significantly reduce the risk of ARF in the first 48 h following
extubation.

37.2.2 Positioning Morbidly Obese Patients for NIV

Positioning is too often overlooked in massively obese patients, although it is a

priority issue and an essential prerequisite for the management of these patients.
Sitting position prevents gravitational atelectasis, unloads the diaphragm from the
pressure exerted by the abdomen, thus facilitating its piston-like downward capac-
ity, and reduces work of breathing by reversing both expiratory flow limitation and
auto-PEEP [9]. Poor positioning of obese patients in ARF may result in NIV failure
and death [10].

37.2.3 Ventilator Settings

Pressure-limited ventilatory modes are preferred over flow-limited modes.

PEEP (or expiratory positive airway pressure (EPAP)) prevents upper airway
collapse and nocturnal arterial desaturation [1]. By maintaining a positive
transpulmonary pressure at expiration, PEEP increases functional residual
capacity, averts gravitational atelectasis, reverses expiratory flow limitation,
and, finally, decreases work of breathing by counterbalancing auto-PEEP [9].
The pressure support level increases alveolar ventilation and thus corrects
respiratory acidosis by improving CO2 removal. In clinical practice, obese
patients in ARF usually need high levels of inspiratory positive airway pressure
(IPAP) (mean, 18 cmH2O; from 12 to 25 cmH2O) and PEEP (mean, 9 cmH2O;
from 5 to 13 cmH2O) [1, 4, 5]. Polysomnography can help identify sleep-disor-
dered breathing (obstructive sleep apnea syndrome (OSAS), hypoventilation
alone, or a combination of OSAS and OHS) to better adapt the ventilator set-
tings for long-term NIV [1].
322 M. Lemyze

Conclusion
NIV and sitting position are the two cornerstones of the initial therapeutic man-
agement of morbidly obese patients in ARF. NIV is consistently successful in
hypercapnic decompensation of OHS. Refractory hypoxemia is the main deter-
minant of NIV failure in these patients.

Key Major Recommendations

• Good positioning (in the sitting position) is an essential prerequisite for
NIV success in the obese patient.
• In type 2 (hypercapnic) respiratory failure of obese patients, bi-level posi-
tive airway pressure should be advanced, as it is consistently successful,
• NIV can be cautiously used in type 1 (hypoxemic) respiratory failure,
especially if the underlying cause is rapidly reversible, but only in an envi-
ronment allowing close monitoring and rapid performance of intubation.
• NIV is helpful in preoxygenating the obese patient before intubation.
• NIV should be systematically performed immediately after extubation to
prevent post-extubation ARF in morbidly obese patients

References
1. Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care.
2010;55:1347–62.
2. Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in hospitalized
patients: prevalence, effects, and outcome. Am J Med. 2004;116:1–7.
3. Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-
mass index since 1980: systematic analysis of health examination surveys and epidemiological
studies with 960 country-years and 9.1 million participants. Lancet. 2011;377:557–67.
4. Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute hypercapnic
respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pul-
monary disease. Am J Respir Crit Care Med. 2012;186:1279–85.
5. Lemyze M, Taufour P, Duhamel A, et al. Determinants of noninvasive ventilation success or
failure in morbidly obese patients in acute respiratory failure. PLoS One. 2014;9(5), e97563.
6. Futier E, Constantin JM, Pelosi P, et al. Noninvasive ventilation and alveolar recruitment
maneuver improve respiratory function during and after intubation of morbidly obese patients:
a randomized controlled study. Anesthesiology. 2011;114:1354–63.
7. Díaz GG, Alcaraz AC, Talavera JC, Pérez PJ, Rodriguez AE, Cordoba FG, Hill NS. Noninvasive
positive-pressure ventilation to treat hypercapnic coma secondary to respiratory failure. Chest.
2005;127:952–60.
8. El-Solh AA, Aquilina A, Pineda L, et al. Noninvasive ventilation for prevention of post-
extubation respiratory failure in obese patients. Eur Respir J. 2006;28:588–95.
9. Lemyze M, Mallat J, Duhamel A, et al. Effects of sitting position and applied positive end-
expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechani-
cal ventilation. Crit Care Med. 2013;41:2592–9.
10. Lemyze M, Guerry MJ, Mallat J, Thevenin D. Obesity supine death syndrome revisited. Eur
Respir J. 2012;40:1568–9.
Noninvasive Ventilation in Chest Wall
Deformities: When and Why 38
Dhruva Chaudhry and Rahul Roshan

Contents
38.1 Introduction 324
38.2 Pathophysiology of Respiratory Failure in Chest Wall Diseases 324
38.3 Mechanism of Action of NIV 325
38.4 NIV in Chest Wall Diseases 326
38.5 Who Should Receive NIV? 328
38.5.1 Prophylaxis Therapy in High-Risk Patients 328
38.5.2 Definite Therapy for Respiratory Failure 328
38.6 How to Deliver NIV 328
38.6.1 Negative Pressure Ventilation 329
38.6.2 NIPPV 329
38.6.3 Contraindications of NIV 330
38.7 Special Conditions 331
38.7.1 Pregnancy in Chest Wall Diseases 331
Conclusion 331
References 331

Abbreviations

EPAP Expiratory positive airway pressure

ICU Intensive care unit
IPAP Inspiratory positive airway pressure
LTOT Long-term oxygen therapy

D. Chaudhry, MD, DNB(Med), DM(PCCM), FICCM, FICP (*)

R. Roshan, MD, DNB, FCCP
Pulmonary & Critical Care Medicine, Pt. B.D. Sharma PGIMS,
Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana 124001, India
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 323

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_38
324 D. Chaudhry and R. Roshan

NIV Noninvasive ventilation

NREM Non-rapid eye movement
PaCO2 Arterial carbon dioxide tension
PaO2 Arterial oxygen tension
PImax Maximal inspiratory pressure
Pdi Transdiaphgramatic pressure
Pdimax Maximal transdiaphgramatic pressure
Ppl Pleural pressure
REM Rapid eye movement

38.1 Introduction

Diseases affecting the chest wall reduce the functional capacity of the diaphragm
and lung, invariably leading to ventilatory failure. Chest wall or thoracic cage defor-
mities can be primary, like idiopathic kyphoscoliosis, ankylosing spondylitis, pec-
tus excavatum, and pectus carinatum, or secondary to pleural fibrosis, thoracoplasty
(after lobectomy or pneumonectomy), or poliomyelitis. These restrictive diseases
can affect the components of the inspiratory pump, including the bony rib cage,
respiratory musculature, and the spine and its articulations, as well as the soft tissue
comprising the abdomen. Respiratory muscle weakness is the most common factor
leading to chest infections, hospital admissions, and early mortality in these patients.
Most of these patients gradually develop nocturnal hypoventilation, initially during
rapid-eye-movement (REM) sleep before progressing to non-REM (NREM) sleep,
eventually leading to daytime chronic ventilatory failure. Management of chronic
ventilatory failure with noninvasive ventilation (NIV) is standard recommended
care. Nocturnal nasal intermittent positive pressure ventilation (NIPPV) has been
shown to increase survival and improve blood gases, respiratory function, sleep
architecture, and quality of life in patients with chest wall diseases.

38.2 Pathophysiology of Respiratory Failure in Chest Wall

Diseases

Restrictive chest wall disease leads to altered pulmonary pathophysiology, with

reduction in total lung capacity, vital capacity, and functional residual capacity but
without changes in residual volume [1, 2]. Diseases like pectus excavatum and pec-
tus carinatum do not appear to have important effects on respiratory pump, whereas
ankylosing spondylitis occasionally leads to severe ventilatory failure as total lung
capacity and functional residual capacity are not reduced. Patients with kyphosco-
liosis, post-tuberculosis sequelae, and post-thoracoplasty have higher risk of venti-
latory failure, being dependent on the degree of deformity and age of onset. The
severity of deformity can be quantified by measuring the angle of primary curves
(Cobb’s angle). An angle greater than 100° suggests severe deformity with increased
risk of respiratory failure, alveolar hypoventilation, and cor pulmonale. Anomalous
38 Noninvasive Ventilation in Chest Wall Deformities: When and Why 325

muscle insertion due to thoracic deformity in diseases like kyphoscoliosis may lead
to muscle weakness. Inspiratory muscle strength is significantly impaired. Chest
wall deformity leads to increased respiratory load due to a fall in chest wall and lung
compliance. A fall in inspiratory capacity is seen due to mechanical disadvantage as
a result of the altered geometry of the rib cage. Increase workload and a decrease in
the ability to generate the force with increased oxygen consumption can lead to
greater risk of respiratory failure due to muscle fatigue. The increase in the respira-
tory load leads to a breathing pattern characterized by low tidal volumes and very
high respiratory rates with increased dead space, alveolar hypoventilation, and dis-
ordered sleep.
Patients with chest wall deformities have a reduced ability to generate maximal
inspiratory pressures (PImax). Severe reductions in the maximal transdiaphgramatic
pressures (Pdimax) along with an increase in pleural pressure (Ppl) and transdiaph-
gramatic pressure (Pdi) deflections during normal breathing is observed. These
pressure changes lead to higher Ppl/ Pdimax and Pdi/ Pdimax ratios, suggesting respira-
tory fatigue. In addition to altered pulmonary pathophysiology, hypoventilation and
central or obstructive sleep apneas also contribute to respiratory failure. A negative
correlation has been noted between PaCO2 and PImax, possibly demonstrating that
inspiratory muscle restriction plays a vital role in the occurrence of respiratory fail-
ure in kyphoscoliosis patients. The increased work of respiration and decreased
respiratory muscle activity during REM sleep contributes to hypercapnia being seen
at this time, before it manifests during the deeper stages of NREM sleep and, later,
in wakefulness.

38.3 Mechanism of Action of NIV

The mechanism behind the benefit of NIV in chest wall diseases is not yet fully
understood [2, 3] (Fig. 38.1). Various factors have been postulated to elaborate these
effects. First, NIV allows chronically fatigued inspiratory muscles to rest and time
to recover, leading to improvement in inspiratory muscle function, ventilation, and
arterial blood gases during the daytime. Second, nocturnal application of NIV atten-
uates hypoventilation during sleep, resets central response to hypercapnia, and
improves ventilation and gas exchange during the day. Third, NIV improves lung
function by recruiting micro-atelectatic lung zones, improving pulmonary distensi-
bility, and providing better ventilation perfusion exchange. Finally, NIV improves
sleep architecture. It alleviates the symptoms mostly related to sleep fragmentation
subsequent to apneas, such as daytime sleepiness, fatigue, morning headache, cog-
nitive dysfunctions, and dyspnea.
NIV has been shown to improve sleep quality, to lead to a rise in PaO2 and a
fall in PaCO2, and to decrease the number of hospitalizations and cost of treat-
ment. Further, NIV has been found to alleviate daytime sleepiness, improve noc-
turnal hypoventilation, increase maximal respiratory pressures, provide greater
ability to perform activities of daily living and better quality of life, and prolong
survival.
326 D. Chaudhry and R. Roshan

ØMuscle fatigue Recruitment of

microatelectatic lung zones
Improved inspiratory Improved ventilation
muscle function perfusion exchange

NIV

Attenuates hypoventilation
Improves sleep architecture
Resets central
hyperresponsiveness to Reduced daytime time
hypercapnia sleepiness

Fig. 38.1 Mechanism of action of NIV in chest wall diseases

38.4 NIV in Chest Wall Diseases

A Cochrane review suggests that the therapeutic benefit of mechanical ventilation

in patients with neuromuscular and chest wall disease is weak but consistent,
indicating short duration relief in the symptoms of chronic hypoventilation [4].
Buyse et al. [5] found that in kyphoscoliosis, NIPPV demonstrated an increase in
PaO2 by 54 %, a fall in PaCO2 by 21 %, and a rise in vital capacity and maximal
static inspiratory mouth pressure by 47 % and 33 %, respectively, but these improve-
ments were not present in patients who received long-term oxygen therapy
(LTOT). In the NIV group, the 1-year survival was higher compared with the
LTOT group (100 % versus 66 %).
Budweiser and coworkers [6] found that pressure support > 15 cmH2O accentu-
ated the fall in PaCO2 during long-term follow-up in patients with restrictive chest
wall diseases. They showed that the inspiratory positive airway pressure (IPAP)–
expiratory positive airway pressure (EPAP)/weight ratio correlated with the fall in
PaCO2 at the first visit after hospital discharge with long-term NIV. Domiciliary
NIV significantly improves quality of life, including dyspnea, fatigue, and emo-
tional status in patients with chest wall disease. Application of NIV improves
38 Noninvasive Ventilation in Chest Wall Deformities: When and Why 327

clinical and physiological response to exercise by alleviating acidosis, hypoxia, and

hypercapnia along with a reduction in perception of breathlessness and effort. NIV
leads to marked improvement in diurnal arterial oxygen and carbon dioxide tensions
(PaO2 and PaCO2) along with a decrease in the days for hospital admission for respi-
ratory failure in patients with kyphoscoliosis or sequelae of previous tuberculosis.
Better quality of sleep was reported by 62 % of the patients and 70 % reported
improvements in activities of daily living [7].
Significant improvement in respiratory and peripheral muscle endurance along
with improvement in arterial blood gases has been seen after administration of NIV
for 3 months among patients with post-tuberculosis sequelae and scoliosis [8]. An
increase in maximal inspiratory pressure of 33–80 % along with a rise in maximal
expiratory pressures by 16 % has been observed in patients with chest wall
diseases.
In a randomized cohort study in an intensive care unit (ICU), the success rate of
NIV in kyphoscoliosis patients with acute respiratory failure was found to be 76.4 %
[9]. The frequency of sepsis and septic shock in patients with NIV failure was greater
than in patients with NIV success. The mortality rate was higher in patients in the
ICU with NIV failure compared with those patients who were initially put on inva-
sive ventilation. The predictors of NIV failure were significantly higher Acute
Physiology and Chronic Health Evaluation (APACHE) II score and increased respi-
ratory rate, with lower Glasgow Coma Scale and pH values. Lung functions and
6-min walk distance were found to improve with pressure support of around 15 cm
H2O with pressure-cycled NIV devices during long-term treatment. PaCO2 ≥ 50 mmHg
at 1 month of home ventilation and comorbidity (Charlson comorbidity index ≥3)
were independent predictors of mortality in chest wall disease treated with noninva-
sive home mechanical ventilation [10].
Newer modes of ventilation such as average volume-assured pressure support
are an effective treatment option in kyphoscoliotic patients with chronic respira-
tory failure, leading to an immediate and long-term improvement of daytime and
nocturnal blood gas exchange. This mode has shown a significant improvement of
diurnal PaO2 and PaCO2, mean blood oxygen saturation during sleep on the 5th
day of NIV and after 1 year of NIV, along with increase in forced vital capacity
after 1 year [11]. Petitjean et al. [12] found that discontinuation of NIV in patients,
initially stabilized on NIV, with chronic ventilatory failure (PaCO2 > 50 mmHg)
due to restrictive chest wall diseases (total lung capacity ≤ 65 % of predicted),
subjects them rapidly to nocturnal respiratory failure and, within days, to diurnal
respiratory failure. Withholding of NIV for more than 24 – 48 h is not
recommended.
Patients are usually compliant with NIV, with average daily use significantly
higher in post-tuberculosis sequelae and post-poliomyelitis patients in comparison
with patients with kyphoscoliosis (9 vs 6 h per day). At present, the compliance rate
of NIV in patients with kyphoscoliosis and polio is reported to be around 80–90 %.
Mortality rate in patients with kyphoscoliosis on long-term home NIV has been
reported as 21 % over 4 years.
328 D. Chaudhry and R. Roshan

38.5 Who Should Receive NIV?

38.5.1 Prophylaxis Therapy in High-Risk Patients

Though there is a little evidence in the literature, NIV may be given as a prophylactic
therapy in asymptomatic high-risk patients having greater chances of ventilatory fail-
ure (vital capacity of 1–1.5 l, early development of scoliosis before the age of 8
years, and a high thoracic curve). In patients with normal daytime blood gas tensions,
the amount of nocturnal hypoxia and hypercapnia, along with presence of complica-
tions such as polycythemia or a high pulmonary artery pressure, may benefit from
nocturnal NIV, but the decision to apply depends upon the physician [3, 13].

38.5.2 Definite Therapy for Respiratory Failure

Patients who are symptomatic and have abnormal blood gas tensions have been
more strongly suggested to benefit from NIV (Table 38.1).

38.6 How to Deliver NIV

Since the 1980s, volume-targeted NIV has been the predominant mode of NIV used
in chest-wall deformity presenting with chronic ventilatory failure. In the last
decade, however, pressure-targeted NIV emerged as a popular alternative because it
is less expensive and is associated with fewer gastrointestinal side effects. Recent
studies have shown equal efficacy of volume-targeted and pressure-targeted modes

Table 38.1 Indications for Clinical

NIV in chest wall diseases
Fatigue, morning headache, hypersomnolence, nightmares,
enuresis
Tiredness, dyspnea, cognitive changes
Cor pulmonale
Physiological
PaCO2 > 45 mmHg
Vital capacity <50 % of the predicted value
Maximal inspiratory pressure < 60 cmH2O
Nighttime arterial desaturation: SaO2 < 90 %; for > 5 min,
or > 10 % of the total recording time
Other indications
Recovering from acute respiratory failure with persistent
hypercapnia
Frequent hospital admissions for acute respiratory failure
Failure to respond to CPAP alone if obstructive sleep apnea
PaCO2 arterial carbon dioxide tension, SaO2 arterial oxygen
saturation, CPAP continuous positive airway pressure
38 Noninvasive Ventilation in Chest Wall Deformities: When and Why 329

of long-term NIV with relation to improvements in gas exchange, sleep architec-

ture, physical activity, and quality of life in patients with chest-wall deformity,
although the pressure-targeted mode has greater leak than volume ventilation.
Benefits of NIPPV by volumetric ventilator or a bi-level positive airway pressure
(BIPAP) device have been found to be equal for patients with kyphoscoliosis, how-
ever, subjective response and tolerance may be slightly better with BIPAP. No sig-
nificant difference has been observed in time needed to successfully adapt to
volume-targeted NIV compared with pressure-targeted NIV in patients with chest-
wall deformity. There is a subgroup of patients who respond well to volume ventila-
tors after failure of initial pressure support modes. NIPPV via a mask has mostly
replaced negative pressure ventilation, but among the patients who cannot tolerate
nasal mask negative pressure ventilation, tracheostomy ventilation can be the only
substitute.

38.6.1 Negative Pressure Ventilation

A cuirass or jacket type of negative pressure ventilator is mostly preferred over a

tank ventilator. These negative pressure ventilators have a major drawback as
patients need to lie on their back throughout the night and have a restricted area of
movement. This becomes especially difficult in patients with a kyphosis, where the
sharp angulation of the spine can become uncomfortable. It can also be cumber-
some to mould a cuirass in patients with a severe thoracic scoliosis. One of the
greatest disadvantages of negative pressure ventilation is greater patient ventilator
asynchrony and its tendency to induce obstructive apneas due to upper airway col-
lapse. The minimum inspiratory and expiratory times are similar to those required
for positive pressure ventilation.

38.6.2 NIPPV

A nasal mask is generally preferred over a full face mask or a mouthpiece (Fig. 38.2).
Patients with kyphoscoliosis are no more prone to NIV complications – mask dis-
placement, nasal ulcers, air leaks, or upper airway obstruction – than other diseases
of ventilatory failure. Both pressure- and volume-preset modes of ventilation can be
used. In the pressure preset mode, a peak inspiratory pressure of 20–25 cmH2O is
often desired with an inspiratory time of 0.8–1 s and an expiratory time of 2 s. The
fast respiratory rate in patients with restrictive chest wall disease mandates a sensi-
tive triggering system with a short response time. Positive end-expiratory pressure
can be beneficial at a pressure of 2–4 cmH2O, but is not absolutely necessary except
in some bi-level pressure-support modes in which it is essential to flush the dead
space. Adequate IPAP-EPAP difference should be ensured for movement of the
chest wall. Because of the rapid, shallow breathing pattern seen in kyphoscoliosis,
the ventilator triggering system should have a short response time to minimize
patient ventilator asynchrony. Failure of trigger on the spontaneous mode during
330 D. Chaudhry and R. Roshan

Clinical sympotms +/– VC < 50 % and MIP< 60 % predicted

ABG (PaCO2 > 45 mmHg)

PSG (SaO2 < 90 %; for >5 min, or >10 % of TRT)

Nocturnal NIV (Preferably AVAPS)

Follow up with PFT, ABG and oximetry every 3–6 months

Clinical or physiological deterioration

Exclude comorbidities and other causes

Reset the pressures

Day + nocturnal NIV

Fig. 38.2 NIV protocol in chest wall diseases. VC vital capacity, MIP maximal inspiratory pres-
sure, ABG arterial blood gas analysis, PaCO2 arterial carbon dioxide tension, PSG polysomnogra-
phy, SaO2 arterial oxygen saturation, TRT total recording time, NIV noninvasive ventilation,
AVAPS average volume-assured pressure support, PFT pulmonary function test

sleep warrants a trial with spontaneous timed mode if air leak has been ruled out.
Supplemental oxygen may be required if the partial pressure of oxygen in arterial
blood is low.

38.6.3 Contraindications of NIV

The contraindications of noninvasive ventilation in chest wall deformities are

no different than in the other diseases. Difficulty in application of the head-
gear, cuirass, or jacket can be an important issue. Lack of motivation along
with psychological factors, such as claustrophobia, are also significant
(Table. 38.2 ).
38 Noninvasive Ventilation in Chest Wall Deformities: When and Why 331

Table 38.2 Contraindications Failure to protect the airway

for NIV in chest wall diseases
Poor cough
Impaired swallowing with chronic aspiration
Excess tracheobronchial secretions
Continuous or nearly continuous ventilation requirement
Anatomical facial deformities preventing appropriate mask
fitting
Poor patient or family motivation
Uncooperative patient

38.7 Special Conditions

38.7.1 Pregnancy in Chest Wall Diseases

Pregnancy may aggravate type II respiratory failure in the presence of a restrictive

thoracic wall disorder. Risk factors appear to be a vital capacity of < 1 l, thoracic sco-
liosis > 100°, hypercapnia, the presence of bilateral diaphragm weakness, or extensive
intercostals muscle weakness in addition to the chest wall disorder. In normal women,
the gravid uterus affects lung function by upward displacement of the diaphragm,
leading to a fall in functional residual capacity and residual volume. These lung func-
tion changes and the raised metabolic needs are offset by rise in cardiac output and
rapid breathing. However, pregnancy in patients with severe kyphoscoliosis may lead
to failure of these adaptive mechanisms, with an increase in the dependant airway
closure causing ventilation perfusion abnormalities and increased respiratory work-
load that may contribute to nocturnal and subsequent daytime respiratory failure.
Such patients generally respond well to noninvasive ventilatory support.

Conclusion
NIV is beneficial in patients with kyphoscoliosis with ventilatory failure. It
improves arterial blood gas abnormalities and provides better lung functions and
quality-of-life sleep architecture. However, predictors of failure and the relative
contraindications should be kept in mind during application of NIV. Positive
pressure ventilators are now preferred over negative pressure ventilators. The
volume-assured pressure support mode may be preferred over conventional pres-
sure support modes. Guidelines need to be developed regarding the use of this
noninvasive mode in restrictive chest wall diseases.

References
1. Casas A, Pavía J, Maldonado D. Respiratory muscle disorders in chest wall diseases. Arch
Bronconeumol. 2003;39(8):361–6.
2. Lisboa C, Díaz O, Fadic R. Noninvasive mechanical ventilation in patients with neuromuscular
diseases and in patients with chest restriction. Arch Bronconeumol. 2003;39(7):314–20.
332 D. Chaudhry and R. Roshan

3. Shneerson JM, Simonds AK. Noninvasive ventilation for chest wall and neuromuscular disor-
ders. Eur Respir J. 2002;20(2):480–7.
4. Annane D, Orlikowski D, Chevret S. Nocturnal mechanical ventilation for chronic hypoventi-
lation in patients with neuromuscular and chest wall disorders. Cochrane Database Syst Rev.
2014;(12): CD001941.
5. Buyse B, Meersseman W, Demedts M. Treatment of chronic respiratory failure in kyphosco-
liosis: oxygen or ventilation? Eur Respir J. 2003;22(3):525–8.
6. Budweiser S, Heinemann F, Fischer W, et al. Impact of ventilation parameters and duration of
ventilator use on noninvasive home ventilation in restrictive thoracic disorders. Respiration.
2006;73(4):488–94.
7. Leger P, Bedicam JM, Cornette A, et al. Nasal intermittent positive pressure ventilation: long-term
follow-up in patients with severe chronic respiratory insufficiency. Chest. 1994;105(1):100–5.
8. Schonhofer B, Wallstein S, Wiese C, et al. Noninvasive mechanical ventilation improves
endurance performance in patients with chronic respiratory failure due to thoracic restriction.
Chest. 2001;119(5):1371–8.
9. Adıgüzel N, Karakurt Z, Gungor G, et al. Management of kyphoscoliosis with respiratory
failure in the intensive care unit and during long term follow up. Multidiscip Respir Med.
2012;7(1):30.
10. Martí S, Pallero M, Ferrer J, et al. Predictors of mortality in chest wall disease treated with
noninvasive home mechanical ventilation. Respir Med. 2010;104(12):1843–9.
11. Piesiak P, Brzecka A, Kosacka M, et al. Efficacy of non invasive volume targeted ventilation in
patients with chronic respiratory failure due to kyphoscoliosis. Adv Exp Med Biol.
2015;838:53–8.
12. Petitjean T, Philit F, Germain-Pastenne M, et al. Sleep and respiratory function after with-
drawal of noninvasive ventilation in patients with chronic respiratory failure. Respir Care.
2008;53(10):1316–23.
13. Consensus Conference Report. Clinical indications for noninvasive positive pressure ventila-
tion in chronic respiratory failure due to restrictive lung disease, COPD and nocturnal hypoven-
tilation. Chest. 1999;116(2):521–34.
Noninvasive Mechanical Ventilation
in Duchenne Muscular Dystrophy: What 39
Have We Learned?

Giuseppe Fiorentino, Antonio Pisano,

and Anna Annunziata

Contents
39.1 Introduction .................................................................................................................. 334
39.2 Discussion and Analysis ............................................................................................. 334
39.2.1 Diurnal and Nocturnal Respiratory Function in DMD.................................. 334
39.2.2 When to Start Noninvasive Mechanical Ventilation...................................... 335
39.2.3 Choice of Ventilator, Interfaces, and Settings ............................................... 336
39.2.4 Complications and Contraindications of NIV ............................................... 336
39.2.5 Causes of NIV Failure ................................................................................... 337
Conclusions ............................................................................................................................ 337
References .............................................................................................................................. 337

Abbreviations

DMD Duchenne muscular dystrophy

FVC Forced vital capacity
IPAP Inspiratory positive airway pressures
PaCO2 Arterial partial pressure of CO2
REM Rapid eye movement
RR Respiratory rate

G. Fiorentino, MD (*) • A. Annunziata, MD

Division of Respiratory Physiopathology and Rehabilitation,
A.O.R.N. “Dei Colli” – Monaldi Hospital, Naples, Italy
e-mail: [email protected]; [email protected]
A. Pisano, MD
Cardiac Anesthesia and Intensive Care Unit,
A.O.R.N. “Dei Colli” – Monaldi Hospital, Naples, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 333

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_39
334 G. Fiorentino et al.

SDB Sleep disordered breathing

VC Vital capacity
VT Tidal volume

39.1 Introduction

Pulmonary complications in Duchenne muscular dystrophy (DMD) are usually

more predictable than in other neuromuscular diseases because they correlate with
overall muscle strength. Respiratory failure in DMD is primarily associated with
restrictive pulmonary disease caused by inspiratory muscle weakness, severe scoli-
osis, reduced lung and chest wall compliance, and ineffective cough because of
respiratory muscle weakness. The majority of patients also develop cardiomyopa-
thy. Respiratory disease is a nearly inevitable complication in adult DMD patients,
and it represents the underlying cause of death in 70 % of DMD patients younger
than 25 years [1].

39.2 Discussion and Analysis

39.2.1 Diurnal and Nocturnal Respiratory Function in DMD

Because, in healthy subjects, vital capacity (VC) increases with growth during the
first decade of life, early respiratory muscle dysfunction may be masked until VC
does not reach its plateau. Accordingly, in DMD patients, VC progressively
decreases by about 5–6 % per year, usually starting around 12 years of age. However,
the rate of this decline may be variable: in particular, a sudden reduction in VC can
be occasionally precipitated by intercurrent events such as a worsening of scoliosis
or infective complications leading to the development of hypoventilation. A forced
vital capacity (FVC) ≤1 l is a predictor of poor outcome, with a survival rate at 5
years of only 8 % if assisted ventilation is not provided [2].
Reductions in maximum inspiratory pressure occur early in the clinical course of
DMD and may precede the reduction in VC. However, despite significant weakness
of the respiratory muscles, pulmonary symptoms are often minimal in the early
stages of the disease. Particularly, hypercapnia is uncommon in patients with DMD
in the absence of pulmonary infections. This is believed to be due to a relative pres-
ervation of diaphragm function until the later stages of the disease. Anyhow, once
hypercapnia develops, the course is rapidly progressive [1].
Sleep-related respiratory disturbances are frequent in DMD. Symptoms of
sleep-disordered breathing (SDB) (headache, somnolence, etc.) should be actively
investigated when VC is less than 30 % of predicted. Sleep-related hypoxemia may
contribute to respiratory failure and to the development of pulmonary hyperten-
sion. To minimize the work and perception of breathing, patients progressively
accelerate their respiratory rate (RR), leading to higher RR/tidal volume (VT) ratio.
39 Noninvasive Mechanical Ventilation in Duchenne Muscular Dystrophy 335

Nevertheless, once this compensatory mechanism no longer allows the patient to

maintain adequate alveolar ventilation, arterial partial pressure of CO2 (PaCO2)
rises [2, 3].
In summary, hypercapnic chronic respiratory failure in DMD patients typically
evolves through four stages: stage 1, SDB without hypercapnia; stage 2, SDB with
severe nocturnal hypoventilation and hypercapnia during rapid eye movement
(REM) sleep; stage 3, SDB with hypercapnia during REM and non-REM sleep;
stage 4, diurnal hypercapnia. At stage 4, mean survival is less than 1 year if ventila-
tory support is not started. When applied at stages 2 and 3, NIV corrects hypercap-
nia and improves both quality of life and survival [3].

39.2.2 When to Start Noninvasive Mechanical Ventilation

The primary goals of noninvasive mechanical ventilation in DMD are to improve

alveolar ventilation, reduce the shunt effect due to hypoxic pulmonary vasoconstric-
tion, and decrease the risk of pulmonary complications. This may lead to reduction
in the rate of hospitalization, prolonged survival, and improvement in quality of life,
and could attenuate the decline in both FVC and maximum voluntary ventilation,
thus delaying the need for tracheostomy and invasive mechanical ventilation [4].
However, the criteria to initiate ventilatory support in DMD patients are not well
defined. Raphael et al. [5] found that prophylactic NIV in normocapnic, asymptom-
atic DMD patients was poorly tolerated and provided no survival benefit. However,
this study has been criticized, primarily due to the lack of information about secre-
tion clearance and nocturnal hypercapnia.
Early initiation of NIV is an increasingly used approach. The initial objective of
prophylactic NIV is to counteract the unavoidable worsening of VC associated with
disease progression. Initiation of night-time NIV before the development of day-
time hypercapnia is beneficial to the patient; in fact, it may relieve symptoms and
improve quality of life, reduce daytime hypercapnia, slow the decline in pulmonary
function, and reduce the risk of intensive care unit admission. In particular, when
NIV is started in the presence of nocturnal hypercapnia alone, the onset of daytime
hypercapnia is delayed, and it usually does not develop until 4–5 years after NIV
initiation [6]. Once patients require NIV, the pressures to be set should be estab-
lished in the sleep laboratory to eliminate nocturnal apneas and hypopneas [7].
As time passes, patients with DMD develop a constant hypoventilation and need
respiratory support 24 h a day. The use of NIV in the daytime is also, mostly, empir-
ically guided. Mechanical ventilation for 18–20 h a day has been described in
patients with VC < 300 ml, whereas a daily ventilator-free time of less than 15 min
has been reported in patients with VC < 10 % of predicted [4]. Worsening of symp-
toms (primarily dyspnea) during the day suggests high energy expenditure in the
attempt to maintain normocapnia, and reversal of symptoms may be expected after
a few hours on daytime NIV. However, evidence in this regard is lacking.
Finally, an obvious indication for late initiation of NIV is daytime hypercapnia.
In fact, NIV is well tolerated in DMD patients with established respiratory failure,
336 G. Fiorentino et al.

resulting in improved daytime arterial blood gases, and can be maintained for a
relatively long time (up to 5–7 years) without the need for invasive mechanical
ventilation [8].

39.2.3 Choice of Ventilator, Interfaces, and Settings

39.2.3.1 Ventilator
The most commonly used noninvasive technique is mouthpiece intermittent positive
pressure ventilation. It has been used successfully, over a period of more than 8
years, in DMD patients with mean FVC of 0.6 l (5 % of predicted) [1, 6]. Two types
of positive pressure ventilators were used: volume ventilators and pressure support
ventilators. Both systems have similar effects on alveolar hypoventilation and on
(partial) respiratory muscle unloading. Newer ventilators combine the advantages
of pressure and volume modalities, providing air leak compensation, targeted vol-
ume, and sensitive triggering for optimal synchronization and comfort. During the
daytime, volume modalities are preferable due to the benefits of air-stacking and the
absence of leak compensations, thus enabling mouthpiece ventilation on demand.
Moreover, many patients with DMD have central sleep apnea and need NIV
machines that allow a respiratory rate to be set [8, 9].

39.2.3.2 Interfaces
The nasal mask remains the first choice as interface for nocturnal ventilation.
Mouthpiece ventilation is well tolerated and does not interfere with eating or speak-
ing. Both nasal and mouthpiece ventilation are a safe and effective form of respira-
tory support for DMD patients who require NIV for 24 h a day [1].

39.2.3.3 Settings
Ventilator parameters may vary widely among individuals. Effective ventilation is
usually achieved with relatively low inspiratory positive airway pressures (IPAP),
between 10 and 15 cm H2O, although the use of inspiratory pressures higher than
20 cm H2O may be needed and have been reported [1, 4]. For volume modalities,
high RR (between 14 and 22 breaths per minute) and VT (up to 10–14 ml/kg of
actual body weight) have been described as initial settings in DMD patients [1, 4].

39.2.4 Complications and Contraindications of NIV

Complications of nasal intermittent positive pressure ventilation include eye irrita-

tion, conjunctivitis, skin ulceration, gastric distention, and emesis into a full face
mask. Facial complications can be avoided by regular follow-up to assess mask fit.
In fragile patients, mask displacement can rapidly lead to severe hypoxemia and
hypercapnia. Contraindications are rare. Education of caregivers and families on
airway clearance techniques during home mechanical ventilation is an important
factor in the success of NIV [8].
39 Noninvasive Mechanical Ventilation in Duchenne Muscular Dystrophy 337

39.2.5 Causes of NIV Failure

Failure of NIV may occur due to technical issues, patient reluctance, or disease
progression. Air leaks are a main problem leading to inefficacy of NIV. Air can
leak between the mask and the skin, or through the mouth. Leaks may be associ-
ated with a high mask pressure, for instance, when the patient and the ventilator are
uncoordinated, or with a low mask pressure, when the muscles controlling the
velolingual and lip sphincters fail to provide an airtight seal. Mouth leaks may also
be secondary to high pharyngeal pressures, for instance, during complete glottic
closure (external leaks). Another possibility to be considered is the presence of
internal leaks: air entering the esophagus and stomach rather than the trachea, or
air being accommodated in the compliant upper (pharyngeal) airway acting as a
shunt compliance. The amount of leaks will depend to a great extent on upper air-
way pressure, which in turn will partly depend on glottic resistance or, in other
words, on glottic narrowing in response to NIV [1, 4]. The strategies to reduce air
leaks include raising RR, decreasing IPAP or VT, or increasing inspiratory to expi-
ratory ratio [4, 8].
However, pulmonary function continues to deteriorate, with patients requiring
increasingly more hours a day of mechanical ventilation and, finally (usually after
3–4 years after NIV initiation), the transition to tracheostomy and invasive positive
pressure ventilation [9].

Conclusions
Chronic respiratory failure is inevitable throughout the disease progression in
patients with DMD. Without NIV, morbidity and mortality are highly likely
toward the end of the second decade of life. Respiratory interventions, particu-
larly the institution of nocturnal noninvasive ventilation, have a major beneficial
effect on survival in DMD.

Key Major Recommendations

• A FVC < 1 l in DMD patients is a predictor of poor outcome within a short
time and should prompt the initiation of NIV. In fact, 5-year survival rate
is only 8 % in these patients if assisted ventilation is not provided.
• Nasal nocturnal ventilation is a safe and effective treatment in hypercapnic
DMD patients.
• No effective care is possible without skilled caregivers and adequate train-
ing and dedication of the patient’s family.

References
1. Finder JD, Birnkrant D, Carl J, et al. Respiratory care of the patient with Duchenne muscular
dystrophy: ATS consensus statement. Am J Respir Crit Care Med. 2004;170(4):456–65.
338 G. Fiorentino et al.

2. Phillips MF, Quinlivan CM, Edwards RH, et al. Changes in spirometry over time as a prognos-
tic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med.
2001;164:2191–4.
3. Fauroux B, Aubertin G, Clement A, et al. Which tests may predict the need for noninvasive
ventilation in children with neuromuscular disease? Respir Med. 2009;103:574–81.
4. Toussaint M, Chatwin M, Soudon P. Mechanical ventilation in Duchenne patients with chronic
respiratory insufficiency: clinical implications of 20 years published experience. Chron Respir
Dis. 2007;4(3):167–77.
5. Raphael J-CC, Chevret S, Chastang C. Randomised trial of preventive nasal ventilation in
Duchenne muscular dystrophy. Lancet. 1994;343(8913):1600–4.
6. Villanova M, Brancalion B, Mehta AD. Duchenne muscular dystrophy: life prolongation by
noninvasive ventilatory support. Am J Phys Med Rehabil. 2014;93(7):595–9.
7. Annane D, Orlikowski D, Chevret S. Nocturnal mechanical ventilation for chronic hypoventi-
lation in patients with neuromuscular and chest wall disorders. Cochrane Database Syst Rev.
2014;12:CD001941.
8. Hamada S, Ishikawa Y, Aoyagi T, et al. Indicators for ventilator use in Duchenne muscular
dystrophy. Respir Med. 2011;105:625–9.
9. Bach JR, Martinez D. Duchenne muscular dystrophy: continuous noninvasive ventilatory sup-
port prolongs survival. Respir Care. 2011;56(6):744–50.
Noninvasive Ventilation in Amyotrophic
Lateral Sclerosis: Key Technical 40
and Practical Applications

Bart Vrijsen, Dries Testelmans, and Bertien Buyse

Contents
40.1 Introduction ................................................................................................................... 340
40.2 Discussion ..................................................................................................................... 340
Conclusion ............................................................................................................................... 343
References ................................................................................................................................ 344

Abbreviations

AAN American Academy of Neurology

ALS Amyotrophic lateral sclerosis
FVC Forced vital capacity
MI-E Mechanical in-exsufflation
MIP Maximal inspiratory mouth pressure
NIV Noninvasive ventilation
PCF Peak cough flow
PEG Percutaneous endoscopic gastrostomy
PSG Polysomnography

B. Vrijsen, PT, MSc (*)

Department of Pulmonology, Leuven University Centre for Sleep/Wake Disorders (E352),
University Hospitals, Herestraat 49, Leuven 3000, Belgium
Faculty of Kinesiology and Rehabilitation Sciences, KULeuven, Leuven, Belgium
e-mail: [email protected]
D. Testelmans, MD, PhD • B. Buyse, MD, PhD
Department of Pulmonology, Leuven University Centre for Sleep/Wake Disorders (E352),
University Hospitals, Herestraat 49, Leuven 3000, Belgium
Department of Clinical and Experimental Medicine, KULeuven, Leuven, Belgium
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 339

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_40
340 B. Vrijsen et al.

40.1 Introduction

Amyotrophic lateral sclerosis (ALS) is the most frequently occurring progressive

neurodegenerative disease in adults, affecting approximately 1.5 out of every
100,000 people per year [1]. ALS is characterized by progressive muscle weakness
of the voluntary muscles. At a certain point in the disease progression, alveolar
hypoventilation occurs because of further progressive weakness of the respiratory
muscles. At that time, noninvasive ventilation (NIV) can be suggested to relieve
symptoms of alveolar hypoventilation.
NIV has been shown to improve survival and quality of life in patients with
ALS [2]. However, with the use of NIV in ALS patients, several difficulties can
occur, such as bulbar weakness, immobility, and sialorrhea, and the question of
when and how to start NIV to assure an appropriate treatment has not been defini-
tively answered. The rapidly evolving devices coming to the market also confront
us with new treatment modalities, and whether they can improve the treatment in the
ALS population is uncertain. Finally, although they show an enormous willingness,
we often see patients in whom NIV is not tolerated at all.

40.2 Discussion

Whether bulbar weakness is present or not in patients with ALS is often a major
difference at the initiation of NIV. Bulbar-affected patients often have problems
with sialorrhea and swallowing. When initiating NIV in patients with sialorrhea, it
is important to reduce the amount of salivary secretions. Medication, such as oxy-
butynin and amitriptyline, and botulinum toxin injections can help patients in the
management of their saliva. Speech therapists can provide useful information on
effective swallowing. During nocturnal NIV, however, the possibility of aspiration
of saliva remains, certainly during use of oronasal interfaces.
The choice of mask is an important issue at initiation of NIV. Oronasal interfaces
can be a solution when mouth leakages are persistent (even after the use of nasal
mask plus chin strap), however, oronasal interfaces can increase the chance of aspi-
ration. Furthermore, oronasal masks can induce obstructive events by causing back-
ward movement of the tongue during inspiration [3].
One of the new modalities in the recently developed devices is target-volume
ventilation. Research on this topic has been performed in patients with chronic
obstructive pulmonary disease, obesity hypoventilation syndrome, and kyphoscoli-
osis. To our knowledge, this research has not been performed in ALS patients.
Theoretically, target-volume ventilation could be an addition to pressure support
ventilation as it could change its pressure during different sleep stages or even in the
further rapid progression of the disease. By increasing pressure, though, the chance
of causing leaks increases, especially in the occurrence of bulbar progression.
The criteria of the American Academy of Neurology (AAN) to initiate NIV in
ALS patients were updated in 2009 [4]. Patients with ALS could be started on NIV in
the presence of symptoms of nocturnal hypoventilation and one of the following cri-
teria: predicted forced vital capacity (FVC) <50 % predicted, maximal inspiratory
mouth pressure (MIP) <60 cm H2O, sniff nasal inspiratory pressure (SNIP) <40 cm
40 Noninvasive Ventilation in Amyotrophic Lateral Sclerosis 341

H2O, or abnormal nocturnal oximetry. The most recent European guidelines suggest
starting NIV when one or more symptoms of respiratory failure are occurring and at
least one parameter similar to the AAN guidelines, except for FVC <80 % predicted
or a morning arterial carbon dioxide >45 mmHg [5]. It is most important to consider
the rapid, and sometimes even unexpected, onset of respiratory failure. Therefore,
routine follow-up of the above-mentioned parameters is necessary so that NIV treat-
ment can be discussed with the patient and family and NIV can be initiated at the right
time. The chance of having an unanticipated emergency tracheostomy can thereby be
strongly reduced. However, the correct timing of starting NIV in severe bulbar patients
should still be studied because these patients often have difficulties in performing
FVC, MIP, and SNIP measurements, and the complaint of orthopnea because of respi-
ratory muscle impairment in these patients is often confused with shortness of breath
caused by difficulties in managing salivary secretions in the supine position.
The discussion about how to monitor NIV titration and follow-up afterwards, not
only in ALS patients, is ongoing. NIV parameters set according the patient’s comfort
during daytime may not ensure adequate nocturnal ventilatory support, because being
asleep influences the ventilatory pattern by inducing modifications of ventilatory con-
trol, upper airway patency, and respiratory muscle recruitment. Until now, no uniform
strategy has been stated regarding how to monitor ALS patients with NIV. Monitoring
can range from a single arterial blood gas measurement to full video-polysomnogra-
phy (PSG). Nocturnal oxygen saturation measurement is now generally accepted as a
minimal measurement during NIV titration, although nocturnal transcutaneous car-
bon dioxide measurement can have great additional value because some patients can
have normal oxygen saturation with an increased carbon dioxide level. Nevertheless,
these measurements do not provide any information about some important interac-
tions between patient and ventilator. Therefore, polygraphy (thoracic-abdominal belts
combined with nocturnal oximetry and flow and pressure recordings) provides addi-
tional information on the synchrony between patient and ventilator and perhaps
explain why NIV is not effective at a certain moment. As alveolar hypoventilation
typically occurs first during rapid-eye-movement sleep, PSG combined with noctur-
nal transcutaneous carbon dioxide measurement can ensure NIV initiation in time, at
the earliest moment of carbon dioxide retention. Furthermore, because sleep is often
disturbed in patients with ALS, the use of PSG during NIV titration could give evi-
dence of improvement in sleep structure and sleep quality.
NIV improves survival and quality of life in ALS patients, but as NIV is initially
used during the night, it is important to improve sleep quality and sleep structure in
these patients. Until recently, only two studies reported on objective sleep parame-
ters in ALS patients with NIV treatment [6, 7]. NIV seemed to have no effect on
sleep because sleep structure did not improve during PSG measurement shortly
after initiation [6]. In a group of ALS patients, already on NIV for 8.3 ± 4.8 months,
a high patient-ventilator asynchrony index and time spent in asynchrony were
observed [7]. No data were reported on sleep architecture in this study, but asyn-
chrony between patient and ventilator could cause an increase in arousals and awak-
enings with deterioration of sleep structure and sleep quality. It is important to
notice that, in both studies, NIV is initiated at home according to patient comfort,
awake efficacy, and awake oxygen saturation. However, a prospective study using
in-hospital PSG to titrate NIV in ALS patients showed an improvement in sleep
342 B. Vrijsen et al.

structure immediately after NIV initiation in patients with none to mild bulbar
involvement. This improvement remained after 1 month of NIV use [8].
At the beginning, NIV is used during the night. But as the disease progresses and
daytime alveolar hypoventilation develops, patients become dependent on NIV dur-
ing the daytime. Mouthpiece ventilation could be tried, but as most of patients have
at least a minimal deterioration of bulbar muscle strength, it becomes difficult to
keep the mouthpiece in place. An alternative is to use a different interface during
daytime. Nasal prongs have minimal contact with the patient’s face and have the
advantage that patients still have good vision and can keep their glasses on.
Alternating interfaces between night and day also ensures different pressure points
on the face, resulting in less chance of skin lesions.
Patients with ALS eventually reach the level of total inability to move or speak,
meaning that they will become unable, if not already at NIV initiation, to solve
problems with the ventilator independently. Therefore, assuring adequate alarms
and a battery, to which the device cycles during power supply failure, seem neces-
sary. The battery cycle life time also becomes important once patients become
dependent of their ventilator during daytime. NIV devices can be placed on the back
of the wheelchair, ventilating the patient via mouthpiece or mask and assuring the
highest possible independence and quality of life.
Patients with ALS, and certainly those with bulbar involvement and those with
daytime NIV, are confronted with nutritional problems and excessive weight loss.
Placement of a percutaneous endoscopic gastrostomy (PEG) is a possible solution,
but being in supine position with a gastrostomy scope in the esophagus for several
minutes can cause major problems in the oxygen saturation and carbon dioxide
levels. Therefore, in these patients, PEG placement can be performed during NIV
use with an adapted mask with an entrance for the gastrostomy scope. In our center,
we always use a volume-controlled mode during the procedure and put the patient
back on the normal settings immediately at the end of the procedure until the effects
of the sedatives are fully dissipated.
Adequate NIV and respiratory physiotherapy are inseparably connected. Clearing
bronchopulmonary secretions is essential for a cooperative performance between the
ventilator and the patient and preventing sputum retention and lower respiratory tract
infections. A cough is sufficient if a peak cough flow (PCF) of 160 l/min is reached.
However, once ALS patients perform a PCF <270 l/min, cough augmentation tech-
niques should be taught to prevent secretion accumulation and respiratory infections.
Several techniques are described to improve cough efficiency: thoracic (abdominal)
thrust, air stacking, and mechanical insufflation-exsufflation (MI-E). Thrust can be per-
formed during the expiratory phase of the cough, improving PCF. Air stacking, per-
formed by a resuscitation balloon or volume-controlled ventilator, increases the
inspiratory capacity before coughing but also, because of the elastic recoil of the lungs,
increase PCF. Air-stacking can also be performed preventively on daily base to avoid
atelectasis and respiratory infection. The combination of both techniques often results
in a higher PCF than each separately. Once thrust and air-stacking become insufficient,
MI-E may be required. In severe bulbar patients though, these cough augmentation
techniques may have no clinical effect and other methods of clearing airway secretions
are necessary. Suctioning or placement of tracheostomy can then be discussed.
40 Noninvasive Ventilation in Amyotrophic Lateral Sclerosis 343

NIV is initially started during the nighttime and is mostly followed by daytime
ventilation. However, ALS progresses in a way that NIV will not be able to compen-
sate for the respiratory muscle weakness and respiratory impairment or (certainly
severe bulbar) patients become intolerant of their ventilation. At that time, one can
choose between two options: palliative sedation using benzodiazepines or opioids if
patients decide to end their life, or tracheal ventilation if patients decide to continue
their life. The decision concerning end-of-life care should be taken in advance as
unwanted tracheostomies should be avoided when patients are admitted to the emer-
gency unit with respiratory failure.

Conclusion
Initiation of NIV in patients with ALS often is accompanied by difficulties.
Bulbar involvement is one of the major issues, having consequences on mask
choice, increasing the risk of aspiration, and defining the appropriate time of
NIV initiation. As patients are not able to move and become completely depen-
dent on their ventilator, ventilators should be carefully selected and a battery is
necessary. The choice of mask should also be made with caution, especially as
patients become increasingly more dependent on their ventilator.
A large diversity is found in monitoring NIV during the start-up procedure,
but nocturnal oximetry measurement is found to be minimal. Polygraphy and
PSG seem to have important additional effects, especially when trying to improve
patient-ventilator synchrony and sleep quality.

Key Recommendations
• When starting patients with ALS on NIV, one should control hypersaliva to
minimize the risk of aspiration and respiratory tract infections.
• It is generally agreed that NIV titration during the daytime is insufficient
as the ventilatory pattern is different between day and night. Nocturnal
oxygen saturation measurement should be a minimum, but transcutaneous
carbon dioxide measurement and polygraphy are excellent additions in
titrating and following-up NIV, as these measurements assure the effi-
ciency and the synchrony between patient and ventilator.
• Advanced care planning is of major importance in ALS, as ALS is a rapid
progressive disease with an uncertain course. Unwanted tracheostomies
should especially be avoided, and the wishes of the patient (and family)
concerning the end of life should be discussed in advance.
• Ventilators and interfaces should be chosen with great care. To assure
the best possible independence and safety, a battery is necessary. As
patients develop daytime hypoventilation and the ventilator is used dur-
ing daytime, different interfaces will be necessary to decrease the risk of
skin lesions.
• To assure a successful treatment with NIV, a respiratory physiotherapist
should be included in the NIV team.
344 B. Vrijsen et al.

References
1. Radunovic A, Mitsumoto H, Leigh PN. Clinical care of patients with amyotrophic lateral scle-
rosis. Lancet Neurol. 2007;6:913–25.
2. Bourke S, Tomlinson M, Williams T, et al. Effects of non-invasive ventilation on survival and
quality of life in patients with amyotrophic lateral sclerosis. Lancet Neurol. 2006;5:140–7.
3. Vrijsen B, Buyse B, Belge C, et al. Upper airway obstruction during noninvasive ventilation
induced by the use of an oronasal mask. J Clin Sleep Med. 2014;10:1033–5.
4. Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient
with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cog-
nitive/behavioral impairment (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1227–33.
5. Andersen PM, Abrahams S, Borasio GD, EFNS Task Force on Diagnosis and Management
of Amyotrophic Lateral Sclerosis, et al. EFNS guidelines on the clinical management of
amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. Eur J Neurol.
2012;19:360–75.
6. Katzberg HD, Selegiman A, Guion L, et al. Effects of noninvasive ventilation on sleep out-
comes in amyotrophic lateral sclerosis. J Clin Sleep Med. 2013;9:345–51.
7. Atkeson A, RoyChoudhury A, Harrington-Moroney G, et al. Patient-ventilator asynchrony
with nocturnal non-invasive ventilation in ALS. Neurology. 2011;77:549–55.
8. Vrijsen B, Buyse B, Belge C, et al. Noninvasive ventilation improves sleep in amyotrophic
lateral sclerosis: a prospective polysomnographic study. J Clin Sleep Med. 2015;11(5):559–66.
Noninvasive Ventilation in Myasthenic
Crises 41
Susana Pinto and Mamede de Carvalho

Content
References ................................................................................................................................ 348

Abbreviations

EPAP Expiratory positive airway pressure

ICU Intensive care unit
IMV Invasive mechanical ventilation
IPAP Inspiratory positive airway pressure
MC Myasthenic crisis
MG Myasthenia gravis
NIV Noninvasive ventilation
PaCO2 Partial pressure of carbon dioxide in arterial blood
RI Respiratory insufficiency
SpO2 Saturation level of oxygen in hemoglobin by arterial puncture

S. Pinto (*)
Neuromuscular Unit, Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal
e-mail: [email protected]
M. de Carvalho
Faculdade de Medicina, Translational and Clinical Physiology Unit, Institute of Molecular
Medicine, Universidade de Lisboa, Lisbon, Portugal
Neuroscience Department, Centro Hospitalar Lisboa Norte – Hospital de Santa Maria,
Lisbon, Portugal

© Springer International Publishing Switzerland 2016 345

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_41
346 S. Pinto and M. de Carvalho

Myasthenic crisis (MC) has long been described as acute neuromuscular respiratory
insufficiency (RI) requiring mechanical ventilation in patients with myasthenia gra-
vis (MG) [1–3]. MC occurs in about 15–20 % of patients with MG, although 30 %
of MG patients experience some degree of respiratory distress [2, 4, 5]. After the
first MC episode, a second crisis occurs in one-third of patients [6]. Respiratory
infection is the main precipitating factor, occurring in 40 % of cases (bacterial pneu-
monia, viral upper respiratory infection, and bronchitis) [4]. Other factors include
acute aspiration pneumonitis (10 %) and changes in medication (8 %), namely with-
drawal of steroids or anticholinesterase medication, initiation of steroids, or amino-
glycoside administration [4]. In 30 % of patients, no precipitating factor is
identifiable [4]. MC tends to occur early in the course of MG, when the disease is
more severe [6]. The advent of newer and more efficacious therapies, including
thymectomy and immunotherapies [7, 8], has diminished MC events, with fewer
cases occurring in patients with longstanding, poorly controlled MG [6].
MC episodes in MG patients have been traditionally managed using intubation
and invasive mechanical ventilation (IMV), which was responsible for an important
reduction in mortality in the 1970s [9]. However, pulmonary complications, namely
atelectasis and pneumonia, are frequent, increasing morbidity and health-care costs
with longer length stays in the intensive care unit (ICU) [4, 10].
The advent of noninvasive ventilation (NIV) brought a new care approach for
these patients. NIV has been successfully used in treating RI from acute to chronic
settings, in patients with primary pulmonary diseases [11] or with different neuro-
muscular diseases [12, 13]. Bi-level NIV allows the delivery of different inspiratory
and expiratory positive pressures in conscious patients, each cycle being triggered
by the patient’s breathing effort. The inspiratory positive airway pressure (IPAP) is
higher than the expiratory positive airway pressure (EPAP). By overcoming the
upper airway resistance and expanding the lungs with lower work effort, IPAP
ensures an adequate air volume and maintains gas exchange. EPAP prevents the
collapse of the alveoli and lower airways at the end of each breathing cycle, prevent-
ing microatelectasis. Different facial or nasal masks allow a personalized choice for
each patient, increasing comfort and tolerance to NIV. In patients with bulbar weak-
ness, facial masks are chosen so that patients can successfully receive the necessary
inspiratory pressure support.
In MG patients with respiratory fatigue, MC can be effectively handled by NIV,
as an alternative to and preventing IMV [14]. In 2002, in the first work to approach
the benefits of NIV in MG, Rabinstein and Wijdicks [14] report that NIV prevented
IMV in 70 % of the trials (7 out of 11 episodes of MC) but failed to alleviate dys-
pnea in patients with established hypercapnia. Presence of hypercapnia
(PaCO2 > 50 mmHg) at the time of NIV institution predicted its failure (p < 0.01),
which occurred mostly within the first 24 h of NIV usage. Seneviratne and cowork-
ers [15] also found that PaCO2 > 45 mmHg on NIV initiation was the only predictor
of its failure (p = 0.04). In their work, 60 episodes of MC were identified in
52 patients; 40 % (24 episodes) were adapted to NIV and the remaining 46 episodes
to IMV (77 %, initially in 36 plus 10 episodes that required IMV after NIV).
41 Noninvasive Ventilation in Myasthenic Crises 347

Although the working definition of MC used by these authors was acute neuromus-
cular RI in MG patients requiring either IMV or NIV, no criteria for the option of
IMV versus NIV was established [15].
IPAP and EPAP parameters reported in the literature for NIV pressure support in
MC care are usually low, averaging 14/6 mmHg [15], 13/5 mmHg (range
10–16/4–6 mmHg) [14], and 15/6 mmHg in a case study [16]. Oxygen supplementa-
tion is provided as necessary to keep SaO2 > 90 mmHg (range 2–10 l/min) [14]. In the
works by Seneviratne et al. [15] and Rabinstein and Wijdicks [14], mean duration of
NIV usage in the hospital was about 5 days (4.3 ± 2.9 days in the study by Seneviratne
et al. [15] and 5 days in the study by Rabinstein and Wijdicks [14], ranging from 4 h
to 16 days). In both studies, length of stay was significantly lower for episodes suc-
cessfully treated with NIV when compared with those treated with IMV (5.6 days,
range 1.5–21 days vs 13.6 days, range 3–60 days [15] and 7 ± 5 days vs 23 ± 16 days,
p = 0.03 [10], respectively). NIV usage also significantly shortened ICU stay with
decreased rates of pulmonary complications. Despite these results, patients continue
today to be offered NIV less frequently (6.5 %, 141 patients vs 21.5 %, 433 patients,
in a total of 37 % of MC patients studied by Alshekhlee et al. [17]).
Patients included in the published articles were discontinued from NIV after the
MC. It is not clear in the article published by Rabinstein and Wijdicks [14] whether
the four patients who were discharged under NIV continued with it thereafter. In our
center, three patients with MG were unable to sleep without NIV support after
MC. The three female patients (ages at diagnosis 26, 56, and 51 years) have a long
evolution of generalized myasthenia gravis (14, 8, and 19 years, respectively) with
poor pharmacological control. They had positive acetylcholine receptor antibodies
(AChR) and were thymectomized. One had a previous history of pulmonary seques-
tration culminating in pulmonary surgery with secondary iatrogenic unilateral dia-
phragm paresis. After MC, patients continued nocturnal NIV (GoodKnight® 420G,
Puritan Bennet® Tyco Healthcare) with facial masks, switching to nasal masks in
periods of bulbar weakness improvement. The patient with unilateral diaphragm
paresis progressively extended the use of NIV through the day due to dyspnea for
progressive lower efforts and presently uses NIV 24 h a day. These three cases
clarify some of the factors that can contribute to the impossibility of achieving a
nocturnal NIV-free period after MC, namely generalized myasthenia with difficult
pharmacological control and preexisting respiratory function limitations, as in the
case with diaphragm paresis. Additionally, previously existing pulmonary obstruc-
tive disorders can be aggravated by atelectasis. These result from inadequate secre-
tion clearance due to expiratory muscle weakness and inadequate cough. Deficient
gas exchange is improved by the pulmonary expansion provided by NIV. Other rea-
sons can be speculated. Sleep is highly demanding for the respiratory function, even
in healthy subjects. In particular, there is a decrease in the respiratory center output,
the upper airways become more flaccid, and the external intercostals and other
inspiratory accessory muscles do not support the functioning of the diaphragm dur-
ing REM sleep. Therefore, the physiologic respiratory stress of sleep on ventilation
can become more demanding following a MC.
348 S. Pinto and M. de Carvalho

In conclusion, there are few studies in the literature addressing the use of NIV in
MC. However, it is the consensus that NIV should be initiated soon after MC diag-
nosis because it improves gas exchange, reduces patient fatigue, and decreases
respiratory complications as well as the duration of the ventilatory support when
compared with IMV. In MC, multicentric randomized trials comparing NIV with
IMV should be initiated to establish firm guidelines for treating MC.

Key Major Recommendations

• NIV should be initiated soon after the diagnosis of MC, as it improves gas
exchange (lowering respiratory work effort and fatigue), decreases respira-
tory complications, and decreases duration of respiratory support when
compared with IMV.
• Facial masks are preferred over nasal masks in MC with bulbar weakness.
• IPAP and EPAP should be adjusted individually, although the usual aver-
age values are 14/6 mmHg (IPAP/EPAP).
• In MC, randomized trials comparing NIV with IMV should be performed.

References
1. Lacomis D. Myasthenic crisis. Neurocrit Care. 2005;3(3):189–94.
2. Bedlack RS, Sanders DB. On the concept of myasthenic crisis. J Clin Neuromusc Dis.
2002;4(1):40–2.
3. Keesey JC. “Crisis” in myasthenia gravis: an historical perspective. Muscle Nerve.
2002;26(1):1–3.
4. Thomas CE, Mayer SA, Gungor Y, et al. Myasthenic crisis: clinical features, mortality, com-
plications, and risk factors for prolonged intubation. Neurology. 1997;48(5):1253–60.
5. Fink ME. Treatment of the critically ill patient with myasthenia gravis. In: Ropper AH, editor.
Neurological and neurosurgical intensive care. 3rd ed. New York: Raven; 1993. p. 351–62.
6. Mayer SA. Intensive care of the myasthenic patient. Neurology. 1997;48 Suppl 5:S70–5.
7. Qureshi AI, Choudhry MA, Akbar MS, et al. Plasma exchange versus intravenous immuno-
globulin treatment in myasthenic crisis. Neurology. 1999;52(3):629–32.
8. Stricker RB, Kwiatkowska BJ, Habis JA, Kiprov DD. Myasthenic crisis: response to plasma-
pheresis following failure of intravenous gamma-globulin. Arch Neurol. 1993;50(8):837–40.
9. Cohen MS, Younger D. Aspects of the natural history of myasthenia gravis: crisis and death.
Ann N Y Acad Sci. 1981;377:670–7.
10. Varelas PN, Chua HC, Natterman J, et al. Ventilatory care in myasthenia gravis crisis: assess-
ing the baseline adverse event rate. Crit Care Med. 2002;30(12):2663–8.
11. Keenan SP, Brake D. An evidence-based approach to noninvasive ventilation in acute respira-
tory failure. Crit Care Clin. 1998;14(3):359–72.
12. Simonds AK, Muntoni F, Heather S, et al. Impact of nasal ventilation on survival in hypercap-
nic Duchenne muscular dystrophy. Thorax. 1998;53(11):949–52.
13. Pinto AC, Evangelista T, Carvalho M, et al. Respiratory assistance with a non-invasive
ventilator (Bipap) in MND/ALS patients: survival rates in a controlled trial. J Neurol Sci.
1995;129:S19–26.
14. Rabinstein A, Wijdicks EF. BiPAP in acute respiratory failure due to myasthenic crisis may
prevent intubation. Neurology. 2002;59(10):1647–9.
41 Noninvasive Ventilation in Myasthenic Crises 349

15. Seneviratne J, Mandrekar J, Wijdicks EFM, Rabinstein AA. Noninvasive ventilation in myas-
thenic crisis. Arch Neurol. 2008;65(1):54–8.
16. Agarwal R, Reddy C, Gupta D. Noninvasive ventilation in acute neuromuscular respiratory fail-
ure due to myasthenic crisis: case report and review of literature. Emerg Med J. 2006;23(1):e6.
17. Alshekhlee A, Miles JD, Katirji B, et al. Incidence and mortality rates of myasthenia gravis
and myasthenic crisis in US hospitals. Neurology. 2009;72:1548–54.
 Part V
Hospital Critical Care Applications:
Critical Care Acute Hypoxemic
Respiratory Failure
Noninvasive Ventilation in Acute
Cardiogenic Pulmonary Edema 42
Chiara Lazzeri, Serafina Valente, Adriano Peris,
and Gian Franco Gensini

Contents
42.1 Respiratory and Hemodynamic Effects of Noninvasive Ventilation: Key Elements ...... 354
42.2 NIV Versus Conventional Treatment ............................................................................ 355
42.3 NIV in ACPE Following Acute Coronary Syndrome ................................................... 356
References ................................................................................................................................ 356

Abbreviations

ACPE Acute cardiogenic pulmonary edema

ACS Acute coronary syndrome
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
NIV Noninvasive ventilation
NPPV Noninvasive positive pressure ventilation
PEEP Positive end-expiratory pressure
RCT Randomized controlled trial

C. Lazzeri, MD (*) • S. Valente, MD

Intensive Care Unit of Heart and Vessels Department, Azienda Ospedaliero-Universitaria
Careggi, Florence, Italy
e-mail: [email protected]
A. Peris
Anesthesia and Intensive Unit of Emergency Department, Azienda Ospedaliero-Universitaria
Careggi, Florence, Italy
G.F. Gensini, MD
Intensive Care Unit of Heart and Vessels Department, Azienda Ospedaliero-Universitaria
Careggi, Florence, Italy
Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi,
Fondazione Don Carlo Gnocchi IRCCS, Florence, Italy

© Springer International Publishing Switzerland 2016 353

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_42
354 C. Lazzeri et al.

Acute cardiogenic pulmonary edema (ACPE) is a life-threatening medical emer-

gency. International guidelines recommend the use of noninvasive ventilation (NIV)
(continuous positive airway pressure (CPAP) or noninvasive positive pressure ven-
tilation (NPPV)) in dyspneic patients with ACPE and a respiratory rate >20 breaths/
min to improve breathlessness and reduce hypercapnia and acidosis (Class IIa rec-
ommendation) [1–3]. In fact, ACPE is one of four NIV applications based on ran-
domized controlled trials (RCTs) and a meta-analysis that have provided NIV grade
A evidence regarding this condition [4], together with chronic obstructive pulmo-
nary disease (COPD) exacerbation, immunocompromised conditions, and ventila-
tor weaning in patients with COPD.
The Canadian clinical practice guidelines recommend NPPV or CPAP as the first
option for ventilator support for patients with ACPE and respiratory failure in the
absence of shock or acute coronary syndrome requiring acute coronary revascular-
ization (grade 1A recommendation) and state that CPAP delivered by mask is just
as effective as NPPV [5]. Similar conclusions were reached by reviews and a meta-
analysis [6–11].

42.1 Respiratory and Hemodynamic Effects of Noninvasive

Ventilation: Key Elements

The terms CPAP and NPPV are sometimes used interchangeably, but they are dif-
ferent. With noninvasive CPAP, an interface (usually a face mask) is used to apply a
pressure greater than atmospheric to the proximal airway throughout spontaneous
breathing, thus splinting open the upper airway, increasing lung volume and intra-
thoracic pressure. The work of breathing is entirely assumed by the patient and the
tidal ventilation is completely dependent on the respiratory muscles. NPPV differs
from CPAP because it has two pressure levels, an inspiratory positive airway pres-
sure (which provides mechanical breaths) and an expiratory positive airway pres-
sure, acting as positive end-expiratory pressure (PEEP).
Acute cardiogenic pulmonary edema is characterized by an increase in left ventricle
filling pressures, causing a rise in pulmonary capillary pressure, and thereafter fluid
overload toward the pulmonary interstitial compartment and alveolar spaces [12]. All
these factors lead to an increase in airway resistance, a decrease in lung diffusion
capacity, a drop in functional residual capacity, and an increased intrapulmonary shunt
effect. Hypoxemia develops, associated with an increase in respiratory effort.
The application of intrathoracic positive pressure in patients with ACPE, particu-
larly with PEEP, has the following cardiovascular effects: (a) a decrease in venous
return and in right ventricle preload; (b) a decrease in transmural pressure (transmu-
ral pressure = intraventricular pressure − intrathoracic pressure); and (c) a reduction
in left ventricle afterload [13–15]. Cardiac output and myocardial contractility may
increase. Moreover, the application of positive pressure produces also respiratory
effects. In particular, it favors alveolar recruitment and increases functional residual
capacity, lung compliance, and alveolar ventilation, with a reduction of the intrapul-
monary shunt and respiratory effort, thus improving oxygenation [16].
42 Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema 355

Compared with conventional oxygen therapy, the application of NIV (both CPAP
and NPPV) [17–20] was associated with faster clinical (reduction of respiratory
frequency and of dyspneic sensation) and blood gas improvements (increased PaO2,
reduction of PaCO2 and acidosis) [21]. NPPV has the potential advantage over
CPAP of assisting the respiratory muscles during inspiration, resulting in faster alle-
viation of dyspnea [22–24].
In a retrospective observational study in consecutive patients admitted for ACPE,
neither acidemia nor the type of acidosis on admission was a risk factor for adverse
outcome in ACPE patients treated with CPAP [25]. Similar results were reported by
our group [26] in 65 consecutive patients with ACPE treated with NIV, character-
ized by a more severe hemodynamic impairment as inferred by the high percentage
of devices used and administration of inotropes.

42.2 NIV Versus Conventional Treatment

CPAP was reported to improve survival and avoid intubation in ACPE patients com-
pared with conventional treatment plus oxygen therapy [8, 27–35], and five system-
atic reviews [6–8, 31, 36] consistently demonstrated a significant reduction in
endotracheal intubation with both types of NIV.
The 3CPO trial (Three Interventions in Cardiogenic Pulmonary Oedema), a
large randomized controlled trial including 1069 patients, showed no difference
in short- or long-term mortality rates between standard oxygen therapy and NIV
treatments in patients presenting to emergency departments with severe
ACPE [21]. This finding was not confirmed in a subsequent meta-analysis [9]
(including the 3CPO and five meta-analyses) [6, 8, 33, 37], which reported a
significant mortality benefit of NPPV in ACPE (fixed effect model, risk ratio
0.75, CI 0.61–0.92).
In a Cochrane review [38], including 21 studies and 1,071 subjects, NIV, compared
with standard care, significantly reduced the need for endotracheal intubation, with a
RR of 0.53 (95 % CI 0.34–0.83) and a NNT (number needed to treat) of 8. There was
also a significant reduction in hospital mortality (RR 0.6, 95 % CI 0.45–0.84) and a
NNT of 13. Similar results were reported by Winck et al. [31], in their meta-analysis,
which showed that, in ACPE patients, CPAP and NPPV both significantly decrease
the need for endotracheal intubation, and CPAP significantly reduces mortality when
compared with standard medical therapy. A reduction in mortality was also reported
by Mariani et al. [27], with NIV delivered through either NPPV or CPAP in ACPE
patients.
A recent meta-analysis [39] (including 78 randomized controlled trials) was spe-
cifically focused on the effect of NIV on mortality in acute care settings. In the sub-
analysis of patients with ACPE, NIV showed a beneficial effect on survival when
applied to treat acute respiratory failure (RR 0.64, 95 % CI 0.45–0.90, p = 0.01,
NNT = 16). However, in trials allowing crossover, with NIV used a rescue therapy,
this benefit was not confirmed. This finding strongly suggests the need to focus
future research on the best timing for NIV treatment in ACPE.
356 C. Lazzeri et al.

42.3 NIV in ACPE Following Acute Coronary Syndrome

Inclusion and exclusion criteria varied among the trials. All 15 trials from 2000 to
2009 excluded patients with cardiogenic shock. In addition, 9 of these 15 trials, and
8 of the 10 trials in the period 2005–2009, also excluded patients who required acute
coronary revascularization [19–22, 40–42], or who had acute coronary syndrome
[43, 44].
An early RCT suggested that NPPV was associated with a greater risk of myo-
cardial infarction than was CPAP [45], but many subsequent RCTs did not confirm
this finding [8, 15, 22, 38, 41, 43, 44]. In the Cochrane review by Vital et al. [38],
NIV was not associated with an increased risk in the incidence of myocardial infarc-
tion (RR 1.24, 95 % CI 0.79–1.95) when compared with standard medical care. In
the meta-analysis by Weng et al. [28], NIV was not associated with an incidence of
new myocardial infarction and, likewise, in the meta-analysis of Li H et al. [46],
which included 12 RCTs with a total of 1,433 ACPE patients, the occurrence of new
cases of myocardial infarction and length of stay were also not significantly differ-
ent between CPAP and NPPV.
According to the available evidence, NIV can be safely used in patients with acute
coronary syndrome (ACS) complicated by acute respiratory failure due to ACPE. In
clinical practice, the use of NIV in these patients seems to still be related to local
practices. In the FINN AKVA study group, including 620 acute heart failure (AHF)
patients [47], NIV was used more frequently in the ACS-AHF than in the non-ACS-
AHF patients (38 % vs 18 %, respectively, p < 0.001) [48], but only half of patients
with cardiogenic shock and pulmonary edema were treated with NIV [47].

Key Major Recommendations

• NIV is indicated in patients with ACPE and acute respiratory failure
because it reduces the need for endotracheal intubation and lowers mortal-
ity rates.
• The choice between NPPV and CPAP is often related to the expertise and
skills of the medical team. NPPV offers the advantage of reducing the work
of respiratory muscles, thereby quickly reducing the sensation of dyspnea.
• NIV can be safely used in patients with ACS complicated by acute respira-
tory failure resulting from ACPE.

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42 Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema 359

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Is NIV Safe and Effective in Patients
with ACPE Due to Diastolic Dysfunction? 43
Andrea Bellone, Massimiliano Etteri, Guido Caironi,
Giorgio Gadda, and Roberto Rossi

Contents
43.1 Introduction ................................................................................................................. 361
43.2 Materials and Methods................................................................................................ 362
43.2.1 Ventilator and Interfaces................................................................................ 362
43.2.2 Bedside Ultrasound ....................................................................................... 363
43.2.3 Randomization .............................................................................................. 364
43.3 Discussion ................................................................................................................... 364
References .............................................................................................................................. 365

43.1 Introduction

A large number of patients presenting with acute cardiogenic pulmonary edema

(ACPE) have preserved left ventricular (LV) systolic function and as a result are
affected by diastolic dysfunction. In these patients, survival is similar to that of
patients with reduced ejection fraction [1, 2]. However, no previous studies have
classified patients with ACPE according to a different pathophysiological class
before continuous positive airway pressure (CPAP) treatment. Therefore, the role of
noninvasive ventilation (NIV) in ACPE with preserved systolic function is not well
known. Agarwal and colleagues [3] suggested that CPAP should be used with

A. Bellone, MD (*) • M. Etteri, MD • G. Caironi, RN • R. Rossi, LN

Emergency Department, Azienda Ospedaliera Sant’Anna (Presidio di Como),
Via Ravona 1, San Fermo della Battaglia, 22100 Como, Italy
e-mail: [email protected]; [email protected]; [email protected];
[email protected]
G. Gadda, LN
Emergency Unit, Azienda Ospedaliera Salvini (Presidio di Rho), 20100 Milan, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 361

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_43
362 A. Bellone et al.

caution in patients with diastolic heart failure because a positive airway pressure
may compromise venous return and decrease LV end-diastolic volume, further lim-
iting stroke volume. On the other hand, one open prospective study demonstrated
that the benefit of CPAP in patients with diastolic heart failure could be due to a
decrease in LV end-diastolic volume (preload) [4]. Moreover, another study showed
that resolution time is not significantly different in patients with ACPE with pre-
served or impaired systolic function submitted to CPAP [5].
To define the safety of NIV in ACPE with preserved ejection fraction, we evalu-
ated, in the emergency setting, the response to NIV according to two different dos-
ages of nitrate.

43.2 Materials and Methods

Data were collected from September 2013 to June 2014. Twenty patients affected by
ACPE and diastolic dysfunction admitted to two emergency departments (Como and
Milan, Italy) were enrolled. The protocol was approved by the institutional review
boards at each institution and written informed consent was obtained for each patient.
Inclusion criteria were the presence of clinical signs of ACPE with preserved left
ventricular ejection fraction (LVEF) and respiratory distress (peripheral oxygen satu-
ration (SpO2) <90 % while breathing room air or <92 % while breathing oxygen
(>35 % of inspiratory oxygen concentration (FiO2), respiratory frequency >25
breaths/min, and active accessory respiratory muscles). Exclusion criteria were: (1)
unstable clinical conditions (need for vasopressor more than 24 h, acute coronary
syndrome, life-threatening arrhythmias); (2) refusal of treatment; (3) weak cough
reflex; (4) agitation or non-cooperation; (5) failure of more than two organs; (6) car-
diac arrest; (7) respiratory arrest requiring tracheal intubation; (8) recent trauma or
burns of neck and face; (9) pregnancy; and (10) LV systolic dysfunction.
ACPE patients underwent a morphological bedside cardiac ultrasound investiga-
tion to exclude those with depressed LV function or valvular abnormalities. The
remaining patients were submitted to NIV for 1 h plus pharmacological therapy and
they were randomly divided according to two different dosages of nitrate:

• Group A = 20 mg of nitrate/50 ml of saline at 4 ml/1 h (total 1.6 mg)

• Group B = 20 mg of nitrate/50 ml of saline at 14 ml/1 h (total 4.8 mg).

Diuretics were similar between the two groups of patients = 60 mg of furose-

mide. Patients’ baseline characteristics are shown in Tables 43.1 and 43.2.

43.2.1 Ventilator and Interfaces

All patients received NIV via a standard intensive care unit ventilator with double-
tube circuit in pressure support mode for 1 h after the initial evaluation. They were
randomly assigned to perform NIV with the nitrate lower than 2 mg = Group A or
nitrate greater than 4.5 mg = Group B.
43 Is NIV Safe and Effective in Patients with ACPE Due to Diastolic Dysfunction? 363

Table 43.1 Baseline values versus 1 h

Baseline vs 1 h (mean ± SD)
Group A Group B
Group A 1h p Group B 1h p
Respiratory rate 42 ± 6.5 29.6 ± 9 <0.01 39 ± 4.3 27.2 ± 4 <0.01
(breaths/min)
Arterial pH 7.29 ± 0.13 7.33 ± 0.5 <0.01 7.30 ± 0.11 7.33 ± 0.6 <0.01
PaCO2 (mmHg) 54.7 ± 12.6 43.7 ± 8 <0.01 52.1 ± 14.9 44.0 ± 9 <0.01
PaO2/FiO2 ratio 163 ± 74 269 ± 72 <0.01 169 ± 63 249 ± 66 <0.01
Bicarbonate (Meq) 19 ± 5 21 ± 7 ns 20 ± 7 22 ± 6 ns
Heart rate (beats/min) 97 ± 26 88 ± 42 ns 106 ± 29 89 ± 38 <0.05

Table 43.2 Patients’ outcomes

Group A Group B p
(n = 10) (n = 10) value
Endotracheal intubation 1 (2.5 %) 0 (0 %) ns
In-hospital death 0 (0 %) 0 (0 %) ns
Transient arterial hypotension (<3 min) 1 (10 %) 5 (50 %) 0.05
Prolonged arterial hypotension to need saline 0 (0 %) 1 (10 %) ns
infusion/NIV withold

The oronasal mask assigned to each patient was chosen according to anthropo-
metric characteristics, minimization of air leaks, and tolerance of the patients.
Among the interfaces available in the two units were the Ultra Mirage™ FFM-NV
(ResMed, San Diego, CA, USA) and the PerforMax Face Mask (Philips Respironics,
Murrysville, PA, USA).
The ventilator settings were decided according to the usual practice: maximal
tolerated inspiratory pressure support to obtain a tidal volume of 6–8 ml/kg of body
weight (never greater than 20 cmH2O) and 5 cmH2O positive end-expiratory pres-
sure (PEEP).

43.2.2 Bedside Ultrasound

All patients underwent a morphological cardiac ultrasound investigation shortly

before NIV. Two-dimensional echocardiogram (SONOS 2000, Hewlett-Packard,
Andover, MA, USA) was performed to qualitatively estimate the LV systolic func-
tion. Patients were considered as having LV systolic dysfunction if the ejection
fraction was estimated <45 %. In the absence of this condition and significant val-
vular abnormalities, patients were considered to have preserved systolic function.
Competency of emergency physician ultrasonographers was demonstrated through
multiple steps. Initially, they underwent a training course of fast echography in an
emergency setting and then they performed at least 100 noncardiac and 75 cardiac
364 A. Bellone et al.

ultrasounds with credentialed supervision. In addition, before the start of this study,
all emergency physicians were given a course in goal-directed echocardiography.

43.2.3 Randomization

Patients were randomly assigned to one of the two treatment groups using opaque,
sealed, numbered envelopes. We used a computer-generated randomization
sequence, which was generated by an independent biostatistician who was not oth-
erwise involved in the trial. The envelopes were kept in the head nurses’ offices in
each institution’s critical care unit. The nurses who opened the envelopes were those
on shift that day or night and totally independent of the enrolment process. They
communicated the random treatment allocation to the attending physician that
assigned the patients to the study group.

43.3 Discussion

The results of the preliminary study show that, in patients with ACPE and preserved
LV systolic function, NIV was safe and effective. In group B, with a higher dosage
of nitrate, there was significant transient hypotension, although in-hospital mortal-
ity, adverse events, and the need for invasive mechanical ventilation were similar in
all treated patients regardless of the nitrate dosage.
In our study, patients with ACPE (clinical signs, chest X-ray, and interstitial
syndrome by ultrasound evaluation) and preserved systolic function and no valvular
abnormalities were supposed to be affected by LV diastolic dysfunction. The
strength of our study is the use of cardiac echoes to assess LV function by emer-
gency department physicians just before bi-level positive airway pressure begins in
patients with acute respiratory distress.
Gudmunsson and colleagues [6] have suggested that eyeballing ejection fraction
may be the most accurate echocardiographic method for the assessment of LV sys-
tolic function and could be used for routine echocardiography instead of formal
methods.
Aurigemma et al. [7] suggested that the effects of positive pressure therapy com-
promise venous return and decrease LV end diastolic volume, further limiting stroke
volume and, hence, cardiac output because of the steep curve for LV diastolic pres-
sure in relation to volume with resultant deterioration in hemodynamics. In contrast,
Gutierrez-Chico and colleagues [8] suggested that chronic diastolic heart failure is
different from ACPE due to diastolic dysfunction, where transthoracic echocardiog-
raphy underestimates LV end diastolic volume.
For this reason, we decided to evaluate patients with ACPE and diastolic dys-
function with a different nitrate dosage. In this way, we could stress the potential
negative effects of positive airway pressure in these patients, but the results of this
preliminary study shows that the application of NIV in patients with ACPE due to
diastolic dysfunction seems to be safe and effective regardless of nitrate dosage.
43 Is NIV Safe and Effective in Patients with ACPE Due to Diastolic Dysfunction? 365

In conclusion, we suggest:

1. NIV is safe and effectiveness in diastolic cardiogenic pulmonary edema

2. The transient arterial hypotension caused by the combination of NIV and nitrate
therapy in patients with diastolic dysfunction does not compromise the beneficial
effects.

Conflict of Interest The authors declare that they have no conflicts of interest.

References
1. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure
with preserved ejection fraction. N Engl J Med. 2006;355:251–9.
2. Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved ejection fraction in a
population-based study. N Engl J Med. 2006;355:260–9.
3. Agarwal R, Agarwal AN, Gupta D, Jindal SK. Evidence based review: non-invasive ventilation
in acute cardiogenic pulmonary edema. Postgrad Med J. 2005;81:637–43.
4. Bendjelid K, Shutz N, Suter PM, et al. Does continuous positive airway pressure by face mask
improve patients with acute cardiogenic pulmonary edema due to left ventricular diastolic dys-
function. Chest. 2005;127:1053–5.
5. Bellone A, Monari A, Cortellaro F, et al. Myocardial infarction rate in acute pulmonary edema:
non-invasive pressure support ventilation versus continuous positive airway pressure. Crit Care
Med. 2004;32:1860–5.
6. Gudmundsson P, Ryberg E, Winter R, Willenheimer R. Visually estimated left ventricular ejec-
tion fraction by echocardiography is closely correlated with formal quantitative methods.
Intern J Cardiol. 2005;101:209–12.
7. Aurigemma GP, Gaasch WH. Diastolic heart failure. N Engl J Med. 2004;351:1097–105.
8. Gutierrez-Chico JL, Zamorano JL, Perez de Isla L, et al. Comparison of left ventricular vol-
umes and ejection fractions measured by three-dimensional echocardiography versus two-
dimensional echocardiography and cardiac magnetic resonance in patients with various
cardiomyopathies. Am J Cardiol. 2005;95:809–13.
Noninvasive Mechanical Ventilation
in Acute Cardiogenic Pulmonary Edema 44
and Cardiac Procedures: How to Choose
the Most Appropriate Mode
and Improve Its Programming

Javier Mendoza Vázquez

Contents
44.1 Introduction ................................................................................................................. 367
44.2 Modes of NIMV and Therapeutic Effects .................................................................. 368
44.3 NIMV Versus Standard Medical Treatment in ACPE ................................................ 368
44.4 NIMV in APCE and Cardiogenic Shock .................................................................... 370
44.5 CPAP or BIPAP? ......................................................................................................... 370
44.6 Programming of NIMV .............................................................................................. 371
44.7 NIMV in Cardiac Procedures...................................................................................... 372
Bibliography .......................................................................................................................... 372

44.1 Introduction

Acute cardiogenic pulmonary edema (ACPE) is a life-threatening situation with

10–20 % risk of in-hospital mortality, especially when it is associated with acute
myocardial infarction [1]. Thus, it is important to treat it appropriately. While
treating the trigger for the ACPE (i.e., fast ventricular rate atrial fibrillation or
myocardial ischemia), treatment must simultaneously be started with intrave-
nous diuretics (which have an immediate venodilator action that reduces pre-
load and subsequent removal of fluid), opiates (which reduce anxiety, relieve
distress associated with dyspnea, reduce preload by venodilator effect, and
reduce sympathetic drive), and possibly a vasodilator if systolic blood pressure
is >110 mmHg or inotropics for patients with hypotension or severe reduction
in cardiac output [2].
While these measures take effect, blood oxygenation must be improved (and CO2
elimination in case of global respiratory failure) and respiratory muscular fatigue

J. Mendoza Vázquez
Acute Cardiac Care Unit, Arnau De Vilanova University Hospital, Lleida, Spain
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 367

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_44
368 J.M. Vázquez

reduced to avoid endotracheal intubation (ETI) and invasive mechanical ventilation

(IMV) that is related to significant morbidity and mortality. Finally, the suffering of
patients with ACPE must be reduced. To achieve all these objectives, noninvasive
mechanical ventilation (NIMV) can be used to apply positive pressure and oxygen
into the airway through an external interface (usually a mask).

44.2 Modes of NIMV and Therapeutic Effects

There are two modes of NIMV:

Continuous positive airway pressure (CPAP): fixed positive pressure is applied

throughout the entire respiratory cycle, increasing oxygenation by alveolar recruit-
ment. Strictly speaking, CPAP is not a true mode of ventilation because it does not
provide any inspiratory support [3]. It is used in hypoxemic respiratory failure.
Bi-level positive airway pressure (BIPAP): there is an expiratory positive airway pres-
sure (EPAP) that recruits alveoli and prevents their collapse, increasing oxygen-
ation and inspiratory positive airway pressure (IPAP), which reduces the inspiratory
effort and diaphragm fatigue, increasing the tidal volume. This is the mode that
should be used in patients with hypercapnia and global respiratory failure and even
in patients without hypercapnia but with signs of significant respiratory fatigue.
Compared with CPAP, BIPAP produces greater improvements in oxygenation and
CO2 clearance and a greater reduction in the work of breathing in patients with
ACPE [1]. However, the superiority of BIPAP over CPAP has not been demon-
strated in reducing mortality in the treatment of ACPE [4].

In summary, application of positive airway pressure with NIMV in ACPE has posi-
tive respiratory effects, improving alveolar ventilation and gas exchange and reducing
respiratory muscular fatigue. It also has hemodynamic effects, by reducing preload and
afterload, which, in patients with ACPE (who are usually “afterload dependent”),
improve cardiac performance and myocardial oxygen imbalance [5] (Fig. 44.1).

44.3 NIMV Versus Standard Medical Treatment in ACPE

In 2013, a meta-analysis was published that included 32 studies (2,916 participants)

to determine the effectiveness and safety of NIMV in the treatment of ACPE. NIMV
added to standard medical treatment (SMT) has several benefits compared with
SMT alone [4]:

• Reduction in the need for ETI, with risk difference (RD) of −12 % (95 % CI
−0.19 to −0.04) and a number needed to treat (NNT) of 8 [4]. Lower ETI favored
BIPAP-treated patients (RR 0.45, 95 % CI 0.26–0.80) [4]. This effect is
44 Noninvasive Mechanical Ventilation in Acute Cardiogenic Pulmonary Edema 369

NIMV

CPAP/BIPAP CPAP BIPAP

↑ Intrathoracic pressure Alveolar recruitment ↑ Tidal Volume

Counterbalancing starling forces

↓ Cava vein retourn ↑ PVR ↓ LV afterload ↓ Pulmonary shunt

↓ RV preload ↑ RV afterload ↑ Blood oxygenation ↑ CO2 removal

↓ LV preload

Preload dependent Afterload dependent

• Normal heart • LV dysfunction + PCWP ≥19 mm Hg
• RV infraction
• Hypovolemia
• OHCM
• Cardiac tamponate
• Pulmonary embolism

↓ CO ↑ CO

↓ Oxygen delivery ↑ Oxygen delivery

Fig. 44.1 BIAP bilevel positive airway pressure, CO cardiac output, CPAP continuous positive air-
way pressure, LV left ventricle, NIMV non invasive mechanical ventilation, OHCM obstructive hyper-
trophic cardiomyopathy, PRV pulmonary vascular resistance, RV right ventricle. Colors: haemodynamic
effects (in red); respiratory effects (in blue) (Modified from Wiesen et al. [5] with permission)

important because of the related complications of IMV. Patients with hypoxic

respiratory failure due to ACPE treated with NIMV have the lowest intubation
rate (10 %) compared with other etiologies [6].
• The impact on mortality remains controversial [3]. The largest randomized
trial [1], with a total of 1,069 patients, did not show an effect on short-term
mortality. This trial was included in the Cochrane meta-analysis [4], which
showed significantly reduced hospital mortality (RR 0.66, 95 % CI 0.48–
0.89). However, the evidence for this potential benefit is derived from small
trials. No difference was found in hospital mortality comparing CPAP and
BIPAP directly [4].
• Reduction in intensive care unit length of stay by 1 day [4].
• There were no significant increases in the incidence of acute myocardial infarc-
tion with NIMV during its application [4], an adverse outcome that was found in
some previous studies.
• Less progressive respiratory distress and neurological failure (coma) [4].

In summary, the use of NIMV is an important part of the treatment of ACPE, and
the sooner it is started, the better. We need to “ventilate the patient” instead of “oxy-
genate the patient.”
370 J.M. Vázquez

44.4 NIMV in APCE and Cardiogenic Shock

There are two groups depending on the haemodynamic effect of the NIMV [5]:

• The afterload-dependent group: Patients with a dysfunctional left ventricle (even

with myocardial infarction) with high pulmonary capillary wedge pressure
(PCWP) are extremely sensitive to changes in afterload. Patients with a PCWP
≥19 mmHg experience improvement in their cardiac output (CO) with the addi-
tion of 3–8 cmH2O of positive end-expiratory pressure (PEEP) [5].
• The preload-dependent group: Patients with normal heart, hypovolemia, right
ventricular infarction, or obstructive hypertrophic myocardiopathy. In all these
patients, NIMV can decrease CO, so adequate intravascular repletion must be
ensured.

Thus, patients with ACPE with left ventricule dysfunction and cardiogenic shock
can have positive hemodynamic effects by using NIMV with moderate levels of
PEEP and CPAP. These patients have tenuous hemodynamic status, therefore inap-
propriate ventilation settings could have severe deleterious effects [5]. Careful pro-
gramming and close monitoring to avoid asynchrony and leaks are important.

44.5 CPAP or BIPAP?

According to blood gas analyses, one should choose CPAP in hypoxemic patients
and BIPAP in patients who are hypercapnic or in global respiratory failure. But one
should also be mindful of clinical factors, and it is not always possible to wait for
blood gas analyses to decide, initially, the modality of NIMV. The initial choice and
programming should be guided by physical signs (e.g., breathing pattern, respira-
tory fatigue signs), comorbidity, patient´s physical features and pressure, flow curve
analysis, and blood gas analysis. Cardiac wasting syndrome, pleural effusion, and
ascites (three common conditions in advanced heart failure patients) and chronic
obstructive pulmonary disease (COPD), a common comorbidity in heart failure
patients, should be kept in mind.
Patients who should preferably be ventilated with BIPAP include those with

• COPD: These patients have greater work of breathing than others and have a ten-
dency to hypercapnia. CPAP can increase the work of breathing working like an
expiratory obstacle that increase hyperinsuflation. Thus, CPAP could aggravate
autoPEEP and consequently increases inspiratory effort. In BIPAP model, an adecu-
ate level of EPAP counterbalances auto-PEEP and decrease inspiratory effort. EPAP
must be carefully titrated from 4 cmH2O (lower than in other patients) because an
excessive level of EPAP can increase the inspiratory effort (for the same reason as
CPAP); excessive IPAP that could aggravate hyperinsufflation should be avoided.
• Significant obesity and ascites: Both increase the diaphragm’s effort to inspire,
so they benefit from BIPAP.
44 Noninvasive Mechanical Ventilation in Acute Cardiogenic Pulmonary Edema 371

• Cardiac cachexia: The muscular weakness in these patients makes more ten-
dency to appear respiratory fatigue, that could be treated and prevent with IPAP.
• Significant pleural effusion, which increases inspiratory effort.
• Important signs of inspiratory fatigue: These include thoracoabdominal dissocia-
tion and sternocleidomastoid activation.
• Inspiratory failure during CPAP: Low volume/min with correct respiratory rate
or correct but with persisting inspiratory fatigue signs and/or hypercapnia.

44.6 Programming of NIMV

General rules for initial programming of NIMV are available, including how to
change it depending of blood gas analyses, physical signs, and analysis of
flow-pressure waveforms and leaks [7]. For patients with ACPE who are treated
with CPAP (hypoxemic patients, those without important fatigue signs or
COPD):

• Begin with 5 cmH2O CPAP and with FiO2 required to achive a pulse oximetry satu-
ration (Sat O2) < 90 %, increase CPAP in 2 cmH2O increments in order to reduce
the FiO2 below 60 % (preferably <50 %) to avoid oxygen toxicity.
• Remember that the maximum CPAP level is 12 cmH2O. If hypoxemia is not cor-
rected, consider increasing FiO2.
• Progressively decrease in 2 cmH2O increments when the patient is
ameliorating.
• If hypercapnia, respiratory fatigue signs, or tidal volume (TV) <7 ml/kg is pres-
ent, change to BIPAP.

Patients treating with BIPAP:

• Begin with 10 cmH2O IPAP and 5 cmH2O EPAP. The goal is to achieve Sat O2
>90 % in chronic hypercapnic patients or >92–95 % in others.
• Program a slope pressure as steep as possible to prolong the expiration cycle to
remove CO2.
• Increase IPAP in 2 cmH2O increments until a TV of 7–8 ml/kg is achieved.
Consider increasing further if the sternocleidomastoid contraction persists, with
a maximum of 25 cmH2O. Rule out excessive EPAP that could lead to increasing
inspiratory effort.
• If saturation <90 % and there is no bradypnea (which can be corrected with
assisted mode) with low VT, consider increasing IPAP. If it is correct, increase
EPAP or FiO2, as with the previous option.
• If abdominal contraction appears (expiratory effort by excessive IPAP), decrease
IPAP. Rule out excessive EPAP also.
• If there is an auto-PEEP pattern in the flow curve: First, consider whether the
dyspnea could be undertreated (opiates). This generates tachypnea, which in
372 J.M. Vázquez

COPD leads to auto-PEEP. Consider bronchodilators if bronchospasm is present.

Second, rule out hyperinsufflation, in which case one should decrease
IPAP. Finally, if the previous possibilities are ruled out, change EPAP until the
auto-PEEP pattern disappears. Keep in mind that the repetitive failed inspirations
is usually secondary to auto-PEEP.

In both modalities one should avoid excessive leaks, adjusting the mask and
procuring a 30–45° position. Nasal masks are not adequate in ACPE because the
mouth is usually open. An oronasal mask is the most commonly used interface.

44.7 NIMV in Cardiac Procedures

Decubitus is required to perform the following cardiologic procedures: catheteriza-

tion, percutaneous valve implantation, definitive and transitory pacemaker implan-
tation, intra-aortic balloon counterpulsation (IABCP), transesophageal
echocardiography (TEE), and electrophysiologic studies. Decubitus reduces the
functional residual capacity and cannot be tolerated by patients with chronic respi-
ratory failure, either COPD or restrictive respiratory failure (i.e., obesity or neuro-
muscular disease) and orthopneic heart failure patients [8]. Furthermore, decubitus
increases the venous return that increases preload and leads to a rise of
PCWP. Therefore, decubitus is not tolerated in acute respiratory failure and can lead
on to acute respiratory failure in some stable patients.
One should not pospone some cardiac procedures because it worsen prognosis,as
in the case of urgent catheterization in acute myocardial infarction, urgent transitory
pacemaker implantation, or IABCP implantation. To achieve decubitus toleration
and avoid general anesthesia, one can use NIMV [9]. Furthermore, in case of femo-
ral artery percutaneous interventions, several hours of decubitus–semi-decubitus
after the procedure may be necessary to ensure correct hemostasis and it could be
required more time during venous femoral transitory pacemaker stimulation or arte-
rial femoral intra-aortic balloon counterpulsation.
Finally, in orthopneic cardiac patients needing TEE, NIMV can be performed
with the TEE probe passed through a modified face mask [9].

Bibliography
1. Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J, 3CPO Trialists. Noninvasive
ventilation in acute cardiogenic pulmonary edema. N Engl J Med. 2008;359:142–51.
2. McMurray JJ, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart
failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure
2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure
Association (HFA) of the ESC. Eur Heart J. 2012;33:1787–847.
3. Mas A, Masip J. Noninvasive ventilation in acute respiratory failure. Int J Chron Obstruct
Pulmon Dis. 2014;9:837–52.
44 Noninvasive Mechanical Ventilation in Acute Cardiogenic Pulmonary Edema 373

4. Vital FM, Ladeira MT, Atallah AN. Non-invasive positive pressure ventilation (CPAP or
bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev.
2013;(5):CD005351.
5. Wiesen J, Ornstein M, Tonelli AR, Menon V, Ashton RW. State of the evidence: mechanical
ventilation with PEEP in patients with cardiogenic shock. Heart. 2013;99(24):1812–7.
6. Antonelli M, Conti G, Moro ML, Esquinas A, Gonzalez-Diaz G, Confalonieri M, et al.
Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypox-
emic respiratory failure: a multi-center study. Intensive Care Med. 2001;27(11):1718–28.
7. Barrot-Cortés E, Sánchez-Gómez E. Manual SEPAR de procedimientos. Ventilación mecánica
no invasiva. Barcelona: Respira-fundación española del pulmón-SEPAR; 2008.
8. Galeas-López JL, Muñoz-Bono J. Ventilación mecánica no invasiva en procedimientos
endoscópicos. In: Esquinas Rodriguez AM, editor. Fundamentos de la organización hospital-
aria en ventilación mecáncia no invasiva. 2011. p. 103–6.
9. Ambrosino N, Guarracino F. Unusual applications of noninvasive ventilation. Eur Respir J.
2011;38:440–9.
Practical Approach to the Use
of Noninvasive Ventilation in Patients 45
with ACPE

Jacobo Bacariza Blanco and Antonio M. Esquinas

Contents
45.1 Introduction ................................................................................................................. 375
45.2 Heart-Lung Interactions during NIV: Why? (The Essentials) .................................... 376
45.3 NIV in Acute Chronic Cardiac Exacerbations: When, How and Where to Do It? ..... 377
References .............................................................................................................................. 380

45.1 Introduction

With regard to current noninvasive ventilation (NIV) practice, there are just four key
A level indications supported by evidence-based medicine: chronic obstructive pul-
monary disease (COPD) exacerbation, pulmonary infiltrates in immunocompro-
mised patients, weaning with COPD, and, finally, cardiogenic pulmonary edema.
These are what Nava [1] called “the fabulous four.” Acute-on-chronic cardiac fail-
ure exacerbation was not among those admitted to this club, but it is the only current
indication among the cardiac diseases. The reason for the use of NIV in this clinical
situation can be explained by the heart-lung interactions during mechanical ventila-
tion (MV). When, how, and especially where to apply NIV are of major concern in
achieving our therapeutic goals. The objective of this chapter is to answer these
questions, why and where, based on current data in the literature.

J.B. Blanco (*)

Department of Critical Care Medicine, Hospital Garcia de Orta, Almada, Portugal
e-mail: [email protected]
A.M. Esquinas
Department of Critical Care Medicine, Hospital Morales Meseguer, Murcia, Spain
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 375

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_45
376 J.B. Blanco and A.M. Esquinas

45.2 Heart-Lung Interactions during NIV: Why? (The

Essentials)

Heart-lung interactions during MV represent the cornerstone of the patient's hemo-

dynamic effects. These interactions are explained by the relationship between posi-
tive pressure ventilation and the cardiovascular system. They are not simple, but
understanding them is mandatory when facing a patient who needs ventilatory sup-
port. Briefly, heart-lung interactions result from the dynamic response of some
physiological factors to balance the metabolic organ demand in a particular clinical
situation. These physiological factors are intravascular volume, blood flow, and car-
diac function, on the one hand, and autonomic and endocrinologic response with
lung volume and transpulmonary pressure (TPP), which is the difference between
alveolar pressure and intrathoracic pressure, on the other hand [2]. When ventilated,
the lung volume changes due to the positive pressure produce a hemodynamic effect
termed by [11] as reverse pulsus paradoxus, which is the increase in systolic arterial
pressure during mechanical inspiration (dUp effect) and the decrease during expira-
tion (dDown effect).
In the left heart, transpulmonary pressure increases and is transmitted backward
through the left atrial chamber, improving venous return and left ventricle preload.
However, this transpulmonary increase leads to another augmentation in the trans-
mural pressure (the distending pressure of a heart chamber), squeezing the heart
chambers and helping to discharge them into the blood flow. The results of this dUp
effect are an increase in the stroke volume (SV) and, thereby, an improvement in the
left systolic outcome [11]. There is also a reduction in the afterload secondary to the
decrease into the transmural left ventricle pressure as a response to the intrathoracic
elevation. Finally, there is a reduction in heart rate (HR), mean arterial pressure
(MAP), and pulse pressure (PP), improving systemic oxygenation and reducing the
myocardial oxygen demand. At this point, the positive pressure ventilation effects
on stroke volume are highly dependent on the global hemodynamic state, with the
reduction effect on the preload being more dominant than the one on the afterload
during the hypovolemic states, which means that, in this situation, the MV will lead
not to an improvement in the SV but to a remarkable reduction. There are no major
concerns regarding the euvolemic or hypervolemic states, where the predominant
effect is on afterload reduction, thus increasing the SV. This allows the appropriate
volume status in the ventilated patient, which is the turning point of the hemody-
namic behavior during MV.
In the right heart, intrathoracic pressure increases the right atrial intravascular
pressure, reducing the driving pressure gradient for venous return and also collaps-
ing the superior cava vein, leading to a preload reduction. With the afterload, the
effect is an augmentation resulting from the pulmonary vascular resistance increase.
As a result, there is a right ventricle SV reduction, and thus a reduction in the vas-
cular congestion and lung edema, once again improving oxygenation and
ventilation.
Regarding respiratory effects, direct oxygenation by O2 administration and alve-
olar unit recruitment, resulting from the direct positive pressure effect on the airway,
45 Practical Approach to the Use of Noninvasive Ventilation in Patients with ACPE 377

improves oxygenation and ventilation and, thereby, the arterial blood gases. MV
contributes to a significant reduction in respiratory muscle effort, as does muscular
oxygen consumption, and systemic oxygen availability is elevated as a result. The
resulting cardiovascular effect is an increase in PaO2 and mixed venous oxygen
(SVO2) and reduction in respiratory rate (RR) and HR.
Based on the main current published studies, Masip and coworkers [4] concluded
in their meta-analysis of 15 selected trials from the period from 1988 to 2005 that
NIV, continuous positive airway pressure (CPAP) and bi-level positive airway pres-
sure (BiPAP), significantly reduced the mortality rate by nearly 45 % compared with
standard medical therapy (SMT) (RR, 0.55; CI 95 %, 0.40–0.78; p = 0.72). Moreover,
when the techniques were compared (and also the SMT), a relevant reduction in the
intubation needs was seen with CPAP (RR, 0.40; 95 % CI, 0.27–0.58; p = .21) and
with BiPAP (RR, 0.48; 95 % CI, 0.30–0.76; p = .24). Furthermore, a meta-analysis by
Mariani et al. [5], and more recently Li et al. [6] and Sun et al. [7], concluded that
when comparing the effects of CPAP versus BiPAP on acute cardiogenic pulmonary
edema (ACPE), there is a relevant decrease in mortality of around 40 % in CPAP and
30 % in BiPAP, without finding once again relevant differences between them in
terms of hospital length of stay or acute myocardial infarction (MI) incidence.
In 1997, [12] when comparing CPAP versus BiPAP, detected a higher MI rate in
the enrolled BiPAP group patients. Because MI is one of the major concerns when
using NIV in acute chronic cardiac patients, several studies have been performed to
clarify this issue. Ho et al. [8], in a meta-analysis published in 2006, confirmed the
lack of a significant trend toward an increase in new-onset acute MI in patients
treated with BiPAP (RR 2.10, 95 % CI 0.91–4.84; p = 0.08). Later papers [7–10]
showed the same results. In conclusion, CPAP is recommended, in addition to SMT,
in patients with severe respiratory failure due to cardiogenic pulmonary edema
(class IIa recommendation, level of evidence A). CPAP must be considered the first-
line intervention in patients with ACPE because it is easier to use than BiPAP and
no differences have been shown between then when comparing both techniques.

45.3 NIV in Acute Chronic Cardiac Exacerbations: When, How

and Where to Do It?

When facing a situation involving acute chronic cardiac exacerbations, there are
some major considerations, including when, where, and how NIV should be used:

1. Where? The location where NIV is used is important because it can determine
the success or the failure of the ventilation. The optimal location depends on the
previous condition of the patient, the total care investment, and the indication or
not for endotracheal intubation (ETI), depending on the patient’s comorbidities.
Patients with indications for ETI can be treated in a conventional cardiology,
respiratory, internal medicine, or even emergency ward, but without the need of
an intermediate unit, if available, and, depending on the patient’s risk factors, an
intensive care unit (ICU). Patients without indications for ETI can be treated in
378 J.B. Blanco and A.M. Esquinas

same wards, but without the need of an intermediate unit. Regarding the interme-
diate care unit, it should have staff educated in NIV. This staff should include
doctors, nurses, and physiotherapists who know the ventilator devices, the
masks, proper hospital protocols for NIV, and hemodynamic monitoring in case
it is needed. The space should be prepared to perform the proper monitoring and
to deal with central venous catheters, arterial lines, and the orotracheal intuba-
tion technique. These intermediate units must be directly connected to the ICU,
or rapid response teams should be available in case of ETI or the necessity for
invasive ventilation and later discharge to the ICU.
2. When? The use of NIV depends on risk factors such as RR >25 bpm, HR
>120 bpm, PaO2/FiO2 <200, pH <7.35, pCO2 >45 mmHg, and the activity of the
accessory muscles. All the patients must have a Glasgow Coma Scale (GCS) >8
and, depending on their APACHE II score (>29), the ICU should be considered
for their medical care.
3. How? Algorithm 45.1 may be useful as a treatment protocol in ACPE.
45 Practical Approach to the Use of Noninvasive Ventilation in Patients with ACPE 379

Initial Assessment
Bedside 60º
Oxygen therapy (face mask FiO2 >60%)
Bronchodilators (b2-agonists/anticholinergic/inhaled glucocorticoids)
Monitoring: MAP, HR, ECG, RR, SatO2, Temp, Urine output
Blood gases: at entrance,-1 hour later-2 hour later
Blood samples (haemogram/coagulation/chemistry/PCR)
Chest RX

Non Indicated NIV

Indication NIV
CPAP BIPAP
Epap : begin 6-8 cm H2O
Increase till max 10 cm H2O
Initiate with 5 cm H2O
target: SatO2 >90%
Increase till max 15 cm H2O
Ipap: begin 10-12 cm H2O
O2 8-10L/min for SpO2 >90%
Increase till max 20 cm H2O
Assessment each 5 minutes and increase 2
target: VC 6–8 mL/KG
cm H2O till max. level or SatO2>95%
Cpap Boussignac? If equipment limitations Assessment each 5 min and increase 2 cm H2O till max level
or achieve target O2 of 8–10L/min SpO2 >90%

Standard Medical Therapy

1/ Diuretics
Furosemide begin 40–60 mg IV bolus every 15 min till diuresis
In ACPE severe : infusion 5–40 mg/H
Max dose 100 mg/6H or 240 mg/24 H
Association if no response : hidroclortiazide 50–100 mg/24H or spironolactone 25–50 mg/24H
2/ Vasodilators.
Nitroglycerine 10–20 µg/min till max 200 µg/min
isosorbide Dinitrate. initiate 1 mg/H and increase till max 10 mg/H
Nitroprusiate: initiate 0.3 µg/KG/min till max 5 µg/KG/min
Evaluate each 5 min
Target : SAP >90 mmHG
3/ Morphine and derivate:
Morphine initial bolus 2,5–5 mg/IV
Assessment and repeat dose 5 mg if needed every 5 min
Target: control of the dyspnea and anxiety relief
4/ Inotropes
Dobutamine 2–20 µg/kg/min
Levosimendan bolus initial 12 mg/kg for 10 min + 0.1 mg/kg/min
Assessment and increase dose if needed
Target: MAP > 65 mmHG

Success Failure
dyspnea control SatO2<85% or pO2/FiO2<100
RR < 25 cpm Coma
HR < 100 bpm Ventricular arrhythmia
Or reduction 20% initial HR/RR HR<60 bpm + hemodynamic instability
PAM <60 mmHG
Cardiac Arrest

Reduce Fio2 till 40%

CPAP reduction 2 cm H2O each 10 min
BIPAP reduction Epap 2 cm H2O each 10 min till 5 cm H2O Orotracheal Intubation + Invasive Mechanical Ventilation
Withdrawal NIV if SatO2>95% for more than >15 min

Algorithm 45.1 Practical approach to the use of noninvasive ventilation in patients with ACPE
380 J.B. Blanco and A.M. Esquinas

Key Major Recommendations

• Positive pressure ventilation improves left ventricular stroke volume
through the predominant effect on afterload reduction in euvolemic or
hypervolemic patients.
• NIV reduces the need for intubation and the mortality rate in patients with
acute chronic cardiac exacerbations compared with standard therapy.
• No difference in myocardial infarction risk has been shown between
patients treated with CPAP/BiPAP versus standard oxygen therapy.
• No significant differences have been shown when studying CPAP versus
BiPAP in terms of hospital mortality or need for intubation. There were no
significant differences between the two ventilatory techniques in terms of
hospital length of stay or risk of myocardial infarction.
• CPAP is recommended, in addition to SMT, in patients with severe respira-
tory failure due to cardiogenic pulmonary edema (class IIa recommenda-
tion, level of evidence A). CPAP must be considered the first-line
intervention in patients with ACPE because it is easier to use than BiPAP
and no differences have been shown between them when the two tech-
niques were compared.
• The best location for NIV use depends on the hospital conditions, the indi-
cation or lack thereof for orotracheal intubation, and the multidisciplinary
team that includes nurses, doctors, and physiotherapists.

References
1. Nava S. Behind a mask: tricks, pitfalls, and prejudices for noninvasive ventilation. Respir Care.
2013;58(8):1367–76.
2. Pinski MR, Polanco PM. Cardiovascular issues in respiratory care. In: Yearbook respiratory
care clinics and applied technologies. International Association of Noninvasive Mechanical
Ventilation. A.M. Esquinas; Murcia Spain 2008.
3. Vieillard-Baron A. Heart lung interactions in mechanical ventilation. In: Backer D, Cholly BP,
Slama M, Vieillard-Baron A, Vignon P, editors. Hemodynamic monitoring using echocardiog-
raphy in the critically III. Philadelphia: Springer; 2011.
4. Masip J, Roque M, Sanchez B, et al. Noninvasive ventilation in acute cardiogenic pulmonary
edema: systematic review and meta-analysis. JAMA. 2005;294(24):3124–30.
5. Mariani J, Macchia A, Belziti C, Deabreu M, Gagliardi J, Doval H, Tognoni G, Tajer
C. Noninvasive ventilation in acute cardiogenic pulmonary edema: a meta-analysis of random-
ized controlled trials. J Card Fail. 2011;17(10):850–9.
6. Li H, Hu C, Xia J, Li X, Wei H, Zeng X, Jing X. A comparison of bi-level and continuous posi-
tive airway pressure noninvasive ventilation in acute cardiogenic pulmonary edema. Am J
Emerg Med. 2013;31(9):1322–7. doi:10.1016/j.ajem.2013.05.043. Epub 2013 Aug 6.
7. Sun T, Wan Y, Kan Q, Yang F, Yao H, Guan F, Zhang J, Li L. Efficacy of noninvasive ventila-
tion on in-hospital mortality in patients with acute cardiogenic pulmonary edema: a meta-
analysis. Zhonghua Xin Xue Guan Bing Za Zhi. 2014;42(2):161–8.
45 Practical Approach to the Use of Noninvasive Ventilation in Patients with ACPE 381

8. Ho KM, Wong K. A comparison of continuous and bi-level positive airway pressure non-
invasive ventilation in patients with acute cardiogenic pulmonary edema: a meta-analysis. Crit
Care. 2006;10:R49. doi:10.1186/cc4861.
9. Rusterholtz T, Bollaert PE, Feissel M, et al. Continuous positive airway pressure vs. propor-
tional assist ventilation for noninvasive ventilation in acute cardiogenic pulmonary edema.
Intensive Care Med. 2008;34:840–6.
10. Ferrari G, Olliveri F, De Filippi G, et al. Noninvasive positive airway pressure and risk of
myocardial infarction in acute cardiogenic pulmonary edema: continuous positive airway pres-
sure vs. noninvasive positive pressure ventilation. Chest. 2007;132:1804–9.
11. Massumi R, Mason D, Zakauddin V, Zelis R, Otero J, Amsterdam E. Reverse pulsus para-
doxus. N Engl J Med. 1976;289:1272–1275
12. Mehta S, Jay GD, Woolard RH, Hipona RA, Connolly EM, Cimini DM, Drinkwine JH, Hill
NS. Crit Care Med. 1997;25:620–628
Noninvasive Ventilation in Acute
and Chronic Heart Failure: Evidence 46
and Key Topics

Simon G. Pearse and Martin R. Cowie

Contents
46.1 Introduction ................................................................................................................. 384
46.2 ACPE: Pathophysiology.............................................................................................. 385
46.3 ACPE: The Role of NIV ............................................................................................. 386
46.3.1 Continuous Positive Airway Pressure ........................................................... 386
46.3.2 BiPAP ............................................................................................................ 387
46.4 SDB in Chronic HF: Epidemiology and Pathophysiology ......................................... 387
46.5 SDB in Chronic HF: NIV ........................................................................................... 388
46.5.1 OSA ............................................................................................................... 388
46.5.2 CSA ............................................................................................................... 389
Conclusions ............................................................................................................................ 390
References .............................................................................................................................. 391

Abbreviations

ACPE Acute cardiogenic pulmonary edema

ASV Adaptive servo-ventilation
BiPAP Bi-level positive airway pressure
CO2 Carbon dioxide
CPAP Continuous positive airway pressure
CRT Cardiac resynchronization therapy
CSA Central sleep apnea
HF Heart failure
HFPEF Heart failure with preserved ejection fraction

S.G. Pearse, MBChB • M.R. Cowie, MD, FRCP (*)

Department of Cardiology, National Heart and Lung Institute, Imperial College
London and the Royal Brompton Hospital, London, UK
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 383

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_46
384 S.G. Pearse and M.R. Cowie

HFREF Heart failure with reduced ejection fraction

LV Left ventricle
NIV Noninvasive ventilation
OMT Optimal medical therapy
OSA Obstructive sleep apnea
PaCO2 Arterial partial pressure of carbon dioxide
PEEP Positive end-expiratory pressure
SDB Sleep-disordered breathing

46.1 Introduction

Heart failure (HF) can be described as a state in which cardiac output is insuffi-
cient for the body’s metabolic requirements at rest, or during exercise, despite
adequate filling pressures. In clinical practice, HF is defined as a syndrome in
which patients have typical symptoms (such as breathlessness, ankle swelling,
and fatigue) and signs (including elevated venous pressure, pulmonary crepita-
tions, or displaced apex beat) resulting from an abnormality of cardiac structure
or function.
Despite significant advances in therapy, HF continues to be a leading cause of
morbidity and mortality. Around 2 % of the adult population of Europe lives with
HF, and in those over 85, the prevalence is as high as 10 %. HF is responsible for
5 % of emergency hospital admissions in Europe over the age of 65, and 30–40 %
of patients die within 1 year of diagnosis.
HF may occur due to abnormalities of systolic function (HF with reduced ejec-
tion fraction – HFREF) or due to impaired filling of the heart in diastole (HF with
preserved ejection fraction – HFPEF), although deficiencies in both elements of the
cardiac cycle are frequently seen in the same patient. HF typically follows a chronic
progressive course with intermittent acute exacerbations caused by identifiable trig-
gers such as arrhythmia, poor compliance, myocardial infarction, or inappropriate
medication such as nonsteroidal anti-inflammatory drugs. HF may also present
acutely de novo, most frequently in the context of acute coronary syndromes or
arrhythmia.
Management of HF can be broadly divided into emergency treatment of acute
HF (often with pulmonary edema) and management of chronic stable HF. Medical
therapy for acute HF complicated by pulmonary edema, including oxygen and intra-
venous loop diuretics, is supported by international guidelines. Intravenous nitrates,
opioids, and inotropes may also be beneficial, as necessary, in selected patients.
Noninvasive ventilation (NIV) has significant theoretical benefits for acute cardio-
genic pulmonary edema (ACPE), but there are inconsistencies in the evidence base.
In chronic stable HF, there is growing interest in the use of NIV in the management
of sleep-disordered breathing (SDB), which is common in chronic HF and associ-
ated with a poorer prognosis. This chapter outlines the current evidence for nonin-
vasive respiratory support in acute and chronic HF.
46 Noninvasive Ventilation in Acute and Chronic Heart Failure: Evidence and Key Topics 385

46.2 ACPE: Pathophysiology

In the lung, fluid is constantly exuded from the alveolar capillaries. This exudate
passes through the alveolar interstitium and airspace and is reabsorbed by the peri-
bronchial lymphatics across a pressure gradient. The rate of exudation depends
upon the hydrostatic pressure within the alveolar capillaries, the permeability of the
capillary walls, and the plasma oncotic pressure. A significant rise in pulmonary
capillary pressure can be compensated for by increased lymphatic drainage. Left
ventricular (LV) failure, systolic or diastolic, results in high end-diastolic pressure
which is conducted back to the left atrium. The atrium can expand to accommodate
some increase in pressure over time, but if the pressure rises acutely or to a marked
degree, pulmonary venous pressure rises. This pressure is in turn passed to the alve-
olar capillaries and the rate of fluid exudation increases, which may exceed the
maximal rate of reabsorption (Fig. 46.1). Fluid first accumulates in the peribroncho-
vascular interstitium before spilling over to the alveolar membranes and flooding
the airspaces.
The presence of excess fluid in the alveolar spaces has several effects. It acts as
a barrier to gas exchange both between the air and the alveolar membrane and
within the edematous membrane cells. It also dilutes the surfactant within the alveo-
lus with the result that surface tension is increased and greater force is required to
inspire. The alveoli are thus predisposed to collapse, which further increases the
work of inspiration according to Laplace’s law (in which the pressure required to
inflate a sphere is inversely related to the diameter). Areas of edema in the lungs
cause shunting of blood and hypoxemia, which is partially counteracted by relative
vasoconstriction in the hypoxic areas. Increased capillary pressure in the lung ulti-
mately leads to rising pulmonary artery pressure and can subsequently cause failure

LEFT ATRIAL PRESSURE [mm. Hg]

12
Wet weight
Dry weight

10

6
LUNG FLUID

0
0 5 10 15 20 25 30 35 40 45
LEFT ATRIAL PRESSURE (mm. Hg)

Fig. 46.1 The effect of rising left atrial pressure on the development of pulmonary edema in a
canine model (Reproduced from Guyton and Lindsey [1]. With kind permission of Wolters Kluwer
Health publishers)
386 S.G. Pearse and M.R. Cowie

of the right ventricle. This pathophysiological sequence can lead to respiratory fail-
ure – impaired gas exchange resulting in hypoxemia (usually defined as PaO2
<8 kPa) – with or without hypercapnia.

46.3 ACPE: The Role of NIV

46.3.1 Continuous Positive Airway Pressure

Continuous positive airway pressure (CPAP) is the simplest form of respiratory sup-
port and has the greatest evidence base in the treatment of ACPE. CPAP provides
constant pressure, typically 5–10 cmH2O, via an airtight facemask, nasal mask, or
helmet throughout the respiratory cycle. The resultant positive end-expiratory pres-
sure (PEEP) helps prevent alveolar collapse and recruits alveoli that have collapsed.
The alveoli are thus maintained at a greater diameter, lung compliance is increased,
and the work of breathing is reduced. Lesser shunting of blood improves oxygen-
ation and the positive intrathoracic pressure reduces venous return, thus reducing
cardiac preload. LV transmural pressure is also reduced, with an effective reduction
in afterload.
The earliest studies of NIV in ACPE compared CPAP plus optimal medical ther-
apy (OMT) with OMT alone [2–4]. CPAP was administered in the emergency room
and/or intensive care unit until respiratory failure resolved, intubation was required,
or the patient was unable to tolerate CPAP further. The weight of evidence demon-
strated an advantage of CPAP over OMT in terms of both in-hospital mortality and
the need for endotracheal intubation. CPAP plus OMT also resulted in more rapid
improvement in oxygenation and respiratory rate and was safe and effective in
elderly patients. A further study revealed a similar benefit of CPAP for HF with both
HFREF and HFPEF [5]. The studies did not, however, demonstrate a survival
advantage for CPAP over OMT at 30-day follow up.
Two larger recent studies have shed some doubt on the benefit of a routine strategy
of NIV in ACPE. The 3CPO trial is the largest multicenter randomized controlled trial
(1,069 patients) comparing CPAP or bi-level positive airway pressure (BiPAP) plus
OMT against OMT alone [6]. Although there was a more rapid reduction in respira-
tory rate, heart rate, hypercapnia, and acidosis in the NIV groups, there was no benefit
for NIV at 7 days for the combined endpoint of intubation or mortality (9.5 % vs
9.8 %, p = 0.87), and no mortality benefit at 30 days (15.2 % vs 16.4 %, p = 0.64).
There was, however, a high frequency of crossover from OMT to NIV on clinical
grounds (16 % of OMT patients; presumably those with the most severe respiratory
distress) and 9 % of NIV patients crossed into the OMT arm, many of whom are likely
to have had less severe respiratory compromise. The mean duration of NIV therapy of
approximately 2 h is also shorter than several previous studies. A further trial random-
ized 124 patients to receive either CPAP plus OMT or OMT alone for ACPE in the
pre-hospital setting [7]. This demonstrated no benefit for CPAP over OMT for the
primary combined outcome of respiratory rate (<25/min) and oxygen saturation
(>90 %) at 1 h (31.7 % vs 35.5 %, p = 0.65). There was no difference in hospital stay,
46 Noninvasive Ventilation in Acute and Chronic Heart Failure: Evidence and Key Topics 387

intubation rates (3.3 % vs 4.8 % p = 0.52), or mortality (10 % vs 11.3 % at 30 days,

p = 0.52), although the study was not powered for these outcomes.
A meta-analysis of the randomized trials, including the “negative” studies above,
concluded there was an overall relative in-hospital mortality advantage for CPAP
over OMT of 28 % and a relative reduction in intubation of 45 % [8]. There was no
reduction in length of hospital stay.

46.3.2 BiPAP

BiPAP provides background positive pressure in the same manner as CPAP but also
gives additional pressure during inspiration (inspiratory positive airway pressure).
This reduces the effort required of the inspiratory muscles and may improve ventila-
tion, with particular benefit for patients with hypercapnia and reduced respiratory
drive or capability.
The evidence base for BiPAP in ACPE is more limited than for CPAP. Trials
show significant heterogeneity, but overall there appears to be a more rapid resolu-
tion of hypercapnia, respiratory rate, and hypoxemia with BiPAP than with
OMT. Some (but not all) studies showed reduced intubation rates with BiPAP, but a
mortality advantage has not been demonstrated. This may be due to small studies in
heterogeneous populations [6, 9].
Studies comparing BiPAP to CPAP have produced inconsistent results [9].
Overall, CPAP and BiPAP produce a similar advantage in terms of improved physi-
ological parameters over OMT, but only CPAP has evidence (albeit variable) for
improved short-term survival. Improvement in hypercapnia appears to be similar for
CPAP and BiPAP.
Early studies found a higher incidence of myocardial infarction in those treated
with BiPAP, but subsequent research with adequate power has repudiated this [10].
In practice, CPAP is a simpler and more extensively studied form of respiratory
support for ACPE and should be considered for those with persistent respiratory
failure not responding to optimal medical therapy. BiPAP should be reserved for
those with hypercapnia unresponsive to CPAP, or with underlying lung disease that
predisposes to hypercapnia with CPAP (such as advanced chronic obstructive pul-
monary disease or obesity hypoventilation syndrome, which may be associated with
HFPEF). The evidence does not support the routine use of NIV for all patents pre-
senting with ACPE, and an individualized approach based on clinical findings and
arterial blood gas analysis is recommended in European HF guidelines [11].

46.4 SDB in Chronic HF: Epidemiology and Pathophysiology

Around 50 % of patients with HF suffer from SDB. This may comprise obstructive
sleep apnea (OSA) or central sleep apnea (CSA), although many patients have a
mixed pattern that may change over the sleep period. In OSA, there is loss of
pharyngeal muscle tone leading to upper airway collapse and obstruction. This is
388 S.G. Pearse and M.R. Cowie

often associated with obesity and retrognathism, and in HF rostral shift of fluid during
sleep leads to edema of the pharynx, exacerbating the tendency to airway collapse. In
CSA, there is an abnormality of the regulation of breathing in the respiratory centers
of the brainstem. The pathophysiology in HF involves reflex hyperventilation due to
activation of pulmonary J receptors by edema and pulmonary congestion, a delayed
circulation time between the alveoli and brainstem, and raised chemosensitivity lead-
ing to relative hyperventilation in response to rises in arterial carbon dioxide (PaCO2).
Hyperventilation leads to falls in PaCO2 to below the apneic threshold, at which point
the neural drive to breathe is inadequate to stimulate respiration. The resultant hypop-
nea or apnea causes the PaCO2 to rise until hyperventilation again occurs and the cycle
is repeated. Recurrent cyclical CSA is termed Cheyne-Stokes respiration.
Both forms of SDB are associated with recurrent arousals from sleep, episodes
of hypoxemia, and enhanced sympathetic nervous system stimulation with increased
catecholamine release. This predisposes to tachycardia, arrhythmia, and – particu-
larly in the case of OSA – hypertension, which may increase the risk of stroke and
myocardial infarction [12]. There is an excess of arrhythmia at night in those with
OSA and increased rate of therapies from implantable cardioverter-defibrillators
[13]. Daytime somnolence is a particular problem for those with OSA, and sufferers
are at increased risk of road traffic accidents.
In OSA, the negative intrathoracic pressure generated by respiratory muscles
attempting to inspire against a collapsed pharynx increases venous return to the
heart and causes a high transcardiac gradient, increasing afterload. The septum
shifts leftward and output from the failing LV is compromised. Abnormalities of
endothelial function are also found in patients with OSA, including a high expres-
sion of the vasoconstrictor endothelin-1 and a blunted response to cholinergic vaso-
dilators [14]. There is an increase in inflammatory markers such as C-reactive
protein (known to be associated with vascular events) and prothrombotic factors
(leading to enhanced platelet aggregation) [15].
The prevalence of CSA increases with the severity of HF and is a marker of poor
prognosis. In a study of patients with moderate to severe LV dysfunction, median
survival amongst those with CSA was 45 months versus 90 months for those with-
out – a difference that persisted even when adjusted for several confounding factors
[16]. Although this demonstrates association rather than causation, the recurrent
hypoxemia, sympathetic stimulation, and changes in pre- and afterload associated
with apnea are presumed to accelerate the vicious cycle of HF. Other risk factors
associated with the development of CSA include male sex, atrial fibrillation, resting
hypocapnia, and age over 60 years.

46.5 SDB in Chronic HF: NIV

46.5.1 OSA

Nocturnal CPAP is an established therapy for symptomatic OSA in the general pop-
ulation, in addition to lifestyle and weight management. CPAP improves daytime
46 Noninvasive Ventilation in Acute and Chronic Heart Failure: Evidence and Key Topics 389

somnolence and may have an effect on hypertension and vascular events. In those
with HF and OSA, CPAP reduces sympathetic activity and ventricular ectopy and
can improve LV and right ventricular function [17]. In one nonrandomized study of
88 patients over a mean of 25 months follow-up, treatment with CPAP was associ-
ated with improved survival versus standard medical therapy (Hazard Ratio (HR)
for death or hospitalization 2.03 in untreated group vs CPAP, 95 % Confidence
Interval (CI) 1.07–3.68, p = 0.03) [18].
Medical therapy for HF may reduce pharyngeal edema and consequently the
severity of OSA, although trial data for this are lacking. Cardiac resynchronization
therapy (CRT) improves LV function in selected patents with left bundle branch
block and HF. Evidence that CRT improves OSA in HF is contradictory and a meta-
analysis concludes no overall improvement [19].
CPAP should therefore be considered for patients with HF and moderate to
severe OSA with symptoms of daytime somnolence, alongside optimization of
medical therapy and CRT as appropriate. There is no consensus as to whether to
recommend CPAP therapy in those with HF and OSA but no daytime somnolence.

46.5.2 CSA

Optimization of medical therapy for HF improves cardiac output, relieves pulmo-

nary congestion, and reduces sympathetic drive. This would be expected to lessen
the inappropriate hyperventilation that underpins CSA, although data for this are
sparse. There is good evidence that CRT can improve CSA in appropriately selected
patients. A recent meta-analysis of 7 trials investigating CRT in HF with SDB
showed a significant mean reduction in Apnea-Hypopnea Index (AHI) of 13.5
events/h for those with predominant CSA, but a nonsignificant reduction of 3.3/h
for OSA [19].
Experience of CPAP in the management of OSA led to research into CSA. Based
on work showing a partial normalization in noradrenaline concentrations and LV
ejection fraction in patients with HF and CSA treated with CPAP, as well as a pos-
sible reduction in mortality [20], a large randomized study (the CANPAP trial [21])
was performed to evaluate clinical endpoints in this group. Over a mean of 2 years
of follow-up of 258 patients, there was no difference in transplant-free survival
between the treated and untreated arms. There was, however, a significant reduction
in AHI (mean reduction of 21 events/h) in those treated with CPAP, which persisted
over 2 years. In addition, post -hoc subgroup analysis showed that those in whom
AHI was suppressed to below 15 events per hour had significantly fewer adverse
events than controls, suggesting a possible therapeutic role for more efficacious
ventilatory techniques [22].
Adaptive servo-ventilation (ASV) is an advanced form of NIV in which the
device provides varying levels of inspiratory pressure support depending on the
patient’s effort and minute ventilation. In addition, the device provides mandatory
breaths during apneas and PEEP to maintain airway patency. This has the effect of
greatly reducing apneas and hypopneas while moderating episodes of
390 S.G. Pearse and M.R. Cowie

Fig. 46.2 The effect of Central Apnea Index

different modalities of NIV 60
on CSA events in HF
(Reproduced from Teschler
et al. [25]. Reprinted with
permission of the 40

Events/hr
American Thoracic
Society. Copyright © 2015
American Thoracic
Society. The American 20
Journal of Respiratory and
Critical Care Medicine is
an official journal of the
American Thoracic
Society) 0
Control Oxygen CPAP Bilevel ASV
VS control: P<0.001 P<0.001 P<0.001 P<0.001
VS ASV: P<0.001 P<0.001 P<0.001 P=0.02

hyperventilation and is effective in both OSA and CSA. ASV is well tolerated and
suppresses CSA more effectively than CPAP [23] (Fig. 46.2). A large randomized
trial powered to detect mortality and morbidity endpoints in CSA (SERVE-HF) has
recently been published [24]. Surprisingly, this reported no change in the combined
mortality-morbidity endpoint with ASV, but a 28 % increase in all-cause mortality
(95 % CI 1.06–1.55, p = 0.01) and a 34 % increase in cardiovascular mortality (95 %
CI 1.09–1.65, p = 0.006). The mechanism of this harm remains to be elucidated. A
further randomized trial in HF (enrolling patients with either OSA or CSA) is
ongoing (ADVENT-HF - NCT01128816).

Conclusions

CPAP may be a useful tool in the management of ACPE in selected patients with
respiratory failure. The role of BiPAP in this setting requires further assessment
but may be considered for patients intolerant of CPAP or with refractory hyper-
capnia. Nocturnal CPAP is of significant benefit for those with OSA and daytime
somnolence and may have additional cardiovascular benefits. The use of NIV in
CSA cannot currently be recommended.
46 Noninvasive Ventilation in Acute and Chronic Heart Failure: Evidence and Key Topics 391

Key Major Recommendations

• In patients with ACPE and respiratory failure, NIV should be initiated
early and up-titrated as tolerated.
• Patients with chronic HF and symptoms of sleepiness or fatigue should
undergo sleep polygraphy or polysomnography to diagnose SDB.
• Patients with OSA should be referred to a specialist for consideration of
nocturnal CPAP.
• Patients with CSA and HF should be established on OMT, including CRT
as indicated.

Acknowledgments MRC’s salary is supported by the National Institute for Health Research
Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital, London. SGP’s salary
is supported by a research grant from Boston Scientific.

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Noninvasive Ventilation in Drug
Overdose: Is It a Potentially Safe 47
Application? Key Practical Implications

Michalis Agrafiotis, Evangelia Serasli, and Venetia Tsara

Contents
47.1 Introduction ................................................................................................................. 393
47.2 Evidence...................................................................................................................... 394
47.3 NIV for the Management of Drug Overdose-Associated
Respiratory Failure: Advantages and Limitations ...................................................... 397
47.4 Practical Issues ............................................................................................................ 398
Conclusion ............................................................................................................................. 399
References .............................................................................................................................. 399

Abbreviations

COPD Chronic obstructive pulmonary disease

EPAP Expiratory positive airway pressure
HDU High dependency unit
ICU Intensive care unit
NIV Noninvasive ventilation

47.1 Introduction

Respiratory complications and acute respiratory failure are common following

acute drug overdose. Respiratory failure in acute drug overdose can present as respi-
ratory pump failure, a compromise of the gas exchange, or a combination of both.

M. Agrafiotis, MD (*) • E. Serasli, MD, PhD • V. Tsara, MD, PhD

Department of Pulmonary Medicine, “Georgios Papanikolaou” General Hospital of
Thessaloniki, Thessaloniki, Greece
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 393

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_47
394 M. Agrafiotis et al.

These manifestations can be a direct consequence of the drug’s pharmacologic

action, while other factors such as aspiration syndromes or complications of treat-
ment may also play an important contributory role [1]. In any case, management
consists of removal of the drug from the organism, administration of antidote (if
available), and supportive measures.
Invasive mechanical ventilation satisfies the need for a secure airway, providing
at the same time an effective support of gas exchange, and it is traditionally consid-
ered the mainstay of management for severe cases of respiratory failure in drug
overdose patients. Noninvasive positive pressure ventilation is alternative method of
ventilation that can effect positive pressure breathing via a noninvasive interface and
has become a widely accepted method for the management of several common con-
ditions, including the hypercapnic exacerbation of chronic obstructive pulmonary
disease (COPD) and cardiogenic pulmonary edema [2].
However, whether noninvasive ventilation (NIV) might also play a role in the
supportive management of drug overdose-associated respiratory failure is an issue
that remains largely obscure. Interestingly, the use of bi-level ventilation for the
management of drug overdose patients was reported as early as 1996 [3]. A more
recent cohort reported on the use of NIV in 157 patients with various causes of
respiratory failure, including five cases with drug overdose, although specific data
on the management and outcome of this subset of patients were not provided [4]. In
another study, NIV was applied to 1 out of 29 patients with respiratory complica-
tions related to drug overdose, while 12 other patients were intubated [5]. Thus,
considering the widespread use and availability of NIV today, it is possible that
some experienced departments might regard it as a suitable option for the manage-
ment of selected cases of respiratory failure caused by drug overdose. Nevertheless,
published experience in that field remains largely anecdotal, and several issues per-
taining to patient selection, practicalities of management, and outcomes have not
yet been clarified.

47.2 Evidence

We searched PubMed and Scopus databases up to October 2014 for papers written
in English, using the following key terms: (“non-invasive” OR “noninvasive”) AND
(“drug overdose” OR “intoxication” OR “poisoning”). Out of 1,161 initially
retrieved articles, we identified 11 eligible papers (all of them case reports) provid-
ing data on the characteristics, management details, and outcomes of patients who
were treated with NIV for drug overdose-associated acute respiratory failure [6–16]
(Table 47.1). Opioids were the most common culprit associated with respiratory
failure (5 out of 11 cases), whereas ventilatory depression (6/11) and non-cardiogenic
pulmonary edema (5/11) were the most common clinical manifestations of drug
respiratory toxicity. Extra-respiratory manifestations were invariably present in all
patients and included impaired consciousness (7/11), circulatory abnormalities
(5/11), and renal failure (4/11). Bi-level ventilation was the preferred noninvasive
mode (6 out of 8 cases with available data). In the majority of the patients (10/11),
 47

Table 47.1 Papers reporting the use of NIV in drug overdose-associated respiratory failure
Type of
Type of noninvasive
First author Implicated toxin respiratory Antidote ventilatory Other
No (year) [Ref.] Sex/age (s) involvement Other complications administered assistance interventions Outcome
1 Pichot Male/24 Cocaine Ventilatory Supraventricular Naloxone Bi-level Magnesium Survived
(2014) [6] Opioids depression tachycardia Amiodarone
NCPE Metabolic acidosis Antibiotics
Vomitus
2 Algren Female/54 Acepromazine Ventilatory CNS depression None Bi-level Activated Survived
(2014) [7] depression Hypotension charcoal
Fluids
Vasopressors
3 Agrafiotis Male/74 Fentanyl Ventilatory CNS depression Naloxone Bi-level None Survived
(2014) [8] (transdermal depression volume
Noninvasive Ventilation in Drug Overdose

patch) assured
Tramadol
4 Naha (2014) Female/18 Amlodipine NCPE Metabolic acidosis Calcium NS Gastric lavage Survived
[9] Atenolol Renal failure gluconate Fluids
Hypotension Vasopressors
5 Koncicki Female/15 Cochicine NCPE Confusion None NS Transfusion Survived
(2013) [10] Diarrhea
Pancytopenia
Renal failure
Rhabdomyolysis
Transaminasemia

(continued)
395
Table 47.1 (continued)
396

Type of
Type of noninvasive
First author Implicated toxin respiratory Antidote ventilatory Other
No (year) [Ref.] Sex/age (s) involvement Other complications administered assistance interventions Outcome
6 Range Male/74 Amiodarone NCPE Renal failure None NS Corticosteroids Died
(2013) [11] Dialysis
Extracorporeal
oxygenation
7 Gonzva Male/20 Methadone Ventilatory CNS depression Naloxone Bi-level Antibiotics Survived
(2013) [12] Cannabis depression
Alcohol NCPE
8 Maraffi Male/27 Cocaine Ventilatory Atrial fibrilation Naloxone CPAP NS Survived
(2011) [13] Heroin depression CNS depression
NCPE
9 Klenner Female/84 Phenprocoumon Alveolar Anemia Vitamin K Bi-level Transfusion Survived
(2008) [14] hemorrhage Coagulopathy Vitamin
K-dependent
clot factors
10 Ridgway Male/54 Methadone Ventilatory CNS depression Naloxone Bi-level Furosemide Survived
(2007) [15] depression Glyceryl trinitrate
NCPE
11 Vogt (2006) Male/42 Amlodipine Cardiogenic CNS depression Calcium CPAP Fluids Survived
[16] Chlorothalidone pulmonary Left heart failure gluconate Inotropes
Mefenamic acid edema Vomitus Vasopressors
Alcohol Renal failure Insulin infusion
Furosemide
Abbreviations: CNS central nervous system, CPAP continuous positive airway pressure, NCPE non-cardiogenic pulmonary edema, NS not specified
M. Agrafiotis et al.
47 Noninvasive Ventilation in Drug Overdose 397

NIV was successful in the management of drug overdose-associated respiratory

failure, with only one patient failing NIV and switched to invasive ventilation; this
patient sustained amiodarone-induced pulmonary toxicity and eventually died [11].

47.3 NIV for the Management of Drug Overdose-Associated

Respiratory Failure: Advantages and Limitations

The rationale behind the use of NIV for the management of drug overdose-associated
respiratory failure stems from the encouraging experience obtained from patients
with hypercapnic COPD exacerbation and cardiogenic pulmonary edema. In these
instances, NIV has been shown to reduce mortality and length of hospital stay and
avert endotracheal intubation, along with its associated complications (e.g., infec-
tions) [2]. Additionally, when NIV was directly compared with invasive mechanical
ventilation in patients with COPD exacerbation, it was associated with a lower fre-
quency of complications, although the rate of NIV failure was high, and eventually
60 % of the NIV-treated patients required intubation [17]. Nevertheless, controlled
clinical studies are needed to explore whether the benefits from NIV application in
these categories of patients might also apply to patients with respiratory failure
related to drug overdose.
A particular advantage in the use of NIV is that it can be applied early in the
course of the disease. In this way, respiratory compromise can be managed at an
initial stage and its complications (e.g., hypercapnic coma) can be prevented, while
in the same time other measures such as drug removal and antidote administration
take immediate effect. Therefore, considering that drug overdose syndromes can be
quickly and fully reversed when promptly diagnosed and treated, NIV can become
a powerful tool in the early management of these patients. Additionally, the applica-
tion of expiratory positive airway pressure (EPAP) could also reduce the tendency
for atelectasis, minimizing the requirements for oxygen, and improve upper airway
patency, averting episodes of obstructive sleep disordered breathing and hypoventi-
lation [18]. The use of NIV could also allow for prolonged periods of ventilatory
support, an important advantage for patients with heavy overdose, chronic respira-
tory disease, or limited physiological reserve. In addition, NIV could also be
regarded as an acceptable alternative option for the management of patients with a
“do-not-intubate” order, as in the case of terminal stage cancer. These patients are
commonly treated with opioids for chronic pain and are particularly prone to their
side effects [19].
This approach, however, has several inherent limitations. First, drug over-
dose patients often present with impaired level of consciousness and inability to
protect the airway. In these cases, and unless the condition can be rapidly
reversed (e.g., by administering naloxone in the case of opioid intoxication), the
requirement for a secure airway takes precedence and endotracheal intubation
should be regarded as the management of choice. On the other hand, in a study
by Duncan et al. [20] involving 73 patients treated for acute poisoning in a high-
dependency unit (HDU), none out of the 12 patients who presented with an
398 M. Agrafiotis et al.

impaired level of consciousness (Glasgow Coma Scale score <8) required intu-
bation or exhibited signs of aspiration. Moreover, the presence of moderate to
severe encephalopathy in COPD patients who received NIV for the management
of acute exacerbation was not associated with higher tracheotomy and mortality
rates compared with endotracheal intubation; however, these results should not
be readily extrapolated to patients with drug overdose [21]. Of note, a success-
ful combination of NIV and antidote administration in cases of opioid-induced
hypercapnic acidosis (with or without non-cardiogenic pulmonary edema) has
been reported by several authors. In this setting, early antidote administration
can promptly improve respiratory acidosis and restore the level of conscious-
ness, creating a “therapeutic window” that obviates the requirement for invasive
airway management and buys time for NIV to control carbon dioxide levels and
reverse hypoxemia [6, 8, 12, 13, 15].
An additional shortcoming is related to the common occurrence of gastric disten-
tion in patients on NIV, a condition that can impair effective ventilatory support and
exacerbate the risk of aspiration. Moreover, the presence of a nasogastric tube can
interfere with mask sealing, and the interface itself can compromise effective gastric
lavage. Both these conditions can contribute to patient discomfort and increase the
risk for NIV failure.
An important consideration also pertains to the frequent occurrence of multiple
organ involvement given that complications as severe hemodynamic instability, pro-
found metabolic acidosis, and renal or hepatic failure are common in patients with
drug overdose and might compromise the effectiveness of NIV, necessitating the use
of invasive ventilation. Finally, caution should be particularly applied in cases with
severe hypoxemia due to acute respiratory distress syndrome, as roughly half of
these patients respond poorly to NIV and will eventually require invasive ventila-
tory support [22].

47.4 Practical Issues

The choice of the ventilatory support method should always be made after a careful
assessment of the individual risk factors in each case. Therefore, intensive care unit
(ICU) ventilators are particularly advantageous for the management of severe
hypoxemia because of their high performance capabilities and because they incor-
porate oxygen blenders that allow exact regulation of the inspired oxygen fraction.
A spontaneous/timed bi-level mode should be preferred in patients with impaired
level of consciousness and blunted ventilatory response, whereas volume guarantee
modes might benefit patients with severe ventilatory depression and poorly con-
trolled hypercapnia. In this regard, measures should also be taken to minimize car-
bon dioxide rebreathing, ideally by using devices with dual-limb circuits. When
single-limb systems are used, either a true expiratory valve or a vented interface
with a minimal dynamic dead space should be employed. In the latter case, the
implementation of EPAP could also reduce carbon dioxide rebreathing by providing
fresh gas flow at the end of expiration [23]. As a general rule, patients with drug
47 Noninvasive Ventilation in Drug Overdose 399

overdose-associated respiratory failure should be admitted and monitored in HDUs

or ICUs and access to invasive ventilation or advanced life support facilities should
be readily available.

Conclusion
There is limited evidence to support the application of NIV for the management
of drug overdose-associated respiratory failure, and invasive mechanical ventila-
tion should be regarded as the definite procedure for ensuring oxygenation and
ventilation and providing protection against aspiration in severely ill patients
with drug overdose. Alternatively, NIV might be an acceptable choice for
selected cases of relatively stable patients with a low risk of aspiration and
absence of overt signs of multiple organ failure. In these cases, a trial of NIV
could be cautiously offered while the patient is being carefully monitored, should
an indication for invasive ventilation appear. In addition, NIV might be consid-
ered for the management of drug overdose-associated respiratory failure when a
“do-not-intubate” decision has been made.

Key Major Recommendations

• NIV is a potentially suitable alternative to invasive ventilation for patients
with drug-overdose associated respiratory failure when there is a low risk
of aspiration, limited involvement of other organ systems, or when a
“do-not-intubate” order is in place.
• Ventilators with oxygen blenders and advanced performance characteris-
tics should be used for the management of severe hypoxemia.
• Spontaneous/timed bi-level modes should be employed for patients with a
blunted ventilatory response. Volume guarantee modes should be consid-
ered in difficult-to-control respiratory acidosis.
• Intensive monitoring should be provided to all patients with drug overdose
who are being treated with NIV.

References
1. Wilson KC, Saukkonen JJ. Acute respiratory failure from abused substances. J Intensive Care
Med. 2004;19(4):183–93.
2. Boldrini R, Fasano L, Nava S. Noninvasive mechanical ventilation. Curr Opin Crit Care.
2012;18(1):48–53.
3. Pollack Jr C, Torres MT, Alexander L. Feasibility study of the use of bilevel positive airway
pressure for respiratory support in the emergency department. Ann Emerg Med.
1996;27(2):189–92.
4. Bülow HH, Thorsager B, Hoejberg JM. Experiences from introducing non-invasive ventilation
in the intensive care unit: a 2-year prospective consecutive cohort study. Acta Anaesthesiol
Scand. 2007;51(2):165–70.
400 M. Agrafiotis et al.

5. Jayakrishnan B, Al Asmi A, Al Qassabi A, Nandhagopal R, Mohammed I. Acute drug over-

dose: clinical profile, etiologic spectrum and determinants of duration of intensive medical
treatment. Oman Med J. 2012;27(6):501–4.
6. Pichot C, Petitjeans F, Ghignone M, et al. Swift recovery of severe acute hypoxemic respira-
tory failure under non-invasive ventilation. Anaesthesiol Intensive Ther. 2015;47(2):138–42.
7. Algren DA, Ashworth A. Acute acepromazine overdose: clinical effects and toxicokinetic
evaluation. J Med Toxicol. 2015;11(1):121–3.
8. Agrafiotis M, Tryfon S, Siopi D, et al. Successful management of drug-induced hypercapnic
acidosis with naloxone and noninvasive positive pressure ventilation. Am J Emerg Med.
2015;33(2):312.e3–4.
9. Naha K, Suryanarayana J, Aziz RA, et al. Amlodipine poisoning revisited: acidosis, acute
kidney injury and acute respiratory distress syndrome. Indian J Crit Care Med. 2014;
18(7):467–9.
10. Koncicki M, Dewan M. A teenager with multiple organ system dysfunction. Pediatr Emerg
Care. 2013;29(3):399–401.
11. Range FT, Hilker E, Breithardt G, et al. Amiodarone-induced pulmonary toxicity – a fatal case
report and literature review. Cardiovasc Drugs Ther. 2013;27(3):247–54.
12. Gonzva J, Prunet B, Deniel C, et al. Early antidote use associated with noninvasive ventilation
in prehospital treatment of methadone intoxication. Am J Emerg Med. 2013;31(2):448.e5–6.
13. Maraffi T, Ruvolo L, Aliberti S, et al. Early application of non-invasive continuous positive
airway pressure in acute respiratory distress syndrome due to a drug overdose: a case report.
Intern Emerg Med. 2011;6(3):275–6.
14. Klenner AF, Friesecke S, Schäper C, et al. Diffuse alveolar hemorrhage with acute respiratory
distress syndrome associated with phenprocoumon therapy. Blood Coagul Fibrinolysis.
2008;19(8):813–5.
15. Ridgway ZA, Pountney AJ. Acute respiratory distress syndrome induced by oral methadone
managed with non-invasive ventilation. Emerg Med J. 2007;24(9):681.
16. Vogt S, Mehlig A, Hunziker P, et al. Survival of severe amlodipine intoxication due to medical
intensive care. Forensic Sci Int. 2006;161(2–3):216–20.
17. Squadrone E, Frigerio P, Fogliati C, et al. Noninvasive vs invasive ventilation in COPD patients
with severe acute respiratory failure deemed to require ventilatory assistance. Intensive Care
Med. 2004;30(7):1303–10.
18. Wang D, Teichtahl H. Opioids, sleep architecture and sleep-disordered breathing. Sleep Med
Rev. 2007;11(1):35–46.
19. Dahan A, Overdyk F, Smith T, Aarts L, Niesters M. Pharmacovigilance: a review of opioid-
induced respiratory depression in chronic pain patients. Pain Physician. 2013;16(2):E85–94.
20. Duncan R, Thakore S. Decreased Glasgow Coma Scale score does not mandate endotracheal
intubation in the emergency department. J Emerg Med. 2009;37(4):451–5.
21. Scala R, Nava S, Conti G, et al. Noninvasive versus conventional ventilation to treat hypercap-
nic encephalopathy in chronic obstructive pulmonary disease. Intensive Care Med.
2007;33(12):2101–8.
22. Antonelli M, Conti G, Esquinas A, et al. A multiple-center survey on the use in clinical prac-
tice of noninvasive ventilation as a first-line intervention for acute respiratory distress syn-
drome. Crit Care Med. 2007;35(1):18–25.
23. Mojoli F, Braschi A. Carbon dioxide rebreathing during noninvasive mechanical ventilation.
In: Esquinas AM, editors. Noninvasive mechanical ventilation. Theory, equipment, clinical
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Atelectasis and Noninvasive Mechanical
Ventilation 48
Paulo Matos

Contents
48.1 Introduction ................................................................................................................. 401
48.2 Discussion ................................................................................................................... 402
48.2.1 Postoperative Atelectasis and NIMV ............................................................ 402
48.2.2 Atelectasis in Neuromuscular Disorders and Critically Ill Patients .............. 403
Conclusion ............................................................................................................................. 404
References .............................................................................................................................. 404

Abbreviations

CPAP Continuous positive airway pressure

EPAP Expiratory positive airway pressure
IPAP Inspiratory positive airway pressure
NIMV Noninvasive mechanical ventilation

48.1 Introduction

Atelectasis is a common finding in hospitalized patients. It contributes to deteriora-

tion of pulmonary function and gas exchange, leading to significant morbidity, mor-
tality, and health-care costs [1]. After thoracic or upper abdominal surgery, the
incidence of atelectasis is high, up to 54–92 %. Multiple factors, such as pleural
opening, postoperative diaphragmatic dysfunction, pain, immobilization, and bed

P. Matos, MD
Pulmonology Department, Coimbra Hospital and University Centre, Coimbra, Portugal
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 401

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_48
402 P. Matos

rest, in addition to possible preexisting respiratory disease, are involved in the

development of atelectasis in this clinical situation [2].
In patients with neuromuscular diseases and in critically ill patients who develop
atelectasis, bronchoscopy and respiratory physiotherapy are the techniques of
choice for treatment. However, physiotherapy is usually neglected and bronchos-
copy is an invasive technique with some contraindications and complications. Some
authors have shown a few clinical cases where noninvasive mechanical ventilation
(NIMV) was useful in treatment of atelectasis [3]. We will discuss the use of con-
tinuous positive airway pressure (CPAP) and NIMV in preventing and treating atel-
ectasis in these two clinical scenarios.

48.2 Discussion

48.2.1 Postoperative Atelectasis and NIMV

Atelectasis occurs regularly during anesthesia induction and persists in the postop-
erative period. This may contribute to significant morbidity, delay in discharge, and
additional health-care costs. It is found in almost 90 % of all patients who are anaes-
thetized, on average involving 10 % of total lung tissue.
During general anesthesia, lung collapse may be caused by three basic mecha-
nisms: compression atelectasis by loss of diaphragm tone and abdominal pressure;
absorption atelectasis, when less gas enters the alveolus than that removed by blood
uptake; and by loss of surfactant, with a rise in surface alveolus tension [4].
In the postoperative period, pulmonary function is substantially decreased. In
addition to the mechanisms that occur during induction and the intrinsic drug effect,
others, such as pain, pleural opening, and diaphragm dysfunction, especially in tho-
racic or upper abdominal surgery, contribute to ventilation/perfusion mismatch,
worsening of hypoxemia, gas exchange, and atelectasis, expressed by a restrictive
syndrome (reduced vital capacity, tidal volume, and functional residual capacity)
and possibly respiratory failure [5]. Diaphragm dysfunction may last from 7 to 10
days after surgery. Bed rest contributes to this scenario.
One of the most feared postsurgical complications are pulmonary infections,
which are predisposed by persistent atelectasis and can cause irreversible loss of
functioning parenchyma. The most important risk factors for postsurgical respiratory
complications, especially atelectasis, are thoracic or upper abdominal surgery (close
to the diaphragm), obesity, chronic obstructive pulmonary disease, and older age.
The prevention of atelectasis has, therefore, always been one of the aims of post-
operative rehabilitation. In the 1980s, it was thought that the application of a posi-
tive pressure through CPAP would, on the one hand, reduce the work of the
respiratory muscles and, on the other, promote early recruitment of poorly aerated
regions of the lungs. The first pioneering studies regarding both abdominal and
thoracic surgery demonstrated that, following radiologic evidence of postoperative
atelectasis, it was possible to reduce or prevent pneumonia and loss of respiratory
function and improve gas exchange. More recently, some researchers have focused
48 Atelectasis and Noninvasive Mechanical Ventilation 403

on the prevention of respiratory complications, starting treatment before the surgery

or immediately after the surgical procedure has been completed.
CPAP or NIMV are commonly used in this clinical circumstance with proven
benefits. Their use promotes lung recruitment and improves oxygenation, without
hemodynamic adverse effects or pleural leaks. The work of breathing is diminished
when using NIMV, providing more effective ventilation and oxygen spare. In car-
diac or lung resection surgery, NIMV was shown to decrease the need for tracheal
intubation and hospital mortality [6]. Many of these benefits are explained by pre-
vention or treatment of preexisting atelectasis.
Kindgen-Milles et al. [7] showed that patients treated prophylactically with
CPAP of 10 cmH2O for 12–24 h after thoracoabdominal surgery (aneurysm of tho-
racoabdominal aorta) had significantly better oxygenation rates and shorter lengths
of intensive care unit and hospital stay. Pasquina et al. [1] reported that when CPAP
was applied in patients who developed postoperative atelectasis (based on roent-
genographic evidence) following cardiac surgeries, there was considerable improve-
ment of atelectasis, as determined by radiological scores.
Lorut et al. [8] reported a large prospective randomized trial involving seven
thoracic surgery departments, investigating postoperative NIMV, and their findings
showed no statistically significant differences in reintubation rate, mortality rates,
and length of hospital stay. However, the authors point out that the selection of
patients, the methodology regarding NIMV, and even the expertise of medical and
nonmedical personnel are essential to good outcomes.
Further studies are needed to identify the best protocol for preventive NIMV in
at-risk patients or curative NIMV in patients who develop postoperative atelectasis
or acute respiratory failure. To our knowledge, the lowest possible pressures should
be used to ensure a satisfactory therapeutic level, keeping patient comfort and safety
in mind. When using CPAP, pressure up to 10 cmH2O may be needed. In pressure
support ventilation, expiratory positive airway pressure (EPAP) should also be used
from 5 to 10 cmH2O, providing support pressures of 6–15 cmH2O, without exceed-
ing inspiratory positive airway pressure (IPAP) of 25 cmH2O.

48.2.2 Atelectasis in Neuromuscular Disorders and Critically Ill

Patients

In patients with neuromuscular disorders and in critically ill patients, atelectasis

may be prevented with respiratory physiotherapy and mechanical insufflation-
exsufflation devices. Nevertheless, respiratory physiotherapy has been largely
ignored in hospitalized patients, especially outside the intensive care unit.
Bronchoscopy is the end-of-line procedure to treat these patients, many of them
with critical diseases and with relative or absolute contraindications to this invasive
treatment. NIMV has been shown to be effective in preventing atelectasis in the
postoperative period, so we might extrapolate this data to prevent atelectasis in these
patients. There are only a few published clinical cases of success treating atelectasis
with NIMV in patients with neuromuscular disorders, acute hypercapnic respiratory
404 P. Matos

failure, and with contraindications to bronchoscopy [9], although we lack prospec-

tive studies to support this NIMV application. The most suitable ventilation mode
in these cases is bi-level pressure support ventilation in spontaneous/timed mode.

Conclusion
NIMV seems to play a major role in preventing and treating atelectasis, and it
should not be delayed in patients known to be at risk. Awareness and training of
personnel, including doctors, nurses, and respiratory therapists, is essential to
NIMV success. Further studies are needed to better identify patients at risk of
atelectasis and, furthermore, elaborate more concise NIMV protocols.

Key Recommendations
• Consider NIMV in patients at risk of developing atelectasis.
• Consider NIMV to treat atelectasis in the postoperative period
• Consider NIMV for treating atelectasis in patients with contraindications
to bronchoscopy.
• Use CPAP/EPAP pressures up to 10 cmH2O without exceeding IPAP of
25 cmH2O in postoperative patients.
• Provide NIMV in an adequate environment and with qualified personnel.

References
1. Pasquina P, Merlai P, Granier JM, Ricou B. Continuous positive airway pressure versus nonin-
vasive pressure support ventilation to treat atelectasis after cardiac surgery. Anesth Analg.
2004;99:1001–8.
2. Vargas FS, Cukier A, Terra-Filho M, et al. Influence of atelectasis on pulmonary function after
coronary artery bypass graft. Chest. 1993;104:434–7.
3. Villalona RM, Alises MA, Lobato SD. Resolution of obstructive atelectasis with non-invasive
mechanical ventilation. Arch Bronconeumol. 2014;50(10):452–3.
4. Magnusson L, Spahn DR. New concepts of atelectasis during general anaesthesia. Br J Anaesth.
2003;91(1):61–72.
5. Jaber S, Jong A, Castagnoli A, Futier E, et al. Non-invasive ventilation after surgery. Ann Fr
Anesth Reanim. 2014;33:487–91.
6. Auriant I, Jallot A, Herve P, Cerrina J, et al. Noninvasive ventilation reduces mortality in acute
respiratory failure following lung resection. Am J Respir Crit Care Med. 2001;164:1231–5.
7. Kindgen-Milles D, Müller E, Buhl R, Böhner H, et al. Nasal-continuous positive airway pres-
sure reduces pulmonary morbidity and length of hospital stay following thoracoabdominal
aortic surgery. Chest. 2005;128(2):821–8.
8. Lorut C, Lefebvre A, Planquette B, Quinquis L, et al. Early post-operative prophylactic non-
invasive ventilation after major lung resection in COPD patients: a randomized controlled trial.
Intensive Care Med. 2014;40:220–7.
9. Duncan S, Negrin R, Mihm FG, Guilleminault C, et al. Nasal continuous positive airway pres-
sure in atelectasis. Chest. 1992;92(4):621–4.
Noninvasive Ventilation in Patients
with Severe Community-Acquired 49
Pneumonia: What Have We Learned?
Key Response Determinants
and Practical Implications

Michele Carron and Francesco Zarantonello

Contents
49.1 Introduction ................................................................................................................. 406
49.2 Discussion and Analysis ............................................................................................. 406
49.2.1 Noninvasive Ventilation Techniques and Devices ......................................... 406
49.2.2 Rationale for NIV in ARF ............................................................................. 407
49.2.3 Rationale for NIV in CAP ............................................................................. 408
Conclusion ............................................................................................................................. 410
References .............................................................................................................................. 412

Abbreviations

ARDS Acute respiratory distress syndrome

ARF Acute respiratory failure
BiPAP Bi-level positive airway pressure
CAP Community-acquired pneumonia
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
FiO2 Fraction inspired oxygen
ICU Intensive care unit
NIV Noninvasive ventilation
OI Oxygenation index
OR Odds ratio
PaCO2 Partial arterial carbon dioxide pressure
PaO2 Partial arterial oxygen pressure

M. Carron, MD (*) • F. Zarantonello, MD

Department of Medicine, Anesthesiology and Intensive Care, University of Padova,
Padova, Italy
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 405

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_49
406 M. Carron and F. Zarantonello

PEEP Positive end-expiratory pressure

PSV Positive inspiratory ventilatory support
RCT Randomized controlled trial
SaO2 Arterial oxygen saturation
SAPS Simplified Acute Physiology Score

49.1 Introduction

In the United States, pneumonia is the most common cause of mortality among
infectious diseases and the sixth most common cause of death overall [1]. Pneumonia
is an infection of the lung parenchyma, which is referred to as community-acquired
pneumonia (CAP) when the infection is acquired outside a hospital or health-care
facility [1]. The incidence of CAP varies with age, increasing from 18/1,000 person-
years in individuals 65–69 years old to 52/1,000 person-years in individuals 85
years and older. Approximately 20–40 % of individuals with CAP will require hos-
pitalization, 10–20 % of whom will have severe CAP [1]. Severe CAP had been
defined as a CAP that requires intensive care unit (ICU) admission. It is associated
with mortality rates as high as 50 %, and almost half of the patients will require
mechanical ventilation [1]. Antimicrobial therapy is the mainstay of CAP treatment,
administered empirically at first and then tailored to culture results when they are
available. Oxygen therapy is often necessary to counteract hypoxemia [1]. If patients
fail to maintain adequate gas exchange (i.e., PaO2 >65 mmHg while receiving sup-
plemental oxygen at a FiO2 of 60 %) and acute respiratory failure (ARF) occurs,
tracheal intubation and mechanical ventilation should be considered [1–4].

49.2 Discussion and Analysis

49.2.1 Noninvasive Ventilation Techniques and Devices

Noninvasive ventilation (NIV) refers to the delivery of assisted mechanical ventila-

tion without an invasive airway conduit [1, 2]. This term includes different NIV
modalities, such as continuous positive airway pressure (CPAP), pressure support
ventilation (PSV), and bi-level positive airway pressure (BiPAP) [2]. CPAP is a
method that delivers constant positive airway pressure noninvasively throughout
both inspiration and expiration [3]. With PSV, the patient breathes spontaneously,
and, when the patient triggers the ventilator, the ventilator delivers a preset addi-
tional level of pressure to assist the patient during the inspiration phase. The tidal
volume varies from breath to breath during PSV [3]. When CPAP is applied with
PSV, it is referred to as positive end-expiratory pressure (PEEP) [3]. BiPAP is a
technique that delivers different levels of pressure during inspiration (IPAP) and
expiration (EPAP) [3]. BiPAP involves the application of two different levels of
positive airway pressure, in contrast to CPAP, which involves the use of only one
positive airway pressure [3].
49 Noninvasive Ventilation in Patients with Severe Community-Acquired Pneumonia 407

NIV can be delivered via many interfaces (nasal mask, face mask, or helmet),
each of which has its own advantages and disadvantages [2]. Appropriate selection
and adequate management of the device are crucial for minimizing the risk of com-
plications and failure during NIV [2, 3]. It is important to choose an interface that
fits properly and minimizes air leaks, and to help the patient become familiar with
the equipment in the first few minutes of NIV [2]. If a patient feels claustrophobic,
the use of a different size or type of mask or helmet may enhance comfort [2]. A
helmet is usually better tolerated than masks, resulting in longer use and lower NIV
failure rates [2, 3] (Fig. 49.1).

49.2.2 Rationale for NIV in ARF

Clinical evidence supports the use of NIV to avoid intubation in patients with ARF due
to chronic obstructive pulmonary disease (COPD) exacerbations and acute cardiogenic
pulmonary edema [2–4]. Although supporting evidence is less abundant, NIV may also
be considered for patients with acute respiratory distress syndrome (ARDS) [2–4]. In
patients with hypoxemic ARF, a trial of NIV is justified if patients are carefully selected
by highly experienced teams in accordance with the available guidelines, while consid-
ering the known risk factors and predictors for NIV failure [2, 3].
Regarding ventilatory strategy, both CPAP and PEEP prevent alveolar col-
lapse, reduce atelectasis by recruiting and stabilizing previously collapsed lung
units, and reduce ventilation/perfusion mismatch and shunt fraction, thereby
resulting in improved gas exchange. They decrease the work of breathing, coun-
terbalancing the inspiratory threshold load imposed by intrinsic PEEP in some
patients (e.g., those with COPD). Furthermore, PEEP and CPAP reduce left ven-
tricular afterload and increase cardiac output. PSV is more effective than CPAP
at achieving improved muscle unloading and relief from dyspnea during
NIV. PSV plus PEEP improves alveolar ventilation compared with that achieved
using CPAP alone [2, 3].

a b

Fig. 49.1 Use of NIV in patients admitted to ICU with severe CAP. The patients received nonin-
vasive mechanical ventilation (PSV with PEEP by Servo Ventilator 300A, MAQUET, Cinisello
Balsamo, MI, Italy) through a face mask (a) and a helmet (b)
408 M. Carron and F. Zarantonello

49.2.3 Rationale for NIV in CAP

Randomized controlled trials (RCTs) describing whether NIV is beneficial in pneu-

monia are scarce. Most have considered very heterogeneous populations of patients
with varying causes of ARF including, even if a small percentage, pneumonia [3].
Ferrer et al. [4], in a study involving 105 ARF patients, showed that BiPAP (BiPAP
Vision, Respironics Inc., Murrysville, PA, USA) produced a faster improvement in
oxygenation and dyspnea in patients receiving NIV and reduced the need for intuba-
tion from 52 % with conventional oxygen therapy to 25 % with NIV (p = 0.01).
Furthermore, NIV was linked to a decreased incidence of septic shock (p = 0.028).
These benefits were also evident for patients with pneumonia, in whom ICU mortality
was reduced from 53 % with conventional therapy to 15 % with NIV (p = 0.03).
The role of NIV in patients with CAP has been reported in the literature, each
with a different response to NIV. To better understand the benefit, the patients
should be considered as part of different subgroups [5–9]. They include a “de novo”
group, defined as patients with CAP without previous cardiac or pulmonary disease;
a “comorbidities” group, defined as CAP in patients with cardiac or pulmonary
diseases (i.e., COPD); and an “immunodepressed” group, defined as CAP in patients
with an impaired immune system due to a hematologic malignancy or being a trans-
plant recipient [5–9].
Whereas older studies consistently reported that NIV in “de novo” CAP patients
was associated with a high likelihood of failure and consequently high intubation
rates, some more recent studies have suggested otherwise. Brambilla et al. [5]
reported promising results in a RCT conducted in 4 Italian ICUs evaluating 81
patients with no history of COPD or heart failure, who developed severe hypoxemia
(PaO2/FiO2 <250 mmHg) due to pneumonia. Patients were randomized to receive
either CPAP (VitalSigns Inc., Totowa, NJ, USA) by helmet or oxygen therapy by
Venturi mask [5]. Compared with those receiving supplemental oxygen therapy,
patients in the CPAP group exhibited a faster improvement in PaO2/FiO2 ratio,
respiratory rate, and dyspnea, and a lower percentage met intubation criteria (15 %
vs 63 %, p <0.001) [5]. In a multicenter RCT comparing CPAP (high-flow genera-
tor, VitalSigns Inc., Totowa, NJ, USA) via a helmet to conventional oxygen therapy
in 47 CAP patients with moderate-severe hypoxemia, Cosentini et al. [6] found that
NIV was associated with a faster improvement in oxygenation (median 1.5 h vs
48 h, p <0.001), but as soon as the CPAP was stopped, oxygenation returned to
lower levels in most patients. The latter finding suggests that longer use of CPAP
may be needed to recruit the flooded alveoli characteristic of the initial phase of
pneumonia [6].
For patients with previous cardiac or pulmonary diseases, the available RCTs
report more encouraging results. In a study of 56 patients with CAP randomized
to receive either conventional oxygen therapy via Venturi mask or noninvasive
PSV (Cesar [Thaema, Antony Cedex, France]; Puritain Bennett 7200 [Puritain
Bennett Co., Overland Park, KS, USA]; Vential [Saime, Savigny-le-Temple,
France]; Servo 900 C [Siemens Elema, Uppsala, Sweden]) via face mask,
49 Noninvasive Ventilation in Patients with Severe Community-Acquired Pneumonia 409

Confalonieri et al. [7] reported a decrease in intubation rate from 50 % with

Venturi mask to 21 % with PSV (p = 0.03) but no reduction in mortality or length
of hospital stay. Subgroup analysis found that COPD patients with hypercapnic
respiratory failure benefited from NIV and had a reduced mortality rate at 2
months (11 % vs 63 %, p = 0.05). More recently, Carrillo et al. [8] prospectively
followed 250 CAP patients treated with BiPAP (BiPAP ST-D and VISION
Ventilator, Respironics, Inc., Murrysville, PA, USA) by means of nasal or face
mask in a highly experienced center. They found that NIV success was more fre-
quent in patients with a history of cardiac and pulmonary disease compared with
those with “de novo” ARF (74 % vs 54 %, p = 0.007) [8].
Immunodepressed patients in whom ARF develops often require mechanical
ventilatory support. In these patients, NIV has the potential to avoid endotracheal
intubation and its complications [2, 3]. In a RCT by Squadrone et al. [9], 40 neutro-
penic patients with ARF, tachypnea, and pulmonary infiltrates were randomized to
early CPAP (WhisperFlow, Caradyne, Ireland) with helmet or conventional oxygen
therapy. Among patients admitted to the ICU, oxygenation was better and the intu-
bation rate was lower in the CPAP than in the control group (p = 0.0001). NIV
showed a reduction in the relative risk for intubation to 0.46 (95 % confidence inter-
val [CI], 0.27–0.78) [9]. A systematic review by Zhang et al. [1], which included
one RCT involving immunodepressed patients with fever and pulmonary infiltrates,
reported that, compared with standard treatment, PSV (Evita, Dräger, Lübeck,
Germany) by means of a full face mask decreased the need for endotracheal intuba-
tion (odds ratio [OR], 0.26; 95 % CI, 0.08–0.85), shortened the ICU length of stay
(mean difference −2; 95 % CI, −3.92 to −0.08), reduced the incidence of complica-
tions (OR, 0.24; 95 % CI, 0.07–0.82), and reduced in-hospital mortality (OR 0.24;
95 % CI, 0.07–0.82). However, NIV did not affect the duration of mechanical ven-
tilation [1].
One of the major issues at present is the concern that submitting a patient to an
ineffective NIV trial will result in more harm than if invasive ventilation is estab-
lished immediately [8, 10]. Carrillo et al. [8] demonstrated in “de novo” CAP
patients that increased duration of NIV before intubation for NIV failure was asso-
ciated with decreased in-hospital survival (adjusted OR, 0.978; 95 % CI, 0.962–
0.995, p = 0.012) [8]. Survivors and nonsurvivors had comparable illness severity
scores at baseline, thereby suggesting that the increased risk was directly related to
postponing intubation after an ineffective NIV trial [8]. Interestingly, delayed intu-
bation in patients with previous cardiac or pulmonary comorbidities did not increase
mortality in the same study [8]. Similar results have been found in other studies,
providing further evidence suggesting that intubation should not be delayed when
patients are not doing well with NIV, because delaying intubation might result in
worse outcome [2, 8].
The possibility of being able to predict an individual patient’s response to NIV
is of great importance to avoiding a delay in intubation after beginning a trial of
NIV in patients with a high likelihood of failure. In the study by Carrillo et al. [8],
variables independently associated with NIV failure in CAP patients were a
410 M. Carron and F. Zarantonello

worsening radiological infiltrate at 24 h after admission and a higher heart rate,

lower PaO2/FiO2 ratio, and lower plasmatic level of bicarbonate after 1 h of
NIV. In 2010, Carron et al. [10] reported the results of their study investigating
various cardiorespiratory parameters as potential predictors of NIV failure. The
study included 64 patients with severe CAP treated with PSV (Servo Ventilator
300A, MAQUET, Cinisello Balsamo, MI, Italy) delivered by means of a helmet
[10]. Intubation was avoided in 44 % of these patients, and a successful NIV trial
was associated with a shorter stay in the ICU and lower ICU and in-hospital mor-
tality rates [10]. The group of patients requiring intubation had a higher Simplified
Acute Physiology Score (SAPS) II at ICU admission and a lower arterial pH
before starting NIV. After the 1st hour of treatment, patients who later required
intubation had a lower arterial pH and PaO2/FiO2 ratio and a higher respiratory
rate, PaCO2, and oxygenation index (OI; calculated as the mean airway pressure x
FiO2 × 100/PaO2) [10]. The only variables independently associated with success-
ful of NIV were a post-trial-to-pretrial increase in PaO2/FiO2 ratio of >42.2 and
decrease of OI of >1.2 [10]. In a review article, Nava et al. [2] noted that the pre-
dictors of NIV failure differed in hypercapnic and hypoxemic ARF. In patients
with hypercapnic ARF, the predictors were an unchanged or worsening arterial
pH, no change or an increase in respiratory rate after 1–2 h of NIV, a higher illness
severity at admission (SAPS II >34), and low patient compliance [2]. Predictors
for failure in patients with hypoxemic ARF were minimum improvement in PaO2/
FiO2 ratio after 1–2 h of NIV, age >40 years, higher illness severity at admission,
and the presence of ARDS or multiorgan system failure [2].

Conclusion
The goal of using NIV is to overcome the acute illness without the need of endo-
tracheal intubation, thereby leading to a reduction in morbidity and mortality
related to invasive mechanical ventilation [3]. The most frequent causes of death
in patients with ARF – septic shock and multiple organ failure – have been
specifically attributed to complications associated with invasive mechanical
ventilation [4].
Although evidence of its effectiveness from clinical studies is still not conclu-
sive, there has been a steady increase in the use of NIV for the treatment of
severe CAP in recent years. Whenever NIV is considered beneficial, it is sug-
gested to apply it as soon as possible and after rigorous selection of appropriate
patients, timely application of a proper ventilation interface, judicious use of
sedation, and continuous monitoring of patients and predictors of NIV failure by
a skilled care team (Table 49.1). The immediate availability of a means to per-
form endotracheal intubation is mandatory to avoid unnecessary and dangerous
delays, especially in patients with factors predictive of NIV failure or those who
fail to achieve previously chosen targets (i.e., adequate oxygenation, dyspnea
relief, and patient comfort).
49 Noninvasive Ventilation in Patients with Severe Community-Acquired Pneumonia 411

Table 49.1 Criteria for selection of patients and for management of a trial of NIV in case of
severe CAP
Success/failure
Criteria for NIV trial (1–2 h) Application of NIV predictors of NIV trial
Increased dyspnea at rest Explain technique to Success
patient
Deterioration of gas exchange (PaO2/FiO2 Choose correct interface Increase of arterial
<300, PaCO2 >45 mmHg, pH <7.35) oxygenation
Respiratory rate >24 breaths per minute Select the proper Decrease in
ventilatory support (i.e., respiratory rate
PS 8–10 mmHg and
PEEP 4–5 mmHg in
case of PSV)
Increased work of breathing, accessory Set FiO2 aiming for Decrease of dyspnea
muscle use, and/or paradoxical SaO2 >90 %
abdominal motion
Absence of contraindication(s) to NIV Optimize patient Significant increase
(respiratory arrest, agitated or comfort of PaO2/FiO2
uncooperative and/or medically unstable Minimize air leakage Decrease of OI
patient, inability to protect airway or
Consider mild sedation Absence of
excessive secretions not managed by
if patient is agitated contraindication(s)
secretion clearance techniques, two or
to NIV
more organ failures).
Monitor comfort, Failure
dyspnea, respiratory Stable or decrease of
rate, oxygen saturation, arterial
indices of NIV success/ oxygenation
failure
Stable or rise in
respiratory rate
Stable or increase of
dyspnea
Stable or decrease of
PaO2/FiO2
Stable or increase of
OI
Presence of
contraindication(s)
to NIV
NIV noninvasive ventilation, FiO2 fraction inspired oxygen, PaO2 partial arterial oxygen pressure,
PaCO2 partial arterial carbon dioxide pressure, PS pressure support, PEEP positive end-expiratory
pressure, PSV pressure support ventilation, SaO2 arterial oxygen saturation, OI oxygenation index
412 M. Carron and F. Zarantonello

Key Major Recommendations

• Invasive mechanical ventilation represents a cornerstone for the treatment
of ARF due to severe CAP.
• NIV may be used with caution in selected and strictly monitored patients
with severe CAP, particularly in those with a history of cardiac or pulmo-
nary disease or who are immunodepressed.
• Predicting success or failure of NIV may reduce the risks of a delayed
intubation in patients with severe CAP.

Conflict of Interest Disclosure The authors have no interests to disclose.

References
1. Zhang Y, Fang C, Dong BR, et al. Oxygen therapy for pneumonia in adults. Cochrane Database
Syst Rev. 2012;3:CD006607.
2. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet.
2009;374:250–9.
3. Ferrer M, Torres A. Noninvasive ventilation for acute respiratory failure. Curr Opin Crit Care.
2015;21:1–6.
4. Ferrer M, Esquinas A, Leon M, et al. Noninvasive ventilation in severe hypoxemic respiratory
failure: a randomized clinical trial. Am J Respir Crit Care Med. 2003;168:1438–44.
5. Brambilla AM, Aliberti S, Prina E, et al. Helmet CPAP vs. oxygen therapy in severe hypox-
emic respiratory failure due to pneumonia. Intensive Care Med. 2014;40:942–9.
6. Cosentini R, Brambilla AM, Aliberti S, et al. Helmet continuous positive airway pressure vs
oxygen therapy to improve oxygenation in community-acquired pneumonia: a randomized,
controlled trial. Chest. 2010;138:114–20.
7. Confalonieri M, Potena A, Carbone G, et al. Acute respiratory failure in patients with severe
community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventila-
tion. Am J Respir Crit Care Med. 1999;160:1585–91.
8. Carrillo A, Gonzalez-Diaz G, Ferrer M, et al. Non-invasive ventilation in community-acquired
pneumonia and severe acute respiratory failure. Intensive Care Med. 2012;38:458–66.
9. Squadrone V, Massaia M, Bruno B, et al. Early CPAP prevents evolution of acute lung injury
in patients with hematologic malignancy. Intensive Care Med. 2010;36:1666–74.
10. Carron M, Freo U, Zorzi M, et al. Predictors of failure of noninvasive ventilation in patients
with severe community-acquired pneumonia. J Crit Care. 2010;25:540.e9–14.
Noninvasive Ventilation in Acute
Respiratory Distress Syndrome 50
Seval Urkmez and Yalim Dikmen

Contents
50.1 Introduction ................................................................................................................... 414
50.2 Discussion ..................................................................................................................... 414
Conclusion ............................................................................................................................... 417
References ................................................................................................................................ 418

Abbreviations

ARDS Acute respiratory distress syndrome

ARF Acute respiratory failure
CPAP Continuous positive airway pressure
EACC European-American Consensus Conference
NPPV Noninvasive positive pressure ventilation
PaO2/FiO2 Ratio of arterial oxygen tension to fractional inspired oxygen
concentration
PEEP Positive end-expiratory pressure
PSV Pressure support ventilation

S. Urkmez • Y. Dikmen (*)

Department of Anesthesiology and Reanimation, Cerrahpasa Medical School, Istanbul
University, Istanbul, Turkey
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 413

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_50
414 S. Urkmez and Y. Dikmen

50.1 Introduction

Acute respiratory distress syndrome (ARDS) is a syndrome of diffuse lung injury

that is characterized by acute dyspnea and tachypnea, severe hypoxemia, bilateral
opacities on the chest X-ray, and decreased respiratory compliance. The European-
American Consensus Conference (EACC) suggested four clinical criteria for a uni-
form definition of ARDS. These are acute onset of hypoxemic respiratory failure
(hypoxemia was defined as the ratio of arterial oxygen tension to fractional inspired
oxygen concentration (PaO2/FiO2) below 300 for acute lung injury and below 200
for ARDS), bilateral infiltrations in chest X-ray, pulmonary capillary wedge pres-
sure below 18 mmHg, and the absence of clinical symptoms of left atrial hyperten-
sion [1]. In 2011, an expert panel convened to update the EACC definitions of
ARDS and the new Berlin definitions were proposed. These definitions make a
classification of ARDS in three stages of severity, from mild to severe [2].
Whatever the definition is, the mainstay of treatment of ARDS is mechanical
ventilation to improve gas exchange and decrease work of breathing. Moreover, the
only evidence-based treatment in ARDS is mechanical ventilation using a lung-
protective strategy with high positive end-expiratory pressure (PEEP) and low tidal
volumes, which almost always necessitates endotracheal intubation [3]. However,
recent efforts have been focused on the use of noninvasive positive pressure ventila-
tion (NPPV) in acute respiratory failure (ARF) to avoid complications associated
with intubation. The guidelines suggest use of NPPV in acute exacerbations of
chronic obstructive pulmonary disease, cardiogenic pulmonary edema, postopera-
tive patients, and immunosuppressed patients with strong evidence [4]. Use of
NPPV in these settings improves outcomes, decreases length of stay in the intensive
care unit and hospital, and lowers costs of hospitalization.

50.2 Discussion

The use of NPPV in hypoxemic ARF, especially in ARDS, is somewhat controver-

sial. Early studies, which compared application of NPPV with standard therapy,
yielded different success rates in different etiologies. For example, in the work of
Antonelli et al. [5], the overall failure rate of NPPV was found to be 30 % in 354
patients, where the highest intubation rate was in ARDS and community-acquired
pneumonia (50 and 51 %, respectively). Generally, in these studies, ARDS patients
comprised only a small portion of the study patients; in the Antonelli et al. study,
only 86 of 354 patients had ARDS. In another randomized controlled study from
Ferrer et al. [6], 105 hypoxemic respiratory failure patients were randomized to
receive either NIPPV or high-concentration oxygen therapy. In this study, most of
the patients had pneumonia or cardiogenic lung edema. Only 7 patients in the NPPV
group and 8 patients in high-concentration oxygen group had ARDS when they
were recruited. Overall, NPPV decreased the need for endotracheal intubation and
rate of septic shock occurrence and decreased mortality in hypoxemic respiratory
failure, but the efficacy of NPPV in ARDS subgroup was poor, and ARDS was
50 Noninvasive Ventilation in Acute Respiratory Distress Syndrome 415

associated with increased need for endotracheal intubation. In their randomized

study, Delclaux et al. [7] observed that use of continuous positive airway pressure
(CPAP) was not effective in preventing endotracheal intubation when compared
with standard oxygen therapy, although it resulted in a physiological improvement
at the early stages.
Actually, there is a strong rationale for the use of NPPV in ARDS. Inflammation
and edema in lung tissue collapse alveoli, decrease inflatable lung volume, and
cause intrapulmonary shunting. Loss of surfactant function and functional residual
capacity cause cyclic opening and closing of alveoli, leading to further lung injury,
and increased elastance of the lungs increases work of breathing. Applying positive
pressure to the airways increases lung volumes, improves alveolar stability, and
decreases work of breathing [8, 9]. All of these may help to stop deterioration in
respiratory function and avoid intubation.
On the other hand, in ARDS, the pressure levels needed to overcome alveolar
collapse may be very high, which by itself necessitates endotracheal intubation for
a firm connection with the ventilator. Indeed, it has been shown that presence of
ARDS and inability to improve PaO2/FiO2 ratio were independent predictors of
NPPV failure [5]. In the Berlin consensus meeting, the experts who evaluated the
evidence on ARDS proposed NPPV as a matter of research in mild ARDS patients
who have a PaO2/FiO2 ratio between 300 and 200 and need low to moderate levels
of PEEP along with low tidal volume ventilation [2].
The suggestion from the Berlin meeting may be rather conservative. Given the
lack of good-quality evidence, the need for further studies is obvious; however,
there are some studies that show a good success rate of NPPV in ARDS patients
with lower PaO2/FiO2 ratios. For instance, another study from Antonelli et al. [10]
showed that endotracheal intubation could be avoided in 54 % of ARDS patients in
a multiple center survey. In this study, 174 patients who fulfilled the EACC criteria
for ARDS were treated with NPPV as a first-line treatment. These patients had a
mean initial PaO2/FiO2 ratio below 120. The success rate of this study contradicts
the findings in the meta-analysis of Agarwall et al. [11]. In this meta-analysis of
three studies, the authors concluded that the addition of NPPV to standard treatment
had no effect on avoidance of endotracheal intubation and intensive care unit (ICU)
mortality, and the use of NPPV in ARDS could not be suggested. One important fact
regarding the trial by Antonelli et al. is that the centers that applied NPPV to the
ARDS patients as initial therapy had considerable experience in NPPV applications.
In a second meta-analysis, which included 13 studies (540 patients), Agarwal et al.
[12] observed that endotracheal intubation could be avoided in 52 % patients, and
NPPV could be used with strict caution in ARDS patients.
These examples show that the use of NPPV in ARDS patients is still a controver-
sial issue. Although a success rate of 50 % in this group of patients should be con-
sidered as a strong signal for the use of NPPV as an initial treatment, several
problems like patient selection, selection of interface and ventilator mode, and signs
of the need for intubation should be kept in mind.
Because ARDS is a syndrome that affects heterogeneous patient populations,
contraindications of NPPV should be kept in mind [13]. These patients may have
416 S. Urkmez and Y. Dikmen

other organ failures and/or hemodynamic instability, and delays in intubation may
cause excessive mortality, which is why the clinician should be cautious when initi-
ating NPPV treatment. Current knowledge prevents using NPPV in patients with
severe ARDS (PaO2/FiO2 <100). In moderate ARDS, patients should be monitored
carefully and intubated at the first instance when needed. For this reason, admitting
patients to the ICU would be appropriate [12].
The aims of NPPV treatment in ARDS are to improve gas exchange (PaO2/FiO2
ratio), relieve dyspnea, and decrease work of breathing. These can be achieved by
choosing the right interface and ventilator mode for the patient. Unfortunately, no
studies have addressed these issues, so the choice should be made depending on
limited experience. In most of the studies investigating NPPV in acute hypoxemic
respiratory failure, an oronasal mask was used as an interface. This has a physio-
logic rationale, as this type of interface minimizes leaks and permit use of higher
airway pressures. Also, keeping the mouth in the mask increases effectiveness and
gives the clinician an opportunity to use modes other than CPAP. In their study,
Antonelli et al. [10] reported that they used either oronasal masks or helmets to
provide noninvasive pressure support ventilation (PSV) with high PEEP. This can
be an important practical approach to increase the success of NPPV. However, it
should be kept in mind that helmets may require use of higher tidal volumes because
some of the volume is needed to distend the helmet, and they may cause synchroni-
zation problems with the ventilator if the pressure or volume changes cannot be
sensed by the ventilator.
It has been shown that the use of CPAP is generally ineffective in avoiding intu-
bation in ARDS patients [7]. Although this application may increase PaO2/FiO2
ratio at the beginning it is ineffective in relieving dyspnea and decreasing work of
breathing. Modes other than PSV of biphasic airway pressure are not studied in the
ARDS setting.
Another issue is the choice of ventilator. As with modes of ventilation, there is no
study comparing the effectiveness of noninvasive and intensive care ventilators.
However, it is logical to use intensive care ventilators because these allow a higher
control on FiO2, better monitoring and alarm capabilities, and a wide range of
modes to choose from.
Patients should be monitored carefully after the institution of NPPV for signs of
failure and need for intubation. An experienced clinician, whether a nurse, respira-
tory therapist, or a physician, should be available at the bedside to assess the effec-
tiveness of NPPV. The first hours of therapy are especially critical; it has been
shown that a lack of improvement of PaO2/FiO2 ratio, dyspnea, and respiratory rate
at the first hour predicts NPPV failure [5, 10].
Once started, application of ventilation support should be sustained for several
days. Because these patients are severely hypoxemic, loss of lung volumes due to a
loss in positive pressure cannot be tolerated. For this reason, leaks around the mask
should be minimized at all times. If the patient does not show signs of NPPV failure
and gas exchange improves, than NPPV can be applied intermittently. In their sur-
vey, Antonelli et al. [10] observed that in the patients who avoided intubation, con-
tinuous NPPV was applied for about 48 h. In this study, the patients who needed
50 Noninvasive Ventilation in Acute Respiratory Distress Syndrome 417

intubation were intubated within 48 h. The main determinants for intubation were
Simplified Acute Physiologic Scale (SAPS) II score above 34 and PaO2/FiO2 ratio
below 175 after 1 h of noninvasive ventilation.

Conclusion
NPPV can be the first treatment in mild and, to some extent, moderate ARDS. It
can be omitted in patients with severe ARDS, where the PaO2/FiO2 levels are
below 100 and the physiological condition is severe (high Acute Physiologic
Score and Chronic Health Evaluation (APACHE) II or SAPS II scores). The
clinician has to regard the risks and benefits of NPPV in all ARF, which are, if
NPPV is successful, reduced rate of nosocomial infections, lower length of stay
in the ICU, and lower mortality; and if NPPV fails is increased mortality, if intu-
bation is delayed. Hypoxemic respiratory failure includes a diverse group of
patients with various etiologic factors, and ARDS can be considered the most
severe form of this clinical condition.
The evidence supporting use of NPPV in ARDS is quite weak, and it can be
suggested that it is contraindicated in these patients. But, considering the benefits
of NPPV, it should be tried early and as the first-line treatment at least in mild
ARDS patients. The selection of interface and ventilator mode should aim to
improve gas exchange by applying high airway pressures, and to alleviate dys-
pnea by application of pressure support during inspiration. During NPPV appli-
cation, patients should be monitored closely for worsening gas exchange and
physiologic status and gas leaks around the mask. When there is no improvement
in patients during the first hours of NPPV, the clinician should not hesitate to
intubate the patient. When NPPV is considered successful, it should be applied
continuously for at least 24 h. The airway pressures should be titrated upwards
by 2–3 cmH2O increments in PEEP and pressure support level, and kept at the
highest levels, which provide the best gas exchange and lowest leakage around
the mask.

Key Points
• NPPV can be used in patients with mild and mild-to-moderate ARDS, but
it should be employed in ICUs, where prompt endotracheal intubation and
invasive mechanical ventilation are feasible.
• Patient selection is of the utmost importance in the success of NPPV in
patients with ARDS.
• Patients with multiple organ failure, high severity scores, severe metabolic
acidosis, or in shock should be intubated for invasive ventilation.
• Patients should be closely monitored for the signs of failure of NPPV in the
first hours; patients with hemodynamic instability, without improvement in
gas exchange or dyspnea, or who cannot tolerate NPPV through a mask
should be intubated promptly.
418 S. Urkmez and Y. Dikmen

References
1. Bernard GR, Artigas A, Brigham KL, et al. Report of the American-European Consensus
Conference on ARDS: definitions, mechanism, relevant outcomes and clinical trial coordina-
tion. The Consensus Committee. Intensive Care Med. 1994;20:225–32.
2. Ferguson ND, Fan E, Camporota L, et al. The Berlin definition of ARDS: an expanded ratio-
nale, justification, and supplementary material. Intensive Care Med. 2012;38:1573–82.
3. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung
injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome
Network. N Engl J Med. 2000;342:1301–8.
4. Keenan SP, Sinuff T, Burns KE, et al. Clinical practice guidelines for the use of noninvasive
positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute
care setting. CMAJ. 2011;83:E195–214.
5. Antonelli M, Conti G, Moro ML, et al. Predictors of failure of noninvasive positive pressure
ventilation in patients with acute hypoxemic respiratory failure: a multi-center study. Intensive
Care Med. 2001;27:1718–28.
6. Ferrer M, Esquinas A, Leon M, et al. Noninvasive ventilation in severe hypoxemic respiratory
failure: a randomized clinical trial. Am J Respir Crit Care Med. 2003;168:1438–44.
7. Delclaux C, L’Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respira-
tory insufficiency with continuous positive airway pressure delivered by a face mask: a ran-
domized controlled trial. JAMA. 2000;284:2352–60.
8. L’Her E, Deye N, Lellouche F, et al. Physiologic effects of noninvasive ventilation during acute
lung injury. Am J Respir Crit Care Med. 2005;172:1112–8.
9. Katz JA, Marks JD. Inspiratory work with and without continuous positive airway pressure in
patients with acute respiratory failure. Anesthesiology. 1985;63:598–607.
10. Antonelli M, Conti G, Esquinas A, et al. A multiple-center survey on the use in clinical prac-
tice of noninvasive ventilation as a first-line intervention for acute respiratory distress syn-
drome. Crit Care Med. 2007;35:18–25.
11. Agarwal R, Reddy C, Aggarwal AN, Gupta D. Is there a role for noninvasive ventilation in
acute respiratory distress syndrome? A meta-analysis. Respir Med. 2006;100:2235–8.
12. Agarwal R, Aggarwal AN, Gupta D. Role of noninvasive ventilation in acute lung injury/acute
respiratory distress syndrome: a proportion meta-analysis. Respir Care. 2010;55:1653–60.
13. Organized jointly by the American Thoracic Society, the European Respiratory Society, the
European Society of Intensive Care Medicine, and the Société de Réanimation de Langue
Française, and approved by ATS Board of Directors, December 2000. International Consensus
Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute
Respiratory failure. Am J Respir Crit Care Med. 2001;163:283–91.
Noninvasive Mechanical Ventilation
in Transfusion-Related Acute Lung Injury 51
Sami Alsolamy, Hasan M. Al-Dorzi, and Yaseen M. Arabi

Contents
51.1 Introduction ................................................................................................................. 420
51.2 Pathogenesis of TRALI............................................................................................... 420
51.3 Risk Factors ................................................................................................................ 420
51.4 Diagnosis and Clinical Manifestations ....................................................................... 421
51.5 Management................................................................................................................ 422
51.6 Physiological Basis for Noninvasive Ventilation in TRALI ....................................... 422
51.7 Evidence for NIV Use in TRALI ................................................................................ 422
Conclusions ............................................................................................................................ 423
References .............................................................................................................................. 424

Abbreviations

ALI Acute lung injury

APACHE II Acute Physiology and Chronic Health Evaluation II
ARDS Acute respiratory distress syndrome
CPAP Continuous positive airway pressure

S. Alsolamy, MD, MPH

Department of Emergency Medicine and Intensive Care Department, King Saud Bin
Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
e-mail: [email protected]
H.M. Al-Dorzi, MD
Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences,
Riyadh, Saudi Arabia
e-mail: [email protected]
Y.M. Arabi, MD, FCCP, FCCM (*)
Intensive Care Department, College of Medicine, King Saud bin Abdulaziz University for
Health Sciences, PO Box 22490, Mail code 1425, Riyadh 11426, Saudi Arabia
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 419

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_51
420 S. Alsolamy et al.

FiO2 Fraction of inspired oxygen

ICU Intensive care unit
NIV Noninvasive ventilation
PaO2 Partial pressure of arterial oxygen
PEEP Positive end-expiratory pressure
PSV Pressure-support ventilation
SpO2 Oxygen saturation
TACO Transfusion-associated circulatory overload
TRALI Transfusion-related acute lung injury

51.1 Introduction

Transfusion-related acute lung injury (TRALI) is a clinical syndrome associated

with the transfusion of blood products. A rare and potentially fatal complication, it
is reported to have a prevalence of 1 in 1,323–5,000 transfused units [1]. It is gener-
ally agreed that TRALI is underdiagnosed and underreported, meaning that its true
incidence is unknown [2]. With growing awareness of the syndrome, however,
reports of TRALI are increasing. TRALI occurs at similar rates in both sexes and in
all age groups [3]. TRALI is estimated to occur in up to 8 % of critically ill patients
who undergo blood transfusion [4].

51.2 Pathogenesis of TRALI

Although the pathogenesis of TRALI is not yet completely understood, a two-hit

mechanism is the currently accepted theory. The first hit is the patient’s condition,
which causes neutrophil sequestration and priming in the lung microvasculature and
an increase in the number of neutrophils within the pulmonary capillary vasculature
[5, 6]. The second hit is related to trigger factors in transfused blood that activate
neutrophils, resulting in damage to the pulmonary capillary endothelium [5].

51.3 Risk Factors

Risk factors for TRALI can be categorized as patient-specific or transfusion-specific

(Table 51.1). Patient-specific risk factors include shock, chronic alcohol abuse, vol-
ume overload, smoking, mechanical ventilation with a high peak airway pressure,
high interleukin-8 levels, liver transplantation, a high Acute Physiology and Chronic
Health Evaluation (APACHE) II score, hematologic malignancy, sepsis, massive
transfusion, and emergency coronary artery bypass grafting [4, 7]. Transfusion-
specific risk factors include plasma from female donors or whole blood, increased
quantities of cognate anti-human leukocyte antigen class II, and volume of anti-
human neutrophil antigen in the blood [7]. In addition, increased numbers of trans-
fusions are associated with increased risk of TRALI [4].
51 Noninvasive Mechanical Ventilation in Transfusion-Related Acute Lung Injury 421

Table 51.1 Risk factors for TRALI

Patient-specific risk factors Transfusion-specific risk factors
Shock Plasma from female donors
Chronic alcohol abuse Whole blood transfusion
Volume overload High quantities of cognate anti-human
leukocyte antigen class II
Smoking High quantities of anti-human neutrophil
antigen
High peak airway pressure in mechanically Massive transfusion
ventilated patients
High interleukin-8 levels FFP or platelets
Liver transplantation
High Acute Physiology and Chronic Health
Evaluation (APACHE) II score
Hematologic malignancy
Sever sepsis
FFP fresh-frozen plasma

51.4 Diagnosis and Clinical Manifestations

The clinical presentation of TRALI is variable. Symptoms and signs may include
dyspnea, hypoxia, tachycardia, hypotension, fever, and pulmonary edema [8]. Chest
radiography may show bilateral infiltrates. TRALI may occur during transfusion or
within 6 h of transfusion [9]. TRALI can be classified as mild, moderate, or severe,
depending on the immediacy of onset, the duration, and the degree of patient
disability.
Large multinational collaborations, such as the National Heart Lung and Blood
Institute Working Group on TRALI and the Canadian Consensus Conference on
TRALI, have developed the following diagnostic criteria [8, 9]:

• New acute lung injury (ALI) during or within 6 h of transfusion.

• Hypoxemia defined as partial pressure of arterial oxygen (PaO2)/fraction of
inspired oxygen (FiO2) ≤300 or oxygen saturation (SpO2) <90 % of room air.
• No evidence of cardiogenic pulmonary edema.
• No preexisting ALI or acute respiratory distress syndrome (ARDS) before
transfusion.

TRALI has been reported to occur later than 6 h after transfusion [10]. This has
led other agencies and authors to extend the window for diagnosis to up to 24–72 h
after transfusion [11]. Despite the presence of these diagnostic criteria, TRALI is
frequently classified as possible, probable, or definite, depending on the temporal
relationship to blood transfusion or coexisting alternative risk factors for ALI [8].
Additionally, it is sometimes difficult make a distinction between TRALI and
422 S. Alsolamy et al.

transfusion-associated circulatory overload (TACO). TACO is a second type of lung

injury related to blood transfusion. It is characterized by the rapid accumulation of
fluid within the interstitial tissue of the lung, resulting from increased intravascular
volume and increased hydrostatic pressure after blood transfusion [12]. The clinical
presentation of TACO is similar to that of TRALI. However, patients with TACO
show symptoms of venous overload, such as an elevated jugular venous pulse,
hypertension, and elevated levels of B-type natriuretic peptide, which are not seen
with TRALI [12].

51.5 Management

TRALI is a self-limited condition that generally lasts for 48–96 h and has a good
prognosis [13]. Its treatment is usually supportive, including oxygen supplementa-
tion, but it frequently requires intensive care unit (ICU) admission [11]. The reported
rates of requirement for mechanical ventilation are variable. In a study from Canada,
Silliman et al. [1] found that only 3 % of TRALI patients required mechanical ven-
tilation, whereas a surveillance program in the United Kingdom reported that 45 %
of TRALI patients required mechanical ventilation [11]. In a series of 37 patients
with TRALI, all patients required oxygen supplementation and 72 % required
mechanical ventilation [14]. In a study of ICU patients who developed TRALI,
78 % of patients were treated with mechanical ventilation, the median duration of
support being 3.6 days (interquartile range, 1.6–7.1 days) [1, 2].

51.6 Physiological Basis for Noninvasive Ventilation in TRALI

TRALI frequently results in acute hypoxemic respiratory failure. Noninvasive ven-

tilation (NIV) has been established as a treatment modality for respiratory failure,
with variable rates of success depending on the cause, severity, and patient charac-
teristics. The beneficial physiological effects of NIV include reduced work of
breathing, decreased inspiratory effort, increased dynamic lung compliance,
increased tidal volume, improved pulmonary gas exchange, and improved arterial
blood gas content [2–6].

51.7 Evidence for NIV Use in TRALI

The use of NIV in ARDS is controversial, as large and specific randomized con-
trolled trials on this topic are lacking. Ferrer et al. randomized 105 patients with
severe hypoxemic respiratory failure, 15 of whom had ARDS, to NIV or high O2 [7,
8, 15]. NIV prevented intubation and was associated with better survival. However,
in another study of 123 patients with acute hypoxemic respiratory failure, 102 had
ARDS, NIV did not reduce intubation or mortality [7, 9]. A meta-analysis of six
randomized controlled trials involving 227 patients concluded that early use of NIV
can decrease the endotracheal intubation rate in patients with ALI, but does not
51 Noninvasive Mechanical Ventilation in Transfusion-Related Acute Lung Injury 423

change the mortality of these patients [2, 10, 12]. A more recent systematic review
and meta-analysis evaluating the efficacy of NIV in non-chronic obstructive pulmo-
nary disease and non-trauma patients with acute hypoxemic respiratory failure con-
cluded that using NIV as adjunctive therapy in patients with heterogeneous causes
of acute hypoxemic respiratory failure decreases the need for intubation, ICU length
of stay, and mortality rate [10, 13]. However, the use of NIV in ARDS is associated
with a failure rate as high as 83 %. In fact, ALI and ARDS have been found to be
independent risk factors for NIV failure in patients with acute hypoxemic respira-
tory failure, together with age >40 years, a Simplified Acute Physiology Score II of
> 35, and PaO2/FiO2 < 146 after 1 h of NIV [2, 11, 14, 16, 17].
Nevertheless, because TRALI usually represents a milder, self-limited form
of ARDS and most patients recover within 48–96 h with supportive care [14, 16,
18], the outcome of TRALI patients with the use of NIV is expected to be differ-
ent than the outcome of those who have ARDS from other causes. No clinical
trials have yet investigated the role of NIV in TRALI. In a prospective cohort
study investigating transfusion risk factors, of 74 patients who developed TRALI,
58 were treated with mechanical ventilation and 10 with NIV [2, 19]. In addition,
a case of severe TRALI associated with myocardial stunning in a 14-year-old girl
treated with NIV has been reported [20, 21]. The use of NIV in TACO has a
potentially greater effect than it does in TRALI because of the similarity of
TACO to cardiogenic pulmonary edema, in which NIV is the preferable initial
mode of assisted ventilation. This is supported by evidence from meta-analyses
reporting that NIV decreases in-hospital mortality in patients with cardiogenic
pulmonary edema [16, 22].
The ventilation modes of NIV that are used in ALI include continuous positive
airway pressure (CPAP) and pressure-support ventilation (PSV) combined with
positive end-expiratory pressure (PEEP). Clinical data show that, compared with
CPAP alone, PSV with PEEP performs better for inspiratory muscle unloading and
improved dyspnea [6, 23].

Conclusions
The key to TRALI management is ventilation and oxygenation support. If NIV
is applied early and restricted to selected patients with mild to moderate severity
in whom the criteria for immediate intubation are absent, it can be safe for
TRALI patients and can improve oxygenation and reduce invasive ventilation
morbidity. Because clinical studies for the use of NIV in patients with TRALI are
lacking, its routine use in these patients has not been clearly established.

Key Major Recommendations

• Transfusion-related ALI is a rare and potentially fatal complication associ-
ated with the transfusion of blood products.
• Ventilation and oxygenation support is key to TRALI management.
• The role of noninvasive ventilation in TRALI is not yet been established
and is controversial.
424 S. Alsolamy et al.

References
1. Silliman CC, Boshkov LK, Mehdizadehkashi Z, et al. Transfusion-related acute lung injury:
epidemiology and a prospective analysis of etiologic factors. Blood. 2003;101:454–62.
2. Gajic O, Rana R, Winters JL, et al. Transfusion-related acute lung injury in the critically ill:
prospective nested case-control study. Am J Respir Crit Care Med. 2007;176:886–91.
3. Kopko PM, Marshall CS, MacKenzie MR, et al. Transfusion-related acute lung injury: report
of a clinical look-back investigation. JAMA. 2002;287:1968–71.
4. Kallet RH, Diaz JV. The physiologic effects of noninvasive ventilation. Respir Care.
2009;54:102–15.
5. Holness L, Knippen MA, Simmons L, et al. Fatalities caused by TRALI. Transfus Med Rev.
2004;18:184–8.
6. L’Her E, Deye N, Lellouche F, et al. Physiologic effects of noninvasive ventilation during acute
lung injury. Am J Respir Crit Care Med. 2005;172:1112–8.
7. Bux J, Sachs UJH. The pathogenesis of transfusion-related acute lung injury (TRALI). Br
J Haematol. 2007;136:788–99.
8. Fung YL, Silliman CC. The role of neutrophils in the pathogenesis of transfusion-related acute
lung injury. Transfus Med Rev. 2009;23:266–83.
9. Girou E, Schortgen F, Delclaux C, et al. Association of noninvasive ventilation with nosoco-
mial infections and survival in critically ill patients. JAMA. 2000;284:2361–7.
10. Toy P, Gajic O, Bacchetti P, et al. Transfusion-related acute lung injury: incidence and risk
factors. Blood. 2011;119:1757–67.
11. Antonelli M, Conti G, Moro M, et al. Predictors of failure of noninvasive positive pressure
ventilation in patients with acute hypoxemic respiratory failure: a multi-center study. Intensive
Care Med. 2001;27:1718–28.
12. Luo J, Wang M-Y, Zhu H, et al. Can non-invasive positive pressure ventilation prevent endo-
tracheal intubation in acute lung injury/acute respiratory distress syndrome? A meta-analysis.
Respirology. 2014;19:1149–57.
13. AlYami MA, AlAhmari MD, Alotaibi H, et al. Evaluation of efficacy of non-invasive ventila-
tion in Non-COPD and non-trauma patients with acute hypoxemic respiratory failure: a sys-
tematic review and meta-analysis. Ann Thorac Med. 2015;10(1):16–24.
14. Toy P, Lowell C. TRALI – definition, mechanisms, incidence and clinical relevance. Best Pract
Res Clin Anaesthesiol. 2007;21:183–93.
15. Ferrer M, Esquinas A, Leon M, et al. Noninvasive ventilation in severe hypoxemic respiratory
failure: a randomized clinical trial. Am J Respir Crit Care Med. 2003;168:1438–44.
16. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute
lung injury: statement of a consensus panel. Transfusion. 2004;44:1774–89.
17. Rana S, Jenad H, Gay PC, et al. Failure of non-invasive ventilation in patients with acute lung
injury: observational cohort study. Crit Care. 2006;10:R79.
18. Barrett NA, Kam PCA. Transfusion-related acute lung injury: a literature review. Anaesthesia.
2006;61:777–85.
19. Moore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment,
and prognosis. Crit Care Med. 2006;34:S114–7.
20. Chapman CE, Stainsby D, Jones H, et al. Ten years of hemovigilance reports of transfusion-
related acute lung injury in the United Kingdom and the impact of preferential use of male
donor plasma. Transfusion. 2009;49:440–52.
21. Piastra M, Luca E, Stival E, et al. Non-invasive ventilation for severe TRALI and myocardial
stunning: report and literature review. Int J Hematol. 2012;96:390–4.
22. Weng C-L, Zhao Y-T, Liu Q-H, et al. Meta-analysis: noninvasive ventilation in acute cardio-
genic pulmonary edema. Ann Intern Med. 2010;152:590–600.
23. Gajic O, Gropper MA, Hubmayr RD. Pulmonary edema after transfusion: how to differentiate
transfusion-associated circulatory overload from transfusion-related acute lung injury. Crit
Care Med. 2006;34:S109–13.
Noninvasive Ventilation in Patients
with Blunt Chest Trauma: What Have 52
We Learned? Key Response
Determinants and Practical Implications

Abhijit Duggal and Tasnim Sinuff

Contents
52.1 Introduction ................................................................................................................. 426
52.2 Discussion ................................................................................................................... 427
52.2.1 Pathophysiology of Lung Injury in Blunt Chest Trauma .............................. 427
52.2.2 Potential Benefits of Early Application of NIV ............................................ 427
52.2.3 Safety of the Use of NIV in Chest Trauma: Overview of the Literature....... 428
52.2.4 Approach to the Use of NIV in Chest Trauma .............................................. 429
52.2.5 Late Application of NIV Does Not Benefit Patients ..................................... 431
52.2.6 Pain Management as an Important Adjunct to the Use of NIV .................... 431
52.2.7 Outcomes of Patients Managed with NIV..................................................... 431
Conclusion ............................................................................................................................. 432
References .............................................................................................................................. 433

Abbreviations

ARDS Acute respiratory distress syndrome

COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
FiO2 Fraction of inhaled oxygen
GCS Glasgow Coma Scale

A. Duggal, MD, MPH, FACP (*)

Department of Pulmonary, Allergy and Critical Care, Cleveland Clinic, Cleveland, OH, USA
e-mail: [email protected]
T. Sinuff, MD, PhD, FRCPC
Department of Critical Care Medicine, Sunnybrook Research Institute, Sunnybrook Health
Sciences Centre, and Interdepartmental Division of Critical Care, University of Toronto,
Toronto, ON, Canada
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 425

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_52
426 A. Duggal and T. Sinuff

ICU Intensive care unit

ISS Injury severity score
NIV Noninvasive ventilation
NPPV Noninvasive positive pressure ventilation
PaO2 Partial pressure of oxygen
PCA Patient-controlled analgesia

52.1 Introduction

Chest trauma is associated with significant morbidity and is second to only head and
spinal-cord injuries as a reason for trauma-associated mortality [1]. Outcomes are
worse in the elderly and in patients with existing lung pathology [1, 2]. The most
common injuries associated with chest trauma are rib fractures, flail chest (fracture
of three or more ribs in two places or multiple rib fractures associated with sternal
fracture), pulmonary contusions, pneumothorax, and hemothorax. Pulmonary con-
tusions have been reported to be present in nearly 20 % of patients with multiple
traumas [1–4].
Chest trauma causes parenchymal damage with direct lung injury and may also
cause hemorrhage into the lung tissue. This causes significant dysfunction of the
alveolar capillary barrier and increases the influx of extravascular lung water [3, 4].
Patients with chest trauma also have significant pain, excessive bronchial secre-
tions, and a diminished cough reflex [5]. All of these factors can result in atelectasis
and ventilation perfusion mismatch, resulting in significant hypoxemia [3, 5]. If this
disruption of the alveolar–capillary barrier is not controlled, 20–30 % of patients
with chest trauma will develop acute respiratory distress syndrome (ARDS) [5, 6].
The risk is highest within the first 72 h of the injury [3, 6]. ARDS in trauma patients
is associated with significant mortality (16–29 %) and morbidity (increased inten-
sive care and hospital lengths of stay) [3–6].
In modern medicine, trauma victims are evaluated using a multidisciplinary
approach with management decisions made according to the mechanism of injury,
anatomic involvement, and staging of the injury. The clinical significance of blunt
chest trauma varies, depending on the size and location of the injury and the extent
of the underlying lung contusion. Clinical management of less severely injured
patients employs multimodal therapy but focuses primarily on the stabilization of
fractures, pulmonary toilet, effective physiotherapy, and early and adequate pain
control [4, 5, 7]. Patients with significant injuries, hemodynamic collapse, closed
head injuries, significant flail chest or lung contusions, or those in immediate need
for surgery undergo intubation and mechanical ventilation [3, 4].
The use of noninvasive ventilation (NIV) in blunt chest trauma is still controver-
sial [4, 5, 7]. This is reflected in the “low grade recommendation” for the use of NIV
in trauma patients by the British Thoracic Society guidelines compared with the “no
recommendation” by the Canadian Critical Care Trials Group/Canadian Critical
Care Society Noninvasive Ventilation Guidelines Group due to a lack of sufficient
52 Noninvasive Ventilation in Patients with Blunt Chest Trauma 427

evidence [3, 5, 7]. Despite the lack of strong evidence to support the use of NIV in
patients with blunt chest trauma, it has gained more prominence in the management
of these patients. This may be attributed to its potential benefits versus harm, com-
pared with mechanical ventilation.
In this chapter, we review the current evidence regarding the use of NIV for
patients with blunt chest trauma and identify the patients who would benefit the
most from this therapeutic modality. We also discuss the most appropriate time to
implement NIV and the safety of its use for patients with blunt chest trauma.

52.2 Discussion

52.2.1 Pathophysiology of Lung Injury in Blunt Chest Trauma

The lung is exquisitely sensitive to compressive or concussive forces [1, 3, 4].

A sudden application of such forces results in parenchymal lacerations and damage
to pulmonary alveolar blood vessels. Three mechanisms have been recognized in
the etiology of pulmonary contusions: (i) the stripping of alveolar tissues from the
hilum because of differential acceleration of the tissues, (ii) damage to the alveoli at
the alveolar-arterial interface, and (iii) a direct concussive injury to the alveoli, asso-
ciated with blunt chest trauma [3–5]. This mechanical injury to the lung results in
intraparenchymal hemorrhage and significant edema formation. The direct mechan-
ical damage to the lung parenchyma as well as additional indirect lung injury due to
an inflammatory cascade results in the development of ARDS in these patients.
Animal studies have shown that, early in the course of blunt chest trauma, poly-
morphonuclear cells infiltrate lung tissue and release numerous cytotoxic products
and further damage the alveolocapillary barrier [3, 4, 7]. This in turn results in
increased permeability and accumulation of protein-rich alveolar and interstitial
edema. Due to this inflammatory cascade and loss of alveolar surfactant, the air-
spaces are destabilized. This process is further complicated by the development of
posttraumatic atelectasis, which results in significant ventilation-perfusion mis-
match and hypoxemia refractory to supplemental oxygen. Atelectasis also interferes
with the clearance of bacteria. The resultant lack of adequate clearance of these
secretions associated with atelectrauma explains why patients with substantial chest
injuries worsen 48–72 h after presentation [3, 5, 7].

52.2.2 Potential Benefits of Early Application of NIV

The benefits of early use of NIV in patients with blunt chest trauma are due to the
avoidance of intubation and mechanical ventilation and its associated complica-
tions. Early identification of at-risk patients with prompt institution of NIV in
appropriate patients may allow for the greatest benefit. Early initiation of NIV may
offer the benefit of a wider and earlier use of ventilator support outside the intensive
care unit (ICU), thereby limiting the development of atelectrauma and minimizing
428 A. Duggal and T. Sinuff

the risk of pneumonia [3–5]. NIV may also significantly lower the risk of ARDS
because of its role in lung recruitment (i.e., limiting lung collapse).
Early use of NIV, through chest stabilization and lung recruitment, prevents the
failure of spontaneous breathing and avoids the need for intubation. The use of NIV
in chest trauma is associated with a significant and rapid improvement in the oxy-
genation and other physiologic variables. The improvement is more pronounced if
the therapy is instituted earlier in the course of the disease, before the onset of respi-
ratory failure [3, 7]. NIV increases the transpulmonary pressure, thus recruiting
poorly ventilated atelectatic regions of the lung, decreases work of breathing, and
improves gas exchange. These finding are similar to studies evaluating the use of
NIV in acute cardiogenic pulmonary edema, acute exacerbation of chronic obstruc-
tive pulmonary disease (COPD), and acute respiratory failure [5–7].
The rate of failure of NIV in patients with blunt chest trauma who developed
acute respiratory distress and respiratory failure is similar to the rates reported for
any cause of acute hypoxemic respiratory failure [8]. In a prospective multicenter
cohort study of hypoxemic patients after pulmonary contusion, the intubation rate
was 18 %, which is significantly lower than the rates reported in patients with
community-acquired pneumonia (50 %) and acute respiratory distress syndrome
(51 %) [8].

52.2.3 Safety of the Use of NIV in Chest Trauma: Overview

of the Literature

Four studies have compared the use of NIV with endotracheal intubation in patients
with chest trauma [5, 7]. Three of these studies used continuous positive airway
pressure (CPAP), and one study used noninvasive positive pressure ventilation
(NPPV). Only two were randomized controlled trials [7]. Unfortunately, all these
studies compared patients with less severe injuries who were treated with NIV, with
those who suffered severe injuries or had decreased levels of consciousness requir-
ing mechanical ventilation [7, 9, 10]. The differences in transfusion requirements of
blood products were also not mentioned in any of the studies [7]. Bolliger et al. [9]
developed the first randomized controlled trial to evaluate the use of CPAP com-
pared with intubation and mechanical ventilation. Patients with significant chest
trauma were randomly allocated to receive CPAP with either epidural or intercostal
nerve for pain control or an endotracheal intubation with systemic analgesia. The
NIV group had a shorter length of stay in the ICU and hospital. However, there were
significant methodological flaws with the study, and the patients in the endotracheal
intubation group had a higher incidence of major abdominal trauma and higher
injury severity scores (ISS). Gunduz et al. [10] published the other trial and also
reported no need for intubation in patients undergoing NIV and, more importantly,
a lower mortality with the use of CPAP compared with endotracheal intubation in a
randomized controlled trial (18 % vs 48 %, p = 0.001). Although this is encouraging,
the results have to be analyzed carefully as the researchers excluded patients under-
going emergent intubation after randomization for the study.
52 Noninvasive Ventilation in Patients with Blunt Chest Trauma 429

Hernandez et al. [11] randomized patients with chest trauma related hypoxemia
to a high-flow oxygen mask or NIV. This trial included patients requiring oxygen by
high-flow mask within the first 48 h after thoracic trauma with PaO2/FiO2 ratio
≤200 for ≥8 h. The utilization of co-interventions, such as epidurals and patient-
controlled analgesia (PCA) for pain control, early chest physiotherapy, and need for
surgical intervention, was also similar in both groups. The authors evaluated the
need for intubation as their primary objective, and survival and length of hospital
stay were secondary objectives. The use of NIV resulted in a significant difference
in the rates of intubation (P = 0.02) [11].
Endotracheal intubation in patients initially managed with NIV has been associ-
ated with decreased survival. Length of stay in ICU was lower in patients with NIV
use compared with invasive mechanical ventilation [5, 7]. These results need to be
assessed carefully as the trials were performed before the era of spontaneous breath-
ing and awakening trials. Additionally, in all studies, ventilated patients received
continuous sedation, whereas the NIV group received either epidural anesthesia or
PCA (Table 52.1).

52.2.4 Approach to the Use of NIV in Chest Trauma

Given the available evidence, a reasonable approach would be to use NIV judi-
ciously in patients with blunt chest trauma. The use of NIV can slow the progression
of lung injury and prevent the need for intubation in select patients. This means
appropriate selection of patients who may benefit, and a trial early in the course of

Table 52.1 Summary of randomized control trials on the use of NIV in blunt chest trauma
Inclusion Control
Study criteria intervention Pain control Outcomes reported
Hernandez PaO2/FiO2 High-flow Epidural analgesia Rates of intubation,
(2010) [11] <200 for >8 h oxygen (bupivacaine and mortality, length of
while fentanyl) stay in ICU and
receiving Remifentanil hospital,
oxygen by infusion complications
high-flow
mask
Gunduz Flail chest; Mechanical Morphine patient ICU mortality, ICU
(2005) [10] PaO2/FiO2 ventilation Controlled analgesia and hospital length
<300; Acute of stay, infections
respiratory
distress
Bollinger Chest trauma Mechanical Lumbar epidural ICU mortality,
(1990) [9] with >3 rib ventilation analgesia length of stay in
fractures (buprenorphine) hospital and ICU,
Insufficient Intercostal nerve complications, and
cough blocks infections, ICU
mechanism
PaO2 partial pressure of oxygen, FiO2 fraction of inhaled oxygen, ICU intensive care unit
430 A. Duggal and T. Sinuff

Table 52.2 Indications and Key indications for NIV in chest trauma
contraindications to the use
Hypoxemia (PaO2/FiO2 ratio 200–300)
of NIV in chest trauma
Flail chest
Significant pulmonary contusion
Presence of underlying lung disease (e.g., COPD)
Contraindications to NIV in chest trauma
Absolute
Inability to protect airway
Significant facial trauma
Upper airway obstruction
Hemodynamic instability
Cardiac arrest
Need for major surgery
GCS <8
High risk for aspiration
ARDS (PaO2/FiO2 ratio <100)
Relative
Major multiorgan trauma
Encephalopathy (GCS 8–10)
Cardiac arrhythmias (if stabilized)
Pneumothorax (if chest tube already inserted)
Moderate ARDS (PaO2/FiO2 ratio 150–200)
PaO2 partial pressure of oxygen, FiO2 fraction of inhaled
oxygen, GCS Glasgow Coma Scale, ARDS acute respiratory
distress syndrome, COPD chronic obstructive pulmonary
disease

the injury and respiratory distress, prior to the development of ARDS and overt
respiratory failure. The identification of patients for whom a trial of NIV would be
appropriate is challenging, partly because there are few reliable selection criteria
(Table 52.2). Because there is no clear threshold of severity for hypoxemia beyond
which NIV is contraindicated, these decisions need to be made on an individual
basis. Patients for whom a trial of NIV is initiated require close monitoring in the
ICU, where endotracheal intubation is promptly available if they deteriorate any
further. Although the optimal duration of the initial NIV trial remains uncertain, a
reasonable expectation would be a response within 1–4 h of initiation. Patients who
are failing an NIV trial should be promptly intubated and mechanically ventilated,
as any delays in endotracheal intubation in patients managed with NIV have been
associated with decreased survival [3–5, 7].
NIV should be avoided in patients with severe and worsening hypoxemia. It has
been shown that many patients with blunt chest trauma deteriorate rapidly on the
second or third posttraumatic day, and thus intubation and mechanical ventilation
become necessary to ensure adequate oxygenation. In studies that compared the use
of NIV with invasive mechanical ventilation, mortality was higher in patients under-
going invasive mechanical ventilation compared with NIV, but, of note, most
patients died as a result of non-thoracic injuries rather than a direct result of
52 Noninvasive Ventilation in Patients with Blunt Chest Trauma 431

respiratory failure [5, 7]. Hence, we need to acknowledge that the progression of
respiratory failure may also be dependent on non- thoracic injuries and other factors
such as transfusion-associated reactions. This reaffirms the need for proper patient
selection and continuous close monitoring of patients being treated with
NIV. Moreover, because these patients can deteriorate quickly, their respiratory and
overall clinical status should be reassessed every 2–4 h when they are undergoing
treatment with NIV. Although the use of NIV in patients with blunt chest trauma has
a vital role in patients with significant injuries, its use should be limited to those
patients who are relatively hemodynamically stable.

52.2.5 Late Application of NIV Does Not Benefit Patients

Failure of NIV has been reported primarily following the period after the initial stabili-
zation of patients. Most of the safety data on the use of NIV derived from observational
studies refers to its use within the first 48–72 h after trauma. Patients who develop
hypoxemic failure later in the course of their hospitalization likely have other factors
present, such as progression of lung contusions or the development of pneumonia or
ARDS, which result in severe hypoxemia and respiratory distress. In trauma patients,
the risk for intubation depends not only on the severity of the gas exchange impairment
but also on the severity of trauma on the extension of lung contusion and on the hemo-
dynamic status. Thus, for patients who do not respond to an early trial of NIV, NIV
should be discontinued as soon as possible within the first 24 h and endotracheal intu-
bation should be considered early to mitigate the potential for harm [3, 7].

52.2.6 Pain Management as an Important Adjunct to the Use of NIV

A major component of care for patients with blunt chest trauma is the need for
adequate pain control. Unfortunately, this aspect of care for these patients is often
overlooked. A close working relationship with the Anesthesia and Pain Control
Service might improve the institution of NIV when a patient with blunt chest trauma
is being evaluated. There is convincing evidence that the use of early epidurals,
nerve blocks, or PCA pumps is associated with better outcomes in these patients [3,
7]. Judicious use of epidurals with good pain control, along with the use of NIV,
prevents the progression of lung injury and ensures earlier discharge from ICU for
these patients. In situations where epidurals are contraindicated or not possible,
analgesia with nerve blocks and PCA should be considered [3, 4, 7].

52.2.7 Outcomes of Patients Managed with NIV

No significant morbidity has been associated with the appropriate use of NIV in
patients with blunt chest trauma. Rates of nosocomial pneumonia range from 20 to
40 % of the patients, but these rates are comparable to all patients with significant lung
contusions and blunt chest trauma [5, 7]. Prolonged use of NIV and a higher PEEP
432 A. Duggal and T. Sinuff

have been identified as risk factors for the development of nosocomial pneumonia, but
these might be a surrogate marker for the severity of the lung contusion rather than the
use of NIV itself [3, 5]. In most individuals with significant lung contusions, there is
a higher risk of development of pneumothoraces, so there is a fear that the use of posi-
tive pressure ventilation has potential to cause or worsen pneumothorax [5, 7]. There
were no differences in the rates of pneumothorax in patients undergoing NIV com-
pared with patients who underwent standard medical management. Due to a lower
physiological risk of barotrauma with the use of CPAP, it might be considered first in
the treatment of patients with severe chest trauma [3, 5].

Conclusion
Ventilatory management in the trauma population is more challenging because
of the difficulty in achieving a balance between the avoidance of further harm to
the lungs and sufficient ventilation. Hence, selection of appropriate patients is
crucial for optimizing NIV success rates and resource utilization. The early use
of NIV is an effective and safe option for patients with blunt chest trauma who
are neurologically intact, hemodynamically stable, and not in respiratory dis-
tress. NIV facilitates chest stabilization and promotes alveolar recruitment, sig-
nificantly reducing the need for the intubation and progression of lung injury.
But NIV is only effective if it is used in the appropriate population and integrated
with other medical and/or surgical therapies. There is no apparent benefit of NIV
in the prevention of intubation in patients with respiratory decompensation. In
fact, delaying intubation in these patients leads to harm.
The use of NIV can be associated with a significant reduction in the incidence
of overall complications, endotracheal intubation rate, length of intensive care
unit stay, and mortality. Therefore, the role of NIV in managing respiratory
insufficiency associated with trauma may become significant if applied to the
properly selected patient at an earlier stage of lung injury by appropriately trained
and experienced personnel. More research is required to determine the optimal
role of NIV in blunt chest trauma. Future studies evaluating the use of NIV in
blunt chest trauma need to be methodologically rigorous and identify patients
early in the course of the disease.

Key Recommendations
• Noninvasive mechanical ventilation for blunt chest trauma should only be
considered in patients who are neurologically intact, hemodynamically
stable, and not in respiratory distress.
• The benefit of NIV is early in the course of blunt chest trauma, prior to the
development of overt respiratory failure.
• There is no apparent benefit of NIV in the prevention of intubation in
patients with respiratory decompensation. Late application of NIV does
not benefit patients.
• Appropriate and early pain management is an important adjunct to the use
of NIV in chest trauma.
52 Noninvasive Ventilation in Patients with Blunt Chest Trauma 433

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8. Antonelli M, Conti G, Moro ML, et al. Predictors of failure of noninvasive positive pressure
ventilation in patients with acute hypoxemic respiratory failure: a multicenter study. Intensive
Care Med. 2001;27:1718–28.
9. Bolliger CT, Van Eeden SF. Treatment of multiple rib fractures. Randomized controlled trial
comparing ventilatory with nonventilatory management. Chest. 1990;97:943–8. doi:10.1378/
chest.97.4.943. PMID:2182301.
10. Gunduz M, Unlugenc H, Ozalevli M, et al. A comparative study of continuous positive airway
pressure (CPAP) and intermittent positive pressure ventilation (IPPV) in patients with flail
chest. Emerg Med J. 2005;22:325–9. doi:10.1136/emj.2004.019786. PMID: 15843697.
11. Hernandez G, Fernandez R, Lopez-Reina P, et al. Noninvasive ventilation reduces intubation
in chest trauma-related hypoxemia: a randomized clinical trial. Chest. 2010;137:74–80.
doi:10.1378/chest.09-1114. PMID: 19749006.
Noninvasive Ventilation in Acute
Respiratory Failure and Severe 53
Neurological Deterioration

Andrés Carrillo, Antonia Lopez, and Pablo Bayoumy

Contents
53.1 Introduction ................................................................................................................. 435
53.2 Neurological Dysfunction in Acute Respiratory Failure ............................................ 436
53.3 Assessment of Neurological Function in Patients with ARF...................................... 436
53.4 Which Is the Treatment of Choice for Patients with ARF
and Neurological Impairment? ................................................................................... 437
53.5 Effectiveness of NIV in Treatment of ARF with Severe
Neurological Dysfunction ........................................................................................... 438
53.5.1 Cases Series ................................................................................................... 438
53.5.2 Case-Control Studies ..................................................................................... 439
53.6 Security of NIV in the Treatment of ARF with Severe Neurological Dysfunction .... 441
53.7 How to Ventilate a Patient with ARF and Severe Neurologic Dysfunction ............... 442
Conclusions ............................................................................................................................ 442
References .............................................................................................................................. 443

53.1 Introduction

Both respiratory and central nervous systems are intimately interconnected

through a delicate balance. Any disorder in this equilibrium can translate to dev-
astating consequences for a patient. Respiratory dysfunction, either acute or
chronic, can cause neurologic impairment [1], and the signs and symptoms
observed in these patients can be caused by hypoxia and/or hypercapnia. The
effects of hypoxia depend on factors such as severity, duration, and speed of
onset. The hypoventilatory processes that produce retention of carbonic anhy-
dride can cause alteration in mental status; nevertheless, patients who are able to

A. Carrillo (*) • A. Lopez • P. Bayoumy

Intensive Care Medicine, Morales Meseguer Hospital, Avda. Marques de los Velez s/n.
30008, Murcia, Spain
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 435

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_53
436 A. Carrillo et al.

maintain a correct oxygenation, showing slight elevations in the partial pressure

of CO2, may not manifest signs and symptoms of neurological dysfunction. The
clinical spectrum of neurologic impairment secondary to respiratory failure is
known as hypercapnic encephalopathy syndrome [2], where patients with a wide
variability of neuropsychiatric symptomatology are grouped. The point of maxi-
mum severity is the hypercapnic hypoxic coma, defined as the presence of coma,
with a Glasgow Coma Score (GCS) of 8 or less, pH <7.20, and PaCO2 >80 mmHg
in an arterial gas analysis [3]. From the pathophysiological point of view, hyper-
capnic encephalopathy syndrome is a complex process, where respiratory altera-
tions are combined (tissular hypoxia, a state of acidosis in the brain tissue, and
cerebrospinal fluid increased by extreme CO2 diffusion), but extrapulmonary
processes also are involved (hemodynamic and renal) and even external factors
such as inadequate oxygen therapy or use of depressant drugs of the central ner-
vous system [2].

53.2 Neurological Dysfunction in Acute Respiratory Failure

The prevalence of neurological dysfunction in acute respiratory failure (ARF) is

not well known. On an epidemiologic study, Carlucci et al. [4] found that the
necessity for mechanical ventilation is produced by hypoxemic ARF in 48 % of
cases, 15 % for acute-on-chronic respiratory failure (ACRF), 7 % for cardiac fail-
ure, and 30 % for coma. However, these authors did not specify the type of coma,
and many cases were likely the result of organic or metabolic rather than respira-
tory causes. Corrado et al. [3] found 150 patients with hypercapnic coma out of a
total of 1430 patients with acute-on-chronic respiratory failure, which is a preva-
lence of 10.4 %. In our intensive care unit between 1996 and 2013, we treated
3962 episodes of severe ARF with noninvasive ventilation (NIV); 988 (24.9 %)
showed some degree of neurological impairment (GCS <15 points) and 256
patients (6.4 %) presented hypercapnic coma. More recently, we also found a
decrease in the number of patients arriving at the hospital with impaired mental
status. In fact, improved care of extra-hospital emergency services with the avail-
ability of NIV devices has improved the care of patients with respiratory failure
significantly (no published data). Neurological impairment can occur with any
etiology of respiratory failure, being more frequent in patients with ACRF, par-
ticularly in patients with chronic obstructive pulmonary disease (COPD) and obe-
sity hypoventilation syndrome [5].

53.3 Assessment of Neurological Function in Patients

with ARF

In numerous published articles, one of the variables analyzed in patients with ARF
is their neurological situation at the onset of therapy or during it. Three scales have
been mainly used for assessment of neurological status: the GCS [6], the
53 Noninvasive Ventilation in Acute Respiratory Failure 437

Kelly-Matthay scale [7], and the encephalopathy scale proposed by Brochard et al.
[8]. In each paper, the authors use their own preferred scale, the Kelly-Matthay scale
being the most used because of its simplicity and the ease of detecting small changes
in mental status of mechanically ventilated patients. The Kelly-Matthay scale has
also shown prognostic value in patients with neurological impairment treated with
NIV [9]. However, none of these scales have been validated for measuring neuro-
logical changes induced by hypoxia-hypercapnia in patients with respiratory failure
treated with NIV. The use of these tools is advised because some studies show that
neurological impairment at the onset of the therapy is a predictive factor for ventila-
tory support failure, and mainly because evolution of neurological impairment dur-
ing the first hours of NIV application predicts much better the success or failure of
therapy [5].

53.4 Which Is the Treatment of Choice for Patients with ARF

and Neurological Impairment?

Classically, the treatment of ARF has been based on the utilization of oxygen ther-
apy and the etiological treatment of the respiratory process. When this initial
approach fails or the patient is in a severe situation, ventilatory support is started.
More recently, NIV has been positioned as a first-line therapy in ARF, having shown
its efficacy for decreasing endotracheal intubation and mortality in different types of
patients with ARF [10].
Although severe encephalopathy (GCS <8–10 or a Kelly Mathay score >4
points) has been proposed as a possible contraindication to the use of NIV [11],
some articles have shown its effectiveness in patients with altered state of con-
sciousness or even coma secondary to respiratory failure. This discussion has
been motivated by a number of reasons that have never been analyzed in well-
designed studies. Controversy exists regarding the use of noninvasive mechanical
ventilation in patients with severe alteration in level of consciousness, with argu-
ments for and against its use. The main argument against the utilization of NIV is
the impossibility of isolation and protection of the airway, which for years has
been considered an indication for endotracheal intubation [12], to prevent a pos-
sible pneumonitis for gastric fluid aspiration, which at the same time is favored by
the existence of positive pressure in an airway not isolated from the digestive
tract. Furthermore, a deteriorating level of consciousness decreases the effective-
ness of cough and respiratory secretions removal, worsening suitable airway
clearance. Finally, it has also been argued that patients with altered mental status
due to respiratory failure cannot properly cooperate and the application of NIV is
therefore more likely to fail. For proponents of these arguments, the presence of
impaired consciousness at baseline and during early hours of NIV therapy is a risk
factor for failure [13]. However, other studies do not show this relationship, or,
because of their focus on complications do not detect improvements [14] and
conclude that the risk of complications related to a low level of consciousness is
overestimated in patients with NIV.
438 A. Carrillo et al.

53.5 Effectiveness of NIV in Treatment of ARF with Severe

Neurological Dysfunction

The controversy about the use of NIV in patients with severe neurological impair-
ment due to ARF has been ongoing for years. Different case series or case-control
methodology studies have attempted to clarify this issue.

53.5.1 Cases Series

The first major series of patients with neurological impairment secondary to ARF
treated with NIV was published by Benhamou et al. [15]. This is a study of 30
elderly patients with ACRF treated with NIV by nasal mask. Six patients had a
normal neurological status, 5 were agitated, 4 were confused, 12 experienced
drowsiness, and 3 patients were in coma. Patients with normal consciousness had a
failure rate of 33.3 %, 25 % failure was observed in patients with drowsiness, 33.3 %
in comatose patients, 80 % in agitated patients, and 50 % in confused patients. NIV-
related complications were common, 5 patients had conjunctivitis, 5 had intoler-
ance, 3 had skin lesions, and 3 experienced atelectasis.
A few years later, a retrospective series of 15 patients with neuromuscular dis-
ease and acute respiratory failure, secondary to respiratory infection or heart failure,
was published [16]. All of the patients presented hypoxia and hypercapnia at admis-
sion. The mean score on the GCS was 10.7 ± 3.6 points. Five patients (33.3 %) had
hypercapnic-hypoxic coma (GCS 6.4 ± 2.1 points) and 5 others obnubilation (GCS
11.8 ± 0.4 points). All patients were treated with NIV with negative pressure.
Therapy was effective in 12 of 15 patients (80 %).
Corrado et al. [3] retrospectively analyzed 150 patients in hypercapnic coma,
with different ACRF etiologies in hypoxic hypercapnic coma treated by “iron lung.”
A nasogastric tube and an oropharyngeal airway were placed in all patients. NIV
failure was defined as the need for endotracheal intubation or death in the hospital.
The mean arterial pH was 7.13 ± 0.3 and the PaCO2 was 112 ± 21 mmHg. The
median duration of NIV was 27 h, with rapid recovery of consciousness (median of
4 h). The treatment was successful in 105 patients (70 %), clearly relating NIV
failure with consciousness level, between 100 % failure of NIV in patients with
GCS 3 points, and 15 % of failure in patients with GCS 8 points. With regard to
NIV-related complications, 5 patients (3.3 %) developed clinical and radiological
findings suggesting aspiration pneumonia, but all were successfully treated without
requiring intubation. Using multivariate analysis, the presence of GCS ≤6 and age
≥70 years were the only two variables associated with NIV failure.
Dueñas et al. [17] published a series of 13 patients with do-not-intubate orders,
admitted to a conventional ward once ICU admission was ruled out, with severe
hypercapnic encephalopathy (GCS ≤7). The mean age was 81 years and 10 patients
were diagnosed with COPD. On admission, the mean arterial pH was 7.18 ± 0.11
and PaCO2 was 92 ± 35 mmHg. Ventilatory therapy was applied by conventional
ventilators, and the mean NIV length was 74 ± 19 h. The evolution showed a coma
53 Noninvasive Ventilation in Acute Respiratory Failure 439

recovery in 78 % of patients within 48 h and 9 patients survived. Complications

such as skin ulcerations on the bridge of the nose were recorded in the 23 % of cases
and transient psychomotor agitation in 30 %, without the need to discontinue venti-
latory therapy in any case.
Both positive and negative pressure noninvasive ventilation have been used in the
same patients to minimize complications [18]. In a series of 152 patients with dif-
ferent ACRF etiologies, the initial treatment was performed with negative pressure
NIV, switching the mode to positive pressure NIV in the presence of intolerance or
complication. In this series of patients, 13 had hypercapnic coma, 11 of whom had
an adequate response to the “iron lung,” and they were discharged alive.
In a prospective series of 95 patients with hypercapnic coma of diverse etiology
[5] treated with NIV, the success rate was 80 %, even slightly higher than patients
with a higher level of consciousness (70 %). This apparent contradiction can be
related to the prevalence of ACRF in the group of patients in coma. At the beginning
of ventilatory therapy, the arterial pH value was 7.13 ± 0.06 and PaCO2 was 99 ± 19.
With the application of NIV, all physiological parameters, with the exception of
respiratory frequency and systolic blood pressure, improved. The improvement of
consciousness status after 1 h with NIV therapy is an independent predictor of NIV
success, and this has repercussions for hospital survival [5]. Complications related
to NIV in coma patients were skin and ocular lesions, 5 cases of abdominal disten-
sion, 3 cases of vomiting, and 1 pulmonary aspiration.

53.5.2 Case-Control Studies

Several studies with a case-control methodology have been published, which

attempt to analyze the impact of positive pressure NIV in patients with neurological
impairment secondary to respiratory failure.
Scala et al. [19] reported a study where patients with severe COPD were ana-
lyzed to assess the effectiveness of NIV according to different degrees of neurologi-
cal involvement. Cases were patients with COPD exacerbation with neurological
impairment, assessed by the Kelly-Matthay scale, divided into three groups: group
I with slight neurological involvement (2 points on the Kelly-Matthay scale), group
II with moderate neurological involvement (3 points), and group III with severe
neurological involvement (>3 points). Controls were patients with 1 point on Kelly-
Matthay scale. Variables used for matching cases and controls were age, gender,
etiology of the COPD exacerbation, serum bicarbonate, severity of respiratory pro-
cess, and the patient’s number of comorbidities. At the NIV onset, pH was 7.31 in
the control group, 7.28 in group I, 7.26 in group II, and 7.22 in group III. Median
GCS score in these four groups had the values 15, 13, 11, and 7 respectively; the
median duration of NIV was 55, 34, 34, and 41 h. The need for intubation was 15 %
for the control group, 25 % for group I, 30 % for group II, and 45 % for group
III. The number of patients with gastric distension was 1, 3, 4, and 7, respectively,
and in all cases was completely reversible. There were no cases of gastric aspiration
or nosocomial pneumonia, even though not all patients had a nasogastric tube.
440 A. Carrillo et al.

Two years later, the same author published a new case-control study comparing
patients with neurological impairment secondary to COPD acute exacerbation
treated with NIV or conventional ventilation [20]. The cases were 20 patients with
diagnosis of COPD exacerbation or who were decompensated by community-
acquired pneumonia, with a score on the Kelly-Matthay scale between 3 and 5,
treated with NIV. Controls were patients with a similar diagnosis admitted during
the same period to the ICU, but treated with endotracheal intubation and conven-
tional ventilation. Patients were matched by age, PaO2/FiO2, PaCO2, basal pH, and
Simplified Acute Physiology Score II (SAPS II). Arterial pH and mean PaCO2 in
NIV patients were 7.22 ± 0.02 and 88 ± 15 mmHg and in controls were 7.22 ± 0.05
and 90 ± 10 mmHg. Oxygen ratio and Kelly-Matthay score were similar in both
groups. Consciousness level improved in NIV patients, after 2 h of therapy going
from a mean of 3.4 ± 0.6 to 2.1 ± 0.8 points, and 1.6 ± 1.0 at 24 h. Length of NIV was
55.1 ± 81 h, and failed in 7 patients (35 %). The placement of a nasogastric tube was
necessary in 3 patients due to gastric distension, and skin lesions were observed in
4 patients. No patient in the NIV group presented gastric aspiration or developed
nosocomial pneumonia. Hospital mortality was 25 % in both groups.
More recently, Zhu et al. [21] reported a study of 43 patients with COPD and
ACRF requiring NIV. Patients were divided into two groups according to the pres-
ence (22 patients) or absence (21 patients) of encephalopathy, defined as a GCS <10
points. Patients were matched by age, gender, smoking, evolution years of COPD,
and previous hospitalization. A nasogastric tube was placed in patients with enceph-
alopathy and in those controls in whom gastric distension was objectified. Arterial
pH in both groups clearly differed: 7.18 ± 0.06 and 7.28 ± 0.07, respectively. NIV
success and hospital mortality in the encephalopathy group were 72.7 and 13.6 %,
whereas in the control group they were 68.2 and 14.3 %. Complications related to
NIV were minor: 5 patients in the encephalopathy group and 4 in control group had
gastric distension, with one bronchoaspiration in the first group that led to endotra-
cheal intubation.
Briones et al. [22] published a study with 24 patients, 12 with severe COPD
exacerbation who came to the emergency room with pH ≤7.25 and neurological
impairment (GCS <8 points). The control group was selected among COPD patients
requiring conventional mechanical ventilation. Patients were matched by Acute
Physiology and Chronic Health Evaluation (APACHE) II, age, arterial pH, and
GCS. The mean GCS score was 6.3 ± 1.5 points in the NIV group and 5.6 ± 1.3 in
controls. Two patients with NIV required orotracheal intubation (16.6 %). Mortality
was 33.3 % in the conventional ventilation group and 16.7 % in patients with NIV
(p = 0.01). The only complications associated with NIV were nasal irritation in one
patient and gastric distension in another.
Scala et al. [23] compared 15 patients with COPD decompensated by pneumonia
with profuse respiratory secretions and encephalopathy. In all patients it was neces-
sary to perform a bronchoscopy for bronchial toilet and they were treated with NIV
or conventional mechanical ventilation. Patients were matched by blood gases,
APACHE III, Kelly-Mathey scale, and severity of pneumonia. The mean arterial pH
of patients was 7.27 in both groups, and the mean PaCO2 was 76 and 78 mmHg in
53 Noninvasive Ventilation in Acute Respiratory Failure 441

the noninvasive and invasive groups. Mean Kelly-Mathey scale scores were 3.4 and
3.2, respectively. Intubation avoidance was achieved in 80 % of NIV patients, and
related complications were four cases of mild facial erythema (26.6 %) and no cases
of pulmonary aspiration.
Finally, Briones et al. [24] designed a study comparing 11 patients with COPD
and altered consciousness (GCS <10 points) treated with NIV in volume assured
pressure support (AVAPS) mode with 11 other patients with exacerbated COPD
treated with bi-level positive airway pressure. The AVAPS group had a faster
improvement of consciousness level and arterial gas analysis.
Final conclusions of these studies were similar. From authors point of view,
hypercapnic encephalopathy is not a contraindication for use of NIV, although it is
expected an increase of failures in most severe forms. On the other hand, despite the
commonly accepted, complications from noninvasive support are neither frequent
nor severe. However, most published series have been submitted by teams with
extensive experience in this ventilatory support, and it is difficult to know whether
these results can be extrapolated to other groups with less experience.

53.6 Security of NIV in the Treatment of ARF with Severe

Neurological Dysfunction

NIV security, applied to patients in hypercapnic coma, refers to the inherent risks of
this ventilatory therapy, which may be exacerbated in patients with consciousness
impairment. In fact, this is why hypercapnic coma has been considered as a contra-
indication for NIV use. However, when referring to complications related to the
technique, the most important and those that can lead to a worsening of ARF (gas-
tric distension, vomiting, aspiration, pneumothorax, pulmonary superinfection, and
intolerance) are rare. The low number of severe complications arising from NIV
could be related to the rapid improvement of consciousness of patients, which could
give rise to a recovery of lung defense mechanisms. Moreover, a decrease in pres-
sures used as the respiratory improvement occurs could minimize the risk of gastric
distention, vomiting, bronchoaspiration, and respiratory nosocomial infection.
Among patients in hypercapnic coma where NIV is applied successfully, mean
recovery time of 15 points on the Glasgow Coma Scale was 4 h [5]. Scala et al. [20]
showed an improvement in neurological status of more than 1 point on the a Kelly-
Matthey scale in patients with severely impaired consciousness within 2 h of NIV
onset. This rapid recovery when ventilation is effective explains the low number of
complications in these patients.
Some measures have been proposed to reduce the risk of complications in these
patients. Although some authors advocate the routine use of a nasogastric tube in an
attempt to reduce gastric distension in comatose patients [21], others do not consider
it necessary, because of the low prevalence of serious complications and the risk of
increasing leaks and encouraging ventilator-patient asynchrony [5]. Although hyper-
capnic coma patients are not more difficult to treat than a conscious patient, some
less severe forms of neurological dysfunction may hinder the application of
442 A. Carrillo et al.

ventilatory support. Agitation and lack of initial collaboration, or when the patient
gradually recovers consciousness, are sometimes additional problems that may influ-
ence patient prognosis. Our initial recommendation is always to treat these problems
with non-pharmacological measures: a caring nurse may ease patient distress, help-
ing the patient to gain strength and motivation to tolerate NIV. In the same way, we
advise applying different interfaces to minimize claustrophobia and discomfort, and
likewise lower pressures, helping with patient collaboration and improving the prob-
ability of success. However, sometimes it is necessary to resort to pharmacological
treatment to improve patient tolerance, although, traditionally, physicians have been
reluctant to treat with medication that is potentially a depressant of consciousness in
patients with NIV. We advocate its use in selected cases. In this sense, we prefer use
opioids or benzodiazepines in punctual bolus, even though we also use, often suc-
cessfully, continuous infusion of these drugs or other anesthetics such as propofol or
dexmedetomidine at low doses, to achieve conscious sedation, which favors patient
cooperation without increasing the risk of complications.

53.7 How to Ventilate a Patient with ARF and Severe

Neurologic Dysfunction

Different studies published about NIV use in the treatment of the most severe forms
of ARF show a wide variability in utilization protocols. There is near unanimity, how-
ever, regarding the use of a ventilation mode based on pressure support, using pressure
support plus positive end-expiratory pressure (PEEP), or ventilation with a double
level of pressure. Support pressure between 10 and 12 cm H2O on a 5–6 cm H2O
PEEP seems an appropriate approach for ventilatory therapy onset. The clinical
response, respiratory as well as neurological, and blood gas controls between 1 and
2 h mark the changes in respiratory parameters. Series that have addressed this issue
show that levels of pressure support, or maximum inspiratory positive airway pressure
(IPAP), required by coma patients are usually higher than those of patients with a bet-
ter situation of consciousness. It is not recommended to exceed 25 cm H2O pressure
support or 30 cm H2O IPAP. The rescue frequency on the ventilator is usually set
between 12 and 16 breaths per minute, with a short rise time. It is advisable to con-
tinue with high pressures while the patient has not fully regained consciousness and
does not present discomfort secondary to pressure/airflow. Once pH is normalized or
nearly normalized, one can begin to reduce the pressure support of the ventilator. We
suggest maintaining continuous NIV during the first 12–24 h of treatment. The wean-
ing of NIV should be performed with a progressive decrease in IPAP or pressure sup-
port levels, especially if they had achieved high pressures for PaCO2 normalization.

Conclusions
Application of NIV in patients with impaired consciousness and ARF should
be restricted to sufficiently trained teams in these kinds of therapies, in a hos-
pital area capable of close monitoring. The medical staff should be aware that
the patient may suffer a sudden deterioration of respiratory status, requiring
53 Noninvasive Ventilation in Acute Respiratory Failure 443

immediate endotracheal intubation. Only in patients with a do-not-intubate

order can ventilatory therapy be used in a conventional ward; all other patients
must be admitted to an intensive care or high-dependency unit. Regardless of
treatment, a patient whose neurological status does not improve in the first
1–2 h with ventilatory therapy and medical treatment should be intubated to
avoid unnecessary delays that could lead to increased patient risk.

Key Recommendations
• Patients with ARF with impaired consciousness can be treated with NIV.
• Severe complications such as abdominal distension, vomiting, and aspira-
tion related to ventilatory support are rare.
• Treatment of patients with hypoxic hypercapnic coma must be performed
by well-trained teams with extensive experience in NIV, as well as in hos-
pital areas that allow close monitoring of patients.

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Noninvasive Ventilation in Cord
Paralysis Diseases: Is It a Possible Safe 54
Indication?

Sven Stieglitz

Contents
54.1 Introduction ................................................................................................................. 446
54.2 Discussion and Analysis ............................................................................................. 446
Conclusion ............................................................................................................................. 449
References .............................................................................................................................. 450

Abbreviations

COPD Chronic obstructive pulmonary disease

FRC Functional residual capacity
FVC Forced vital capacity
NM Nasal mask
OHS Obesity hypoventilation syndrome
PEEP Positive end-expiratory pressure
Pimax Maximal inspiratory pressure
RV Residual volume
VC Vital capacity

S. Stieglitz, MD
Department of Pneumology and Cardiology, Petrus Hospital Wuppertal, Academic Teaching
Hospital of the University of Duesseldorf, Carnaper Str. 48, Wuppertal 42283, Germany
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 445

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_54
446 S. Stieglitz

54.1 Introduction

About three-quarters of the cases of patients with seriously impaired spinal cord
function result from traumatic injuries. Epidural abscesses, tumors or metastatic
lesions, vascular incidents, or syringomyelia are less common. Therefore, the onset
of paralysis is usually sudden, whereas it may be subacute in the other circum-
stances [1]. A spinal cord injury leads to multiple nonrespiratory (severe depres-
sion; immobility; bradycardia; loss of bowel, bladder, and sexual function; decubiti;
and infections) and respiratory diseases (respiratory muscle paralysis, impaired
speaking and coughing).
The impairment depends on the level of injury. Traumatic spinal cord injury of
the cervical spine and also of the upper thoracic spine can lead to respiratory insuf-
ficiency, often due to concomitant thorax trauma or lung contusion. The respiratory
failure is often transient if the trauma is below C4. Nevertheless, injuries above C3
lead to nearly complete respiratory muscle paralysis. In this case, patients recruit
the trapezius, platysma, mylohyoid, and sternohyoid muscles to assist the sterno-
mastoid muscles with respiration [1]. The situation is further complicated when
additional central alveolar hypoventilation occurs. The automatic control of breath-
ing is disturbed by disrupting the reticulospinal pathways of the upper cervical cord
(lesions ventrally located). Lesions located laterally preserve the automatic control
but impair voluntary ventilation [1]. Studies examining the control of breathing
inconsistently report a normal ventilatory response to carbon dioxide [2].
Above C6, the sympathetic innervation of the heart is interrupted, which leads to
an increased vagal tone with bradycardia. This may lead to cardiac arrest during
suction in intubated patients and sometimes a transient pacemaker is necessary.
Depending on the level of spinal cord injury, peripheral paralysis of the arms, legs,
or both will occur, followed later by spasticity.
In about 5 % of the cases, a syringomyelia above or below the initial lesion
occurs within 6 months or after many years. This can result in a worsening of the
neurological impairment [3].
The symptoms of upper spinal cord injury are dyspnea, which may be aggravated
in the sitting position, due to paralysis of respiratory muscles. This also impairs
coughing because the inspiratory phase of cough consists of a deep inspiration.
Additionally, the expiratory muscles that contribute to cough are also paralyzed.
Consequently, secretion plugging and development of atelectasis develop. For simi-
lar reasons, speech is impaired and patients speak in a low voice.

54.2 Discussion and Analysis

The respiratory mechanics of upper spinal cord injury may be regarded as a proto-
type of a neuromuscular disorder. Lung function shows a restrictive pattern with
reduced vital capacity (VC) and total lung capacity (TLC). Patients typically
develop rapid shallow breathing. There are limited data on lung function of spinal
cord injuries above C4, but VC values of about 20 % of predicted normal may be
54 Noninvasive Ventilation in Cord Paralysis Diseases: Is It a Possible Safe Indication? 447

measured. The absent tone of the chest wall muscles results in a reduction of the
chest wall recoil pressure. If compliance is measured by esophageal catheter, the
typical findings are a normal or even increased compliance but a markedly reduced
transpulmonary pressure at TLC (Pel 100). C4-7 injury leads to a forced vital capac-
ity (FVC) of 52 % and a maximal inspiratory pressure (Pimax) of 64 % predicted
normal, whereas T3-12 injuries lead to a FVC of 69 % and a Pimax 79 % of pre-
dicted normal [1]. The body position has a considerably stronger influence on lung
function compared with healthy subjects. Unlike normal subjects, patients with cer-
vical cord transection have an increase in VC and Pimax and a decrease of RV and
FRC when changing from the seated to the supine posture. In the sitting position,
the diaphragm is pulled down by the abdomen, whereas in the supine position, the
abdomen pushes the diaphragm upward [4]. Furthermore, the loss of the intercostal
muscle function may move the upper rib cage paradoxically inwards during inspira-
tion [5]. Spinal cord injuries between C3 and C8 usually do not lead to ventilatory
failure. But respiratory failure may develop more often with comorbidities (e.g.,
chronic obstructive pulmonary disease (COPD), obesity, sleep apnea).
Patients suffering from acute respiratory insufficiency due to acute spinal trauma
are usually intubated, followed by tracheostomy. Nevertheless, VC and the periods
of spontaneously breathing may be reduced by tracheostomy due to diaphragm
deconditioning, tube-induced airway secretions, hyperventilation causing hypocap-
nia, impaired ability to cough, and loss of glottis valving [6]. Furthermore, there are
data indicating that patients who underwent tracheostomy after an acute spinal
injury have an increased risk of airway complications compared with those who
were intubated for 3–4 weeks with subsequent NIV after extubation [7]. An increase
of VC after decannulation can be observed.
Nevertheless, a common long-term treatment for high-level quadriplegic patients
with chronic respiratory failure is tracheostomy and invasive out-of-hospital venti-
lation. Long-term invasive ventilation has numerous complications that apply to the
tracheostomy itself (e.g., tracheomalacia, tracheal stenosis, stomal enlargement
with air leakage and tube migration, hemorrhage, and granulation formation) [8] as
well to critical incidents due to the invasive ventilation (e.g., accidental disconnec-
tion and mucous plugging) [9]. This contributes to a mortality rate of 37 % in 3 years
for spinal cord injured patients on tracheostomy [10].
Some aspects of spinal cord injury are important with regard to NIV. If the spinal
injury leads to a paralysis of the hands and arms, the patient will not be able to apply
the interface for NIV autonomously. Once NIV is started and the mask is fit to the face,
the patient will be neither able to remove the mask nor to activate the nurse call system.
Patients under these conditions require special attention by the treating doctors and
nurses and modified nurse call systems are required. In this context, the use of a nasal
mask is preferred because of the ability to allow some (and sometimes improved)
speech, thereby enabling the patient to shout for help during critical incidents.
The impairment of the respiratory muscles is due to paralysis and not an increased
load as in COPD or obesity hypoventilation syndrome (OHS). The time on NIV is
often longer compared with other diseases and can exceed 20 h and even more. On
the other hand, due to the reduced chest wall recoil pressure, patients with spinal
448 S. Stieglitz

cord injury do not require high inspiratory pressures. On the contrary, patients are
often hyperventilated, which results in hypocapnia and electrolyte disturbance. The
latter problem is even marked in invasive ventilation. Therefore, a more careful set-
ting of the initial NIV parameters and monitoring of the patient are important in
spinal cord injury.
The extensive time on NIV sometimes requires interfaces other than full face
mask, and the use of a mouthpiece or a combination of different interfaces is com-
mon practice [8]. Using a mouthpiece usually requires NIV without PEEP and a
volume-controlled mode. The alarm on the ventilator must be switched off. It must
be ensured that the ventilator used does not turn off in a standby mode. Ventilators
that fulfill these requirements usually require non-vented masks, which have to be
considered when a dual mode is used. Establishing a daytime mode using a mouth-
piece and a volume-controlled mode without PEEP (frequency set at zero) followed
by a nighttime mode using a nasal mask with a pressure-controlled mode with PEEP
is one possible way to establish NIV in spinal cord paralysis. Such a complex ven-
tilator setting is facilitated by ventilators that allow the setting of two different
modes that can be activated alternatively (Fig. 54.1).
Another serious problem with high-level quadriplegia is reduced effectiveness of
coughing, which requires elimination techniques of bronchial secretions such as
mechanically assisted coughing. This problem is not solved by intubation and inva-
sive ventilation, and simple tracheal sucking does not avoid the occurrence of atel-
ectasis. In this regard, NIV is superior to invasive ventilation, especially when using
specialized techniques like “air stacking.” Air stacking permits volitional sighing,
shouting, and assisted coughing.

Fig. 54.1 Patient with tetraplegia using a mouthpiece during the day (volume-controlled ventila-
tion with volume set at 500 ml, frequency 0, expiratory trigger off, inspiratory pressure sensitive)
and a nasal mask (NM) during the night. The mouthpiece has an angle and a small rill so that the
patient may hold the mouthpiece by their incisors. Compared with NM, the patient prefers the
mouthpiece
54 Noninvasive Ventilation in Cord Paralysis Diseases: Is It a Possible Safe Indication? 449

An alternative treatment approach consists of electrophrenic nerve stimulation.

For patients with no ventilator-free breathing ability or ability to grab a mouthpiece
for noninvasive ventilation, electrophrenic pacing may be an alternative ventilator
approach or may simplify decannulation [11]. Decannulation and establishing sub-
sequent NIV is usually possible with patients who have a functioning bulbar mus-
culature [12]. The ability of neck rotation may also be a decision-making aid in
establishing NIV, because it simplifies the use of a mouthpiece for ventilation.
Compared with invasive ventilation, NIV improves quality of life, decreases
nursing requirements and costs, improves the quality of speech [13], is more effec-
tive in coughing, and facilitates transition to the community. NIV also permits the
ability of glossopharyngeal breathing, which is a safeguard in the event of ventila-
tory equipment failure.

Conclusion
Is NIV safe in spinal cord paralysis? There is clear evidence that NIV can be
used in a safe manner in spinal cord paralysis. Actually, when neck rotation is
possible and bulbar musculature is intact, NIV is superior compared with inva-
sive ventilation concerning quality of life, nursing requirements and costs,
effectiveness of coughing, and speech. The preferred devices for NIV adapta-
tion are the nasal mask, nasal pillows, and the mouthpiece, whereas full face
and total face masks should be avoided. Compared with other diseases leading
to chronic hypercapnic failure (e.g., COPD, OHS), patients with spinal cord
injury require longer time periods on NIV but a lower inspiratory pressure.
Because hyperventilation is common, a more intensive monitoring after initia-
tion and during the course of treatment is required. Additional problems of spi-
nal cord paralysis, such as hypophonia and reduced effectiveness of coughing,
may also be improved with NIV.

Key Major Recommendations

• NIV is the preferred approach to ventilation in patients with spinal cord
injury.
• Special care has to be taken because of the patients’ limb paralysis, which
affects self-management of NIV and requires interfaces such as a
mouthpiece.
• NIV in patients with spinal cord injury is characterized by long periods on
NIV (often ≥20 h) but with low pressure settings due to the reduced elastic
recoil of the chest wall.
• Because hyperventilation is common, special awareness of hypocapnia
and electrolyte disturbance is necessary.
• Problems such as hypophonia and reduced effectiveness of coughing
require solutions like secrete elimination techniques that have to be estab-
lished alongside initiation of NIV.
450 S. Stieglitz

References
1. Thomas K. Aldrich, Raymond Tso. The lungs and neuromuscular diseases. In: Mason JR,
Courtney Broaddus V, Murray JF, Nadel JA, editors. Murray and Nadel’s textbook of respira-
tory medicine, vol. 2. 4th ed. Philadelphia: Elsevier Saunders; 2000. p. 2283–310.
2. Stone DJ, Keltz H. The effect of respiratory muscle dysfunction on pulmonary function.
Studies in patients with spinal cord injuries. Am Rev Respir Dis. 1963;88:621–9.
3. Biyani A, el Masry WS. Post-traumatic syringomyelia: a review of the literature. Paraplegia.
1994;32(11):723–31. doi:10.1038/sc.1994.117.
4. Estenne M, Ketelbant P, Primo G, Yernault JC. Human heart-lung transplantation: physiologic
aspects of the denervated lung and post-transplant obliterative bronchiolitis. Am Rev Respir
Dis. 1987;135(4):976–8.
5. Estenne M, De Troyer A. Relationship between respiratory muscle electromyogram and rib
cage motion in tetraplegia. Am Rev Respir Dis. 1985;132(1):53–9.
6. Bach JR. Inappropriate weaning and late onset ventilatory failure of individuals with traumatic
spinal cord injury. Paraplegia. 1993;31(7):430–8. doi:10.1038/sc.1993.72.
7. Fishburn MJ, Marino RJ, Ditunno Jr JF. Atelectasis and pneumonia in acute spinal cord injury.
Arch Phys Med Rehabil. 1990;71(3):197–200.
8. Bach JR, Alba AS. Noninvasive options for ventilatory support of the traumatic high level
quadriplegic patient. Chest. 1990;98(3):613–9.
9. Stieglitz S, George S, Priegnitz C, Hagmeyer L, Randerath W. Frequency and management of
respiratory incidents in invasive home ventilation. Chron Respir Dis. 2013;10(3):135–40.
doi:10.1177/1479972313493099.
10. Splaingard ML, Frates Jr RC, Harrison GM, Carter RE, Jefferson LS. Home positive-pressure
ventilation. Twenty years’ experience. Chest. 1983;84(4):376–82.
11. Bolikal P, Bach JR, Goncalves M. Electrophrenic pacing and decannulation for high-level
spinal cord injury: a case series. J Spinal Cord Med. 2012;35(3):170–4. doi:10.1179/2045772
311Y.0000000056.
12. Bach JR, Goncalves MR, Hamdani I, Winck JC. Extubation of patients with neuromuscular
weakness: a new management paradigm. Chest. 2010;137(5):1033–9. doi:10.1378/
chest.09-2144.
13. Toki A, Hanayama K, Ishikawa Y. Resolution of tracheostomy complications by decannula-
tion and conversion to noninvasive management for a patient with high-level tetraplegia. Top
Spinal Cord Inj Rehabil. 2012;18(2):193–6. doi:10.1310/sci1802-193.
Noninvasive Mechanical Ventilation
in Older Patients 55
Cuneyt Salturk, Zuhal Karakurt, and Huriye Berk Takir

Contents
55.1 Introduction ................................................................................................................. 452
55.2 Pathophysiology .......................................................................................................... 452
55.3 NIMV and Acute Respiratory Failure......................................................................... 453
55.4 NIMV and Chronic Respiratory Failure ..................................................................... 454
55.5 Technical Aspects ....................................................................................................... 454
55.6 Palliative Use of NIMV .............................................................................................. 455
Conclusion ............................................................................................................................. 455
References .............................................................................................................................. 456

Abbreviations

ARF Acute respiratory failure

COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
CRF Chronic respiratory failure
DNI Do-not-intubate order
ICU Intensive care unit
NIMV Noninvasive mechanical ventilation

C. Salturk, MD (*) • Z. Karakurt, MD • H.B. Takir, MD

Respiratory Intensive Care Unit Clinic, Sureyyapasa Chest Diseases and Thoracic Surgery
Teaching and Research Hospital, Istanbul 34732, Turkey
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 451

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_55
452 C. Salturk et al.

55.1 Introduction

Prolonged human life has led to an increase in intensive care unit (ICU) admissions
of older patients (>65 years). Older patients constitute 42–52 % of ICU admissions
and 60 % of ICU days [1]. With limited ICU beds and an ever-increasing elderly
population, physicians need to be aware of the differences in treatment and diagno-
ses of these patients, to provide the best care.
The incidence of acute respiratory failure (ARF) increases significantly with age
[2]. Aggressive treatment of ARF, such as invasive mechanical ventilation, should
be limited in these patients, especially those over 80, due to their low survival rate.
Thus, noninvasive mechanical ventilation (NIMV) plays a crucial role in the treat-
ment of ARF in these patients. As with the younger population, NIMV also
decreases intubation and mortality rates in these patients with exacerbations of
chronic obstructive pulmonary disease (COPD) and acute pulmonary edema. It also
prevents post-extubation ARF [3]. In addition, NIMV is frequently recommended
for the respiratory support of patients with a do-not-intubate (DNI) order as comfort
palliative treatment [4].
The aim of this chapter is to define and elaborate the particular circumstances
related to NIMV treatment indications, methods, recommendations, and outcomes
in older patients.

55.2 Pathophysiology

Aging is a process that leads to a decrease in physiological reserves in the respi-

ratory system, as well as in other organ systems. Loss of function in the respira-
tory system is due to changes, both in the chest wall and the lung [5]. Increased
stiffness and consequent decreased compliance of the thoracic cage is caused by
cartilage calcification, kyphosis, and vertebral collapse [5]. Reduction in respira-
tory muscle strength may cause a reduction in the strength of the diaphragm and
accessory respiratory muscles, resulting in decreased maximal inspiratory and
expiratory pressures [5]. Decreased elasticity with age causes the loss of support-
ing tissues around the small airways with a resulting increased tendency for air-
way closure at small volumes [5]. Thus, the smaller airways lead to less ventilation
and ultimately a ventilation-perfusion mismatch. The ventilatory response to
hypoxia and hypercapnia also decreases in the older population [5]. Decreased
mucociliary clearance in older patients can also be a handicap for NIMV treat-
ment [5].
NIMV improves many of the above-mentioned adverse changes. For instance, it
corrects collapsed alveoli and ventilation-perfusion mismatch, and it facilitates
reduction in work of breathing by applying positive end-expiratory pressure [6]. It
also reduces the afterload in patients with acute cardiogenic pulmonary edema by
increasing intrathoracic pressure. NIMV resets decreased carbon dioxide sensitivity
of the ventilatory center [6]. It raises lung volume, improves lung compliance, and
reduces dead space [6].
55 Noninvasive Mechanical Ventilation in Older Patients 453

55.3 NIMV and Acute Respiratory Failure

The incidence of ARF increases with each decade until the age of 85 years [7]. In
addition to physiological changes in the respiratory system with aging, comorbidi-
ties (cardiac, neurological, and infectious), the presence of acute illness (malnutri-
tion, delirium), and prior respiratory disease may all predispose older patients to
ARF [7]. Non-pulmonary causes of ARF are more common in older patients and
these added complexities in the etiology lead to diagnostic difficulties. Nonspecific
presentations and atypical manifestations also contribute to difficulties in
diagnosis.
Ray et al. [8] prospectively evaluated 514 patients (mean age of 80 years) who
presented with ARF to the emergency department. Congestive heart failure (43 %),
pneumonia (35 %), COPD exacerbation (32 %), and acute pulmonary embolism
(18 %) were the primary causes, whereas pneumothorax, lung cancer, severe sepsis,
and acute asthma were less frequent (<5 %). The authors postulated that almost half
of the patients admitted to the emergency department with ARF had a multiple
diagnosis.
Age is one of the prognostic factors for ICU patients, however, it should not be
considered as a criterion for the selection of patients in intensive care alone.
Comorbidities, previous health, and the patient’s functional status are more impor-
tant when determining treatment options [9]. In older patients with ARF, NIMV
should be considered the first choice of ventilatory support. It is more comfortable,
has fewer complications, and has better short-term results compared with invasive
mechanical ventilation [4].
After excluding upper airway obstruction, physicians should determine whether
the respiratory failure is acute or subacute. If there is a subacute history of respira-
tory failure, NIMV treatment should be the first and consistent choice of treatment.
If there is no subacute history of respiratory failure, the prior clinical status of the
patient should be assessed. In the presence of a poor previous clinical status, pallia-
tive NIMV should be considered. In cases with good prior clinical status, treatment
should focus on determining the etiology. Invasive mechanical ventilation may be
the treatment of choice only when the etiology is known and after discussion with
family or relatives.
The incidence of COPD increases with age, and, in addition, acute exacerbations
become more frequent [9]. NIV is well tolerated and has a high success rate in older
patients, even when disabilities or dementia are present. NIMV decreases the rate of
endotracheal intubation, ventilator days, and ICU length of stay [10].
Chronic heart failure (CHF) is the most frequent cause of hospitalization in
patients aged >65 years [11]. These patients usually present with acute pulmo-
nary edema and ARF. In patients with CHF, continuous positive airway pressure
(CPAP) reduces afterload and improves left ventricular function. It is considered
the first line of care (at 0.98–1.23 kPa) in patients with acute pulmonary edema,
but should be used with caution in patients with myocardial infarction [11].
NIMV may be used in cases of CPAP treatment failure or significant hypercap-
nia. Mehta et al. [12] compared CPAP and NIMV and found a speedier
454 C. Salturk et al.

improvement in respiratory rate, hypercapnia, and dyspnea scores with NIMV,

but also a higher rate of myocardial infarction. Studies conducted in recent years
have shown that CPAP decreases mortality in patients with acute cardiogenic
pulmonary edema [13].
The higher incidence of pneumonia in older patients is associated with the pres-
ence of COPD. The effect of NIMV treatment in patients with ARF caused by
pneumonia is controversial. In a randomized clinical study, NIMV was associated
with a decrease in respiratory rate and only those patients with ARF caused by
pneumonia with preexisting COPD required intubation [14]. On the other hand,
another study showed a >60 % intubation rate in patients with ARF secondary to
pneumonia, without COPD [15]. NIMV should be considered in patients with ade-
quate secretion control, and with the presence of COPD.

55.4 NIMV and Chronic Respiratory Failure

The success of NIMV has been proven in the long-term treatment of chronic respi-
ratory failure (CRF) caused by chest wall disorders, neuromuscular diseases, and
morbid obesity. It improves daytime gas exchange, quality of life, and length of
hospital stay (16). On the other hand, results with the use of long-term NIMV ther-
apy for obstructive diseases, mainly COPD, are controversial.
In older patients, chest wall disorders are the most frequent cause of restrictive
CRF. Obesity, which is increasingly prevalent in all ages, is another important etiol-
ogy. In elderly subjects with associated parenchymal diseases such as tuberculous
sequelae, bronchiectasis is usually present. Age is not a restriction for long-term
NIMV and indications for long-term NIV treatment for elderly patients do not differ
from their younger counterparts.
Data on domiciliary NIMV in elderly patients are limited. Farrero et al. (17) stud-
ied 43 patients with chronic hypercapnic respiratory failure who began domiciliary
ventilation at age 75 or above. The distribution of these patients according to their
diagnosis was as follows: 11 (25%) had kyphoscoliosis, 14 (33 %) had post-
tuberculosis sequelae, 9 (21 %) had neuromuscular disease, 8 (19 %) were hypoven-
tilatory, and 1 (2 %) had bronchiectasis plus kyphosis. Their results showed the
efficacy of NIMV in the elderly in terms of improved arterial blood gases and noctur-
nal desaturations, and a decrease in hospital admissions. Compliance was also good in
this elderly population, that is, 8.3 (3.1) h/day, comparable to the general population.
Therefore, domiciliary NIMV treatment should be recommended in all patients
who successfully pass the initial trial period, regardless of age.

55.5 Technical Aspects

A decrease in elastic recoil in elderly lungs causes an increased risk for barotrauma.
Therefore, methods that preserve spontaneous ventilation are preferred in older
patients with ARF. Pressure support ventilation is usually the first choice, but
55 Noninvasive Mechanical Ventilation in Older Patients 455

pressure controlled assisted ventilation may also be used. Facial masks covering the
nose and mouth are the most efficient for NIMV due to ARF due to less leakage.
In the chronic setting, a ventilator should be easy to use, contain a battery, and be
light and portable. Although there is no study showing clinical superiority, pressure
preset ventilators are preferred to volume preset ventilators. Nasal masks are pre-
ferred for domiciliary NIMV, however, nasal pillows may sometimes be used for
better local skin tolerance.

55.6 Palliative Use of NIMV

Management of ARF in very old patients (>80 years) may comprise lesser use of inva-
sive ventilation and less admission to ICU due to their low survival rate compared with
“younger” elderly patients (age < 80 years). Patients in this age group may be candi-
dates for a DNI order. Refusing ICU admission is common among older patients, espe-
cially those with chronic respiratory disorders and cancer. Palliative use of NIMV in
patients with a DNI order was first studied by Benhamou et al. [14]. They found that
NIMV was successful in 60 % of these patients and well tolerated in 75 %. In another
prospective study including 114 patients (aged > 63 years) with DNI orders, survival
after hospital discharge was 72 % in the case of acute pulmonary edema, 52 % in
COPD, and worse in patients with pneumonia or cancer [15]. The prognosis was heav-
ily influenced by the underlying cause of respiratory failure, efficiency of cough, and
mental status, and again by the initial selection of patients. Palliative NIMV is regularly
performed in the ICU as well as in the medical wards and the emergency department.
Indeed, because of the chronic shortage of ICU beds, NIMV may be better imple-
mented outside ICU. Some hospitals have created special units to perform NIMV treat-
ment. Vargas and colleagues [3] studied elderly DNI patients with ARF. They treated
these patients with NIMV in a half-open geriatric ward with trained physicians and
nurses. After 12 h of NIMV in the geriatric ward, 75 % of these patients were able to
be discharged. Hospital mortality was related to the admission diagnosis and was espe-
cially high in cases of active end-stage cancer or hypoxemic respiratory failure.
Dyspnea is a common symptom in patients with terminal disease, and if the
cause is irreversible it is called terminal dyspnea. NIMV is used to relieve dyspnea
near the end of life. However, pharmacological treatment of dyspnea and anxiety
should be at a maximum dose, both before and during the course of therapy. Note
that realistic expectations about the purpose and effectiveness of treatment should
be given to the relatives of the patient.

Conclusion
An increase in the elderly population has led to an increased frequency of admis-
sions to hospitals and ICUs of older patients with respiratory failure. Avoiding
invasive ventilation in these patients increases the frequency of NIMV treatment.
In the acute setting, NIMV is preferred in the majority of cases, and the decision
is based on the previous status of the patient and the level of comorbidities. CRF
patients with restrictive respiratory failure are the most responsive to NIMV,
456 C. Salturk et al.

although this is controversial when there is concomitant obstructive disease.

NIMV is used for palliative therapy of ARF in patients with a DNI order as well
as the palliative treatment of dyspnea.

Key Major Recommendations

• NIMV is well tolerated and has a high success rate in older patients with
ARF resulting from COPD.
• Age is not a restriction for long-term NIMV, and domiciliary NIMV treat-
ment should be recommended in all patients who successfully pass the
initial trial period.
• Palliative use of NIMV in patients with a DNI order is recommended and the
prognosis is heavily influenced by the underlying cause of respiratory failure.

References
1. Marik PE. Management of the critically ill geriatric patient. Crit Care Med. 2006;34(Suppl):176–
82. Review.
2. Behrendt CE. Acute respiratory failure in the United States: incidence and 31-day survival.
Chest. 2000;118(4):1100–5.
3. Vargas N, Vargas M, Galluccio V, et al. Non-invasive ventilation for very old patients with
limitations to respiratory care in half-open geriatric ward: experience on a consecutive cohort
of patients. Aging Clin Exp Res. 2014;26(6):615–23.
4. Nava S, Grassi M, Fanfulla F, et al. Non-invasive ventilation in elderly patients with acute
hypercapnic respiratory failure: a randomized controlled trial. Age Ageing. 2011;40:444–50.
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8. Ray P, Birolleau S, Lefort Y, et al. Acute respiratory failure in the elderly: etiology, emergency
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9. Muir JF, Benhamou D, Molano C, et al. Noninvasive ventilation: a remedy for geriatric
patients. ERS Monograph 43. 2009;19:286–306.
10. El Solh AA, Ramadan FH. Overview of respiratory failure in older adults. J Intensive Care
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11. Rasanen J, Heikkila J, Downs J, et al. Continuous positive airway pressure by face in acute
cardiogenic pulmonary oedema. Am J Cardiol. 1985;55:296–300.
12. Mehta S, Jay G, Woolard RH, et al. Randomised, prospective trial of bilevel versus continuous
airway pressure in acute pulmonary oedema. Crit Care Med. 1997;25:620–8.
13. Crane SD, Elliott MW, Gilligan P, et al. Randomized controlled comparison of continuous
positive airways pressure, bilevel noninvasive ventilation, and standard treatment in emer-
gency department patients with acute cardiogenic pulmonary oedema. Emerg Med J.
2004;21:155–61.
14. Benhamou D, Girault C, Faure C, et al. Nasal mask ventilation in acute respiratory failure.
Experience in elderly patients. Chest. 1992;102:912–7.
15. Levy M, Tanios MA, Nelson D, et al. Outcomes of patients with do not intubate orders treated
with noninvasive ventilation. Crit Care Med. 2004;32:2002–7.
Role of Noninvasive Mechanical
Ventilation in Difficult Weaning 56
Inderpaul Singh Sehgal, Sahajal Dhooria,
Ashutosh N. Aggarwal, and Ritesh Agarwal

Contents
56.1 Introduction.................................................................................................................. 458
56.2 Definitions.................................................................................................................... 458
56.2.1 Weaning Failure............................................................................................. 458
56.2.2 Weaning in Progress....................................................................................... 459
56.2.3 Classification of Weaning............................................................................... 459
56.2.4 Criteria for Weaning....................................................................................... 459
56.3 Pathophysiology of Weaning Failure........................................................................... 459
56.4 Assessment Tools for Weaning.................................................................................... 460
56.4.1 Respiratory Frequency-to-Tidal Volume Ratio (f/VT).................................... 460
56.4.2 Diaphragm Ultrasonography.......................................................................... 461
56.4.3 Integrative Weaning Index.............................................................................. 461
56.5 Weaning Trials............................................................................................................. 461
56.5.1 Spontaneous Breathing Trial.......................................................................... 461
56.5.2 Pressure Support Ventilation.......................................................................... 462
56.5.3 Synchronized Intermittent Mandatory Ventilation......................................... 462
56.6 Role of NIV in Weaning.............................................................................................. 462
56.6.1 Rationale of NIV in Weaning Failure............................................................. 463
56.7 Role of NIV in Difficult/Prolonged Weaning (Weaning Strategy).............................. 463
56.7.1 NIV in Weaning Patients with AECOPD....................................................... 463
56.7.2 NIV in Weaning Patients of Acute Hypoxemic Respiratory Failure............. 466
56.7.3 NIV in Weaning Patients with Acute-on-Chronic Respiratory Illness........... 467
56.7.4 NIV in Weaning Patients with Acute Respiratory Failure
of Heterogeneous Causes............................................................................... 467
Conclusion.............................................................................................................................. 468
References............................................................................................................................... 470

I.S. Sehgal, MD, DM • S. Dhooria, MD, DM • A.N. Aggarwal, MD, DM, FCCP •
R. Agarwal, MD, DM, FCCP (*)
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and
Research, Chandigarh, India
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 457

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_56
458 I.S. Sehgal et al.

56.1 Introduction

Mechanical ventilation is an essential part of the management of critically ill

patients. It involves provision of positive pressure, either using invasive (endotra-
cheal tube, tracheostomy) or noninvasive (oronasal or face mask) methods. The use
of invasive mechanical ventilation is associated with several complications, both
infectious (ventilator-associated pneumonia) and noninfectious (volutrauma, baro-
trauma, ventilator-induced diaphragmatic dysfunction, and others). Hence, in sev-
eral situations, especially acute exacerbations of chronic obstructive pulmonary
disease (COPD) and cardiogenic pulmonary edema, a trial of noninvasive ventila-
tion (NIV) is preferred prior to intubation [1–6]. However, in some clinical circum-
stances, endotracheal intubation is inevitable [7–10]. Once the underlying respiratory
illness starts recovering, the patient is ready to be weaned off the mechanical venti-
latory support. Weaning is defined as a process that involves liberation of a person
from mechanical ventilation and from the endotracheal/tracheostomy tube [11].
The management of a patient with respiratory failure comprises of a continuum
of six steps [11]: (1) treatment of acute respiratory failure; (2) diagnosis of the prob-
ability of weaning; (3) assessment for weaning; (4) determination of the ability of a
patient to breathe spontaneously through a spontaneous breathing trial (SBT); (5)
removal of the endotracheal tube (extubation); and (6) reintubation, if the patient is
unable to breathe spontaneously. Failure in identification of stage 2 and assessment
of readiness to wean (stage 3) is considered the most important factor responsible
for delay in weaning. Delay in weaning or prolonged mechanical ventilation has
several adverse outcomes, including increased risk of ventilator-associated compli-
cations, and adds to the cost of management [12–14]. In this chapter, we review the
role of NIV in weaning patients from invasive ventilation in critical care. We spe-
cifically look at the role of NIV in facilitating extubation in patients who fail SBT,
without discussing the role of NIV in established post-extubation respiratory failure
or the role of NIV in preventing reintubation in those with planned extubation (as a
preemptive strategy for preventing reintubation) [15].

56.2 Definitions

56.2.1 Weaning Failure

Weaning failure is defined as either failure of SBT or need for reintubation or death
within 48 h of extubation [11]. Failure of SBT is characterized by a combination of
objective (respiratory rate >30 breaths/min, heart rate of >110 beats/min, hypoten-
sion, cardiac arrhythmias, hypoxemia, or acidosis) and subjective (agitation, altered
mental status, diaphoresis, labored breathing, and others) parameters [7–9, 16–19].
56  Role of Noninvasive Mechanical Ventilation in Difficult Weaning 459

56.2.2 Weaning in Progress

Weaning in progress is a term used to define an intermediate category of wean-

ing process wherein the patient is liberated from invasive mechanical ventila-
tion but needs the support of NIV to facilitate weaning [11]. Patients with
difficult weaning have high morbidity and mortality up to 40 %. Patients with
prolonged weaning usually require long-term ventilatory support, with only
50 % alive at 5 years [11].

56.2.3 Classification of Weaning

Weaning is classified into three categories [11]: (1) simple weaning is a condition in
which the patient proceeds from initiation of weaning to successful extubation on
the first attempt without difficulty; (2) difficult weaning is a condition in which the
patient fails initial weaning and requires up to three SBTs or as many as 7 days from
the first SBT to achieve successful weaning; (3) prolonged weaning is a condition
in which the patient fails at least four weaning attempts or requires >7 days of wean-
ing after the first SBT.

56.2.4 Criteria for Weaning

The decision to initiate the weaning process is a clinical art and requires a combina-
tion of certain criteria (Table 56.1) that need to be accomplished before applying
weaning assessment methods.

56.3 Pathophysiology of Weaning Failure

Patients who face weaning difficulties usually develop rapid shallow breathing on
liberation from positive pressure ventilation. This results in dynamic hyperinflation
and development of intrinsic positive end-expiratory pressure (iPEEP) [6, 20, 21].
The iPEEP, along with high ventilatory demand, leads to an increase in the respira-
tory work of breathing and causes respiratory muscle fatigue, thus causing weaning
failure. The increase in respiratory work of breathing is further compounded by
cardiovascular responses associated with removal of positive pressure ventilation,
leading to an increase in the venous return along with escalation in resistance to left
ventricular outflow [22]. An inappropriate cardiovascular response, especially in
those with compromised left ventricular function, further increases the load on
already-burdened respiratory muscles [23].
460 I.S. Sehgal et al.

Table 56.1 Criteria for Subjective parameters

readiness for weaning
Resolution of the disease for which the patient needed
(combination of one or more
ventilatory support
of the following)
Good effective cough/ability to clear secretions
Absent or minimal tracheobronchial secretions
Clear sensorium/ no delirium
Absent or minimal neuromuscular weakness
Objective parameters
Respiratory rate ≤35/min
Heart rate ≤140/min
Resolution of hypotension or minimal need of
vasopressors

SpO2 >89 % on ≤ FiO2 0.4 (or Pa O2 / Fi O2 ³ 150 mmHg )

PEEP ≤8 cmH2O

Pa CO2 £ 45mmHg
MIP ≤ −20 to −25 cmH2O
VT >5 ml/kg
RSBI <105 breaths/min/l
MIP maximum inspiratory pressure, PEEP positive end expi-
ratory pressure, RSBI rapid shallow breathing index, VT tidal
volume

56.4 Assessment Tools for Weaning

A weaning assessment tool should ideally be able to correctly identify all the indi-
viduals who can be safely liberated from the ventilator. Patients who meet the wean-
ing criteria should be screened with one of the weaning assessment tools. The
various weaning assessment tools include respiratory frequency-to-tidal volume
ratio, maximum inspiratory pressure, integrative weaning index, diaphragm ultra-
sound, and others. The currently available methods for weaning assessment are far
from perfect, thus creating a need for an ideal assessment tool.

56.4.1 Respiratory Frequency-to-Tidal Volume Ratio (f/VT)

Also known as rapid shallow breathing index (RSBI), the f/VT is measured during
spontaneous breathing for 1 min. During spontaneous breathing, the ventilator is set
at a pressure support of 0 cm of H2O or continuous positive airway pressure (CPAP)
of 0 cm H2O. A RSBI of 100 discriminates between successful weaning and failure,
with a value of <100 suggesting a successful weaning trial with a sensitivity of 0.97
and a specificity of 0.65 [24].
56  Role of Noninvasive Mechanical Ventilation in Difficult Weaning 461

56.4.2 Diaphragm Ultrasonography

Mechanical ventilation can lead to rapidly progressive diaphragmatic weakness and

may hinder weaning from ventilation [25]. Bedside ultrasound is a useful modality
to assess the diaphragm function. In a single-center study involving mechanically
ventilated patients, diaphragm dysfunction (excursion of <10 mm on M-mode)
could be identified in 29 % patients by using bedside ultrasound. Presence of dia-
phragmatic dysfunction on ultrasound assessment was associated with prolonged
weaning time (17 vs 4 days, p < 0.01) and a longer time spent on mechanical ventila-
tion (24 vs 9 days, p < 0.01) [26].

56.4.3 Integrative Weaning Index

A prospective study assessed a combination of several factors (respiratory system

compliance x arterial oxygen saturation/f/VT ratio) to predict the weaning from
mechanical ventilation. The Integrative Weaning Index (IWI) performed better than
several other parameters, including RSBI, tidal volume (Vt), tracheal airway occlu-
sion pressure in the first 0.1 s (P 0.1), the product of P 0.1 and f/Vt (P 0.1 × f/Vt),
respiratory rate (f), static compliance of the respiratory system (Cst), and ratio of
arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) with an area
under the receiver-operating characteristic (ROC) curve of 0.96 [27].

56.5 Weaning Trials

Once the patient is assessed for weaning and is considered suitable for weaning, a
weaning trial is instituted before extubation. An ideal weaning trial should be able
to identify all the individuals who will successfully tolerate extubation. The wean-
ing techniques that are used include SBT, automated tube compensation, pressure
support ventilation (PSV), and synchronized intermittent mechanical ventilation
(SIMV).

56.5.1 Spontaneous Breathing Trial

SBT is the oldest and most commonly employed method used for weaning [16].
It involves removing the patient from the ventilator and providing supplemental
oxygen by using a T-piece or T-tube device or a pressure support of 5–8 cm of
H2O in adults [19, 28–30]. A pooled analysis of nine randomized trials compar-
ing PSV SBT versus T-piece trial SBT did not find any difference between the
methods or the pressure used in weaning success, intensive care unit (ICU)
mortality, reintubation rate, length of stay in ICU or long-term weaning unit,
and pneumonia [30]. However, PSV was more effective in predicting successful
462 I.S. Sehgal et al.

SBT in patients with simple weaning compared with T-piece trial [19, 30]. A
few studies have also used CPAP of 5 cm H2O for SBT [30]. It is reasoned that
provision of CPAP maintains functional residual capacity at a level similar to
that following extubation. Further, CPAP also helps maintain the patency of
small airways, especially in patients with COPD [31]. However, in patients with
poor left ventricular function, provision of CPAP may falsely predict successful
extubation [23].

56.5.2 Pressure Support Ventilation

PSV is another commonly used method for weaning. With PSV, all the breaths are
patient triggered, flow cycled, and provide ventilatory support that is gradually
reduced over time until patient is successfully liberated from mechanical ventila-
tion. Both inspiratory positive airway pressure (IPAP) or pressure support and expi-
ratory positive airway pressure (EPAP) or CPAP are reduced gradually by 1–2 cm
of H2O until an acceptable IPAP of 5–7 cm of H2O and EPAP of 0–5 cm of H2O is
reached [19].

56.5.3 Synchronized Intermittent Mandatory Ventilation

With SIMV, ventilation is assisted intermittently either as mandatory or as sponta-

neous breaths. During the spontaneous mode there is no support to the respiratory
muscle, which have an additional burden to overcome dead space due to ventila-
tory circuit [5, 32]. This increased burden leads to fatigue of respiratory muscles
and hence weaning failure and increased need for invasive mechanical ventilation.
Therefore, the use of SIMV as a mode for weaning is discouraged. SIMV can also
be combined with PSV, where the spontaneous breaths are assisted by pressure
support. However, even this mode is inferior as the respiratory center and respira-
tory muscles have to alter their output in anticipation of the next breath, which may
either be mandatory or spontaneous. Moreover, it does not does not allow partition-
ing of the work of breathing performed by either the ventilator or the patient
[5, 32–35].

56.6 Role of NIV in Weaning

Noninvasive ventilation has been used in three different scenarios for weaning:
(i) advancing extubation in patients with difficult or prolonged weaning (weaning
strategy); (ii) avoidance of reintubation after extubation in patients with post-
extubation respiratory failure (management strategy); and (iii) to prevent develop-
ment of post extubation respiratory failure (prophylactic strategy). Herein, we
discuss only the weaning strategy.
56  Role of Noninvasive Mechanical Ventilation in Difficult Weaning 463

56.6.1 Rationale of NIV in Weaning Failure

By reducing the work of breathing and preventing the development of the rapid
shallow breathing pattern, NIV may be useful where weaning has failed. Further,
EPAP akin to positive end-expiratory pressure acts as an external splint and helps in
avoiding dynamic hyperinflation seen in patients with COPD. NIV by its favorable
cardiovascular effects may also facilitate weaning [3, 4, 6, 15, 36, 37].

56.7 R
 ole of NIV in Difficult/Prolonged Weaning (Weaning
Strategy)

NIV has been tried in the management of acute respiratory failure as a strategy to
shorten the weaning process and facilitate liberation from invasive mechanical ven-
tilation, especially in patients with COPD [38–40]. The trial design in most studies
involved patients who failed SBT; they were subsequently randomized to continued
invasive ventilation or extubated and initiated on NIV. The results of nine random-
ized controlled trials (RCTs) evaluating the role of NIV in augmenting extubation
are summarized in Tables 56.2 and 56.3. Of the nine studies identified, three studies
included patients with acute exacerbation of COPD (AECOPD) [38–40], while
three studies encompassed patients with acute respiratory failure due to heteroge-
neous etiology (COPD, heart failure, pneumonia, thoracic trauma, and chest wall
deformity) [41–43]. One study comprised patients with acute hypoxemic respira-
tory failure [44], and two studies involved patients with acute-on-chronic respira-
tory failure (COPD, persistent asthma, bronchiectasis, obesity hypoventilation
syndrome, restrictive lung diseases, and others) [45, 46]. The most common wean-
ing assessment tool applied in all the studies was SBT with duration ranging
between 5 min and 2 h. Weaning success, as defined by the lack of need of reintuba-
tion within 48–72 h of extubation or hospital survival, was reported in eight studies.
Other parameters reported included duration of invasive mechanical ventilation,
length of ICU/hospital stay, hospital mortality, and complications associated with
invasive mechanical ventilation and weaning.

56.7.1 NIV in Weaning Patients with AECOPD

Three randomized trials involving 120 patients of acute exacerbation of COPD

have assessed the role of NIV in weaning patients with AECOPD [38–40].
Weaning success (avoidance of re-intubation) was reported in two studies. The
use of NIV was associated with successful weaning in 86 % (39/45) of the patients,
whereas the use of conventional methods led to successful weaning in 71 %
(32/45). In comparison with invasive mechanical ventilation, the use of NIV was
associated with a comparable improvement in arterial blood gas and clinical
parameters such as respiratory rate and sensorium, and a lesser incidence of
464 I.S. Sehgal et al.

Table 56.2 Summary of studies describing use of noninvasive pressure ventilation (NIV) in dif-
ficult weaning
Type Weaning Weaning
Author/year of No. of Comparator Cause of respiratory trial success
of study study patients strategy (n) failure given (p value)
Nava et al. RCT 50 NIV vs PSV AECOPD T-piece 22/25 vs
(1998) [38] (25 vs 25) trial 17/25
(0.002)
Girault RCT 33 NIV vs PSV AECOPD, 2h 13/17 vs
et al. (17 vs 16) restrictive lung T-piece 12/16
(1999) [46] disease, mixed lung trial (>0.05)
disease
Ferrer et al. RCT 43 NIV vs AECOPD, heart T-piece 18/21 vs
(2003) [41] conventional failure, pneumonia, trial 16/22
weaning thoracic trauma, (>0.05)
strategy (21 vs post-operative
22)
Trevisan at RCT 65 NIV vs IMV AECOPD, heart 30 min 15/28 vs
al. (2008) (28 vs 37) failure, pneumonia, T-piece 15/37
[43] thoracic trauma, trial (NA)
post-operative
Prasad RCT 30 NIV vs PSV AECOPD 2h NA
et al. (15 vs 15) T-piece
(2009) [40] trial
Girault RCT 208 NIV vs PSV vs Chronic 5 mins-2 46 vs 32
et al. oxygen hypercapnic h T-piece vs 20
(2011) [45] therapy (69 vs respiratory failure trial (<0.001)
69 vs 70) due to COPD,
persistent asthma,
bronchiectasis,
obesity-
hypoventilation
syndrome, chest
wall deformity,
sequelae of
pulmonary
tuberculosis
Vaschetto RCT 20 NIV vs PSV Acute hypoxemic 30 min 9/10 vs
et al. (10 vs 10) respiratory failure SBT 5/10
(2012) [44]
Tawfeek RCT 42 NIV vs SIMV AECOPD, heart 2 h SBT 18/21 vs
et al. (21 vs 21) failure, pneumonia, 11/21
(2012) [42] thoracic trauma, (<0.05)
post-operative,
neuromuscular
disease
El-Shimy RCT 40 NIV vs SIMV AECOPD 0.5–2 h 17/20 vs
et al. (20 vs 20) SBT 15/20
(2013) [39] (0.049)
AECOPD acute exacerbation of COPD, COPD chronic obstructive pulmonary disease, IMV inva-
sive mechanical ventilation, PSV pressure support ventilation, RCT randomized control trial, SBT
spontaneous breathing trial, SIMV synchronized intermittent mandatory ventilation
Table 56.3 Outcome parameters in studies describing noninvasive ventilation as a weaning strategy
Total duration of
Total duration of ventilatory support (both Length of ICU stay, Length of hospital In hospital Complication related to
Author/year IMV, in days NIV and IMV), in days in days stay, in days deaths (n) IMV and weaning (n)
Nava et al. 10.2 ± 6.8 vs NA 15.1 ± 5.4 vs NA 2 vs 7 NA
(1998) [38] 16.6 ± 11.8 24 ± 13.7
Girault et al. 4.56 ± 1.85 vs 11.54 ± 5.24 vs 3.46 ± 1.42 12.35 ± 6.82 vs 27.12 ± 14.33 vs 0 vs 2 6 vs 9
(1999) [46] 7.69 ± 3.79 14.06 ± 7.54 27.69 ± 13.09
Ferrer et al. 9.5 ± 8.3 vs 11.4 ± 8 vs 20.1 ± 13.1 14.1 ± 9.2 vs 27.8 ± 14.6 vs 2 vs 9 5 vs 16
(2003) [41] 20.1 ± 13.1 25 ± 12.5 40.8 ± 21.4
Trevisan et al. 7.5 ± 7.8 vs 10 ± 9.1 14.9 ± 9.9 vs 17.3 ± 10.5 18.9 ± 11.3 vs 34.5 ± 20.6 vs 9 vs 10 8 vs 28
(2008) [43] 20.8 ± 10.9 42.4 ± 24.5
Prasad et al. 6.20 ± 5.20 vs NA 8.47 ± 4.79 vs NA 5 vs 9 6 vs 5
(2009) [40] 7.47 ± 6.38 10.80 ± 5.28
Girault et al. 7.5 [4.5–15.5] vs 7.5 17.5 [9.5–28] vs 16 vs 9 vs 9 33 vs 35 vs 43
(2011) [45] [4.5–14.5] vs 7.5 7.5 [4.5–14.5] vs
[4.5–17.5]a 7.5 [4.5–17.5]a
Vaschetto et al. 8 vs 15 NA 15 ± 11 vs 21 ± 13 NA 2 vs 3 3 vs 5
(2012) [44]
Tawfeek et al. 12.8 ± 8.3 vs NA NA NA 2 vs 6 4 vs 19
(2012) [42] 22.3 ± 13.3
56  Role of Noninvasive Mechanical Ventilation in Difficult Weaning

El-Shimy et al. 35 ± 1.63 vs NA 9.50 ± 3.2 vs NA 5 vs 9 0 vs 16

(2013) [39] 47 ± 2.25 11.4 ± 2.70
All values are expressed as mean ± SD unless otherwise stated
IMV invasive mechanical ventilation, NA not available
a
Median with interquartile range
465
466 I.S. Sehgal et al.

nosocomial pneumonia. The use of NIV was not without complications, which
included dryness of mouth, abrasion of nasal skin, claustrophobia, gastric disten-
sion, poor quality of sleep, and others.
The first RCT included 50 patients with severe COPD [38], with 35 of these
patients receiving long-term oxygen therapy. Most patients (approximately 50 %)
had comorbid illnesses, including rhythm disturbances, hypertension, diabetes mel-
litus, heart failure, and others. The application of NIV for weaning significantly
reduced the need for invasive ventilation and ICU stay; it was associated with a
higher 60-day survival. The other two trials did not mention the severity of underly-
ing COPD and comorbid conditions [39, 40]. In the two trials reporting the weaning
time, the NIV group had shorter weaning times in comparison with the control arm
(invasive mechanical ventilation) [39, 40]. Further, the mean IPAP and EPAP
(15.07 ± 1.27 and 6.21 ± 0.43 cm of H2O, respectively) in the NIV arm and the mean
pressures in the invasive arm (18.21 ± 1.1 cm of H2O above PEEP of 5 cm of H2O)
were similar in the two groups [40].
Thus, in carefully selected patients with AECOPD who fail initial weaning trials,
the use of NIV may be associated with a reduction in weaning time, less need for
invasive mechanical ventilation, lower incidence of nosocomial pneumonia, better
survival rates, and superior weaning rates.

56.7.2 NIV in Weaning Patients of Acute Hypoxemic Respiratory

Failure

Only one single-center feasibility study has described the use of NIV as a weaning
strategy in patients with acute hypoxemic respiratory failure [44]. Ten patients
each were randomized to undergo either a NIV-based strategy or a conventional
(invasive PSV) strategy for weaning from invasive mechanical ventilation. The
etiology of ARDS included both direct (thoracic trauma, aspiration pneumonia,
pneumonia) and indirect (sepsis, pancreatitis, blood transfusion related) causes,
with baseline Acute Physiology and Chronic Health Evaluation (APACHE) II
scores ranging from 8 to 13. Extubation failure was defined as an inability to sus-
tain spontaneous unassisted breathing for 48 consecutive hours without the need
for invasive or noninvasive ventilation. The use of NIV resulted in weaning suc-
cess in 90 % of the patients compared with 50 % in the conventional arm. There
were three ICU deaths in the conventional arm and only one death in the NIV arm.
Three patients in the invasive PSV arm required tracheostomy, whereas none
needed tracheostomy in the NIV arm. The most common cause of death was mul-
tiorgan failure. One additional patient in the NIV arm succumbed to underlying
comorbid illness (chronic kidney disease and diabetes mellitus) after discharge
from the ICU. Although NIV resulted in a significantly shorter duration of inva-
sive ventilation, overall 28-day ventilation-free days (invasive and NIV) and
weaning time were similar in the two groups.
There is sparse evidence on the role of NIV in facilitating extubation in patients
recovering from acute hypoxemic respiratory failure. Thus, NIV should not be used
56  Role of Noninvasive Mechanical Ventilation in Difficult Weaning 467

in weaning this group of patients. More evidence is required regarding the use of
NIV in weaning patients with acute hypoxemic respiratory failure.

56.7.3 NIV in Weaning Patients with Acute-on-Chronic

Respiratory Illness

Two trials have addressed the role of NIV in acute-on-chronic respiratory dis-
eases [45, 46]. Both trials included patients (n = 241) with chronic respiratory
disorders such as COPD, persistent asthma, bronchiectasis, restrictive lung dis-
orders, and others. In the first trial, 33 patients were randomized to either NIV
(n = 17) or the conventional mode of weaning (n = 16) [46]. Weaning failure was
defined as inability to sustain unassisted ventilation for at least 5 days or death or
reintubation. Most of the included patients had severe underlying disease as
defined by previous history of intubation (n = 12) or need for long-term oxygen
therapy (LTOT) (n = 10). Although the NIV group had fewer days on invasive
mechanical ventilation, there was no difference in weaning success, mortality, or
complications. A subsequent larger multi-center study randomized patients
(n = 208) into three groups (NIV group, invasive PSV, and oxygen therapy group)
[45]. Patients in the non-NIV group were allowed NIV trial prior to reintubation,
after extubation failure. Weaning failure was defined as an inability to sustain
unassisted ventilation for at least 7 days or death or reintubation. The duration of
7 days was included to account for late NIV failure. In this study also, apart from
a decline in the duration of invasive mechanical ventilation, no difference was
seen in the weaning success rate, hospital mortality, or complications. The lack
of difference in this study could be explained by the use of NIV prior to reintuba-
tion in both the non-NIV arms.
Thus, current evidence supports judicious use of NIV as a weaning strategy in
patients with chronic respiratory diseases, as NIV may improve weaning results in
these patients by shortening the duration of intubation and reducing the risk of post-
extubation acute respiratory failure.

56.7.4 NIV in Weaning Patients with Acute Respiratory Failure

of Heterogeneous Causes

Three trials have addressed the role of NIV in weaning from invasive mechanical
ventilation in acute respiratory failure due various causes such as acute exacerba-
tion of COPD, asthma, heart failure, postoperative respiratory failure, thoracic
trauma, post-tuberculosis sequelae, pneumonia, and others [41–43]. The initial
trial randomized 43 consecutive patients with acute respiratory failure in two arms
using either NIV or the conventional approach (invasive PSV) as a weaning strat-
egy [41]. Patients who failed SBT for 3 consecutive days and were considered
difficult to wean were enrolled in the study. Successful weaning was defined as
ability to sustain spontaneous breathing at least for 3 consecutive days and
468 I.S. Sehgal et al.

extubation failure was defined as the need for reintubation within 72 h of extuba-
tion. The use of NIV resulted in significant reduction in duration of total and
invasive mechanical ventilation and ICU and hospital stay, better hospital sur-
vival, fewer complications, and need for tracheostomy. There was no difference in
the reintubation rate in the two study arms, although the patients in the conven-
tional arm were allowed a trial of NIV before attempting reintubation. Use of the
conventional weaning approach (odds ratio (OR), 6.6; 95 % confidence interval
(CI), 1.1–38.8) and age >70 years (OR, 5.1; 95 % CI, 1.7–15) had higher odds of
death in the study population on multivariate analysis [41]. In another trial of 65
patients with a similar study population, the use of NIV resulted in less risk of
complications and a trend toward shorter ICU and hospital stay. The patients in
this study were sicker at baseline compared with the previous study and had mul-
tiple comorbidities [43]. A study of 42 patients compared NIV using proportional
assist ventilation (PAV) with conventional weaning using SIMV with pressure
support (SIMV-PS); PAV-NIV resulted in significantly higher weaning success
with shorter duration of mechanical ventilation and fewer complications (ventila-
tor-associated pneumonia, pneumothorax, sepsis, and others) [42]. There was no
difference in the 60-day survival. However, the positive results in this study could
also be the result of the use of the SIMV mode for weaning in the comparator arm
that has been associated with poor outcomes [18].
Thus, the current evidence suggests a possible role of NIV in reducing the dura-
tion of invasive mechanical ventilation in weaning patients with heterogeneous
causes of respiratory failure. However, variable results in the three studies do not
provide conclusive evidence in support of NIV in reducing mortality or ICU and
hospital stay and improving weaning success.

Conclusion
The use of NIV in difficult weaning should be restricted in patients with COPD
and other hypercapnic respiratory failure states such as bronchiectasis and
chronic asthma. In our ICU, we use NIV as a tool for weaning patients with the
aforementioned conditions who fail two attempts at weaning using the SBT strat-
egy (Table 56.4). Importantly, a strict vigil needs to be maintained to identify
NIV failure and intubate the patients at the earliest sign of failure.
56  Role of Noninvasive Mechanical Ventilation in Difficult Weaning 469

Table 56.4 Practical approach to the use of NIV in difficult weaning

Underlying conditions Chronic obstructive pulmonary disease
Long standing asthma
Bronchiectasis
Weaning readiness Significant improvement in the underlying condition
Respiratory rate <32 breaths/min
Fi O2 requirement less than 0.4

PEEP ≤5 cm H2O
Good cough reflex
Normal in mental status
Minimal airway secretions
Hemodynamically stable
Spontaneous breathing At least on two occasions defined by one or more of the following:
trial failure Increase in respiratory rate ≥40 breaths/min (or >25 % of
baseline)
Sp < 85% despite Fi O2 of 0.5
  O2
Pa > 55mmHg (or >20 % of baseline) and pH <7.3
  CO2
Heart rate >140 beats/min or <50 beats/min (or increase or
decrease by >25 % of baseline)
Alteration in mental status or agitation associated with
diaphoresis
Hypotension (systolic BP <90 mmHg) or hypertension (systolic
BP >180 mmHg)
Cardiac arrhythmia
NIV application Full face mask
Start with IPAP of 8 cm H20 and EPAP of 4 cm H20
Titrate to clinical endpoints of respiratory rate <30 breaths/min;
SpO2 ³ 90% with Fi O2 < 0.4; Pa CO2 < 50 mmHg with pH between 7.3
and 7.4
NIV failure (defined at Increase in respiratory rate ≥40 breaths/min (or >25 % of baseline)
30 min and 1 h)
SpO2 < 85% despite Fi O2 of 0.5

Pa CO2 > 55mmHg (or >20 % of baseline) and pH <7.3

Heart rate >140 beats/min or <50 beats/min (or increase or decrease
by >25 % of baseline)
Alteration in mental status or agitation associated with diaphoresis
Hypotension (systolic BP <90 mmHg) or hypertension (systolic BP
>180 mmHg)
Cardiac arrhythmia
Pooling of secretions
Gasping respiration
BP blood pressure, PEEP positive end expiratory pressure
470 I.S. Sehgal et al.

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6. Agarwal R, Gupta R, Aggarwal AN, Gupta D. Noninvasive positive pressure ventilation in
acute respiratory failure due to COPD vs. other causes: effectiveness and predictors of failure
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8. Gupta D, Nath A, Agarwal R, Behera D. A prospective randomized controlled trial on the
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9. Sharma S, Agarwal R, Aggarwal AN, Gupta D, Jindal SK. A survey of noninvasive ventilation
practices in a respiratory ICU of North India. Respir Care. 2012;57(7):1145–53.
10. Agarwal R, Reddy C, Aggarwal AN, Gupta D. Is there a role for noninvasive ventilation in
acute respiratory distress syndrome? Respir Med. 2006;100(12):2235–8.
11. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J.
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Psychological Factors as Determinants
of Noninvasive Continuous Positive 57
Airway Pressure Response: Key Practical
Aspects and Topics

Alex H. Gifford

Contents
57.1 Introduction ................................................................................................................. 474
57.2 Current Gaps in General Knowledge .......................................................................... 474
57.3 The Psychology of Decision-Making About NIPPV
in Amyotrophic Lateral Sclerosis ............................................................................... 475
57.4 How the Clinician Influences NIPPV Acceptance by the Patient............................... 475
57.5 NIPPV Acceptance by Older Patients......................................................................... 476
57.6 NIPPV Acceptance by Children ................................................................................. 477
Conclusion ............................................................................................................................. 478
References .............................................................................................................................. 478

Abbreviations

ALS Amyotrophic lateral sclerosis

ARF Acute respiratory failure
CRF Chronic respiratory failure
HRQOL Health-related quality of life
ICU Intensive care unit
IMV Invasive mechanical ventilation
NIPPV Noninvasive positive pressure ventilation
RRT Renal replacement therapy

A.H. Gifford, MD
Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center,
Lebanon, NH, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 473

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_57
474 A.H. Gifford

57.1 Introduction

Surprisingly little has been published about the ways in which psychological
factors influence acceptance and tolerance of noninvasive positive pressure ven-
tilation (NIPPV) by patients with acute and chronic respiratory insufficiency.
Much of what has been written pertains to the latter circumstance when the
natural history of the underlying condition, usually a progressive neuromuscular
disease, permits a measure of forethought by the patient and caregivers about
how NIPPV stands to impact health-related quality of life (HRQOL) and what
lifestyle adjustments need to be made before it can be initiated. The proposition
of long-term NIPPV has been shown to elicit distinct cognitive and behavioral
perspectives within patients and their families that have been categorized by
some authors using semi-structured interviewing and interpretive phenomeno-
logical techniques. Patients whose acute respiratory failure (ARF) is treated
with NIPPV are often anxious and scared by the experience of dyspnea. These
responses may be heightened and sustained, however, by underlying psychiatric
disorders of which clinicians may or may not be aware and which may inform
the need to titrate sedating medications and/or offer close emotional support to
improve NIPPV tolerance. In an isolated report, NIPPV actually mitigated agi-
tation in an older male patient, but this provides only anecdotal support for its
utility in this context [1].

57.2 Current Gaps in General Knowledge

The literature review performed for this chapter has revealed several deficien-
cies in our knowledge about psychological factors associated with responses to
NIPPV. First, a dearth of information exists regarding how anxiety, depression,
or even psychosis, affect NIPPV tolerance in ARF. Evidence from several case
series [2–4] suggests that the alpha-2-adrenergic receptor agonist dexmedeto-
midine facilitates NIPPV tolerance during ARF by inducing anxiolysis without
insulting central ventilatory drive. These reports are limited by small numbers
of patients, a focus on the pharmacodynamics of the drug, and lack of a system-
atic appraisal of the psychological status of the patients. Second, data on chil-
dren are conspicuously limited. A single descriptive study of young children
with chronic respiratory failure (CRF) has determined that alternative NIPPV
interfaces must be found in approximately 20 % of patients, mostly due to
facial discomfort, but any contributions of psychological factors to this require-
ment were not given [5]. Third, practice guidelines for the initiation and main-
tenance of NIPPV in patients with affective and/or behavioral disorders are
currently unavailable. Lastly, novel strategies to enhance the acceptance of
NIPPV, like meditation, hypnosis, and acupuncture, are appealing but
unsubstantiated.
57 Psychological Factors as Determinants of Noninvasive Continuous 475

57.3 The Psychology of Decision-Making About NIPPV

in Amyotrophic Lateral Sclerosis

A number of psychological and illness severity factors inform decision-making

about NIPPV in patients with amyotrophic lateral sclerosis (ALS). In recently pub-
lished work, Martin et al. [6] provide a detailed appraisal of the physical, cognitive,
and psychological characteristics of 32 ALS patients who had been diagnosed at
least 6 months earlier and who made one or more decisions regarding NIPPV and/
or gastrostomy tube placement during the 3-month follow-up interval. In the subset
of patients who died during the observation period, NIPPV decisions were made
closer to the end of life (mean: 2.7 ± 2.2 months) than gastrostomy tube placement
decisions (mean: 6.1 ± 4.2 months). The authors had such limited post-NIPPV
refusal data that NIPPV and gastrostomy tube placement decisions (acceptance or
refusal) were analyzed together, an important caveat in the interpretation of their
findings. Not surprisingly, a greater burden of physical ailments was associated with
decisions made within the observation period. Patients who felt that they under-
stood their illness less well, those with a proactive attitude about decision-making,
and those with fewer depressive symptoms were more likely to refuse either
intervention.
The study of Martin et al. [6] highlights the potential for knowledge limitation
and apathy to complicate decision-making about NIPPV in ALS and refutes the
argument that depressed patients are more likely to refuse this intervention out of a
sense of relegation and/or deference to input from their caregivers. The authors
concluded that ALS patients who have a more passive approach to interventions and
fewer years of education, in contrast to those who were better informed about the
disease and had clear opinions about interventions, may benefit from assistance to
make informed decisions. Often, though, the benefits of NIPPV on HRQOL in ALS
motivate patients to continue using it and have led some to view it as being worth
the effort [2]. Patients who have refused NIPPV have expressed that it undermines
their sense of identity, dignity, and/or autonomy [3]. Some of these patients have
cited concerns about claustrophobia, loss of control, and vomiting while wearing
the mask as reasons for declining NIPPV [3]. That some patients with ALS readily
accept this intervention while others promptly refuse it underscores the need for
clinicians to explore the psychological forces that drive the decision-making pro-
cess for each patient (Table 57.1).

57.4 How the Clinician Influences NIPPV Acceptance by

the Patient

The extent to which clinicians are compassionate, receptive, and circumspect in

their counseling about NIPPV can significantly influence a patient’s perspective
about therapy. In the report by Ando et al. [3], some ALS patients felt that their
476 A.H. Gifford

Table 57.1 Psychological Amyotrophic lateral sclerosis (ALS)

influences on acceptance and
Perceptions of choice and control [9]
tolerance of NIPPV
Acceptance and need [9]
Aspects of fear [9, 13]
Active coping styles [14]
Preservation of the self [15]
Acute exacerbation of chronic obstructive pulmonary
disease (AECOPD)
Experience of anxiety, panic, and loss of control [8]
Experience of mobilizing willpower [8]
Respiratory failure (multiple etiologies)
Anticipatory anxiety [11]
Home versus institutional environment [12]
Claustrophobia [16]
Perception of compassion by caregivers (especially upon
initiation of treatment) [7]
Ability to maintain positive outlook about treatment despite
its strenuousness [7]
Reduced sensory abilities (older patients) [10]
Reduced satisfaction with achievements in life and
expectations for future (older patients) [10]

clinicians were forcing NIPPV on them. This perception was associated with a gen-
eralized disdain for hospitals and a sense of threatened autonomy. The focus of cli-
nicians can easily drift to alarms on ventilatory equipment and physiological
parameters like oxyhemoglobin saturation and away from the psychological needs
of patients. This can unintentionally lead patients to question the efficacy of treat-
ment and feel subjugated to technology; moreover, family members can feel guilty
about asking clinicians to explain the rationale for NIPPV in the care of their loved
one [7]. Tolerance of NIPPV can be improved when patients trust that their clini-
cians will be attentive to their emotional and physical needs and when continuity of
care by the same clinicians is maintained [8]. Patients are also quite cognizant of the
expertise that their clinicians have with NIPPV and/or the underlying disease for
which it is being used [9]. More research is needed to elucidate the attitudes and
practices that clinicians should foster to best help patients and their families cope
with NIPPV.

57.5 NIPPV Acceptance by Older Patients

Life experiences and concerns about HRQOL are factors that shape the preferences
of older patients for NIPPV. In the ETHICA study [10], investigators questioned
whether octogenarians who had either been admitted to hospital for treatment of a
chronic disease or who lived in a nursing home or assisted-living facility would
agree to intensive care unit (ICU) admission for a future hypothetical illness
57 Psychological Factors as Determinants of Noninvasive Continuous 477

requiring the use of NIPPV and/or renal replacement therapy (RRT). Of note, the
authors excluded patients with cognitive impairment and included those with rea-
sonably good functional status. They found that refusal rates for NIPPV, invasive
mechanical ventilation (IMV), and RRT (after IMV) were 27 %, 43 %, and 63 %,
respectively. Married patients were nearly three times more likely than those who
were unmarried to refuse NIPPV (RR 2.9, 95 % 1.5–5.8, p = 0.002). Patients with
lower scores on an inventory that measured the integrity of sensory faculties and
satisfaction with achievements in life and expectations for the future were also more
likely to refuse NIPPV. The authors point out that in emergency situations, clini-
cians are often not privy to information about HRQOL, and in the absence of a sur-
rogate decision maker and/or an advanced directive, they may render life-sustaining
services out of sheer necessity. This scenario highlights the importance of earnest
and timely communication among clinicians, patients, and their family members
about goals and values.

57.6 NIPPV Acceptance by Children

Because children often cannot intellectualize the experience of being treated with
NIPPV, they are susceptible to considerable anticipatory anxiety, which can evolve
into a formidable barrier to therapy. In an intriguing pilot study, Delord et al. [11]
performed medical hypnosis in nine children with CRF with the objective of accli-
matizing them to NIPPV. In the youngest patient, a technique based on distraction
was used, whereas in the older children, indirect or direct hypnotic suggestions were
employed to progressively induce psychocorporeal relaxation. These authors found
that a median of three sessions were needed to achieve acceptance of NIPPV for 6
or more hours per night. After 6 months of sustained hypnotherapy, median objec-
tive compliance with NIPPV was 7.5 h per night in eight of the nine patients. The
parents of one patient were instructed in the hypnotherapy technique and performed
it at home. Interestingly, the investigators noted that anxiety was also reduced in the
parents of treated children and concluded that this fact alone could have promoted
successful NIPPV use.
A 1997 survey of long-term ventilation in children throughout the United
Kingdom identified 136 cases with sufficient descriptive information [12]. Of
the 93 children who received long-term ventilation at home, 52 (56 %) used
NIPPV delivered by face or nasal masks, reflecting the preponderance of neu-
romuscular diseases in this subset of patients. Forty-three (53 %) of the 81
school-age children requiring NIPPV attended mainstream educational institu-
tions. The authors of this study advanced the position that providing NIPPV at
home is the “best option for meeting the child’s psychological needs and
enhancing quality of life.” Although this statement is probably correct, their
work and others like it did not glean from the patients themselves specific data
about emotional well-being as it relates to supported ventilation. Additional
studies are needed to flesh out the many psychological determinants of NIPPV
tolerance in children.
478 A.H. Gifford

Conclusion
In summary, most of the research about the psychological determinants of
NIPPV outcomes has been conducted in patients with ALS or other neuromus-
cular diseases. Significantly less inquiry has been undertaken in children and
older patients and in patients of all ages with ARF. Clinicians are sometimes
unaware of the extent to which patients with emotional and/or behavioral diffi-
culties need close support and guidance, regardless of whether these difficulties
arise from or are unassociated with the use of NIPPV.

Key Recommendations
• Discuss the anticipated benefits of NIPPV on HRQOL and potential draw-
backs of treatment, such as lifestyle adjustments, with patients at an early
stage of illness.
• Empower patients to have some degree of control over the apparatus and
settings as they become acclimatized to NIPPV.
• Elicit patient concerns about NIPPV using an empathetic tone and lan-
guage that is compatible with the level of education and comprehension of
the patient.
• Life experiences and future plans in older patients and anticipatory anxiety
in children play important roles in NIPPV acceptance and/or tolerance.

References
1. Yamamoto N, Fukuda Y, Shiba H, et al. Noninvasive positive pressure ventilation improved
refractory behavioral and psychological symptoms of dementia in an elderly adult with type 2
respiratory failure. J Am Geriatr Soc. 2012;60:1576–8.
2. Demuro JP, Mongelli MN, Hanna AF. Use of dexmedetomidine to facilitate non-invasive ven-
tilation. Int J Crit Illn Inj Sci. 2013;3:274–5.
3. Akada S, Takeda S, Yoshida Y, et al. The efficacy of dexmedetomidine in patients with nonin-
vasive ventilation: a preliminary study. Anesth Analg. 2008;107:167–70.
4. Takasaki Y, Kido T, Semba K. Dexmedetomidine facilitates induction of noninvasive positive
pressure ventilation for acute respiratory failure in patients with severe asthma. J Anesth.
2009;23:147–50.
5. Ramirez A, Delord V, Khirani S, et al. Interfaces for long-term noninvasive positive pressure
ventilation in children. Intensive Care Med. 2012;38:655–62.
6. Martin NH, Landau S, Janssen A, et al. Psychological as well as illness factors influence
acceptance of non-invasive ventilation (NIV) and gastrostomy in amyotrophic lateral sclerosis
(ALS): a prospective population study. Amyotroph Lateral Scler Frontotemporal Degener.
2014;15:376–87.
7. Ingadottir TS, Jonsdottir H. Technological dependency–the experience of using home ventila-
tors and long-term oxygen therapy: patients’ and families’ perspective. Scand J Caring Sci.
2006;20:18–25.
8. Torheim H, Gjengedal E. How to cope with the mask? Experiences of mask treatment in
patients with acute chronic obstructive pulmonary disease-exacerbations. Scand J Caring Sci.
2010;24:499–506.
57 Psychological Factors as Determinants of Noninvasive Continuous 479

9. Greenaway LP, Martin NH, Lawrence V, et al. Accepting or declining non-invasive ventilation
or gastrostomy in amyotrophic lateral sclerosis: patients’ perspectives. J Neurol. 2015;
262(4):1002–13.
10. Philippart F, Vesin A, Bruel C, et al. The ETHICA study (part I): elderly’s thoughts about
intensive care unit admission for life-sustaining treatments. Intensive Care Med. 2013;
39:1565–73.
11. Delord V, Khirani S, Ramirez A, et al. Medical hypnosis as a tool to acclimatize children to
noninvasive positive pressure ventilation: a pilot study. Chest. 2013;144:87–91.
12. Jardine E, O’Toole M, Paton JY, et al. Current status of long term ventilation of children in the
United Kingdom: questionnaire survey. BMJ. 1999;318:295–9.
13. Lemoignan J, Ells C. Amyotrophic lateral sclerosis and assisted ventilation: how patients
decide. Palliat Support Care. 2010;8:207–13.
14. Ando H, Chakrabarti B, Angus RM, et al. Experience of long-term use of non-invasive ventila-
tion in motor neuron disease: an interpretative phenomenological analysis. BMJ Support
Palliat Care. 2014;4:50–6.
15. Ando H, Williams C, Angus RM, et al. Why don’t they accept non-invasive ventilation?:
insight into the interpersonal perspectives of patients with motor neurone disease. Br J Health
Psychol. 2015;20(2):341–59.
16. Gay PC, Hess DR, Hill NS. Noninvasive proportional assist ventilation for acute respiratory
insufficiency. Comparison with pressure support ventilation. Am J Respir Crit Care Med.
2001;164:1606–11.
 Part VI
Hospital Critical Care Applications:
Critical Care Postoperative
Preoperative Noninvasive Ventilation:
Key Practical Recommendations 58
and Evidence

R. Zaimi, J. Bardet, and Patrick Bagan

Contents
58.1 Introduction ................................................................................................................. 483
58.2 Discussion and Analysis Main Topic .......................................................................... 484
Conclusion ............................................................................................................................. 486
References .............................................................................................................................. 487

Abbreviations

COPD Chronic obstructive pulmonary disease

FEV1 Forced expiratory volume on first second
NIV Noninvasive ventilation
VC Vital capacity

58.1 Introduction

The risk factors of postoperative respiratory complications can be dependent on the

patient, the anesthesia, or the surgery. Prevention therefore targets each of these fac-
tors when possible. Despite the efficacy of different prevention methods, pulmonary
outcomes after surgery still cause a high rate of postoperative morbidity and
mortality.
Noninvasive ventilation (NIV) has been used in the preoperative period and stud-
ies show its potential benefits in the preoperative prevention of pulmonary

R. Zaimi, MD • J. Bardet, MD • P. Bagan, MD (*)

Thoracic and Vascular Department, Victor Dupouy Hospital, Argenteuil, France
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 483

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_58
484 R. Zaimi et al.

complications. Therefore, further studies need to be performed to provide more

precision of NIV use before surgery, elucidate the selection criteria of the patients,
and prove its efficacy in a large cohort of patients.

58.2 Discussion and Analysis Main Topic

Pulmonary complications are the most frequent causes of postoperative morbidity

and mortality. The principal risk factors are age, smoking, lung diseases, location of
surgery, and hospital stay [1]. Several methods of prevention and treatment of these
complications have been used over the years and have proven their efficacy, includ-
ing oxygen therapy, aerosols, physiotherapy, and NIV. Usually, respiratory care has
been used in the postoperative period, in patients with asthma, and chronic obstruc-
tive pulmonary diseases.
Preoperative prevention of respiratory complications is crucial in decreasing
respiratory morbidity, especially in high risk patients. Patients requiring respiratory
rehabilitation can be selected by preoperative evaluation. Smokers should have a
smoking cessation program, as it is known that reducing smoking to 50 % or stop-
ping it decreases risk of bronchospasm and postoperative pneumonia when the pro-
gram is in effect at least 6–8 weeks before surgery [2].
Bronchodilator medication in chronic obstructive pulmonary disease (COPD)
patients increases forced expiratory volume in 1 second (FEV1) and vital capacity
(VC) and reduces airway resistance by 24 h, which is essential when surgery has to
be performed in short delays [2]. Chest physiotherapy performed 2–4 weeks before
surgery facilitates dealing with exercise in the postoperative period and reduces
risks of postoperative atelectasis and pneumonia. These methods are currently used
and can be associated with NIV in the preoperative period to improve the prevention
of respiratory postoperative morbidity.
Several studies have observed that NIV reduces infectious problems of invasive
ventilation and enhances comfort of the patient [3]. Its efficacy in acute respiratory
failure in obstructive diseases such as asthma and COPD and in acute cardiogenic
pulmonary edema is proven [3]. Its use has been extended to surgical fields by
studying its benefits in patients who develop respiratory failure after surgery.
Most reports of postoperative NIV were concerned with thoracic and upper
abdominal surgery, specialties with high rates of pulmonary complications. Major
changes in respiratory function occur when the site of surgery is closer to the dia-
phragm. In this case, the surgical site associated with anesthesia and postoperative
pain causes a diaphragmatic dysfunction and lung volumes decrease, leading to
postoperative hypoxemia and acute respiratory failure [1].
Several other studies have demonstrated the efficacy of NIV in various types of
surgery: it reduces extravascular lung water after cardiac surgery [3], improves lung
mechanics and oxygenation after coronary artery bypass surgery [3], decreases pul-
monary dysfunction following gastroplasty [3], reduces atelectasis, improves oxy-
genation, and decreases infectious risk in patients with postoperative hypoxemia
after abdominal surgery [4, 5].
58 Preoperative Noninvasive Ventilation: Key Practical Recommendations and Evidence 485

In parallel to the postoperative period, benefits of NIV were studied in preoperative

prevention of respiratory morbidity and mortality. Postoperative pulmonary complica-
tions are related to surgery and anesthesia, and they consist principally of atelectasis,
pneumonia, respiratory failure, and exacerbation of chronic lung diseases [6, 7]. The
identification of the risk factors for postoperative pulmonary complications is crucial
in defining the prevention modalities in the preoperative period. Smetana et al. [6], in
their systematic review, found that age, American Society of Anesthesiologists (ASA)
class II or greater, functional dependence, COPD, congestive heart failure, surgical
site, emergency surgery, prolonged surgery, and a low serum albumin level were high
risk factors of pulmonary postoperative complications. This may help to define the
group of patients who would benefit the most from preoperative NIV.
Few authors have studied prophylactic use of NIV. The selection criteria were
different; Bagan et al. [7] reported the contribution of preoperative rehabilitation
and NIV in patients with stage I and II lung cancer; inclusion criteria were FEV1,
diffusing capacity of the lungs for carbon monoxide (DLCO), and maximal oxygen
consumption (VO2 max) below the lower threshold or patients with high risk of
cardiac morbidity. Perrin et al. [8], in their study of preoperative noninvasive venti-
lation in patients undergoing lobectomy for lung cancer, fixed a FEV1 below 70 %
as an inclusion criterion. Benefits of the rehabilitation program were studied accord-
ing to respiratory criteria in both studies. Paleiron et al. [9], in their protocol of
preoperative noninvasive ventilation in pulmonary resection surgery, fixed respira-
tory parameters as inclusion criteria (FEV1/VC <70 %, FEV1 < 80 %, VC < 80 %,
CPT < 80 %), cardiac failure, and obesity.
With patients, FEV1 seemed significantly improved after a NIV program [7, 8],
and even allowed pulmonary resection in patients who had limited respiratory func-
tions [7]. For the same type of surgery (lung resection), modality of application of
preoperative NIV varied from one center to another; it was performed 2 weeks prior
surgery, for 1 h, 3 times a day in the Bagan et al. report [7], whereas in the series by
Perrin et al., NIV was performed 1 week prior to surgery, in at least five 1-h periods
per day [8]. In both reports, postoperative application of NIV was systematic. For
Paleiron et al. [9], NIV was required 1–2 weeks prior to surgery, twice a day for a 3-h
period, and postoperative application was performed only in case of complications.
Despite the differences in the manner of application of NIV in the perioperative
period, authors noted its benefits on the postoperative outcomes, such as decreasing
atelectasis and pneumonia [7] and reducing hypoxemia and pulmonary function
impairment [8]. In addition to its benefits on prophylactic perioperative application
in pulmonary resection, NIV use was also reported in prevention of pulmonary
complications in aortic aneurysm surgery in patients who were smokers (>40 pack-
ets per year) with COPD. In another report of Bagan et al. [10], preoperative NIV
was performed 2 weeks prior to surgery, 3 times a day, for a 30-min period, and,
comparatively, the rate of pulmonary complications and the mean hospital length of
stay in the intensive care unit were significantly lower in the NIV group. It was also
observed that postoperative application of NIV was made easier when patients were
prepared for it in the preoperative period, in fact, observance rate was higher after
surgery.
486 R. Zaimi et al.

In general, NIV seems to be efficient the in perioperative period. First performed

after thoracic and upper abdominal surgery, many authors demonstrated its benefits
in the postoperative period in various other surgeries. More recently, its indication
was extended to the preoperative period, especially in lung resection, and the few
reports show its efficacy. NIV is safe and well tolerated when applied correctly in
specific selected patients. Failure is usually due to side effects and also to intoler-
ance related to patient discomfort or claustrophobia. To optimize the use of NIV,
clinicians can adapt the adequate inflation pressure by making frequent readjust-
ments. Patient coaching and encouragement can also contribute to a reduction in the
failure rate [3].

Conclusion
The aim of NIV in the perioperative period is not to replace the other measures
of prevention of pulmonary risk factors; all methods of prevention should be
used in association to reduce pulmonary complications and improve postopera-
tive lung function. Smoking cessation, evaluation and equilibration of chronic
lung disease, congestive heart failure, and other comorbidities, and nutrition care
for patients with low serum albumin level should be always performed prior to
an operation, but this must not delay the surgery.
Although perioperative NIV was considered by several authors to have effective
benefits, its value in the preoperative period still needs to be demonstrated. To date,
few reports have evaluated preoperative NIV, and the cohort of patients was not
sufficient to prove with good evidence the positive impact of NIV. Furthermore,
selection criteria and modalities of application were different, depending on the
study and the local conditions of the different centers. A multicenter, standardized
study with a large cohort is required to assess the impact of preoperative NIV and
to precise to which group of patients it should be performed. In the future, the
report of Paleiron and colleagues about the evaluation of preoperative NIV prior to
pulmonary resection will perhaps provide more answers to the question of the effi-
cacy of preoperative NIV, as the study (PréOVNI GFPC 12–01) is controlled, ran-
domized, and multicentric.
The advances in research on preoperative NIV may decrease postoperative
pulmonary complications and also permit improvement of respiratory status in
patients who initially could not support a surgical treatment.

Key Major Recommendations

• We recommend preoperative NIV in patients undergoing abdominal and
thoracic surgery, with limited respiratory function (FEV1 <80 %).
• NIV should be performed at least 1 week before surgery, twice a day for a
1-h period. Postoperative NIV can be completed in case of respiratory
complications.
• Patients having preoperative NIV should be included in prospective trials
to set international parameters for its indication and application.
58 Preoperative Noninvasive Ventilation: Key Practical Recommendations and Evidence 487

References
1. Kenneth G, Torrington MD, Henderson C. Perioperative respiratory therapy (PORT). A pro-
gram of preoperative risk assessment and individualized postoperative care. Chest.
1988;93:946–51.
2. Delay JM, Jaber S. Préparation respiratoire des patients insuffisants respiratoires chroniques.
Presse Med. 2012;41:225–33.
3. Mehta S, Hill SN. Noninvasive ventilation. Am J Respir Crit Care Med. 2001;163:540–77.
4. Squadrone V, Coha M, Cerutti E, et al. Continuous positive airway pressure for treatment of
postoperative hypoxemia. JAMA. 2005;293:589–95.
5. Kindgen-Milles D, Buhl R, Gabriel A, et al. Nasal continuous positive airway pressure. A
method to avoid endotracheal reintubation in post operative high-risk patients with severe
nonhypercapnic oxygenation failure. Chest. 2000;117:1106–11.
6. Smetana GW, Lawrence VA, Cornell JE. Preoperative pulmonary risk stratification for noncar-
diothoracic surgery: systematic review for the American College of Physicians. Ann Intern
Med. 2006;144:581–95.
7. Bagan P, Ben Abdesselam A, Dakhil B, et al. Réhabilitation et VNI avant exérèse pulmonaire
chez les patients à haut risque opératoire. Rev Mal Respir. 2013;30:414–9.
8. Perrin C, Jullien V, Vénissac N, et al. Prophylactic use of noninvasive ventilation in patients
undergoing lung resectional surgery. Respir Med. 2007;101:1572–8.
9. Paleiron N, André M, Grassin F, et al. Evaluation de la ventilation non invasive préopératoire
avant chirurgie de résection pulmonaire. Etude pré OVNI GFPC 12–01. Rev Mal Respir.
2013;30:231–7.
10. Bagan P, Bouayad M, Benabdesselam A, et al. Prevention of pulmonary complications after
aortic surgery: evaluation of prophylactic noninvasive perioperative ventilation. Ann Vasc
Surg. 2011;1–3. doi:10.1016/j.avsg.2010.10.020.
Intraoperative Noninvasive Ventilation:
Key Technical and Practical 59
Recommendations

Luca Cabrini, Giovanni Landoni, and Alberto Zangrillo

Contents
59.1 Introduction ................................................................................................................. 490
59.2 Discussion and Analysis ............................................................................................. 490
59.2.1 NIV to Prevent ARF During Surgery in Patients with Respiratory
Diseases ......................................................................................................... 490
59.2.2 NIV to Treat ARF During Surgery................................................................ 491
59.2.3 NIV to Improve Ventilation in Healthy, Sedated Patients During Surgery ... 491
59.2.4 NIV to Facilitate Tracheal Intubation ........................................................... 491
59.2.5 Practical Recommendations .......................................................................... 492
Conclusions ............................................................................................................................ 492
References .............................................................................................................................. 493

Abbreviations

ARF Acute respiratory failure

COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
FOB Fiber-optic bronchoscopy
NIV Noninvasive ventilation
NPPV Noninvasive positive pressure ventilation

L. Cabrini, MD (*) • G. Landoni • A. Zangrillo

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Hospital, Vita-Salute
University, Via Olgettina 60, Milan 20132, Italy
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 489

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_59
490 L. Cabrini et al.

59.1 Introduction

Noninvasive ventilation (NIV) has traditionally been applied to treat acute respira-
tory failure (ARF) in pulmonary wards, intensive care units, and emergency depart-
ments [1]. New indications (such as prevention of ARF) and new settings
(pre-hospital and ordinary wards) have been proposed and evaluated. In particular,
NIV has been evaluated in the perioperative period to prevent or to treat postopera-
tive pulmonary complications and ARF. NIV proved effective in improving relevant
outcomes in surgical patients, especially when applied in high-risk patients in the
postoperative period [2].
Furthermore, a growing number of studies have reported the application of NIV
in the operating theatre. During surgery, NIV could be of help at least in four condi-
tions: to prevent ARF in patients in whom tracheal intubation must be avoided or
was refused, to treat ARF in the same patients, to improve ventilation in sedated
patients, or as an aid for tracheal intubation/airway management [3–6]. In the fol-
lowing section, the main indications and available evidence are reported. Relevant
technical and practical aspects will be addressed.

59.2 Discussion and Analysis

59.2.1 NIV to Prevent ARF During Surgery in Patients

with Respiratory Diseases

In patients with a very labile respiratory function, postoperative weaning from

mechanical ventilation and tracheal extubation can be difficult or even impossible.
On the other hand, avoiding intraoperative curarization and tracheal intubation
when feasible could prevent the risk of ARF and emergent tracheal intubation dur-
ing surgery, mainly due to the surgery itself, the anesthetic strategy (especially if it
includes sedation or spinal/epidural anesthesia), and the position (e.g., supine decu-
bitus in orthopnoic patients). As a consequence, when the risk of causing a perma-
nent dependency from mechanical ventilation is considered too high, an otherwise
indicated surgery can be denied by the surgeon or the anesthetist; similarly, the
patient can refuse to undergo surgery when facing this risk.
Noninvasive ventilation can be a logical solution when curarization is not abso-
lutely required. NIV can support the respiratory function, allowing maintenance of
the correct position. Moreover, NIV can counterbalance the respiratory depression
associated to sedative and local anesthetic agents.
So far, at least 16 papers, including 24 patients with severe respiratory limitation
(7 already on chronic NIV treatment), have reported the application of NIV to pre-
vent ARF during surgery [4, 5]. The procedures included ophthalmic, urologic, tho-
racic, orthopedic, neurosurgical, and cardiac interventions. ARF was prevented in
all cases. Face mask and nasal mask use was reported. NIV was mainly applied as
noninvasive positive pressure ventilation (NPPV), but continuous positive airway
pressure (CPAP) was also used.
59 Intraoperative Noninvasive Ventilation: Key Technical and Practical 491

59.2.2 NIV to Treat ARF During Surgery

At least six papers described the application of NIV in 86 patients undergoing

NIV during different kinds of surgery for an established ARF [4, 5]. In most
cases, general anesthesia tracheal intubation had been previously excluded due
to the poor patient conditions, including severe chronic obstructive pulmonary
disease (COPD) or neuromuscular diseases. Surgery was successfully com-
pleted in all cases. Moreover, five cases of vaginal delivery and six cases of
caesarean section in which NIV was used to treat ARF have been published.
All cases were completed uneventfully, although one mother (affected by cys-
tic fibrosis) died 10 days after the caesarean section due to pneumonia. NPPV
was almost always the applied NIV modality; most patients were already on
domiciliary NIV.

59.2.3 NIV to Improve Ventilation in Healthy, Sedated Patients

During Surgery

Deep sedation is frequently used in patients undergoing surgery without general

anesthesia. Respiratory depression and inability to keep the airway open may ensue
even in healthy patients if sedated [7]. NIV could help in improving spontaneous
ventilation and in keeping the airway open, similar to manual ventilation with an
oropharyngeal cannula in place. Four Japanese papers including more than 500
patients reported NIV use in the operating theatre with this aim, mainly during
orthopedic or gynecologic surgery under spinal/epidural anesthesia plus sedation
[4, 5]. Nasal mask and NPPV were always applied. In two cases, NIV failed to
maintain the airway open, so other tools were required. All other cases were suc-
cessful and no major complications were observed.

59.2.4 NIV to Facilitate Tracheal Intubation

Tracheal intubation in patients with difficult airway management can be chal-

lenging; the same is true in patients with an augmented risk of hypoxemia during
the procedure, for example, morbidly obese patients and patients with lung dis-
ease. In these cases, NIV can improve pre-oxygenation as compared with manual
ventilation before tracheal intubation [8–10]. Moreover, fiber-optic bronchos-
copy (FOB)-guided tracheal intubation through the nasal or oral route can be
performed during NIV to minimize the risk of hypoxemia. Different technical
solutions have been tested, but dedicated interfaces are also available. At least 10
studies including almost 300 patients evaluated NIV use with this aim, although
some studies were performed in the intensive care unit [3, 5]. Only one failure
was recorded, without any other complications. Two randomized controlled trials
compared NIV with laryngeal mask and oxygen therapy, and NIV was safer in
both studies.
492 L. Cabrini et al.

59.2.5 Practical Recommendations

Application of NIV in these risky settings requires accurate preoperative planning

[4, 5]. Patients should be informed and, whenever possible, trained to tolerate
NIV. Ethical aspects can be complex and must be addressed and documented before
surgery. All staff must be aware of the scope and limits of NIV, and cooperation
from the surgeon is required. Strict patient monitoring must be in place. If tracheal
intubation is an available option, all the equipment to perform it immediately must
be present. Preoperative patient preparation should be carefully optimized, if pos-
sible, to maximize ventilator function during surgery. Many sizes and models of
masks should be available to allow the patient to tolerate NIV for the entire proce-
dure. When NIV-aided tracheal intubation is performed, dedicated masks might be
the safest choice.
Finally, but most relevant, the staff must be highly expert in crucial aspects of
NIV, such as the choice of interface and the ventilatory setting. Patient’s tolerance
and NIV efficacy and safety strongly depend on the competence and experience of
the anesthesiologist. NIV use in this setting can be dangerous in untrained hands.

Conclusions
In surgical patients, a growing number of studies have suggested that NIV could
help to prevent ARF in patients in whom tracheal intubation must be avoided or
was refused, to treat ARF in the same patients, to improve ventilation in sedated
patients, or as an aid for tracheal intubation/airway management. In expert hands,
NIV proved effective and safe, with a very low failure rate and no complications.
Careful monitoring and cooperation among the staff are key elements. However,
so far, evidence came almost entirely from case series or observational studies.
Randomized controlled trials are required to better assess efficacy and safety of
NIV in the operating theatre.

Key Major Recommendations

• In the operating theatre, NIV help to prevent ARF in patients in which
tracheal intubation must be avoided or was refused, to treat ARF, to
improve ventilation in sedated patients, or as an aid for tracheal intubation/
airway management.
• NIV application in the operating room requires an expert and cooperative
team, careful patient preparation, strict monitoring, and a full array of
equipment.
• So far, few data of low quality are available on these novel indications.
Despite the promising results, more studies are required to assess NIV effi-
cacy and safety in the operating theatre.
59 Intraoperative Noninvasive Ventilation: Key Technical and Practical 493

References
1. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet.
2009;374:250–9.
2. Jaber S, Chanques G, Jung B. Postoperative noninvasive ventilation. Anesthesiology.
2010;112(2):453–61.
3. Cabrini L, Nobile L, Cama E, et al. Non-invasive ventilation during upper endoscopies in adult
patients. A systematic review. Minerva Anestesiol. 2013;79:683–94.
4. Cabrini L, Nobile L, Plumari VP, et al. Intraoperative prophylactic and therapeutic non-
invasive ventilation: a systematic review. Br J Anaesth. 2014;112:638–47.
5. Esquinas AM, Jover JL, Úbeda A, et al. Non-invasive mechanical ventilation in the pre- and
intraoperative period and difficult airway. en nombre del Grupo de Trabajo Internacional de
Ventilación Mecánica No Invasiva Anestesiología y Críticos. Rev Esp Anestesiol Reanim.
2015; pii: S0034-9356(15)00016-X doi:10.1016/j.redar.2015.01.007. Epub ahead of print on
pubmed.
6. Esquinas A, Zuil M, Scala R, et al. Bronchoscopy during non-invasive mechanical ventilation:
a review of techniques and procedures. Arch Bronconeumol. 2013;49:105–12.
7. Tobias JD, Leder M. Procedural sedation: a review of sedative agents, monitoring, and man-
agement of complications. Saudi J Anaesth. 2011;5:395–410.
8. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxygenation
before intubation of hypoxic patients. Am J Respir Crit Care Med. 2006;174:171–7.
9. Delay JM, Sebbane M, Jung B, et al. The effectiveness of noninvasive positive pressure venti-
lation to enhance preoxygenation in morbidly obese patients: a randomized controlled study.
Anesth Analg. 2008;107:1707–13.
10. Baumann HJ, Klose H, Simon M, et al. Fiber optic bronchoscopy in patients with acute hypox-
emic respiratory failure requiring noninvasive ventilation – a feasibility study. Crit Care.
2011;15:R179.
Use of NIMV in the Early Postoperative
Period: Key Practical Aspects and Clinical 60
Evidence

Emre Erbabacan

Contents
60.1 Introduction ................................................................................................................. 496
60.2 Discussion and Analysis Main Topic .......................................................................... 496
60.2.1 Cardiac Surgery ............................................................................................. 496
60.2.2 Thoracic Surgery ........................................................................................... 497
60.2.3 Abdominal Surgery ....................................................................................... 497
60.2.4 General Considerations ................................................................................. 497
Conclusion ............................................................................................................................. 499
References .............................................................................................................................. 499

Abbreviations

BIPAP Bi-level positive airway pressure

CPAP Continuous positive airway pressure
EPAP Expiratory positive airway pressure
FiO2 Fraction of inspired oxygen
ICU Intensive care unit
IPAP Inspiratory positive airway pressure
NIMV Noninvasive mechanical ventilation
PARF Postoperative acute respiratory failure
PEEP Positive end-expiratory pressure
PSV Pressure support ventilation

E. Erbabacan, MD
Department of Anesthesiology and Reanimation, Istanbul University, Cerrahpasa Medical
School, Istanbul, Turkey
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 495

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_60
496 E. Erbabacan

60.1 Introduction

Although the surgical and anesthesia techniques have advanced vastly in the past
decades, postoperative respiratory complications such as atelectasis formation,
related pneumonia, decrease in pulmonary volumes, diaphragm dysfunction, and
postoperative acute respiratory failure (PARF) are still major problems, especially
in high-risk patients. PARF is observed in 5–10 % of patients undergoing major
thoracic or abdominal surgery and is closely associated with outcome [1].
Anesthesia decreases muscle tone; surgery affects the thoracoabdominal
muscles and diaphragm. As the functional residual capacity decreases and clos-
ing capacity is unaffected, atelectasis occurs. In addition, pain related to the
surgical incision can cause hypoventilation. All these factors lead to hypox-
emia. [2]. Although noninvasive mechanical ventilation (NIMV) is used mainly
in the intensive care units (ICU), use of NIMV during the early postoperative
period in the recovery room has also become widespread to help reduce the
prevalence of PARF [3]. NIMV reduces the work of breathing, increases venti-
lation, and prevents atelectasis formation. Preventing the occurrence of PARF
can also prevent endotracheal reintubation, hemodynamic impairment, longer
hospital stay durations, increased costs, and, most importantly, higher morbid-
ity and mortality [4].
NIMV treatment should be considered in the early postoperative period when
dyspnea, respiratory rates over 25/min, and use of accessory muscles are observed
and when PaCO2 is above 45 mmHg, pHa is below 7.35, and PiO2/FiO2 values are
below 250. However, it should not be initiated in patients with hemodynamic insta-
bility, facial surgery, poor cooperation or Glasgow Coma Scale below nine, and
unstable arrhythmias.

60.2 Discussion and Analysis Main Topic

NIMV can be used in high-risk patients as a prophylactic measure and it also can be
used for curative purposes in patients with PARF to avoid intubation. Different stud-
ies support the efficiency of prophylactic and curative NIMV in different types of
surgeries.

60.2.1 Cardiac Surgery

Zarback et al. [5] used either continuous prophylactic nasal continuous positive
airway pressure (CPAP) for 6 h following extubation or standard postoperative oxy-
gen support in 500 patients undergoing cardiac surgery and showed that continuous
CPAP increased arterial oxygenation and reduced pulmonary complications and the
rate of ICU admission. Olper et al. [6] showed that postoperative bi-level positive
airway pressure (BIPAP) and CPAP are effective treatments in patients with devel-
oped respiratory failure following cardiac surgery.
60 Use of NIMV in the Early Postoperative Period 497

60.2.2 Thoracic Surgery

Thoracic surgery carries a higher risk for PARF compared with cardiac surgery. In
their randomized clinical trial, Perrin et al. [7] administered prophylactic preoperative
and postoperative NIMV treatment to patients with severe obstructions undergoing
lung resection. They found that oxygenation and lung volumes improved, whereas
hospital stay duration decreased compared with patients who received standard post-
operative treatment. In a study by Lefebvre et al. [8], 89 patients with both hypercap-
nic and hypoxemic PARF following lung resection surgery were administered early
curative NIMV in the ICU, and the overall success rate of NIMV was 85.3 %, con-
firming the feasibility and efficacy of NIMV in PARF following lung resection.

60.2.3 Abdominal Surgery

Abdominal surgery can result in diaphragm dysfunction, which can lead to PARF. As
the incision approaches the diaphragm, the dysfunction may worsen. Kindgen-
Milles et al. [4] showed that prophylactic use of CPAP with a pressure of 10 cmH2O
for 12–24 h improved oxygenation and shortened the ICU stay in patients undergo-
ing thoracoabdominal aortic surgery. In patients with PARF who underwent abdom-
inal surgery, Conti et al. [9] administered NIMV with helmet in one group and with
face mask in the other group and showed that NIVM improves PiO2/FiO2 and is an
alternative method to conventional ventilation.

60.2.4 General Considerations

As also noted in the studies mentioned above, use of NIMV in the early postoperative
period is effective in both preventing and treating PARF. It improves arterial oxygen-
ation and decreases intubation rate compared with standard medical therapy. An
issue that needs further debate is when, how, and how long to use it. In patients with
severe PARF where deep hypoxia (PiO2/FiO2 < 120), metabolic acidosis with base
excess higher than −5 mEq/L, or shock is present, and patient is not able to protect
the airways or clear the secretions, early endotracheal intubation should be consid-
ered instead of curative NIV therapy. On occasion, delaying endotracheal intubation
can also be life threatening. Instead of giving specific targets, patients’ preoperative
arterial blood gas samples and previous respiratory and cardiac state should be taken
into account in deciding the intubation need and ending NIMV therapy. However, an
uncooperative patient with values <150 even after 4 h of effective NIMV should be
considered as a candidate for invasive mechanical ventilation.
Although noninvasive ventilators, which administer CPAP or BIPAP modes, are
common in recovery rooms, some anesthesiologists and respiratory therapists also
prefer to use ICU ventilators in postoperative care units. The most common ventila-
tion modes are CPAP, BIPAP, assisted spontaneous breathing, or pressure support
ventilation (PSV) [10]. Some practitioners also consider CPAP with high-flow
498 E. Erbabacan

generators as an effective option. PSV mode has some advantages, mainly in patients
with nasogastric tubes because indented tidal volumes can be reached against the leak.
The aim should be the lowest inspiratory pressures or volumes that will improve
the oxygenation, decrease the respiratory rate, and not impair patient comfort. In
our practice, we use CPAP with high-flow generators and CPAP, BIPAP, and PSV
with different types of ventilators in the recovery room and postoperative care unit.
When using CPAP, we prefer starting with a pressure level of 5 cmH2O and increase
up to 10 cmH2O according to patient need and comfort. When using BIPAP, we start
with expiratory positive airway pressure (EPAP) values of 5 cmH2O and inspiratory
positive airway pressure (IPAP) values of 12 cmH2O. In PSV mode, we start with a
positive end-expiratory pressure (PEEP) level of 5 cmH2O and increase inspiratory
pressure 2 cmH2O above PEEP progressively to a maximum 15–20 cmH2O to reach
the desired tidal volumes of 6–8 ml/kg. PEEP is increased to a maximum value of
10 cmH2O if needed. but with the condition of preventing the increase of maximum
inspiratory pressure above 25 cmH2O, mainly in patients with anastomosis in the
upper digestive tract. The initial FiO2 level we use is 40 %. We increase FiO2 levels
up to 60 % to keep SpO2 levels above 95 % (90 % in patients with a severe chronic
obstructive pulmonary disease). If the NIMV administration is prophylactic, an
administration of 60 min is usually enough following extubation in the recovery
room. Arterial blood gas samples should be checked at 2-h intervals, and, if the need
occurs, NIMV treatment should be started again. If PARF is suspected or occurs,
NIMV for curative purposes should be started with the same settings and therapy
should be directed according to the response of the patient. In curative treatment, we
prefer using NIMV for 4 h initially and then for 60 min at 3-h intervals. Between the
NIMV treatments, patients breathe through a Venturi mask or nasal oxygen is used.
The length of the treatment is shortened when possible, aiming for an improved
oxygenation and metabolic state and comfort without NIMV. Our recommendations
are based on our clinical experience rather than a randomized clinical trial.
NIMV practitioners must share the justified concern of surgeons about damage to
a recent surgical anastomosis. Mainly in surgeries with upper gastrointestinal tract,
there is a higher risk related to indigested air and high peak inspiratory pressures.
Hence, extra care must be taken in these types of patients (mainly in patients under-
going esophagus and gastric resections and bariatric surgery). Although a peak inspi-
ratory pressure above 25 cmH2O is not recommended in using NIMV for PARF,
20 cmH2O should be chosen as a limit in these patients to prevent PARF and protect
the anastomosis. Use of nasogastric tubes should be used to monitor the air accumu-
lation in the gastrointestinal tract as an alarm to change the ventilator settings.
Different types of interfaces may be used during postoperative NIMV. The most suit-
able choice usually depends both on the characteristics of the patient and the surgery as
no advantage has been shown between the different types of masks [10]. Interface that
minimizes the leak and is the one that the patient is most comfortable with may be used.
However, in patients who have undergone facial surgery or have facial anomalies, use of
a helmet can be more effective and enable the use of NIMV. An important aspect of
NIMV with helmets is to use higher inspiration pressures compared with face masks.
60 Use of NIMV in the Early Postoperative Period 499

Conclusion
Abdominal, thoracic, and cardiac surgeries have negative effects on respiratory
function during the postoperative period. NIMV can be helpful in overcoming
these negative issues. In addition to its curative effect on postoperative respira-
tory failure, NIMV in the early postoperative period can also be used as a pro-
phylactic treatment in high-risk patients in recovery rooms and decrease ICU
admission.

Key Major Recommendations

• NIV can be used in high-risk patients as a prophylactic measure, and it also
can be used for curative purposes in patients with PARF to avoid
intubation
• The aim should be the lowest inspiratory pressures or volumes that will
improve oxygenation, decrease respiratory rate, and not impair patient
comfort.
• The NIV practitioners must share the justified concern of surgeons about
damage to a recent surgical anastomosis. A peak inspiratory pressure of
20 cmH2O should be chosen as a limit in these patients to prevent PARF
and protect the anastomosis.
• The most suitable choice of interface, mask or helmet, usually depends
both on the characteristics of the patient and the surgery.

References
1. Warner DO. Preventing postoperative pulmonary complications: the role of the anesthesiolo-
gist. Anesthesiology. 2000;92(5):1467–72.
2. Jaber S, De Jong A, Castagnoli A, et al. Non-invasive ventilation after surgery. Ann Fr Anesth
Reanim. 2014;33:487–91.
3. Glossop AJ, Shephard N, Bryden DC, et al. Non-invasive ventilation for weaning, avoiding
reintubation after extubation and in the postoperative period: a meta-analysis. Br J Anaesth.
2012;109:305–14.
4. Kindgen-Milles D, Müller E, Buhl R, et al. Nasal-continuous positive airway pressure reduces
pulmonary morbidity and length of hospital stay following thoracoabdominal aortic surgery.
Chest. 2005;128(2):821–8.
5. Zarbock A, Mueller E, Netzer S, et al. Prophylactic nasal continuous positive airway pressure
following cardiac surgery protects from postoperative pulmonary complications: a prospec-
tive, randomized, controlled trial in 500 patients. Chest. 2009;135:1252–9. doi:10.1378/
chest.08-1602.
6. Olper L, Cabrini L, Landoni G, et al. Non-invasive ventilation after cardiac surgery outside the
intensive care unit. Minerva Anestesiol. 2011;77:40–5.
7. Perrin C, Jullien V, Vénissac N, et al. Prophylactic use of noninvasive ventilation in patients
undergoing lung resectional surgery. Respir Med. 2007;101:1572–8.
8. Lefebvre A, Lorut C, Alifano M, et al. Noninvasive ventilation for acute respiratory failure
after lung resection: an observational study. Intensive Care Med. 2009;35:663–70.
500 E. Erbabacan

9. Conti G, Cavaliere F, Costa R, et al. Noninvasive positive-pressure ventilation with different

interfaces in patients with respiratory failure after abdominal surgery: a matched-control study.
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Anaesth. 2011;55:325–33.
Noninvasive Mechanical Ventilation
After Cardiac Surgery 61
Gökhan İnangil and Ahmet Ertürk Yedekçi

Contents
61.1 Introduction ................................................................................................................. 502
61.2 Cardiac Surgery and Acute Respiratory Failure ......................................................... 502
61.3 NIMV in the Postoperative Period .............................................................................. 503
Conclusion ............................................................................................................................. 506
References .............................................................................................................................. 507

Abbreviations

ARDS Acute respiratory distress syndrome

ARF Acute respiratory failure
CO Cardiac output
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
CPB Cardiopulmonary bypass
FRC Functional residual capacity
ICU Intensive care unit
LV Left ventricle
NIV Noninvasive ventilation

G. İnangil, MD (*)
Department of Anesthesiology and Reanimation, GATA Haydarpasa Training Hospital,
Istanbul 34668, Turkey
e-mail: [email protected]; [email protected]
A.E. Yedekçi, MD
Department of Anesthesiology and Reanimation, Girne Military Hospital, Girne,
Turkish Republic of North Cyprus
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 501

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_61
502 G. İnangil and A.E. Yedekçi

PEEP Positive end-expiratory pressure

PPV Positive pressure ventilation
PVR Pulmonary vascular resistance
RV Right ventricle
VC Vital capacity

61.1 Introduction

Major changes in respiratory function occur in all patients after cardiac surgery,
which has a relatively high incidence of postoperative acute respiratory failure.
Noninvasive ventilation (NIV) is used clinically in the treatment of cardiogenic pul-
monary edema, decompensated chronic obstructive pulmonary disease (COPD),
and hypoxemic respiratory failure. It is also used in the postoperative period to
improve gas exchange, decrease work of breathing, and reduce atelectasis, both as
preventive therapy and as a curative tool to avoid reintubation [1]. The aim of this
chapter is to review the effects of cardiac surgery and cardiopulmonary bypass
(CPB) on postoperative lung dysfunction and postoperative use of NIV after cardiac
surgery and discuss physiology and clinical practice with recommendations.

61.2 Cardiac Surgery and Acute Respiratory Failure

Patients undergoing cardiac surgery experience physiologic stresses from general

anesthesia, thoracotomy, CPB, surgical manipulation, diaphragm dysfunction, ster-
notomy, postoperative pain, fluid overload, and massive transfusion. Each of these
in itself may lead to pulmonary dysfunction, and acute respiratory failure (ARF)
may develop. These effects may worsen clinical prognosis in the presence of preex-
isting risk factors including severe COPD and congestive heart failure [2–4].
Almost all patients undergoing cardiac surgery have some degree of postoperative
lung dysfunction, with an incidence of about 25 %. While patients with adequate pulmo-
nary reserve can tolerate this dysfunction well, 2–5 % of patients are at risk of developing
severe lung dysfunction leading to increased morbidity, mortality, and prolonged hospi-
talization. Postoperative pulmonary complications such as pleural effusion (27–95 %),
atelectasis (16.6–88 %), and acute respiratory distress syndrome (ARDS) (0.5–1.7 %)
may occur after cardiac surgery, as cardiac surgery causes systemic inflammatory
response, which causes lung injury. There are several factors affecting pathogenesis of
postoperative pulmonary dysfunction after cardiac surgery and that are also related to the
patient’s preoperative pulmonary status and the degree of procedural stress [2, 5].
Factors related to general anesthesia include supine position, neuromuscular
block, altered chest wall compliance, acute functional residual capacity (FRC), and
vital capacity (VC) reduction, which results in ventilation-perfusion mismatch and
abnormal pulmonary shunt fraction. Opioids used commonly in cardiac anesthesia
practice reduce hypoxic and hypercapnic ventilatory response postoperatively. As a
result, a reduction of VC and FRC of lungs can lead to the onset of hypoxemia and
61 Noninvasive Mechanical Ventilation After Cardiac Surgery 503

atelectasis with increased work of breathing, which increases oxygen consumption

and myocardial work [3, 5].
Postoperative ARF risk is also increased in cardiac surgery when the internal mam-
mary artery used for grafting. Topical and systemic cooling, use of CPB, and surgical
manipulations during surgery are risk factors specific to cardiac surgery. The CPB pro-
cedure allows extracorporeal maintenance of both circulation and respiration during a
non-beating heart at hypothermic temperatures. It is the most likely factor for causing
ARF, with two different mechanisms. Whereas interruption of ventilation results in
collapsed lungs, causing atelectasis, interruption of pulmonary circulation results in
pulmonary ischemia, causing release of inflammatory mediators. Systemic inflamma-
tory response induces intrapulmonary aggregation of leukocytes and platelets, causing
further impairment of gas exchange, atelectasis, and increased pulmonary shunt frac-
tion. Because anticoagulation with heparin is essential for CPB after termination of
CPB, protamine is used for reversal. Administration of protamine is also associated
with systemic reactions and pulmonary hypertension. These many interrelated factors
cause ARF after CPB, especially with CPB time exceeding 120 min and massive trans-
fusion, and additional risk factors of prolonged ventilation and extubation failure post-
operatively are reported. Furthermore studies report that off-pump cardiac surgery is
associated with lower postoperative pulmonary complication rates [5].
Postoperative respiratory complications may be expected in the majority of
patients undergoing cardiac surgery, especially if CPB is performed, for the reasons
mentioned above.

61.3 NIMV in the Postoperative Period

After cardiac surgery, patients are transferred to the intensive care unit (ICU) under
anesthesia with ventilation support with an endotracheal tube. In this period, most
patients are under the effects of both anesthesia and curarization, and ventilatory
support plays important role because the operated heart and affected lungs work by
interacting with each other to supply oxygen demands of tissues. After arriving in
the ICU, the patient is warmed, allowed to awaken, and observed for hemodynamic
instability and surgical complications.
In recent experience, fast-track cardiac anesthesia has become the standard of
care, allowing rapid recovery and early tracheal extubation in many centers. About
25 % of cardiac surgical patients were extubated within 4 h of ICU arrival, and
about half within 8 h of ICU arrival. Hemodynamically stable patients with normal
left ventricular (LV) function preoperatively, with adequate rewarming and postop-
erative analgesia, may be considered for early extubation. About 8 % of patients
need prolonged mechanical ventilation, which is defined as >72 h following ICU
arrival, and about 7 % required reintubation after extubation [3].
Although cardiac function was improved with valve repair or replacement and
myocardial oxygen delivery improved with revascularization, cardiac performance
may be lower than the preoperative status for a period of time after CPB. This ven-
tricular dysfunction is usually a temporary state of contractile impairment and is
usually treated with positive inotropic agents. Generally, coronary revascularization
504 G. İnangil and A.E. Yedekçi

procedures are mostly performed with CPB, which is associated with myocardial
damage. It is difficult to predict the response of the heart to the altered loading condi-
tions after valve repair surgery. This critical period starts with the termination of CPB
and continues in the ICU. Patients with normal preoperative LV function are expected
to recover 90 % of baseline LV function by 4 h postoperatively in the presence of an
uncomplicated intraoperative course for revascularization procedures [3].
During invasive ventilation postoperatively, FRC is maintained by positive end-
expiratory pressure (PEEP), but, after extubation, FRC and oxygen transfer decrease
and derecruitment of alveolar units occurs with poor coughing, lack of respiratory exer-
cise, and pleural effusions. Thus, following extubation, it is essential to prevent atelec-
tasis and development of pulmonary complications and to maintain oxygenation [5, 6].
In the last 20 years, postoperative NIV has been evaluated as a preventive and
curative tool to avoid reintubation. NIV can be applied as continuous positive air-
way pressure (CPAP), a fixed level of positive airway pressure during whole respira-
tory cycle in spontaneously breathing patients, and as positive pressure ventilation
(PPV) whereby the ventilator supports the inspiratory effort of patient. This tech-
nique improves gas exchange, decreases work of breathing, and reduces atelectasis
while increasing patient comfort, allowing coughing and communication, and
reducing need for sedation. It also reduces costs and workload [1, 7, 8].
The available evidence suggests that CPAP and NIV could be effectively used to
improve oxygenation and reduce the incidence of complications such as pneumo-
nia, atelectasis, and the need for endotracheal intubation after abdominal and tho-
racic surgery, which results in greater length of stay, morbidity, and mortality. Both
conventional ventilators and portable ventilators can be used for this purpose [1, 8].
Cardiac surgery patients can benefit from NIV, restoring lung volumes and
reducing the work of breathing. Both PPV NIV and CPAP are frequently used in
clinical practice to prevent development of atelectasis and improve gas exchange
postoperatively after extubation. Studies have shown that the use of NIV may
increase lung aeration, increase FRC, and prevent collapse of alveolar units during
the postoperative period of abdominal surgery with radiologic imaging [1, 7].
Prophylactic nasal CPAP with pressures of 10 cmH2O following cardiac surgery
has also been shown to improve arterial oxygenation, reduce incidence of pulmo-
nary complications and reintubation rates, and reduce readmission rate to the ICU,
with better patient tolerance when used outside the ICU. It is also simple and inex-
pensive, as PEEP is generated by a PEEP valve and high-flow gas source, thus not
requiring a ventilator [6].
However, interventions to support the respiratory function may have both benefi-
cial and undesirable side effects inasmuch as pulmonary physiology and cardiac
function vary in spontaneously breathing and mechanically ventilated patients. ARF
may also develop as a result of the use of an improper ventilatory strategy, with high
volumes causing mechanical stress and biotrauma or inadequate PEEP levels that
lead to atelectasis and impairment of lung function. Atelectasis and the loss of func-
tional alveolar units has been accepted as the main pathophysiological mechanism
of postoperative hypoxemia and intrapulmonary shunt [5, 6].
PPV causes intrathoracic pressure changes, which can affect preload, afterload,
heart rate, and myocardial contractility because respiration and circulation are
61 Noninvasive Mechanical Ventilation After Cardiac Surgery 505

interdependent physiological processes. The use of mechanical ventilation in

affected lungs and an operated heart increases the complexity of this interaction.
Ventilatory strategies should be used with care because the tendency to cardiovas-
cular instability may occur easily in the early post-bypass patient [9].
Increased intrathoracic pressure during mechanical ventilation is also transmit-
ted to the heart chambers, pericardium, and to the vascular structures. PPV increases
both intrathoracic and right atrial pressures during inspiration, reduces venous
return, right ventricular (RV) preload, and cardiac output (CO). In the presence of
PEEP, these pressures remain above the atmospheric pressure throughout both
inspiration and expiration, and usually 8–10 cm H2O is enough to reduce CO
throughout the respiratory cycle [8].
Patients with LV failure and pulmonary edema are associated with an increased
preload and afterload. By limiting venous return and lowering LV afterload, PPV or
PEEP application can improve the CO. PEEP also provides alveolar patency against
alveolar edema and reduces risk of atelectasis. Consequently, an increase in intra-
thoracic pressure can increase CO in patients with LV dysfunction and reduced
ventricular compliance [9].
Because RV physiology is inadequate, tolerating afterload increases the effect of
PPV in patients with RV dysfunction can be inconvenient. Pulmonary vascular resis-
tance (PVR) is affected mainly by lung volumes and depends on the balance between
the vascular tone of alveolar and parenchymal vessels. Increases in PEEP or lung
inflation above FRC impair RV function by increasing PVR. As lung volume falls
from FRC toward residual volume, PVR increases again with terminal airway col-
lapse, leading to pulmonary hypoxic vasoconstriction. Thus, both PEEP application
and the cautious delivery of conservative tidal volumes should be considered for
preventing excessive increase in PVR and unfavorable circulatory effects, especially
in patients with postoperative RV failure or hypovolemia [8, 9].
Patients with asthma have increased resistance in the airways and hyperinflated
lungs. Special care should be taken to avoid excessive gas trapping. Mechanical
ventilation with smaller volumes and adequate expiratory time to reduce auto-PEEP
is essential [9, 10].
Before initiating NIV, possible surgical complications such as anastomosis leak-
age, hemorrhage, pneumothorax, and cardiac tamponade should be excluded.
Sufficient communication must be established with the patient so that the procedure
is well understood, as patient cooperation is essential. It is useful to describe this
procedure to patients with preoperative risk factors for postoperative ARF prior to
the operation. Preoperative prophylactic inspiratory muscle training is also advised
to improve respiratory muscle function and gas exchange. It is reported that training
has reduced the need for prolonged ventilatory support (>24 h) from 26 to 5 % [3].
Ventilator settings should be set at the lowest inspiratory pressures possible for
patient comfort while providing effective gas exchange. This may be achieved by
starting with only 3–5 cmH2O PEEP. After starting 3–5 cmH2O pressure support,
slightly increase the pressure support by 2–3 cmH2O, allowing patient to adapt the
mask and the ventilator until adequate expiratory tidal volume is achieved with
acceptable respiratory rate and arterial oxygenation. The PEEP could be increased
as needed to improve oxygenation without adverse hemodynamic effects up to
506 G. İnangil and A.E. Yedekçi

7–10 cmH2O with cautious monitoring. It is recommended not to exceed an insuf-

flation pressure (PPV + PEEP) of 20–25 cmH2O. Duration of NIV should be
30–45 min at 2–4 h intervals according to the patient’s clinical status to avoid facial
skin lacerations [1].
The Society of National Adult Cardiac Surgery Database Thoracic Surgeons
offers a customized model to predict prolonged ventilation. Factors assessing risk
status include age, gender, body surface area, presence of diabetes or renal failure,
chronic lung disease, cerebrovascular and peripheral vascular disease, and emer-
gency or unstable status preoperatively. Mild to moderate COPD was not assessed
as a major risk for postoperative morbidity and mortality as expected but rated as a
factor in many models. COPD patients, especially with age more than 75 years and
receiving steroids, have higher rates of pulmonary complications, atrial fibrillation,
and death. Obesity is indicated not to increase ARF postoperatively [3].

Conclusion
Pulmonary complications are frequent after cardiac surgery because many com-
plex mechanisms involve both surgical stress and systemic inflammatory pro-
cesses. Thus, protective ventilation strategies during surgery and CPB are essential
for preventing postoperative respiratory complications. Postoperative NIV
requires an experienced and trained team and continuous hemodynamic monitor-
ing. The effects of PEEP and PPV on the hemodynamic system should be care-
fully monitored so that tailored management of both the respiratory and
cardiovascular system can be obtained. Although NIV is shown to be effective in
preventing postoperative ARF, it remains controversial in the treatment of ARF.
Further randomized controlled studies should be performed to better identify the
patients who may benefit from NIV after cardiac surgery, and clinical guidelines
and protocols should be established [8, 11].

Key Major Recommendations

• Before initiating NIV, possible surgical complications such as anastomosis
leakage, hemorrhage, pneumothorax, and cardiac tamponade should be
excluded. Sufficient communication must be established with the patient
so that the procedure is well understood, as patient cooperation is
essential.
• Ventilator settings should be set at the lowest inspiratory pressures possible
for patient comfort while providing effective gas exchange. It is recom-
mended not to exceed insufflation pressure (PPV + PEEP) of 20–25 cmH2O.
• Patients should be monitored for ventilator asynchrony, mask intolerance,
gastric distension, and facial skin lacerations.
• Postoperative NIV requires an experienced and trained team and continu-
ous hemodynamic monitoring in critical patients. The effects of PEEP and
PPV on the hemodynamic system should be carefully monitored so that
tailored management of both the respiratory and cardiovascular systems
can be achieved.
61 Noninvasive Mechanical Ventilation After Cardiac Surgery 507

References
1. Jaber S, Chanques G, Jung B. Postoperative noninvasive ventilation. Anesthesiology.
2010;112:453–61.
2. Schreiber JU, Lancé MD, de Korte M, et al. The effect of different lung-protective strategies
in patients during cardiopulmonary bypass: a meta-analysis and semiquantitative review of
randomized trials. J Cardiothorac Vasc Anesth. 2012;26:448–54.
3. Higgins TL, Yared JP. Postoperative respiratory care. In: Kaplan JA, editor. Kaplan’s cardiac
anesthesia. Philadelphia: Saunders Elsevier; 2006. p. 1087–102.
4. Cabrini L, Plumari VP, Nobile L, et al. Non-invasive ventilation in cardiac surgery: a concise
review. Heart Lung Vessel. 2013;5:137–41.
5. Badenes R, Lozano A, Belda FJ. Postoperative pulmonary dysfunction and mechanical venti-
lation in cardiac surgery. Crit Care Res Pract. 2015;2015:420513.
6. Zarbock A, Mueller E, Netzer S, et al. Prophylactic nasal continuous positive airway pressure
following cardiac surgery protects from postoperative pulmonary complications: a prospec-
tive, randomized, controlled trial in 500 patients. Chest. 2009;135:1252–9.
7. Landoni G, Zangrillo A, Cabrini L. Noninvasive ventilation after cardiac and thoracic surgery
in adult patients: a review. J Cardiothorac Vasc Anesth. 2012;26:917–22.
8. Guarracino F, Ambrosino N. Non invasive ventilation in cardio-surgical patients. Minerva
Anestesiol. 2011;77:734–41.
9. Shekerdemian L, Bohn D. Cardiovascular effects of mechanical ventilation. Arch Dis Child.
1999;80:475–80.
10. Tonković T, Baronica R, Pavlović DB, et al. Effects of the mechanical ventilation on the car-
diovascular system. Signa Vita. 2014;9(Supp l):41–4.
11. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for
respiratory failure after extubation. N Engl J Med. 2004;350:2452–60.
Noninvasive Ventilation in the Post-
extubation Period: What Have 62
We Learned? Evidence and Key Practical
Recommendations

Christophe Girault, Gaëtan Beduneau,

and Dorothée Carpentier

Contents
62.1 Introduction ................................................................................................................. 510
62.2 Concerns with Weaning/Extubation from MV ........................................................... 510
62.2.1 Definitions ..................................................................................................... 510
62.2.2 Epidemiology and Impact of Weaning/Extubation Difficulties .................... 511
62.3 Role of NIV in the Post-extubation Period ................................................................. 511
62.3.1 Definitions and Objectives ............................................................................ 511
62.3.2 Physiopathological Rationale to Apply NIV in the Post-extubation Period . 511
62.3.3 Clinical Rationale to Apply NIV in the Post-extubation Period ................... 512
62.3.4 Results of NIV Use in the Post-extubation Period ........................................ 512
62.4 Limits of NIV Application in the Post-extubation Period .......................................... 515
Conclusion ............................................................................................................................. 516
References .............................................................................................................................. 516

Abbreviations

ARF Acute respiratory failure

COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
CRF Chronic respiratory failure
ICU Intensive care unit

C. Girault, MD (*) • G. Beduneau, MD

Department of Medical Intensive Care Medicine, Charles Nicolle University Hospital,
Rouen University, 1, rue de Germont, Rouen 76031, France
UPRES EA 3830-IRIB, Institute for Biomedical Research, Rouen University, Rouen, France
e-mail: [email protected]
D. Carpentier, MD
Department of Medical Intensive Care Medicine, Charles Nicolle University Hospital,
Rouen University, 1, rue de Germont, Rouen 76031, France

© Springer International Publishing Switzerland 2016 509

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_62
510 C. Girault et al.

MV Mechanical ventilation
NIV Noninvasive ventilation
PSV Pressure support ventilation
RCT Randomized controlled trial
SBT Spontaneous breathing trial

62.1 Introduction

Invasive endotracheal mechanical ventilation (MV) can lead to an excess of morbid-

ity and even mortality in intensive care unit (ICU) patients [1]. In this context, non-
invasive ventilation (NIV) has been developed for the management of the
post-extubation period, including weaning/extubation from MV and management
of post-extubation acute respiratory failure (ARF) [2, 3] (Fig. 62.1). Its results
should be distinguished according to the strategy used and populations involved.

62.2 Concerns with Weaning/Extubation from MV

62.2.1 Definitions

Weaning from MV is the entire process that allows passing more or less quickly
from MV to spontaneous breathing, or “de-ventilation,” leading to extubation.
Weaning failure is classically defined as failure of a spontaneous breathing trial
(SBT), whereas extubation failure is defined as the need for early reintubation

NIV in the post-extubation period

Indication Weaning/extubation management Post-extubation ARF management

Weaning difficulties Weaning (SBT) success Weaning/extub. success

Condition
(one or more SBT failure) Risk factors for extubation Secondary ARF

Reducing intubation Post-extub ARF / Post-extub. ARF treatment

Objective duration re-intubation prevention / re-intubation avoidance

NIV as Preventive Curative

Strategy Weaning/extub. (prophylactic) (rescue)
technique post-extub. NIV post-extub. NIV

Fig. 62.1 Strategies for using NIV in the post-extubation period (NIV noninvasive ventilation,
ARF acute respiratory failure, SBT spontaneous breathing trial, post-extub. post-extubation
62 Noninvasive Ventilation in the Post-extubation Period: What Have We Learned? 511

(48–72 h) after a planned extubation [1, 3]. Nevertheless, the definition of weaning
success or failure should also now consider the development of post-extubation NIV,
described as “weaning in progress” [1]. In this situation, the time needed to assess
weaning/extubation failure should probably be longer, possibly up to 7 days [4].

62.2.2 Epidemiology and Impact of Weaning/Extubation

Difficulties

MV can lead to many complications, including prolonged MV due to weaning/extu-

bation difficulties, delaying the extubation time, as well as risk of reintubation and its
own complications; all these situations may increase the patient’s morbidity-mortality.
Weaning/extubation difficulties may also be related to the underlying disease, and
chronic obstructive pulmonary disease (COPD) patients represent one of the main
high-risk populations [1, 3]. Hence, the ICU clinician should consider the feasibility
and potential issue of the weaning/extubation process as soon as possible, according
to the underlying status, to optimize the weaning/extubation conditions, limit the MV
duration, and eventually propose alternative techniques to conventional weaning.

62.3 Role of NIV in the Post-extubation Period

62.3.1 Definitions and Objectives

When applying NIV in the post-extubation period, the ICU clinician should consider
three different indications according to their respective objectives and reported results
in the literature [5] (Fig. 62.1). The objective of NIV used as a weaning/extubation
technique (to facilitate early liberation from MV) is to reduce MV duration (intuba-
tion) in patients exhibiting weaning difficulties (one or more SBT failures). The objec-
tive of NIV used for the management of post-extubation ARF is to avoid reintubation
according to two strategies: either to prevent the occurrence of post-extubation ARF
in patients at risk of extubation failure (i.e., preventive or prophylactic NIV strategy)
(Table 62.1), or to treat the occurrence of post-extubation ARF following an extuba-
tion (24–48 h) that most often is scheduled (i.e., curative or rescue strategy).

62.3.2 Physiopathological Rationale to Apply NIV in the Post-

extubation Period

Despite the absence of endotracheal prosthesis, NIV can meet the physiological
objectives of any type of mechanical ventilation (decrease in the work of breathing,
improvement in the breathing pattern, gas exchange, and dyspnea) with a good
hemodynamic tolerance [2, 6]. Therefore, NIV application in the post-extubation
period should consider the following main objectives: to counteract the different
physiopathological factors involved in the weaning/extubation failure, to help
512 C. Girault et al.

Table 62.1 Risk factors for Age ≥ 65 years

extubation failure based on
APACHE II score > 12 (day of extubation)
selection criteria of
randomized controlled trials Chronic respiratory disease (COPD)
[21–25] Heart failure
More than one comorbidity (other than heart failure)
More than one consecutive SBT failure
PaCO2 > 45 mmHg during SBT or following extubation
Inefficient cough
Post-extubation stridor
Morbid obesity (BMI ≥ 35 kg/m2)
COPD chronic obstructive pulmonary disease, SBT sponta-
neous breathing trial, BMI body mass index

physicians with difficulties in predicting results of the weaning/extubation process,

and, finally, to treat or prevent the occurrence of a post-extubation ARF, sometimes
not foreseeable. Finally, it should be kept in mind that NIV is as efficient and benefi-
cial when there is an underlying hypercapnia (PaCO2 > 45 mmHg), a frequent situa-
tion in cases of weaning/extubation failure [1, 3].

62.3.3 Clinical Rationale to Apply NIV in the Post-extubation

Period

Weaning/extubation from MV should be considered as a true challenge for the ICU

clinician. The clinical basis to apply NIV in the post-extubation period is closely
related to the epidemiological and physiopathological data involved in weaning/
extubation difficulties and failure, as mentioned above. In addition, efficacy and
clinical benefit of NIV in morbidity and mortality (avoiding intubation, reducing
nosocomial infections, and survival improvement) for the initial management of
hypercapnic ARF, leading to routine practice in severe acute exacerbation in COPD
patients [7], also represents a strong argument for using NIV in the post-extubation
period. In fact, the ICU clinician must find the optimal compromise between the
risks of unduly prolonged intubation and those of a too early weaning and extuba-
tion process [5]. Therefore, any strategy with the aim of reducing morbidity and
mortality of prolonged MV or reintubation appears relevant and should be devel-
oped to improve patient prognosis, particularly in those at high risk of weaning/
extubation failure [1, 3].

62.3.4 Results of NIV Use in the Post-extubation Period

62.3.4.1 NIV as a Weaning/Extubation Technique from Mechanical

Ventilation
Two noncontrolled clinical studies have previously suggested the feasibility of
NIV in this indication [8, 9]. Thereafter, six randomized controlled trials (RCTs)
that compared weaning with NIV to conventional weaning were conducted
62 Noninvasive Ventilation in the Post-extubation Period: What Have We Learned? 513

[1, 10–14] (Table 62.2). The results were in favor of NIV in five of the studies [4,
10–13] (Table 62.2). These RCTs have also been included in four systematic
reviews or meta-analyses [5, 15–17]. The large Cochrane systematic review (994
patients, 16 RCTs including the six previous English RCTs) stratified its results
according to the underlying respiratory disease (COPD or mixed chronic

Table 62.2 Characteristics of the main randomized controlled trials applying NIV in the post-
extubation period
Indications/ Population NIV modalities/ NIV Main
studies [ref.] Study type characteristics control group experience results
Weaning/extubation (control group: invasive conventional weaning or oxygen therapy)
Nava et al. Multicentric Selected CRF, PSV, FM, Cont, ≥5 years Favor
[10] (3 centers) COPD n = 50 ICUv/PSV NIV
Girault Monocentric Selected CRF, PSV or ACV, FM ≥5 years Favor
et al. [11] mixed or N, Int. ICUv/ NIV
(COPD = 51 %) PSV
n = 33
Ferrer et al. Multicentric Selected CRF, BiPAP, FM or N, ≥5 years Favor
[12] (3 centers) mixed Cont., SPEv/PSV NIV
(COPD = 44 %) or ACV
n = 43
Wang et al. Multicentric Selected CRF, BiPAP, FM, Int., – Favor
[13] (11 centers) COPD n = 90 SPEv/PSV or NIV
IMV
Prasad Monocentric Selected CRF, BiPAP, FM, – Similar
et al. [14] COPD n = 30 Cont., SPEv/PSV
Girault Multicentric Selected CRF, PSV or BiPAP, ≥10 years Favor
et al. [4] (13 centers) mixed FM, Cont., ICUv NIV
(COPD = 69 %) or SPEv/PSV or
n = 208 T tube/O2 #:
Post-extubation ARF prevention (control group: standard oxygen therapy)
Nava et al. Multicentric Heterogenous (CRF/ PSV or BiPAP, ≥10 years Favor
[21] (3 centers) COPD = 33 %) at FM or N, Int., NIV
risk of extubation ICUv. or SPEv/O2
failure n = 97
Ferrer et al. Multicentric Heterogenous (CRF/ BiPAP, FM, Cont, ≥10 years Favor
[22] (2 centers) COPD = 51 %) at SPEv/O2 NIV
risk of extubation
failure n = 162
Ferrer et al. Multicentric selected CRF BiPAP, FM, Cont, ≥10 years Favor
[23] (3 centers) (COPD = 70 %) at SPEv/O2 NIV
risk of extubation
failure n = 106
NIV noninvasive ventilation, COPD chronic obstructive pulmonary disease, CRF chronic respira-
tory failure, PSV pressure support ventilation ± positive end-expiratory pressure, ACV assist con-
trol ventilation, IMV intermittent mandatory ventilation, O2 standard oxygen therapy, BiPAP
bi-level positive airway pressure, T tube weaning with spontaneous breathing trials on T piece, FM
or N mask or nasal mask, Cont./Int. NIV applied continuously or intermittently, ICUv/SPEv NIV
applied with an ICU or specific dedicated ventilator, #: 3 groups of randomization = NIV versus
conventional weaning versus standard oxygen therapy
514 C. Girault et al.

respiratory failure (CRF)) [17]. Finally, available data show that NIV used as an
early weaning/extubation technique in medical populations, mainly COPD or CRF
patients, permits a significant decrease in the following outcome parameters:
weaning failure, risk of reintubation, duration of MV not related to weaning, ICU
and in-hospital length of stay, MV complications (nosocomial pneumonia, trache-
ostomy), and mortality. Furthermore, the benefit with regard to survival may be
more important, as there is an underlying COPD and hypercapnia
(PaCO2 > 45 mmHg) during the SBT. Early extubation relayed with NIV appears,
therefore, to be a reliable, safe, and beneficial weaning technique in difficult-to-
wean medical patients, mainly those with COPD.
Except for CRF patients, few clinical data are currently available for weaning/
extubation from MV with NIV. To our knowledge, only two older noncontrolled
studies have suggested the potential role of NIV in early extubation of surgical [18]
or trauma [19] patients. More recently, in a pilot study, an experienced team has
shown that NIV could also be useful in the early extubation of hypoxemic ARF
patients [20].

62.3.4.2 NIV and Management of Post-extubation ARF

Preventive Post-extubation NIV

Prior to the occurrence of post-extubation ARF, NIV should be considered earlier
after extubation, particularly in patients at risk for extubation failure, that is, for
reintubation (Table 62.1). Three large, prospective RCTs compared the use of pre-
ventive post-extubation NIV to standard oxygen therapy in mixed CRF or COPD
patients having passed a successful SBT but being considered at risk for extubation
failure [21–23] (Table 62.2). One other underpowered RCT included only 40
patients with severe COPD [24], and preventive post-extubation NIV has also been
applied in a case-control study conducted in obese patients [25]. Only the first two
RCTs [21, 22] have been pooled in a meta-analysis [26]. Overall, the findings show
that NIV, applied early following scheduled extubation in patients considered at risk
of reintubation, prevents the occurrence of post-extubation ARF, decreases the rein-
tubation risk, and may, therefore, improve the morbidity and mortality of patients.
Moreover, the benefit regarding mortality appears more relevant as there is an
underlying hypercapnia (PaCO2 > 45 mmHg) during or following the SBT. Therefore,
this hypercapnia may be considered as a simple objective and useful criteria for
clinicians to consider preventive post-extubation NIV, particularly in cases of under-
lying COPD.
In this indication, however, it is essential to research risk factors for extubation
failure, as preventive post-extubation NIV cannot be routinely applied to all intu-
bated patients. Indeed, several studies have shown that systematic use of preventive
NIV in nonselected populations could be only slightly [27] or not beneficial [28],
and even potentially deleterious [29], compared with standard oxygen therapy.
In surgical patients, interesting physiological results (oxygenation, diaphrag-
matic dysfunction, atelectasis) have been obtained with preventive post-extubation
NIV [30–32], but outcome results appear discordant in terms of benefit and the risk
62 Noninvasive Ventilation in the Post-extubation Period: What Have We Learned? 515

of post-extubation ARF and reintubation, length of stay, and survival, even in sur-
gical patients with COPD [33]. Of note, most of these studies used continuous
positive airway pressure (CPAP) rather than pressure support ventilation (PSV)
mode.

Curative Post-extubation NIV

Two observational clinical studies have suggested the feasibility and benefit of
NIV in this indication [34, 35]. Thereafter, two prospective RCTs comparing
curative NIV with standard oxygen therapy in a nonselected medical population
with post-extubation ARF were found negative [36, 37], the second even suggest-
ing that NIV could be deleterious in this indication, with an increase in ICU mor-
tality by delaying the reintubation time [37]. Consequently, these negative results
have dramatically limited the clinical research and, currently, no RCT is available
in this field, particularly in hypercapnic post-extubation ARF. Nevertheless, there
are some arguments that promising results could probably be still considered with
“curative NIV” in more selected population like patients with COPD: (1) the ben-
efit of NIV in the initial management of hypercapnic ARF in these patients; (2) the
increased use of NIV in the post-extubation period in epidemiological study, in
part in this particular indication [38]; and (3) the success rates of NIV used as a
“rescue” strategy in studies assessing NIV as a weaning/extubation technique (45
and 58 %) [4], in those evaluating preventive post-extubation NIV (63 %) [23],
and in the negative RCT by Esteban et al. (75 %) [37]. Therefore, further well-
conducted RCTs are still warranted in this indication. For instance, current results
should prompt clinicians to be cautious in using curative NIV routinely in the
management of post-extubation ARF in medical ICU patients so as not to delay
reintubation.
More studies have been conducted in surgical ICU patients in this indication. In
the post-operative period, curative post-extubation NIV has been shown to improve
oxygenation and decrease atelectasis, reintubation risk, pneumonia, length of stay,
and even mortality, according to the studies, after abdominal, cardiothoracic, and
solid organ transplantation surgery [15, 39].

62.4 Limits of NIV Application in the Post-extubation Period

To date, outside of the post-operative setting, all studies that have suggested or dem-
onstrated a benefit of post-extubation NIV have involved selected medical popula-
tions suffering from underlying chronic respiratory disease, mainly COPD [1,
10–14, 22, 23, 34, 35]. Current available data in this field suggest that NIV use in
the post-extubation period first requires knowledge of the principles of weaning/
extubation from MV and also NIV techniques and surveillance. The risk factors for
weaning/extubation failure must be known and underlying hypercapnia
(PaCO2 > 45 mmHg) during the weaning/extubation period should be looked for.
Finally, patients must be able to be reintubated without delay and at any time if
needed.
516 C. Girault et al.

Conclusion
Since the last consensus conferences on weaning and NIV [1, 2], the manage-
ment of weaning/extubation and post-extubation ARF with NIV can now be con-
sidered in ICU patients. Provided a sufficient acquired experience with NIV,
current data should prompt ICU physicians to apply post-extubation NIV in
selected medical populations, such as COPD patients, in cases of weaning diffi-
culties, or to prevent post-extubation ARF in high-risk patients. Hypercapnia
during or following SBT appears to be a useful criteria for decision-making in
these indications. Regarding curative post-extubation NIV, despite the lack of
formal current evidence, it can be used with cautious in some surgical popula-
tions and should probably be tested before reintubation in COPD patients. In all
cases, the clinician should keep in mind that post-extubation NIV needs rigorous
analysis of the risk/benefit ratio for the patient so as not to unnecessarily delay
reintubation.

Key Practical Recommendations

• When applying NIV in the post-extubation period, the ICU clinician
should consider three different strategies: NIV as a weaning/extubation
technique in difficult to wean patients (one or more SBT failure), NIV to
prevent post-extubation ARF in high-risk patients of extubation failure
(preventive or prophylactic NIV strategy), and NIV to treat the occurrence
of post-extubation ARF within 24–48 h of an extubation (curative or rescue
strategy).
• Post-extubation NIV should be reserved to centers with expertise in NIV
techniques.
• NIV can be used as a weaning/extubation technique in difficult-to-wean
CRF patients, mainly those with COPD.
• Preventive post-extubation NIV can be used after planned extubation in
patients considered at risk for extubation failure.
• Because of the lack of evidence, curative post-extubation NIV should not
be routinely used in the nonselected population. However, it could proba-
bly be applied in some surgical populations and patients with COPD.

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Perioperative Adverse Events
in Obstructive Sleep Apnea and Use 63
of Noninvasive Mechanical Ventilation:
Key Topics and Clinical Implications

C. Gregoretti, A. Braghiroli, G. Insalaco, A. Cortegiani,

and R. Corso

Contents
63.1 Introduction ................................................................................................................. 520
63.2 Preoperative Evaluation .............................................................................................. 521
63.3 Intraoperative Management ........................................................................................ 523
63.4 Postoperative Management ......................................................................................... 524
63.4.1 Role of Noninvasive Ventilation.................................................................... 524
63.5 Role of CPAP in the Perioperative Period .................................................................. 525
63.5.1 Indication for Perioperative CPAP Use ......................................................... 528
63.5.2 Possible Recommendations ........................................................................... 528
63.5.3 Indication for Perioperative NPPV Use ........................................................ 529
63.5.4 Possible Indications for NPPV ...................................................................... 529
Conclusion ............................................................................................................................. 530
References .............................................................................................................................. 530

C. Gregoretti (*)
Critical Care Medicine Department, “Città della salute e della scienza” Hospital, Torino, Italy
e-mail: [email protected]
A. Braghiroli
“S. Maugeri” Foundation, IRCCS, Dept Pulmonary Rehabilitation, Scientific Institute
of Veruno (NO), Veruno, Italy
G. Insalaco
National Research Council of Italy, Institute of Biomedicine and Molecular Immunology
“A. Monroy”, Palermo, Italy
A. Cortegiani
Department of Biopathology and Medical Biotechnologies (DIBIMED), Section of Anesthesiology,
Analgesia, Emergency and Intensive Care, Policlinico “P. Giaccone,” University of Palermo,
Palermo, Italy
R. Corso
Emergency Department, Anesthesia and Intensive Care Unit, “G.B. Morgagni” Hospital,
Forlì, Italy

© Springer International Publishing Switzerland 2016 519

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_63
520 C. Gregoretti et al.

63.1 Introduction

Obstructive sleep apnea (OSA) is a condition occurring in a portion of the general

population, unpredicted until a few years ago [1–3], and has been implicated as a
comorbid factor in various clinical conditions. OSA is the result of a complex
overlap of several features that compromise the ability of the upper airways to
maintain patency during sleep [4–6]. Although abnormalities of airway struc-
tures – such as enlarged tonsils and uvula, micrognatia, and wide neck circumfer-
ence linked to obesity – can be a facilitating factor, passive characteristics of the
upper airways, which compromise the ability of pharyngeal dilators to maintain
upper airway patency, can be blamed from less than a third of the total burden [4].
A partial (hypopnea) or total (apnea) obstruction of airflow leads to the same con-
sequence: local reflex, hypercapnia, acidosis, hypoventilation, and hypoxia stimu-
late arousal centers, leading to the resumption of wakefulness muscular tone.
These changes and an increased ventilatory effort overcome the obstruction, and
ventilation resumes [7]. This repetitive collapse of the upper airways may happen
cyclically many times per night. The arousals cause sleep fragmentation and sym-
pathetic activation, leading to peripheral vasoconstriction, increased systolic and
diastolic blood pressure, and a rise in heart rate, even as the cardiac output contin-
ues to fall after the reopening of the airway [8]. The associated intermittent
hypoxia causes systemic inflammation with a mechanism very similar to isch-
emia/reperfusion damage [9], causing cardiovascular consequences, decreased
cerebral blood flow and oxygenation [10, 11], and alteration of electric conduc-
tion (e.g., supraventricular and ventricular ectopy, sinoatrial and atrioventricular
block, atrial fibrillation) [12, 13]. Although obesity has been considered a classic
risk factor for OSA, today it is clear that the majority of OSA patients are non-
obese and the figures are so high that OSA is now considered more common than
asthma among adults.
A few studies have used polysomnography (PSG) to determine the frequency of
OSA in the surgical population [14–17]. In most instances, the frequency of OSA
was higher than the prevalence in the general population and varies with the type of
surgical intervention. For instance, bariatric surgery, which is addressed mainly to
super-obese patients, is burdened with a prevalence as high as 70 % [18], presum-
ably due to the high percentage of fat tissue in the neck. Finkel et al. [19] found that
24 % of surgical patients were at high risk based on a screening tool, but almost 4
out of 5 patients (81 %) had not been previously diagnosed with OSA.
Chronic untreated OSA is an independent risk factor for increased mortality in
the general population [20], but in the perioperative management it determines an
additional treatment due to upper airway collapsibility and associated comorbidi-
ties. Memtsoudis et al. [21] found a higher risk of pulmonary complications (PPCs)
in OSA patients after non-cardiac surgery. Flink et al. [22] reported a 53 % inci-
dence of postoperative delirium in OSA patients versus 20 % in non-OSA patients.
A meta-analysis concluded that patients with OSA undergoing non-cardiac surgery
have a higher incidence of postoperative O2 desaturation, respiratory failure, cardiac
events, and ICU transfers than those without OSA [23].
63 Perioperative Adverse Events in Obstructive Sleep Apnea 521

It is possible that the repetitive episodes of hypoxia occurring every night make
these patients less fragile according to the mechanism called “pre-conditioning” [9,
24], compensating for the higher incidence with a lower mortality. Indeed, one
study found that neither an OSA diagnosis nor suspected OSA were associated with
an increased 30-day or 1-year postoperative mortality [25]. These data were con-
firmed by Mokhlesi et al. [26, 27] in two cohorts of surgical patients who showed an
increased number of complications but failed to demonstrate an increase in
mortality.
As a matter of fact, this body of evidence associating OSA with adverse periop-
erative outcomes calls to implement perioperative strategies aimed at improving
safety. Various authors have suggested guidelines or clinical algorithms to improve
the perioperative care of these patients [28–30]. The aim of this chapter is to deter-
mine the effects of perioperative sedatives and anesthetics in surgical patients with
OSA, to suggest a diagnostic and therapeutic path, and to define the role of nonin-
vasive ventilation to prevent/treat the respiratory events.

63.2 Preoperative Evaluation

We can summarize the possible scenario the clinician has to face before surgery as
follows [31]:

1. Patients with a diagnosis of OSA who are receiving treatment.

2. Patients with OSA already diagnosed who are not receiving treatment yet, are
noncompliant with treatment, or with unsuccessful treatment.
3. Patients without a diagnosis of OSA who show an unexplained hypoxemia, poly-
cythemia, hypercapnia, pulmonary hypertension, or right- side heart failure.

These patients could have an undiagnosed, and often severe, OSA and represent
a large proportion of those who undergo surgery [32]. They often have the typical
symptoms of OSA, such as heavy snoring, witnessed apneas, unrefreshed sleep,
excessive daytime sleepiness and/or sleepiness at the examination, obesity, short
thick neck, tonsillar hypertrophy, and retrognathia. Although these clinical features
are suggestive of OSA, they are not reliable predictors of the presence or severity of
the disease [31], since only nocturnal monitoring allows a firm diagnosis and stag-
ing (Fig. 63.1). Obviously, the extended use of PSG or ambulatory monitoring for
preoperative screening is not feasible, but given the high prevalence of this condi-
tion and the high number of undiagnosed OSA patients, all surgical patients should
be screened for OSA. As a result, several tools have been developed to meet this
need for simple, economic, and sensitive bedside screening tests for the detection of
patients with suspected OSA [30, 33, 34]. The quickest and the simplest to use
seems to be the STOP Questionnaire [35], further implemented including questions
about additional risk factors for OSA such as body mass index (B), age (A), neck
circumference (N), and gender (G); the modified tool is called the STOP-BANG
Questionnaire (Fig. 63.2). The STOP-BANG questionnaire was originally
522 C. Gregoretti et al.

Snoring

YES NO

Excessive At least 2
Daytime other
Yes sleepiness symptoms NO

NO Yes

At least 1
At least 1 At least 1 other other
predisposing symptom + 1 symptom + 2
factor (*) predisposing Yes predisposing
NO Yes factor (*) NO factor (*)

NO
Yes

High Suspect Low Suspect

Upper airway soft tissue hypertrophy

PREDISPOSING FACTORS craniofacial abnormalities
BMI >25
Snoring
Observed apneas
Excessive daytime sleepiness (Ess >10)
Choking/Gasping
Nocturia
SYMPTOMS Depression
Irritability
Headache on awakening
Neurocognitive disorders
Erectile dysfunction
Decreased libido
Gastroesophageal reflux

Fig. 63.1 Diagnostic flow chart in patients with symptoms and clinical signs suggesting a sleep-
related obstructive sleep apnea. BMI body mass index, ESS Epworth Sleepiness Scale
63 Perioperative Adverse Events in Obstructive Sleep Apnea 523

S. Snoring (observed during sleep)

Do you snore loudly (louder than talking or loud enough to be heard through
closed doors)?
Yes No
T. Tiredness (in the daytime)
Do you often feel tired, fatigued or sleepy during daytime? Yes No
O. Observed apnea
Has anyone observed you stop breathing during your sleep? Yes No
P. Blood Pressure
Do you have or are you being treated for high blood pressure? Yes No
B. Body Mass Index
BMI more than 35 kg/m2? Yes No
A. Age
Age over 50 yr old? Yes No
N. Neck circumference
Neck circumference greater than 40 cm? Yes No
G. Gender
Gender male? Yes No

Fig. 63.2 The STOP-BANG Questionnaire. A high risk of sleep apnea is defined as a score of 3
or more; low risk of sleep apnea, a score of less than 3

developed in the surgical population but has been validated in various patient popu-
lations [36–38]. Patients with STOP-BANG scores 0–2 may be considered at low
risk, 3–4 at intermediate risk, and 5–8 at high risk of OSA [37]. Corso et al. [38]
showed that STOP-BANG scores indicative of a high risk of OSA confer a height-
ened risk of postoperative complications in patients undergoing elective surgery,
confirming its value to predict OSA severity and triage patients in the perioperative
period.

63.3 Intraoperative Management

Although patients with severe OSA seem to be at higher risk of perioperative com-
plications [39], careful observation and early intervention should be recommended
for patients with all grades of severity of sleep-disordered breathing [31, 40].
Various strategies can be employed to reduce the risks and avoid adverse outcomes.
Preoperatively, the use of anxiolytic premedication is not recommended [41]. There
is evidence that regional anesthesia (RA) is preferable over general anesthesia (GA)
whenever possible [42]. Regional anesthesia minimally affects respiratory drive, it
avoids the side effect of anesthetic agents, particularly on the arousal responses
524 C. Gregoretti et al.

during apneic episodes. Regional anesthesia may also avoid or reduce the need for
sedative drugs and opioids during the entire perioperative period. It has been well
established that the presence of OSA may lead to difficulties in airway management
both in terms of difficult mask ventilation and tracheal intubation [43–46]. Although
these findings do not imply that awake intubation is necessary in all patients with
OSA, prudence dictates that clinicians should have immediate access to alternative
techniques to secure the airway and ventilate the patient. There is evidence that
many anesthetic agents cause exaggerated responses in patients with sleep apnea.
Drugs such as thiopentone, propofol, opioids, benzodiazepines, and nitrous oxide
may blunt the tone of the pharyngeal musculature that acts to maintain airway
patency. The choice of induction and maintenance agents is probably not important,
although it would seem reasonable to avoid large doses of long-acting drugs. This is
true with both neuromuscular blocking agents and benzodiazepines. As a matter of
fact, anesthesia techniques using short half-life agents should be advised to avoid
any residual drugs in the respiratory system [47, 48]. Whenever the patient is extu-
bated, whether early in the operating room or later in the recovery room or in the
ICU, the patient should be fully awake [49]. Full recovery from neuromuscular
blockade should be proven by a neuromuscular blockade monitor. In the case of
difficult airways, guidelines for safe extubation should be followed [50].

63.4 Postoperative Management

The postoperative disposition of the OSA patient will depend on three main compo-
nents: invasiveness of the surgery, severity (known or predicted) of OSA, and
requirement for postoperative opioids. The American Society of Anesthesiologists
(ASA) guidelines suggest that all patients with known or suspected OSA who have
received general anesthesia should be monitored in the PACU (post-anesthesia care
unit). However, there are currently no evidence-based guidelines addressing the
optimal length of monitoring required in the PACU and the ASA recommendations
are difficult to adhere to, especially in the context of a community hospital [50].

63.4.1 Role of Noninvasive Ventilation

All patients with OSA or at high risk of having OSA are at possible risk of worsen-
ing to acute respiratory failure (ARF). In that case, the patient becomes incapable of
maintaining his/her normal value of arterial blood gases due to an acute lung and/or
respiratory pump failure. As mentioned above, a potential cause of immediate post-
operative hypoxia is upper airway obstruction causing apnea [51]. However, symp-
toms of OSAs can be exacerbated during the postoperative period as a result of
deterioration of the airway condition and rapid eye movement (REM) sleep rebound
caused by opioids predisposing to PPCs and adverse outcomes [51, 52]. Patients
with OSA after surgery are at high risk of PPCs, not only for adverse effects linked
to their underlying disease but also because of pulmonary complications – that is,
63 Perioperative Adverse Events in Obstructive Sleep Apnea 525

formation of atelectasis – which increase significantly the risk for pneumonia and
ARF [53]. The risk of respiratory events and PPC could be related to the type of
surgery [31], with the higher risk being related to upper airway surgery, for the con-
sequent edema of the pharyngeal district [54, 55], and thorax and upper abdomen
surgery, for consequent respiratory muscle impairment [56, 57]. Surgery of any type
can be burdened by a higher risk of complications in OSA patients [40, 58].
Noninvasive ventilation (NIV), as widely described in the chapters of the present
book, refers to the noninvasive delivery via an external interface through the patient’s
native airways (mouth, nose, or both) of intermittent positive pressure ventilation
(NPPV) or continuous positive airway pressure (CPAP). NIV may improve gas
exchange and reduce patient’s effort as invasive mechanical ventilation (IMV)
delivered via endotracheal tube or tracheostomy, but differently from IMV, NIV
does not interfere with patient native upper airways and, in particular, with glottis
function [59–62]. The aims of NIV are to partially compensate for the decreased
respiratory function by reducing the work of breathing; to improve alveolar recruit-
ment with better gas exchange (oxygenation and ventilation); and to reduce left
ventricular afterload, increasing cardiac output and improving hemodynamics. So it
may be an important tool to prevent (prophylactic treatment) or to treat (curative
treatment) acute respiratory failure avoiding intubation [53].
CPAP and NPPV have different physiological effects on a patient’s respiratory
system and hemodynamics that need some clarifications. Applying noninvasive
positive pressure without bypassing the upper airways (oronasal cavities, the phar-
ynx, the larynx including the epiglottis, glottis and subglottis, and upper esophageal
sphincter) introduces to the original equation of motion a new variable, namely the
pressure needed to overcome upper airway resistances [63]. The glottis, vocal cords,
and genioglossus change their activation and function in phase with inspiration and
expiration [64, 65]. This explains the results of Parreira et al. [66] demonstrating
closure of the glottis at increasing levels of assist pressure, causing a reduction of
the effective ventilation. Moreau-Bussière et al. [67] demonstrated that the activa-
tion of the thyroarytenoid muscle (a glottal constrictor) at high levels of noninvasive
pressure delivery impeded ventilation. As a matter of fact, the equation of motion
should be slightly modified from the original equation: Papp = Pel + Pres + intrinsic
positive end expiratory pressure (PEEPi), where Pel is the pressure needed to over-
come the elastic recoil of the lung (PL) and the chest wall (PCW) and Pres is the pres-
sure needed to overcome the lower airways resistances. During NIV, Pres is the
pressure needed to overcome both resistances of the lower (PLA) and the upper air-
ways (PUO), so Pres = (PUO + PLA).

63.5 Role of CPAP in the Perioperative Period

Unlike NPPV, during CPAP the pressure applied to the respiratory system is only
generated by the patient’s respiratory muscles (Papp = PMusc). In this case, transpul-
monary pressure, which is generated by the respiratory muscles, has to overcome
the upper airway resistances, which means that in patients with OSA CPAP is
526 C. Gregoretti et al.

effective on the lower airways only if it opens the upper airways [68, 69]. CPAP
maintains a constant pressure in the upper airways during inspiration and expiration
that acts as a pneumatic splint, allowing patency of the upper airway throughout the
respiratory cycle [70–72]. Beyond this, CPAP is aimed at improving arterial blood
gases and at decreasing work of breathing by:

1. Increasing functional residual capacity;

2. Stabilizing the chest wall distortion;
3. Improving left ventricular performance in chronic heart failure
4. Offsetting PEEPi (in patients with COPD).

CPAP is aimed at improving oxygenation through an amelioration of ventilation-

perfusion mismatch by promoting alveolar recruitment [73] and by maintaining the
alveoli open and by counteracting PEEPi alone in association with NPPV [74–76].
Although “genuine” CPAP is commonly used for mild hypoxemic ARF without
clear signs of respiratory muscle fatigue, the level of evidence of CPAP effective-
ness as a single mode of ventilation support in manifested ARF without cardiopul-
monary edema (CPE) is still low [77]. CPAP is also aimed at improving left
ventricular performance in chronic heart failure and is considered as a first-line
therapy in CPE [78–81. To understand the mechanism of CPAP in patients with
OSA it is necessary to focus on the complex mechanisms of heart-lung interaction
(Fig. 63.3). With each obstructive event and the associated hypoxemia and hyper-
capnia, there is a generation of a deep subatmospheric intrathoracic pressure (ITP)
due to the occluded airway with associated left ventricular afterload, increased pul-
monary artery pressures, decreased left ventricular compliance, and increased myo-
cardial oxygen demand [68]. The heart and lungs share a common intrathoracic

Loop of effects on the heart of OSA-

related negative intrathoracic pressure

IV septum
shift
Ø LV pre-load

Ødiastolic
filling
Ø Stroke Volume

Ø contractility

Ø BP syst e diast
Ø Coronary
perfusion

Fig. 63.3 Loop of effects on the heart of OSA-related negative intrathoracic pressure. BP blood
pressure, IV inter-ventricular, LV left ventricle, OSA obstructive sleep apnea
63 Perioperative Adverse Events in Obstructive Sleep Apnea 527

compartment. The heart feels as a “container” the modification of ITP generated

during changes of transpulmonary pressure during tidal breathing and accordingly
modifies both venous return to the heart and left ventricular (LV) ejection pressure
[82]. ITP decreases with inspiratory efforts and reducing right atrial pressure will
augment venous return and its pressure gradient. In turn, the increase in right ven-
tricular (RV) filling increases RV output, but dilating the right ventricle may theo-
retically cause the shift of intraventricular septum into the left ventricle, decreasing
its diastolic compliance and arterial pulse pressure (pulsus paradoxus) [82]. With
sustained decreases in ITP, as may occur with inspiration against an occluded air-
way (Mueller maneuver), this transient increase in venous return declines with the
increased blood flow to the left ventricle and the intraventricular septum returns to
its neutral position [83]. However, the decreasing ITP also increases LV afterload
because LV ejection occurs into an arterial circuit in which the surrounding pressure
is atmospheric pressure, not ITP [82]. LV afterload reflects the maximal wall stress
on the left ventricle during ejection. According to the Laplace theorem, LV wall
stress is a function of the product of the transmural pressure and the radius of cur-
vature of the left ventricle [82]. This increased afterload explains the development
of acute pulmonary edema in patients with severe airways obstruction or with OSA
with repetitive negative swings during deep sleep. The increasing wall stress causes
subendocardial ischemia and impairs LV systolic performance for a while, even
after the strain phase of the increases ITP is over.
The oxygen desaturation leads to an increase in pulmonary vascular resistance
due to hypoxic pulmonary vasoconstriction. In OSA patients, CPAP improves car-
diovascular performance and decreases heart failure by reducing the incidence of
both negative swings in ITP and arterial desaturation [84]. Interestingly, patients
with chronic heart failure (CHF) have a prolonged depression in LV performance
following ITP, even in the absence of hypoxemia [85]. Patients with CHF have
increased circulating blood volume. Thus, negative swings in ITP will induce a
greater increase in venous return than in healthy volunteers, suggesting that RV
dilation is the primary cause of depressed LV performance [82]. Theoretically, mea-
sures aimed at reducing circulating blood volume, but also aimed to decrease LV
afterload, would limit LV depression during OSA events [82].
Interestingly, Kaw et al. [86], in a study reporting the perioperative outcomes in a
large cohort of patients undergoing cardiac surgery, comparing those with and with-
out pulmonary hypertension (PH), found that 27 patients encountered significant
postoperative complications. Patient characteristics significantly associated with
postoperative mortality and morbidity on univariate analysis were affected by diabe-
tes mellitus (DM), OSA, and chronic renal insufficiency (CRI). CPAP, by reducing
the obstructive events, should also reduce the risk of increasing LV afterload.
CPAP is usually provided by a flow generator that delivers constant positive pres-
sure or by ventilators [53, 87–90]. Although the intrathoracic pressure delivered by
high-flow CPAP used in intensive care units cannot be compared to the unpredict-
able levels obtained with the devices commonly used for home treatment of OSA,
they are all able to maintain the upper airways open, preventing the occurrence of
obstructive events.
528 C. Gregoretti et al.

When CPAP is delivered by a bi-level turbine-driven ventilator, equal levels of

inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure
(EPAP)/positive end-expiratory pressure (PEEP) generate CPAP.

63.5.1 Indication for Perioperative CPAP Use

As mentioned above, CPAP remains the most effective therapy for OSA, acting as a
pneumatic splint to maintain upper airway patency. It appears that the consistent use
of CPAP therapy prior to surgery and immediately after surgery holds the best
potential for decreasing postoperative complications. However, CPAP does not pro-
vide adequate protection against central apnea, associated with the deterioration of
airway condition caused by opioids. Although there are no studies addressing this
topic, the use of NPPV with a back-up respiratory rate (i.e., spontaneous timed (ST)
mode or assisted pressure controlled ventilation (APCV)) may be advisable [91].

63.5.2 Possible Recommendations

• If possible, patients with OSA should be treated with at least 4–6 weeks of CPAP
before surgery, because an increase in pharyngeal size and a decrease in tongue
volume have been noted on magnetic resonance imaging after 4–6 weeks of
nasal CPAP therapy [92, 93].
• During induction of anesthesia, CPAP may be indicated to maintain upper air-
ways patency. Eastwood et al. [94] studied 25 patients undergoing minor surgery
on their limbs, and they found that patients who needed positive pressure to
maintain airway patency had more severe sleep-disordered breathing.
• During regional anesthesia, sleep-disordered breathing can occur after even
minor surgical procedures on the limbs [94].
• After extubation of the surgical patient. Extubation should be performed only when
the patient is sufficiently awake, showing an adequate muscle tone in the upper
airway, and should be monitored carefully to ensure that the upper airway remains
unobstructed. In patients with known OSA, nasal CPAP in the preoperative setting
should be started after extubation. Nasal or facial CPAP should be applied if airway
obstruction is persistent even after the correct positioning of the patient. The CPAP
pressure may need to be adjusted to obtain optimal efficacy. Patients who are unable
to sustain spontaneous breathing through an obstructed airway may need NPPV or
to undergo reintubation. In one investigation, patients with OSA who received nasal
CPAP before surgery and thereafter on an almost continuous basis for 24–48 h for
all sleep periods did not experience major complications [95]. Rennotte et al. [95]
found that CPAP, started before surgery and resumed immediately after extubation,
enabled the safe management of a variety of surgical procedures in patients with
OSA, as well as the use of sedative, analgesic, and anesthetic drugs without major
complications. Those who conducted the study recommended that every effort
63 Perioperative Adverse Events in Obstructive Sleep Apnea 529

should be made to identify patients with OSA and to perform CPAP therapy
before surgery. Monitoring may need to be continued in an intermediate care
setting for a longer period than that required in patients who do not have
OSA. Nursing the patient in the lateral position may be helpful for patients
whose airway obstruction is worse in the supine posture. Morbidly obese patients
are at elevated risk of perioperative pulmonary complications, including airway
obstruction and atelectasis. CPAP may improve postoperative lung mechanics
and reduce postoperative complications in patients undergoing abdominal sur-
gery. Neligan et al. [90] found that in 40 morbidly obese patients with OSA
undergoing laparoscopic bariatric surgery with standard anesthesia care who
were randomly assigned to receive CPAP via the Boussignac system immedi-
ately or 30 min after extubation (Boussignac group) or supplemental oxygen
(standard care group), the administration of CPAP immediately after extubation
maintains spirometric lung function at 24 h after laparoscopic bariatric surgery
better than CPAP started in the PACU.

63.5.3 Indication for Perioperative NPPV Use

Different from CPAP, the pressure applied to the respiratory system (Papp) may be
generated completely by the ventilator (Papp = PVent) or to a variable degree (depend-
ing from the operator setting) by the ventilator and the respiratory muscles
(Papp = PMusc + Pvent). NPPV is usually applied in the acute settings in pressure-
controlled mode both time cycled (APCV) or flow cycled (PSV).
PSV increases tidal volume while unloading the inspiratory muscles [73, 96, 97].
Furthermore, EPAP/PEEP added to PSV may counteract the effects of intrinsic
positive end-expiratory pressure (PEEPi) in COPD patients, further improving dys-
pnea, gas exchange, and inspiratory muscle effort. The majority of NIV studies in
ARF use PSV, and it is the most often used mode in COPD exacerbation [76].
There is a paucity of literature regarding the use of NPPV in the perioperative
patients.

63.5.4 Possible Indications for NPPV

• Patients with overlap syndrome

• During induction of anesthesia in difficult-to-ventilate patients. The combination
of PEEP plus NPPV may allow ventilation [90, 94].
• Patients undergoing upper airway surgery where postoperative swelling in the
upper airways may worsen OSA [54, 55]
• Nonrestricted postoperative opioid analgesia when CPAP become ineffective in
maintaining airway patency and alveolar ventilation
• All other indications for NPPV after surgery [31, 53, 91]
530 C. Gregoretti et al.

In patients with OSA with an overlap syndrome, as in other diseases, there could
be a rationale behind expiratory trigger adjustability (see cycling variable) to cope
with different respiratory mechanics and thus improve patient-ventilator synchrony;
the higher the value (i.e., 50 %), the lower the inspiratory time and vice versa.
Usually, COPD patients benefit from a value around 40 %, whereas restrictive con-
ditions benefit from lower values (i.e., 5–25 %) [98–100].
Pressure rise time (PRT) setting can also interfere as the expiratory trigger in mechani-
cal inspiratory time [101, 102]. Restrictive conditions usually benefit from medium-range
PRT and vice versa in obstructive conditions such as COPD [99, 101–105].
The set-up level of positive inspiratory pressure can be above (usually labeled as
PSV) or below the EPAP/PEEP level (usually labeled as IPAP), according to the
manufacturer. Some ventilators allow one to preset the set-up mode (above or below
PEEP/EPAP) before use, according to the operator’s choice [106]. In addition, some
turbine-driven ventilators allow one to set a back-up rate (the so-called ST mode).
APCV is an assisted-controlled, pressure-controlled, time-cycled mode where
the operator sets a preset respiratory rate and inspiratory time. Its use during NIV
may find a rationale in the presence of a large amount of leaks hindering expiratory
cycling in pressure-controlled, flow-cycled mode [107, 108], in very restrictive con-
ditions not supporting a flow-cycled breath, or when a back-up rate is needed.

Conclusion
Perioperative management of OSA is characterized by a variety of problems
requiring the joint effort of anesthesiologists, surgeons, and sleep experts.
Anesthesiologists have the opportunity to closely observe patients in the PACU
and can provide important information on where “the patient is going.” Appropriate
perioperative protocols are the best way to avoid perioperative complications
associated with this common syndrome. Last but not least, in daily practice, anes-
thesiologists need simple solutions to avoid “choking” the PACU and overcrowd-
ing the critical care environments [40]. However, well-designed studies on the
postoperative effect of CPAP and NIPPV in surgical patients with OSA are
required to determine its role in the postoperative management of these patients.

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 Part VII
Hospital Critical Care Applications:
Non Invasive Ventilation in Critically Cancer
Respiratory Failure and Noninvasive
Mechanical Ventilation in Cancer 64
Patients: Global Overview

S. Egbert Pravinkumar and Antonio M. Esquinas

Contents
64.1 Introduction ................................................................................................................. 539
64.2 Epidemiology of Hypoxemic ARF ............................................................................. 540
64.3 NPPV in Hypoxemic ARF .......................................................................................... 540
64.4 ARF in Immunosuppressed and Cancer Patients ........................................................ 541
64.5 NPPV in Cancer Patients ............................................................................................ 542
64.6 Indications and Contraindications .............................................................................. 543
64.7 Complications of NPPV.............................................................................................. 544
References .............................................................................................................................. 544

64.1 Introduction

Acute respiratory failure (ARF) is a common occurrence in cancer patients and is

associated with a high mortality rate. The role of NPPV in immunosuppressed,
hematological malignancies and solid tumors is an area that interests researchers
and clinicians alike. Several randomized controlled trials and systematic reviews
have confirmed the benefits of noninvasive positive pressure ventilation (NPPV) in
patients with exacerbation of chronic obstructive pulmonary disease (COPD).
Benefits achieved from NPPV in patients with COPD are largely a result of the
avoidance of invasive mechanical ventilation (IMV) and its complications, includ-
ing worsening of preexisting infections, morbidity and mortality, ventilator-
associated pneumonia (VAP), ventilator-associated lung injury, increased need for

S.E. Pravinkumar, MD, FRCP (*)

Department of Critical Care, Unit 112, UT-M.D. Anderson Cancer Center, Houston,
TX, 77030, USA
e-mail: [email protected]
A.M. Esquinas, MD, PhD, FCCP
Intensive Care and Noninvasive Ventilatory Unit, Hospital Morales Meseguer, Murcia, Spain

© Springer International Publishing Switzerland 2016 539

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_64
540 S.E. Pravinkumar and A.M. Esquinas

sedation resulting in prolonged ventilation, ventilator dependence, and upper air-

way complications related to endotracheal tube [1]. The use of NPPV in COPD with
hypercapnic ARF is no longer debated and is now considered as first-line interven-
tion before considering endotracheal intubation (ETI) and IMV.
The role of NPPV has been most recently studied in hypoxemic ARF. In this
group of patients, several studies have shown that NPPV not only reduced mechani-
cal ventilation and length of intensive care unit (ICU) stay but was associated with
fewer complications [2]. Inasmuch as one of the major benefits of NPPV is the
reduction of nosocomial infection, patients who are at high risk, such as those who
are immunosuppressed, have hematological malignancies or chemotherapy-induced
neutropenia, or have undergone organ transplantation, may be particularly likely to
benefit from NPPV. Guidelines published by the American Thoracic Society and the
Infectious Diseases Society of America in the management of nosocomial infec-
tions have provided high-grade evidence-based recommendations on the prevention
of nosocomial infections. The guidelines recommend the use of NPPV whenever
appropriate in the management of ARF and the avoidance of ETI and IMV when-
ever possible [3].

64.2 Epidemiology of Hypoxemic ARF

Hypoxemic ARF is the most common reason for ICU admission and ventilatory
support. An epidemiological prospective survey of 42 ICUs in Europe (26 univer-
sity and 16 non-university hospitals) looked at 1,337 admissions over a period of 3
weeks; 689 patients required ventilatory support [4]. ETI and IMV was the mode of
treatment in 581 patients (84 %) and NPPV was used as first-line treatment in 108
patients (16 %). The conditions precipitating ARF were hypoxemic ARF, including
acute cardiogenic pulmonary edema (55 %), coma (30 %), and hypercapnic ARF
(15 %). In this epidemiological study of patients who needed ETI and IMV, mortal-
ity rates were much higher in the hypoxemic ARF group than in hypercapnic ARF
(47 % vs 27 %). The 28-day hospital mortality was 41 % in those who needed ETI
and IMV, compared with 22 % in those who received NPPV (p < 0.001). The inci-
dence of VAP was 2 % in those who were successfully managed with NPPV com-
pared with 19 % in those who needed IMV (p < 0.002).

64.3 NPPV in Hypoxemic ARF

Studies in hypoxemic ARF using NPPV have shown varied results, and the outcome
is dependent on population selection. An increasing number of trials are emerging,
looking at the benefits of NPPV in selected groups with hypoxemic ARF. A system-
atic review of randomized controlled trials (RCTs) of NPPV use in hypoxemic ARF
shows convincing evidence that NPPV decreased the need for ETI and IMV [5].
NPPV also decreased the ICU length of stay and mortality. However, unlike hyper-
capnic ARF, hypoxemic ARF encompasses several diagnoses and comprises a
64 Respiratory Failure and Noninvasive Mechanical Ventilation in Cancer Patients 541

heterogeneous population. This heterogeneity was observed in multiple studies.

Hence, it would be misleading to conclude that NPPV is beneficial for all patients
with hypoxemic ARF. Notably, NPPV has had limited success in patients with acute
respiratory distress syndrome (ARDS) and lobar consolidation. Further study of
specific patient groups with hypoxemic ARF will provide insights into the manage-
ment of ARF using NPPV [5].
A well-conducted systematic review assessed the effects of NPPV in patients
with hypoxemic ARF not due to CPE [1]. The study looked at eight RCTs from six
countries that compared NPPV plus standard therapy versus standard therapy alone
in 366 patients. The study results are as follows: NPPV was associated with a sig-
nificantly lower rate of ETI and IMV (RR 0.23, 95% CI: 0.10, 0.35), reduction in
length of ICU stay of 1.9 days (95% CI: 1, 2.9), reduced ICU mortality of 17 %
(95% CI: 8, 26) and no statistically significant effect on hospital mortality. Based on
currently available evidence, routine use of NPPV for hypoxemic ARF is not rec-
ommended. However, based on a selected population analysis, NPPV should be
strongly considered for immunosuppressed and post-thoracotomy patients, and its
use in other groups should be carefully monitored to ensure beneficial effect.
A recent systematic review and meta-analysis of NPPV in an acute setting shows
favorable results in a wide variety of conditions [6]. NPPV was associated with a
reduction in mortality, especially when applied early in patients with COPD, pul-
monary edema, ARF of mixed etiology, and in postoperative ARF. NPPV also has
a favorable outcome in a selected patient population when used for prevention of
post-extubation ARF and for weaning from IMV. However, the benefits are noted
when NPPV is used earlier in the course of ARF.

64.4 ARF in Immunosuppressed and Cancer Patients

Hypoxemic ARF is a common occurrence in immunocompromised patients and in

those with malignancies, both hematological malignancies and solid tumors. It is
often a dreaded condition in cancer patients due to the high mortality related to ETI
and IMV. New types and modalities of chemotherapy and radiation therapy, circu-
lating pluripotent hematopoietic cell grafts, and bone marrow transplantation have
contributed to the increase in successful treatment of solid and hematologic malig-
nancies. However, these regimens may predispose patients to various life-threatening
complications, such as infection, hemorrhage, capillary leak syndrome, radiation
toxicity, and drug-related toxicity. The lung is the target organ most frequently
involved in these complications.
Inasmuch as most cancer patients have muscle fatigue, diffuse pulmonary infil-
trates, and depressed organ function and reserve as a result of treatment, they are
more vulnerable to rapid clinical deterioration and developing ARF. The most com-
mon type of respiratory failure in this group of patients is “lung” failure, although it
is not uncommon to see “ventilatory pump” failure as the cause of ARF. Several
studies have looked at the outcome of patients with acute myelogenous leukemia
and recipients of bone marrow transplantation who needed ETI and IMV [7]. Only
542 S.E. Pravinkumar and A.M. Esquinas

two variables have been shown to be independently associated with mortality of

cancer patients in the ICU, and neither the type of cancer (i.e., solid or hematologic
malignancy) nor the presence or absence of neutropenia was independently associ-
ated with mortality. The first independent predictor of ICU mortality is the severity
of the patient’s clinical condition on admission, as recorded by various scores, such
as the Simplified Acute Physiologic Score (SAPS I and SAPS II) and the Acute
Physiologic and Chronic Health Evaluation (APACHE II and APACHE III). The
second and “stronger” independent predictive factor of mortality is the need for ETI
and IMV, inasmuch as VAP and worsening of a preexisting infection are significant
complications in intubated patients.

64.5 NPPV in Cancer Patients

In a retrospective study of patients with solid or hematologic cancer admitted to the

ICU for ARF, the survival rate for cancer patients (n = 105) in the period 1996–1998
was significantly higher than those (n = 132) admitted between 1990 and 1995
(39 % vs 18 %, respectively; p = 0.0003). Multivariate analysis showed that the use
of NPPV in the later period was associated with a marked improvement in survival
[8]. Other studies using NPPV in cancer patients are summarized in Table 64.1.

Table 64.1 NPPV in cancer patients with hypoxemic ARF [7]

Study Patient population and intervention Outcome
Tognet Hematological malignancies (HM) ICU mortality: IMV vs NPPV:
1994 100 % vs 55 % significantly lower
mortality in NPPV group
Meduri Cancer patients with do-not-intubate Improved survival and hospital
1994 orders discharge in NPPV group
Solid tumor (ST) and HM
Conti Immunosuppressed and HM Improvement in blood gases and
1998 respiratory rate <1 h of NPPV –
68 % survived to discharge
Hilbert Fever, neutropenia, AHReF, HM CPAP avoided ETI in 25 % CPAP
2000 Intermittent CPAP success: all survived
Hilbert RCT, NPPV vs standard care (SC), fever, Reduced ETI, complications, ICU
2001 pulmonary infiltrate, immunosuppressed, death, and hospital death in NPPV
HM n = 52 group
Principi Pulmonary infiltrate, HM, mask vs helmet NPPV intolerance: helmet NPPV
2004 NPPV (0 %) vs mask NPPV (50 %)
Rocco Helmet NPPV vs mask NPPV, fever, Helmet NPPV vs mask NPPV ETI:
2004 immunosuppressed, organ transplant, 36 % vs 63 %
pulmonary infiltrates, HM ICU mortality: (31 %) vs (47 %)
Hospital mortality: 37 % vs 53 %
Meert Solid tumors and HM, NPPV for ICU survival: 57 %
2003 hypoxemic ARF ETI: 25 %
64 Respiratory Failure and Noninvasive Mechanical Ventilation in Cancer Patients 543

64.6 Indications and Contraindications

The immediate goals of NPPV therapy should be aimed at relieving patient symp-
toms and reducing the work of breathing. The intermediate goals should be to
improve and stabilize gas exchange and optimize patient ventilator comfort and
synchrony; the ultimate goal is avoidance of ETI and IMV. The success of therapy
depends on a highly motivated, committed, and knowledgeable team and careful
patient selection with the help of a well-structured NPPV guideline (Table 64.2).
Application of NPPV early in the process of ARF, along with careful and rigorous

Table 64.2 NPPV for cancer patients (©The University of Texas M.D. Anderson Cancer Center
NPPV guideline)
Eligibility criteria Contraindications
Clinical (all) Absolute (any)
Acute respiratory failure Cardiopulmonary arrest
Dyspnea pH < 7.25
Accessory resp. muscle use Upper airway obstruction
Paradoxical abdominal movement Facial trauma
RR > 25 Uncontrolled arrhythmia
Adequate airway protection Untreated SBP ≤ 90 mmHg
Adequate secretion clearance GCS ≤ 8
Undrained pneumothorax
Gas exchange criteria (any) Relative
FiO2 ≥ 0.60 Copious secretions
PaO2 ≤ 60 mmHg on room air Confusion/agitation
PaO2 ≤ 75 mmHg on any FiO2 GCS 9–13
PaO2:FiO2 < 200 Two or more organ failures
PaCO2 ≥ 50 Focal consolidation on CXR
pH > 7.30
Radiological criteria (any) Bowel obstruction
Pulmonary Infiltrates Recent facial/ upper airway/GI surgery
No pneumothorax Pregnancy
Thoracic surgery < 6 weeks

Blood gases 1 and 4 h post NPPV Blood gases 1 and 4 h Post NPPV
NPPV success NPPV failure
Clinical criteria (two or more) Clinical criteria (any)
Patient tolerates NPPV Patient intolerant to NPPV
Tolerates periods “off” NPPV Persistent dyspnea
Dyspnea reduced (score) RR ≥ 35
RR ≤ 35 Urgent need for ETI
Awake and alert Development of contraindications
GCS ≤ 8 (worsening mental status)
Gas exchange criteria (2 or more) Gas exchange criteria (any)
Improvement in ABG Failure of ABG improvement
FiO2 ≤ 0.7 and SpO2 > 92 FiO2 ≥ 0.7 and SpO2 ≤ 92
PaO2 ≥ 65 on FiO2 < 0.6 PaO2 ≤ 65 on FiO2 > 0.6
pH > 7.30 pH ≤ 7.30
PaO2:FiO2 ≥ 100 from baseline PaO2:FiO2 ≤ 100 from baseline
544 S.E. Pravinkumar and A.M. Esquinas

monitoring, is vital to the success of NPPV therapy. Other factors include location
and availability of a wide variety of interfaces to suit the patient’s morphological
and comfort needs.
NPPV failure should be identified early to avoid unnecessary delays in ETI and
IMV. For this reason, several centers offer NPPV therapy in the ICU, high-
dependency care units, and respiratory intermediary care units. Staffing ratios and
24-h physician coverage is also important in considering NPPV outside of the
ICU. Some of the predictors of NPPV failure include elevated ICU severity of ill-
ness scores, presence of ARDS or lobar consolidation, PaO2/FiO2 ratio <150 even
after 1 h of NPPV, pH− <7.30 on initiation, and failure of pH improvement in 1–2 h.

64.7 Complications of NPPV

Complications of NPPV are predominantly interface related, such as facial discom-

fort (30–50 %) and skin erythema (20–35 %). Less common (5–10 %) problems
include claustrophobia, nasal ulceration, and acneiform rash. Complications related
to pressure and flow include nasal congestion (20–50 %), sinus/ear pain (10–30 %),
nasal/oral dryness (10–20 %), eye irritation (10–20 %), and gastric distension
(5–10 %). Major complications such as aspiration pneumonia, hypotension, and
pneumothorax are less than 5 %.

Key Recommendations
• NPPV can be effectively used in the management of ARF.
• NPPV has several benefits, including decreased rates of ETI and IMV,
VAP, mortality, and ICU and hospital length of stay.
• Patient selection and early application are crucial.
• A highly committed and motivated team, along with a structured guideline,
is important to the success of NPPV.

References
1. Keenan SP, Sinuff T, Cook DJ, Hill NS. Does noninvasive positive pressure ventilation improve
outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care Med.
2004;32:2516–23.
2. Brochard L. Noninvasive ventilation for acute respiratory failure. JAMA. 2002;288:932–5.
3. American Thoracic Society/Infectious Diseases Society of America. Guidelines for the man-
agement of adults with hospital-acquired, ventilator-associated, and healthcare-associated
pneumonia. Am J Respir Crit Care Med. 2005;171:388–416.
4. Carlucci A, Richard JC, Wysocki M, Lepage E, Brochard L. SRLF Collaborative Group on
Mechanical Ventilation. Noninvasive versus conventional mechanical ventilation: an epidemio-
logic survey. Am J Respir Crit Care Med. 2001;163:874–80.
64 Respiratory Failure and Noninvasive Mechanical Ventilation in Cancer Patients 545

5. Keenan SP, Sinuff T, Cook DJ, Hill NS. Which patients with acute exacerbation of chronic
obstructive pulmonary disease benefit from noninvasive positive pressure ventilation? A sys-
tematic review of the literature. Ann Intern Med. 2003;138:861–70.
6. Cabrini L, Giovanni L, Oriani A, et al. Noninvasive ventilation and survival in acute care set-
tings: a comprehensive systematic review and metaanalysis of randomized control trials. Crit
Care Med. 2015;43:880–8.
7. Nava S, Cuomo AM. Acute respiratory failure in the cancer patient: the role of non- invasive
mechanical ventilation. Crit Rev Oncol Hematol. 2004;51:91–103.
8. Azoulay E, Alberti C, Bornstain C, Leleu G, Moreau D, Recher C, Chevret S, et al. Improved
survival in cancer patients requiring mechanical ventilatory support: impact of non-invasive
ventilatory support. Crit Care Med. 2001;29:519–25.
Noninvasive Versus Invasive Ventilation
in Patients with Hematological 65
Malignancies

Massimo Antonelli, Giorgio Conti,

and Giuseppe R. Gristina

Contents
65.1 Introduction ................................................................................................................. 548
65.2 Discussion ................................................................................................................... 548
Conclusion ............................................................................................................................. 551
References .............................................................................................................................. 552

Abbreviations

AIDS Acquired immune deficiency syndrome

ALI Acute lung injury
ARDS Adult respiratory distress syndrome
ARF Acute respiratory failure
CPAP Continuous positive airway pressure
GCS Glasgow Coma Score
ICU Intensive care unit
IMV Invasive mechanical ventilation
NIV Noninvasive ventilation
PaO2:FiO2 O2 arterial pressure to inspiratory O2 fraction
PEEP Positive end-expiratory pressure
PICU Pediatric intensive care unit
SAPS Simplified Acute Physiology Score
SOFA Sequential Organ Failure Assessment Score

M. Antonelli, MD • G. Conti, MD
Institute of Intensive Care and Anesthesiology, Catholic University of the Sacred Heart, Rome, Italy
e-mail: [email protected]; [email protected]
G.R. Gristina, MD (*)
Department of Intensive Care Unit S.Camillo, Forlanini Hospital, Rome, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 547

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_65
548 M. Antonelli et al.

65.1 Introduction

In the last two decades, the survival of patients with hematological malignancies has
improved because of new chemotherapeutic regimens, bone marrow transplanta-
tion, peripheral stem cell rescue, and better supportive measures [1]. At the same
time, several investigators have underlined a worsened outcome for granulocytope-
nic patients requiring supportive therapies in the intensive care unit (ICU), particu-
larly those undergoing tracheal intubation and invasive mechanical ventilation
(IMV) for acute respiratory failure (ARF) [2–9], a common complication of hema-
tologic malignancies (and of their treatment), often affected by a poor prognosis.
This significantly increased risk of death [3, 5] results from the combination of
several different conditions: lung damage induced by opportunistic infections, the
direct toxicity of chemotherapy on lung tissue, and complications directly generated
by endotracheal intubation. Based on sound evidence on this topic, a consensus
exists regarding the use of early noninvasive ventilation (NIV) with the aim of
reducing the endotracheal intubation rate and the associated infectious complica-
tions [10–12].

65.2 Discussion

Tognet et al. [13] were the first to report interesting clinical results with the intermit-
tent application of NIV in patients with hematologic malignancies; 6 out of 11
patients with ARF were successfully treated with NIV through a face mask, with
different levels of pressure support and positive end-expiratory pressure (PEEP).
Four years later, Conti and colleagues [14] evaluated the use of NIV delivered via
nasal mask in 16 consecutive patients with hematological malignancies and
ARF. Fifteen out of 16 patients showed a clear-cut and sustained improvement in
gas exchange: PaO2:FiO2 after 1 h of treatment increased from 87 ± 22 to 175 ± 64,
and continued to improve in the following 24 h (p<0.01). Two patients failed to
improve, were intubated, and subsequently died from sepsis. Three other patients
died from complications unrelated to ARF. Eleven patients were discharged with
stable spontaneous breathing after a mean length of ICU stay of 4.3 ± 2.4 days.
In 2001, a prospective, controlled, randomized trial evaluated NIV to avoid intu-
bation and associated complications in immunocompromised patients admitted to
the ICU for hypoxemic ARF (PaO2:FiO2 < 200), fever, and lung infiltrates [15].
Fifty-two patients (30 patients with hematological malignancies and neutropenia,
18 who received immunosuppressant to prevent rejection after solid organ trans-
plantation, and 4 with acquired immune deficiency syndrome (AIDS)) were ran-
domized to receive conventional treatment (oxygen plus aggressive medical therapy)
or NIV plus conventional treatment. NIV was intermittently administered with a
face mask. NIV significantly reduced the rate of intubation (46 % vs 77 %, p = 0.003)
and serious complications (50 % vs 81 %, p = 0.02). Both ICU (38 % vs 69 %,
p = 0.03) and hospital mortality (50 % vs 81 %, p = 0.02) were also significantly
reduced.
65 Noninvasive Versus Invasive Ventilation in Patients with Hematological Malignancies 549

These findings show that the early intermittent application of NIV ameliorates
the prognosis of immunocompromised patients admitted to the ICU. It is interesting
to note that the most impressive results were obtained in the subgroup of patients
with hematological malignancies and neutropenia, suggesting a safe, effective, and
extensive clinical application of NIV under these conditions.
Ten years later, thanks to advances in equipment technology with performing
interfaces and optimal staff training, Squadrone et al. [16] investigated the effective-
ness of continuous positive airway pressure (CPAP) delivered through a transparent
plastic helmet in the hematological ward, to treat acute lung injury (ALI) and pre-
vent ICU admission and IMV in 40 hematological patients in the early stages of
ARF. Patients were randomized to receive oxygen (N = 20) or oxygen plus CPAP
(N = 20). At randomization, PaO2:FiO2 in the control group was 282 ± 41 and in
CPAP group was 256 ± 52 mmHg. Fewer patients who received CPAP needed ICU
admission for mechanical ventilation compared with controls (4 vs 16 patients;
p = 0.0002). CPAP reduced the relative risk of developing need of ventilatory sup-
port to 0.25 (95 % CI; OR 0.10–0.62). Among patients admitted to ICU, the intuba-
tion rate was lower in the CPAP group than in the control group (2 vs 14 patients;
p = 0.0001). CPAP reduced the relative risk for intubation to 0.46 (95 % CI: RR
0.27–0.78). These findings suggest that early use of CPAP on the hematological
ward in patients with initial derangement of gas exchanges is safe and prevents a
worse evolution to ALI requiring IMV in the ICU.
More recently, a large retrospective analysis of prospectively collected data
between 2000 and 2006 evaluated 1,302 patients with hematological malignancies
admitted with ARF to 158 Italian ICUs [10]. This was the largest report published
so far. Only 274 (21 %) of the patients were treated on admission with NIV. Compared
with patients receiving IMV since the onset of respiratory failure, those initially
treated with NIV were generally younger, with lower Simplified Acute Physiology
Score (SAPS) II scores and higher Glasgow Coma Score (GCS). ALI was signifi-
cantly more frequent in the NIV group, but the prevalence of adult respiratory dis-
tress syndrome (ARDS) in the two groups was similar. The IMV and NIV groups
also had similar rates of organ failure after ICU admission (434 out of 1028 (42 %)
vs 120 out of 274 (44 %); p = 0.64). Analysis of patients with ALI or ARDS revealed
no significant correlation between mortality and type of ventilation (OR 0.77, 95 %
CI 0.45–1.30; p = 0.32), although the IMV subgroup had significantly higher SAPS
II scores (means: 58 = 19 % vs 49 = 17 % in the NIV group, p <0.0001). The NIV
group exhibited significantly lower ICU and hospital mortality, shorter ventilation
periods, and shorter ICU lengths of stay than the IMV group. In a multivariate
analysis, after adjustments for group-assignment propensity scores, an initial NIV
trial was associated with lower hospital mortality than immediate recourse to IMV
(OR 0.73, 95 % CI 0.53–1.00; p = 0.05). Independent risk factors for mortality
included ARDS, septic shock, stroke (on or after ICU admission), and higher SAPS
II scores but not neutropenia (OR 1.411; 95 % CI 0.945–1.2106; p = 0.0926). More
than a half (54 %) of the NIV patients never required endotracheal intubation (suc-
cessful NIV subgroup). In the other 127 (46 %), NIV was replaced with IMV after
3 ± 3 days (unsuccessful NIV subgroup). These two subgroups were similar in terms
550 M. Antonelli et al.

of age, underlying diseases, organ failure rates at ICU admission, and reasons for
ICU admission, but ALI/ARDS was almost twice as common in the unsuccessful
NIMV subgroup (42 % vs 24 %; p = 0.002). Multivariate analysis identified two
major risk factors for NIV failure: baseline illness severity reflected by SAPS II
scores (OR 2.012, 95 % CI 1.006–4.026; p = 0.048); and ALI/ARDS at admission
(OR 2.266, 95 % CI 1.346–3.816; p = 0.002). This study indicates that (1) ARF
patients with hematological malignancies may represent <1 % of total ICU admis-
sions; (2) NIV is attempted in only around 20 % of these cases; (3) when successful,
NIV is generally associated with shorter mechanical ventilation periods and ICU
stays, less severe post-admission infections, and lower ICU and hospital mortality;
(4) after adjustment for the propensity to receive NIV ab initio, the noninvasive
approach is significantly associated with lower mortality than immediate IMV; and
(5) roughly half of the NIV trials failed, and the patients had to be intubated .
In 2014 and 2015, Azoulay et al. [17, 18] published two studies related to the
prognostic impact of ARDS and neutropenia on critically ill patients with malignan-
cies. The data in the first study derived from a cohort of 1,004 patients (86 % with
hematological malignancies and 14 % with solid tumors), 44.2 % of whom had
neutropenia. According to the Berlin definition [19], 252 (25.1 %) patients had
mild, 426 (42.4 %) moderate, and 326 (32.5 %) had severe ARDS due to infectious
causes of various origin. Mortality was 59, 63, and 68.5 %, respectively (p = 0.06).
Three hundred and eighty-seven patients (38.6 %) received NIV, 276 (71 %) subse-
quently required endotracheal ventilation. Hospital mortality was 64 % overall, with
a mortality rate higher for severe ARDS. Solid tumors, primary ARDS, and later
admission period were associated with lower mortality. Risk factors for higher mor-
tality were allogeneic bone-marrow transplantation, higher Sequential Organ
Failure Assessment (SOFA) score, NIV failure, severe ARDS, and invasive fungal
infection. This study showed that, in cancer patients, 90 % of ARDS cases were
related to documented infection, including one-third due to invasive fungal infec-
tions. Mortality decreased over time (from 89 % in 1990–1995 to 52 % in 2006–
2011; p <0.0001), but NIV failure was associated with increased mortality. The
same group of researchers published a second study aimed at assessing the hospital
outcome in 289 critically ill neutropenic cancer patients admitted into the ICU, and
at identifying the risk factors for unfavorable outcome. Overall, 131 patients died
during their hospital stay (hospital mortality 45.3 %). Four variables were associ-
ated with a poor outcome: allogeneic transplantation (OR 3.83; 95 % CI 1.75–8.35),
need for IMV (OR 6.57; 95 % CI 3.51–12.32), microbiological documentation (OR
2.33; CI 1.27–4.26), and need for renal replacement therapy (OR 2.77; 95 % CI
1.34–5.74). Ninety-one patients received NIV as first-line intervention for their
ARF, but NIV was not a protective factor for mortality.
In the neonatal and pediatric setting, CPAP has been extensively used across the
world. Over the last few years there has been a dramatic increase in the utilization
of NIV for respiratory support in a variety of pediatric settings. NIV has been
recently proposed also in pediatric patients affected by hematological malignancies
complicated by hypoxemic ARF of various origins. Piastra et al. [20] successfully
treated 23 consecutive immunocompromised children with NIV for early ARDS
65 Noninvasive Versus Invasive Ventilation in Patients with Hematological Malignancies 551

through a face mask or a helmet. Admission parameters and severity scores between
NIV responders and nonresponders were not different, with early and sustained
PaO2:FiO2 improvement in almost 80 % of all cases. Thirteen out of 23 patients
(54.5 %) avoided intubation and were discharged from the pediatric intensive care
unit (PICU); 10 patients required intubation: 2 of them survived while 8 patients
died. NIV responders showed a PICU and hospital mortality significantly lower
(p <0.001), and their length of stay in the PICU stay was shorter (p = 0.03), with a
lower heart and respiratory rate at the end of treatment (p <0.001 and p = 0.048,
respectively).
These positive results were not confirmed in a later “real-world” study where the
authors reported a higher NIV failure (requiring intubation and IMV) and mortality
rate in hematological patients with ARF [21]. However, in the same study, a delay
from the time of ICU admission and the start of NIV was associated with an
increased risk for failure, which was also an independent predictor for worse out-
come. These data suggest the need for an early NIV administration but also for a
sensitive trigger to identify those patients who do not rapidly respond to NIV and
need a prompt endotracheal intubation.
The Society of Critical Care Medicine charged a task force with producing rec-
ommendations for the use of NIV as a palliation in patients with terminal diseases
and malignancies [22]. The task force suggested use of NIV for patients who choose
to forego endotracheal intubation. NIV should be applied after careful discussion of
the goals of care, with explicit parameters for success and failure, by experienced
personnel, and in appropriate health-care settings.
A similar approach was analyzed by Azoulay et al. [23]. They concluded that,
although NIV is increasingly used as a palliative strategy to alleviate the symptoms
of respiratory distress in dying patients, more research is needed aimed at identify-
ing benefits from palliative NIV that are not related to patient comfort, a good end-
of-life process, or family and caregiver satisfaction.

Conclusion
The survival of patients with hematological malignancies requiring intensive
therapy has improved over the years, even though the mortality rate remains
close to 50 %. These results were achieved thanks to a better understanding of
the mechanisms, improvements to specific therapies, and a more sophisticated
approach to organ failures. ARF represents the most frequent complication in
these patients. The current management of critically ill hematological patients
with ARF admitted to the ICU includes a trial of NIV to avoid endotracheal intu-
bation. However, failure of NIV may lead to an increased mortality.
Knowledge of the specific features and accurate selection of hematological
patients to receive NIV are key factors for a good outcome and prognosis. A
skilled team and the correct equipment are also two cornerstones for the optimal
use of NIV in and out of the ICU. When clinicians chose this strategy, early
application and careful evaluation of the potential risks and patient comfort are
essential. This is crucial in the pediatric setting. Parameters such as GCS score,
aim of NIV, severity of infection, and hemodynamic stability can help in the
552 M. Antonelli et al.

selection of potential candidates to receive NIV. Patients undergoing allogeneic

hematopoietic stem cell transplantation frequently require ICU admission for
transplant-related toxicities. In these patients, whose prognosis is often poor, a
careful balance between the costs and risks/benefits NIV and IMV is still needed.

Key Major Recommendations

• Patients with hematological malignancies should receive NIV early at the
onset of hypoxemia (PaO2:FiO2).
• Patients with hematological malignancies receiving NIV should be
promptly intubated when there is no improvement in gas exchange after
the first hours of NIV.
• Risk factors for higher mortality such as allogeneic bone-marrow trans-
plantation, severely modified SOFA, severe ARDS, and invasive fungal
infection should induce on invasive ventilation ab initio.
• The option to deliver NIV in pediatric patients with hematological malig-
nancies is safe provided that the risks/benefits ratio is closely respected.
• In patients with hematological malignancies asking to forgo invasive ven-
tilation or at the end of their life, NIV may dignify the last days, allowing
a peaceful death and reducing also the psychological stress of the family
and caregivers.

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Noninvasive Mechanical Ventilation
in Critically Ill Patients 66
with Hematological Malignancy:
Flow Chart, Evidence, and Key Practical
Recommendations

Pieter Depuydt

Contents
66.1 Introduction ................................................................................................................. 555
66.2 Analysis and Discussion ............................................................................................. 556
66.2.1 Does NIV Improve Outcome in Hematology Patients with ARF? ............... 556
66.2.2 Timing and Place of NIV .............................................................................. 557
66.2.3 Diagnostic and Therapeutic Approach in NIV-Treated Patients
with Hematological Malignancy ................................................................... 557
66.2.4 Avoiding NIV Failure .................................................................................... 558
66.2.5 NIV in Patients with Hematological Malignancy
with a Do-Not-Intubate Order ....................................................................... 558
66.2.6 NIV in Patients with Hematological Malignancy at the End of Life ............ 559
Conclusion ............................................................................................................................. 559
References .............................................................................................................................. 561

66.1 Introduction

The number of patients with hematological malignancy admitted to the intensive

care unit (ICU) is increasing, and there are multiple reasons for this trend. The life
expectancy of patients with hematological malignancy is often no longer prohibitive
for ICU referral, as therapeutic advances have led to higher cure rates, more extended
remission periods, and prolonged survival, even in the presence of active disease.
Longer survival also increases the time-at-risk for developing a life-threatening
infection or other complication of the disease or its therapy. In addition, new che-
motherapeutic or immune-modulating agents and treatment regimes have expanded
the spectrum of toxicities and complications. Critical care itself, in general and for

P. Depuydt, MD, PhD

Department of Intensive Care, Ghent University Hospital, De Pintelaan 185,
Ghent 9000, Belgium
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 555

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_66
556 P. Depuydt

these patients in particular, has progressed considerably as well, and reluctance to

admit these patients to the ICU has largely disappeared. A multicenter prospective
study documented an encouraging 39 % hospital survival rate for critically ill
patients with hematological malignancy [1].
Acute respiratory failure (ARF) is the main reason for ICU referral of patients
with hematological malignancy and is an independent predictor of mortality, espe-
cially when mechanical ventilation is required. Noninvasive mechanical ventilation
(NIV) has been advocated as the preferable first-line form of ventilatory support in
these patients when there is no condition requiring immediate intubation (such as
hemodynamic instability, lack of free airway, or imminent respiratory arrest). Over
the last decade, the use of NIV in patients with hematological malignancy has
increased in everyday practice, mirroring the expanding use of NIV in general ICU
patients over a range of types and causes of respiratory failure. In recent years,
experience has been gained with the use of NIV in patients with ARF and a do-not-
intubate order. This chapter summarizes the recent evidence and controversy regard-
ing the optimal use of NIV in patients with hematological malignancy.

66.2 Analysis and Discussion

66.2.1 Does NIV Improve Outcome in Hematology Patients

with ARF?

Enthusiasm for the use of NIV in patients with hematological malignancy is based
on the results of a small number of randomized controlled trials (RCTs) and a larger
number of observational studies. A pilot RCT in hypoxemic patients with underly-
ing immunosuppression showed lower intubation rates and mortality in patients
assigned to the NIV arm compared with the oxygen-only arm. This sparked the
initial interest in NIV for patients with hematological malignancy, though it did
itself not include patients with malignancy [2]. In a landmark study from 2001,
Hilbert et al. [3] made a similar observation of lower intubation rates and mortality
in immunocompromised patients assigned to NIV early in the course of ARF, com-
pared with treatment with oxygen only; this study included a significant number of
patients with hematological malignancy. In an Italian study of patients with hema-
tological malignancy with incipient ARF in the ward, patients who were random-
ized to CPAP compared with oxygen required referral to the ICU and intubation less
often [4]. In contrast, in a German RCT in allogeneic bone marrow transplant recip-
ients with ARF, NIV did not prevent intubation and had no effect on survival [5].
Apart from these RCTs, a number of observational studies found lower mortality
rates in patients with hematological malignancy treated with NIV compared with
invasive mechanical ventilation; this finding was not consistent over all studies,
however [6–8]. In the interpretation of observational data, one must account for the
fact that an association observed in a nonrandomized trial may not reflect causality
and that, in a real-life setting, patients eligible for a trial of NIV are different from
patients who are immediately intubated. In addition, higher survival rates in patient
66 Noninvasive Mechanical Ventilation in Critically Ill Patients 557

categories such as “successful NIV” or “NIV only” may overestimate the benefit of
NIV as such categorization biases toward a favorable outcome by excluding patients
in whom NIV failed. More recent studies have attempted to correct for confounders
that obscure the relationship between NIV and outcome. A study that adjusted the
association of NIV and mortality for the probability of receiving NIV by a propen-
sity score found a protective effect associated with the use of NIV [6]. The authors
of the OUTCOMEREA study group applied a marginal structural model to adjust
for the effects of time-dependent covariates in a large dataset of patients treated with
first-line NIV as compared with invasive ventilation only, collected over 15 years.
An association between lower mortality and NIV was only present in patients with
acute-on-chronic respiratory failure (mainly chronic obstructive pulmonary disease
(COPD) patients) but not in patients with new-onset ARF, regardless of whether
they had underlying immunosuppression [7].

66.2.2 Timing and Place of NIV

In the observational data, the success rate of NIV ranges from 25 to 54 %, but is consis-
tently lower than the NIV success rate in the RCTs (54–90 %). Apart from a more care-
ful patient selection in the RCTs, this difference is likely attributable to a different timing
of NIV. In the RCTs, all patients received NIV from the onset of ARF, whereas the time
between ARF onset and the initiation of NIV was highly variable (and frequently
unknown) in the observational data. Late referral to the ICU, late initiation of NIV, more
profound hypoxemia, and additional organ failure have been associated with increased
risk for NIV failure. As such, the potential benefit of a trial of NIV is likely optimal
when patients are selected in an early stage of ARF. Based upon the available data, NIV
should definitely not be used as a last resort to avoid intubation when other therapies
have failed. Although in the study by Squadrone et al. [4] a continuous positive airway
pressure (CPAP) program was successfully set up in the hematological ward itself, NIV
in patients with hematological malignancy preferably should be treated in an ICU set-
ting, given the relatively high risk of NIV failure. Timely and close communication with
the attending intensive care physician is therefore essential.

66.2.3 Diagnostic and Therapeutic Approach in NIV-Treated

Patients with Hematological Malignancy

Although it has been suggested that NIV offers a certain form of lung protective
effect (by preventing alveolar collapse through positive end-expiratory pressure or
by limiting the required fraction of inspired oxygen), it is more likely that NIV is a
purely supportive therapy that buys time until ARF resolves and that causes less
iatrogenic damage than invasive mechanical ventilation. It is important to keep in
mind that ARF in patients with hematological malignancy may result from a diverse
range of pulmonary insults, both direct and indirect, of which some are more revers-
ible than others. The ultimate prognosis is, to a large extent, defined by the cause of
558 P. Depuydt

ARF and, compared with the absence an etiologic diagnosis, being able to identify
the cause itself has been associated with better outcome [9]. Initiating NIV should
not postpone or obviate the search for the etiology of ARF, and evidently, not the
empirical or directed etiologic therapy. NIV may permit and even facilitate bron-
choscopy and bronchoalveolar lavage, but imaging with high-resolution computed
tomography may be more challenging under NIV.

66.2.4 Avoiding NIV Failure

Failure of NIV is associated with increased mortality. To some extent, this probably
relates to failure of the causative therapy directed at the cause of ARF or to a refractory
state of ARF. However, unduly prolonging NIV may exert harm by delaying intuba-
tion. This is suggested by the observation that late referral to the ICU and an increasing
duration of NIV application are independent predictors of mortality [8]. Similarly, in
the aforementioned study by Schnell et al. [7], failure of NIV was independently asso-
ciated with increased mortality after adjustment for time-dependent covariates. Careful
selection of patients is therefore essential, not only with regard to the presence of (rela-
tive) contraindications for NIV, but also estimating the probability that ARF is likely to
be reversed within a short period of time. Efforts should be made to improve tolerance
of NIV, but one must bear in mind that persisting discomfort or agitation, especially in
hypoxemic ARF, may be an early warning sign of inappropriate use of NIV. Positive
pressures should by slowly titrated upward to allow patients to accommodate. Careful
adjustment of the ventilator settings while observing patient-ventilator synchrony is
important, paying attention to inspiratory and expiratory pressures, trigger sensitivity,
and inspiratory and expiratory cycling. Different ventilator modes may be tried under
the assumption that no mode has been shown to be superior to another. The patient-
ventilator interface should be chosen on an individual basis, preferably trying different
types, and a compromise must be achieved between permitting a certain amount of
pressure leak and avoiding pressure sores or claustrophobia. Judicious sedation with
the use of short-acting agents such as remifentanil and dexmedetomidine may increase
the success rate of NIV; however, sedation should not be allowed to mask respiratory
deterioration. Attention should be given to try to allow some sleep, to preserve circa-
dian rhythm, and to maintain orientation in time and space. If patients remain depen-
dent on NIV for more than 24–36 h, without signs that ARF is resolving, one should
consider cessation of NIV and semi-elective intubation to avoid the adverse effects
associated with late NIV failure. Intubation should also be strongly considered at any
time if PaO2/FiO2 levels fall below 200 or when additional organ failure develops.

66.2.5 NIV in Patients with Hematological Malignancy

with a Do-Not-Intubate Order

As NIV permits patients to be awake and to communicate, it is an attractive way to

provide mechanical ventilator support while preserving the patient’s autonomy and
66 Noninvasive Mechanical Ventilation in Critically Ill Patients 559

ability to interact with his or her family and loved ones. In addition, it requires only
minimal or no sedation, which shortens the time spent in the ICU. Minimal sedation
levels are advocated to prevent the occurrence of delirium and perhaps the long-lasting
cognitive and functional deficits associated with it. As a trial of NIV may offer a com-
promise between an increase in the patient’s chance to survive an ARF event and a
limitation of the risk of embarking on a prolonged ICU stay and its associated compli-
cations, it may be of particular value in patients with a do-not-intubate (DNI) order
and a potentially reversible ARF event. Although data on this particular use of NIV in
patients with hematological malignancy are lacking, a recent prospective observa-
tional study in general ICU patients with a DNI order showed that NIV could be suc-
cessfully applied in more than 60 % of patients [10]. Tolerance of NIV was good to
excellent in 34 %, sleep was qualified as good at least one time under NIV in 38 %,
and oral intake was possible in 66 %. Importantly, in patients that survived their ICU
and hospital stay, functional status afterward was not significantly different compared
with the pre-ICU status. Evidently, data on the use of NIV in the specific population
of patients with hematological malignancy with a DNI code are eagerly awaited.

66.2.6 NIV in Patients with Hematological Malignancy

at the End of Life

A more controversial issue is whether or not NIV should be offered to patients with
hematological malignancy with ARF when their disease is refractory or in a termi-
nal phase, and when the aim of therapy is to provide palliation of symptoms rather
than to try to extend survival. Although NIV may provide more rapid relief of dys-
pnea than medication, this may be at the expense of introducing other discomfort
such as disruption of sleep, claustrophobia, or pressure sores. The main drawback is
that the initiation of NIV subjects the patient to a high-tech procedure in a highly
clinical environment at a time when care should move away from aggressive inter-
ventions to focus on the creation of comforting surroundings and preparation for a
“good death.” NIV may offer some precious time to patients and families to say
goodbye but may, on the other hand, prolong the dying process and cause additional
anxiety and distress. In the absence of good data, offering NIV for this indication
should be the exception rather than a rule. If NIV is considered in this setting, it
should be for a limited time and in the context of a holistic approach to palliation.
At any moment, the benefits, such as permitting time to settle things, say goodbye,
or come to terms with death, should be balanced against the discomfort or emo-
tional suffering endured by the patients and their relatives.

Conclusion
NIV is a well-established supportive treatment in patients with ARF and may
also be considered as a first-line ventilatory strategy in patients with hematologi-
cal malignancy, taking into account several caveats. Although NIV can avert
intubation and thus improve outcome in a significant number of patients, it may
also increase mortality in those patients in whom it fails. The overall impact of
560 P. Depuydt

NIV on outcome in patients with hematological malignancy with ARF remains

unproven. A subset of patients with hematological malignancy is likely to benefit
from NIV, especially those with early-onset ARF, no or limited additional organ
failure, and a cause of ARF that is likely to be reversible in a short time. In these
patients, a trial of NIV can be offered but should be monitored closely for signs
of response or impending failure. NIV should not be allowed to cause delays in
intubation when this is appropriate, which is the case when stagnation or pro-
gression of organ failure occurs. In addition, NIV may have a role as an upper
limit of ventilatory support in selected patients with a DNI order.

Key Major Recommendations

• NIV may be considered in early stages of ARF in patients with hemato-
logical malignancy.
• NIV should be avoided in late-stage (>48 h) or severe (PaO2/FiO2 <200)
ARF in patients with hematological malignancy.
• NIV should be accompanied by a thorough search for the etiology of ARF
in patients with hematological malignancy.
• Response to and tolerance of NIV should be carefully assessed, and per-
sisting intolerance or worsening organ failure should prompt intubation.
• Prolonged use of NIV (>48 h) in patients with hematological malignancy
should be avoided.

Flow chart:

Decision algorithm regarding choice of type of ventilator support in hematological patient with ARF
(and full therapy code)

General contra-indications for NIV? Yes

Immediate intubation

No

Acute-on-chronic, hypercapnic
Type of ARF? Strongly consider NIV

New onset, hypoxemic

Severity of ARF? Severe ARF (P/F<200) and/or

Onset of ARF? Consider intubation
Associated organ failure? Onset >48h and/or

>1 associated organ failure

Non-severe, early-onset,
no or 1 organ failure

Known or suspected cause,

potentially rapidly reversible
Cause of ARF? Strongly consider NIV

Known or suspected cause,

no rapid reversal expected
Consider intubation

Unknown cause
Consider NIV, while
pursuing diagnostic search
66 Noninvasive Mechanical Ventilation in Critically Ill Patients 561

References
1. Azoulay E, Mokart D, Pène F, et al. Outcomes of critically ill patients with hematologic malig-
nancies: prospective multicenter data from France and Belgium. J Clin Oncol.
2013;31:2810–8.
2. Antonelli M, Conti G, Bufi M, et al. Noninvasive ventilation for treatment of acute respiratory
failure in patients undergoing solid organ transplantation: a randomized controlled trial.
JAMA. 2000;283:235–41.
3. Hilbert G, Gruson D, Vargas D, et al. Noninvasive ventilation in immunosuppressed patients
with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med.
2001;344:481–7.
4. Squadrone V, Massaia M, Bruno B, et al. Early CPAP prevents evolution of acute lung injury
in patients with hematologic malignancy. Intensive Care Med. 2010;36:1666–74.
5. Wermke M, Schiemanck S, Hoffken G, et al. Respiratory failure in patients undergoing alloge-
neic hematopoietic SCT - a randomized trial on early non-invasive ventilation based on stan-
dard care hematology wards. Bone Marrow Transplant. 2012;47:574–80.
6. Gristina G, Antonelli M, Conti G, et al. Noninvasive versus invasive ventilation for acute respi-
ratory failure in patients with hematologic malignancies: a 5-year multicenter observational
study. Crit Care Med. 2011;39:2232–9.
7. Schnell D, Timsit JF, Darmon M, et al. Noninvasive mechanical ventilation in acute respiratory
failure: trends in use and outcome. Intensive Care Med. 2014;40:582–91.
8. Adda M, Coquet I, Darmon M, et al. Predictors of noninvasive ventilation failure in patients
with hematologic malignancy and acute respiratory failure. Crit Care Med.
2008;36:2766–72.
9. Azoulay E, Thiéry G, Chevret S, et al. The prognosis of acute respiratory failure in critically
ill cancer patients. Medicine. 2004;83:360–70.
10. Azoulay E, Kouatchet A, Jaber S, et al. Noninvasive mechanical ventilation in patients having
declined tracheal intubation. Intensive Care Med. 2013;39:292–301.
Noninvasive Ventilation in Patients
with Solid Malignancies 67
Pascal Kingah and Ayman O. Soubani

Contents
67.1 Introduction ................................................................................................................. 564
67.2 Causes of ARF in Patients with Solid Malignancies .................................................. 564
67.3 Outcome of NIV in Patients with Malignancy............................................................ 564
67.4 Predictors of NIV Success and Failure ....................................................................... 567
67.5 Applications of NIV in Patients with Solid Malignancies .......................................... 568
67.5.1 Acute Hypoxic Respiratory Failure............................................................... 568
67.5.2 Acute Hypercapnic Respiratory Failure ........................................................ 569
67.5.3 Treatment of Comorbid Diseases .................................................................. 569
67.5.4 Palliative Treatment in Patients with Do-Not-Intubate Orders ..................... 569
67.5.5 Acute Respiratory Failure Following Surgery .............................................. 570
67.5.6 NIV and Bronchoscopy ................................................................................. 571
67.5.7 NIV outside of the ICU ................................................................................. 571
67.6 NIV Settings ............................................................................................................... 572
Conclusion ............................................................................................................................. 572
References .............................................................................................................................. 573

P. Kingah, MD
Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University
School of Medicine, Detroit, MI, USA
A.O. Soubani, MD (*)
Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University
School of Medicine, Detroit, MI, USA
Medical ICU, Harper University Hospital, 3990 John R-3 Hudson, Detroit, MI, 48201, USA
Pulmonary and Critical Care, Karmanos Cancer Center, Detroit, MI, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 563

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_67
564 P. Kingah and A.O. Soubani

67.1 Introduction

Acute respiratory failure (ARF) refers to a rapidly progressive inability of the respi-
ratory system to perform one or both of its gas exchange functions, which includes
oxygenation and carbon dioxide elimination. This is usually life threatening espe-
cially when it occurs in patients with underlying malignancy. In patients with acute
leukemia or lymphoma, the incidence of ARF ranges from 10 to 20 % and increases
to 40 % in those with neutropenia or bone marrow transplantation [1, 2]. ARF in
patients with solid tumors has a lower incidence of about 1–5 %, with about 44–50 %
mortality when these patients were admitted to the intensive care unit (ICU) and
required some form of ventilation [3–6]. Recent studies have shown that, in patients
with ARF, noninvasive ventilation (NIV) can prevent the need for invasive mechani-
cal ventilation, hence reducing the risks associated with this form of ventilation as
well as reducing ICU and hospital stay [7–10]. There have also been reports of
lower 30-day mortality with the use of NIV compared with invasive mechanical
ventilation [11]. The purpose of this chapter is to provide an overview of the use of
NIV in patients with solid malignancies emphasizing on indications and outcome.

67.2 Causes of ARF in Patients with Solid Malignancies

There are a variety of conditions that may cause ARF in patients with solid malig-
nancies (Table 67.1). Infections caused by opportunistic and non-opportunistic
organisms are a major consideration. Neutropenia and corticosteroid therapy are
risk factors for opportunistic infections in this patient population. Noninfectious
etiologies include pulmonary embolism, metastasis, atelectasis from endobron-
chial lesions causing obstruction, lymphangitic spread, diffuse alveolar hemor-
rhage, pleural effusions, and hemorrhage from an endobronchial tumor [1, 12,
13]. The treatment of solid malignancies may also contribute to ARF, with drug-
induced pulmonary toxicity, radiation-induced pulmonary toxicity, and complica-
tions of diagnostic and therapeutic procedures. Post-lung resection ARF reported
in the acute setting following lung resection has been related to acute respiratory
distress syndrome (ARDS) or atelectasis. Comorbid illnesses including cardiac
disease, chronic obstructive pulmonary disease (COPD), asthma, interstitial, and
occupational lung diseases could worsen in these patients, predisposing them to
develop ARF.

67.3 Outcome of NIV in Patients with Malignancy

Most of the studies that address the use of NIV in cancer patients focus on patients
with hematological malignancies (Table 67.2). These studies have shown improved
outcome of patients with ARF managed by NIV compared with invasive mechani-
cal ventilation. In one study of 1,302 patients with hematologic malignancies admit-
ted to the ICU with ARF, NIV was attempted in 21 % of these patients and 46 % of
67 Noninvasive Ventilation in Patients with Solid Malignancies 565

Table 67.1 Causes of acute Infectious

respiratory failure in patients
Pneumonia
with solid malignancies
Bacteria
Viral
Post obstructive
Opportunistic infections
Fungal
PCP
Noninfectious
Related to cancer
Airway obstruction
Pulmonary hemorrhage
Lymphangitic pulmonary spread
Pleural effusion
Related to cancer treatment
Drug-induced pulmonary toxicity
Radiation-induced pulmonary toxicity
Complications of diagnostic and therapeutic procedures
Comorbid illnesses
COPD/asthma
Interstitial and occupational lung diseases
Cardiac disease

them later required invasive mechanical ventilation [7]. Favorable outcomes were
encountered in NIV patients, with mortality of 46 % compared with 69 % in patients
who were initially put on invasive mechanical ventilation and 77 % in patients who
failed NIV and later required.
Studies that specifically evaluate the outcome of patients with solid malignancies
and ARF treated by NIV are sparse. Two major studies have reported on the use of
NIV in patients with solid malignancies. The most recent study by Azoulay et al.
[21] in 2014 was a retrospective analysis of data from six previously published ret-
rospective and prospective studies on patients with malignancy admitted to the ICU
in 14 university and university-affiliated hospitals in France and Belgium. In this
review, there were 147 (14.6 %) patients with solid malignancy, in whom breast and
lung cancers were the most commonly encountered. NIV was used in 387 patients,
among whom 174 survived and 213 did not survive, with a 64 % overall mortality.
Among the 387 patients initiated on NIV, 276 subsequently required mechanical
ventilation. NIV failure was strongly associated with the severity of ARDS, with
patients failing in the moderate to severe categories by the Berlin definition.
Following a multivariate analysis, patients with solid tumors were independently
associated with lower mortality, OR 0.51 (0.34–0.77) p = 0.002. As illustrated in
Fig. 67.1, mortality from solid tumors also decreased over time compared with
hematologic malignancies.
Table 67.2 Mortality rates, ICU length of stay of patients with malignancy treated with using NIV in studies published in the last two decades (1994–2014)
566

NIPPV failure Hospital

Number of Mean ICU requiring mortality
Author, year Study design Type of malignancy patients on NIPPV Location days intubation rate (%)
Tognet et al. Prospective cohort Hematologic 18 ICU 8.5 12 67
1994 [14]
Conti et al. Prospective Hematologic 16 ICU 4.3 1 31.3
1998 [8] cohort
Hilbert et al. Prospective cohort Hematologic 64 ICU 7 48 44
2000 [15]
Hilbert et al. Prospective randomized Hematologic 26 ICU 7 12 50
2001 [10] trial
Azoulay et al. Retrospective cohort Hematologic 48 ICU 7 27 43.7
2001 [16] and Solid organ
Principi et al. Prospective matched Hematologic 17 Oncology NR 7 47
2004 [17] cohort ward
Rocco et al. Prospective matched Hematologic 19 ICU 9 9 53
2004 [18] cohort Solid organ
Soares et al. Prospective cohort Hematologic 19 ICU NR NR 37
2005 [13] and solid organ
Adda et al. Retrospective Hematologic 99 ICU NR 53 61
2008 [19]
Depuydt et al. Retrospective cohort Hematologic 166 ICU 6 14 67
2010 [21, 24]
Gristina et al. Retrospective Hematologic 274 ICU 9 77 49
2011 [7]
Azoulay et al. Retrospective Hematologic 387 ICU NR 276 33
2014 [20] and solid organ
Azevedo et al. Prospective cohort Hematology and 85 ICU 6 45 55
P. Kingah and A.O. Soubani

2014 [24] solid organ

Lemiale et al. Randomized controlled Hematologic and 130 ICU NR 49 0
2014 [1] trial Solid organ
67 Noninvasive Ventilation in Patients with Solid Malignancies 567

Fig. 67.1 Hospital Hospital mortality

mortality according to
period of admission to the
ICU in patients with
1.0
hematological malignancy
(dotted bars; p < 0.0001)
and with solid tumor (gray
bars; p < 0.0001) [21] 0.8

0.6

0.4

0.2

0
1990-95 1996-2000 2000-2006 2007-2011
Error bars: 95,00% Cl

The other major study that reported on the use of NIV in solid malignancies was
a prospective study by Azevedo et al. [22], which was a multicenter study carried
out in 28 ICUs in Brazil. In their patient population, 227 (86 %) patients had solid
malignancies and only 36 (14 %) patients had hematologic malignancies. The most
frequently encountered malignancies were lung, breast, and lower gastrointestinal
cancers. NIV was initially used in 85 patients (32.3 %), and 45 (47.9 %) of these
patients required mechanical ventilation. Patients who ended up only using NIV had
a mortality of 40 %, whereas those who required mechanical ventilation had a mor-
tality rate of 68.9 %. Reasons for NIV failure were not evaluated in this study.
Multivariate analysis to identify independent risk factors for mortality did not reveal
that the type of tumor was a risk factor, but significant risk factors for mortality
included medical admission, cancer status, tumor as a reason for ventilator support,
poor performance status, NIV followed by mechanical ventilation, use of mechani-
cal ventilation only, and higher SOFA (sequential organ failure assessment) scores.

67.4 Predictors of NIV Success and Failure

Major factors found to be associated with NIV failure following multivariate anal-
ysis include respiratory rate > 20 breaths per minute, organ failure, particularly
renal insufficiency requiring renal replacement therapy, hemodynamic instability
requiring vasopressors, ARDS, PaO2/FiO2 < 146 1 h after NIV initiation, persis-
tent organ failure over the first few ICU days, pneumonia, pH <7.25, excessive air
568 P. Kingah and A.O. Soubani

Table 67.3 Predictors of success and failure of NIV in patients with malignancy
Major predictors of NIV success Good performance status especially if ambulatory
Absence of airway involvement
No recurrence of cancer
Age <40
Major predictors of NIV failure Respiratory rate >20 bpm
Renal insufficiency requiring renal replacement therapy
Hemodynamic instability requiring pressors
ARDS with PaO2/FiO2 ratio <146 1 h after NIV
pH <7.25
Lack of tolerance to NIV
High APACHE II >29 or SAPS II >35
More diffuse pulmonary infiltrates on chest imaging

leak, lack of tolerance, agitation during NIV, high severity of illness scores
(APACHE II ≥29 or SAPS II ≥35), and longer duration of NIV dependency [5, 13,
19–21, 23] (Table 67.3). The above predictors should serve as a guideline when
making decisions on the initial respiratory support for patients with hematologic
malignancy in ARF.
It is also imperative to understand the characteristics of patients with malignan-
cies who have had favorable outcomes with the use of NIV. Following multivariate
logistic regression, patient factors that have been associated with favorable out-
comes include good performance status, especially if patient is ambulatory, age less
than 40, no recurrence of cancer, and absence of airway involvement [13]. Patients
with solid tumors were better candidates than those with hematologic malignancy
(OR 0.51 (0.34–0.77) p = 0.002). Patients with ARDS from primary malignancy had
better outcomes than those with ARDS from secondary or undermined causes (OR
0.41 (0.2–0.88) p = 0.02) [21, 22].

67.5 Applications of NIV in Patients with Solid Malignancies

67.5.1 Acute Hypoxic Respiratory Failure

NIV with the use of continuous positive airway pressure (CPAP) has been shown to
correct hypoxemia, particularly in patients with pulmonary edema [24]. CPAP
offers a high inspired oxygen content, increases mean airway pressure, and improves
ventilation to collapsed areas of the lungs by recruitment of under-ventilated lung.
This action is similar to positive end-expiratory pressure in mechanically ventilated
patients. In patients with malignancies, 90 % of ARDS cases are related to an infec-
tion [21]. In patients with moderate to severe ARDS according to the Berlin severity
categories, higher NIV failures were noted in recent reports [21, 22]. Approximately
70 % of patients with moderate ARDS failed NIV, and 79.1 % of patients with
severe ARDS failed [21]. The use of NIV to treat hypoxia in this group of patients
should be avoided.
67 Noninvasive Ventilation in Patients with Solid Malignancies 569

67.5.2 Acute Hypercapnic Respiratory Failure

NIV unloads inspiratory muscles, hence reducing work of breathing. This, in turn,
reduces the respiratory rate and increases alveolar ventilation, which causes a fall in
PaCO2. NIV is particularly useful in patients with neuromuscular diseases associ-
ated with certain types of solid malignancies leading to hypercapnia [24]. NIV has
also been shown to be effective in patients with hypercapnic respiratory failure due
to COPD [25].

67.5.3 Treatment of Comorbid Diseases

Patients with COPD are at a much higher risk of developing lung cancer than the
average population [26, 27]. Lung cancer remains an important cause of death in
patients with COPD [28]. Studies have also shown that patients with hypoxemic
acute respiratory failure due to community-acquired pneumonia in COPD respond
to the use of NIV [29, 30].

67.5.4 Palliative Treatment in Patients with Do-Not-Intubate

Orders

NIV is particularly useful in patients with do-not-intubate (DNI) orders who present
with ARF due to causes that could be easily reversible, such as cardiogenic pulmo-
nary edema or COPD exacerbation. The international consensus conference in
intensive care medicine approved the use of NIV in patients who have ARF with a
reversible cause if the patients are not to be intubated [31]. In 2001, an international
consensus that included the American Thoracic Society (ATS), European Society of
Intensive Care Medicine (ESICM), Société de Réanimation de Langue Française
(SRLF), and the European Respiratory Society (ERS) was the first to address this
issue, and considered palliative NIV as appropriate in selected patients in whom
endotracheal ventilation is not an option provided the cause of ARF is reversible
and NIV improves patient comfort. The Society for Critical Care Medicine (SCCM)
task force recommended an approach for deciding when to offer NIV to patients in
whom mechanical ventilation could not be performed. This conference, which
occurred in 2007, adopted an approach that involved a daily assessment of NIV
objectives, which were classified into three categories: NIV as life support for
patients with DNI orders, NIV as life support for patients receiving comfort care
only, and NIV as life support for patients without any treatment-limitation deci-
sions. Palliative NIV was defined by the first and second categories [32].
In a review on palliative NIV in patients with ARF, Azoulay et al. [33] reported
several unanswered questions in the literature available at the time. Their major
concerns included the uncertainty whether palliative ventilation increased duration
of life or if it extended the dying process, absence of qualitative observational data
to determine actual benefits of palliative NIV, and whether palliative NIV should be
570 P. Kingah and A.O. Soubani

performed in incapacitated patients to either improve survival or alleviate symp-

toms of respiratory distress.
A study by Nava et al. [34] evaluated the effectiveness of NIV in reducing dys-
pnea and the amount of opiates needed in patients with solid malignancy. In this
multicenter, multinational randomized controlled trial, 200 patients from seven dif-
ferent countries were randomized to either NIV or oxygen via the Venturi mask. NIV
was found to be effective in reducing dyspnea rapidly in the NIV group after the first
hour of treatment, and the average change in Borg scale was −0.58, 95 % CI (−0.92
to −0.23). The amount of opiates needed was significantly decreased in the NIV
group: 26.9 mg versus 59.4 mg, difference of −32.4 mg, 95 % CI (−47.5 to −17.4).
Eleven (11 %) patients in the NIV group discontinued treatment. This was mainly
due to mask intolerance and anxiety. Patient selection remains crucial, as NIV should
only be attempted on patients who are alert, cooperative, and able to cough [35].

67.5.5 Acute Respiratory Failure Following Surgery

ARF following surgery for underlying solid malignancies is a new and growing
indication for NIV. In a study by Yu et al. [36], NIV was used a first-line interven-
tion for patients with ARDS following esophagectomy for esophageal cancer.
Intubation was avoided in 30 patients (30/64, 48.4 %). NIV was used as initial treat-
ment in 48 patients and 16 were converted to invasive mechanical ventilation due to
active bleeding, hemodynamic instability and neurologic disturbances. Patients
treated with NIV had a lower ICU length of stay, 11.5 days compared to 33.1 days
in patients on invasive mechanical ventilation. The 28-day hospital mortality rate
among patients treated with NIV was much lower as well, 6.25 % compared to
21.9 % in patients who were treated with invasive mechanical ventilation. In this
study, the use of NIV appeared to be safe in treating ARDS/ALI following esopha-
gectomy, but conversion to invasive ventilation should be considered early in
patients with postoperative complications, including acute kidney injury, cardiac
arrest, and patients with severe ARDS [36].
A few earlier studies reported on the use of NIV in patients with ARF following lung
resection, but most of the indications for lung resection were for COPD. One of these
studies reported that NIV decreased the need for endotracheal intubation and improved
outcome [37]. Another study by Auriant et al. [38], in 2001, of patients with ARF fol-
lowing lung resection for lung cancer compared, by randomizing prospectively, stan-
dard therapy with and without NIV. In-hospital deaths and subsequent endotracheal
intubations were fewer in the NIV group compared with the standard therapy group. In
the NIV group, there were 3 deaths out of 24 patients (12.5 %) and in the standard
therapy group 9 deaths out of 24 patients (37.5 %), p = 0.045. Endotracheal intubation
with mechanical ventilation was required in 12 out of 24 (50 %) patients with standard
care and only 5 out of 24 (20.8 %) in patients randomized to NIV, p = 0.035. There was
no significant difference in ICU length of stay. NIV appears to be safe in reducing the
need for mechanical ventilation in patients with lung cancer and respiratory failure fol-
lowing lung resection, although more studies are needed to validate these findings.
67 Noninvasive Ventilation in Patients with Solid Malignancies 571

67.5.6 NIV and Bronchoscopy

There are limited reports of performing bronchoscopy while the patient is on

NIV. The scenarios that would apply to this are either that the patient is already on
NIV and needs bronchoscopy for diagnostic or therapeutic purposes or that NIV is
started to support the patient’s respiratory status during the procedure. In patients
with solid malignancies, bronchoscopy may be considered during NIV for bron-
choalveolar lavage, removal of secretions, investigation of the source of hemopty-
sis, obtaining endobronchial biopsies, or performing rigid bronchoscopy for
endobronchial treatment of cancer with laser, electrocautery, or cryotherapy. In a
study of 40 patients with acute hypoxemic respiratory failure on NIV who under-
went bronchoscopy, 53 % of patients were immunosuppressed and 10 % had solid
malignancies. The procedure was completed with no major complications in all
patients. Mild hypoxemia developed in 5 % of patients. Bronchoalveolar lavage
yielded diagnostic information in 68 % of patients [39].
Another study compared NIV and high-frequency nasal cannula (HFNC) during
bronchoscopy in critically ill patients with acute hypoxemic respiratory failure [40].
Twenty-five percent of the patients had solid malignancies. Bronchoscopy was well
tolerated in all patients except one. Three patients in the NIV group and one patient
in the HFNC group were intubated within 24 h after the end of bronchoscopy
(p = 0.29). The conclusion of the study was that NIV was superior to HFNC with
regard to oxygenation before, during, and after bronchoscopy in patients with mod-
erate to severe hypoxemia. Performing bronchoscopy while the patient is under NIV
requires high skill and expertise by the bronchoscopist and close monitoring of the
patient in a critical care environment. Precautions should be in place to intubate the
patient immediately if the need arises. Details of bronchoscopy during NIV have
been outlined in a review by Esquinas et al. [41].

67.5.7 NIV outside of the ICU

Initiation and monitoring of NIV in patients with ARF is generally recommended to

take place in a critical care environment, such as the ICU, respiratory care unit, or
intermediate care unit. In these units there is close monitoring of the patient, with a
low patient-to-nurse ratio, presence of respiratory care therapists, and involvement
by intensivists. There are, however, certain circumstances where NIV can be used
outside of the ICU, especially in cancer patients. Instituting NIV early in cancer
patients may avoid later intubation and mechanical ventilation, which has tradition-
ally been associated with high mortality. Also, early NIV in patients with cancer and
acute hypoxemic respiratory failure has been associated with better outcome. Other
factors that may lead to consideration of NIV in cancer patients are lack of ICU
beds, patient or family refusal of transfer to the ICU, and the use of this therapy as a
palliative tool to relieve dyspnea in patients with advance malignancy. In a question-
naire, 157 respondents from 51 countries (66 %) indicated that they use NIV outside
of the ICU, and the common indications were pneumonia in immunocompromised
572 P. Kingah and A.O. Soubani

patients (63 %) and palliation (51 %) [42]. There are only few studies in cancer
patients that have shown that starting NIV outside of the ICU is clinically feasible
with reasonable results [17]. However, the use of NIV outside of the ICU should fol-
low the same precautions as in the ICU, including no hemodynamic or neurologic
compromise, no evidence of moderate or severe ARDS (PaO2/FiO2 ratio >200), and
there should be close monitoring of the patient, and skilled nursing staff present.
There should also be detailed hospital policy in place to regulate this application.

67.6 NIV Settings

Similar to invasive mechanical ventilation, administration of NIV has two major

modes of ventilation: pressure limited and volume limited. Proportional assist ven-
tilation, which is a relatively new mode that targets patients effort, can also be used
[20]. In the pressure-limited mode, the ventilator applies a set pressure both during
inspiration and expiration continuously. CPAP of 10 cmH2O is the recommended
level used in several reports, but it could also be titrated from 2.5 to 12.5 cmH2O
using increments of 2–3 cmH2O [24, 43]. This mode is most useful in correcting
hypoxemia and during management of cardiogenic pulmonary edema. Bi-level pos-
itive airway pressure (BIPAP) can also be used, which requires setting two different
pressure levels, one during inspiration (pressure support) and the other during expi-
ration (CPAP). This mode of NIV is effective in patients with dyspnea and hyper-
capnic respiratory failure and may be useful in patients with pulmonary infiltrates
and hypoxemic respiratory failure. There are no clear recommendations on the pres-
sure settings with this mode of ventilation. The choice of initial pressures depends
on factors such as personal experience, clinical setting, arterial blood gases, and
patient tolerance. Usually, clinicians start with CPAP of 3–5 cmH2O and inspiratory
pressure of 8–12 cmH2O above CPAP. If necessary, pressure changes are made
gradually, depending on the patient’s dyspnea, tolerance, and minute ventilation.
Oxygen supplementation should target oxygen saturation above 89 % [44]. Volume-
limited Non-invasive Positive Pressure Ventilation (NIPPV) is usually administered
via a ventilator that is more expensive, heavier, and has sophisticated alarm systems.
It is usually set in assist control mode to allow for spontaneous patient triggering.
The backup rate is set slightly below the patient’s breathing rate [20].

Conclusion
NIV use in patients with solid malignancies presenting with ARF has been
shown to be beneficial in avoiding invasive mechanical ventilation and reducing
mortality and hospital length of stay. The main indications for NIV in this patient
population are acute hypercapnic respiratory failure, palliative support of respi-
ratory symptoms, treatment of comorbid cardiopulmonary illnesses, and in
selected patients with acute hypoxemic respiratory failure, postoperative respira-
tory failure, and during bronchoscopy. Although NIV offers benefits, patient
selection is crucial, as several other studies have revealed that patients with mod-
erate to severe ARDS, high severity of illness, and acute renal failure requiring
67 Noninvasive Ventilation in Patients with Solid Malignancies 573

renal replacement therapy did not benefit from NIV and NIV use resulted in
higher mortality once they were intubated. Patient selection remains the primary
challenge for clinicians caring for these patients.

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 Part VIII
Hospital Critical Care Applications:
Non Invasive Ventilation in Upper Airways,
Endoscopy Procedures and Sedation
Noninvasive Ventilation in Difficult
Endotracheal Intubation 68
Igor Barjaktarevic, Jeffrey Albores, and David Berlin

Contents
68.1 Introduction ................................................................................................................. 578
68.2 Difficult Intubation ..................................................................................................... 578
68.3 Rationale for NIV in Difficult Intubation ................................................................... 579
68.4 Physiologic Benefits of NIV in ETI ............................................................................ 579
68.4.1 Ventilation ..................................................................................................... 580
68.4.2 Oxygenation .................................................................................................. 580
68.4.3 Splinting the Upper Airways ......................................................................... 581
68.4.4 Hemodynamic Effect..................................................................................... 582
68.4.5 Patient Comfort and Safety ........................................................................... 583
68.5 Procedure .................................................................................................................... 583
68.6 Limitations of NIV during ETI ................................................................................... 588
Conclusions ............................................................................................................................ 588
References .............................................................................................................................. 588

Abbreviations

CPAP Continuous positive airway pressure

ETI Endotracheal intubation
FRC Functional residual capacity
ILM Intubating laryngeal mask

I. Barjaktarevic, MD, MSc • J. Albores, MD

Division of Pulmonary and Critical Care Medicine, David Geffen School
of Medicine at UCLA, Los Angeles, CA, USA
e-mail: [email protected]; [email protected]
D. Berlin, MD (*)
Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College,
New York, NY, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 577

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_68
578 I. Barjaktarevic et al.

LMA Laryngeal mask airway

NIV Noninvasive positive pressure ventilation
PEEP Positive end-expiratory pressure

68.1 Introduction

Noninvasive positive pressure ventilation (NIV) is a validated treatment for acute

and chronic respiratory failure in selected patients. The need for endotracheal intu-
bation (ETI) and mechanical ventilation is usually considered a failure of
NIV. However, the use of NIV immediately before and during ETI may improve the
safety of the transition to invasive mechanical ventilation by a number of mecha-
nisms. In this chapter, the use of NIV as an adjuvant to ETI is discussed, with a
focus on the use of NIV during a predicted difficult intubation.

68.2 Difficult Intubation

ETI is an essential part of anesthesia care and the support of critically ill patients.
Paradoxically, ETI is associated with a number of life-threatening complications. These
complications are more likely during “difficult intubation.” This is defined as intubation
requiring more than three attempts, for longer than 10 min, or the need for use of an
alternative intubation device after a failed attempt. Difficult intubation may lead to seri-
ous soft tissue damage and is the major cause of death and anoxic brain injury during
anesthesia care [1]. The incidence of difficult intubation varies greatly in different series.
Ideally, clinicians should be able to predict whether intubation will be difficult
and adjust their airway plan. Although there are a number of useful clinical scales
to help predict difficult intubation, they are not highly sensitive or specific. Some of
the rules, such as the Mallampati classification, predict the quality of view of the
airway using direct laryngoscopy. The Mallampati classification, however, was not
designed to predict difficulty with video laryngoscopy nor does it predict difficulty
passing the endotracheal tube. The LEMON mnemonic is a more holistic approach
to predicting difficult intubation. It includes factors such as mouth opening, cervical
mobility, and anatomical obstruction (Table 68.1).
The narrow definition of difficult intubation refers to the placement of the endotra-
cheal tube during laryngoscopy. A broader meaning can include clinical scenarios in
which ETI can contribute to clinical deterioration even if laryngoscopy and tube place-
ment are technically easy. Critically ill patients have poor physiologic reserve and have
little tolerance of the stressors of ETI. These stressors occur to varying degrees in all
patients. While usually insignificant in the healthy population, they can be severe in
critically ill patients. For example, patients with respiratory failure and high metabolic
rates are intolerant of hypoventilation or apnea during ETI. Similarly, patients with
intracranial hypertension or right ventricular failure do not tolerate hypercapnia and
hemodynamic consequences of ETI. In these scenarios, we can predict a high risk of
deterioration during ETI even if laryngoscopy and tube passage are easy. Of course, the
combination of difficult laryngoscopy and tube passage with poor physiologic reserve is
the perfect storm of factors that can lead to catastrophic deterioration during ETI. As a
68 Noninvasive Ventilation in Difficult Endotracheal Intubation 579

Table 68.1 Mnemonic “LEMON” in evaluation for a potentially difficult airway

Mnemonic Description
Look externally Obesity, micrognathia, evidence of previous head and neck surgery or
irradiation, presence of facial hair, dental abnormalities (poor dentition,
dentures, large teeth), narrow face, high and arched palate, short or thick
neck, and facial or neck trauma
Evaluate using Normal mouth opening is 3 (of the patient's) fingerbreadths; a normal
the 3:3:2 rule mandible dimension will likewise allow 3 fingerbreadths between the mentum
and the hyoid bone; and the notch of the thyroid cartilage should be 2
fingerbreadths below the hyoid bone
Mallampati In patients with a Mallampati score of 1, the entire posterior pharynx is easily
classification visualized; with a 4, no posterior structures can be seen. Patients with a higher
Mallampati grade tend to have poorer visualization during direct laryngoscopy
Obstruction Evaluation for stridor, foreign bodies, and other forms of sub- and
supraglottic obstruction
Neck mobility Patient with rheumatoid arthritis or suspected traumatic cervical spine
injury, and in whom the cervical spine has been immobilized by a cervical
collar, have limited neck mobility by definition

result, the rate of complications such as cardiac arrest, hypotension, and critical hypox-
emia are much higher in critically ill patients than in anesthesia for elective surgery

68.3 Rationale for NIV in Difficult Intubation

Because NIV can support gas exchange, it is logical to consider its use as a way to
improve the safety of difficult intubation. Theoretically, NIV may increase patients’
tolerance of prolonged attempts to perform ETI. Therefore, clinicians could consider
starting NIV when they predict difficult ETI. Similarly, clinicians could consider plac-
ing NIV if the patient will not tolerate even brief periods of apnea. The benefits of
NIV as part of a preoxygenation /ventilation strategy have been studied. Alternatively,
clinicians could use NIV with a nasal interface to support the patient during oral ETI.
NIV is widely used as an alternative to invasive mechanical ventilation for acute
respiratory failure, and although NIV may be effective in preventing the need for
ETI, there is a high mortality risk in patients who require ETI despite NIV [2]. Most
concerning, there is a high risk of death during emergent ETI after a failed trial of
NIV for acute respiratory failure. We speculate that removal of NIV prior to ETI
may lead to catastrophic deterioration in gas exchange, partially due to significant
lung derecruitment. NIV support during ETI may be an especially attractive idea in
the setting of failed NIV and a necessary transition to invasive mechanical ventila-
tion. In this setting, adjusting the settings and mask for NIV may allow the clinician
to continue it as partial support of gas exchange during ETI.

68.4 Physiologic Benefits of NIV in ETI

NIV can support the patient during ETI through multiple possible mechanisms
(Table 68.2). These mechanisms are reviewed in detail below.
580 I. Barjaktarevic et al.

Table 68.2 Physiologic Preoxygenation

benefits of NIV during ETI
Prevention of alveolar de-recruitment
Persistent gas exchange
Splinting upper airways open
Reducing the hemodynamic alterations during ETI
Reduce the level of respiratory distress prior to ETI

68.4.1 Ventilation

Apnea during ETI is usually well tolerated in patients undergoing elective surgical
procedures. The rise in PCO2 during apnea is nonlinear, but approximates 3–4
mmHg · min−1. The rate of PCO2 rise will be much greater if the patient has an
increased metabolic rate. Fever, tissue injury, and systemic inflammation associated
with acute illness can greatly increase metabolic rate and CO2 production. Therefore,
clinicians should anticipate complications of ETI in patients with a high metabolic
rate and a disease process that makes them intolerant of hypercapnia. In these
patients, continuing ventilation during the intubation process may be beneficial.
NIV can improve gas exchange during ETI by cyclically augmenting the trans-
pulmonary pressure gradient to maintain alveolar ventilation. NIV can maintain a
satisfactory level of ventilation, even during deep sedation, as demonstrated in a
case series of its application in procedural anesthesia [3]. In patients undergoing
intubation during spontaneous breathing, NIV can theoretically decrease the work
of breathing and improve ventilation by augmenting tidal volumes.

68.4.2 Oxygenation

Traditionally, clinicians perform intubation after induction of anesthesia. After neu-

romuscular blockade, the lungs recoil to the functional residual capacity (FRC).
During apnea, gas exchange continues as mixed venous blood continues to flow to
the alveolar capillary bed. Therefore, the FRC is the air reservoir that supplies the
circulation with oxygen during apnea. Both the volume of air in the FRC as well as
its partial pressure of oxygen determine how quickly arterial desaturation occurs
during apnea. The rate of total oxygen consumption in the tissues as well as the
magnitude and distribution of pulmonary blood flow also determine the time to
desaturation. To lengthen the time before desaturation, clinicians have patients
spontaneously breathe high FiO2 to fill the FRC with pure oxygen. This preoxygen-
ation is effective in patients presenting for anesthesia for elective surgery [4].
However, standard methods of preoxygenation are ineffective due to the deranged
physiology of critically ill patients. In critically ill patients, atelectasis commonly
reduces FRC and increases the right-to-left shunt fraction. Shock may reduce pul-
monary blood flow. Moreover, the high oxygen consumption during acute illness
can reduce mixed venous oxygen saturation. All of these factors lead to hypoxia
during ETI. Patients with an oxygen saturation less than or equal to 93 % during
preoxygenation uniformly desaturate to <90 % during intubation [5].
68 Noninvasive Ventilation in Difficult Endotracheal Intubation 581

A number of investigators have shown that NIV may be superior to standard pre-
oxygenation in appropriate scenarios. Through positive pressure, NIV can recruit atel-
ectatic lung in some patients, thereby increasing the size of the FRC and reducing shunt
fraction. It can also decrease the work of breathing during spontaneous ventilation.
Moreover, by increasing alveolar ventilation, NIV can increase the alveolar oxygen
content by CO2 washout. Finally, NIV can decrease the excessive work of breathing
made by critically ill patients. Theoretically, this can raise mixed venous oxygen satu-
ration and improve the effectiveness of preoxygenation. The recruitment and benefit of
preoxygenation with NIV can continue even after ETI is completed [6].
Given the success of NIV for preoxygenation, investigators have used NIV dur-
ing ETI to prevent desaturation. NIV can be a form of apneic oxygenation. If the
airway is patent, any high-flow oxygen device can promote the replacement of alve-
olar gas that flows into the alveolar capillary beds through bulk flow. Therefore,
high-flow nasal cannula (HFNC) can be used as an apneic oxygenation method,
leading to reduced prevalence of severe hypoxemia during intubation of critically ill
patients with mild-to-moderate hypoxemia in a pilot study [7]. However a random-
ized controlled trial found that HFNC during emergent ETI of patients with severe
hypoxemia did not prevent desaturation [8]. It is possible that high-flow devices
have limited benefits during ETI because they provide little (if any) lung recruit-
ment and ventilation. NIV during intubation via a nasal interface could theoretically
promote lung recruitment through positive end-expiratory pressure (PEEP). The
possible benefits of PEEP are especially important because anesthesia and supine
positioning cause atelectasis and promote desaturation during ETI.
The ability of NIV to promote alveolar recruitment may be especially important
because of denitrogenation. Preoxygenation with high FiO2 effectively removes inert
nitrogen from the alveolar air spaces and blood. Unfortunately, nitrogen normally acts
as a pneumatic splint to maintain the patency of unstable lung units. Without nitrogen,
the partial pressure of gas is very low in mixed venous blood returning to capillaries.
Denitrogenation, therefore, increases the gas pressure gradient from alveoli compared
with alveolar capillary blood. After denitrogenation, oxygen will rapidly flow from
the alveoli into the capillaries, leading to alveolar instability and atelectasis, a physi-
ological phenomenon also demonstrated on computed tomography imaging [9].
PEEP facilitates alveolar recruitment, which can counteract the adverse effect of deni-
trogenation on lung recruitment and improve oxygenation. Additionally, nasal NIV
during ETI can also aid oxygenation by partially supporting ventilation.
The principle that oxygenation can be supported by nasal NIV throughout the
process of intubation has been demonstrated for bronchoscopic [10] and direct
laryngoscopic intubation [11].

68.4.3 Splinting the Upper Airways

During deep sedation, airway obstruction commonly occurs at the level of the soft
palate. Anesthesia reduces the tone of the pharyngeal muscle dilators, which nar-
rows the anteroposterior diameter of the airway. These effects are most prominent
in the supine position. This pattern of airway obstruction in anesthesia is similar to
582 I. Barjaktarevic et al.

Fig. 68.1 Fiber-optic

video images of a patient’s
hypopharynx
demonstrating the
pharyngeal splinting action
of nasal CPAP (Rothfleisch
et al. [12])

obstructive sleep apnea. In both situations, the application of nasal NIV can relieve
the airway obstruction. Nasal NIV can displace the soft palate anteriorly, which
partially prevents the leakage of air out the oropharynx. Incremental increases in
positive airway pressures lead to a linear increase in airway area at a given airway
level. Therefore, nasal NIV can serve as a pneumatic splint for the oropharynx dur-
ing anesthesia. Pilot data demonstrate that this splinting can aide ETI. Figure 68.1
shows fiber-optic video images from a morbidly obese patient’s hypopharynx. Nasal
NIV (continuous positive airway pressure (CPAP) 20 cm H2O) relieved upper air-
way obstruction during fiber-optic-guided nasotracheal intubation [12].

68.4.4 Hemodynamic Effect

Hemodynamic instability commonly complicates ETI in critically ill patients. The

hemodynamic effects of NIV during ETI are complex, and it can be difficult to predict
their net effect in critically ill patients. NIV can decrease both venous return to the
heart and left ventricular afterload. This can effectively treat pulmonary edema from
68 Noninvasive Ventilation in Difficult Endotracheal Intubation 583

left ventricular failure. Through this mechanism, NIV may be able to improve the
safety of ETI. However, positive pressure ventilation frequently decreases cardiac out-
put by decreasing the pressure gradient for venous return to the heart. Additionally,
hyperinflation from positive pressure can elevate pulmonary vascular resistance and
impede right ventricular output. Therefore, NIV can also worsen hemodynamics
before or during ETI. Theoretically, using NIV prior to ETI could make the hemody-
namic consequences of positive pressure ventilation manifest prior to ETI, allowing
clinicians to treat the hemodynamic instability prior to sedation and ETI.

68.4.5 Patient Comfort and Safety

When respiratory failure is severe, clinicians may be forced to perform urgent ETI
before they have had the opportunity to properly assess and prepare the patient for
airway management. In select situations, clinicians may use NIV to temporarily
stabilize the patient while preparing the patient and equipment for safer ETI. With
partial support from NIV, the clinician may be able to use alternative intubation
strategies such as bronchoscopic intubation in situations when intubation by direct
laryngoscopy will be difficult.

68.5 Procedure

There are several case reports and series published on different procedural tech-
niques using NIV in ETI. Little data exist on the choice of airway interface. For
preoxygenation, a full face mask can be used. The full face mask can increase the
FiO2 by limiting the amount of entrained air through the mouth. Moreover, full face
masks limit air leak through the mouth and can help maintain PEEP. However, full
face masks contribute to upper airway obstruction in anesthetized supine patients by
displacing the tongue posteriorly. As discussed above, nasal interfaces can stent the
upper airway open and allow oral ETI.
The mode of NIV can influence the effectiveness of ventilation. Patients with non-
compliant respiratory systems require higher levels of inspiratory pressure to increase
delivered tidal volumes. In this scenario, bi-level positive airway pressure (BIPAP)
may be the best mode. Patients with upper airway obstruction may require higher
levels of end-expiratory pressure, so CPAP may be appropriate. If the patient is anes-
thetized, a mode with a set respiratory rate is recommended such as spontaneous/
timed (S/T) mode. Regardless of the mode and settings, it is essential to monitor the
patient on NIV and determine whether the patient has adequate exhaled tidal volume
and minute ventilation. If not, the clinician should evaluate for airway obstruction,
excessive leak, dynamic hyperinflation, and inadequate driving pressure.
There are multiple techniques of ETI during NIV (Table 68.3). Aoyama et al.
[13] performed fiber-optic-guided intubation during positive pressure ventilation
with a laryngeal mask airway (LMA), intubating laryngeal mask (ILM), or endos-
copy mask (Patil mask). In this technique, LMA or ILM were initially inserted
Table 68.3 NIV techniques during ETI
584

Author/report Procedural technique Findings

Aoyama et al. Positive pressure LMA or ILM inserted followed by insertion of tracheal tube into the tube Ventilation during intubation with
ventilation during fiber-optic of the LMA or ILM. Fiber-optic intubation performed with application of endoscopy mask greater than that with
intubation: comparison of the 20 cmH2O PPV through the tracheal tube. In the endoscopy (Patil) mask the LMA or ILM, but gastric
laryngeal mask airway, intubating group, fiber-optic intubation performed while PPV maintained through the insufflation was more frequent
laryngeal mask, and endoscopy Patil mask
mask techniques
Nafeh et al. Fiber-optic tracheal PEEP of 7.5 cmH2O obtained by a Boussignac valve powered by an None of the severely obese patients
intubation through a Boussignac oxygen flow of 30 l/min affixed to a face mask. Fiber-optic orotracheal experienced decrease in oxygen
valve to maintain continuous intubation carried out through the Boussignac valve. General anesthesia saturation during this intubation
oxygenation during intubation in accomplished when the tracheal tube had advanced to the glottis technique
severely obese patients: 11 cases
Rothfleisch et al. Facilitation of Emergent nasotracheal intubation using a fiber-optic bronchoscope with Fiber-optic video images of this
fiber-optic nasotracheal intubation simultaneous application of CPAP 20 cmH2O to the contralateral nares patient’s hypopharynx demonstrate the
in a morbidly obese patient by using a nasal pillow that helped maintain ventilation and facilitated pharyngeal splinting action of nasal
simultaneous use of nasal CPAP visualization of anatomic landmarks and translaryngeal passage of the CPAP thus applied (Fig. 68.1)
bronchoscope
Wong et al. Awake bronchoscopic BIPAP initially applied for preoxygenation. Single-use air-Q orally Oxygen saturation 97 % was
intubation through an air-Q with inserted in sitting position and BIPAP was applied to the air-Q, followed maintained during the intubation
the application of BIPAP by the insertion of endotracheal tube via the air-Q to 14 cm. ETT cuff process
inflated, and BIPAP connected to the ETT through a flexible connector
with a bronchoscope port. Bronchoscope advanced through the flexible
connector past the well-visualized glottis to the carina. ETT cuff deflated
and advanced over the bronchoscope into the trachea. ETT cuff reinflated
after confirmation of position
I. Barjaktarevic et al.
 68

Barjaktarevic et al. Bronchoscopic BIPAP delivered via nasal interface. Oral airway covered with 5 % All 10 patients intubated in the first
intubation during continuous nasal lidocaine ointment placed in the oropharynx. After sufficient topical attempt. Hypotension was the most
positive pressure ventilation in the anesthesia, intubating (Williams) airway placed in the oropharynx. ETT frequent complication. Mean decrease
treatment of hypoxemic inserted into the Williams airway and bronchoscope placed through the in oxyhemoglobin saturation during the
respiratory failure ETT and into the distal trachea. ETT inserted into the trachea using the procedure was 4.7 + 3.1
bronchoscope as the stylet. Bronchoscope withdrawn slowly to allow
visualization of the tip of the endotracheal tube in good position within the
trachea. Nasal NIV then removed (Fig. 68.2)
Cataldo et al. The Nasal The NOVA technique utilized nasal NIV during direct laryngoscopy and Potential elimination of apneic period
Oxygenation and Ventilation of the intubation (Fig. 68.3) during intubation
Airway (NOVA) Technique, a new
and safer approach to airway
management in the critically ill
patient
Noninvasive Ventilation in Difficult Endotracheal Intubation
585
586 I. Barjaktarevic et al.

followed by insertion of a tracheal tube into the tube of the LMA or ILM. Fiber-
optic intubation was performed during positive pressure ventilation at a pressure of
20 cm H2O that was continued through the tracheal tube. In the Patil mask group,
fiber-optic intubation was performed while positive pressure ventilation was main-
tained through the Patil mask. The ventilation was better during intubation with the
endoscopy mask than that with the LMA or ILM. However, gastric insufflation was
also more frequent. This study was performed in patients prior to elective surgery
and may not accurately reflect conditions in critically ill patients.
Nafeh et al. [14] performed fiber-optic-guided intubation in 11 severely obese
patients while maintaining CPAP with a Boussignac valve (Vygon Medical,
Montgomeryville, PA, USA) during the entire intubation procedure. The patients
received oral alprazolam or hydroxyzine and nasopharyngeal application of lido-
caine 5 %. The patients were placed in a half-sitting position during oxygenation
and the anesthesia procedure. PEEP of 7.5 cm H2O was obtained by a Boussignac
valve powered by an oxygen flow of 30 l/min and affixed to a face mask. After ini-
tiation of remifentanil, fiber-optic orotracheal intubation was carried out through the
Boussignac valve. General anesthesia was accomplished when the tracheal tube had
advanced to the glottis. No patient experienced a decrease in oxygen saturation.
This study was also performed in elective surgical patients.
Rothfleisch et al. [12] described a case report where they emergently nasotrache-
ally intubated a morbidly obese patient using a fiber-optic bronchoscope with simul-
taneous application of CPAP 20 cm H2O to the contralateral nares using a nasal
pillow that helped maintain ventilation. The CPAP treatment also facilitated visual-
ization of the anatomic landmarks and translaryngeal passage of the bronchoscope.
Wong et al. [15] described an awake bronchoscopic intubation in an obese patient
with a difficult airway and acute respiratory failure. BIPAP was initially applied for
preoxygenation given repeated oxygen desaturation. A single-use air-Q was orally
inserted in the sitting position and BIPAP was applied to the air-Q, followed by the
insertion of endotracheal tube via the air-Q to 14 cm. The endotracheal tube cuff
was inflated, and BIPAP was connected to the endotracheal tube through a flexible
connector with a bronchoscope port. A bronchoscope was advanced through the
flexible connector past the well-visualized glottis to the carina. The endotracheal
tube cuff was deflated and advanced over the bronchoscope into the trachea. The
endotracheal tube cuff was reinflated after confirmation of position. Oxygen satura-
tion of 97 % was maintained during the intubation procedure.
Barjaktarevic et al. [10] performed bronchoscopic-guided intubation with NIV in
10 patients with acute hypoxemic respiratory failure. These patients were initially
treated with NIV, had progressive hypoxemic respiratory failure, subsequently
failed NIV, and required rescue ETI. BIPAP was initially delivered via a full face
mask that was later changed to a nasal interface in anticipation of rescue orotracheal
intubation. Patients were ventilated with nasal NIV and placed in a semi-recumbent
position. An oral airway was covered with 5 % lidocaine ointment and placed in the
oropharynx. After sufficient topical anesthesia, an intubating (Williams) airway was
placed in the oropharynx and systemic sedation was administered (no
68 Noninvasive Ventilation in Difficult Endotracheal Intubation 587

Fig. 68.2 Bronchoscopic

intubation during
continuous nasal positive
pressure ventilation

Fig. 68.3 The NOVA technique utilizing nasal NIV during direct laryngoscopy and intubation

neuromuscular blockade was used). The endotracheal tube was inserted into the
Williams airway and the bronchoscope was placed through the endotracheal tube
and into the distal trachea. The endotracheal tube was then placed into the trachea
using the bronchoscope as the stylet. The bronchoscope was withdrawn slowly to
allow visualization of the tip of the endotracheal tube in good position within the
trachea. The endotracheal tube cuff was inflated, and the tube was attached to the
invasive mechanical ventilator circuit. The nasal NIV was then removed (Fig. 68.2).
Cataldo et al. [11] applied the Nasal Oxygenation and Ventilation of the Airway
(NOVA) technique with nasal mask NIV during rapid sequence intubation and
direct laryngoscopy in critically sick patients requiring ETI (Fig. 68.3). They pro-
posed that partially ventilating a paralyzed patient during rapid sequence intubation
may eliminate the apneic period altogether.
588 I. Barjaktarevic et al.

68.6 Limitations of NIV during ETI

Application of NIV greatly increases the complexity of ETI. The equipment costs
include the use of the ventilator, the disposable airway interface and ventilator tub-
ing, and the personnel to set up the equipment. Adding unfamiliar equipment and
procedures can distract practitioners during emergency airway management. Using
NIV during ETI may require more time and may not be feasible when there is insuf-
ficient time to properly prepare the patient and equipment. Many patients do not
tolerate NIV due to patient-ventilator asynchrony. Adequate patient selection and
careful titration and adjustment of NIV settings (mode, interface, and pressure titra-
tion) are essential.
Blood and excessive secretions in the airway may render NIV ineffective and
NIV may need to be avoided in patients at high risk of vomiting and aspirating gas-
tric contents. This complication is more likely if the patient has impaired gastric
emptying. The risk exists with an insufflation pressure > 20 cm H2O, which can be
easily obtained using manual ventilation, so limiting the positive pressure can
decrease the risk of aspiration [6, 16]. Routine use of a nasogastric tube is not war-
ranted. Most complications of NIV are local and related to the tightly fitting mask,
such as local skin damage, mask leak, and eye irritation.

Conclusions
NIV is a well-validated treatment in selected patients with respiratory failure.
NIV can also be used to support the patient during ETI. As an emerging concept,
new data are needed to define the best clinical situations for its use.

Key Major Recommendations

• Clinicians should consider using nasal NIV during ETI when it will be
beneficial to have a pneumatic stent for the upper airway or when it is
essential to continue gas exchange during the procedure.

References
1. Henderson JJ, et al. Difficult Airway Society guidelines for management of the unanticipated
difficult intubation. Anaesthesia. 2004;59(7):675–94.
2. Antonelli M, et al. Predictors of failure of noninvasive positive pressure ventilation in patients
with acute hypoxemic respiratory failure: a multi-center study. Intensive Care Med. 2001;
27(11):1718–28.
3. Strayer RJ, Caputo ND. Noninvasive ventilation during procedural sedation in the ED: a case
series. Am J Emerg Med. 2015;33(1):116–20.
4. Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during emergency
airway management. Ann Emerg Med. 2012;59(3):165–75.e1.
5. Davis DP, Hwang JQ, Dunford JV. Rate of decline in oxygen saturation at various pulse oximetry
values with prehospital rapid sequence intubation. Prehosp Emerg Care. 2008;12(1):46–51.
6. Baillard C, et al. Noninvasive ventilation improves preoxygenation before intubation of
hypoxic patients. Am J Respir Crit Care Med. 2006;174(2):171–7.
68 Noninvasive Ventilation in Difficult Endotracheal Intubation 589

7. Miguel-Montanes R, et al. Use of high-flow nasal cannula oxygen therapy to prevent desatura-
tion during tracheal intubation of intensive care patients with mild-to-moderate hypoxemia.
Crit Care Med. 2015;43(3):574–83.
8. Vourc’h, M, et al. High-flow nasal cannula oxygen during endotracheal intubation in hypox-
emic patients: a randomized controlled clinical trial. Intensive Care Med. 2015;98(1):28–33.
9. Edmark L, et al. Optimal oxygen concentration during induction of general anesthesia.
Anesthesiology. 2003;98(1):28–33.
10. Barjaktarevic I, Berlin D. Bronchoscopic intubation during continuous nasal positive pressure
ventilation in the treatment of hypoxemic respiratory failure. J Intensive Care Med. 2015;
30(3):161–6.
11. Cataldo S, Pedro M, Lokhandwala B. The Nasal Oxygenation and Ventilation of the Airway
(NOVA) technique, a new and safer approach to airway management in the critical ill patient.
SOJ Anesthesiol Pain Manag. 2014;1(2):1–4.
12. Rothfleisch R, et al. Facilitation of fiberoptic nasotracheal intubation in a morbidly obese
patient by simultaneous use of nasal CPAP. Chest. 1994;106(1):287–8.
13. Aoyama K, et al. Positive pressure ventilation during fibreoptic intubation: comparison of the
laryngeal mask airway, intubating laryngeal mask and endoscopy mask techniques. Br
J Anaesth. 2002;88(2):246–54.
14. Nafeh S, et al. Fiberoptic tracheal intubation through a Boussignac valve to maintain continu-
ous oxygenation during intubation in severely obese patients: 11 cases. J Clin Anesth. 2011;
23(4):345–6.
15. Wong DT, Wang J, Venkatraghavan L. Awake bronchoscopic intubation through an air-Q(R)
with the application of BIPAP. Can J Anaesth. 2012;59(9):915–6.
16. Ho-Tai LM, et al. Gas leak and gastric insufflation during controlled ventilation: face mask
versus laryngeal mask airway. Can J Anaesth. 1998;45(3):206–11.
Lung Ultrasound and Noninvasive
Ventilation 69
Giovanni Ferrari, Alberto Milan, and Giovanni Volpicelli

Contents
69.1 Introduction ................................................................................................................. 592
69.2 Lung Ultrasound and Alveolar Recruitment during Mechanical Ventilation ............. 592
69.3 Diaphragm Ultrasound to Estimate Work of Breathing during NIV .......................... 594
69.4 Lung Ultrasound and Weaning: Future Applications ................................................. 595
Conclusions ............................................................................................................................ 595
References .............................................................................................................................. 596

Abbreviations

ACPE Acute cardiogenic pulmonary edema

ARDS Acute respiratory distress syndrome
CPAP Continuous positive airway pressure
DT Diaphragm thickness
LUS Lung ultrasound
NIV Noninvasive ventilation
PEEP Positive end-expiratory pressure

G. Ferrari (*)
SC Pneumologia, Ospedale Mauriziano Umberto I, Largo Turati n. 62, Torino, Italy
e-mail: [email protected]
A. Milan
Hypertension Unit, Division of Internal Medicine, Department of Medical Sciences,
University Hospital AOU Città della Salute e della Scienza di Torino,
University of Torino, Torino, Italy
e-mail: [email protected]
G. Volpicelli
Department of Emergency Medicine, S.C.D.O, Medicina d’Urgenza, Ospedale
Universitario San Luigi Gonzaga, Orbassano, Torino, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 591

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_69
592 G. Ferrari et al.

PS Pressure support
PTPdi Transdiaphragmatic pressure-time product
TF Thickening fraction

69.1 Introduction

Until the end of the last century, the lung was considered an organ poorly accessible
to ultrasound, with the exception of the application for the study of pleural effu-
sions. However, notwithstanding its limitations, ultrasound has been increasingly
used in the last 15–20 years for examination of the lung in many conditions, such as
pneumonia, atelectasis, interstitial syndromes, pneumothorax, and evaluation of
diaphragm dysfunction. The advantages of lung ultrasound (LUS) are ease of use at
bedside, the repeatability of the examination without exposure to ionizing radia-
tions, and the relatively short learning curve. Many studies have been published
demonstrating the diagnostic potential of LUS in several clinical situations, but, to
the best of our knowledge, scant literature exists on LUS during noninvasive venti-
lation (NIV).
This chapter focuses on the importance of LUS in patients undergoing mechani-
cal ventilation. LUS may have an important therapeutic impact in decision-making
processes in patients undergoing mechanical ventilation. In the study of Xirouchaki
and coworkers [1], LUS changed the clinical behavior in 47 % of patients undergo-
ing mechanical ventilation in the intensive care unit. These changes involved either
invasive maneuvers, such as chest tube insertion, bronchoscopy, and continuous
veno-venous hemofiltration (CVVH), or noninvasive maneuvers, such as positive
end-expiratory pressure (PEEP) titration, recruitment maneuvers, and antibiotic
therapy. Moreover, the authors found that one-fifth of the ultrasound examinations
revealed findings compatible with diagnoses that were not in the differential diag-
nosis after the primary evaluation [1].
This chapter examines the potential of LUS in the assessment of alveolar recruit-
ment and the estimation of the work of breathing during NIV, and also the possibil-
ity of using LUS as a new index of discontinuation from mechanical ventilation.

69.2 Lung Ultrasound and Alveolar Recruitment during

Mechanical Ventilation

In critically ill patients, LUS can be easily performed at bedside. Interstitial syn-
drome, lung consolidations, and pleural effusion can be easily recognized. According
to the first international consensus conference on point-of-care lung ultrasound, the
examination targeted to the diagnosis of the interstitial syndrome should be per-
formed in four chest areas per side (an eight-zone examination) [2]. However, the
experts validated two other methods: a more rapid anterior two-region scan in criti-
cally ill patients and evaluation of 28 rib interspaces in the cardiology setting. LUS
showed its potential in the first diagnosis and follow-up of lung consolidations and
69 Lung Ultrasound and Noninvasive Ventilation 593

the differential diagnosis between pulmonary embolism, pneumonia, or compres-

sive and obstructive atelectasis [2]. In lung consolidation, acute respiratory distress
syndrome (ARDS), and pulmonary congestion, LUS can be useful to assess semi-
quantitatively and monitor changes in lung aeration by observing the progression of
four fundamental sonographic patterns: normal aeration, multiple B-lines, coales-
cent B-lines, and consolidation [2–5].
To the best of our knowledge, there is only one study that has evaluated the use
of LUS for the assessment of continuous positive airway pressure (CPAP) treatment
in patients with acute cardiogenic pulmonary edema (ACPE) [6]. The authors of this
study compared the efficacy of prehospital CPAP plus medical treatment as opposed
to oxygen plus medical treatment in patients with ACPE, using LUS to evaluate
response to treatment. Although the study suffers from some limitations, the use of
LUS to assess the outcome after treatment was of interest. The authors found a sig-
nificant decrease in the number of B-lines in patients with ACPE treated with CPAP
in comparison with standard medical treatment.
Assessment of lung recruitment is important not only in ACPE, but it is also
crucial in the management of patients with ARDS. In critically ill patients, LUS has
gained an important role in the evaluation of lung consolidations and, according to
some studies, LUS can be used as a diagnostic tool for the assessment of lung
recruitment induced by PEEP [5, 7].
Assuming that in ARDS the visible ultrasound pattern corresponds to a degree of
lung aeration, Bouhemad and coworkers [5] studied prospectively 40 patients with
ALI/ARDS undergoing invasive mechanical ventilation. They associated the pres-
ence of multiple spaced B-lines with moderate decrease in lung aeration (interstitial
syndrome), coalescent B lines with more severe decrease in lung aeration, and lung
consolidation containing white points characterized by an inspiratory reinforce-
ment, the so-called dynamic air bronchogram, with complete loss of lung aeration.
In the study, the authors used the pressure-volume curve as a gold-standard method
to measure lung recruitment and find out that PEEP-induced recruitment could be
accurately estimated by LUS. In another study, the authors, using the same re-
aeration score, used LUS to assess lung aeration during weaning and concluded that
the determination of aeration changes during a spontaneous breathing trial could
predict the post-extubation distress more accurately than natriuretic peptides or car-
diac filling pressure estimated by echocardiography [8].
There are no original blind studies on lung recruitment during NIV and only one
conference abstract, in which the authors evaluated re-aeration score as a predictive
tool in patients treated with NIV [9]. In this trial, LUS was performed before start-
ing NIV, after 5 min, and after 60 min of NIV treatment. LUS patterns were defined
using the same classification validated in the study of Bouhemad [5]. Out of 16
patients enrolled, 5 failed NIV treatment. A significant difference in re-aeration
score between the two groups (patients who failed and patients who were treated
successfully with NIV) was found after 1 h of treatment. In this preliminary report,
the authors concluded that a re-aeration cut-off value of 0 could predict NIV suc-
cess, with a sensitivity of 91 % and a specificity of 80 %. No data are provided on
gas exchange during treatment and the results must be interpreted cautiously.
594 G. Ferrari et al.

However, if confirmed in larger trials, these results might support the use of LUS as
an effective tool to evaluate patient response during NIV. This may be extremely
useful, because in patients with pneumonia or ARDS, the percentage of failure to
NIV treatment is high [10, 11], while, to date, the most reliable variables associated
with NIV success are the improvement in gas exchange and a low clinical score as
assessed by Simplified Acute Physiology Score (SAPS) II [10, 12]. LUS could be
of help in the early recognition of patients who will fail NIV treatment, thus avoid-
ing a possible delay in endotracheal intubation, a condition that is associated with
an unfavorable outcome. Further original studies are warranted to establish the reli-
ability of LUS in patients with hypoxemic respiratory failure treated with NIV.

69.3 Diaphragm Ultrasound to Estimate Work

of Breathing during NIV

Even if scant literature exists on NIV and LUS, ultrasonography has great diagnos-
tic potential in patients undergoing mechanical ventilation, either invasive or nonin-
vasive. In an elegant study, Vivier et al. [13] hypothesized that measurement of
diaphragm thickness (DT) could reflect the magnitude of diaphragmatic work,
thereby helping to optimize ventilatory setting. In particular, the relationship
between DT and the level of pressure support (PS) was investigated.
Diaphragmatic ultrasound was performed, placing the transducer in the zone of
apposition of the diaphragm in the midaxillary line. The thickness of the muscle
was recorded in time motion mode [14]. Thickness was measured at end inspiration
(Tei) and at end expiration (Tee), and thickening fraction (TF) was assessed with the
following formula: Tei – Tee/Tei %. Transdiaphragmatic pressure was recorded by
measurement of esophageal and gastric pressure; the transdiaphragmatic pressure-
time product (PTPdi) per breath was obtained by measuring the area under the Pdi
signal from the onset of its positive deflection to its return to baseline. Out of 14
patients enrolled in the study, the quality of the ultrasound image was good in 12
and not acceptable in only 2. Records of the diaphragm images were obtained ini-
tially during spontaneous breathing and subsequently during NIV treatment, at dif-
ferent PS levels (5, 10, and 15 cmH2O applied randomly). Tidal volume increased
with the increase of PS, and the increase in PS was associated with the decrease of
PTPdi and of TF. Furthermore, TF correlated significantly with PTPdi [13].
This study is important as it is the first to have evaluated the usefulness of dia-
phragm ultrasound to assess the work of breathing in patients weaned from MV
with noninvasive PS. One of the most important and reliable methods to measure
patient muscle effort is PTPdi. However, this method is invasive, requires high
expertise, and is only applicable in the setting of research studies. On the other
hand, the ease of use and the reproducibility of ultrasound allow frequent bedside
reassessment of the patients. In the study of Vivier et al. [13], the authors showed
that, during NIV, the thickening of the diaphragm is related to the muscular effort
itself and this result, if confirmed by further studies, could be of help in the predic-
tion of weaning from mechanical ventilation.
One of the criticisms that can be made of the measurement of diaphragmatic
thickness is its reliability and reproducibility. Cohn and coworkers [15], however,
69 Lung Ultrasound and Noninvasive Ventilation 595

showed that ultrasound measurement of the diaphragm correlated significantly with

the measure obtained with a ruler in cadavers. Regarding reproducibility, measure-
ment of diaphragm thickness showed a high intra- and interobserver reproducibility
[13, 16], and another study [17] demonstrated that diaphragmatic ultrasound is also
highly reproducible in patients under mechanical ventilation.

69.4 Lung Ultrasound and Weaning: Future Applications

The important role of ultrasound in assessing diaphragm function has already been
studied, but the attention of the researchers has only more recently focused on the
use of LUS in weaning from mechanical ventilation. Before focusing on ultrasound
and weaning, the researchers have evaluated diaphragm function in healthy sub-
jects, either assessing diaphragm displacement, either diaphragm thickening during
inspiration. One study evaluated diaphragm motion in healthy subjects, identifying
normal values of diaphragm excursion [18]. By positioning the probe below the
costal margin, between the mid-clavicular and anterior axillary line, the movement
of the right hemi-diaphragm could be assessed in most of the patients, while the
visualization of the left hemi-diaphragm was more difficult due to the poor acoustic
window of the spleen. Mean excursions were measured and reference values for
quiet breathing, deep breathing, and voluntary sniffing were assessed.
Diaphragm thickness has been also evaluated in healthy subjects by placing the
probe in the zone of the apposition of the diaphragm [15]. Ultrasound measure-
ments were reproducible at different lung volumes, ranging from residual volume to
total lung capacity.
The ease of use and the noninvasiveness characteristic of diaphragm ultra-
sound contrasts with the complicated traditional methods of diaphragm evalua-
tion, some relying also on the use of ionizing radiation. Diaphragm function has
been studied, assessing its movement during inspiration [19, 20] and measuring
thickening fraction [16]. Both methods are highly reproducible and may detect
diaphragm dysfunction and predict weaning failure. If compared with traditional
methods used to assess diaphragm function (measurement of trans-diaphrag-
matic pressure, phrenic nerve stimulation, fluoroscopy, and electromyography),
ultrasound is simple, rapid, and noninvasive. Ultrasound can be repeated several
times without any risk to the patient, providing important information on his or
her respiratory function.
Alhough there is the need for confirmation by further studies, available literature
data suggest that ultrasound of the diaphragm has an important potential in predicting
patients who may fail a weaning attempt. However, as no data exist in literature on the
use of LUS in weaning from NIV, future research should be particularly addressed to
the investigation of the role of diaphragm ultrasound in patients undergoing NIV.

Conclusions
LUS has widespread application in clinical practice in assessing and monitoring
many pulmonary conditions. However, scant literature exists on the application
of ultrasound during NIV. Future studies on LUS may provide physicians with
important data regarding how to titrate extrinsic PEEP in patients undergoing
596 G. Ferrari et al.

NIV or assess patient-ventilator asynchrony [21]. One of the future applications

will be the application of diaphragm evaluation for the assessment of the patient
with acute respiratory failure undergoing NIV.

References
1. Xirouchaki N, Kondili E, Prinianakis G, et al. Impact of lung ultrasound on clinical decision
making in critically ill patients. Intensive Care Med. 2014;40(1):57–65.
2. Volpicelli G, Elbarbary M, Blaivas M, et al. International evidence-based recommendations
for point-of-care lung ultrasound. Intensive Care Med. 2012;38(4):577–91.
3. Agricola E, Bove T, Oppizzi M, et al. “Ultrasound comet-tail images”: a marker of pulmonary
edema: a comparative study with wedge pressure and extravascular lung water. Chest. 2005;
127(5):1690–5.
4. Bouhemad B, Liu ZH, Arbelot C, et al. Ultrasound assessment of antibiotic-induced pulmo-
nary reaeration in ventilator-associated pneumonia. Crit Care Med. 2010;38(1):84–92.
5. Bouhemad B, Brisson H, Le-Guen M, et al. Bedside ultrasound assessment of positive end-
expiratory pressure-induced lung recruitment. Am J Respir Crit Care Med. 2011;183(3):
341–7.
6. Strnad M, Prosen G, Borovnik Lesjak V. Bedside lung ultrasound for monitoring the effective-
ness of prehospital treatment with continuous positive airway pressure in acute decompensated
heart failure. Eur J Emerg Med. 2014. doi:10.1097/MEJ.0000000000000205.
7. Arbelot C, Ferrari F, Bouhemad B, et al. Lung ultrasound in acute respiratory distress
syndrome and acute lung injury. Curr Opin Crit Care. 2008;14(1):70–4.
8. Soummer A, Perbet S, Brisson H, et al. Ultrasound assessment of lung aeration loss during
a successful weaning trial predicts postextubation distress*. Crit Care Med. 2012;40(7):
2064–72.
9. Nobile L, Beccaria P, Zambon M et al. Lung ultrasound reaeration score: a useful tool to pre-
dict non-invasive ventilation effectiveness. 34th international symposium on intensive care and
emergency medicine. Crit Care. 2014;18(Suppl 1):P1–502.
10. Antonelli M, Conti G, Esquinas A, et al. A multiple-center survey on the use in clinical prac-
tice of noninvasive ventilation as a first-line intervention for acute respiratory distress syn-
drome. Crit Care Med. 2007;35(1):18–25.
11. Rana S, Jenad H, Gay PC, et al. Failure of non-invasive ventilation in patients with acute lung
injury: observational cohort study. Crit Care. 2006;10(3):R79.
12. Antonelli M, Conti G, Moro ML, et al. Predictors of failure of noninvasive positive pressure
ventilation in patients with acute hypoxemic respiratory failure: a multi-center study. Intensive
Care Med. 2001;27(11):1718–28.
13. Vivier E, Mekontso Dessap A, Dimassi S, et al. Diaphragm ultrasonography to estimate
the work of breathing during non-invasive ventilation. Intensive Care Med. 2012;38(5):
796–803.
14. Wait JL, Nahormek PA, Yost WT, et al. Diaphragmatic thickness-lung volume relationship
in vivo. J Appl Physiol (1985). 1989;67(4):1560–8.
15. Cohn D, Benditt JO, Eveloff S, et al. Diaphragm thickening during inspiration. J Appl Physiol
(1985). 1997;83(1):291–6.
16. Ferrari G, De Filippi G, Elia F, et al. Diaphragm ultrasound as a new index of discontinuation
from mechanical ventilation. Crit Ultrasound J. 2014;6(1):8.
17. Goligher EC, Laghi F, Detsky ME, et al. Measuring diaphragm thickness with ultrasound in
mechanically ventilated patients: feasibility, reproducibility and validity. Intensive Care Med.
2015;41(4):642–9.
69 Lung Ultrasound and Noninvasive Ventilation 597

18. Boussuges A, Gole Y, Blanc P. Diaphragmatic motion studied by m-mode ultrasonography:

methods, reproducibility, and normal values. Chest. 2009;135(2):391–400.
19. Lerolle N, Guérot E, Dimassi S, et al. Ultrasonographic diagnostic criterion for severe dia-
phragmatic dysfunction after cardiac surgery. Chest. 2009;135(2):401–7.
20. Kim WY, Suh HJ, Hong SB, et al. Diaphragm dysfunction assessed by ultrasonography: influ-
ence on weaning from mechanical ventilation. Crit Care Med. 2011;39(12):2627–30.
21. Matamis D, Soilemezi E, Tsagourias M, et al. Sonographic evaluation of the diaphragm in
critically ill patients. Technique and clinical applications. Intensive Care Med. 2013;39(5):
801–10.
Noninvasive Ventilation in Cardiac
Procedures: Key Technical 70
and Practical Implications

Francesco Sbrana, Bruno Formichi, and Antonio Pisano

Contents
70.1 Introduction ................................................................................................................. 600
70.2 Cardiac Catheterization Laboratory ............................................................................ 600
70.3 Percutaneous Cardiac Valve Procedures ..................................................................... 601
70.4 TEE ............................................................................................................................. 602
70.5 Electrophysiological Procedures................................................................................. 604
References .............................................................................................................................. 605

Abbreviations

AMI Acute myocardial infarction

AS Aortic stenosis
CPAP Continuous positive airway pressure
EPAP Expiratory positive airway pressure
FiO2 Inspiratory oxygen fraction
ICU Intensive care unit
IPAP Inspiratory positive airway pressure

F. Sbrana, MD
Lipid Apheresis Unit, Fondazione Toscana Gabriele Monasterio,
Via Moruzzi, 1, Pisa 5614, Italy
e-mail: [email protected]
B. Formichi, MD
Division of Anesthesia and Intensive Care, National Research Council – Institute of Clinical
Physiology and Fondazione Toscana Gabriele Monasterio, Via Moruzzi, 1, Pisa 5614, Italy
e-mail: [email protected]
A. Pisano, MD (*)
Cardiac Anesthesia and Intensive Care Unit, A.O.R.N. “Dei Colli” – Monaldi Hospital,
via L. Bianchi 80131, Naples, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 599

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_70
600 F. Sbrana et al.

MR Mitral regurgitation
NIV Noninvasive ventilation
PaCO2 Arterial partial pressure of CO2
PCI Percutaneous coronary intervention
PEEP Positive end-expiratory pressure
PSV Pressure support ventilation
SaO2 Arterial oxygen saturation
TAVI Transcatheter aortic valve implantation
TEE Transesophageal echocardiography

70.1 Introduction

Noninvasive ventilation (NIV) is broadly used in patients with both chronic and
acute respiratory failure, both inside and outside the intensive care unit (ICU).
Moreover, NIV may be applied to allow safe sedation in several clinical contexts
and increasingly is used to treat or even prevent postoperative pulmonary complica-
tions after major surgery. Today, NIV is also increasingly used during nonsurgical
cardiac procedures in which there is an actual risk of respiratory distress or failure,
such as percutaneous coronary interventions (PCI) performed in patients with pul-
monary edema secondary to acute myocardial infarction (AMI), as well as percuta-
neous valve procedures, which mostly involve high-risk patients who often need
sedation. Finally, the use of NIV to aid less-invasive diagnostic cardiac procedures
such as transesophageal echocardiography (TEE) has been reported.
Although some concerns regarding the use of NIV in these procedures may exist,
a team well trained in managing NIV often may carry them out safely, even in
highly compromised patients. The following sections describe the use of NIV in the
cardiac catheterization laboratory, during percutaneous cardiac valve procedures, to
aid TEE examination, and during electrophysiological procedures, focusing on both
technical and clinical aspects.

70.2 Cardiac Catheterization Laboratory

Procedures performed in the cardiac catheterization laboratory include coronary

angiography, PCI, percutaneous closure of septal defects, and transcatheter car-
diac valve stents [1]. Coronary angiography and PCI are usually performed with-
out sedation and/or ventilatory support. Accordingly, these procedures do not need
anesthesia care, except when respiratory distress or hemodynamic instability coex-
ist, due to AMI, pulmonary edema, or heart failure.
Yamamoto and colleagues [2] successfully used NIV in 261 patients with pulmo-
nary edema (secondary or not to AMI) undergoing coronary angiography and
PCI. In this retrospective, single-center study, patients received continuous positive
airways pressure (CPAP) via a full or total face mask using a BiPAP Vision machine
70 Noninvasive Ventilation in Cardiac Procedures 601

(Respironics, Murrysville, PA, USA) as first-line treatment. The initial positive end-
expiratory pressure (PEEP) was 4–10 cmH2O and was subsequently adjusted to
improve patient comfort. Inspiratory oxygen fraction (FiO2) was set to achieve an
arterial oxygen saturation (SaO2) > 95 %. If the patient complained of dyspnea at
30 min after initiation of CPAP treatment, NIV with a bi-level positive airway pres-
sure (BiPAP) modality was started. NIV effectively improved oxygenation and low-
ered the tracheal intubation rate in patients with cardiogenic pulmonary edema of
all etiologies, including AMI.
Whereas percutaneous closure of septal defects is usually performed under gen-
eral anesthesia with tracheal intubation, transcatheter cardiac valve procedures can
be also performed in awake patients with sedation and the aid of NIV [3, 4], as
discussed in the following section.

70.3 Percutaneous Cardiac Valve Procedures

Surgery is the standard of care for valve diseases such as aortic stenosis (AS) or
mitral regurgitation (MR). However, percutaneous procedures represent an alterna-
tive in patients for whom the risk of surgery is considered too high, due to older age,
poor general health status, or severe comorbidities. In particular, about 30 % of
patients with AS belongs to this “inoperable”/high-risk subset [3]. In these patients,
transcatheter aortic valve implantation (TAVI) allows minimization of surgical
stress (by avoiding sternotomy and cardiopulmonary bypass, and decreasing the
duration of intervention). Moreover, TAVI can usually be performed under local
anesthesia, thus avoiding the potential risks of general anesthesia, tracheal intuba-
tion, and mechanical ventilation [4]. However, the supine position, which is neces-
sary during the procedure (usually lasting at least 1.5 h), is often poorly tolerated by
orthopneic patients, especially when respiratory diseases coexist. Accordingly,
sedation is generally required, with possible further worsening of respiratory func-
tion and gas exchanges.
Guarracino and colleagues reported the use of NIV during TAVI in five
patients with orthopnea and severe chronic pulmonary disease (pulmonary
fibrosis in four patients and silicosis in one patient) [4], as well as in patients
undergoing transfemoral [5] or transaxillary [3] TAVI who needed intraproce-
dural TEE, which may contribute to respiratory impairment. The five patients
with severe pulmonary comorbidities underwent CoreValve (Medtronic, CV
Luxembourg) implantation and received pressure support ventilation (PSV) by
a Vision NIV ventilator (Respironics Inc., Murrysville, PA, USA) connected to
an adult oronasal mask (VIP 75TM 7500 Series V masksTM, Hans Rudolph, Inc.,
Kansas City, MO, USA). PSV was initially set at 8–12 cmH2O, with a PEEP of
4–6 cmH2O and a FiO2 of 0.35–0.5, and was subsequently adjusted to maintain
a SaO2 >92 % and an arterial partial pressure of CO2 (PaCO2) <50 mmHg. All
patients were adequately sedated to be comfortable during the entire procedure.
No complications occurred.
602 F. Sbrana et al.

Theoretically, even percutaneous mitral repair (mitral clip) could be performed

in awake patients with the aid of NIV [6], which may also allow safe intraprocedural
TEE (see below). However, to the authors’ knowledge, there are no literature reports
in this regard.

70.4 TEE

TEE has been used for many years both as a diagnostic tool, mostly in patients with
severe cardiac diseases (e.g., atrial fibrillation, prosthetic valve dysfunction, and
infective endocarditis), and as a monitoring adjunct for percutaneous cardiac proce-
dures, including TAVI and, more recently, mitral clip, which are usually performed
in high-risk patients [3–5, 7]. Because TEE often causes temporary arterial blood
gas worsen during and after examination, respiratory failure and/or severe cardiac
arrhythmias may occur in frail patients undergoing diagnostic or intraprocedural
TEE [5]. For example, orthopneic patients may develop respiratory failure due to
the supine position, in addition to the presence of the probe [6]. Moreover, because
TEE is a relatively invasive procedure, possibly causing pain, dangerous reflexes,
and emotional distress, sedation is often required to perform the exam. However,
sedation itself, besides the examination-related stress, may cause cardiorespiratory
failure, while general anesthesia may result in significant complications, primarily
respiratory, and is generally poorly tolerated by high-risk cardiac patients [5, 6, 8].
The use of NIV to aid TEE examination in severely ill, high risk patients has
been suggested in recent years [3, 5, 8]. Indeed, under these circumstances, NIV
could both improve patient tolerance to the examination and allow safe sedation.
Guarracino et al. [3, 5] reported the use of NIV via a modified face mask to support
TEE examination in severe, orthopneic cardiac patients undergoing transcatheter aor-
tic valve implantation or valvuloplasty. The TEE probe was passed through a vertical
hole obtained on the anterior part of an adult oronasal NIV mask (VIP 75 7500 Series
V masks) by a surgical cutter. No air leakage was observed. PSV, with an inspiratory
positive airway pressure (IPAP) of 8–12 cmH2O, a PEEP of 4–6 cmH2O, and a FiO2
of 0.35–0.5 was used. NIV was administered for the entire procedure and for the fol-
lowing 2 hours, and appeared to be effective in allowing orthopneic patients to lie in
the supine position and in preventing respiratory failure due to sedation.
More recently, Pisano et al. [8] performed TEE during NIV through a helmet in a
poorly cooperative ICU patient, with multiple severe comorbidities, who developed
cardiorespiratory failure following high-risk replacement of a malfunctioning mitral
mechanical prosthesis. No change of ventilator settings or modality (PSV) was neces-
sary. Tidal volumes, respiratory rate, arterial blood gases, and hemodynamic param-
eters remained unchanged during and after the procedure. Moreover, NIV allowed
adequate sedation, thus avoiding general anesthesia and tracheal intubation.
However, a technical issue limits the possibility of performing TEE through a
helmet. In fact, the airtight ports for catheters or probes available on helmets are not
large enough to allow insertion and movements of the TEE probe. Pisano and col-
leagues used the larger airtight port that is located on the Castar R Next helmet
70 Noninvasive Ventilation in Cardiac Procedures 603

Fig. 70.1 TEE

examination through a
non-invasive ventilation
helmet in a sedated patient.
Part of a tracheostomy
foam dressing is used as an
airtight sleeve (arrow).
Reproduced from Pisano
et al. [8]

a b

Fig. 70.2 The Janus full face mask. (a). Closed. (b). Opened. Courtesy of Biomedical (Florence,
Italy)

(StarMed, Mirandola, Italy), after removing the inner airtight sleeve. The resulting
gross air leakage was avoided by using part of a tracheostomy foam dressing
(Pharmaplast, Alexandria, Egypt), rolled up around the portion of the probe that
crossed the helmet, as an airtight sleeve (Fig. 70.1). The availability on NIV helmets
of a multipurpose airtight port, allowing insertion and adequate movements of the
TEE probe, may be desirable if further research will confirm safety and effective-
ness of this, as well as other endoscopic procedures, through NIV helmets.
Conversely, oronasal masks provided with an airtight port for endoscopy, which
also allows TEE examination, are already available on the market. In particular, an
openable full face mask exists (Janus, Biomedical, Florence, Italy) (Fig. 70.2),
604 F. Sbrana et al.

which can be applied to the patient even after the TEE probe has been positioned,
allowing NIV to start, if necessary (unexpected respiratory distress or need of seda-
tion) without stopping the exam [6].

70.5 Electrophysiological Procedures

Patients undergoing electrophysiological mapping, which is a catheter-based proce-

dure for ventricular arrhythmias, or catheter ablation for atrial fibrillation are required
to lie motionless on the table for several hours, and repeated stimuli from ablation
are sometimes painful. For these reasons, patients usually need deep sedation or
general anesthesia.
Sbrana et al. [9] described a case series of patients who underwent catheter abla-
tion for atrial fibrillation. In these patients, NIV and deep sedation were started after
trans-septal puncture. NIV was performed through a latex-free total face mask
(Respironic®, Murrysville, PA, USA) (Fig. 70.3) connected to a Garbin ventilator
(Linde Inc., Herrsching, Germany) in spontaneous/temporized mode, applying
incorporated algorithms to improve patient-ventilator synchrony by adjusting to
changing breathing patterns and dynamic leaks. During the procedure, in addition
to routine monitoring, serial arterial blood gas analyses and invasive arterial pres-
sure monitoring were performed. IPAP, expiratory positive airway pressure (EPAP),
and respiratory rate were modified according to the clinical response, including
patient tolerance, to obtain an exhaled tidal volume of 6–8 ml/kg; the FiO2 require-
ment to maintain SaO2 above 92 % was ≤0.4.
In this group of patients, no respiratory complications, problems due to gastric
distention, issues related to the ventilation interface (mask), NIV discomfort, or
significant hemodynamic effects due to positive pressure ventilation were reported.
Furthermore, these patients maintained (although with respiratory parameters in the
physiological range) better arterial blood gases and acid–base balance compared

Fig. 70.3 A patient

ventilated through the
Respironic® latex-free
total face mask during
catheter ablation for atrial
fibrillation
70 Noninvasive Ventilation in Cardiac Procedures 605

with a deep sedation group without NIV [10]. Finally, a continuous monitoring of
tidal volume, air leak, and actual minute ventilation during the entire procedure
contributed to patient safety.

Key Major Recommendations

• NIV should be considered in patients with pulmonary edema (including
patients with acute myocardial infarction) undergoing coronary angiogra-
phy and PCI.
• NIV may have an additional role in the anesthetic management of percuta-
neous cardiac valve procedures (TAVI and mitral clip) and electrophysio-
logical procedures.
• The use of NIV to aid TEE examination in severely ill, high-risk patients
could both improve patient tolerance to the examination and allow safe
sedation.
• Skilled personnel, adequate monitoring, and appropriate ventilatory inter-
faces allow the safe use of NIV during most cardiac procedures, minimiz-
ing complications in frail or high-risk patients.

References
1. Hamid A. Anesthesia for cardiac catheterization procedures. Heart Lung Vessel. 2014;
6(4):225–31.
2. Yamamoto T, Takeda S, Sato N, et al. Noninvasive ventilation in pulmonary edema complicat-
ing acute myocardial infarction. Circ J. 2012;76(11):2586–91.
3. Guarracino F, Covello RD, Landoni G, et al. Anesthetic management of transcatheter aortic
valve implantation with transaxillary approach. J Cardiothorac Vasc Anesth. 2011;25:
437–43.
4. Guarracino F, Cabrini L, Baldassarri R, et al. Noninvasive ventilation for awake percutaneous
aortic valve implantation in high-risk respiratory patients: a case series. J Cardiothorac Vasc
Anesth. 2011;25(6):1109–12.
5. Guarracino F, Cabrini L, Baldassarri R, et al. Non-invasive ventilation-aided transoesophageal
echocardiography in high-risk patients: a pilot study. Eur J Echocardiogr. 2010;11:554–6.
6. Cabrini L, Zangrillo A, Landoni G. Preventive and therapeutic noninvasive ventilation in car-
diovascular surgery. Curr Opin Anaesthesiol. 2015;28(1):67–72.
7. Peterson GE, Brickner ME, Reimold SC. Transesophageal echocardiography: clinical indica-
tions and applications. Circulation. 2003;107(19):2398–402.
8. Pisano A, Angelone M, Iovino T, et al. Transesophageal echocardiography through a non-
invasive ventilation helmet. J Cardiothorac Vasc Anesth. 2013;27(6):e78–81.
9. Sbrana F, Ripoli A, Formichi B. Safety and utility of noninvasive ventilation during deep seda-
tion for catheter ablation of atrial fibrillation. J Cardiothorac Vasc Anesth. 2014;28(1):e6–8.
10. Sbrana F, Ripoli A, Formichi B. Anesthetic management in atrial fibrillation ablation proce-
dure: adding non-invasive ventilation to deep sedation. Indian Pacing Electrophysiol J. 2015
(in press). doi:10.1016/j.ipej.2015.07.003
Noninvasive Mechanical Ventilation
During Bronchoscopy: Key Technical 71
and Clinical Evidence

Raffaele Scala

Contents
71.1 Introduction ................................................................................................................. 607
71.2 Pitfalls of Bronchoscopy and NIMV .......................................................................... 608
71.3 Rationale for the Combined Use of NIMV and FBO ................................................. 609
71.4 Clinical Evidence of NIMV-Bronchoscopy Synergy .................................................. 610
71.5 Special Situations ........................................................................................................ 614
71.5.1 Difficult Intubation ........................................................................................ 614
71.5.2 Obstructive Sleep Apnea Syndrome.............................................................. 615
71.5.3 Interventional Procedures During RB ........................................................... 615
71.6 Practical Issues ............................................................................................................ 616
Conclusions ............................................................................................................................ 618
References .............................................................................................................................. 619

71.1 Introduction

Among the procedures that are routinely used in both general intensive care units
(ICUs) and respiratory intensive care units (RICUs), bronchoscopy and noninvasive
mechanical ventilation (NIMV) constitute “musts” for clinicians who face challeng-
ing scenarios in critically ill patients. Flexible bronchoscopy (FBO) represents a
well-defined step in the diagnostic flowchart of severe community-acquired and
hospital-acquired pneumonia, as well as acute interstitial lung diseases [1]. This is
due to its wide range of ancillary diagnostic procedures, including bronchoalveolar
lavage (BAL), protected specimen brush (PSB), transbronchial need aspiration,
transbronchial lung biopsy (TBLB) and endobronchial ultrasound [1]. Although it

R. Scala, MD, FCCP

Respiratory Ward and Pulmonary Intensive Care Unit, S. Donato Hospital,
Via Nenni, 8 -52100, Arezzo, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 607

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_71
608 R. Scala

has less major application, rigid bronchoscopy (RB) plays a crucial role in perform-
ing interventional procedures (laser, argon plasma, and stent position) in critical
patients with tracheal or main bronchial stenosis, massive hemoptysis, and inhaled
foreign body, especially in pediatric patients [2].
NIMV includes negative and positive pressure ventilatory techniques that have
been shown to achieve the “goals of mechanical ventilation” (i.e., unload respira-
tory muscles, improve pulmonary gas exchange, and increase alveolar ventilation)
without the risk of conventional mechanical ventilation (CMV)-correlated compli-
cations. Because of the tremendous technological improvements in ventilators and
interfaces, positive-pressure NIMV (ppNIMV) has become the first-line ventilatory
treatment in different patterns of acute respiratory failure (ARF), including acidotic
chronic obstructive pulmonary disease (COPD) exacerbations, cardiogenic pulmo-
nary edema, and immunosuppressed conditions. Compared with standard medical
therapy, ppNIMV reduces the rate of endotracheal intubation (ETI) and its compli-
cations, as well as mortality and length of stay in hospital [3]. Conversely, negative-
pressure NIMV (npNIMV), mainly delivered by an “iron lung,” is now performed
only in a few expert centers to manage selected patients (e.g., COPD exacerbations
nonresponsive to ppNIMV, respiratory distress syndrome, and weaning difficulty,
especially in pediatric patients) [4].
In this chapter, the rationale, clinical indications, scientific evidence, practical
issues, and risks for the synergistic use of bronchoscopy during NIMV are reported.

71.2 Pitfalls of Bronchoscopy and NIMV

Even with its widespread application in the ICU/RICU, bronchoscopy can be chal-
lenging and risky in nonintubated patients with ARF. This is the case with diagnos-
tic FBO in subjects admitted to the ICU/RICU for severe hypoxemia caused by lung
infiltrates of unknown origin. Performing bronchoscopy in critically ill patients
presents potential complications that can be related to the procedure itself, patient-
related factors, and the bronchoscopist’s experience. The cardiopulmonary patho-
physiological effects of FBO have been well investigated [1, 2].
The bronchoscope occupies 10–15 % of the normal tracheal lumen, causing an
increase in resistance of the airway and a drop in tidal volume with the augmenta-
tion of work of breathing. Consequently, the patient develops a rapid shallow breath-
ing pattern with a risk of impending respiratory muscle fatigue, worsening of gas
exchange, and the need for mechanical ventilation. Because of the incomplete expi-
ratory lung emptying, FBO can facilitate “air trapping” with a generation of intrin-
sic positive end-expiratory pressure (PEEP), which is particularly deleterious in
COPD [1, 2].
Hypoxemia occurs with insertion of the bronchoscope into the trachea and
becomes worse when BAL is performed, as a consequence of ventilation-perfusion
(V/Q) mismatch. The application of suction through the bronchoscope channel low-
ers airway pressure at the end of expiration, facilitating early alveolar closure and
hypoxemia. As a matter of a fact, FOB induces arterial oxygen pressure (PaO2) to
71 Noninvasive ventilation During Bronchoscopy 609

decrease between 10 and 20 mmHg [1, 2]. The use of analgo-sedation during FBO
to reduce patient discomfort may worsen gas exchange further through drug-induced
hypoventilation. These pulmonary changes persist after the procedure is completed,
and the time that the gas exchange takes to normalize ranges from 15 min in normal
subjects to several hours in patients with lung disease. All this justifies the use of
supplemental O2 in patients undergoing FBO at risk of oxygen desaturation [1].
FBO-induced sympathetic stimulation and hypoxemia can lead to an increase in
heart rate and cardiac output with the heart’s augmented oxygen consumption.
Decreased intrathoracic pressure caused by the augmented respiratory muscle
efforts (i.e., deeper negative transdiaphragmatic swings during inspiration) pro-
duces an increase in both right ventricular preload and left ventricular afterload.
Consequently, FBO may trigger cardiac arrhythmias in 11–40 % of the cases and,
less frequently, cardiogenic pulmonary edema and acute coronary syndrome, espe-
cially in patients with preexisting heart disease [1].
Thoracic societies recommend avoiding FBO and BAL in patients with hypox-
emia that cannot be corrected to at least a PaO2 of 75 mmHg or to an oxygen satura-
tion (SpO2) of ≥90 % with supplemental oxygen [1]. In these higher-risk patients,
when noninvasive diagnostic tests are not conclusive, avoiding FBO means being
compelled to use empirical treatment. As a consequence, when bronchoscopy is
mandatory, only CMV can assure adequate ventilation during the maneuver.
Unfortunately, CMV is not free of complications.
Cardiopulmonary pathophysiological changes observed during FBO are more
exaggerated during intervention procedures performed with RB, especially because
of airway obstruction by the bronchoscope, prolonged suctioning, low inspiratory
fraction of O2 (FiO2) (to prevent laser combustion), and respiratory depression
resulting from analgo-sedation [2].
Despite its increasing clinical application in critical respiratory patients, the fail-
ure rate of ppNIMV varies between 5 and 60 %, depending on numerous factors,
including the cause of ARF, excessive secretions, hypercapnic encephalopathy
(HE), agitation, patient-ventilator asynchrony, and sleep disturbances [5].
Unsuccessful ppNIMV was found to be independently associated with death, espe-
cially in patients with “de novo” hypoxemic ARF [3]. Among all causes, inefficacy
in spontaneously clearing airways of an excessive burden of secretions plays an
important role in determining ppNIMV failure in 33–61 % of cases [3, 5]. This is a
result of the noninvasive interfaces that do not allow direct access into the airways
(Table 71.1).

71.3 Rationale for the Combined Use of NIMV and FBO

There is a strong pathophysiological rationale for combining bronchoscopy and

NIMV for the management of respiratory critical patients because the limitations of
one technique may be counterbalanced by the properties of the other. In other words,
NIMV may be of help in performing safe bronchoscopy in ARF patients, and FBO
may increase the chance of success in patients at risk of NIMV failure.
610 R. Scala

Table 71.1 Advantages and disadvantages of bronchoscopy and noninvasive ventilation

Bronchoscopy Noninvasive ventilation
Advantages
Diagnosis in suspected pneumonia Improving gas exchange
Diagnosis in diffuse lung diseases Reduced work of breathing
Clearing of mucous from airway Reduced heart work-load
Treatment of airways obstruction Avoidance of ETI and CMV
Disadvantages
Increased airway’s resistance Failure in case of burden of secretion
Increased work of breathing
Worsening of gas exchange
Increased heart workload

ppNIMV is able to prevent and correct the cardiopulmonary alterations induced

by bronchoscopy through three mechanisms: (1) compensation of the bronchoscope-
correlated extra-resistive work of breathing by means of the unloading of respira-
tory muscles leading to a more favorable breathing pattern and diaphragmatic
load-force relationship; (2) improvement of pulmonary gas exchange due to a better
V/Q ratio and the correction of hypoventilation; and (3) counterbalancing of the
increased heart workload by means of a marked relief of respiratory muscle effort
with a reduced negative inspiratory intrathoracic pressure. Keeping the patient on
ppNIMV after bronchoscopy may prevent the derangement of lung function that
can last several hours after the procedure [6].
As a result of the clearing the airways in the early phases of ppNIMV, FBO may
improve ventilation and, therefore, reduce the need for ETI in patients with an unfa-
vorable balance between excessive burden of secretions and inefficient spontaneous
clearance after the failure of chest physiotherapeutic techniques [6].
Three different acute scenarios of synergistic interaction between FBO and
ppNIMV may be encountered in the ICU/RICU environment: (1) patients on O2
therapy who undergo diagnostic FBO under ppNIMV assistance (for prevention of
mandatory noninvasive or invasive ventilatory support in O2-supported patients); (2)
patients already on ppNIMV who undergo diagnostic FBO under ventilation (for
prevention of CMV in ppNIMV-supported patients); and (3) patients requiring ETI
for an excessive burden of bronchial secretions who undergo early therapeutic and
diagnostic FBO during ppNIMV (as an alternative to mandatory CMV in ppNIMV
plus FBO-supported patients) (Fig. 71.1).

71.4 Clinical Evidence of NIMV-Bronchoscopy Synergy

The majority of the published studies have used ppNIMV to prevent respiratory dete-
rioration in spontaneously breathing hypoxemic patients undergoing FBO who do not
still require ppNIMV for ARF [6] (Table 71.2). Antonelli et al. [7] were the first to
report on ppNIMV-assisted FBO; they performed BAL in eight immunocompromised
71 Noninvasive ventilation During Bronchoscopy 611

Severe Diagnostic and

Therapeutic
FBO or RB
Acute Respiratory failure

Moderate Diagnostic
FBO

Mild Diagnostic
FBO

NIMV to prevent NIMV alternative

O2-therapy ETI-CMV of ETI-CMV

Fig. 71.1 Potential scenarios for synergistic application of bronchoscopy and noninvasive ventila-
tion according to the severity of acute respiratory failure, the baseline support of the patients, and the
purposes of bronchoscopy. FBO flexible bronchoscopy, NIMV noninvasive mechanical ventilation,
ETI-CMV endotracheal intubation conventional mechanical ventilation, RB rigid bronchoscopy

patients with severe hypoxemia (PaO2/FiO2 ≤ 100 mmHg) due to suspected pneumo-
nia. The use of ppNIMV was associated with significant improvements in PaO2/FiO2
and SpO2 during bronchoscopy. FBO with NPPV was well tolerated, and no patient
required ETI. Two patients died 5–7 days after FBO from unrelated complications
of the underlying illness. A causative pathogen was identified by BAL in all patients,
and six of them responded to treatment and survived hospital admission.
In a subsequent study, Da Conceicao et al. [8] investigated the feasibility of
ppNIMV-assisted FBO in a 10 COPD patients admitted to ICU for pneumonia with
hypoxemic-hypercapnic ARF (PaO2 = 53 ± 13 mmHg; PaCO2=67 ± 11 mmHg).
During FBO with ppNIMV, SpO2 increased from 91 ± 4.7 % at baseline to 97 ± 1.7 %.9.
There were no changes in PaCO2 and PaO2 during the hour following the end of pro-
cedure. FBO under NIPPV was performed without complications and was well toler-
ated in 8 patients. No patient required ETI within 24 h, and all patients survived.
In the first randomized controlled trial (RCT), conducted on 30 patients with
PaO2 ≤ 125 mmHg despite high-flow oxygen mask (i.e., 10 l/min) requiring diag-
nostic FBO, Maitre et al. [9] showed significantly higher SpO2 values during FBO
and 30 min thereafter with CPAP, compared with oxygen-therapy, using a new
device open to the atmosphere (CPAP Boussignac). Not only did the patients in the
oxygen group develop hypoxemia during FBO, but 5 patients in the oxygen group
(compared with none in the CPAP group) also required ventilatory assistance (1
 612

Table 71.2 Studies on the combined use of FBO and ppNIMV in acute respiratory failure
Support
Author, year Study No. patients ARF pattern pre-FBO Indication FBO FBO procedure ETI (%)
Antonelli, 1996 Prospective NIMV: 8 Hypoxemic Oxygen Diagnostic BAL NIMV: 0
Da Conceicao, Prospective NIMV: 10 Hypoxemic- Oxygen Diagnostic BAL NIMV: 0
2000 hypercapnic
Maitre, 2000 RCT CPAP: 15 Hypoxemic Oxygen Diagnostic BAL, br. biopsy CPAP: 6.7
O2: 15 O2: 46.7
Antonelli, 2002 RCT NIMV: 13 Hypoxemic Oxygen Diagnostic BAL NIMV: 7.7
O2: 13 O2: 15.4
Chiner, 2010 Prospective NIMV: 35 Hypoxemic Oxygen Diagnostic BW, PSB,BAL, 0
Therapeutic br. biopsy
Heunks, 2010 Prospective NIMV: 12 Hypoxemic Oxygen Diagnostic BAL NIMV: 8.3
Scala, 2010 Case control NIMV: 15 Hypoxemic- NIMV Diagnostic BAL NIMV: 20
hypercapnic
CMV: 15 Therapeutic
Baumann, 2011 Prospective NIMV: 40 Hypoxemic NIMV Diagnostic BAL NIMV 10
Clouzeau, 2011 Prospective NIMV: 23 Hypoxemic NIMV Diagnostic BAL NIMV: 17.4
Agarwall, 2012 Prospective NIMV: 6 Hypoxemic Oxygen Diagnostic BAL, TBLB NIMV: 1.7
R. Scala
71 Noninvasive ventilation During Bronchoscopy 613

ppNIMV and 4 CMV) within 6 h following the procedure (p = 0.003). A causative

infectious agent was identified in 14 cases, with two diagnoses of carcinomatous
lymphangitis (one by BAL and one by bronchial biopsy); fat embolism and drug-
induced hypersensitivity pneumonia were diagnosed in 2 patients.
Subsequently, in another RCT involving 26 patients with nosocomial pneumo-
nia and PaO2/FiO2 ≤ 200 mmHg, Antonelli et al. [10] evaluated the effectiveness
and safety of ppNIMV versus conventional oxygen supplementation before, dur-
ing, and after diagnostic FBO. Application of ppNIMV was associated with
increase in PaO2/FiO2 by 82 %, in contrast to a decline in PaO2/FiO2 of 10 % in
the oxygen group during FBO. Furthermore, in the ppNIMV group, PaO2/FiO2
remained higher, heart rate was lower, and there was no reduction in mean arterial
pressure in comparison with a 15 % decrease from the baseline in the control
group 60 min after FBO. Eighteen patients had significant growth of a pathogen
found in BAL fluid. One patient in the ppNIMV group and 2 patients in the con-
trol group required non emergency ETI. Four patients in the ppNIMV group and
7 patients in the oxygen group died from complications of their underlying dis-
ease 5–7 days after study entry. The same group also found the helmet for deliver-
ing NIMV to be safe in avoiding gas exchange deterioration in 4 hypoxemic
patients [11].
Chiner et al. [12] evaluated nasal mask for delivering ppNIMV while the FBO
was performed orally using a bite block sealed with an elastic glove finger in 35
patients with a mean PaO2/FiO2 of 168. A total of 35 bronchoaspirates, 21 PSB, 11
BAL, and 8 bronchial biopsies were performed. In contrast to other studies, patients
developed hypoxemia during the procedure, with SpO2 decreasing to 86 % during
FBO, probably as a result of excessive mouth-air leaks during nasal NIMV. The
clinical course was favorable in 66 %; there was a relatively high rate of need of
CMV (11 % of the cases occurring 5 ± 4 days after FBO) and in-hospital mortality
(33 % of the cases occurring 3 ± 2 days after FBO), mainly correlated with the
underlying disease.
Heunks et al. [13] reported the use of a novel total face mask for delivering
NIMV during diagnostic FBO in 12 hypoxemic patients (mean PaO2/FiO2 = 192 ± 23).
The procedure was successful in all patients; in only 1 patient SpO2 decreased to
86 % during FBO. A microbiological diagnosis was established in 8 of 12 patients.
All the reported studies have shown that ppNIMV is able to ensure adequate gas
exchange during FBO in spontaneously breathing hypoxemic patients, thus avoid-
ing ET. There is only one study that reported the use of FBO in patients with hypox-
emic ARF requiring ppNIMV before the procedure. Baumann et al. [14] evaluated
40 hypoxemic patients requiring ppNIMV (PaO2/FiO2 = 176 ± 54) who underwent
FOB for suspected pneumonia. FBO was successfully performed without complica-
tions. BAL yielded diagnostic information in 68 % of the patients. The mean PaO2/
FiO2 ratio improved at the end of FBO after 120 min. Four patients (10 %) required
ETI during the first 8 hours after the procedure.
Agarwal et al. [15] published a pilot experience of ppNIMV-assisted FBO for
performing BAL and TBLB in six severely hypoxemic patients (PaO2/FiO2 < 200)
with diffuse interstitial lung diseases. There was significant improvement in
614 R. Scala

respiratory rate and PaO2/FiO2, and significant decline in heart rate after application
of ppNIMV. FBO was well tolerated and all subjects maintained SpO2 > 92 % dur-
ing the procedure. One subject required ETI due to hemoptysis. There was no evi-
dence of pneumothorax in any subject. A definite diagnosis was obtained in five
(two malignancies, one lymphoma, one sarcoidosis, and one pneumocystis pneu-
monia) of the six patients only with TBLB, which enabled their successful manage-
ment. Although the authors concluded that ppNIMV-assisted TBLB is feasible in
patients with ARF and diffuse pulmonary infiltrates, this approach should be per-
formed only in centers showing wide experience with both ppNIMV and FBO, as
well as with the management of TBLB complications (i.e., pulmonary hemorrhage
and pneumothorax). More studies are required to adequately define the utility and
safety of NIMV-assisted TBLB.
The last scenario of a synergistic interaction between the two techniques deals
with the usefulness of FBO as therapeutic tool to avoid ppNIMV failure in ARF
patients with an excessive burden of secretions [6]. In the context of decompensated
COPD patients requiring ETI because of impaired mucous clearance, Scala et al.
[16] postulated that the early suction of secretions with FBO performed during
ppNIMV is feasible and effective. In a matched case-control study, the authors com-
pared 15 acutely decompensated COPD patients with copious secretion retention
and HE resulting from community-acquired pneumonia undergoing early FBO plus
BAL during ppNIMV in an expert RICU with 15 controls receiving CMV in the
ICU. Two hours of ppNIMV plus FBO significantly improved gas exchange, senso-
rium, and cough efficiency without major complications (e.g., cardiovascular
events, emergent ETI, or pneumothorax). Improvement in PaCO2 and pH, hospital
mortality, and durations of hospitalization and ventilation were similar in both
groups. ppNIMV significantly reduced serious infectious complications compared
with CMV, as well as the need for tracheostomy. Even though this ppNIMV strategy
may be a successful alternative to CMV in selected COPD patients within expert
units, larger RCTs are necessary to confirm this result and, therefore, to test the
efficacy of the FBO-ppNIMV protocol applied to an earlier time course of COPD
decompensations when ETI is not mandatory by comparing ppNIMV alone versus
ppNIMV with early FBO [16].

71.5 Special Situations

71.5.1 Difficult Intubation

The combined use of FBO and ppNIMV to perform ETI may be useful in peculiar
clinical contexts. In a RCT performed on 32 patients with an anticipated difficult
intubation in ear-nose-throat surgery, Bourgain et al. [17] demonstrated that, during
FBO performed under propofol, ppNIMV improves ventilation efficiency compared
with spontaneous breathing. ETI is particularly risky and difficult in patients with
severe hypoxemic ARF who deteriorate despite a trial of ppNIMV. The lack of clear
benefit of ppNIMV in these patients is at least in part due to an increased mortality
71 Noninvasive ventilation During Bronchoscopy 615

risk during rescue ETI. Maintaining ppNIMV during ETI may prevent alveolar de-
recruitment and derangement of gas exchange. This concept was demonstrated by
Bailard et al. [18] in a RCT study conducted on 53 hypoxemic patients requiring
ETI in ICU. The authors showed that SpO2 values were significantly greater if pre-
oxygenation before ETI was performed with ppNIMV rather than with a conven-
tional non-rebreather bag-valve mask.
In the first pilot French study, Da Conceiçao et al. [19] assessed the feasibility and
safety of a new technique of FBO-assisted naso-tracheal-intubation with ppNIMV
delivered via an adapted endoscopic facial mask under conscious sedation in 16
patients with hypoxemic-hypercapnic ARF (PaCO2 = 64 ± 26 mmhg, PaO2/
FiO2 = 142 ± 70) who required CMV due to late ppNIMV failure. The FBO intubation
was performed without any failure or complication. SpO2 significantly improved dur-
ing ETI with values kept over 90 % during the procedure. In another US pilot study,
Barjaktarevic et al. [20] reported a series of 10 nonconsecutive hypoxemic patients
who developed failure of ppNIMV via full face mask, showing a PaO2/FiO2 ratio <
100. The subjects were orally intubated under the guide of FBO, keeping ppNIMV
delivered via the nasal route. Adopting this new technique, ETI was successfully per-
formed without major complications; one-third of the patients developed arterial
hypotension, mainly correlated with the use of analogo-sedation. Only a mild drop in
SpO2 (4.7 ± 3.1 %) was reported during the procedure. These preliminary experiences
require confirmation by large RCTs comparing conventional versus FBO-guided ETI
under ppNIMV in patients with impending ppNIMV failure. It may be speculated that
this new procedure for rescue ETI in case of ppNIMV failure is likely to be more
advantageous in patients with predicted or proven difficult direct laryngoscopy.

71.5.2 Obstructive Sleep Apnea Syndrome

Patients with obstructive sleep apnea syndrome (OSAS) are at high risk of develop-
ing severe hypoxemia under and after sedation during surgical or endoscopic proce-
dures [21]. This is particularly true in the case of FBO performed with the use of
sedatives, which may precipitate the collapse of airways in OSAS patients and aug-
ment the degree of FOB-induced hypoxemia. ppNIMV counteracts negative inspi-
ratory pressures and the hypotonicity of the upper airway muscles in OSAS patients.
The positive pressure generated by ppNIMV allows for the laryngeal structures to
be identified as the device passes the hypopharynx and is introduced through the
vocal chords. This aspect is fundamental in OSAS patients with predicted difficult
intubation [21].

71.5.3 Interventional Procedures During RB

The application of intermittent positive pressure and jet-ventilation are the two stan-
dard ventilatory modes that guarantee effective ventilation during RB. Patients can
also be managed with assisted spontaneous breathing. Unfortunately, these
616 R. Scala

ventilatory strategies have important limitations during RB, such as requirement of

higher FiO2, ineffective control of ventilatory output with risk of acidosis, need for
higher doses of opioids, and prolonged recovery time [2, 22].
In two RCTs, Vitacca et al. [23, 24] demonstrated that, compared with both
assisted spontaneous breathing and external high-frequency oscillation, npNIMV
delivered by a poncho-wrap to support interventional RB procedures under general
anesthesia, was associated with less incidence and severity of respiratory acidosis,
less requirement of increased O2 supply, lower use of opioids, shorter recovery time,
and less need for assisted-manual ventilation.

71.6 Practical Issues

It is recommended that FBO NIMV procedures should be performed in an ICU or

RICU setting, or a standard bronchoscopy room capable of dealing with any cardio-
pulmonary complications and the management of airways [6]. ppNIMV should be
initiated at least 15–20 min before bronchoscopy. There are no published papers
comparing the different ventilatory modes. The easiest mode of assisting FBO in
hypoxemic patients consists of delivering CPAP by means of a Boussignac system
with a face mask [6, 9]. This system accelerates the air molecules in the form of
microjets that generate a “virtual valve” through a turbulence effect. The gas veloc-
ity transforms into pressure, depending on the flow of gas provided. Usually, CPAP
is set at 10 cmH2O with FiO2 of 1.0 and then the pressure is eventually increased,
based on SpO2 values. As this CPAP device remains open to the atmosphere, it has
the advantage of allowing easy maintenance of a positive pressure and CPAP deliv-
ery while FBO is being performed [9].
Pressure-support ventilation has been the most commonly used mode of ppNIMV
[3, 5, 6]. An initial pressure support of 10 cmH2O is recommended during the pro-
cedure, with low PEEP levels (e.g., 5 cmH2O) [6]. With advanced ventilators pro-
vided with a double-tube circuit and accurate ventilatory monitoring, pressure
support is titrated to achieve an expiratory tidal volume of 8–10 ml/kg and respira-
tory rate below 25 min−1. FiO2 is initially set at 0.5 and then changed to achieve
SpO2 values above 90 %; accordingly, an ICU ventilator capable of delivering FiO2
from high-pressure sources is recommended [16].
NIMV setting adjustments can be made during the procedure [6]:

(a) If there is hypoxemia despite FiO2 1.0, PEEP may be increased by steps of
2 cmH2O until SpO2 ≥90 % is reached; patients who remain hypoxemic
despite high FiO2 and PEEP levels are not good candidates for NIMV-assisted
FBO.
(b) Hypercapnia and respiratory acidosis have to be corrected by raising pressure
support levels to improve effective alveolar ventilation before FBO.

Regarding the interfaces, almost all types of masks have been used. The most
widely used are orofacial masks [6]. Currently, endoscopic face masks usually
71 Noninvasive ventilation During Bronchoscopy 617

Nasal/full-facemask Nasal/helmet

Oral/total-face mask

Oral/full-facemask

Oral/nasal mask

Fig. 71.2 Different combinations of access of the bronchoscope into the airways (nasal or oral
route) and interfaces used for delivering noninvasive ventilation

have two orifices: one for the administration of gas and a second that is sealed
and distensible as it allows for an endoscope to be introduced. FBO with
ppNIMV can be performed with a helmet [11] or a total face mask [13]. Chiner
et al. [12] used a handmade system of a membrane made out of a latex glove
coupled with a bite block with a small incision; this maintains the pressure
administered by the ventilator through a nasal mask, and bronchoscopy is car-
ried out orally with good results.
The bronchoscope can be introduced through both the nasal and oral routes,
depending on the mask used and operator experience [6] (Fig. 71.2). With face
masks, the nasal or oral pathways can be used. The introduction of the broncho-
scope into the nares through the face mask can be a difficult step, as the broncho-
scope has to be considerably manipulated, which not only prolongs the procedure
but can also cause trauma to the nasal mucosa. To facilitate easy passage, the bron-
choscope is initially passed through the face mask, and the tip of bronchoscope is
gently passed through the nose until the vocal cords are visible. With the helmet,
either nasal or oral entry can be used, with the patient sitting or in supine decubitus
[11]. Likewise, the use of Boussignac CPAP, because it is an open system, allows
for oral or nasal entry [6, 9].
Delivery of ppNIMV does not necessarily imply greater sedation. For topical
anesthesia, lidocaine is used as with standard FBO. Some authors propose the use
of analgesic (opioids) and/or sedative drugs (benzodiazepines, propofol) for FBO
under ppNIMV to reduce patient discomfort, but it is essential to have experience in
drug management [6].
618 R. Scala

It is recommended to carry out the procedure with the patient in a semi-recumbent

position, which is implied by the anterior entry of the bronchoscope. However,
ppNIMV itself has been used in supine decubitus to optimize respiratory parameters
in other explorations such interventional cardiology or in suspected dynamic airway
collapse [6].
As in all interventions in high-risk patients, it is recommended to keep the time
as shorter as possibile. The mean duration of NIMV-assisted FBO is approximately
8 min [6]. ppNIMV should be maintained with a setting similar to that prior to FBO
within 15 and 90 min after the end of the procedure [6].
ppNIMV may induce gastric distension and increased risk for pulmonary
aspiration. The abdominal pressure can reduce functional residual capacity and
add a restrictive component to the work of breathing. Lower pressures of the
ventilator and semi-recumbent patient position may reduce this risk [3, 6]. There
are other complications related to FBO (e.g., gas exchange derangement, bleed-
ing, poor collaboration, etc.), whose resolution is approached as in a standard
FBO with prompt ETI availability [1, 2, 6]. There are no data about the rate of
pneumothorax during NIMV-assisted TBLB. However, because the procedure is
performed under positive pressure, the risk should not to be underestimated as
pneumothorax was reported as a complication during both acute and chronic
ppNIMV. Accordingly, facilities for inserting chest drainage should be promptly
available. Less frequently, there may be major cardiovascular complications
(malignant arrhythmias, acute coronary syndrome, cardiac arrest), which can be
minimized through proper patient selection and monitoring during bronchos-
copy. Nasal or facial injuries appear only after prolonged NIMV use [6].
Contraindications of this procedure are those of ppNIMV itself, such as cardiac
arrest, severe encephalopathy, gastrointestinal bleeding, severe hemodynamic insta-
bility, history of facial surgery or trauma, recent esophageal-gastric interventions,
and inability to protect the airway [3, 5, 6]. There are other absolute contraindica-
tions of bronchoscopy itself, such as recent acute coronary syndrome, severe
arrhythmias, and severe coagulopathies if biopsy is planned [1, 2, 6].

Conclusions
An increasing amount of data suggest the use of bronchoscopy during NIMV in
ARF to avoid or reduce the need of ETI. Despite a strong rationale for the com-
bined use of the two techniques, there is not still enough evidence for a large-
scale application of this strategy in all clinical scenarios. The majority of the
available data are in favor of the “help” given by NIMV to diagnostic bronchos-
copy in high-risk hypoxemic patients. Preliminary findings report the successful
help given by early bronchoscopy to NIMV in patients with hypoxemic-hyper-
capnic ARF who are likely to fail because of hypersecretion. This combined
approach should be performed only in centers with wide experience with both
NIMV and bronchoscopy, where close monitoring and ETI facilities are
promptly available.
71 Noninvasive ventilation During Bronchoscopy 619

Key Major Recommendations

• Some scenarios represent contraindications for NIMV and bronchoscopy,
such as severe hypoxemia for the latter and accumulated tracheobronchial
secretions for the former.
• There is a strong pathophysiological rationale for combining bronchos-
copy and NIMV for the management of respiratory critical patients because
the limitations of one technique may be counterbalanced by the properties
of the other.
• ppNIMV is helpful to support diagnostic FBO in high-risk hypoxemic
patients, and FBO may increase the chance of ppNIMV success by remov-
ing the burden of secretion
• npNIMV is the more effective ventilatory mode to support patients during
the interventional procedure performed with RB in general anesthesia.
• The bronchoscopy-NIMV combined procedure must be performed only in
the ICU or RICU setting, or whenever there is a suitable monitoring of the
patient and a team with good expertise in both techniques and in the man-
agement of airways (i.e., ETI) and cardiopulmonary complications.

References
1. Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society Bronchoscopy Guideline
Group. British thoracic society guideline for diagnostic flexible bronchoscopy in adults:
accredited by NICE. Thorax. 2013;68(Suppl 1):i1–i44
2. Wahidi MM, Herth FJ, Ernst A. State of the art: interventional pulmonology. Chest.
2007;131:261–74.
3. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009;374:250–9.
4. Corrado A, Gorini M. Negative-pressure ventilation: is there still a role? Eur Respir J.
2002;20:187–97.
5. Ozyilmaz E, Ugurlu AO, Nava S. Timing of noninvasive ventilation failure: causes, risk fac-
tors, and potential remedies. BMC Pulm Med. 2014;14:19.
6. Esquinas A, Zuil M, Scala R, et al. Bronchoscopy during non-invasive mechanical ventilation:
a review of techniques and procedures. Arch Bronconeumol. 2013;49:105–12.
7. Antonelli M, Conti G, Riccioni L, et al. Noninvasive positive-pressure ventilation via face mask
during bronchoscopy with BAL in high-risk hypoxemic patients. Chest. 1996;110:724–8.
8. Da Conceiçao M, Genco G, Favier JC, et al. Fiberoptic bronchoscopy during noninvasive
positive-pressure ventilation in patients with chronic obstructive lung disease with hypoxemia
and hypercapnia. Ann Fr Anesth Reanim. 2000;19:231–6.
9. Maitre B, Jaber S, Maggiore SM, et al. Continuous positive airway pressure during fiberoptic
bronchoscopy in hypoxemic patients. A randomized double-blind study using a new device.
Am J Respir Crit Care Med. 2000;162:1063–7.
10. Antonelli M, Conti G, Rocco M, et al. Noninvasive positive-pressure ventilation vs conven-
tional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy.
Chest. 2002;121:1149–54.
620 R. Scala

11. Antonelli M, Pennisi MA, Conti G, et al. Fiberoptic bronchoscopy during noninvasive positive
pressure ventilation delivered by helmet. Intensive Care Med. 2003;29:126–9.
12. Chiner E, Sancho-Chust JN, Llombart M, et al. Fiberoptic bronchoscopy during nasal non-
invasive ventilation in acute respiratory failure. Respiration. 2010;80:321–6.
13. Heunks LM, de Bruin CJ, van der Hoeven JG, et al. Noninvasive mechanical ventilation for
diagnostic bronchoscopy using a new face mask: an observational feasibility study. Intensive
Care Med. 2010;36:143–7.
14. Baumann HJ, Klose H, Simon M, et al. Fiberoptic bronchoscopy in patients with acute hypox-
emic respiratory failure requiring noninvasive ventilation–a feasibility study. Crit Care.
2011;15:R179.
15. Agarwal R, Khan A, Aggarwal AN, et al. Bronchoscopic lung biopsy using noninvasive ven-
tilatory support: case series and review of literature of NIV-assisted bronchoscopy. Respir
Care. 2012;57:1927–36.
16. Scala R, Naldi M, Maccari U. Early fiberoptic bronchoscopy during noninvasive ventilation in
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acquired pneumonia. Crit Care. 2010;14:R80.
17. Bourgain JL, Billard V, Cros AM. Pressure support ventilation during fibreoptic intubation
under propofol anaesthesia. Br J Anaesth. 2007;98:136–40.
18. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxygenation
before intubation of hypoxic patients. Am J Respir Crit Care Med. 2006;174:171–7.
19. Da Conceiçao M, Favier JC, Bidallier I, et al. Fiber-optic intubation with non-invasive ventila-
tion with an endoscopic facial mask. Ann Fr Anesth Reanim. 2002;21:256–62.
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ventilation in the treatment of hypoxemic respiratory failure. J Intensive Care Med. 2015;30:
161–6.
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ment of patients with obstructive sleep apnea: navigating through uncertainty. Anesthesiology.
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in 2008 patients. Chest. 1996;11:1536–42.
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Sedation and Analgesia for Noninvasive
Ventilation in Intensive Care 72
Yalim Dikmen

Contents
72.1 Introduction ................................................................................................................. 621
72.2 Discussion ................................................................................................................... 622
72.2.1 Sedative and Analgesic Drugs ....................................................................... 623
References .............................................................................................................................. 625

Abbreviations

ARF Acute respiratory failure

COPD Chronic obstructive pulmonary disease
ETI Endotracheal intubation
ICU Intensive care unit
NPPV Noninvasive positive pressure ventilation
PaO2/FiO2 Ratio of arterial oxygen tension to fractional inspired oxygen concentration

72.1 Introduction

The use of noninvasive positive pressure ventilation (NPPV) in patients with acute
respiratory failure is increasing dramatically. It is now considered the first-line treat-
ment in certain types of acute respiratory failure such as acute exacerbations of

Y. Dikmen
Department of Anesthesiology and Reanimation, Cerrahpasa Medical School,
Istanbul University, Istanbul, Turkey
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 621

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_72
622 Y. Dikmen

chronic obstructive pulmonary disease (COPD), acute cardiogenic edema, asthma,

and in patients with immunosuppression. The main aim of NPPV in these settings
is to avoid endotracheal intubation (ETI) by correcting gas exchange, relieving
symptoms of dyspnea, and decreasing work of breathing. It is now known that
avoiding intubation prevents complications associated with invasive mechanical
ventilation, decreases rates of nosocomial infections, and shortens length of inten-
sive care unit (ICU) and hospital stay.
These positive effects of NPPV are dependent on patient tolerance during ventila-
tion, and it may be difficult in the presence of claustrophobic sensation, excessive air
leaks around the interface, and patient-ventilator dys-synchronies. These may neces-
sitate the presence of health-care staff at the bedside during the initial hours of appli-
cation. If the patient learns to breathe through the ventilator, and if the support may
overcome the respiratory distress (i.e., correct gas exchange and unload respiratory
muscles without causing too much dyssynchrony) then the need for help and reassur-
ance decreases. As a result of skin lesions caused by the mask, abdominal distension,
dryness of upper airways, and neuropsychological distress, patient discomfort may
worsen, leading to poor acceptance of NPPV. In these instances, application of a seda-
tive may increase patient tolerance and help to avoid endotracheal intubation.

72.2 Discussion

Although sedation and analgesia are well established in patients with invasive venti-
lation, the use of sedatives and analgesics during NPPV is a controversial issue. An
updated guideline for management of pain, agitation, and delirium in the ICU has
been published [1]. This guideline suggests the use of opioid analgesics and lighter
levels of sedation, with scales to assess depth of sedation; however, it does not
address the use of analgesics and sedation in patients on noninvasive ventilation.
In general, the use of sedatives and narcotic analgesics may be seen as relatively
contraindicated because they can depress the level of consciousness, interfere with
upper airway reflexes, and may lead to endotracheal intubation. On the other hand,
use of sedatives and/or opioids may be helpful in alleviating agitation and dyspnea
in patients with respiratory distress and may increase patients’ tolerance to
NPPV. The success of noninvasive ventilation may depend on patient acceptance
and tolerance of the mask interface. In an epidemiologic survey conducted by
Carlucci et al. [2], tolerance to the mask was significantly lower in patients who
failed noninvasive ventilation. In this study, 52 of 108 patients required early termi-
nation of noninvasive ventilation, and in 22 % of these cases the reason for failure
was the patient’s refusal to continue NPPV. Another survey showed that the physi-
cians perceived mask tolerance as one of the most important problems in NPPV
application [3]. In this web-based survey on the use of noninvasive ventilation in
general wards, 67.5 % of the respondents reported patient refusal or mask intoler-
ance as problems associated with NPPV.
In the setting of mask intolerance or patient agitation, sedation or analgesics can
be considered. On the other hand, as sedative and opioid analgesic drugs also have
72 Sedation and Analgesia for Noninvasive Ventilation in Intensive Care 623

anxiolytic effects and depress respiratory drive and central perception, they may be
helpful in patients with respiratory distress by alleviating symptoms associated with
dyspnea [4]. These drugs along with other non-pharmacologic interventions have
the potential to increase patient tolerance and acceptance, and NPPV success in
patients with ARF.
There is currently no established protocol or consensus on the use of sedatives
and analgesics during noninvasive ventilation, and the effects of sedation and anal-
gesia during NPPV remain controversial due to a lack of knowledge and experience.
One survey study published in 2007 investigated the sedation practices during non-
invasive ventilation [5]. In this study, 790 physicians from Europe and North
America responded to the survey, indicating varying rates of sedative use and differ-
ing choices of sedatives and hand restraints. In general, the use of sedatives and
analgesics was low; the percentages of North American and European physicians
who used sedatives and analgesics more than 25 % of the time were 45 % and 26 %,
respectively. North Americans used sedatives and analgesics more frequently than
their European counterparts, and intensive care physicians were more likely to use
them than other physicians. The drugs chosen for sedation and analgesia were
mainly benzodiazepines (33 % of the respondents) and opioids (22 % of the respon-
dents); regimens containing propofol or dexmedetomidine were quite infrequent
(7 % and 5 %, respectively). Drug choice was dependent on clinical experience and
lack of effect on respiratory drive. Only 14 % of the respondents reported the use of
a specified protocol for sedation during NPPV, and assessment was done by clinical
observation rather than sedation scales (63 % vs 32 %).
The practices observed in this study may be considered outdated today in the
light of the new guidelines [1] and findings of the studies showing the association of
benzodiazepines with delirium [6]. These literature show a need for avoidance of
benzodiazepine use in intensive care patients and applying analgosedation where
opioids play a major role, in addition to use of scales and protocols to keep the seda-
tion levels as light as possible.
In general, sedation may not be needed routinely during noninvasive ventilation,
but there may be some situations, mainly poor acceptance, in which sedatives may
be indicated. Before initiating any sedative, the physician should keep in mind that
the chosen interface and ventilator mode can be a contributing factor to patient dis-
comfort. Face masks with tight fittings or large leaks from around the mask, con-
tinuous high flow provided by the ventilator, or patient ventilator dyssynchrony may
be the factors associated with patient agitation and refusal of the mask [7]. The
physician should be ready to choose different interfaces to improve patient comfort
and change ventilator settings according to patient comfort.

72.2.1 Sedative and Analgesic Drugs

The ideal sedative should be effective in controlling anxiety and discomfort without
causing respiratory depression or depression of upper airway reflexes. The level of
sedation should easily be titrated to keep the patient awake or easily arousable [8].
624 Y. Dikmen

Table 72.1 Doses of sedative drugs used in NPPV [8]

Drug Bolus dose Infusion dose
Dexmedetomidine 1 μ/kg 0.2–0.7 μg/kg/h
Midazolam 0.05 mg/kg 0.05–0.1 mg/kg/h
Remifentanil – 0.025 μg/kg/min
Propofol – 0.4 μg/ml (down to 0.2 ml – target plasma concentration)

For this purpose, propofol and benzodiazepines are used as the drugs of choice.
However, reports claiming unwanted effects of benzodiazepines, and the introduc-
tion of the α-adrenergic agonist dexmedetomidine, have shifted the choice away
from benzodiazepines. The advent of short-acting synthetic morphine derivatives
has made analgosedation using drug combinations more feasible. The doses of sed-
ative drugs used during NPPV are listed in Table 72.1.
In a study conducted by Conti et al. [9], the effects of sufentanil on respiratory
drive, respiratory pattern, and gas exchange were investigated in intubated patients
during pressure support ventilation. In this study, no changes in hemodynamic or
respiratory parameters were observed with the use of 0.2–0.3 μg/kg/h sufentanil
infusion for 24 h. Newer drugs have a better safety profile than sufentanil and are
used in ICUs for sedation and analgesia in intubated patients.
There are several recent studies, where remifentanil and dexmedetomidine is
used to facilitate NPPV in patients whom refuse this treatment due to intolerance.
Both drugs have shorter half-life and lower risk of unwanted effects.
Rocco et al. [10] reported 61 % of 36 patients with acute hypoxemic failure, who
refused NPPV, were able to receive the treatment after sedation with remifentanil
(0.025 μg/kg/min). The mortality rate in the successfully ventilated patient group
was 14 %, whereas it was 50 % in the patients who required ETI despite remifent-
anil infusion. In a pilot study conducted on 12 patients who refused NPPV, only 4
needed ETI with the infusion of remifentanil [11]. The authors concluded that the
use of remifentanil sedation was safe and effective in patients who refused noninva-
sive ventilation.
Huang et al. [12] compared dexmedetomidine and midazolam in NPPV failure
due to patient refusal in a randomized study. Of the 62 treated patients with cardio-
genic pulmonary edema, 20 had failed NPPV despite sedative infusions. The failure
rate was 44.8 % in the midazolam group and 21.2 % in the dexmedetomidine group.
The reasons for NPPV failure were inability to increase PaO2/FiO2 ratio, worsening
hemodynamic status, and inability to cope with secretions. In patients with success-
ful NPPV, dexmedetomidine resulted in shorter ICU stay and lower rates of respira-
tory infections, although the success rate and mortality were similar in both groups.
In a randomized, double-blind, controlled trial, dexmedetomidine was compared
with placebo in patients receiving NPPV for ARF [13]. The patients were random-
ized to study groups within 8 h of NPPV, and received infusions for 72 h or until
intubation or weaning. The study failed to show any advantage of initiating dexme-
detomidine with noninvasive ventilation on tolerance, the patients were not selected
from the ones who had intolerance to interface or agitation.
72 Sedation and Analgesia for Noninvasive Ventilation in Intensive Care 625

Propofol is widely used for conscious sedation during diagnostic interventions. It

provides an easily controllable level of sedation with fast recovery after cessation of
drug application. Clouzeau et al. [14] used propofol during fiber-optic bronchoscopy in
patients with acute hypoxemic respiratory failure with noninvasive pressure support.
The authors reported that an infusion regimen targeting plasma propofol concentra-
tions was safe and effective in relieving patient discomfort without any adverse effects.
All of the above publications were reports of the results of preliminary or pilot
studies with limited numbers of patients, generally with intolerance to
NPPV. Although not conclusive, there are signs of a beneficial effect of analgoseda-
tion to relieve discomfort and improve patient acceptance of noninvasive ventila-
tion. An important aspect of these studies is that all of them were conducted in
ICUs, where all means of monitoring are available. The issue of whether sedation
can be used in settings other than ICUs is controversial, and it may be dangerous
because patients cannot be monitored as closely as in the ICU environment. It would
be reasonable to admit the patients who refuse NPPV to the ICU to provide sedation
before initiating invasive ventilation (i.e., endotracheal intubation).

Key Major Recommendations

• Use of sedation by titrating to a predetermined level may be beneficial in
patients who refuse NPPV due to intolerance to interface, air leaks, or
respiratory distress by increasing the success of noninvasive ventilation.
• The choice of drugs for sedation must be made considering their ease of
dose titration and unwanted respiratory and cardiovascular effects.
• If necessary, sedation should be applied with the patient under close moni-
toring, preferably in the ICU.

References
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2. Carlucci A, Richard JC, Wysocki M, et al. Noninvasive versus conventional mechanical venti-
lation. An epidemiologic survey. Am J Respir Crit Care Med. 2001;163:874–80.
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for acute respiratory failure in general non-monitored wards. Respir Care. 2015;60:586–92.
doi:10.4187/respcare.03593.
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doi:10.1586/ers.13.5; quiz 135.
5. Devlin JW, Nava S, Fong JJ, et al. Survey of sedation practices during noninvasive positive-
pressure ventilation to treat acute respiratory failure. Crit Care Med. 2007;35:2298–302.
6. Mehta S, Cook D, Devlin JW, et al. Prevalence, risk factors, and outcomes of delirium in mechani-
cally ventilated adults. Crit Care Med. 2015;43:557–66. doi:10.1097/CCM.0000000000000727.
7. Longrois D, Conti G, Mantz J, et al. Sedation in non-invasive ventilation: do we know what to
do (and why)? Multidiscip Respir Med. 2014;4(9(1)):56. doi:10.1186/2049-6958-9-56.
626 Y. Dikmen

8. Scala A. Sedation during non-invasive ventilation to treat acute respiratory failure. Shortness
of Breath. 2013;2:35–43.
9. Conti G, Arcangeli A, Antonelli M, et al. Sedation with sufentanil in patients receiving pres-
sure support ventilation has no effects on respiration: a pilot study. Can J Anaesth. 2004;51:
494–9.
10. Rocco M, Conti G, Alessandri E, et al. Rescue treatment for noninvasive ventilation failure due
to interface intolerance with remifentanil analgosedation: a pilot study. Intensive Care Med.
2010;36:2060–5. doi:10.1007/s00134-010-2026-y.
11. Constantin JM, Schneider E, Cayot-Constantin S, et al. Remifentanil-based sedation to treat
noninvasive ventilation failure: a preliminary study. Intensive Care Med. 2007;33:82–7.
12. Huang Z, Chen YS, Yang ZL, et al. Dexmedetomidine versus midazolam for the sedation of
patients with non-invasive ventilation failure. Intern Med. 2012;51:2299–305.
13. Devlin JW, Al-Qadheeb NS, Chi A, et al. Efficacy and safety of early dexmedetomidine during
noninvasive ventilation for patients with acute respiratory failure: a randomized, double-blind,
placebo-controlled pilot study. Chest. 2014;145:1204–12.
14. Clouzeau B, Bui HN, Guilhon E, et al. Fiberoptic bronchoscopy under noninvasive ventilation
and propofol target-controlled infusion in hypoxemic patients. Intensive Care Med. 2011;
37(12):1969–75. doi:10.1007/s00134-011-2375-1.
Use of Noninvasive Ventilation
in the Course of Extracorporeal 73
Membrane Oxygenation

Adriano Peris, Maria Cristina Cozzolino, and Morena Ferraro

Contents
73.1 Introduction ................................................................................................................. 627
73.2 Discussion and Analysis ............................................................................................. 629
73.2.1 Application Fields ......................................................................................... 629
Conclusions ............................................................................................................................ 630
References .............................................................................................................................. 631

Abbreviations

ARDS Acute respiratory distress syndrome

COPD Chronic obstructive pulmonary disease
ECCO2R Extracorporeal CO2 Removal
ECMO Extracorporeal membrane oxygenation
IMV Invasive mechanical ventilation
NIV Noninvasive ventilation

73.1 Introduction

Over the years, the therapeutic approach to respiratory failure in its various forms
was based on a mechanistic approach. The most important innovation was the
replacement of natural ventilation controlled by the negative pressure of the pleura

A. Peris (*) • M.C. Cozzolino • M. Ferraro

Emergency and TRauma ICU-Regional ECMO Referral Center,
Careggi Teaching Hospital-Florence (ITA), Florence, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 627

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_73
628 A. Peris et al.

with a positive pressure induced by an external device that is still based on the bio-
mechanical principles of more than 50 years ago. Invasive mechanical ventilation
(IMV), which is technologically more advanced in its expression, requires the trans-
fer of a flow of gas at positive pressure at the level of the carina. This type of ventila-
tion is optimized in the presence of a complete adaptation of the patient and a
nonoffensive ventilation mode, meeting the needs of the lung-chest wall system,
using triggers and automatic detection of compliance.
Noninvasive mask ventilation is still included in the initial stages of anesthe-
sia and is considered to be preparatory ventilation in conditions of respiratory
failure awaiting definitive clinical decisions, such as tracheal intubation, or opti-
mization of extrapulmonary physiological parameters that might prevent intuba-
tion. Clinical studies have established that it is possible to continue without
intubation, maintaining positive ventilation even for prolonged periods of time,
by exploiting the recruitability of lung areas to low ventilation-perfusion ratio
and contextually maintaining a gas flow for the CO2 wash-out. In this new set-
ting, there is little new knowledge about the physiology of positive pressure
ventilation. The skills of the operators have had to gradually be oriented to the
appropriate choice of sedation techniques, optimization of cardiocirculatory
function, and physiotherapy. Widespread use of noninvasive ventilation (NIV)
has stimulated clinicians to improve the capability to anticipate the conditions
of low compliance with NIV treatment, thus preventing hypoxia and acidosis,
both of which synergistically lead to emergency intubation and hinder the sub-
sequent recovery of the lung.
The limit of a system of this type, with, on the one hand, a perfectly working
device (a ventilator) and, on the other, a patient who is tolerant and perfectly adapted
to the ventilation, is that it is unstable system. In acute conditions, NIV requires the
reversibility of the pathophysiological process underlying the respiratory failure,
and therefore its stability is time correlated.
The extension of the therapeutic window is especially useful to avoid tracheal
intubation, which is an important morbidity factor. Especially in patients at high
infectious risk, prevention of bacterial colonization and multidrug resistance are
decisive factors for the prevention of mortality and can even contribute to the com-
pletion of therapeutic programs such as lung transplantation. In some centers
where extracorporeal membrane oxygenation (ECMO) is routinely applied in
patients who are candidates for lung transplant or in the presence of acute respira-
tory distress syndrome (ARDS) refractory to treatment, protocols have been devel-
oped that apply NIV associated with ECMO. The attractive hypothesis of this
association is essentially based on the possibility of ensuring ventilation without
intubation even for long periods, and consequently avoiding prolonged use of seda-
tive drugs and opioids. With this approach, it is possible to maintain the patient's
ability to participate in the ventilation and physiotherapy with beneficial effects on
the recovery phase. Maintaining NIV is also facilitated, in theory, by the use of
ECMO, thanks to the stability of oxygenation, carbon dioxide blood content, and
blood pH, preventing phases of distress that can lead to NIV failure and subsequent
invasive ventilation.
73 Use of Noninvasive Ventilation in the Course of Extracorporeal Membrane 629

73.2 Discussion and Analysis

ECMO is an important therapeutic strategy that was developed and first used over
40 years ago to support an adult patient with refractory respiratory failure. Recent
evidence suggests that ECMO may positively impact survival in adult patients with
refractory respiratory failure [1]. Over the past decades, the use of extracorporeal
respiratory support has increased and different modalities have been described.
Veno-venous ECMO may be initiated as a treatment strategy for patients with severe
acute respiratory failure, including ARDS. Additionally, partial extracorporeal sup-
port systems have been suggested for less severe respiratory failure. These devices
prevalently remove carbon dioxide from blood, providing limited oxygenation. For
a long time, the approach of replacing the failing native lung with an artificial organ
was used as a salvage therapy for patients with profound gas-exchange abnormali-
ties despite IMV. The advantages of the technique are well established, but there are
also well-known disadvantages, such as an increased risk for nosocomial pneumo-
nia, neurological disorders associated with prolonged analog-sedation, and activa-
tion of inflammation, leading to ventilator-induced lung injury [2].
In the last decade, some groups have began to consider ECMO as an alternative
to IMV in selected groups of patients; this approach is frequently called “awake
ECMO.” In theory, several activities could play a positive role during awake ECMO,
such as spontaneous feeding, physiotherapy, and interaction with relatives and med-
ical staff. An important factor is the preservation of diaphragm function; further-
more, the well-known detrimental effects of IMV (barotrauma, pneumothorax,
decrease in cardiac output, ventilation-associated pneumonia, and ventilator-
associated lung injury) can be avoided [3].
During awake ECMO, different devices for supplementary oxygen delivery can be
used, ranging from oxygen facial mask to NIV. The use of ventilatory support such as
continuous positive airway pressure/NIV could be necessary to exploit residual oxy-
genation function of the native lung or to prevent progressive lung derecruitment.

73.2.1 Application Fields

The most important indication for awake ECMO is as a bridge to lung transplanta-
tion, to avoid muscle deconditioning, neuromuscular complications, and hospital-
acquired infections caused by intubation and sedation. Numerous centers have
reported the strategy of employing ECMO as a bridge to lung transplantation with-
out invasive ventilation. Fuehner et al. [4] evaluated the outcomes of patients treated
with the awake ECMO strategy as a bridge to transplantation. Patients in the awake
ECMO group required shorter postoperative IMV and showed a trend toward a
shorter postoperative hospital stay. Crotti et al. [5] found that patients who maintain
spontaneous breathing on NIV during ECMO bridging have a lower morbidity
before and after lung transplantation.
Another application field for NIV and “awake extracorporeal support” is for the
treatment of patients with severe chronic obstructive pulmonary disease (COPD).
630 A. Peris et al.

For patients experiencing acute respiratory failure due to a severe exacerbation of

COPD, NIV has been shown to significantly reduce mortality and hospital length of
stay compared with respiratory support with IMV. Lower mortality has been
reported in patients successfully treated with NIV compared with IMV, and NIV has
thus become a standard of care in severe exacerbation of COPD [6]. Despite contin-
ued improvements in NIV administration, refractory hypercapnia and hypercapnic
acidosis necessitate IMV. On the other hand, particularly in this group of patients,
the use of IMV frequently leads to lung damage and concomitant complications,
such as pneumothorax and pneumomediastinum. This suggests that any technique
that increases the avoidance of IMV in severe COPD exacerbation is likely to be of
clinical benefit.
The use of extracorporeal CO2 removal (ECCO2R) has been reported in acute
exacerbations of COPD. This is a strategy that could reduce the requirement of
IMV. In the study of Kluge et al. [7], 21 patients treated with partial ECCO2R, at the
point of failing support with NIV were compared retrospectively with patients who
had been treated conventionally with IMV after failing NIV. The results of this
study showed that 90 % of the patients treated with ECCO2R did not require intuba-
tion and invasive respiratory support. Moreover, this group showed a trend toward
reduced length of hospital stay.
A novel concept is the use of awake ECMO in patients with ARDS to avoid the
complications of invasive ventilation. Wiesner et al. [8] reported a single case of
awake ECMO in a 26-year-old woman with ARDS following septic shock who
failed NIV and refused invasive ventilation. The patient fully recovered and was
discharged from the hospital 8 days after decannulation. Hoeper et al. [9] described
six cases of ARDS treated with ECMO instead IMV; the patients suffered from
isolated lung failure and most were immunocompromised, potentially obtaining
particular benefit from avoiding endotracheal intubation. Of course this strategy
will not replace IMV as the standard ARDS treatment, but it may become a feasible
alternative in carefully selected patients in which one might consider the use of
ECMO during NIV treatment.

Conclusions
NIV is now a widespread therapeutic approach in patients with several causes of
respiratory failure. Referral centers for respiratory failure and ARDS treatment
should develop procedures that can be applied in patients needing respiratory
support with the purpose of preventing intubation. Currently, the most intuitive
ECMO application in cooperative patient is the preemptive treatment of patients
affected by end-stage lung disease, particularly cystic fibrosis, awaiting lung
transplant. In the last 5 years, respiratory failure associated with flu outbreaks,
especially the influenza A (H1N1) pandemic flu, has increased the use of ECMO,
leading to better knowledge of this therapeutic approach in ARDS patients.
Some centers have extended the use of extracorporeal support in patients with
ARDS initially treated with NIV. Although the use of awake ECMO in acute
hypoxic respiratory failure is still under investigation and the subject of debate,
considering the safety of NIV treatment during ECMO, this approach should be
73 Use of Noninvasive Ventilation in the Course of Extracorporeal Membrane 631

implemented through specific clinical procedures as a feasible therapeutic strat-

egy in selected patients with ARDS.
The main limiting factor to this approach is represented by the late involvement
of ECMO referral centers in the treatment of patients with ARDS, usually after the
failure of conventional treatment. A future approach, based on early involvement
of experienced centers during the earliest stages of respiratory failure, can provide
the opportunity to increase the number of patients treated with the awake ECMO
strategy. Of course, the use of NIV treatment in patients undergoing extracorporeal
support, even with the low blood-flow technique (ECCO2R), should be restricted to
selected centers highly experience in extracorporeal treatment.

Key Major Recommendations

• Use the awake ECMO strategy in patients awaiting lung transplant.
• Implement specific clinical procedures of NIV treatment during ECMO
support in patients with ARDS.
• Involve referral ECMO centers early in the treatment of patients with
ARDS, using awake ECMO as the main target and indicator of efficacy.
• ECMO should be restricted to selected centers that are highly experienced
in extracorporeal treatment.

References
1. Patroniti N, Zangrillo A, Pappalardo F, et al. The Italian ECMO network experience during the
2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks.
Intensive Care Med. 2011;37(9):1447–57.
2. Schmidt M, Pellegrino V, Combes A, et al. Mechanical ventilation during extracorporeal mem-
brane oxygenation. Crit Care. 2014;18(1):203.
3. Nosotti M, Rosso L, Tosi D, et al. Extracorporeal membrane oxygenation with spontaneous
breathing as a bridge to lung transplantation. Interact Cardiovasc Thorac Surg. 2013;16(1):
55–9.
4. Fuehner T, Kuehn C, Hadem J, et al. Extracorporeal membrane oxygenation in awake patients
as bridge to lung transplantation. Am J Respir Crit Care Med. 2012;185(7):763–8.
5. Crotti S, Iotti GA, Lissoni A, et al. Organ allocation waiting time during extracorporeal bridge
to lung transplant affects outcomes. Chest. 2013;144(3):1018–25.
6. Chandra D, Stamm JA, Taylor B. Outcomes of noninvasive ventilation for acute exacerbations
of chronic obstructive pulmonary disease in the United States, 1998–2008. Am J Respir Crit
Care Med. 2012;185(2):152–9.
7. Kluge S, Braune SA, Engel M, et al. Avoiding invasive mechanical ventilation by extracorpo-
real carbon dioxide removal in patients failing noninvasive ventilation. Intensive Care Med.
2012;38(10):1632–9.
8. Wiesner O, Hadem J, Sommer W, et al. Extracorporeal membrane oxygenation in a nonintu-
bated patient with acute respiratory distress syndrome. Eur Respir J. 2012;40(5):1296–8.
9. Hoeper MM, Wiesner O, Hadem J, et al. Extracorporeal membrane oxygenation instead of
invasive mechanical ventilation in patients with acute respiratory distress syndrome. Intensive
Care Med. 2013;39(11):2056–7.
Noninvasive Ventilation Outside the ICU
74
Laura Pasin, Pasquale Nardelli, and Alessandro Belletti

Contents
74.1 Introduction ................................................................................................................. 634
74.2 Discussion and Analysis ............................................................................................. 634
74.2.1 Evidence of NIV Success .............................................................................. 634
74.2.2 Optimal Use of Noninvasive Ventilation ....................................................... 635
Conclusions ............................................................................................................................ 636
References .............................................................................................................................. 637

Abbreviations

AHRF Acute hypoxemic respiratory failure

ALI Acute lung injury
ARDS Acute respiratory distress syndrome
ARF Acute respiratory failure
COPD Chronic obstructive pulmonary disease
ICU Intensive care unit
NIV Noninvasive ventilation

L. Pasin, MD (*) • P. Nardelli, MD • A. Belletti, MD

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Hospital,
Via Olgettina 60, Milan 20132, Italy
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 633

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_74
634 L. Pasin et al.

74.1 Introduction

The use of noninvasive ventilation (NIV) for the treatment of patients with acute
respiratory failure (ARF) has markedly increased in the last decades. Currently,
NIV can be considered the first-choice therapy in the treatment cardiogenic pul-
monary edema, chronic obstructive pulmonary disease (COPD) exacerbations,
and acute hypoxemic respiratory failure (AHRF), especially in immunocompro-
mised patients. In addition to these well-established indications, NIV is also
commonly used in conditions in which response to NIV is less clear, including
asthma, chronic neuromuscular and neurologic diseases, and pneumonia in non-
immunocompromised patients. The increasing knowledge of NIV efficacy and
physicians’ familiarity with managing this technique have been accompanied by
a progressive reduction of the number of available intensive care unit (ICU) beds
worldwide. Therefore, as confirmed by a recent international web-based survey,
the use of NIV in general wards is common and growing [1, 2]. In fact the per-
centage of hospitals using NIV in general wards was reported to have increased
from 10 % in 2005 [3] to 66 % in 2014 [1].

74.2 Discussion and Analysis

74.2.1 Evidence of NIV Success

According to published evidence, NIV treatment is supported by a large number of

randomized clinical trials showing a statistically significant mortality reduction in
patients affected by ARF in different contexts, such as weaning from invasive
mechanical ventilation, respiratory acidosis, acute exacerbation of COPD, and
AHRF [4].
Strong evidence from meta-analyses of randomized clinical trials has proved that
the addition of NIV to standard medical care improves the outcome of patients with
acute cardiogenic pulmonary edema or COPD exacerbation [5, 6]. Nonetheless,
NIV can be used to support patients with ARF from other etiologies. In fact, an
international web-based survey [1] showed that, worldwide, other frequent causes
of ARF commonly treated by NIV outside the ICU are neuromuscular diseases,
postoperative ARF, and pneumonia in immunocompromised patients. Moreover,
NIV is often prescribed in non-immunocompromised patients with pneumonia, in
asthma and thoracic trauma, or as a palliative treatment.
However, while the effectiveness of NIV in avoiding the need for endotra-
cheal intubation and reducing related mortality in patients with AHRF has been
widely supported in recent decades, the efficacy of NIV in AHRF that is not
related to COPD or acute pulmonary edema is debated. Currently, controversies
still exist regarding NIV application in community-acquired pneumonia, acute
asthma, post-extubation respiratory failure, chest trauma, rapidly progressive
neurological diseases, acute lung injury (ALI), and acute respiratory distress
syndrome (ARDS).
74 Noninvasive Ventilation Outside the ICU 635

Table 74.1 Contraindi- Absolute:

cations to NIV application
Inability to protect airways
Significantly altered mental status
Inability to cooperate with wearing and fitting mask
Apnea
Respiratory arrest
Shock
Pneumothorax
Recent facial fractures
Recent esophageal, laryngeal, or gastric surgery
Rapid clinical deterioration
Inadequate staff to closely monitor the patients in case of
deterioration
Relative:
Significant chest trauma
Nausea and vomiting
Agitation
Cardiac arrhythmias
Cardiac ischemia or acute myocardial infarction

Patients with community-acquired pneumonia treated with NIV were often asso-
ciated with poor outcome in the literature. However, more recent studies reported
better outcomes in patients treated with NIV in this context [8]. Therefore, large,
randomized clinical trials are needed to confirm these recent, positive findings. On
the contrary, recent reviews on the use of NIV in acute asthma concluded that there
is not enough evidence to support the use of NIV in this setting and that medical
treatment alone may usually be effective [7].
Regarding post-extubation respiratory failure, no trials have proved the benefit of
NIV treatment in ARF during the first 48–72 h after extubation. Furthermore, one
multicenter randomized clinical trial even found an increased mortality rate in the
group of patients treated with NIV, probably due to delayed reintubation. As a
result, current guidelines suggest that NIV should not be routinely used in patients
who develop post-extubation respiratory failure [9].
Current evidence does not support the routine use of NIV in patients with ALI/ARDS
and chest trauma because of lack of well-designed randomized clinical trials [8, 10].

74.2.2 Optimal Use of Noninvasive Ventilation

Regardless the underlying cause of ARF and the above-discussed limitations of

NIV application, patients with exclusion criteria for NIV should be carefully identi-
fied. Absolute and relative contraindications to NIV are presented in Table 74.1.
The identification of the right patients likely to benefit from NIV therapy can be
considered the key to NIV success outside ICU, along with the recognition of NIV
636 L. Pasin et al.

failure and avoiding delayed intubation when indicated. However, it is not always
easy to identify which patients will initially benefit from treatment. Usually, sub-
jects likely to fail NIV are older, with a lower level of consciousness, more severe
hypoxia, tachypnea, and respiratory acidosis. Moreover, clinical signs that can be
unclear on presentation generally become more definitively predictive of NIV fail-
ure if they persist after 2 h of starting NIV [11, 12].
No current guidelines suggest the use of one specific interface among the others,
nor one mode of noninvasive positive-pressure ventilation, a model of ventilator, or
an optimal triggering for NIV application [9]. Nonetheless available evidence on
patients with ARF suggests that the first choice of interface should be the oronasal
mask or full face mask. Different interfaces should be available in case of patient
intolerance to the oronasal mask or full face mask, or if complications such as facial
cutaneous lesions occur.

Conclusions
The use of NIV in general wards is common and growing worldwide. Strong
published evidence has proved that the addition of NIV to standard care improves
outcomes of patients with COPD exacerbation or acute cardiogenic pulmonary
edema. Controversies still exist regarding NIV application in conditions in which
response to NIV is less clear, such as community-acquired pneumonia, acute
asthma, post-extubation respiratory failure, chest trauma, rapidly progressive
neurological diseases, ALI, and ARDS. Therefore large, well-designed, random-
ized clinical trials are needed in these settings. Moreover, definitive and specific
guidelines and protocols for the management of NIV in the general ward are
warranted.

Key Major Recommendations

• The use of NIV outside ICU should be encouraged, expecially in patients
with COPD exacerbation or acute cardiogenic pulmonary edema.
• Patients with exclusion criteria for NIV should be carefully identified.
• Early recognition of NIV failure, avoiding delayed intubation when indi-
cated is one of the keypoint of NIV success outside ICU.
• The first choice interface should be the oronasal mask or the full face mask
but different interfaces should be always available in case of patients’
intolerance.
• Improvement in staff training and introduction of standardized protocols
could help making NIV safer and more common when applied in general
non-monitored wards.
74 Noninvasive Ventilation Outside the ICU 637

References
1. Cabrini L, Esquinas A, Pasin L, Nardelli P, Frati E, Pintaudi M, Matos P, Landoni G, Zangrillo
A. An international survey on noninvasive ventilation use for acute respiratory failure in gen-
eral non-monitored wards. Respir Care. 2015;60(4):586–92. doi: 10.4187/respcare.03593.
2. Cabrini L, Antonelli M, Savoia G, Landriscina M. Non-invasive ventilation outside of the
intensive care unit: an Italian survey. Minerva Anestesiol. 2011;77(3):313–22.
3. Burns KE, Sinuff T, Adhikari NK, Meade MO, Heels-Ansdell D, Martin CM, Cook DJ. Bilevel
positive pressure ventilation for acute respiratory failure: survey of Ontario practice. Crit Care
Med. 2005;33(7):1477–83.
4. Landoni G, Comis M, Conte M, Finco G, Mucchetti M, Paternoster G, Pisano A, Ruggeri L,
Alvaro G, Angelone M, Bergonzi PC, Bocchino S, Borghi G, Bove T, Buscaglia G, Cabrini L,
Callegher L, Caramelli F, Colombo S, Corno L, Del Sarto P, Feltracco P, Forti A, Ganzaroli M,
Greco M, Guarracino F, Lembo R, Lobreglio R, Meroni R, Monaco F, Musu M, Pala G, Pasin
L, Pieri M, Pisarra S, Ponticelli G, Roasio A, Santini F, Silvetti S, Székely A, Zambon M,
Zucchetti MC, Zangrillo A, Bellomo R. Mortality in Multicenter Critical Care Trials:
An Analysis of Interventions With a Significant Effect. Crit Care Med. 2015;43(8):1559–68.
doi: 10.1097/CCM.0000000000000974.
5. Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Noninvasive positive pressure ventilation to treat
respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane
systematic review and meta-analysis. BMJ. 2003;326:185–9. [PMC free article] [PubMed]
6. Masip J, Roque M, Sánchez B, Fernández R, Subirana M, Expósito J. Noninvasive ventilation
in acute cardiogenic pulmonary edema. Systematic review and meta-analysis. JAMA. 2005;
294:3124–30.
7. Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, Rowe
BH, Smith BJ. Non-invasive positive pressure ventilation for treatment of respiratory failure
due to severe acute exacerbations of asthma. Cochrane Database Syst Rev. 2012;12:CD004360.
doi: 10.1002/14651858.CD004360.pub4.
8. Ferrer M, Torres A. Noninvasive ventilation for acute respiratory failure. Curr Opin Crit Care.
2015;21(1):1–6. doi:10.1097/MCC.0000000000000173.
9. Keenan SP, Sinuff T, Burns K, Canadian Critical Care Trials Group/Canadian Critical Care
Society Noninvasive Ventilation Guidelines Group, et al. Clinical practice guidelines for the
use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway
pressure in the acute care setting. CMAJ. 2011;183(3):E195–214.
10. Karcz MK, Papadakos PJ. Noninvasive ventilation in trauma. World J Crit Care Med.
2015;4(1):47–54. doi:10.5492/wjccm.v4.i1.47. eCollection 2015.
11. Hill NS. Where should noninvasive ventilation be delivered? Respir Care. 2009;54(1):62–70.
12. Confalonieri M, Garuti G, Cattaruzza MS, Osborn JF, Antonelli M, Conti G, et al. A chart of
failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J.
2005;25(2):348–55.
 Part IX
Non Invasive Ventilation in Sleep Medicine
Anatomical, Physical, and Psychological
Factors of NIV Interfaces 75
Zoltan Tomori, Viliam Donic, Pavol Torok,
and Josef Firment

Contents
75.1 Introduction ................................................................................................................. 642
75.1.1 Anatomical and Physical Factors of NIV Interfaces ..................................... 642
75.1.2 Analysis of the NIV Effects and Their Comparison to Airway Reflexes...... 642
75.2 Assessment of UA Resistance: UA Patency/Collapsibility ........................................ 643
75.3 Discussion ................................................................................................................... 644
75.3.1 Valvular Function of UA during Sleep .......................................................... 644
75.3.2 Psychological Factors .................................................................................... 646
Conclusion ............................................................................................................................. 646
References .............................................................................................................................. 647

Abbreviations

AHI Apnea hypopnea index

ARDS Adult respiratory distress syndrome
AspR Aspiration reflex
CPAP Continuous positive airway pressure
e-sigh Extended sigh

Z. Tomori (*) • V. Donic

Department of Human Physiology, Faculty of Medicine, Safarik University,
Kosice, Slovak Republic
e-mail: [email protected]
P. Torok
Faculty of Medicine, Clinic of Anesthesiology and Intensive Medicine, East-Slovakian
Institute of Heart and Vascular Diseases, Safarik University, Kosice, Slovak Republic
J. Firment
Faculty of Medicine, Clinic of Anesthesiology and Intensive Medicine,
University PJ Safarik, Kosice, Slovakia

© Springer International Publishing Switzerland 2016 641

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_75
642 Z. Tomori et al.

CR Cough reflex
EEG Electroencephalogram
EMG Electromyogram
ExpR Expiration reflex
NIPPV Noninvasive positive pressure ventilation
NIV Noninvasive ventilation
Pcrit Critical pressure
PEEP Positive end-expiratory pressure
SAHS Sleep apnea hypopnea syndrome
SDB Sleep-disordered breathing
TI Inspiratory time
UA Upper airways
UANP Upper airway negative pressure

75.1 Introduction

75.1.1 Anatomical and Physical Factors of NIV Interfaces

The upper airways (UA), as the crossroads of the respiratory and gastrointestinal
systems, have a valvular function, serving respiration in addition to providing swal-
lowing and other gastrointestinal functions, as well as speech, psychological, and
other activities. The function and mechanisms of the UA are complex, largely
depending on the balance of two main factors: anatomically imposed mechanical
loads (one-third of cases) and neuromuscular factors (two-thirds of cases). Structural
anatomical changes include hypertrophy of tonsils, adenoid vegetations in children,
retrognathia, and various craniofacial variations, as well as increased fatty tissue
deposition around the pharynx and submucosal edema, narrowing the pharyngeal
lumen. The neuromuscular factors are realized by different sphincter mechanisms
and various airway reflexes. The upper, medial, and lower pharyngeal constrictors
represent the sphincters. Pharyngeal dilation results from phasic activation of M.
genioglossus (GG), supported by tonic contraction of the tensor palatini.

75.1.2 Analysis of the NIV Effects and Their Comparison

to Airway Reflexes

The effect of breathing through a tracheal tube and/or the UA on the respiratory
drive was analyzed in dogs [2]. A tracheal tube containing a fenestration allowed
communication also with the UA, and could differentiate the reflex effect of the
negative or positive pressure, acting either from the lower or upper airways. After
tracheal occlusion with closed fenestration, the inspiratory time (TI) of both the
increasing diaphragmal electromyogram (EMG) activity and the decreasing tracheal
pressure was prolonged during wakefulness and sleep, weakening the inhibitory
effect of lung inflation, caused by the Hering-Breuer inflation reflex. After tracheal
75 Anatomical, Physical, and Psychological Factors of NIV Interfaces 643

and nasal occlusion, the opening of fenestration allowed transmission of negative

intrathoracic pressure but not the flow to the UA. Therefore, TI was further pro-
longed, but the change was smaller, indicating an additional but weaker inhibitory
effect from the UA receptors. In addition, the UA negative pressure reflexively acti-
vated the dilatory GG muscle during both wakefulness and sleep (rapid eye move-
ment and non-rapid eye movement). Therefore, there was no collapse of the UA and
the tracheal and mouth pressure practically did not differ [2]. In anesthetized rats, a
negative pressure (> −20 cmH2O) in the UA increased the activity of UA muscle and
changed the thoracic respiratory outflow. This stabilized the UA and minimized the
collapsing stress to which it is subjected during inspiration. In the response to UA
transmural pressure changes, the tongue retractor and pharyngeal constrictor mus-
cles also play a role in keeping the UA patent. After a tracheal closure during expira-
tion, the next inspiration was postponed, imitating central sleep apnea [3].
Noninvasive intermittent positive pressure ventilation (NIPPV) with 4 cmH2O
in a nonsedated neonatal lamb through a tracheostomy evoked active glottal nar-
rowing, resulting from a decrease in the crico-thyroidal (CT) dilator and increase
in the thyro-arytenoideus (TA) constrictor EMG in response to stimulation of
tracheo-broncho-pulmonary receptors but not from the upper airways. However,
similar positive pressure applied to the totally isolated UA did not evoke laryngo-
constriction, but during the inspiratory phase in the lamb, breathing though a tra-
cheotomy, there was an increase of airway pressure in the mask and an increased
activation of CT-dilator muscle [6]. Vocal cord adduction was induced in cats by
application of negative pressure to lower airways and even more strongly from the
subglottal area [7]. These seemingly contradictory results can be explained partly
by use of different conditions: various animal species compared with humans, pre-
medication, anesthesia, possible damage of laryngeal nerve supply during vagot-
omy, and sleep or wakefulness. However, they are in agreement with the effect
of two distinct airway reflexes: the sniff- and gasp-like aspiration reflex (AspR),
characterized by deep inspiration and laryngo-dilation, elicited from the naso- and
oro- pharynx, and the so-called expiration reflex (ExpR), manifesting with laryngo-
constriction and prompt expiration, evoked from the larynx and lower airways by
mechanical contact and by negative or positive pressure stimulation [4].
UA negative pressure (UANP) influences the diaphragmal inspiratory activity
not only in animals but also in infants. Compared with separate occlusion of lower
airways, brief occlusion of upper and lower airways reduced the maximum airway
pressure and the slope of airflow rate with a threshold of suction pressure −4 cmH2O
and latency around 0.12 s, suggesting that UA suction reflexively inhibits the tho-
racic inspiratory muscles [5].

75.2 Assessment of UA Resistance: UA Patency/Collapsibility

The UANP reflex, with afferents in the trigeminal, glossopharyngeal, and superior
laryngeal nerves, can modify the lumen of UA by activation of dilatory muscles
(GG and tensor palatini), as well as the upper, medial, and lower constrictors [6, 7].
644 Z. Tomori et al.

The valvular function of the UA influences both the airway patency (measured by
pharyngeal resistance) and the anatomical airway narrowing/collapsibility
(reflected by necessary positive end-expiratory pressure) observed in patients with
severe sleep apnea hypopnea syndrome (SAHS), with apnea hypopnea index 75/h.
The UANP, in addition to primary activation, also induces a secondary inhibition of
GG muscle activity to prevent aspiration by allowing UA collapsibility together
with modification of diaphragmal activity.

75.3 Discussion

Full face masks are used more frequently in NIV in acute cases to avoid analgo-
sedation and prevent laryngeal swelling caused by intubation [8, 9]. NIV can be
applied in clinical wards 24 h a day, with a possibility of gradual weaning. In
chronic conditions, use of a nasal mask is preferred, for less static dead space and
fewer skin irritations and claustrophobic effects, and because it allows better com-
fort for eating, drinking, expectoration, and communication [10, 11]. Nasal pillows
or plugs and mouthpieces are used less often [1].

75.3.1 Valvular Function of UA during Sleep

The valvular function of UA changes significantly during sleep, particularly in

patients with sleep-disordered breathing (SDB) manifested by snoring. In adult
patients with SAHS, there is a collapse of the UA, which occurs at low negative and
even positive inspiratory airway pressures. The critical pressure (Pcrit) separating
SAHS patients from healthy subjects is −5 cmH2O. The occlusion of the UA is
caused by passive mechanical loads in one-third of cases and by active neuromus-
cular compensation in two-thirds. However, closing of the UA also develops at less
negative Pcrit in children with mild SDB, compared with controls, indicating a
higher pharyngeal collapsibility. The lowest positive nasal pressure allowing effec-
tive flow at maintained airway patency was tested. The mean value of this so-called
flow-dependent positive airway pressure in SAHS patients was 6.6 ± 1.2 cmH2O. The
closing Pcrit in SAHS patients is less negative than the opening pressure, and both
change dynamically throughout the respiratory cycle and in various stages of sleep,
as well as in different body positions during sleep.
A change of valvular system activity allows stimulation of various regions of the
airways during NIV, resulting in different effects. Animal experiments indicated
that mechanical and other methods of stimulation of the upper and lower airways
evokes three different airway reflexes. Stimulation of the oro- and nasopharynx
evokes strong inspiratory effort (gasp or sniff-like aspiration reflex, or AspR),
caused by reflex activation of the brainstem inspiratory generator. A similar reaction
can also be evoked by a voluntary sniff. On the contrary, stimulation of the larynx
evokes strong expiratory effort (expiration reflex, or ExpR), as a result of reflex
activation of the brainstem expiratory generator. Stimulation of the lower airways
75 Anatomical, Physical, and Psychological Factors of NIV Interfaces 645

Fig. 75.1 Reflex arch indicating the afferent (A), central (C), and efferent (E) components of the
AspR, ExpR, and cough reflex and their voluntary counterparts (From Tomori et al. [4])

evokes the cough reflex, characterized by deep inspiration, followed by rapid and
strong expiratory effort, caused by reflex activation of the inspiratory and followed
subsequently by the expiratory generator. [4, 12–15] The afferent (A), central (C),
and efferent (E) parts of these three airway reflexes are indicated in Fig. 75.1.
Obesity and craniofacial abnormalities significantly influence the collapsibility
of upper airways in patients with SDB. On the other hand, GG muscle contrac-
tion evoked by electrical stimulation increased the cross-sectional area of both the
velopharynx and nasopharynx and decreased the critical pressure from 1.2 ± 3.3
to −0.7 ± 3.8 cmH2O without affecting pharyngeal stiffness in patients with SDB.
Sitting posture and sniffing position decreases the collapsibility of passive pharynx
in patients. UA anatomic loads in combination with mechanical trauma, caused by
snoring and apneic episodes, can initiate an inflammatory process. This can lead to
a series of ultrastructural changes, aggravating neuromechanical defects manifest-
ing in SAHS. In adult respiratory distress syndrome (ARDS), there is a decrease of
646 Z. Tomori et al.

alveolar volume (alveolar derecruitment), where continuous positive airway pres-

sure (CPAP) improves oxygenation. A recruitment maneuver with extended sigh
(e-sigh), using CPAP with high values (>40 cmH2O) for 40 min, can be adapted to
the patient according to flow volume curves and positive end-expiratory pressure
(PEEP) >15 cmH2O. Such treatment also evokes in most patients alveolar recruit-
ment and increase in tidal volume and better cardiorespiratory tolerance. Similar
high pressure and constantly increased PEEP, induced by shortening of the expira-
tory time, can be obtained using a patented device called the ParaVent from Kalas
(Povazska Bystrica, Slovakia), providing alveolar recruitment in addition to an
expulsive effect adjustable in patients with pulmonary edema [13].

75.3.2 Psychological Factors

There are many unpleasant side effects of NIV, including claustrophobia, distur-
bance of sleep, decrease of mobility, and noise of the ventilator. However, domicili-
ary NIPPV with average daily use of ventilator for 10.5 ± 2 h in 6 patients of
79 ± 3 years treated 31 ± 17 months for hypercapnic restrictive-pulmonary disease
indicated good tolerance and compliance with very good general results. The hospi-
talization rate decreased from 40 ± 31 days/year during treatment to 13 ± 14 days
and to 0.8 + −0.4 days for 2 successive years. All patients showed improved arterial
blood gases (from PaCO2 66 ± 10 to 46 ± 9 mmHg, p = 0.04). The results indicated
that the scores for mental health, social well-being, vitality, and social functioning
did not differ from those of age-matched controls. Therefore, old age cannot be
considered per se as a contraindication to NIPPV in patients with well-accepted
indications, and the cost/benefit ratio may be favorable.

Conclusion
Anatomical, physical, and psychological factors provide many advantages for
successful application of NIV, indicated and performed according to guidelines,
and including NIPPV in the older population. Modification of NIV using larger
volume has therapeutic use, or when applied preferentially to upper or lower
airways through provocation of valvular function, it also has a reflex effect, typi-
cal of the region involved.

Key Major Recommendations

Benefits of the chapter are proposals for non-invasive ventilation using a mask
for management of respiratory failure in patients:
• Minimalizing leakage around the mask with a tight fit, preventing interface
that does not cause side effect.
• Using a comfortable interface that does not cause side effects.
• Providing a compensation for leakage with increased volume or pressure.
The aim of successful NIV is to maximize ventilation and improve patient-
ventilator synchrony[1].
75 Anatomical, Physical, and Psychological Factors of NIV Interfaces 647

References
1. Elliott MW. The interface: crucial for successful noninvasive ventilation. Eur Respir J.
2004;23:7–8.
2. Eastwood PR, Curran AK, Smith CA, et al. Effect of upper airway negative pressure on inspi-
ratory drive during sleep. J Appl Physiol. 1998;84:1063–75.
3. Ryan S, Mc Nicholas WT, Regan RG, et al. Reflex respiratory response to changes in upper
airway pressure in the anaesthetized rat. J Physiol. 2001;537:251–65.
4. Tomori Z, Donic V, Benacka R, et al. Reversal of functional disorders by aspiration, expira-
tion, and cough reflexes and their voluntary counterparts. Front Respir Physiol. 2012; article
00467: 1–14. doi: 10.3389/fphys.2012.
5. Thach BT, Shaft GL, Pickens DL, et al. Influence of upper airway negative pressure reflex on
response to airway occlusion in sleeping infants. J Appl Physiol. 1989;67:749–55.
6. Horner RL, Innes JA, Holden HB, et al. Afferent pathway(s) for pharyngeal dilatory reflex to
negative pressure in man: a study of upper airway anaesthesia. J Physiol. 1991;436:31–44.
7. Patil SP, Schneider H, Marx JJ, et al. Neuro mechanical control of upper airway patency during
sleep. Appl Physiol. 2007;102:547–56.
8. Eckert DJ, McEvoy RD, George KE, et al. Genioglossus reflex inhibition to upper-airway
negative pressure stimuli during wakefulness and sleep in healthy males. J Physiol. 2007;582:
1193–205.
9. Horner RL. Contribution of passive mechanical loads and active neuromuscular compensation
to upper airway collapsibility during sleep. J Appl Physiol. 2007;102:510–2.
10. Schwartz AR, Patil SP, Schneider H, et al. Modeling pathogenic mechanisms of upper airway
function in the molecular age. Eur Respir J. 2008;32:255–8.
11. Constantin JM, Jaber S, Futier E, et al. Respiratory effects of different recruitment maneuvers
in acute respiratory distress syndrome. Crit Care. 2008;12(2):R50. doi:10.1186/cc6869.
12. Tomori Z, Donic V. Influence of down regulation and up-regulation of cough using airway
reflexes and breathing maneuvers: chapter 1. In: Esquinas AM, editor. Noninvasive ventilation
in high-risk infections and mass casualty events. Wien: Springer; 2014. p. 3–6.
13. Donic V, Torok P, Tomori Z. Preventing the spread of aerosol infection during application of
high-frequency jet ventilation by mask. In: Esquinas AM, editor. Noninvasive ventilation in
high-risk infections and mass casualty events. Wien: Springer; 2014. p. 45–7.
14. Korpas J, Tomori Z. Cough and other respiratory reflexes. Karger Basel. 1979. p. 379.
15. Tomori Z, Donic V, Benacka R, Jakus J, Gresova S. Resuscitation and auto resuscitation by
airway reflexes in animals. Cough. 2013;9(1):21. doi:10.1186/1745-9974-9-21.
Identification of Therapeutic CPAP
for the Treatment of Obstructive 76
Sleep Apnea: Key Major Topics
and Clinical Implications

Oreste Marrone, Adriana Salvaggio, Anna Lo Bue,

and Giuseppe Insalaco

Contents
76.1 Introduction ................................................................................................................. 650
76.2 Analysis and Discussion ............................................................................................. 651
Conclusions ............................................................................................................................ 654
References .............................................................................................................................. 654

Abbreviations

AASM American Academy of Sleep Medicine

AHI Apnea/hypopnea index
CPAP Continuous positive airway pressure
OSA Obstructive sleep apnea
REM Rapid eye movement

O. Marrone, MD (*) • A. Salvaggio, MD • A. Lo Bue, MD • G. Insalaco, MD

Italian National Research Council – Institute of Biomedicine and Molecular Immunology,
Palermo, Italy
e-mail: [email protected]; [email protected]; [email protected];
[email protected]

© Springer International Publishing Switzerland 2016 649

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_76
650 O. Marrone et al.

76.1 Introduction

Continuous positive airway pressure (CPAP) counterbalances forces leading to

upper airway narrowing or collapse during sleep and is the most widely used treat-
ment for obstructive sleep apnea (OSA). In patients with OSA, progressively higher
CPAP levels applied during sleep turn obstructive apneas into hypopneas, hypop-
neas into continuous inspiratory flow limitation, with or without snoring, and flow
limitation into unobstructed breathing (Fig. 76.1). When breathing becomes unob-
structed, “respiratory arousals,” that is, arousals that may follow increased inspira-
tory efforts associated with obstructed breathing, are eliminated, while sleep
becomes more stable and sleep cycles more regular, contributing to improvements
in subjective sleep quality, daytime sleepiness, and quality of life usually observed
after already few nights of CPAP application [1]. In addition, relief of upper airway
obstruction is associated with resolution of intermittent hypoxemia and hemody-
namic swings that accompany obstructive events, with a consequent reduction in
long-term morbidity and mortality [2].
The objectives of OSA treatment are elimination of symptoms and of health risks
related to upper airway obstruction during sleep. If treatment by CPAP is planned,
patients must be previously instructed and adapted. These aspects are beyond the
scope here. In this chapter, we will review procedures for choosing modalities to
define therapeutic CPAP levels and will discuss their effectiveness. In fact, several
methods may be adopted to identify which pressure must be prescribed to each
patient, sometimes leading to different results. Today, however, according to
European experts, the best procedures to establish the effective CPAP level remain
unknown [3].

Fig. 76.1 Example of effects of increasing CPAP levels on sleep breathing pattern in a patient
with obstructive sleep apnea. Upper left panel: obstructive apneas; upper right panel: obstructive
hypopnea; lower left panel: inspiratory flow limitation, no hypopnea; lower right panel: unob-
structed breathing
76 Identification of Therapeutic CPAP for the Treatment of OSA 651

76.2 Analysis and Discussion

Monitoring during sleep can allow observation of the effects of CPAP on breathing,
and help to identify the pressure to prescribe. CPAP titration consists of the applica-
tion of various CPAP levels during sleep to find the pressure that may best correct
respiratory disorders.
Manual CPAP titration in the sleep laboratory is the oldest titration method. It is
performed during a full night polysomnographic recording, while a technician man-
ually modifies pressure administered by a CPAP device. All signals generally
recorded during polysomnography have an important role: electroencephalogram,
electrooculogram, and chin electromyogram for recognition of sleep stages and
arousals; body position to control CPAP effects in each posture; pressure at the
mask to monitor the CPAP level that is administered; and signals for detection of
snoring, airflow, respiratory movements, and oxyhemoglobin saturation to observe
modifications in breathing characteristics as CPAP level is changed. In particular, as
regards airflow, monitoring by a pneumotachograph is recommended, as a flattened
shape in the inspiratory portion of the flow signal recorded by this method is indica-
tive of flow limitation. The titration polysomnographic study should include the
recording of some rapid-eye-movement (REM) sleep and of some sleep time in the
supine posture, inasmuch as REM sleep, and, even moreso, supine posture, may
require the application of higher CPAP levels [4]. The American Academy of Sleep
Medicine (AASM) allows split-night polysomnographies (first part of the night for
diagnosis, last part for CPAP titration), provided that the diagnostic part of the poly-
somnogram lasts a minimum of 2 hours and documents an apnea/hypopnea index
(AHI: number of apneas + hypopneas per hour of sleep) of at least 40, while the
CPAP titration part is carried out for more than 3 hours, including REM sleep with
the patient in the supine position [5].
More recently, automatic CPAP titration by means of “auto-CPAP” machines has
been introduced (“autotitration”). Auto-CPAP devices are designed to automati-
cally deliver a variable CPAP level that should correspond to the lowest required
pressure in each moment. Today, most auto-CPAP devices are designed to eliminate
all obstructive events and inspiratory flow limitation, and to distinguish central
apneas with open airway, not requiring pressure augmentations, from apneas with a
closed airway. They are able to record several types of information during their
application, including pressures delivered, air leaks, and respiratory events detected,
and can usually calculate AHI. Principles of operation of auto-CPAP devices can be
different. Likewise, their efficacy may differ among patients, although several mod-
ern devices are effective in the correction of upper airway obstruction and reliable
in the vast majority of patients.
Autotitration can be performed with the application of an auto-CPAP device dur-
ing a standard polysomnographic study. A technician may assist autotitration, with
the task to control the polysomnographic recording and the patient. Analysis of the
polysomnographic study allows us to verify the relationship between pressures that
have been delivered and breathing characteristics, sleep architecture, and body pos-
tures. In this way, it is possible to select the CPAP level that proves most appropriate
652 O. Marrone et al.

for correction of upper airway obstruction. This method is recognized as a valid

alternative to traditional manual titration [6], but differences in costs and time
required for the two procedures are limited.
As an alternative to the search for optimal CPAP with polysomnography, unassisted
autotitration without any monitoring, except that provided by the auto-CPAP machine
itself, has been introduced. With this method, an auto-CPAP is given to the patient for
nocturnal self-application. Data collected and elaborated by the machine are down-
loaded, and periods with excessive air leaks are discarded from analysis. The 90th or
95th percentile pressure (i.e., the pressure that is not exceeded for 90 or 95 % of the time
of the auto-CPAP application) is usually considered equivalent to the manually titrated
pressure. Lack of external monitoring during auto-CPAP application can lead to errors
in the recognition of optimal CPAP level. Both administration of excessively high pres-
sures and under-correction of obstruction are possible. Erroneous pressure administra-
tion may go undetected if no monitoring in addition to the one performed with the
auto-CPAP itself is done. AHI calculated by the auto-CPAP machines may help to iden-
tify some unsatisfactory autotitrations. Recent studies have validated the values of AHI
calculated by some auto-CPAP devices. However, reliability of these calculations
depends on the software of each device and may vary between machines [7].
The pressure to prescribe to each patient has been indicated as “optimal” pressure.
It should correspond to the lowest CPAP that eliminates upper airway obstruction in
all sleep stages and body postures. However, the real need to fully correct all degrees
of upper airway obstruction is uncertain [8], and the application of very high CPAP
levels for the purpose of preventing any obstructive episode may be counterproduc-
tive, because it may result in the appearance of central apneas or in discomfort that
may discourage patients from treatment. In fact, the AASM considers optimal titra-
tions those resulting in AHI <5, but still adequate those where the AHI is reduced by
75 % even though it remains >10 [4]. However, an AHI >10 is representative of a
significant alteration of the breathing pattern, and even the AASM recommends
repeating CPAP titration if the number of residual events during CPAP is high.
The strongest argument against nocturnal monitoring for very precise determina-
tions of a CPAP level to prescribe is that the pressure needed to fully open the upper
airway can vary not only within nights, mainly in association with sleep stage or
posture changes, but also between nights. Today, the existence of a precise optimal
pressure is questioned [9], and the role of single-night, either manual or automatic,
titrations, not to speak of split-night procedures, is discussed.
As polysomnographic monitoring for multiple nights is not easily feasible and
has high costs, it has been proposed that unassisted autotitration without external
monitoring be performed for several nights. The average of the 90th or 95th percen-
tile pressures on all nights of auto-CPAP application could represent an appropriate
pressure for treatment. Progressive adaptation of the patient during consecutive
nights to sleep with CPAP could prevent errors associated with poor sleep quality or
lack of REM sleep, minimize errors due to the absence of an external monitoring,
and enhance successive compliance to treatment. Some cases of poor performance
of the auto-CPAP machine may remain undetected if no nocturnal instrumental
monitoring is performed. However, even simple cardiorespiratory monitoring
76 Identification of Therapeutic CPAP for the Treatment of OSA 653

performed after autotitration while wearing CPAP at the fixed level previously
determined may be helpful in identifying uncommon but possible cases of unsatis-
factory autotitrations. In our experience, a disadvantage of unassisted autotitration
is that, despite previous training, not all patients are able to start sleeping with CPAP
if they do not initially have a support from a caregiver.
The number of nights for the unassisted autotitration method is not standardized.
A small number of nights could make it an economical procedure because of the
lack of complex monitoring and analysis, and of technical assistance. Multiple-
night unassisted autotitration has been recognized as a possible valid alternative to
polysomnographic titration, but with recommendations to rely on auto-CPAP
devices that have been better validated and to strictly keep in touch patients after
initiation of CPAP treatment [6]. However, it has been shown that, in a subset of
patients, inter-night variability of the effects of each pressure level is so high that no
single effective pressure for prescription can be identified. In such patients the use-
fulness of any CPAP titration would be limited, and the most appropriate CPAP
treatment will be by means of variable pressure levels, such as those delivered by
auto-CPAP devices [10].
To further simplify CPAP prescription procedures, it has been proposed, rather
than titrating CPAP, to prescribe a pressure calculated by means of predictive equa-
tions. Different predictive equations for therapeutic CPAP have been elaborated.
Calculated pressure values differ to some extent according to the equation. Generally,
agreement between calculated and titrated values decreases when extreme (very low
or very high) pressure levels are required by the patient for treatment [11]. Today,
predictive equations are not considered reliable substitutes for titration [8].
In the last years, it has been emphasized that CPAP prescription and long-term
treatment should carefully take into consideration a patient’s symptoms, life quality,
tolerance and adherence to treatment, and, possibly, benefits on blood pressure con-
trol. These effects may, to some extent, guide clinicians to modify the pressure previ-
ously prescribed on the basis of the results of nocturnal monitoring [12]. However, it
must be kept in mind that, in some cases, clinical criteria may lead to erroneous
interpretations of the effectiveness of CPAP on respiratory disorders. In fact, improve-
ment in sleepiness may occur despite incomplete resolution of upper airway obstruc-
tion, due to a placebo effect or, on the contrary, sleepiness may persist despite normal
breathing; compliance to treatment may be good even with subtherapeutic pressure;
and OSA treatment does not always result in effects on blood pressure.
It has been investigated whether untreated asymptomatic OSA may have prog-
nostic implications. In this regard, contrasting results have been reported.
However, the results of most studies suggest that, in asymptomatic subjects, OSA
may be less dangerous, but it is not harmless [13], especially in patients with
severe disorders. Therefore, incomplete correction of respiratory disorders may
expose patients to persistence of increased cardiovascular risk, and an instrumen-
tal monitoring is advisable, at least before CPAP prescription or after treatment
initiation, even in patients highly compliant to the treatment and with a good cor-
rection of symptoms.
654 O. Marrone et al.

Conclusions
CPAP prescription can be a challenging task. It should simultaneously ensure the
correction of upper airway obstruction during sleep, the reversal of the symp-
toms related to OSA, and good adherence to the treatment. These aims are
promptly obtained in many, but not all patients. In fact, an optimal pressure for
the correction of obstructive events may be difficult to recognize in some patients,
or may fluctuate between nights. Furthermore, evaluation of therapeutic pressure
based on objective nocturnal recordings, patient’s symptoms, or compliance to
treatment may show some differences. A careful instrumental and clinical evalu-
ation should lead to the prescription of a CPAP treatment that may be the most
appropriate for each patient.

Key Major Recommendations

• Before prescribing CPAP, choose an instrumental monitoring that may be
reliable for the identification of the best pressure. For most patients, differ-
ent options are available, provided that an expert physician evaluates their
outcomes.
• Prescribe to each patient the CPAP level that may best eliminate obstruc-
tive respiratory events.
• Evaluate subjective and clinical findings after initiation of CPAP treat-
ment, whatever the procedure that has been adopted for CPAP
prescription.
• Take into consideration subjective indications given by each patient to
slightly modify the therapeutic pressure or to reconsider CPAP titration.

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Dual-Mode Noninvasive Mechanical
Ventilation: Key Technical and Practical 77
Applications

Grazia Crescimanno, Andrea Vianello, and Oreste Marrone

Contents
77.1 Introduction .................................................................................................................... 658
77.2 Principles of Operation and Setting of Dual-Control Modes of Ventilation .................. 658
77.2.1 Consequences of Leaks on Efficacy of Ventilation ............................................ 659
77.2.2 Clinical Trials on Dual-Mode Ventilators .......................................................... 661
Conclusions ............................................................................................................................. 665
References ............................................................................................................................... 665

Abbreviations

AVAPS Average volume-assured pressure support

COPD Chronic obstructive pulmonary disease
CRF Chronic respiratory failure
HI-PS High-intensity pressure support
HRQL Health-related quality of life
IBW Ideal body weight

G. Crescimanno, MD (*)
Italian National Research Council, Institute of Biomedicine and Molecular Immunology,
Palermo, Italy
Department of Pneumology, Villa Sofia – Cervello Hospital, Palermo, Italy
Via Ugo La Malfa, 153, Palermo 90146, Italy
e-mail: [email protected]
A. Vianello, MD
Respiratory Pathophysiology Division, University-City Hospital of Padova, Padua, Italy
e-mail: [email protected]
O. Marrone, MD
Italian National Research Council, Institute of Biomedicine and Molecular Immunology,
Palermo, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 657

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_77
658 G. Crescimanno et al.

iVAPS Intelligent volume-assured pressure support

NMD Neuromuscular disease
OHS Obesity hypoventilation syndrome
PEEP Positive end-expiratory pressure
PS Pressure support
PSV-VS Pressure support ventilation volume security
PSV-VTG Pressure support ventilation with guaranteed volume
PtCO2 Transcutaneous carbon dioxide pressure
VAPS Volume-assured pressure support

77.1 Introduction

The primary goal of mechanical ventilation is the maintenance of adequate gas

exchanges, which can be achieved either by volume or pressure ventilation. During
pressure ventilation, the airway pressure is fixed and the tidal volume is variable. An
increase in pulmonary resistance can lead to a drop in tidal volume and to alveolar
hypoventilation. During volume ventilation, tidal volume is fixed, whereas the airway
pressure is variable and depends on the respiratory system mechanics and patient effort.
An increase in respiratory drive, for example, due to fever, can result in insufficient
alveolar ventilation and asynchrony. In the past, volume ventilation has been extensively
used to guarantee a constant volume in acute patients with altered chest wall compliance
and airway resistance, as well as in patients with different kinds of respiratory failure
who require continuous ventilator support during sleep. However, since recent studies
have shown that pressure ventilation is more comfortable than volume ventilation [1]
and can compensate better if there are leaks [2], new ventilatory modes have been
designed and developed to offer volume stability and avoid disadvantages related to
volume ventilation. These news modes, called “dual-control modes” or “volume target
pressure ventilation,” are hybrid modes aimed at administering pressure ventilation and,
at the same time, ensuring that the target tidal volume is reached despite changes in
airway resistance or pulmonary elastance conditions [3]. In simple terms, they combine
the advantages of volume ventilation (constant tidal volume and preservation of minute
ventilation) and pressure ventilation (adaptability of flow to patient’s requirements, i.e.,
variable flow). Dual-mode ventilators were initially developed for invasive mechanical
ventilation in the intensive care environment, but their use has progressively extended to
noninvasive ventilation (NIV), both for hospital and home utilization.

77.2 Principles of Operation and Setting of Dual-Control

Modes of Ventilation

Although dual-control modes can work in different ways, they all assure stable arte-
rial CO2 levels by maintaining adequate minute ventilation when impedance of the
respiratory system increases. Dual-control “within a breath” refers to a technique
whereby the ventilator, after the setting of a minimal inspiratory pressure, switches
to volume control in the middle of a breath if the target volume cannot be reached
77 Dual-Mode NIV: Key Technical and Practical Applications 659

by the pressure ventilation mode. In this option, the flow changes from decelerated
to fixed, so as to warrant the desired tidal volume, while the inspiratory pressure
passively increases. An acronym generally used to indicate ventilators working with
this modality is PSV-VTG (pressure support ventilation with guaranteed volume).
Dual-control “breath to breath” ventilators work in a way that, if the tidal volume
decreases, the pressure progressively varies from breath to breath within a preset
pressure range until the desired target volume is reached. Acronyms generally used
for ventilators working with this modality are PSV-VS or PSV-VG (pressure sup-
port ventilation-volume security or -volume guaranteed), and AVAPS (average
volume-assured pressure support) (Fig. 77.1).
The iVAPS (intelligent volume-assured pressure support) is a dual-control mode
in which the target is not tidal volume (like PSV-VT and AVAPS) but alveolar ven-
tilation. It is an autotitrating mode of ventilation that has appeared on the market in
recent years. While taking into account a predicted anatomical dead space, it varies
respiratory rate and pressure support within preset limits to maintain a target alveo-
lar ventilation. If ventilation falls below the target, the ventilator responds to the
change quicker than the previous dual-control ventilators, increasing pressure sup-
port at a higher rate.
In dual-control ventilators, the target tidal volume must always be set. In addition,
depending on the ventilator algorithm, minimal and maximal pressure, inspiratory
flow rate, or inspiratory time may be required to set. There are no official recommen-
dations about which target tidal volume should be set, and in most centers, indica-
tions provided by manufacturers are adopted. According to these indications, in most
studies, dealing with patients with different diseases, the minimal tidal volume was
set at about 8 ml/kg of ideal weight, with a range between 7 and 12. However, no
comparative studies between settings have been performed. Both in the within-a-
breath and in the breath-to-breath modes, if the preset minimal target volume is too
low, it may lead to an increase in respiratory rate, which may cause an increase in the
work of breathing. Instead, if the set tidal volume is too high, the ventilator may raise
the pressure support and possibly cause barotrauma or hemodynamic compromise,
or lead to the appearance of intrinsic positive end-expiratory pressure (PEEP).
In the breath-to-breath mode, the pressure range is manually or automatically
set. If the maximum set pressure limit is too high it could not only cause barotrauma
but also an undesired increase in the delivered volume. On the other hand, if the
minimal preset inspiratory pressure is too low, the drop in pressure that follows
leaks may cause hypoventilation.
In the within-a-breath mode, inspiratory flow rate or time is set. If the minimal
inspiratory flow rate is set too low, lung inflation may be slow, with a late switch
from pressure to volume control and an undesired prolongation of inspiratory time.
An inspiratory time that is too long can cause expiratory asynchrony.

77.2.1 Consequences of Leaks on Efficacy of Ventilation

An important issue to address is the behavior of volume target mode in the presence
of unintentional leaks. Contal et al. [4] tested seven home ventilators on a bench
model adapted to simulate leaks. They found that tidal volume provided by the
660 G. Crescimanno et al.

A
t
1 2

V° Ti Max

t
B

t
I E I E
V ti = Vt V ti = Vt
b
Pressure

IPAP max

IPAP min

EPAP
15 30 45 60 Time

VOLUME

Target
volume

15 30 45 60 Time

Fig. 77.1 Upper panel A: dual-control “within-a-breath” mode. The figure shows that, if the target
volume cannot be reached by the pressure ventilation mode, the ventilator switches from pressure
to volume control. The flow changes from decelerated to fixed (b) and inspiratory pressure passively
increases (a). Target volume (Vt) is adjusted according to the measured inspiratory volume (Vti). Ti
max = preset maximum inspiratory time. (Reproduced with permission from ResMed). Lower panel
B: Dual-control “breath-to-breath” mode. The figure shows that if the tidal volume is not reached,
the pressure progressively increases from breath to breath within a preset pressure range until the
desired target volume is obtained (Reproduced with permission from Philips Respironics)
77 Dual-Mode NIV: Key Technical and Practical Applications 661

software in the presence of leaks was underestimated by all devices, and that, for
most devices, bias increased with higher insufflation pressures. Similarly, Lujàn
et al. [5] evaluated the reliability of the tidal volume provided by five ventilators in
a bench test with simulated leaks. They found that all the tested ventilators underes-
timated tidal volume, and that the higher the leak, the higher the difference between
the estimated and the actual tidal volume. By contrast, Sogo et al. [6], who evalu-
ated the same ventilators in similar conditions, found that inspiratory leaks were
followed by overestimates of tidal volume by most of ventilators. They also found
that, in the presence of expiratory leaks, the behaviors of each of the tested ventila-
tors were different; three ventilators underestimated and one ventilator overesti-
mated the tidal volume. Independently from these contrasting results, which may be
the result of different study designs and protocols, it is important to emphasize that,
when large leaks occur, data provided by the ventilator software may not always be
reliable. In clinical practice, where the behavior of leaks is often erratic, this may
translate into a difficult assessment of patients’ ventilation. Inclusion of algorithms
that calculate the pressure loss as a function of the flow exiting the ventilator may
increase the reliability of tidal volume estimation.
Tidal volume estimation by dual-control ventilators during air leaks may vary
with circuit configuration. Khirani et al. [7] studied the ability of seven home
dual-mode ventilators to maintain the preset minimal target volume during leaks
with different circuit configurations. They reported that all studied ventilators
with a single-limb circuit were able to maintain the minimal preset tidal volume
during leaks; only one ventilator overcompensated during prominent leaks. By
contrast, with the exception of one ventilator model, all the studied ventilators
with a single circuit and an expiratory valve, or with a double circuit, failed to
maintain the minimal tidal volume during leaks, because they misinterpreted
leaks as an increase in tidal volume and therefore decreased their inspiratory
pressure to the minimal preset level. Similar results were reported by Carlucci
et al. [8]. However, Lujan et al. [9] have shown that the introduction of a random
leak also influences the performance of commercial ventilators with a single-
limb circuit, and that inspiratory leaks decrease the delivered tidal volume, with
an important clinical impact in terms of hypoventilation. Thus, an effective esti-
mation of ventilation during leaks may depend on the circuit and the configura-
tion of the ventilator and may vary with the ventilator model. The loss of accuracy
in estimated tidal volume may also cause patient-ventilator asynchrony, although
this point has not been specifically addressed in most of the previously cited
studies.

77.2.2 Clinical Trials on Dual-Mode Ventilators (Table 77.1)

77.2.2.1 Clinical Trials on the PSV-VTG Ventilation Mode

A precursor of modern dual-mode ventilators was described by Amato et al. [10] in
1992. These authors published the results of a clinical trial, performed in intubated
patients with acute respiratory failure, which compared a dual mode of ventilation,
Table 77.1 Major trials on Dual-mode NIV available in the literature
662

Authors Ventilator Setting Patients Duration Outcomes with target mode

Storre et al. (2006) Synchrony Fixed PS vs AVAPS 10 stable 6 weeks Improved nocturnal gas exchange; no variation in
Cross-over 7–10 ml/kg IBW OHS sleep quality and HRQL
Pressure max 30 cmH2O
Janssen et al. (2009) Synchrony Fixed PS vs AVAPS 12 stable 2 nights Improved nocturnal gas exchange; decreased
Cross-over 8–10 ml/kg AB OHS comfort, subjective and objective sleep quality
Pressure max 30 cmH2O
Crisafulli et al. Synchrony Fixed PS vs AVAPS 9 stable 2 weeks No variation in diurnal gas exchange and comfort
(2009) Cross-over 8 ml/kg IBW COPD Better subjective sleep efficiency
Pressure max 30 cmH2O
Jaye et al. (2009) AutoVPAP Fixed PS vs iVAPS 20 stable 2 months No differences in nocturnal gas exchange and sleep
Cross-over Autotitrating NMD quality
Pressure max 21 cmH2O
Ambrogio et al. Synchrony Fixed PS versus AVAPS 28 2 nights No differences in nocturnal gas exchange and sleep
(2009) Cross-over 8 ml/kg IBW stable quality; greater minute ventilation
or 110 % of baseline VT CRF
Pressure max 30 cmH2O
Crescimanno et al. Idea Ultra Fixed PS versus PSV-VG 28 stable 2 nights No differences in nocturnal gas exchange, comfort
(2011) Cross-over 8–10 ml/kg IBW NMD and subjective sleep quality; more asynchrony
Pressure max 20 cmH2O
Murphy et al. (2012) Synchrony Fixed PS versus AVAPS 46 stable 3 months No differences in daytime gas exchanges
Parallel group 8–10 ml/kg IBW Super OHS
Pressure max 22 cmH2O
Briones Claudett Synchrony Fixed PS vs AVAPS 22 acute 1–2–3– More rapid improvement of diurnal gas exchange
et al. (2013) Parallel group 8–12 ml/kg IBW and after COPD 12–24 h and recovery of consciousness (GCS)
stability 6–8 ml/kg
Pressure max 26 cmH2O
G. Crescimanno et al.
 77

Ekkernkamp et al. STELLAR Fixed HI-PS vs iVAPS 14 COPD 2 nights No differences in nocturnal gas exchanges and
(2014) Cross-over Autotitrating 6 weeks sleep quality in short term, greater decrease in
Pressure max 25 cmH2O PtCO2 and better subjective sleep quality long term
with iVAPS
Kelly et al. (2014) STELLAR Fixed PS vs iVAPS 18 mixed 1 month No differences in nocturnal gas exchanges and
Cross-over Autotitrating CRF sleep quality. Better compliance in naïve patients
Pressure max 18 cmH2O
Oscroft et al. (2014) STELLAR Fixed PS vs iVAPS 34 stable 3 months No differences in daytime and nocturnal gas
Parallel group Autotitrating COPD exchanges or compliance
Pressure max 25 cmH2O
Storre et al. (2014) VIVO 40–50 Fixed HI-PS vs PS-VT 10 COPD 3 months No differences in nocturnal gas exchange,
Cross-over 8 ml/kg IBW/110 % Vt tolerance, sleep quality
pressure max 35 cmH2O
PS pressure support, AVAPS average volume-assured pressure support, OHS obesity hypoventilation syndrome, HRQL health-related quality of life, COPD
chronic obstructive pulmonary disease, iVAPS intelligent volume pressure support, NMD neuromuscular disease, IBW ideal body weight, HI-PS high intensity
pressure support, PtCO2 transcutaneous carbon dioxide pressure, CRF chronic respiratory failure
Dual-Mode NIV: Key Technical and Practical Applications
663
664 G. Crescimanno et al.

called volume-assured pressure support (VAPS), and operating with within-a-

breath, volume ventilation. The authors concluded that this new mode of ventilation
was beneficial in terms of improvement in blood gases, workload, and synchrony.
Only one study compared PSV-VTG ventilation with conventional noninvasive
pressure support ventilation (PSV), which is the most widely used ventilation
modality [11]. In this study, the possible role of PSV-VTG in patients affected by
neuromuscular disease was evaluated in a cross-over, short-term, randomized study.
The results showed that PSV-VTG did not offer any advantage in comparison with
pressure support, and that it could predispose to patient-ventilator asynchronies.

77.2.2.2 Clinical Trials on AVAPS

AVAPS has been more extensively studied than the within-a-breath mode, both in
acute and stable patients. Several clinical trials have been published that compared
AVAPS with PSV. Most studies were done on patients ventilated during sleep.
In 2006, Storre et al. [12] performed a long-term study (6 weeks) on clinically
stable patients affected by obesity-hypoventilation syndrome (OHS). They found a
significantly lower nocturnal transcutaneous CO2 during AVAPS than during PSV
without differences in sleep quality and comfort. In 2008, Janssen et al. [13] per-
formed a similar study on 12 patients affected by OHS using the AVAPS mode, and
similarly concluded that it controlled nocturnal hypoventilation better than PSV, but
at the expense of a slight worsening in objective and subjective sleep quality and in
comfort of ventilation. In the following year, Crisafulli et al. [14] reported similar
effects on arterial blood gases and no difference in comfort with NIV between
AVAPS and PSV in 9 patients with chronic obstructive pulmonary disease (COPD).
Ambrogio et al. [15] explored the role of AVAPS in patients affected by obstructive
or restrictive chronic respiratory failure and, unlike Janssen, did not observe any
improvement in sleep quality with AVAPS with respect to fixed PSV. However, they
found that minute ventilation was higher during AVAPS than during PSV. Another
study on OHS was performed in super-obese patients by Murphy et al. in 2012 [16].
In that study, no difference between effects of AVAPS and fixed-level PSV on day-
time gas exchanges was found after three months of follow-up. Briones Claudett
et al. [17] have carried out a prospective interventional controlled study in 22
patients with COPD exacerbation and hypercapnic encephalopathy. Interestingly,
they observed a more rapid recovery of patients treated with AVAPS than with PSV,
although they were not able to demonstrate differences in terms of length of hospital
stay or days on NIV. Finally, Storre et al. [18] compared AVAPS with high-intensity
PSV in 10 COPD patients. They did not find differences in tolerance, sleep quality,
health-related quality of life, exercise capacity, and lung function.

77.2.2.3 Clinical Trials on IVAPS

Four studies have been published about clinical effects of iVAPS. The first clinical
trial was performed by Jaye et al. [19] in 2009 in 20 patients with neuromuscular
diseases. The authors reported that iVAPS and standard bi-level ventilation pro-
duced comparable control of nocturnal blood gases in these patients. These results
were confirmed by a second study performed in 2014 by the same group in patients
77 Dual-Mode NIV: Key Technical and Practical Applications 665

naïve to NIV [20]. Ekkernkamp et al. [21] compared the impact of iVAPS and of
PSV in patients with COPD at different times after their initiation. They found no
differences in the short term, but some advantages in gas exchange and subjective
sleep quality after 6 weeks. By contrast, Oscroft et al. [22], in a long-term study in
patients with COPD found similar physiological outcomes under iVAPS or bi-level
ventilation.

Conclusions
In recent years, hybrid modes have been developed to overcome some drawbacks
of volume and pressure ventilation. The advantages of dual-mode ventilators
have not yet been definitely established. Some studies have examined only tech-
nical aspects of dual ventilation and not clinical observations on patients. Among
clinical studies, overall, 4 of 12 reported a more rapid improvement in gas
exchange using dual-mode ventilators than traditional pressure ventilators.
However, results reported so far are inconsistent, possibly due to the different
algorithms and circuit configurations of the ventilators used for comparisons
with dual-control ventilators. Additionally, in most trials, the recruited patients
were already accustomed to some mode of NIV before using a dual-volume tar-
geting mode. Little information is available on the effects of dual-mode ventila-
tors on sleep quality and patient ventilator-interaction.
In the future, it will be necessary to standardize the nomenclature for dual
modes of NIV. Besides, further clinical studies are needed. In fact, while ventilator
manufacturers need to demonstrate engineering success in a lung model to obtain
marketing approval both in the United States and in Europe, individual patients’
responses to alternative modes of ventilation may greatly differ in clinical practice.
This should be born in mind when new modes of ventilation are tested.

Key Major Recommendations

• Take into consideration how the ventilator algorithm works to assure target
volume.
• Prefer a single-limb circuit configuration.
• Consider dual modes if you need to use high pressures either in the acute
or long-term setting.
• Consider dual modes if long-term patient adherence to treatment is
expected to be inadequate.
• Monitor the patient’s unintentional leaks and do not use dual modes if they
cannot be governed.

References
1. Betensley AD, Khalid I, Crawford J, et al. Patient comfort during pressure support and volume
controlled-continuous mandatory ventilation. Respir Care. 2008;53:897–902.
666 G. Crescimanno et al.

2. Mehta S, McCool FD, Hill NS. Leak compensation in positive pressure ventilators: a lung
model study. Eur Respir J. 2001;17:259–67.
3. Branson RD, Davis Jr K. Dual control modes: combining volume and pressure breaths. Respir
Care Clin N Am. 2001;7:397–408.
4. Contal O, Vignaux L, Combescure C, et al. Monitoring of noninvasive ventilation by built-in
software of home bilevel ventilators: a bench study. Chest. 2012;141:469–76.
5. Luján M, Sogo A, Pomares X, et al. Effect of leak and breathing pattern on the accuracy of
tidal volume estimation by commercial home ventilators: a bench study. Respir Care. 2013;
58:770–7.
6. Sogo A, Montanyà J, Monsó E, et al. Effect of dynamic random leaks on the monitoring accu-
racy of home mechanical ventilators: a bench study. BMC Pulm Med. 2013;13:75.
7. Khirani S, Louis B, Leroux K, et al. Harms of unintentional leaks during volume targeted pres-
sure support ventilation. Respir Med. 2013;107:1021–9.
8. Carlucci A, Schreiber A, Mattei A, et al. The configuration of bi-level ventilator circuits may
affect compensation for non-intentional leaks during volume-targeted ventilation. Intensive
Care Med. 2013;39:59–65.
9. Luján M, Sogo A, Grimau C, et al. Influence of dynamic leaks in volume-targeted pressure
support non invasive ventilation: a bench study. Respir Care. 2015;60:191–200.
10. Amato MB, Barbas CS, Bonassa J, et al. Volume-assured pressure support ventilation
(VAPSV). A new approach for reducing muscle workload during acute respiratory failure.
Chest. 1992;102:1225–34.
11. Crescimanno G, Marrone O, Vianello A. Efficacy and comfort of volume-guaranteed pressure
support in patients with chronic ventilatory failure of neuromuscular origin. Respirology.
2011;16:672–9.
12. Storre JH, Seuthe B, Fiechter R, et al. Average volume-assured pressure support in obesity
hypoventilation: a randomized crossover trial. Chest. 2006;130:815–21.
13. Janssens JP, Metzger M, Sforza E. Impact of volume targeting on efficacy of bi-level non-
invasive ventilation and sleep in obesity-hypoventilation. Respir Med. 2009;103:165–72.
14. Crisafulli E, Manni G, Kidonias M, et al. Subjective sleep quality during average volume
assured pressure support (AVAPS) ventilation in patients with hyperapnic COPD: a physical
pilot study. Lung. 2009;187:299–305.
15. Ambrogio C, Lowman X, Kuo M, et al. Sleep and non-invasive ventilation in patients with
chronic respiratory insufficiency. Intensive Care Med. 2009;35:306–13.
16. Murphy PB, Davidson C, Hind MD, et al. Volume targeted versus pressure support non-
invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised
controlled trial. Thorax. 2012;67:727–34.
17. Briones Claudett KH, Briones Claudett M, Sang Wong MC, et al. Noninvasive mechanical
ventilation with average volume assured pressure support (AVAPS) in patients with chronic
obstructive pulmonary disease and hypercapnic encephalopathy. BMC Pulm Med. 2013;13:12.
18. Storre JH, Matrosovich E, Ekkernkamp E, et al. Home mechanical ventilation for COPD:
high-intensity versus target volume noninvasive ventilation. Respir Care. 2014;59:1389–97.
19. Jaye J, Chatwin M, Dayer M, et al. Autotitrating versus standard noninvasive ventilation:
a randomised crossover trial. Eur Respir J. 2009;33:566–71.
20. Kelly JL, Jaye J, Pickersgill RE, et al. Randomized trial of ‘intelligent’ autotitrating ventilation
versus standard pressure support non-invasive ventilation: impact on adherence and physiolog-
ical outcomes. Respirology. 2014;19:596–603.
21. Ekkernkamp E, Storre JH, Windisch W, et al. Impact of intelligent volume-assured pressure
support on sleep quality in stable hypercapnic chronic obstructive pulmonary disease patients:
a randomized, crossover study. Respiration. 2014;88:270–6.
22. Oscroft NS, Chadwick R, Davies MG, Quinnell TG, Smith IE. Volume assured versus pressure
preset non-invasive ventilation for compensated ventilatory failure in COPD. Respir Med.
2014;108:1508–15.
Results of Servo-ventilation and Other
Ventilatory Modes in Sleep Apnea 78
Syndrome: Key Topics and Practical
Implications

Dominic Dellweg, Markus Wenzel, and Jens Kerl

Contents
78.1 Introduction ................................................................................................................. 667
78.2 Ventilator Modes for Sleep Syndromes with Altered Respiratory Drive.................... 668
Conclusion ............................................................................................................................. 671
References .............................................................................................................................. 671

78.1 Introduction

Sleep apnea is comprised of different breathing abnormalities that occur during

sleep. These syndromes can mainly be divided into disorders with airflow obstruc-
tion and into disorders with altered respiratory drive, as well as the combination of
both [1]. For patients with obstructive sleep apnea, continuous positive airway pres-
sure (CPAP), which was first introduced in 1981, is the usual form of treatment [2].
CPAP can be applied in form of a fix pressure or in an automatic mode in which the
CPAP machine titrates treatment pressure to measured indices of airflow obstruc-
tion [3]. Pressure therapies applying different pressure levels during inspiration and
expiration might be used in case of pressure intolerance and allow for lower pres-
sures during expiration without compromising airway patency [4].
Breathing disorders with altered respiratory drive in adults have to be separated
according to their etiology:

1. Primary central sleep apnea

2. Central apnea with Cheyne-Stokes respiration
3. Central sleep apnea of high altitude

D. Dellweg, PhD (*) • M. Wenzel, MD • J. Kerl, MSc

Department for Respiratory Medicine, Critical Care and Sleep Medicine,
Kloster Grafschaft, Annostr. 1, Schmallenberg 57392, Germany
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 667

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_78
668 D. Dellweg et al.

4. Central sleep apnea related to other (e.g., neurologic) diseases

5. Central sleep apnea syndrome provoked by medication, drugs, and substances
6. Pressure therapy-induced central apnea (complex sleep apnea)

These entities are the domain of more sophisticated ventilation modes, which
will be reviewed in this chapter.

78.2 Ventilator Modes for Sleep Syndromes with Altered

Respiratory Drive

During centrally mediated apneas, there is no isometric contraction of the respira-

tory muscles, resulting in cessation of respiratory flow. CPAP given in this instance
will not generate a breath in the absence of an inspiratory effort. CPAP might
improve central apneas in heart failure patients by other mechanisms, such as pre-
load reduction, but it does not have an impact on mortality in these patients [5]. For
this reason, central apnea syndromes have become the domain of ventilator modes
with different pressures during inspiration and expiration, usually known as bi-level
or BIPAP (bi-level positive airway pressure) therapy, or more sophisticated modes
that change pressure levels in view of the patient’s breathing effort. In general, ces-
sation of respiratory drive occurs when carbon dioxide is lowered below the apneic
threshold [6], measured in the carotid body chemoreceptors [7]. Chronic hyperven-
tilation with a reduction of the CO2 baseline appears to play an important role here
because baseline CO2 will be closer to the apneic threshold [8–10]. For this reason,
elevation of CO2 by means of increased inspiratory CO2 fraction of the addition of
dead space to ventilation can ameliorate central apneas [11].
During an apnea, CO2 rises until breathing stimulus reappears. The stability of
this feedback system of breathing control depends on the magnitude of the loop
gain. Loop gain is the mathematical ratio of breathing response to the magnitude of
the perturbation [12]. If the response is too high, reflected by a ration greater than 1,
a steady correction will not be achieved [12]. In this instance, it is of importance that
any type of pressure therapy should be targeted to lower the loop gain ratio.
Figures 78.1, 78.2, and 78.3 illustrate modes of functioning of bi-level-S, bi-level-
ST, and servo-ventilation in patients with central apneas. It is obvious that S-mode
ventilation will augment the emergence of central apneas because ventilation sup-
ports spontaneous breath but fails to give support during central apneas. S-mode
ventilation will therefore increase the loop gain ratio (Fig. 78.1). ST-mode ventila-
tion does not really impact loop gain ratio because ventilator support is given during
the patient’s efforts as well as during times of apneas (Fig. 78.2). Servo-ventilation,
in contrast, decreases the loop gain ratio because ventilator support compensates for
the patient’s respiratory pattern because pressure support is given in disproportion
to spontaneous breaths (Fig. 78.3).
On the basis of this pathophysiological background, it is not surprising that the
usual bi-level noninvasive positive-pressure ventilation (NPPV) might even worsen
breathing patterns dominated by central apneas [13]. Proportional-assist ventilation,
on the other hand, which applies pressure in proportion to the patient’s effort,
78 Results of Servo-ventilation and Other Ventilatory Modes in Sleep Apnea 669

Pat. effort

Pat. effort

Bilevel S-mode

Fig. 78.1 Functioning of a bi-level ventilator in the spontaneous mode (S-mode). Notice that
patient ventilation is augmented while no support is given during phases of apnea

Fig. 78.2 Functioning of a bi-level ventilator in the spontaneous-timed mode (ST-mode). Notice
that ventilator support is given during breathing efforts as well as during apneas

Pat. effort

Pat. effort

Servoventilation

Fig. 78.3 Functioning of a servo-ventilator. Notice that ventilator support is given disproportion-
ately to breathing efforts

promotes periodic breathing [14]. If ventilation is given in disproportion to patient

effort, it is likely to improve central apneic breathing patterns. Servo-ventilation has
such a disproportional approach, and several studies have shown the superiority of
different servo-ventilators in this instance [15–17].
670 D. Dellweg et al.

Servoventilation Servoventilation
60 group 30 group
Apnea - hypopnea - index / h

NPPV group NPPV group

50

Apnea - index / h
40 20
p=0.001
30 p=0.027

20 10

10

0 0
No treatment After six NPPV / After six No treatment After six NPPV / After six
weeks of servo- weeks of weeks of servo- weeks of
CPAP ventilation NPPV /servo- CPAP ventilation NPPV /servo-
treatment titration ventilation treatment titration ventilation
treatment treatment
Servoventilation Servoventilation
25 group 60 group
NPPV group NPPV group
Central - apnea - index / h

Desaturation - index / h
50
20
40
p<0.0001
15
30 p<0.0001

10
20

5 10

0 0
No treatment After six NPPV / After six No treatment After six NPPV / After six
weeks of servo- weeks of weeks of servo- weeks of
CPAP ventilation NPPV /servo- CPAP ventilation NPPV /servo-
treatment titration ventilation treatment titration ventilation
treatment treatment

Fig. 78.4 Servo-ventilation compared with bi-level ventilation (IPPV group) in patients with
complex sleep apnea. Note that only servo-ventilation compensates central events after 6 weeks
follow-up [18]

Our research group showed that the effect of ventilation on the human breathing
pattern can change over time [18]. In this randomized controlled trial in patients with
persistent CPAP-induced central apneas, known as complex sleep apnea, bi-level ven-
tilation improved central breathing pattern in the short term, but resulted in reemer-
gence of central apneas after 6 weeks. Servo-ventilation, on the other hand, compensated
apneas permanently (Fig. 78.4). It is therefore recommended to choose the type of
noninvasive pressure support wisely and reevaluate treatment effect over time.
In terms of outcome, servo-ventilation has been shown to effectively reduce the
apnea-hypopnea index [15–19] and improve sleep quality [17], quality of life [20],
and left ventricular ejection fraction in chronic heart failure patients [20, 21 ].
A recent multicenter trial however showed, that servo-ventilation might
increase mortality in patients with an ejection fraction below 45 % [22].
Newer-generation servo-ventilators share the capability to regulate expiratory
pressure according to the grade of upper airway obstruction using techniques that
are also used in automatic CPAP devices (APAP).
It is important to know that function differs between servo-ventilators. Due to
patent law, different companies have developed different algorithms. The main goal
of servo-ventilators is to keep ventilation constant. Whereas some devices measure
the actual flow and are programmed to keep flow constant, others detect relative
minute ventilation in shifting timeframes. Algorithms providing automatic back-up
78 Results of Servo-ventilation and Other Ventilatory Modes in Sleep Apnea 671

rates as well as autotitration of expiratory pressure are also different between servo-
ventilators. For this reason, these devices are not arbitrarily interchangeable but
must be titrated individually to each patient [23, 24].
More sophisticated feedback control systems have been introduced for the
treatment of central and mixed sleep apnea, but they appear to have a low toler-
ance [25]. Studies comparing this approach to conventional servo-ventilation are
missing to date.

Conclusion
For obstructive sleep apnea, conventional CPAP therapy remains the gold stan-
dard. Central apneas, however, require a more targeted approach. Central apneas
are usually caused by variations in CO2 regulation. To achieve CO2 homeostasis,
ventilation must compensate for apneas without augmentation of uncompromised
breathing efforts. Servo-ventilators deliver pressure disproportional to the patient’s
own breathing effort and stabilize the human CO2 feedback-control system.

References
1. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med.
1976;27:465–84.
2. Sullivan CE, Issa FG, Berthon-Jones M, et al. Reversal of obstructive sleep apnoea by continu-
ous positive airway pressure applied through the nares. Lancet. 1981;1:862–5.
3. Randerath W, Parys K, Lehmann D, et al. Self-adjusting continuous positive airway pressure
therapy based on the measurement of impedance. A comparison of free pressure variation and
individually fixed higher minimum pressure. Respiration. 2000;67:272–9.
4. Wenzel M, Kerl J, Dellweg D. Expiratory pressure reduction (C-Flex Method) versus fix CPAP
in the therapy for obstructive sleep apnoea. Pneumologie. 2007;61:692–5.
5. Bradley TD, Logan AG, Kimoff RJ, et al. Continuous positive airway pressure for central sleep
apnea and heart failure. N Engl J Med. 2005;353:2025–33.
6. Dempsey JA. Crossing the apnoeic threshold: causes and consequences. Exp Physiol.
2005;90:13–24.
7. Nakayama H, Smith CA, Rodman JR, et al. Carotid body denervation eliminates apnea in
response to transient hypocapnia. J Appl Physiol. 2003;94:155–64.
8. Xie A, Rutherford R, Rankin F, et al. Hypocapnia and increased ventilatory responsiveness in
patients with idiopathic central sleep apnea. Am J Respir Crit Care Med. 1995;152:1950–5.
9. Xie A, Skatrud JB, Puleo DS, et al. Apnea-hypopnea threshold for CO2 in patients with con-
gestive heart failure. Am J Respir Crit Care Med. 2002;165:1245–50.
10. Hanly P, Zuberi N, Gray R. Pathogenesis of Cheyne-Stokes respiration in patients with conges-
tive heart failure. Relationship to arterial PCO2. Chest. 1993;104:1079–84.
11. Thomas RJ. Alternative approaches to treatment of central sleep apnea. Sleep Med Clin.
2014;9:87–104.
12. White DP. Pathogenesis of obstructive and central sleep apnea. Am J Respir Crit Care Med.
2005;172:1363–70.
13. Johnson KG, Johnson DC. Bilevel positive airway pressure worsens central apneas during
sleep. Chest. 2005;128:2141–50.
14. Younes M, Ostrowski M, Thompson W, et al. Chemical control stability in patients with
obstructive sleep apnea. Am J Respir Crit Care Med. 2001;163:1181–90.
15. Allam JS, Olson EJ, Gay PC, et al. Efficacy of adaptive servoventilation in treatment of
complex and central sleep apnea syndromes. Chest. 2007;132:1839–46.
672 D. Dellweg et al.

16. Arzt M, Wensel R, Montalvan S, et al. Effects of dynamic bilevel positive airway pressure
support on central sleep apnea in men with heart failure. Chest. 2008;134:61–6.
17. Teschler H, Dohring J, Wang YM, et al. Adaptive pressure support servo-ventilation: a novel
treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;
164:614–9.
18. Dellweg D, Kerl J, Hoehn E, et al. Randomized controlled trial of noninvasive positive pres-
sure ventilation (NPPV) versus servoventilation in patients with CPAP-induced central sleep
apnea (complex sleep apnea). Sleep. 2013;36:1163–71.
19. Morgenthaler TI, Gay PC, Gordon N, et al. Adaptive servoventilation versus noninvasive posi-
tive pressure ventilation for central, mixed, and complex sleep apnea syndromes. Sleep.
2007;30:468–75.
20. Philippe C, Stoica-Herman M, Drouot X, et al. Compliance with and effectiveness of adaptive
servoventilation versus continuous positive airway pressure in the treatment of Cheyne-Stokes
respiration in heart failure over a six month period. Heart. 2006;92:337–42.
21. Oldenburg O, Schmidt A, Lamp B, et al. Adaptive servoventilation improves cardiac function
in patients with chronic heart failure and Cheyne-Stokes respiration. Eur J Heart Fail. 2008;
10:581–6.
22. Cowie MR, Woehrle H, Wegscheider K, et al. Rationale and design of the SERVE-HF study:
treatment of sleep-disordered breathing with predominant central sleep apnoea with adaptive
servo-ventilation in patients with chronic heart failure. Eur J Heart Fail. 2013;15:937–43.
23. Javaheri S, Brown LK, Randerath WJ. Clinical applications of adaptive servoventilation
devices: part 2. Chest. 2014;146:858–68.
24. Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive
servoventilation: part 1: operational algorithms. Chest. 2014;146:514–23.
25. Oldenburg O, Bitter T, Wellmann B, et al. Trilevel adaptive servoventilation for the treatment
of central and mixed sleep apnea in chronic heart failure patients. Sleep Med. 2013;14:
422–7.
Contribution of Back-Up Respiratory
Rate Setting in Noninvasive Ventilation 79
Jean-Paul Janssens, Dan Adler, Patrick Pasquina,
and Olivier Contal

Contents
79.1 Introduction ................................................................................................................. 674
79.2 Bi-Level Pressure Cycled Ventilation: S (Spontaneous)
or S/T (Spontaneous/Timed) Mode? ........................................................................... 675
79.3 High or Low BURR in COPD .................................................................................... 677
79.4 Respiratory Rate and Data Provided by Ventilator Software...................................... 678
79.5 Items to Be Explored .................................................................................................. 678
Conclusion ............................................................................................................................. 678
References .............................................................................................................................. 679

Abbreviations

ABG Arterial blood gases

ACV Assist-control ventilation
BURR Back-up respiratory rate
CHRF Chronic hypercapnic respiratory failure
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure

J.-P. Janssens, MD (*) • D. Adler, MD • P. Pasquina

Division of Pulmonary Diseases, Geneva University Hospitals,
4-6 rue Gabrielle-Perret-Gentil, Geneva 14 1211, Switzerland
e-mail: [email protected]; [email protected]; [email protected]
O. Contal, PhD
University of Health Sciences, Lausanne, Switzerland
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 673

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_79
674 J.-P. Janssens et al.

EPAP Expiratory positive airway pressure

HMV Home mechanical ventilation
LTOT Long-term oxygen therapy
NIV Noninvasive ventilation
NPPV Noninvasive positive pressure ventilation
PaCO2 Arterial partial pressure of carbon dioxide
PCRIT Pharyngeal critical pressure
PEEPi Intrinsic positive end-expiratory pressure
PS Pressure support
PSG Polysomnography
PtcCO2 Transcutaneous partial pressure of carbon dioxide
PTPes Pressure time product based on esophageal pressure
RR Respiratory rate
S Spontaneous mode
S/T Spontaneous/timed mode

79.1 Introduction

Although crucial in clinical practice, few publications report details of ventilator

settings for long-term home mechanical ventilation (HMV), and clinical practices
may vary considerably from one center to another. Recommendations for ventilator
settings for HMV have been summarized by a task force of the American Association
for Sleep Medicine (AASM) [1]. However, these guidelines suggest a polysomnog-
raphy (PSG)-based titration of NIV (which is difficult to implement in many coun-
tries) and reflect the experience of sleep laboratories dealing mostly electively with
sleep-disordered breathing and obesity hypoventilation. This chapter comments on
the use of a back-up respiratory rate (BURR) mostly in pressure-cycled home ven-
tilation, based on the available published studies.
Noninvasive (or invasive) ventilation for HMV can be provided using vol-
ume- or pressure-cycled ventilators. Volume-cycled devices are usually used
either in controlled (respiratory rate is determined by the ventilator irrespective
of the patient’s efforts) or assist-control modes (respiratory rate is determined by
the ventilator but the patient may receive either controlled or assisted breaths).
Usually, BURR is set either just below the spontaneous respiratory rate (RR) or
slightly higher than spontaneous RR [2, 3]. Indeed, BURR frequencies used with
volume-cycled devices are on average slightly higher than those set on pressure-
cycled bi-level devices [2, 3]. A controlled mode, or a high BURR in an assist-
control mode, is frequently used in patients with neuromuscular disorders whose
inspiratory muscles are too weak to trigger the ventilator: a high BURR allows the
patient to be passively and comfortably ventilated. High BURR may also allow
the ventilator to “capture” the patients’ respiratory mode and correct abnormal
respiratory patterns (i.e., high respiratory rate/low tidal volume or episodes of
nocturnal tachypnea).
79 Contribution of Back-Up Respiratory Rate Setting in Noninvasive Ventilation 675

79.2 Bi-Level Pressure Cycled Ventilation: S (Spontaneous)

or S/T (Spontaneous/Timed) Mode?

Use of a BURR in certain groups of patients is a subject of controversy. It is gener-

ally accepted that, in patients at risk to develop nocturnal alveolar hypoventilation
and/or central apnea, the use of a BURR is recommended, or even mandatory [1].
Such is the case for most neuromuscular disorders. For the same reason, several
centers prefer volume-cycled to pressure-cycled devices in these indications, irre-
spective of whether ventilation is invasive (tracheotomy) or not: volume-cycled
devices guarantee a tidal volume and minute ventilation set by the clinician (although
leaks may compromise their efficacy); furthermore, until recently, these devices had
alarms that were not present on many pressure-cycled home ventilators. These
devices do not usually provide an “S” (spontaneous) mode option.
When central hypoventilation and/or central apnea can be reasonably excluded,
AASM guidelines recommend the “S” mode as a default setting for HMV [1]. There
is very little support for this option in published data. In an early study, Restrick et al.
[4] found no difference in terms of nocturnal SpO2 and daytime arterial blood gas
(ABG) levels between pressure support ventilation and assist-control ventilation
with a BURR in a heterogeneous group of 12 patients under noninvasive ventilation
(NIV) for chronic hypercapnic respiratory failure (CHRF). No sleep studies were
performed, however, and the results of ACV on correction of PaCO2 were subopti-
mal. Casanova et al. [5] performed a 1-year randomized controlled trial comparing
long-term oxygen therapy (LTOT) with LTOT plus NIV in 52 patients with chronic
obstructive pulmonary disease (COPD). NIV was provided using a bi-level pressure
support (PS) ventilator set in a spontaneous (“S”) mode. No sleep studies were per-
formed. Five patients interrupted the study in the NIV group because of intolerance
to NIV (the reason reported by the authors was “too high pressures,” although aver-
age inspiratory positive airway pressure was 12 ± 2 cmH2O). After 1 year, none of the
physiological or clinical outcomes had improved significantly in the NIV plus LTOT
group versus the control subjects. In a 3-month randomized controlled trial of 36
patients with obesity hypoventilation, Piper et al. [6] compared CPAP with bi-level
PS in an “S” mode, after exclusion of patients with severe nocturnal CO2 retention or
residual hypoxemia after CPAP titration. There was no report of sleep-disordered
breathing induced by bi-level ventilation, and tolerance and clinical impact of both
modes were similar. Total sleep time, sleep efficiency, respiratory disturbance index
during rapid-eye-movement (REM) and non-REM sleep, and Epworth Sleepiness
Scale did not differ significantly between CPAP and bi-level ventilation.
In post hoc analysis from a randomized controlled study of volume-targeted PS
versus fixed PS for obesity hypoventilation (n = 46 patients completed the trail),
Murphy et al. [7] found that patients who had a higher proportion of pressure-
controlled breaths delivered by the ventilator (>50 %) had significantly higher
improvements in nocturnal oximetry and capnometry measures. A study by Contal
et al. [8] aimed to compare the impact of no BURR (“S” mode) versus either low
BURR or high BURR in 10 stable patients with obesity hypoventilation syndrome
(OHS), on long term HMV, and all using the same device. All subjects underwent
676 J.-P. Janssens et al.

Flow

Pressure

Thoracic
movement

Abdominal
movement

96
96

96
96
96
95
95
95
95

95

95

95
95
95
95
94
94
94

94
94
94

94
94

94

94
94

94

94
93

93
93
93

93

93
93

93
92
92
92

92

92

92

92

92
92

92
92
92

92
Saturation
91

91

91
91

91

91
91
91

91
91
90

90
90
90
90

90
90

90
90

90
90
90
89
89
89
89

89
89

89

89
88
88
88
88
88

88
88
88

52
51
50

50

50

50
49
49

49

49

49
49

49

49
49
48

48

48

48
48

48
48
48

48

48

48

48
Cardiac
47
47
47
47

47

47

47
47

47
47

47
47
46

46
46

46
46

46
46
46

46

46
46

46

46
46
46
46
46
frequency
45
45
45
45
45

45
45
45
45
45
45

45
45

45
45
45
45

45
45
45
45
45
45

45
45
45
45
45
45

45
44

0.011 0.001
a 0.009 n.s. b 0.001 n.s.

80 25

70
20
60

50 15

40
10
30

20
5
10

0 0
No Low High No Low High
BURR BURR BURR BURR BURR BURR

Fig. 79.1 (a) Occurrence of central apnea in patients under NIV for stable OHS: impact of
absence of BURR. From top to bottom: flow, pressure, thoracic, and abdominal movements; SpO2
and pulse rate. (b) Changes in central apnea-hypopnea index and mixed apnea-hypopnea index
according to absence of BURR, low BURR, or high BURR in patients under NIV for stable OHS
(Adapted from Ref. [8])

three consecutive sleep studies with either no BURR, low BURR, or high BURR, in
random order, and without any other change in ventilator settings. Absence of
BURR was associated with a marked increase in both central and obstructive events,
suggesting that at least a low BURR was necessary to prevent central events induced
by positive pressure ventilation (Fig. 79.1). Increase in obstructive events without
any BURR may have been related to too low expiratory positive airway pressure
(EPAP) values. However, interestingly, both low and high BURR stabilized the
upper airways and decreased simultaneously central, mixed, and obstructive events.
79 Contribution of Back-Up Respiratory Rate Setting in Noninvasive Ventilation 677

Correction of obstructive events with high BURR might be related to airway pres-
sure being always above PCRIT (pharyngeal critical pressure, which reflects upper
airway collapsibility). Quality of sleep was subjectively lower with a high BURR,
although excellent tolerance to a high BURR has been reported.
In normal subjects, Parreira et al. [9] compared the quality of sleep under bi-level
NPPV, using either an “S” mode or a BURR of 17 or 25/min; under NPPV with an
“S” mode, periodic breathing and central apneas were common, sometimes with
large drops in SpO2.

79.3 High or Low BURR in COPD

Fauroux et al. [10] performed a physiological study in 10 patients with cystic fibro-
sis (age 15.0 ± 4.4 years), comparing work of breathing (WOB) with volume- and
pressure-cycled ventilators at different frequencies of BURR. The authors showed
that increasing BURR decreased WOB estimated by pressure time product based on
esophageal pressure (PTPes)/min, and that PTPes/min was lowest at the highest
BURR tolerated.
Adjusting BURR may also be critical in COPD. In acute respiratory failure, the
respiratory drive of patients with COPD is high, and use of a BURR is probably
unnecessary (Nicholas Hart, personal communication). However, in CHRF related to
COPD, Dreher et al. [11] have suggested that “high intensity” ventilation (combining
high pressure support and high BURR) may be more efficient for correction of ABG,
improving dyspnea, and daytime Pulmonary Function Tests (PFT) than “low-inten-
sity” ventilation (lower pressure support and BURR). This concept has been chal-
lenged by Murphy et al. [12] in a randomized 12-week cross-over trial, comparing
“high-intensity” ventilation (i.e., high pressure and high BURR, set at 16 ± 2/min)
with “high pressure” with a low BURR (set at 6/min). The authors found no differ-
ence in any of the physiological endpoints tested (mean nocturnal usage, ABG, objec-
tive and subjective sleep quality, and health-related quality of life (HRQL), albeit for
the respiratory domain of the Severe Respiratory Insufficiency (SRI) Questionnaire).
Noteworthy is the high rate of drop-outs in this study because of intolerance to NIV.
Thus, although “high-intensity” ventilation appears to have a favorable impact
on major physiological and subjective endpoints, the contribution of the “high
BURR” component may be of minor importance. BURR settings may, in fact, have
different impacts according to patient phenotype, Intrinsic positive end-expiratory
pressure (PEEPi), and importance of airway obstruction. Adler et al. [13] studied a
specific phenotype of severe COPD with hyperinflation and “deventilation dys-
pnea” (i.e., sustained and invalidating dyspnea after cessation of NIV). The author’s
hypothesis was that too high pressure support led to progressive dynamic hyperin-
flation during nocturnal ventilation, leading to increased PEEPi, patient-ventilator
asynchrony (PVA), and discomfort when interrupting NIV. Decreasing pressure
support, slightly increasing BURR, and time to peak pressure improved PVA and
morning discomfort without increasing PtcCO2.
678 J.-P. Janssens et al.

79.4 Respiratory Rate and Data Provided by Ventilator

Software

Most home ventilators now provide built-in software that summarizes compliance,
pattern of use, average tidal volume and minute ventilation, leaks, apnea and hypop-
nea, and respiratory rate. Some devices estimate the actual RR of the patient, and
the percentage of respiratory cycles triggered (or cycled) by the patient (or the ven-
tilator). This information theoretically allows determination of the extent to which
the patient triggers the ventilator, or is “captured” and passively ventilated by the
device. In a cross-sectional description of ventilator data provided by built-in soft-
ware in 150 patients, the percentage of respiratory cycles triggered by the ventilator
was highest in patients with neuromuscular disorders (23 %) versus the other indi-
cations combined (on average 50–65 %), reflecting a common practice, which is to
“capture” the RR of these patients [14].
The reliability of this information is influenced by leaks: a low percentage of
inspiratory cycles triggered by the patient may either result from ineffective inspira-
tory efforts, or may reflect a patient “controlled” by the ventilator, and resting on the
BURR. The analysis of this information is further subject to the reliability of moni-
toring of leaks, which changes markedly from one device to another, and according
to the level of pressure support [15].

79.5 Items to Be Explored

The use of a BURR seems to impact on respiratory centers and have a stabilizing
effect on obstructive, mixed, and central events, although this should be confirmed
in settings other than OHS. Use of a high BURR in COPD remains controversial.
Although it may favor a more appropriate ventilator mode in severe COPD, it does
not seem to be a necessary component of the “high-intensity” ventilation proposed
by certain German groups. New automated devices with auto-adjusting pressure
support, EPAP, and BURR are potentially an important breakthrough to facilitate
implementation of home NIV. However, they must be tested and – until they are
clearly independently validated – require monitoring by respiratory polygraphy or
polysomnography.

Conclusion
There is little evidence to support the use of a spontaneous mode in HMV. If this
option is chosen, the clinician must be aware that the absence of a BURR may be
associated with an increase in central apnea, or hypopnea, as clearly described in
normal subjects and patients with OHS. It may also further destabilize the upper
airway. Conversely, a BURR may paradoxically stabilize upper airways. Use of
a high BURR may improve PVA, may decrease work of breathing in certain
groups of patients, and is frequently used in neuromuscular disorders. Although
there are few publications describing ventilator settings by diagnostic group, the
most frequent option, in bi-level pressure support, is the use of a BURR just
below spontaneous respiratory rate.
79 Contribution of Back-Up Respiratory Rate Setting in Noninvasive Ventilation 679

Take Home Messages

• Spontaneous mode (absence of BURR) is associated with an increase in
central apnea and hypopnea in normal subjects and subjects with OHS and
may destabilize upper airway.
• There is little evidence to support the use of a spontaneous mode in home
mechanical ventilation. If this option is chosen, the impact must be moni-
tored by nocturnal polygraphy or polysomnography.
• “High-intensity ventilation” combining high pressure support and high
BURR may increase the benefit of NIV on arterial blood gases, symptoms,
and PFT in stable hypercapnic COPD. The contribution of high BURR in
this setting has, however, been challenged.
• High BURRs are commonly used in neuromuscular disorders to reduce the
risk of central apnea, hypopnea, and hypoventilation and allow the patient
to be passively ventilated.
• The interaction between BURR and respiratory centers in central apnea-
hypopnea syndromes requires further study.

References
1. Berry RB, Chediak A, Brown LK, et al. Best clinical practices for the sleep center adjustment
of noninvasive positive pressure ventilation (NPPV) in stable chronic alveolar hypoventilation
syndromes. J Clin Sleep Med. 2010;6:491–509.
2. Janssens JP, Derivaz S, Breitenstein E, et al. Changing patterns in long-term noninva-
sive ventilation: a 7-year prospective study in the Geneva Lake area. Chest. 2003;123:
67–79.
3. Leger P, Bedicam JM, Cornette A, et al. Nasal intermittent positive pressure ventilation. Long-
term follow-up in patients with severe chronic respiratory insufficiency. Chest.
1994;105:100–5.
4. Restrick LJ, Fox NC, Braid G, et al. Comparison of nasal pressure support ventilation with
nasal intermittent positive pressure ventilation in patients with nocturnal hypoventilation. Eur
Respir J. 1993;6:364–70.
5. Casanova C, Celli BR, Tost L, et al. Long-term controlled trial of nocturnal nasal positive pres-
sure ventilation in patients with severe COPD. Chest. 2000;118:1582–90.
6. Piper AJ, Wang D, Yee BJ, et al. Randomised trial of CPAP vs bilevel support in the treatment
of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax.
2008;63:395–401.
7. Murphy PB, Davidson C, Hind MD, et al. Volume targeted versus pressure support non-
invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised
controlled trial. Thorax. 2012;67:727–34.
8. Contal O, Adler D, Borel JC, et al. Impact of different backup respiratory rates on the efficacy
of noninvasive positive pressure ventilation in obesity hypoventilation syndrome: a random-
ized trial. Chest. 2013;143:37–46.
9. Parreira VF, Delguste P, Jounieaux V, et al. Effectiveness of controlled and spontaneous modes
in nasal two-level positive pressure ventilation in awake and asleep normal subjects. Chest.
1997;112:1267–77.
10. Fauroux B, Louis B, Hart N, et al. The effect of back-up rate during non-invasive ventilation
in young patients with cystic fibrosis. Intensive Care Med. 2004;30:673–81.
680 J.-P. Janssens et al.

11. Dreher M, Storre JH, Schmoor C, et al. High-intensity versus low-intensity non-invasive ven-
tilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax.
2010;65:303–8.
12. Murphy PB, Brignall K, Moxham J, et al. High pressure versus high intensity noninvasive
ventilation in stable hypercapnic chronic obstructive pulmonary disease: a randomized cross-
over trial. Int J Chron Obstruct Pulmon Dis. 2012;7:811–8.
13. Adler D, Perrig S, Takahashi H, et al. Polysomnography in stable COPD under non-invasive
ventilation to reduce patient-ventilator asynchrony and morning breathlessness. Sleep Breath.
2012;16:1081–90.
14. Pasquina P, Adler D, Farr P, et al. What does built-in software of home ventilators tell us? An
observational study of 150 patients on home ventilation. Respiration. 2012;83:293–9.
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Nasal High Flow: Novel Approach
for Ventilatory Assist During Sleep 80
Hartmut Schneider and Jason P. Kirkness

Contents
80.1 Introduction ................................................................................................................... 682
80.2 Sleep-Disordered Breathing .......................................................................................... 682
80.3 Medical and Technical Requirements for Using NHF during Sleep ............................ 682
80.4 Effect of Sleep on Ventilatory Responses to NHF ........................................................ 683
80.5 Mechanisms of Action .................................................................................................. 684
80.6 Clinical Implications of NHF During Sleep ................................................................. 685
80.6.1 High Flow Alleviates Upper Airway Obstruction .......................................... 685
80.6.2 Hypercapnic Respiratory Failure .................................................................... 686
80.6.3 Obesity Hypoventilation ................................................................................. 686
80.6.4 Overlap (COPD/OSA) Syndrome ................................................................... 687
80.7 Summary: Clinical Implications of NHF During Sleep................................................ 688
References ................................................................................................................................ 689

Abbreviations

BiPAP Bi-level positive airway pressure

COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
ICU Intensive care unit
LTOT Long-term oxygen therapy
NIV Noninvasive mechanical ventilation
OSA Obstructive sleep apnea

H. Schneider, MD PhD (*) • J.P. Kirkness, PhD

Division of Pulmonary, Critical Care and Sleep Medicine, Johns Hopkins University,
Baltimore, MD, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 681

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_80
682 H. Schneider and J.P. Kirkness

80.1 Introduction

Respiratory failure is the most common complication of pulmonary and chest wall
disorders. An open nasal cannula system for delivering warm and humidified air or
oxygen at higher flow rates (2–50 l/min) has been shown to assist ventilation in the
acute setting in adults and children as well as in the subacute setting to ease respira-
tory symptoms in patients with severe, end-stage respiratory failure. The concept of
delivering high flow through an open nasal cannula (NHF) has been extended to
assist ventilation during sleep. This chapter reviews the medical and technical
requirements needed to use NHF during sleep and their effects on ventilation. The
reason for this review is the promise of NHF becoming an alternative to conven-
tional ventilatory assist such as nocturnal oxygen, positive pressure support, and
nocturnal ventilation.

80.2 Sleep-Disordered Breathing

It is well established that sleep plays a vital restorative role in maintaining health
across the life span and particularly in patients with underlying cardiopulmonary
disease. It is increasingly recognized, however, that sleep is a vulnerable state that
can augment cardiopulmonary stress and induce disturbances in breathing pattern
and blood gas exchange that are subsumed as sleep-disordered breathing.
Sleep-disordered breathing has generally been attributed to pathogenic alterations
in either the upper airway or ventilatory control leading to reductions in tidal vol-
umes, tachypnea, and increased work of breathing. Continuous and bi-level posi-
tive airway pressure (CPAP and BiPAP) and noninvasive ventilation (NIV) via a
nasal/facial mask are the mainstream treatment for sleep-disordered breathing, but
adherence rates are even lower than those for long-term oxygen treatment (LTOT)
[1]. Thus, a majority of patients with severe chronic obstructive pulmonary disease
(COPD) and obstructive sleep apnea (OSA) are insufficiently treated because they
cannot tolerate a nasal mask or oxygen cannula. For these patients, NHF of warm
and humidified air may represent an alternative means to improve sleep-disordered
breathing.

80.3 Medical and Technical Requirements for Using NHF

during Sleep

NHF of oxygen or room air through an open nasal cannula was first introduced to
improve oxygenation in infants and children with hypoxic respiratory failure. It was
then extended to adult pulmonary care to improve outcomes for patients in various
intensive care unit (ICU) settings. An extensive review of the use of NHF in the
acute and subacute settings are provided elsewhere [2, 3] in several reviews. There
are, however, several technical and medical necessities uniquely required for using
NHF to treating sleep-disordered breathing:
80 Nasal High Flow: Novel Approach for Ventilatory Assist During Sleep 683

Fig. 80.1 NHF devices for use during sleep in the home. Left: myAIRVO™, Right: TNI®
softFlow

1. Minimal noise due to turbulent nasal expiratory airflow. Flow rates are lower
than commonly used in the ICU (i.e., 10–35 l/min, most use 20–25 l/min).
2. Optimal comfort through individual temperature (30–35 °C) and humidification
(80–95 % RH) preference.
3. Appropriate portability and independence from wall or tank pressured airflow.
4. Adequacy for home requires negligible or no side effects due to cannula size or
position in the nares. Cannula to nares cross-sectional area ratio is ideally <80 %
and does not disperse water droplets.
5. Improved sleep quality (immediate efficacy) on the first night.
6. Approved medical device reimbursable for home use.

Although several NHF medical devices (e.g., TNI® softFlow, TNI® medical AG,
Würzburg, Germany; Precision Flow, Vapotherm, Exeter, NH, USA; myAIRVO™,
Fisher & Paykel, East Tamaki, Auckland, NZ) and cannula systems (AcuCare
HFNC, ResMed, Bella Vista, Australia; Optiflow, Fisher & Paykel, East Tamaki,
Auckland, NZ; Salter-Style® 1600HF, Salter Labs, Arvin, CA, USA) exist for use in
various hospital settings using pressurized air outlets, the most commonly use
devices that are suited for use during sleep at home, illustrated in Fig. 80.1, meet all
of the aforementioned technical requirements.

80.4 Effect of Sleep on Ventilatory Responses to NHF

Whereas most studies demonstrate a marked improvement in oxygenation with

increasing air-flow rates, inconsistencies exist with regard to the respiratory pattern
response to NHF. The majority of studies tested responses to NHF during wakeful-
ness. Although some patients may have stayed awake throughout the protocols,
others may have dozed off, given the comfort and relief of respiratory stress with
NHF. In particular, several studies indicate that patients reduce their respiratory
684 H. Schneider and J.P. Kirkness

rates when using NHF, but this response was not consistent across individuals and
between studies [4]. One study demonstrated that respiratory rate responses to NHF
were markedly dependent on the sleep/wake state [4]. During wakefulness, respira-
tory rate slowed and tidal volume increased in response to NHF, whereas during
sleep there was no change in respiratory rate but a reduction in tidal volume. Of
note, the respiratory rate response during wakefulness preserved minute ventilation,
whereas NHF during sleep was associated with an approximately 20 % decrease in
minute ventilation. The physiologic mechanisms for the wakefulness ventilatory
responses observed with NHF are unclear. Nevertheless, if these responses are pres-
ent in patients with cardiorespiratory diseases, it may help to treat patients with
COPD. These patients often adopt pursed-lip breathing to lower their respiratory
rate and prolong expiratory time to alleviate expiratory and dynamic hyperinflation.
Pursed-lip breathing is, however, associated with an increased work of breathing
and patients cannot maintain this pattern over a longer time period. NHF responses,
in fact, resemble the breathing pattern of pursed-lip breathing. Thus, NHF may
provide a therapeutic benefit for patients who cannot or will not adopt a slow and
deep breathing pattern. NHF may also be beneficial for subjects who have high dead
space ventilation due to tachypnea or a rapid, shallow breathing pattern, particularly
during sleep. NHF may help to prevent development of respiratory failure in patients
who suffer from increased ventilatory loads during sleep.

80.5 Mechanisms of Action

Although nasal high flow increases pharyngeal pressure (see Fig. 80.2), it differs
from CPAP during the expiratory phase [5]. The contribution of the cannula size/
nasal valve area and nasal cannula flow rate determine expiratory pressure. There
are two main explanations for the difference in expiratory resistance responses
between NHF and CPAP. NHF exerts a jet-flow effect that creates a pressure gradi-
ent across the flow-restricted nose segment, whereas CPAP increases the pressure at
the nares without creating a further pressure gradient across the valve area.
Furthermore, CPAP only minimally increases pressure during expiration, indicating
that air-flow resistance during expiration remained relatively constant with
CPAP. Stiffening of the nasal passage may also contribute to a greater expiratory
resistance with increasing expiratory air flow. Regardless of the mechanism, NHF is
not like minimal CPAP; rather, it serves as a means to increase resistance to expira-
tory air. When NHF is present, the pressure at onset of inspiration remains above
atmosphere for most of the inspiratory phase, raising the driving pressure for inspi-
ration. Despite similar patient acceptance [6], improvements in inspiratory air-flow
dynamics and increases in expiratory resistance make NHF a distinctly different
form of ventilatory assistance compared with CPAP.
Several studies have examined the effect of NIV or CPAP on ventilation and gas
exchanges in patients with COPD. Increasing levels of CPAP increases minute ventila-
tion without a change in arterial blood gases, indicating that patients’ ventilatory
responses to CPAP would differ from responses to NHF. Likewise, NHF would also
differ from responses to NIV. During NIV, nasal or facial masks impose added
80 Nasal High Flow: Novel Approach for Ventilatory Assist During Sleep 685

NHF off NHF 20 L/min

Expiration
200
Airflow
(ml/s)
–200
Inspiration

2 5

PSG
(cm H2O) 4
3
–15

Fig. 80.2 Effects of NHF at 20 l/min on upper airway obstruction. Mechanisms by which NHF
alleviates inspiratory airflow limitation (for details, see Schneider et al. [9])

dead-space volume. Improvements in alveolar ventilation must first overcome this

added dead-space volume, which often requires the application of either high tidal vol-
umes or high transpulmonary pressures, both of which are rarely well tolerated. In vitro
imaging methods utilizing flow-dependent tracer-gas clearance models demonstrated
increasing dead-space washout with increasing NHF rates. An anatomically based
model established complete tracer-gas removal from the nasal cavities within 1.0 s. The
level of clearance in the nasal cavities increased by 1.8 m /s for every 1.0 /min increase
in the rate of NHF, which is capable of reducing dead-space re-breathing [7].
A reduction in dead-space volume to assist breathing has been used in patients
with tracheotomies by insufflating fresh air into the tracheal tube. In these studies,
reductions in dead-space volumes as low as 40 ml have been shown either to
decrease arterial CO2 from 46 to 40 mmHg, if tidal volume remained unchanged, or
to reduce minute ventilation and work of breathing with no or only minimal reduc-
tions in arterial CO2 [8]. The ventilatory responses to nasal NHF, therefore, resem-
ble more those of tracheal gas insufflation. Thus, the principles of tracheal gas
insufflation appear more suitable to explaining physiologic and clinical responses of
nasal NHF than CPAP and NIV.

80.6 Clinical Implications of NHF During Sleep

80.6.1 High Flow Alleviates Upper Airway Obstruction

Several studies in patient populations demonstrate that NHF increases the end-
expiratory pressure. These increases are sufficient to alleviate inspiratory flow limi-
tation in adults and children. Several studies to date have been published to confirm
686 H. Schneider and J.P. Kirkness

this hypothesis. NHF's mechanism of action on upper airway function was first
determined in adult patients with varying degrees of upper airway obstruction.
Airflow dynamics and supraglottic pressure responses to NHF were examined. At a
rate of 20 l/min, NHF increased nasal pressure by approximately 2 cmH2O, and
increased in inspiratory airflow by approximately 100 ml/s. This increase in pharyn-
geal pressure and airflow can explain the improvement of snoring and hypopneas as
follows: the peak inspiratory airflow for hypopneas and for flow-limited breaths
average approximately 150–200 ml/s. The additional flow from NHF, therefore, will
increase the inspiratory airflow to 250–300 ml/s, a level previously associated with
stabilization of breathing patterns [9] (see Fig. 80.2).
The increase in inspiratory airflow has been associated with an improvement in
OSA severity in adults [9] and the effect was comparable to CPAP in children [10].

80.6.2 Hypercapnic Respiratory Failure

New evidence exists that NHF may improve ventilation even in the absence of upper
airway obstruction. In patients with a mild degree of COPD (Global Initiative on
Obstructive Lung Disease (GOLD) I–II), the use of NHF during sleep has been
associated with a reduction in arterial CO2 compared with room air. In another
study, NHF was used during wakefulness in addition to supplemental oxygen since
patients had severe COPD (Gold IV) requiring oxygen treatment [11]. In these
patients, NHF and supplemental oxygen also reduced respiratory rate, and lowered
arterial CO2 by more than 10 % in some individuals, indicating that alveolar ventila-
tion had improved and ventilation had become more effective with NHF. Moreover,
there are an increasing number of case reports and even randomized clinical trials
showing that the application of NHF daily or nightly improves overall health out-
comes. However, whether nocturnal use of NHF can prevent nocturnal hypercapnia
and improve daytime outcomes similar to NIV remains to be established.

80.6.3 Obesity Hypoventilation

Additional data regarding ventilator support independent of inspiratory flow limita-

tion is available from studies of children. McGinley et al. [10] demonstrated that, in
patients with rapid shallow breathing, NHF markedly reduced the respiratory rate
and inspiratory duty cycle, even if inspiratory flow limitation was not fully restored
(see Fig. 80.3). The precise mechanism for improving gas exchange and efficacy of
ventilation is not fully understood. It is possible that NHF may have reduced CO2
production by lowering work of breathing, or it reduced the dead-space ventilation
by washing out anatomic dead space of the nasal cavity. Alternatively, NHF may
have reduced intrapulmonary dead space by opening up atelectasis through slight
increase in positive end-expiratory pressure. Regardless of the mechanism, the data
from patients with COPD indicate that nasal insufflations reduced the load of breath-
ing, particularly in patients with rapid shallow breathing pattern. Nevertheless,
80 Nasal High Flow: Novel Approach for Ventilatory Assist During Sleep 687

Expiration Baseline NHF 20 L/min Baseline

Airflow
Inspiration

Thorax
abdomen
SaO2 95

(%)
80
110
Heart rate
(b/min) 70

Expiration

Airflow
Inspiration

Thorax
abdomen
95
SaO2
(%)
80

110
Heart rate
(b/min) 70
Respiratory rate = 36/min, T1/TT = 0.75 Respiratory rate = 23/min, T1/TT = 0.45
VM = 12 L/min VM = 4 L/min
Heart Rate: 90/min Heart rate: 75/min

Fig. 80.3 Changes in respiratory pattern in obesity hypoventilation. The effect of NHF on a rapid
shallow breathing pattern in an obese child (10 years old) demonstrates that both the respiratory
rate and the minute ventilation decrease substantially. Note also that the oxygenation improves and
heart rate is lowered, indicating improved gas exchange and reduction in sympathetic activity

additional clinical studies are warranted to determine NHF’s effectiveness in these

patients.

80.6.4 Overlap (COPD/OSA) Syndrome

Investigators have demonstrated that the prevalence of nocturnal hypoxemia

increases with the severity of COPD in a large, multi-center, community-based
cohort study, and that the presence of nocturnal hypoxemia cannot be predicted
from daytime PaO2 levels. Although the pathogenesis of nocturnal hypoxemia in
COPD is unclear, it is likely due to decreases in neuroventilatory drive that normally
occur during sleep and particularly during rapid-eye-movement sleep. A loss of
drive to upper airway dilator muscles during sleep leads universally to the develop-
ment of partial or complete upper airway obstruction, also known as inspiratory
airflow limitation or OSA. The combination of OSA and COPD is a well-recognized
risk factor for worse outcomes and, thus, justifies the separate term of an overlap
syndrome. In contrast, less evidence exists for inspiratory airflow limitation without
688 H. Schneider and J.P. Kirkness

NHF Room air NHF 20 (L/min) O2 (3 L/min)

EOG
EEG
EEG
100
SaO2
80
55
TcCO2
25

. 20
V
0

Rc

4 min

Fig. 80.4 Overlap syndrome. Effects of NHF and oxygen in a 75-year-old patient with COPD
with hypopnea during sleep. For details, see the text

sleep apnea. Although inspiratory airflow limitation is well tolerated in normal sub-
jects during sleep, in COPD, however, even subtle degrees of inspiratory airflow
limitation can compromise ventilation, nocturnal oxygenation, and sleep quality. In
an effort to stabilize ventilation in COPD subjects during sleep, investigators have
administered oxygen and heliox. These treatments have been largely ineffective,
presumably because these interventions did not mitigate airflow limitation during
either inspiration or expiration. An alternative therapy is suggested by investigators
who have demonstrated low levels of CPAP to be effective in relieving inspiratory
and expiratory flow limitation. Fig. 80.4 shows a recording example of a sleep and
breathing pattern of a 74-year-old patient who had inspiratory flow limitation lead-
ing to repetitive hypopneas with intermittent hypoxia and sleep fragmentation. NHF
stabilized breathing pattern while on room air (left and middle NHF period). On
oxygen at 3 l/min (right period), the patient developed severe sleep apnea of longer
duration compared with the hypopneas on room air and stronger arousal responses
as noted by larger tidal volumes in the inter-apneic periods. Note that the oximeter
signal on oxygen remained constant at 98 %. This example shows that NHF can
stabilize breathing pattern in patients with overlap syndrome who have mild upper
airway obstruction (hypopneas rather than apneas) and that the use of oxygen can
worsen the breathing pattern. This recording example also amplifies that oximetry
alone is not sufficient to detect worsening in breathing pattern.

80.7 Summary: Clinical Implications of NHF During Sleep

An open nasal cannula system delivering warm and humidified air at a flow rate of
20 l/min (NHF) can effectively lower ventilatory requirements to provide ventila-
tory assistance for disordered breathing during sleep in those with COPD. A
80 Nasal High Flow: Novel Approach for Ventilatory Assist During Sleep 689

reduction in dead-space ventilation, alterations in inspiratory air-flow dynamics,

and increases in expiratory resistance make NHF a distinctly different form of ven-
tilatory assistance compared with CPAP. NHF may also play a role in protecting
patients with respiratory failure, as it can reduce arterial CO2 and alleviate rapid
shallow breathing, thereby increasing efficacy of breathing. Although there is evi-
dence that daily or nightly use improves overall health outcomes, it remains to be
established whether nocturnal use of NHF can prevent nocturnal hypercapnia and
improves daytime outcomes similar to NIV.

References
1. McEvoy RD, Pierce RJ, Hillman D, Esterman A, Ellis EE, Catcheside PG, O’Donoghue FJ,
Barnes DJ, Grunstein RR. Nocturnal non-invasive nasal ventilation in stable hypercapnic
COPD: a randomised controlled trial. Thorax. 2009;64:561–6.
2. Lee JH, Rehder KJ, Williford L, Cheifetz IM, Turner DA. Use of high flow nasal cannula in
critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med.
2013;39:247–57.
3. Sotello D, Rivas M, Mulkey Z, Nugent K. High-flow nasal cannula oxygen in adult patients: a
narrative review. Am J Med Sci. 2015;349:179–85.
4. Mundel T, Feng S, Tatkov S, Schneider H. Mechanisms of nasal high flow on ventilation dur-
ing wakefulness and sleep. J Appl Physiol. 2013;114:1058–65.
5. Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive
airway pressure. Br J Anaesth. 2009;103:886–90.
6. Sowho MO, Woods MJ, Biselli P, McGinley BM, Buenaver LF, Kirkness JP. Nasal insufflation
treatment adherence in obstructive sleep apnea. Sleep Breath. 2014;19(1):351–7.
7. Moller WG, Celik S, Feng P, Bartenstein G, Meyer O, Eickelberg O, Schmid O, Tatkov
S. Nasal high flow clears anatomical dead space in upper airway models. J Appl Physiol. 2015.
DOI: 10.1152/japplphysiol.00934.2014
8. Tagaito Y, Schneider H, O’Donnell CP, Smith PL, Schwartz AR. Ventilating with tracheal gas
insufflation and periodic tracheal occlusion during sleep and wakefulness. Chest.
2002;122:1742–50.
9. Schneider H, O’hearn DJ, Leblanc K, Smith PL, O’Donnell CP, Eisele DW, Peter JH, Schwartz
AR. High-flow transtracheal insufflation treats obstructive sleep apnea. A pilot study. Am J
Respir Crit Care Med. 2000;161:1869–76.
10. McGinley B, Halbower A, Schwartz AR, Smith PL, Patil SP, Schneider H. Effect of a high-
flow open nasal cannula system on obstructive sleep apnea in children. Pediatrics.
2009;124:179–88.
11. Nilius G, Franke KJ, Domanski U, Ruhle KH, Kirkness JP, Schneider H. Effects of nasal insuf-
flation on arterial gas exchange and breathing pattern in patients with chronic obstructive pul-
monary disease and hypercapnic respiratory failure. Adv Exp Med Biol. 2013;755:27–34.
NIV Adaptation Process: Implications
of Team: Key Practical 81
Recommendations and Evidence

Pawel J. Kuca and Witold Z. Tomkowski

Contents
81.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 692
81.2 Lessons from CPAP Adherence and Nonadherence for OSA . . . . . . . . . . . . . . . . . . 692
81.3 Adaptation to NIV in the Acute Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 694
81.4 Adaptation to NIV in the Chronic Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 695
81.5 Common Problems in the Adaptation Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700
81.5.1 Malfunction of Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700
81.5.2 Physiotherapist’s Role in Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 701

Abbreviations

COPD Chronic obstructive pulmonary disease

CPAP Continuous positive airway pressure
EPAP Expiratory positive airway pressure
IPAP Inspiratory positive airway pressure
NIV Noninvasive mechanical ventilation
OSA Obstructive sleep apnea
pCO2 Partial pressure of carbon dioxide
PEEP Positive end-expiratory pressure
RF Respiratory failure
RFT Respiratory function tests
UL Unintentional leak

P.J. Kuca, MD, PhD (*) • W.Z. Tomkowski, MD, PhD

Cardio-Respiratory Intensive Care, National Tuberculosis and Lung Diseases Research
Institute, Plocka 26, Warsaw 01-138, Poland
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 691

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_81
692 P.J. Kuca and W.Z. Tomkowski

81.1 Introduction

Over the past two decades, noninvasive ventilation (NIV) has assumed a central role
in the treatment of patients with hypoxemic and hypercapnic respiratory failure
(RF) in the acute or chronic setting. The main advantage of NIV in acute RF is
avoiding endotracheal intubation and its related complications, preventing severe
sedation and tracheostomy, improving patient comfort, and preserving defense
mechanisms [1]. The most convincing evidence supporting NIV use in the acute
setting has been shown for patients with exacerbation of chronic obstructive pulmo-
nary disease (COPD) or acute cardiogenic pulmonary edema. The clinical indica-
tions for NIV have increased in recent years and are now well defined for the
treatment of chronic RF secondary to restrictive thoracic diseases and for COPD as
high-intensity NIV. Results indicate that, for patients with chronic restrictive RV
who use it, NIV improves quality of life, prolongs survival, enhances gas exchange,
and provides better sleep quality.
Once the decision to start NIV has been made, it is essential to choose a proper
ventilator, ventilation mode, and interface, and to construct a detailed plan for ade-
quate location for and precise monitoring of the use of NIV [1]. Adaptation process
plays an important role in the efficacy and safety of NIV treatment. Unfortunately,
this problem is poorly addressed in the literature. Moreover, current international
guidelines are usually disease-specific and concentrate on technical aspects of NIV
in acute RF. Therefore, a deeper understanding of adherence and nonadherence for
specific forms of NIV – continuous positive airway pressure (CPAP) in the treat-
ment of patients with obstructive sleep apnea (OSA) – may be helpful for detecting
critical factors for NIV adaptation success in other conditions. Educational, sup-
portive, and behavioral interventions to improve adaptation for CPAP in adult popu-
lations with OSA are reviewed.
Implementation protocols for NIV in acute RF, significant for adaptation, have
been precisely described by British Thoracic Society Standards of Care Committee
and Canadian Critical Care Society NIV Guidelines Group. Two adaptation strate-
gies for chronic setting have been described: one for patients with COPD, based on
high-intensity NIV and started in the hospital, and another for patients with restric-
tive, neuromuscular, and obesity problems with ventilation, with hospital or home
implementation.
At the end common problems with adaptation process, depended on staff mem-
bers or organizing structure, and troubles with equipment malfunctions, important
for adaptation, were discussed.

81.2 Lessons from CPAP Adherence and Nonadherence

for OSA

CPAP is the standard treatment for OSA, first described by Sulivan et al. in 1981.
CPAP has been demonstrated to improve daytime performance, reduce daytime
sleepiness, reduce automobile accidents, normalize sleep architecture, decrease
81 NIV Adaptation Process: Implications of Team: Key Practical Recommendations 693

blood pressure, and reduce other cardiovascular events. To reach these beneficial
effects, CPAP should be used regularly. CPAP adherence in patients with OSA has
been intensively studied. The main endpoint of most studies was CPAP usage time
per night. Despite the efficacy of CPAP in reversing sleep apnea, of those studies
using the cut point of at least 4 h per night to define adherence, 29–83 % of patients
were nonadherent [2].
One important way to improve adherence is to understand that the pattern of
adherence that is established early, within the first week of treatment, predicts long-
term use. It is also important to know that there are many patients who refuse to
consider treatment for OSA because of the nature of CPAP as a mechanical mask-
and machine-based therapy. This nonacceptance of therapy is therefore the crucial
cause of nonadherence. It has been observed that improvements in symptoms, day-
time sleepiness, neurological behavior, blood pressure, and quality of life occur
with greater use. Some studies suggest that even low levels of application provide
some benefits. Other studies have demonstrated a dose-response relationship [2]. In
fact, any use is better than no use, but greater gains in clinical outcomes may be
obtained with longer nightly durations of CPAP therapy.
Various factors associated with good adherence can be identified, including
patient characteristics (female gender, increasing age), parameters of disease sever-
ity, aspects of the technological interface, factors related to the initial exposure to
CPAP, and psychological and social variables. Patient education is recommended
in all patients receiving CPAP therapy for OSA before, during, and shortly after the
initiation of treatment. There is stronger support for the symptomatic severity of OSA
to influence adherence. Increased nasal resistance affects CPAP use and initial accep-
tance of this treatment. Initial presentation of CPAP in a supportive, controlled envi-
ronment may influence adherence outcomes. There is a strong suggestion that having
someone available to reinforce the important benefits of the treatment, to immediately
troubleshoot any interface-related problems, and to provide education may enhance
CPAP adherence. There have been reports that the sensation of claustrophobia may
interfere with use. The initial perception of CPAP as a desirable and effective treat-
ment may be a critical factor in patient acceptance of CPAP. Patient perception of the
risk of the illness, benefit of treatment, and volition to use the therapy, formed during
the first week, also affect adherence. Social support, partner interaction, and partner
sleep quality were important for the adherence to treatment [2].
There are three interventions that improve CPAP adherence in patients with
OSA: humidification of the airway, patient selection for different modalities of
CPAP, and behavioral interventions [3]. It was concluded in a Cochrane review that,
in CPAP-naive patients with severe OSA, low-quality evidence indicates that sup-
portive interventions that encourage people to continue to use their CPAP machines
increase usage compared with usual care. Moderate-quality evidence shows that a
short-term educational intervention results in a modest increase in CPAP usage.
Low-quality evidence indicates that behavioral therapy leads to a large increase in
CPAP machine usage [4].
Our current understanding of CPAP adherence suggests that adherence is a mul-
tifactorial, complex, clinical problem that requires similarly designed approaches to
694 P.J. Kuca and W.Z. Tomkowski

effectively address poor CPAP adherence in the OSA population. It recognizes the
significance of adaptation to NIV in the acute and chronic settings.

81.3 Adaptation to NIV in the Acute Setting

The use of NIV to treat patients with acute RF has been expanded in the last two
decades. NIV is particularly indicated in COPD with respiratory acidosis, acute
hypercapnic RF secondary to chest wall deformity or neuromuscular diseases, car-
diogenic pulmonary edema, and weaning from tracheal intubation [5].
NIV is not suitable for all patients with RF. If used indiscriminately, patients who
would be managed more appropriately by tracheal intubation will receive subopti-
mal treatment. Use of NIV in patients in whom it is unlikely to be beneficial is also
undesirable. It is essential that NIV be applied in an appropriate clinical area by
trained staff using the optimal ventilator mode, settings, and interface for the patient
with adequate monitoring [6].
Sequential steps for delivering NIV in patients with acute RF are presented in
Fig. 81.1. Figure 81.2 provides a practical explanation of all steps for NIV starting
in acute RF [5].
Adaptation of NIV in a unit requires education, a program of development, and
an opportunity to provide feedback to the team [7]. The main reasons for low use of
NIV are lack of physician knowledge, inappropriate NIV equipment, poor previous
experience, and inadequately trained staff. Experience in NIV is the most important
precondition for success in adaptation of NIV in acute patients. The location for
starting NIV should have facilities for monitoring, rapid access to endotracheal

Selection of patients

Collaboration
Staff with adequate
among physicians,
skills and Choice of location nurses, respiratory
experience
therapists, families

Patient agreement and

motivation

Selection of interface

Selection of ventilation mode and

ventilator setting, monitoring

Start of NIV

Fig. 81.1 Sequential steps for delivering NIV in patients with acute RF [1]
81 NIV Adaptation Process: Implications of Team: Key Practical Recommendations 695

Education •Plan an adequate training of all staff with calibrated protocol

Enviroment •Choose the setting where start NIV according to the severity of ARF

•Select patients according to likelihood of success. team experience.

Indication
location.availability of intubation. do-not-intubate status

Information •Explain the technique to competent patients to improve their compliance

•Choose the interface(s) best fitting facial anatomy: consider also a

Equipment rotating strategy with different interfaces to enhance comfort
•Choose a ventilator with good air-leak compensation provided with a
display of flow/pressure/volume curves

•Choose a pressometric mode (i.e.pressure support) with PEEP

Starting •Start with low pressures, then increase gradually depending on comfort
ventilation •Set adequately FiO2 and essential alarms
•Tighten the straps of the interface enough to avoid leaks, but not too tight

•Check clinical status, monitor SpO2, measure blood gases periodically

Monitoring •Reset ventilator according to patient-ventilatory synchrony. comfort. leaks
ventilation •Prevent skin lesions(i.e. protective devices, rotating interfaces)
•conisder humidification and. carefully sedation

Fig. 81.2 Practical explanation for all steps for NIV starting in acute RF [5]

intubation and invasive ventilation, and an adequate number of experienced staff.

The model of hospital care varies from country to country. The most important fac-
tors in determining where NIV should be started are need for monitoring, monitor-
ing capabilities of the unit, experience of the staff, and time response to NIV. NIV
should be started early, immediately after the patient's consent, because a delay may
permit further deterioration and increase the likelihood of failure. The physician has
an obligation to identify the disease to be treated with NIV and to exclude from NIV
patients with contraindications. Continuous monitoring is needed to verify the clini-
cal efficacy. Adherence to NIV may be improved by providing suitable humidifica-
tion, and patient comfort may be improved by a soft sedation. Patient motivation is
a critical issue for adaptation during NIV to enhance favorable outcomes [7].

81.4 Adaptation to NIV in the Chronic Setting

There are two important and distinct strategies for the use of NIV in the chronic
setting: one COPD and another in restrictive thoracic diseases, obesity hypoventila-
tion syndrome, and neuromuscular disorders with chronic RF.
The rationale for long-term NIV for COPD patients is still disputed. Fortunately,
a promising NIV technique has been described and introduced into clinical prac-
tice [8]. High-intensity NIV is defined as long-term (chronic) NIV aimed at maxi-
mally improving gas exchange. This means that the patient should achieve
696 P.J. Kuca and W.Z. Tomkowski

normocapnia or, if hypercapnia cannot be totally avoided, the lowest possible

level of pCO2 in arterial blood using high ventilatory settings, as maximally toler-
ated or necessary. From the physiological point of view, high-intensity NIV is an
effective procedure and improves several variables and parameters. High-intensity
NIV now is the first-choice method for home mechanical ventilation in patients
with COPD.
This approach clearly contrasts with the conventional, low-intensity approach. It
might be speculated that high-intensity NIV would not be as well tolerated as low-
intensity NIV in COPD. In fact, the opposite is true: patients spent, on average, 3.6
more hours per day on NIV when using high-intensity NIV compared with the low-
intensity strategy. Interestingly, dropouts occurred in the low- but not the high-
intensity group. More effective ventilation, as achieved by more aggressive forms of
NIV, results in better patient adherence, which is attributable to improved quality of
life and more effectively ameliorated symptoms [8].
An important part of the adaptation process with high-intensity NIV for COPD
patients consume is the time spent on the introduction. More days (on average
2.5) were spent in the hospital to acclimatize patients to high-intensity NIV com-
pared with low-intensity NIV. Other important factors include greater amounts of
leakage during night ventilation and induction in cardiac output. Special consid-
eration should be given to patients with heart failure and antihypertensive treat-
ment. High-intensity NIV is typically established in a step-wise approach in the
hospital [8]. The typical order of single steps for initiation and optimal adaptation,
as well as pitfalls and problem-solving advice for individual tracks of the adapta-
tion process, have been precisely described by Windisch [8] and are presented in
Table 81.1.
Great progress has been made in NIV modalities for the treatment of restrictive
chronic RF. NIV improves quality of life, prolongs survival, enhances gas
exchange, and provides better sleep quality. Currently, indications are well defined
for patients with neuromuscular and chest wall diseases, complications of tubercu-
losis, obesity hypoventilation syndrome, and other syndromes involving alveolar
hypoventilation [9].
Most patients committed to chronic NIV undergo the traditional adaptation and
follow-up in hospital. The period of adaptation to NIV for patients who are initiat-
ing treatment usually takes place on a scheduled in-patient basis, although it has
been reported to have been undertaken successfully in day hospitals, outpatient
clinics, and even in the patient’s home. Good infrastructure, adequate equipment,
and home-care staff have allowed home treatment to be as efficient as conven-
tional hospitalization [9]. Possibly more important than where the adaptation pro-
cess takes place is the motivation, experience, and dedication of the caregivers
assigned to carry it out. In fact, adaptation and follow-up in the patient’s home is
as efficient as that conducted within the hospital framework, but with the added
benefit of utilizing the patient’s family environment. Table 81.2 lists steps for
adaptation and the follow-up protocol for chronic NIV in stable patients with
chronic restrictive RF.
81 NIV Adaptation Process: Implications of Team: Key Practical Recommendations 697

Table 81.1 Practical approach for high-intensity NIV adaptation and problem solving in patients
with COPD [8]
Adaptation approach for high-intensity NIV
Use NIV in the daytime first, with the primary aim of establishing tolerance, but also with
control of blood gases and vital parameters including blood pressure
Start with assisted NIV first
For this purpose, the lowest back-up respiratory rate and most sensitive trigger threshold are
typically used in addition to low inspiratory positive airway pressure (IPAP) levels, normally
ranging between 12 and 16 cmH2O
Expiratory positive airway pressure (EPAP) levels are low at this time
Once assisted NIV is tolerated, carefully increase IPAP in a step-wise approach until maximal
tolerance is reached, usually up to 30 (range 20–40) cmH2O
The tolerated maximum may differ greatly between individuals
Increase the respiratory rate just beyond the spontaneous rate (not more) to establish controlled
ventilation, but avoid excessively high respiratory rate settings that cause dynamic
hyperinflation
Set EPAP to avoid dynamic hyperinflation according to subjective comfort (usually 3 and 6
cmH2O), and, similarly, set the inspiratory:expiratory ratio to 1:2 or lower
EPAP settings may be higher when upper airway obstruction is simultaneously treated (COPD
+ obstructive sleep apnea syndrome)
Once daytime tolerance is acceptable, apply nocturnal NIV
Do not apply nocturnal NIV too early when the patient is not comfortable with daytime NIV
Adjust ventilator settings according to subjective tolerance and nocturnal monitoring of blood
gases.
Sometimes settings can be modified considerably at the first control visit in the hospital after
the patient has been acclimatized to NIV at home for some weeks
Problem solving in adaptation to high-intensity NIV
Tolerance of higher IPAP levels can last from minutes to several days or even weeks:
individual adjustment is inevitable
Sometimes significant modification of settings is feasible at the first control in-hospital visit
after having discharged patients for acclimatization in the home environment
In cases of coexisting upper airway obstruction, higher EPAP levels are required
On the other hand, higher EPAP reduces the effective IPAP (which is IPAP minus EPAP); thus,
avoid high EPAP levels if not required
For controlled NIV (final aim), respiratory rates are typically set to 1 breath·min−1 higher than
during spontaneous breathing; thus, avoid excessively high respiratory rates, even though
controlled ventilation is the aim
Try out several masks
For nocturnal NIV, use oronasal masks because of potentially substantial leakage; for daytime
NIV, a nasal mask is often better tolerated
Several days in hospital are usually necessary to establish high-intensity NIV
Use humidification in cases of dry mucous membrane
Leakage is unavoidable, but should be kept as low as possible
Gastrointestinal side-effects can be managed by medication, positioning, and adjustment
(reduction) of ventilator settings; here, pressure-limited NIV is superior to volume-limited
NIV
Care must be taken in patients with preexisting cardiac disease because high-intensity NPPV
may induce a reduction in cardiac output
 698

Table 81.2 Adaptation and follow-up protocol for chronic NIV in stable patients with chronic restrictive RF
(a) Adaptation to chronic NIV (hospital and home)
Day 1 Day 2 Day 3/4 Day 4/5 Day 5/6
Pneumonologist Initial visit Clinical visit Clinical visit Clinical visit Discharge visit
Adaptation Tolerance Tolerance Tolerance
Parameters Synchrony Synchrony Synchrony
Modification
parameters
Nurse Clinical visit Clinical visit Clinical visit Clinical visit Clinical visit
Tolerance Tolerance Tolerance Arterial gases
Training Problems Problems Pulse oximetry
Physiotherapist Training Training
Visit Visit
Respiratory Respiratory
exercises exercises
Comments Quality of life questionnaire (SF-36), Borg Continue We initiate Only nocturnal ventilation. We If the results are
dyspnea score and degree of dependency with daily nocturnal assess ventilation efficacy with: acceptable
(Barthel index) are measured. ventilation, ventilation arterial blood gases at baseline (3 h (disappearance or
We decide the type of mask the patient will 2 h/morning (for at least after ending nocturnal ventilation); decrease of
use and we adapt it. and 2 h/ 6 h). Nocturnal pulse oximetry with hypercapnia to at
We initiate ventilation, 2 h/morning and afternoon. ventilation. least 10 mmHg, with
2 h/afternoon, with no nocturnal ventilation. If hypoxemia is not corrected, normal pH), the
oxygen can be added. patient is discharged.
P.J. Kuca and W.Z. Tomkowski
(b) Chronic NIV follow-up (home or pulmonary outpatient consultation)
Pneumonologist Nurse Physiotherapist
1st month Clinical visit Arterial gases
3rd month Clinical visit RFT SF-36 questionnaire and Borg scale Clinical visit
Arterial gases
Nocturnal pulse oximetry
6th month Clinical visit RFT SF-36 questionnaire and Borg scale Clinical visit
Arterial gases
Nocturnal pulse oximetry
Modified from Domenech-Clar et al. [9]. RFT respiratory function tests
81 NIV Adaptation Process: Implications of Team: Key Practical Recommendations
699
700 P.J. Kuca and W.Z. Tomkowski

81.5 Common Problems in the Adaptation Process

81.5.1 Malfunction of Equipment

The most frequent problems during adaptation are related to low compliance, patient
discomfort, high unintentional leaks (ULs), and insufficient correction of arterial
blood gases. Many equipment malfunctions are easy to diagnose during a detailed
medical history with a systematic checklist of ventilator-associated symptoms. ULs
are the most common problem in NIV, both in the acute and the chronic setting.
Poor compliance may also be precisely assessed by ventilation software. Psychiatric
or cognitive disorders may interfere with compliance. Phobias related to masks and
claustrophobia may be improved through hypnosis or behavioral therapy [10].
Good communication and a structured discharge plan adapted to the individual
are required. The patients, families, and caregivers should complete competency
training on how to operate the equipment, identify simple problems, and when and
how to seek advice [10]. In all families, reassessment and retraining as well as pro-
vision of problem-solving plans are necessary. Written information and educational
materials should be available during and after adaptation.

81.5.2 Physiotherapist’s Role in Adaptation

In many countries, the assessment, education, and care of patients with pulmonary
disorders in acute and chronic settings are managed by pulmonologists and nurses.
During the first 1–2 h of NIV, clinicians’ time with the patients is intensive and
leads to adaptation success. In a few specialized hospitals, some physiotherapists
are trained and involved in patients’ adaptation to NIV, but the role of physiothera-
pists is still undefined. They should be involved as an important part of the care
team in monitoring physiological responses to therapies, supervising exercise train-
ing, and performing airways clearance techniques in cases requiring more intensive
treatment.

Conclusions and Key Major Recommendations

• The process of adaptation to NIV is complex and many sequential steps for
successful NIV delivery in patients with acute and chronic RF are needed.
• The successful adaptation to NIV in acute settings is determined by proper
selection of patients, interface, ventilation mode, and monitoring. The
patient's status is usually severe, therefore, patient agreement and motiva-
tion are important but not determinative for adaptation success. Close
monitoring in an appropriate location are of primary importance for NIV
adaptation.
• Adaptation to NIV in patients with chronic RF needs support not only in
the patient-machine interaction. Many psychological, social, and behav-
81 NIV Adaptation Process: Implications of Team: Key Practical Recommendations 701

ioral factors influence adaptation to chronic NIV. Some information comes

from the adherence to CPAP in the OSA population. Step-by-step adapta-
tion procedures are proposed for high-intensity NIV in COPD and for
restrictive chronic RF diseases.
• In all steps, effective patient–health-care provider communication should
be an integral part of practice before and during adaptation of NIV. It may
enhance favorable NIV outcome.

References
1. Bello G, Depascale G, Antonelli M. Noninvasive ventilation: practical advice. Curr Opin Crit
Care. 2013;19:1–8.
2. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy. The
challenge to effective treatment. Proc Am Thorac Soc. 2008;5:173–8.
3. Esquinas Rodriguez AM, Scala R, Soroksky A, et al. Clinical review: humidifiers during non-
invasive ventilation – key topics and practical implications. Crit Care. 2012;16:203.
4. Wozniak DR, Lasserson TJ, Smith I. Educational, supportive and behavioural interventions to
improve usage of continuous positive airway pressure machines in adults with obstructive
sleep apnea. Cochrane Database Syst Rev. 2014;(1):CD007736.
5. Scala R, Latham M. How to start a patient on NIV. In: Elliott MW, Nava S, Schonhofer B, edi-
tors. Principles and practice of non-invasive ventilation and weaning. London): Horder Arnold;
2010. p. 70–83.
6. British Thoracic Society Standards of Care Committee. Non-invasive ventilation in acute
respiratory failure. Thorax. 2002;57:192–211.
7. Diaz-Lobato S, Mayorales-Alises S. Setting up and organizing a noninvasive ventilation unit
for hospital and home therapy. Arch Bronconeumol. 2005;41:579–83.
8. Windisch W. Noninvasive positive pressure ventilation in COPD. Breathe. 2011;8:114–23.
9. Domenech-Clar R, Nauffal-Mansur D, Compte-Torreo L, et al. Adaptation and follow-up to
noninvasive home mechanical ventilation: ambulatory versus hospital. Respir Med.
2008;102:1521–7.
10. Simonds AK. Risk management of the home ventilator dependent patient. Thorax.
2006;61:369–71.
Adherence to and Complications of CPAP
in Obstructive Sleep Apnea: Key 82
Determinants

Ahmed S. BaHammam, Aisha Hussain,

and Mohammad Al-Asmri

Contents
82.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 704
82.2 Definition of Good CPAP Compliance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 704
82.3 Factors That May Affect CPAP Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 705
82.3.1 Factors Related to Patients’ Characteristics
and Disease Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 705
82.3.2 Factors Related to the CPAP Device and Its Side Effects . . . . . . . . . . . . . 705
82.3.3 Psychological and Social Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 706
82.3.4 Factors Related to CPAP Titration Protocol . . . . . . . . . . . . . . . . . . . . . . . 707
82.4 How to Track CPAP Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707
82.5 Interventions to Improve CPAP Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 708
82.6 Common CPAP Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 709
82.6.1 Mask Intolerance and Claustrophobia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 710
82.6.2 Nasal Congestion or Dryness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 711
82.6.3 Nasal Bridge Redness or Ulceration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 711
82.6.4 Gastric Distension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 711
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 711
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 712

A.S. BaHammam, MD, FRCP (*)

Department of Medicine, The University Sleep Disorders Center,
College of Medicine, King Saud University, Strategic Technologies
Program of the National Plan for Sciences and Technology and Innovation,
Box 225503, Riyadh 11324, Saudi Arabia
e-mail: [email protected]
A. Hussain, MD • M. Al-Asmri, MD
Department of Medicine, The University Sleep Disorders Center, College of Medicine,
King Saud University, Riyadh, Saudi Arabia
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 703

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_82
704 A.S. BaHammam et al.

Abbreviations

AHI Apnea hypopnea index

ATS American Thoracic Society
CPAP Continuous positive airway pressure
ESS Epworth sleepiness scale
MSLT Multiple sleep latency test
OSA Obstructive sleep apnea
PAP Positive airway pressure

82.1 Introduction

Obstructive sleep apnea (OSA) is a disorder that is characterized by obstructive

apneas and hypopneas resulting from repetitive collapse of the upper airway during
sleep, which is attributed to several causes that can be classified into anatomical
factors such as maxillofacial structure changes or redundant soft tissues of the upper
airway and physiological factors such as defects in upper airway muscles and func-
tion. OSA is a serious medical illness. If left untreated, OSA increases both morbid-
ity and mortality [1, 2]. OSA has been shown to increase the risk of hypertension,
stroke, and cardiovascular complications [1, 2]. Moreover, OSA increases the risk
of motor vehicle accidents.
Continuous positive airway pressure (CPAP) is the treatment of choice for
OSA. It is an effective therapy that reduces morbidity and mortality; however, CPAP
adherence remains a major obstacle [3]. CPAP compliance has been reported to
range from 20 to 84 %, depending on the design of the study, the definition of com-
pliance, and the population examined [4].
This chapter discusses CPAP compliance, factors that influence compliance, how
to monitor CPAP compliance, interventions to improve CPAP compliance, and
common side effects of CPAP therapy.

82.2 Definition of Good CPAP Compliance

The question of how much CPAP use equates to good adherence is not clearly
known because there is a dose-response relationship between the duration of CPAP
use and clinical improvement in several outcome parameters [3, 5]. An accepted
definition of good CPAP adherence is CPAP usage for at least 4 h/night on more
than 70 % of nights during the duration of assessment [6]. However, there is no
good evidence to support this definition. Data suggest that usage of CPAP for as
little as 2 h results in improvement in certain outcomes such as daytime sleepiness,
as reflected by the Epworth sleepiness scale (ESS) and the multiple sleep latency
test (MSLT) [7, 8]. Furthermore, a number of studies including randomized con-
trolled trials have demonstrated improvements in functional outcomes, cognitive
82 Adherence to and Complications of CPAP in Obstructive Sleep Apnea 705

function, and blood pressure in patients treated with CPAP for less than 4 h/night,
70 % of the nights [6, 9–11]. Therefore, it is not correct to label patients who use
CPAP for less than 4 h as noncompliant. An official American Thoracic Society
(ATS) statement on CPAP use defined CPAP users as adherent to therapy if they use
CPAP regularly for more than 4 h/night or if they use CPAP more than 2 h/night and
have clinical improvement in OSA-related symptoms such as daytime sleepiness or
quality of life or improvement in OSA-associated health impairments such as hyper-
tension and diabetes [5]. This definition is more comprehensive because it takes into
account the clinical improvements with CPAP use even if patients do not meet the
strict criteria of 4 h/night and 70 % of the time. Nevertheless, therapists should
always aim for full-time CPAP use during sleep.

82.3 Factors That May Affect CPAP Adherence

Several studies have been conducted to define factors that influence or predict CPAP
use and adherence. These factors can be categorized into (1) factors related to
patients’ characteristics and disease features; (2) psychological and social factors;
(3) factors related to the CPAP device and its side effects; and (4) factors related to
CPAP titration protocol.

82.3.1 Factors Related to Patients’ Characteristics and Disease

Features

An association has been reported between CPAP adherence and the severity of OSA
as expressed by the apnea hypopnea index (AHI), oxygen desaturation (time spent
with oxygen saturation <90 % during sleep), and daytime sleepiness [12–16].
However, this association was found to be weak when other factors were included
in the analysis [3]. Several studies reported that race might influence CPAP adher-
ence. The available data suggest lower CPAP adherence in African Americans than
Caucasians [17–19]. Moreover, lower socioeconomic status has been reported to be
associated with worse adherence to CPAP in subjects with good standardized access
to health care and treatment [17].

82.3.2 Factors Related to the CPAP Device and Its Side Effects

The technology of CPAP therapy has developed significantly since its first descrip-
tion in 1981 [20]. In spite of this, around 60 % of patients experience side effects
that may influence their adherence [21, 22].
Heated humidification has been developed to adjust inhaled air humidity and
temperature to improve acceptance and hence adherence. Although heated humidi-
fication reduces inhaled air dryness [23], studies that examined the use of heated
humidity with CPAP delivery reported inconsistent findings [24, 25]. The effect of
706 A.S. BaHammam et al.

heated humidification during CPAP therapy is influenced by several factors, includ-

ing air leak, interface, room temperature, temperature of inhaled gas, humidity of
the environment, airflow, and pressure used [26]. Future studies are needed assess
the role of humidification during CPAP titration in patients with mouth breathing
and patients requiring high positive airway pressure.
A new advancement in CPAP technology is the development of auto-titrating
CPAP and pressure relief (Flex-technology). In general, studies have shown no
clinically significant improvement in adherence by using the new technology. Two
meta-analyses have assessed the differences between auto-titrating CPAP and con-
ventional CPAP in the treatment of OSA. Ayas et al. [27] reported that auto-titrating
CPAP and conventional CPAP were similar in adherence rates, elimination of respi-
ratory events, and improvement of subjective sleepiness. In a recent meta-analysis
that included 24 randomized controlled trials, Stanley et al. [28] reported improved
CPAP compliance by 11 min per night and reduced sleepiness as measured by the
ESS by 0.5 points in the auto-titrating CPAP group. However, the reported improve-
ments in ESS and compliance are not of clinical significance [28]. Nevertheless,
auto-titrating CPAP may enhance adherence in subgroups of patients who have per-
sistent side effects, those needing higher CPAP pressure, and young patients [29, 30].
Pressure relief CPAP (C-Flex™, Phillips Respironics, Murrysville, PA, USA)
was developed to solve pressure-intolerance reported by some patients. Studies that
assessed the effect of pressure relief CPAP have reported conflicting results [31–
35]. A randomized, controlled trial that included four sites in the United States and
Germany reported no difference in CPAP adherence among patients who used pres-
sure relief CPAP compared with conventional CPAP at 30, 90, and 180 days [33].
Another 3-month, double-blinded, parallel-arm randomized controlled trial com-
pared compliance with C-Flex versus conventional CPAP, and analyzed objective
and subjective sleepiness and vigilance among patients with severe OSA [32]. There
were no significant differences between groups in terms of CPAP compliance, sub-
jective sleepiness, sleep quality, health-related quality of life, or treatment comfort.
Moreover, there was no significant difference between the two groups in the sleep
latency values measured by the modified maintenance of wakefulness test [32].
Nevertheless, pressure release or flex mode may be helpful for patients who com-
plain of discomfort during breathing on CPAP, especially when exhaling.

82.3.3 Psychological and Social Factors

Several studies have demonstrated that depression is common among OSA patients
[36]. Theoretically, the presence of depression may influence the adherence to
CPAP therapy in OSA patients. Previous studies have reported conflicting results. In
a questionnaire-based study that assessed self-reported adherence to CPAP therapy
in 178 established CPAP users, depression was associated with lower CPAP use
[37]. On the other hand, a study that objectively assessed the adherence of 122 OSA
patients to CPAP therapy 1 month after beginning CPAP treatment reported no
effect of depression on CPAP adherence [38]. Two other small studies found no
association between CPAP use and depression [39, 40]. A study that used 1 week of
82 Adherence to and Complications of CPAP in Obstructive Sleep Apnea 707

home-based auto-CPAP titration and monitored adherence objectively in 240

CPAP-naive OSA patients reported depression as an independent predictor of fewer
hours of auto-CPAP use [41]. However, most of the previous studies did not control
for confounders that may influence adherence, such as OSA symptoms (e.g., day-
time sleepiness) or comorbid conditions of OSA and depression (e.g., insomnia).
Future studies should examine the effect of treatment of depression on CPAP accep-
tance and adherence, and should control for possible confounders that may interact
with depression and influence CPAP adherence.
Social factors have also been shown to affect CPAP adherence in OSA patients.
CPAP users who are married or in a live-in relationship show higher compliance com-
pared with those who live alone [39, 42]. A spouse or partner may provide feedback
about the effect of CPAP therapy such as elimination of symptoms and improvement
in quality of life, which could contribute to higher CPAP compliance [43].

82.3.4 Factors Related to CPAP Titration Protocol

The first exposure of patients to CPAP is a critical factor that may influence subse-
quent adherence. CPAP titration can be done during a full-night, in-laboratory ther-
apeutic sleep study (following a full-night diagnostic sleep study) or using a
split-night protocol (both diagnostic study and CPAP titration are combined in one
study). Moreover, titration can be done using unattended auto-titrating CPAP. Studies
that compared the full-night, in-laboratory therapeutic sleep study with the split-
night sleep study have shown that the protocol used does not influence CPAP adher-
ence [44]. Studies that compared CPAP adherence between unattended auto-titrating
CPAP and in-laboratory titration reported conflicting results regarding adherence
rates [45]. An earlier retrospective study that examined the effect of in-laboratory
sleep study and CPAP titration against unattended auto-titrating CPAP at home on
subsequent CPAP adherence reported no difference in the number of nights of
CPAP use between the two groups; however, patients who underwent in-laboratory
titration used CPAP for more hours per night compared with patients who under-
went unattended auto-titrating CPAP (4.1 vs 2.9 h; p < 0.05) [46]. More recent stud-
ies, however, showed no clinically significant differences in adherence rates between
the two titrating protocols [47, 48]. In a multicenter, randomized clinical trial com-
paring home-based unattended portable monitoring for diagnosis and auto-titrating
CPAP with in-laboratory sleep study and CPAP titration [47], CPAP adherence
(defined as percentage of night used ≥4 h) was 12.6 % higher among the auto-
titrating CPAP group [47]. Therefore, unattended CPAP titration is an acceptable
option in patients with a high likelihood of moderate to severe OSA.

82.4 How to Track CPAP Adherence

Earlier studies that reported CPAP adherence relied on self-reports. Self-reports

overestimate CPAP use by approximately 1 h/night when compared with objec-
tively measured CPAP use [49–51]. To overcome this inaccuracy, the manufacturers
708 A.S. BaHammam et al.

of CPAP machines developed tracking systems to monitor CPAP adherence and

efficacy. Hour meter recording systems, which measure machine-on time, were
developed initially and, subsequently, mask-on recording systems were developed.
Data are stored in the CPAP machine and can be downloaded to a computer through
a card containing a microprocessor chip, a modem, or a web-based server, which
allows objective measurement of CPAP therapy adherence [22]. New tracking sys-
tems provide information about residual sleep-disordered breathing, hours of CPAP
use, and mask leak, and some systems provide a number of different flow signals
[5]. CPAP adherence can be reliably determined from CPAP tracking systems,
which provide important information to the treating team. As a result, third-party
players such as Medicare mandate the use of CPAP adherence tracking systems to
continue reimbursement for CPAP beyond the first 3 months of treatment [5].
However, the residual respiratory events and leak data from CPAP tracking systems
are not as easy to interpret and the definitions of these parameters are inconsistent
between manufacturers and not well validated [5]. Tracking systems can be used on
all positive airway pressure devices used to treat OSA patients, including conven-
tional CPAP, auto-titrating CPAP, and bi-level PAP devices. An official statement
from the ATS recommends standardization of nomenclature on the CPAP tracking
reports [5]. Despite the above-mentioned limitations, tracking systems are helpful
in daily clinical practice to solve problems related to the device such as air leaks,
treat residual respiratory events, and enhance CPAP adherence. Nevertheless, stud-
ies are needed to document the usefulness of the CPAP tracking systems and to
assess their effects on OSA outcomes.

82.5 Interventions to Improve CPAP Adherence

A multidisciplinary approach is needed to improve adherence to CPAP therapy

through proper orientation, psychological and social support, and education pro-
vided to the patient about the disease, its complications, and benefits of CPAP ther-
apy [21, 39]. Based on studies that examined different interventional strategies to
enhance CPAP adherence, interventions can be categorized as supportive, educa-
tional, and behavioral. Supportive interventions focus on support, “reinforcement,”
and enhanced access to health-care services. Educational interventions emphasize
enhancing patient knowledge about the diagnosis and treatment of OSA. Behavioral
intervention strategies use cognitive behavioral therapy by expert interventionists to
enhance adherence. A recent Cochrane meta-analysis that included 30 randomized
parallel controlled trials assessed the effectiveness of educational, supportive, and
behavioral strategies in encouraging CPAP adherence in CPAP-naive patients with
severe OSA [52]. Compared with usual care, supportive ongoing interventions
increased machine usage by about 50 min per night (low-quality evidence), and
increased the number of participants who used their machines for longer than 4 h/
night from 59 to 75 % (low-quality evidence) [52]. Educational interventions
increased machine usage by about 35 min per night (moderate-quality evidence),
and increased the number of participants who used their machines for longer than
4 h/night from 57 to 70 % (low-quality evidence). Behavioral therapy led to
82 Adherence to and Complications of CPAP in Obstructive Sleep Apnea 709

substantial improvement in average machine usage of 1.44 h per night (low-quality

evidence) and increased the number of participants who used their machines for
longer than 4 h/night from 28 to 47 % (low-quality evidence) [52].

82.6 Common CPAP Complications

More than 65 % of patients who use a CPAP machine complain of some side effects
during usage [21]. Nevertheless, most of these side effects can be resolved. The
most commonly encountered problems are mask leaks, nasal congestion, and
removal of mask during sleep [53, 54]. It is estimated that up to two-thirds of
patients do not adhere to CPAP because of side effects [21]. Table 82.1 presents
common problems encountered during CPAP use and the proposed solutions.

Table 82.1 Common problems during CPAP use and proposed solutions
Problem Causes Possible interventions
Claustrophobia Anxiety Use CPAP machine gradually; try to
Face mask increase an hour at a time every night.
Use CPAP and apply the mask while
watching TV or listening to music.
Do not overtighten the straps on the mask.
Difficulty High pressure Use “ramp” feature on the machine.
tolerating Use auto-CPAP or pressure relief (Flex
blowing air technology)
Relaxation and desensitization techniques.
ENT evaluation to check for possible nasal
obstruction.
Leaky mask/air Poorly fitting mask Try adjusting the mask and interface straps
leak Improperly adjusted straps to get a better fit.
Incorrect mask size Refit the mask, making sure it does not sit
High pressure too high on the nasal bridge.
Apply the mask while air is blowing
through the circuit to help seal the mask on
contact.
Try nasal pillows or a different style of
mask.
Skin irritation Wrong mask size Try different masks or nasal pillows until a
or pressure Dirty mask comfortable mask is found.
sores Headgear not adjusted Good hygiene of the mask.
properly Make sure not to overtighten the mask.
Unintentionally Nose is congested Check for proper mask fit or size.
removing the Mask discomfort Using a chin strap may help keep the device
CPAP device on the patient’s face.
during sleep Advise patient to use a heated humidifier.
Review desensitization techniques with the
patient.
Activate the disconnect alarm if available.
Treat nasal congestion if existing.
(continued)
710 A.S. BaHammam et al.

Table 82.1 (continued)

Problem Causes Possible interventions
Dry mouth/ Wrong mask size Refit for a different mask or try a full face
mouth breather Air leak mask.
Patient sleeps with his/her A chin strap may help in keeping the mouth
mouth open closed.
Headgear not adjusted Advise patient to use a heated humidifier.
properly
Annoyed by the Dirty air filter Make sure the air filter is clean
noise/noisy Faulty machine Check the device with the medical supplier
machine to ensure it is working properly.
Wear earplugs.
Air in the High pressure Start with a low CPAP pressure and
stomach/ Air swallowing increase the pressure gradually.
aerophagia Try not to use high pillows that can block
the airways.
Eat dinner 3–4 h before sleep.
Usually disappears with continuous use
Dry, stuffy nose Nasal congestion Use heated humidifier.
Prescribe a nasal steroid spray or normal
saline.
Eye discomfort Wrong mask size Try a different type of mask or nasal
or irritation Mask not fit properly pillows.
Adjust the mask, do not overtighten.
Air hunger Mask leak Check mask or interface leak.
Check CPAP setting if needed to adjust the
ramp.
Use chin strap if the patient sleeps with his/
her mouth open.

82.6.1 Mask Intolerance and Claustrophobia

One of the most common side effects of CPAP use is mask intolerance due to the
wrong choice of style or size of mask or claustrophobia. Proper mask selection is an
important step in management. Mask selection should take into consideration
patient preferences, air leak, and adequate fit. Patients may develop anxiety and
complain of feelings of suffocation. Claustrophobia occurs in approximately 15 %
of CPAP users and has been associated with lower CPAP adherence [55]. To solve
this problem, patients may be asked to hold the mask up to the face without fixing
the straps. Once they feel comfortable, they can fix the straps. Additional techniques
such as biofeedback and progressive muscle relaxation before applying CPAP may
help [56]. Using alternative masks with smaller size such as nasal pillows may help
reducing claustrophobia and anxiety [57, 58]. Another common side effect related
to masks is mask leakage, which may cause eye dryness and irritation and dry
82 Adherence to and Complications of CPAP in Obstructive Sleep Apnea 711

mouth and throat. Moreover, mask leak may increase the risk of developing central
apneas, which may decrease CPAP compliance [59].

82.6.2 Nasal Congestion or Dryness

Nasal problems such as nasal congestion, dryness, and rhinorrhea are frequently
encountered among CPAP users. Air leak may increase the risk of developing nasal
dryness, congestion, and rhinorrhea. Therefore, air leak should be ruled out in
patients with nasal symptoms. Topical inhaled steroids are frequently prescribed to
treat nasal symptoms among CPAP users. A randomized, double-blinded, placebo-
controlled study that evaluated the effect of inhaled nasal steroids on nasal symp-
toms and CPAP use reported no significant difference in CPAP compliance or nasal
symptoms between the two groups [60]. Heated humidifiers have been used to ame-
liorate nasal symptoms. When nasal steroids were compared with heated humidifi-
ers, the group using heated humidifiers had fewer nasal symptoms with CPAP use
[61]. Patients who have low compliance because of nasal obstruction due to nasal
pathology such as nasal septal deviation or inferior turbinate hypertrophy may ben-
efit from surgical intervention [62].

82.6.3 Nasal Bridge Redness or Ulceration

Nasal bridge redness or ulceration result from the wrong choice of the mask or
excessive tightening of mask straps. Patients may tighten the straps to reduce air
leak around the mask. It is essential to choose the mask with the best fit and to train
patients on the correct way of applying masks.

82.6.4 Gastric Distension

Some patients complain of gastric distension when using CPAP. These symptoms
are usually transient and disappear with regular use.

Conclusion
OSA is a common medical problem with serious medical complications. CPAP
is an effective treatment that reduces the risk of several complications if used
regularly during sleep. However, patient adherence to CPAP therapy is a major
challenge for the treating team. New technology allows the treating team to
assess CPAP compliance and the presence of residual respiratory events or air
leak with more accuracy. Several factors have been associated with poor compli-
ance, including side effects of the CPAP machine. Therefore, support, education,
712 A.S. BaHammam et al.

and behavioral therapy are needed to improve CPAP adherence among patients.
Additionally, close follow-up of patients on CPAP therapy, particularly in the
first few week of CPAP use, is essential to enhance CPAP compliance.

Recommendations
• OSA is a common disorder with serious comorbidities. Therefore, every
effort should be made to diagnose and treat OSA patients.
• CPAP is an effective therapy for OSA; however, adherence to therapy is a
major obstacle. Therefore, CPAP adherence should be monitored regularly
over time.
• CPAP compliance should be assessed using the new tracking systems.
• Intensive educational and support programs with frequent follow-up of
patients on CPAP are recommended to enhance adherence.
• Most of the problems arising during CPAP therapy can be resolved during
follow up.

Acknowledgment This work was supported by a grant the Strategic Technologies Program of the
National Plan for Sciences and Technology and Innovation in the Kingdom of Saudi Arabia.

Conflicts of Interest The authors have no conflicts of interest to declare.

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“Deventilation Syndrome” in CPAP Users
with Obstructive Sleep Apnea: Clinical 83
Impact and Solutions

Çiğdem Akyol Beyoğlu, Aylin Özdilek,

and Emre Erbabacan

Contents
83.1 Introduction ................................................................................................................. 718
83.2 Discussion and Analysis ............................................................................................. 718
83.2.1 CPAP ............................................................................................................... 720
83.3 Mechanisms Underlying Deventilation Syndrome ..................................................... 721
83.3.1 PVA ................................................................................................................. 721
83.3.2 Poor Sleep Pattern ........................................................................................... 722
83.3.3 Other Possible Reasons ................................................................................... 722
Conclusion ............................................................................................................................ 722
References .............................................................................................................................. 723

Abbreviations

AHI Apnea hypopnea index

Auto-PEEP Auto-positive end-expiratory pressure
COPD Chronic obstructive pulmonary disease
CPAP Continue positive airway pressure
NIV Noninvasive ventilation
OSA Obstructive sleep apnea
OSAS Obstructive sleep apnea syndrome
PAP Positive airway pressure

Ç. A. Beyoğlu, MD (*) • A. Özdilek, MD • E. Erbabacan, MD

Department of Anesthesiology and Reanimation, Cerrahpasa School of Medicine,
Istanbul University, Istanbul, Turkey
e-mail: [email protected]; [email protected];
[email protected]

© Springer International Publishing Switzerland 2016 717

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_83
718 Ç.A. Beyoğlu et al.

PSG Polysomnography
PVA Patient-ventilator asynchrony
RERAs Respiratory effort-related arousals

83.1 Introduction

Obstructive sleep apnea (OSA) is a common respiratory sleep disorder that is char-
acterized by repetitive partial or complete collapse of the upper airway. Repeated
episodes of pharyngeal collapse lead to cessation of airflow for 10 or more seconds,
identified as apneas, and decrease in airflow by 30 %, called hypopneas [1].
Diagnosis is based on the sum of apneas and hypopneas per hour of sleep. The hall-
mark symptom is excessive daytime sleepiness and impaired functioning in daily
activities. Fortunately, there are several kinds of treatment for OSA patients, includ-
ing weight loss, pharmacological treatment, surgery and continuous positive airway
pressure (CPAP). The most effective treatment is CPAP, which uses a mask to
deliver a calibrated level of pressure to keep the airway open, thus significantly
attenuating the occurrence of apneas and hypopneas [2]. However, nocturnal nonin-
vasive mechanical ventilation (NIV) in OSA patients may result in severe morning
deventilation dyspnea, commonly named “deventilation syndrome,” just after inter-
ruption of the NIV therapy [3, 4]. This aspect of OSA CPAP use is a newer topic in
the literature, and the mechanisms and treatment are controversial. In this chapter,
we review a detailed description of deventilation syndrome, the pathways that cause
it, its clinical impact, and solutions.

83.2 Discussion and Analysis

OSA is a sleep-related disorder characterized by intermittent partial or complete

collapse of upper airway during sleep, despite ongoing breathing efforts. It affects
2–4 % of the middle-aged population [5]. When airway obstruction occurs, the
inspiratory airflow can be either reduced or completely absent [1]. These respiratory
events may lead to intermittent hypoxemia and hypercapnia, cortical arousals, and
surges of sympathetic activity [5]. Respiratory effort-related arousals (RERAs) are
defined as arousals from sleep that do not technically meet the definitions of apneas
or hypopneas but do disrupt sleep [6]. The brain responds to the lack of oxygen by
alerting the body and cessation of inspiration, and restores the breath as a reflex
mechanism.
It seems that gender, age, and weight are risk factors for OSA, but the basic
pathology is not defined clearly. The underlying causes are thought to be the upper
airway anatomy, response capability of the upper airway dilator muscles to respira-
tory challenge during sleep, the propensity to wake from increased respiratory drive
during sleep, the stability of the respiratory control system, and the potential for
state-related changes in lung volume to influence these factors [7]. Mechanistically,
83 “Deventilation Syndrome” in CPAP Users with Obstructive Sleep Apnea 719

in addition to central respiratory drive, the genioglossus is modulated by local reflex

mechanisms that respond to negative pharyngeal pressure [7]. Rapid changes in
negative intrapharyngeal pressure activate the muscle. Reduction in oropharyngeal
muscle tone provokes the upper airway obstruction. According to Poiseuille’s law,
if a tube's diameter decreases, there must be an increase in pressure to maintain a
flow rate, whether for a gas or a liquid. In the upper airway, this can be supplied by
creating a more negative intrathoracic pressure. This results in further narrowing of
the upper airway and obstruction and worsens the clinical impact.
OSA symptoms include snoring, gasping for air, non-restorative sleep, daytime
sleepiness, poor memory and attention, cognitive dysfunction, depression, and anxi-
ety. Symptoms are related to short-term and transient sleep breath disorder events
and impairment of sleep quality. The disorder is defined as obstructive sleep apnea
syndrome (OSAS) when at least five apnea or hypopnea episodes occur in 1 h with
clinical symptoms such as daytime sleepiness.
Apnea hypopnea index (AHI) is used as a classification of the severity of the
disease. AHI is calculated by dividing the number of apnea and hypopnea events by
the number of hours of sleep. Using the AHI, OSA can be classified as mild (AHI
5–14), moderate (AHI 15–29), and severe (AHI ≥ 30). Clinical symptoms are as
follows:

Mild OSA: Involuntary sleepiness during activities that require little attention, such
as watching TV or reading
Moderate OSA: Involuntary sleepiness during activities that require some attention,
such as meetings and presentations
Severe OSA: Involuntary sleepiness during activities that require more active atten-
tion, such as talking or driving

Overnight polysomnography (PSG) is the gold standard for the diagnosis of

OSA. Overnight PSG is performed by a technician in a sleep laboratory. Multiple
physiologic signals are monitored during sleep that fall into three branches: cardiac,
respiration, and sleep deepness. A trained polysomnogram technologist and a sleep
physician analyze the collected data. The data gives a strong opinion about the
patient’s airflow, how it affects the physiologic status, and an accurate course of the
disease. It is a preferable way to decide CPAP device parameters under PSG, so that
incorrect pressure settings can be recognized easily.
Positive airway pressure (PAP) therapy is the gold standard and the most effec-
tive noninvasive treatment modality for OSA patients. Applying positive pressure
to the upper airway continuously prevents the pharyngeal muscles from collapsing
and keeps the airway open. However, in some cases, patients suffer from severe
dyspnea just after interruption of NIV after an entire night of treatment with
NIV. Patients cannot get out of the bed or perform daily activities at least 30 min
after cessation of NIV [3]. This is called “deventilation syndrome,” and possible
pathways and treatment are controversial. To highlight the mechanisms underlying
deventilation dyspnea, it is important to understand the role of CPAP in patients
with OSA.
720 Ç.A. Beyoğlu et al.

83.2.1 CPAP

CPAP supplies a continuous, constant supra-atmospheric pressure to the airway in

both inspiration and expiration by pressure of the ventilator circuit. It is the most
common and effective respiratory therapy for OSA patients [1]. The CPAP device is a
high-flow generator that pumps compressed room air via a bellows system. The gen-
erator provides a continuous positive pressure to the upper airway via a low-resistance
breathing circuit and a mask connected at the end. Every mask has its own exhalation
valve, which directly influences the leak level. Air leaks may also result from gaps
between the mask and skin or mouth, leaks during nasal ventilation, or nasal leaks
during mouthpiece ventilation. Pressure requirements differ according to the leak
level. Mask leaks can be avoided by using compatible masks fitted to the mouth,
nose, or face. Patients must be educated about not mouth breathing while sleeping if
using a nasal mask or not using the nostrils to breathe if using a mouth mask.
Interfaces used for CPAP therapy have a direct impact on CPAP compliance and
treatment success. Leaks are usually well tolerated, but a large level of leaks may
affect ventilator cycling adversely and result in arousals. Therefore, devices that can
compensate for leak are desirable. Leakage compensation capability differs by NIV
device. The important issue is to achieve a harmony between the patient, interface,
and device. The internal dead space of NIV masks varies by mask style and may
influence the hypercapnia and leak levels, so it must therefore be kept in mind.
The CPAP device increases the flow when the pressure is low in inspiration and
decreases the flow when the pressure is high in expiration, so it supplies the continu-
ous positive pressure. The lowest pressure level to eliminate the upper airway
obstruction during sleep is the “optimal” CPAP. An appropriate CPAP therapy elim-
inates the clinical symptoms such as snoring and cortical arousals, provides a satis-
factory sleep pattern, and improves quality of life.
Conventionally, CPAP parameters are set up in sleep laboratory under PSG by a
sleep technician [5]. It is performed in a limited time in one night and the parame-
ters are not changed after the appropriate adjustments. More recently, auto-CPAP
devices have been introduced to deliver variable pressure levels related to the
requirements of the patient during sleep to optimize the pressure. An auto-CPAP
automatically titrates the minimum pressure level required for the patient. The
device does not deliver a constant pressure, rather, it measures the resistance in the
patient’s breathing and provides the minimum pressure at a set time. The efficacy of
auto-CPAP machines is variable, and they collect data to guide the clinician to
examine the efficacy of the therapy.
The best method is to set the CPAP device parameters during PSG to ensure the
efficacy of the treatment. The optimum pressure level is the lowest one applied to
the patient to keep the airway open. The aim of this treatment is to eliminate the
following respiratory events: apneas, hypopneas, RERAs, and snoring [6]. Patient-
ventilator asynchrony (PVA) and discomfort may occur when the clinician fails to
optimize the ventilator parameters. Technical properties of the machine, such as
trigger efficiency, pressurization speed, and air leak compensation, are important in
optimizing the ventilator settings. PVA is frequent in patients who are thought to be
treated efficiently [8].
83 “Deventilation Syndrome” in CPAP Users with Obstructive Sleep Apnea 721

83.3 Mechanisms Underlying Deventilation Syndrome

83.3.1 PVA

PVA is suggested to be the main problem leading to deventilation syndrome [3].

The PVA index is the number of asynchrony events divided by the total respiratory
rate as the sum of number of ventilator cycles (triggered or not) and unrewarded
efforts × 100. It is used to determine the severity of asynchrony.

83.3.1.1 Auto-Positive End-Expiratory Pressure

Auto-positive end-expiratory pressure (auto-PEEP) is also referred to as occult
PEEP, intrinsic PEEP, or dynamic hyperinflation. Auto-PEEP is one of the most
important reasons for PVA [8]. In patients with obstructive airways disease,
increased resistance leads to ineffective inspiration and expiration. Auto-PEEP
occurs when expiration is ineffective and the air is trapped in the alveoli. The patient
feeling air hunger increases the velocity of inspiration to get air into the lungs.
When air gets into the lungs it cannot get out because of the obstruction. Incomplete
emptying of the lungs leads to an excessive amount of air at the end of the expira-
tory phase. This leads to stretching of the lungs (hyperinflation) and impairment of
the diaphragmatic contractility.
Residual pressure formed at the end of expiration exceeds the atmospheric pres-
sure. Air flow cannot be reestablished until there is a pressure gradient from the
mouth to the alveoli. The patient needs to increase the effort to initiate inspiratory
airflow. Spontaneously breathing patients with air-trapping must generate a negative
pressure equal to the level of auto-PEEP to initiate inspiratory flow. Hyperinflation
and high end-expiratory pressure, at the end, lead to the increased work of breathing
and development of rapid-shallow breathing. This promotes dynamic hyperinflation
and increases auto-PEEP.
The airway obstruction should be improved to break this vicious cycle. Applying
CPAP is the most effective way to treat air trapping and auto-PEEP. The key to
administration of CPAP is to set the CPAP level higher than the auto-PEEP because
air trapping worsens if CPAP pressure remains under the auto-PEEP level.
Reflex mechanisms from both chemoreceptors and mechanoreceptors that con-
trol the activity of pharyngeal dilator muscles are reduced during sleep [9]. Impaired
activity of the pharyngeal dilator muscle during sleep plays a critical role in deter-
mining airway collapse in OSA patients. It has been observed that, during wakeful-
ness, the activity of the pharyngeal dilator muscles in OSA patients is increased to
overcome compromised pharyngeal anatomy. Once awake, the patient’s improved
pharyngeal dilator muscle tone overcomes the adverse forces causing obstruction
and hyperinflation in the lungs. This is the recovery period from deventilation
dyspnea.

83.3.1.2 Trigger Asynchrony

Ineffective triggering, auto-triggering, and double-triggering can be monitored dur-
ing CPAP treatment in patients with. In patients with OSA, ineffective triggering
and double-triggering are the most commonly seen patterns of PVA. [10]. Ineffective
722 Ç.A. Beyoğlu et al.

triggering is a lack of ventilatory response to patient’s effort. High pressure support

levels and high tidal volumes result in auto-PEEP, which leads to hyperinflation,
especially in patients with chronic obstructive pulmonary disease (COPD) overlap-
ping. Patients cannot override the existing PEEP and the effort cannot initiate the
ventilator cycle. Adjusting the ventilator settings can significantly reduce PVA fre-
quency. Reducing the pressure support level is the most effective method of elimi-
nating PVA related to ineffective triggering [8, 10]. Auto-triggering is a cycle
delivered by the ventilator without patient triggering. Reducing inspiratory trigger
sensitivity can help dissolve this problem. Double-triggering occurs when the ven-
tilator inspiratory time is shorter than the patient’s inspiratory time. The patient’s
effort is not completed at the end of the first cycle and triggers a second cycle. The
solution is increasing the inspiratory time.

83.3.2 Poor Sleep Pattern

Repetitive hypoxia and hypercapnia and cortical arousals in OSA patients lead to
abnormal sleep architecture and poor sleep quality. CPAP treatment may improve
poor sleep pattern, but if CPAP treatment is insufficient, then residual sleepiness is
a major consequence and may play a role in daytime sleepiness and chronic fatigue
[4]. However, it is not a clear reason for deventilation dyspnea because it is a chronic
challenge for OSA patients, and deventilation dyspnea is not seen after cessation of
CPAP therapy.

83.3.3 Other Possible Reasons

Coexisting medical problems such as impaired lung function coexisting with

chronic obstructive airway disease, central apnea, depression, and sedative drugs
complicate treatment and CPAP compliance and may aggravate symptoms.
However, they are not a likely cause of acute dyspnea after cessation of CPAP ther-
apy. Further evaluation under PSG will help to determine the roles of these factors
in deventilation syndrome.

Conclusion
The most common treatment for patients with OSA is CPAP. CPAP treatment
presents some challenges for the patient, such as adjustment to the CPAP device,
erroneous pressure level set-up, poor awareness about of the dead space and leak
level of the device, and coexisting medical problems. These factors may play a
role in hyperinflation under CPAP therapy, which causes deventilation syndrome.
Deventilation syndrome is defined as severe morning dyspnea just after cessation
of CPAP. The patient cannot get out of bed or perform daily activities for 30 min.
In this period, the patient awakens and reverses the adverse effects of inaccurate
CPAP application with an improvement in muscle tone and then goes on with
daytime activities. To avoid the syndrome, it is important to determine the
83 “Deventilation Syndrome” in CPAP Users with Obstructive Sleep Apnea 723

appropriate pressure level required by the patient, to keep in mind the leak levels
and dead spaces present with the interfaces and the leak compensation capability
of the CPAP device, and to be aware of the requirement of pressure changes dur-
ing therapy. Deventilation syndrome is a new term and needs further research to
clarify the mechanism and overcome the symptoms.

Key Major Recommendations

• CPAP is the key method for OSA treatment. Optimal monitoring always
should be performed when titrating the optimum pressure level.
• Clinicians must be aware of the properties of the interfaces and their leak
levels and the requirements for pressure changes during CPAP treatment.
• Deventilation syndrome should alert the clinician to check the ventilation
parameters and coexisting medical challenges.
• The key to determining the optimum CPAP for the patient is taking into
consideration the patient and ventilator properties so as to avoid deventila-
tion syndrome.

References
1. Kielb SA, Ancoli-Israel S, Rebok GW, Spira AP. Cognition in obstructive sleep apnea-
hypopnea syndrome (OSAS): current clinical knowledge and the impact of treatment.
Neuromol Med. 2012;14:180–93.
2. Atwood Jr CW. Progress toward a clearer understanding of the role of bilevel positive airway
pressure therapy for obstructive sleep apnea. J Clin Sleep Med. 2013;9(4):337–8.
3. Adler D, Perring S, Takahashi H, Espa F, Rodenstein D, Pepin JL, Janssens JP. Polysomnography
in stable COPD under non-invasive ventilation to reduce patient–ventilator asynchrony and
morning breathlessness. Sleep Breath. 2012;16(4):1081–90.
4. Esquinas AM, Ucar ZZ, Kirakli C. Deventilation syndrome in severe COPD patients during
long-term noninvasive mechanical ventilation: poor sleep pattern, hyperinflation or silent
chronic muscular fatigue? Sleep Breath. 2014;18:225–6.
5. Chan AS, Philips CL, Cistuli PA. Obstructive sleep apnoea – an update. Intern Med J.
2010;40:102–6.
6. Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, PArthasarathy S, Quan SF,
Rowley JA, Positive Airway Task Force; American Academy of Sleep Medicine. Clinical
guidelines for the manual titration of positive airway pressure in patients with obstructive sleep
apnea. J Clin Sleep Med. 2008;4(2):157–71.
7. Eckert DJ, Malhotra A. Pathophysiology of adult obstructive sleep apnea. Proc Am Thorac
Soc. 2008;5(2):144–53.
8. Chao DC, Scheinhorn DJ, Stearn-Hassenpflug M. Patient-ventilator trigger asynchrony in pro-
longed mechanical ventilation. Chest. 1997;112:1592–9.
9. Mannarino MR, Di Filippo F, Pirro M. Obstructive sleep apnea syndrome. Eur J Intern Med.
2012;23(7):586–93.
10. Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard L. Patient-ventilator asynchrony
during assisted mechanical ventilation. Intensive Care Med. 2006;32:1515–22.
Psychological Factors in Noninvasive
Home Ventilation Users 84
Alicia Carissimi, Denis Martinez, and Cintia Zappe Fiori

Contents
84.1 Introduction ................................................................................................................. 726
84.2 Noninvasive Ventilation on Psychological Symptom ................................................. 726
84.3 Discussion ................................................................................................................... 727
References .............................................................................................................................. 728

A. Carissimi, PhD (*)

Graduate Program in Medicine: Psychiatry, Universidade Federal do Rio Grande do Sul
(UFRGS), Rio Grande do Sul (RS), Brazil
Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350,
Porto Alegre, RS, 90035-003, Brazil
e-mail: [email protected]
D. Martinez, MD, PhD
Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio
Grande do Sul (UFRGS), Rio Grande do Sul (RS), Brazil
Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350,
Porto Alegre, RS 90035-003, Brazil
Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do
Sul (UFRGS), Porto Alegre, RS, Brazil
e-mail: [email protected]
C.Z. Fiori, PhD
Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio
Grande do Sul (UFRGS), Rio Grande do Sul (RS), Brazil
Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350,
Porto Alegre, RS, 90035-003, Brazil
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 725

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_84
726 A. Carissimi et al.

Abbreviations

CPAP Continuous positive airway pressure

OSA Obstructive sleep apnea
POMS Profile of Mood States

84.1 Introduction

Continuous positive airway pressure (CPAP), a noninvasive respiratory therapy

technique, is the main treatment for obstructive sleep apnea (OSA). OSA is a com-
mon sleep breathing disorder, defined as recurrent episodes of obstructed breath-
ing during sleep. Such episodes cause repeated arousals, sympathetic hyperactivity,
and intermittent hypoxia. The influence of OSA on psychological factors is still
debatable.
The consequences of OSA comprise serious anatomical damage to the brain,
indicated by neuroimaging [1, 2]. In animal models of OSA, intermittent hypoxia
causes neuronal apoptosis [3] and demyelination [4]. Despite such clear insult to the
brain, no well-defined relationship between OSA and psychological symptoms has
been recognized. The reversal of psychological symptoms after the elimination of
apneas by CPAP would substantiate a causal relationship.
This chapter examines the response of the psychological symptoms after treatment
with CPAP, searching for conclusive evidence on the of role apneas on OSA patients’
mental health. As discussed below, this field of knowledge is far from settled.

84.2 Noninvasive Ventilation on Psychological Symptom

We performed a systematic literature search of the MEDLINE and Cochrane data-

bases. We identified 187 articles, using MeSH (Medical Subject Headings) entry
terms by the PICO strategy. We selected eligible studies according to our inclusion
criteria (Table 84.1). The primary aim of the review was to find studies that evalu-
ated the change in psychological symptoms after CPAP therapy in OSA patients.
Twenty studies met inclusion criteria. Only three studies were randomized trials
with adequate power to allow discussion.

Table 84.1 Search strategy

Population Obstructive sleep apnea
Intervention Continuous positive airway pressure
Outcome Psychological or psychiatric symptoms
Design Observational and experimental studies
Duration Any follow-up length
Excluded Review studies; adherence to CPAP therapy; age<18 years; animal studies;
cognitive symptoms
84 Psychological Factors in Noninvasive Home Ventilation Users 727

84.3 Discussion

Improvement of psychological symptoms has been observed in several studies after

CPAP use for treatment of OSA. Because most studies are not controlled, the over-
all results are inconclusive. In addition, many studies report negative results.
Considering that an effect size of 0.2 could be clinically relevant, samples size in a
randomized trial should be of at least 30 patients per group.
The studies with adequate design and sufficient number of subjects are reviewed
in detail below. All were published in peer-reviewed journals.
In 2004, Barnes et al. [5] published a study of 80 patients undergoing 3-month
CPAP and mandibular advancement splint treatment in a three-arm crossover trial,
compared with placebo tablet. The depression scores evaluated by Beck Depression
Inventory [6], did not improve significantly compared with placebo. Nevertheless,
CPAP improved only general mood, compared with placebo, evaluated by Profile of
Mood States (POMS) [7]. POMS consists of a 5-point scale with six factors. General
mood score is calculated adding the scores for tension, depression, anger, fatigue,
and confusion and subtracting the vigor score.
In 2007, Haensel et al. [8] studied 25 patients in CPAP and placebo groups over
2 weeks. Both groups showed improvement in POMS subscales: total score, ten-
sion, fatigue, and confusion after treatment. There was no significant interaction
between time and treatment for any of the POMS subscales, indicating that this
improvement was nonsignificantly different from placebo.
In a study published in 2012, with 71 patients using therapeutic and placebo
CPAP during 3 weeks, 56 patients completed the study [9]. There were no signifi-
cant changes in the Center for Epidemiologic Studies Depression Scale [10], POMS
Depression, POMS Tension, and Brief Symptom Inventory of Depression and
Anxiety scores [11]. No time × treatment interaction was found. The Center for
Epidemiologic Studies Depression Scale is a screening test for depression and
depressive disorder and contains 20 items in 9 different groups as defined by the
American Psychiatric Association Diagnostic and Statistical Manual. The 53-item
Brief Symptom Inventory is a short version of Symptom Check-list-90-Revised,
and it was designed to assess levels of psychological distress.
We calculated the probability of beta error in accepting the null hypothesis in the
three studies above. In the study of Barnes et al. [5], the POMS scale had an 81 %
power and Beck Depression Inventory had a 76 % power to detect differences
between treatments in a trial. In the other two studies mentioned, the psychological
evaluation had a power of 5% and 40% to detect differences between treatments.
It was difficult to analyze the 20 studies obtained from the literature because 6
had uncontrolled design. They were performed with sample sizes varying from 5 to
30 in each group, used 14 types of instruments to assess the symptoms, and treat-
ment follow-up ranged from 7 days to 1 year. Studies assessing the symptoms for a
longer time are uncontrolled. Overall, the only significant result was that CPAP
improved general mood evaluated by POMS compared with placebo [5]. This result
represents insufficient evidence of a medically relevant relationship of OSA with
mental health.
728 A. Carissimi et al.

Before the role of OSA as a cause of mental distress can be accepted, the efficacy
of CPAP to control psychological symptoms in patients with OSA needs to be
investigated through randomized controlled trials with long-term follow-up and
large sample size. In addition to being well designed and powered, research should
address other dimensions of psychological distress, not being limited to scales of
anxiety and depression, two disorders that seem to be unrelated to OSA or at least
do not improve after OSA treatment. Depression and anxiety are common disorders
as well as OSA. The coexistence of these conditions may be only a concomitance of
events, without any causal connection.
In a nonrandomized controlled study performed by our group, we observed sig-
nificant improvement in somatization scores after CPAP [12]. This suggests that
OSA may be the cause of a variety of “functional” symptoms [13]. These symptoms
have been attributed to psychological stress because, until now, a sleep study to rule
out OSA is not considered part of the psychological assessment. It is necessary to
explore unchartered dimensions of mental suffering before dismissing the OSA-
psychological complaints link.
Considering that no study currently available is sufficiently powered and well
designed as to allow accepting the negative results, it is difficult to reach any con-
clusion on this matter. Although highly plausible, the effect of OSA on mental
health remains elusive.

Key Major Recommendations

• The indication of home noninvasive ventilation to treat psychological
symptoms in OSA patients is not supported by the current literature.
• Additional well-designed and adequately powered clinical trials are needed
to examine the response of the psychological symptoms to OSA treatment
with CPAP.
• Future studies should address other dimensions of psychological distress,
such as somatization, not being limited to scales of anxiety and
depression.

References
1. Macey PM, Kumar R, Woo MA, Valladares EM, Yan-Go FL, Harper RM. Brain structural
changes in obstructive sleep apnea. Sleep. 2008;31(7):967–77.
2. Morrell MJ, Jackson ML, Twigg GL, Ghiassi R, McRobbie DW, Quest RA, Pardoe H, Pell GS,
Abbott DF, Rochford PD, Jackson GD, Pierce RJ, O’Donoghue FJ, Corfield DR. Changes in
brain morphology in patients with obstructive sleep apnoea. Thorax. 2010;65(10):908–14.
3. Baronio D, Martinez D, Fiori CZ, Bambini-Junior V, Forgiarini LF, Pase da Rosa D, Kim LJ,
Cerski MR. Altered aquaporins in the brains of mice submitted to intermittent hypoxia model
of sleep apnea. Respir Physiol Neurobiol. 2013;185(2):217–21.
4. Kim LJ, Martinez D, Fiori CZ, Baronio D, Kretzmann NA, Barros HM. Hypomyelination,
memory impairment, and blood-brain barrier permeability in a model of sleep apnea. Brain
Res. 2015;9(1597):28–36.
84 Psychological Factors in Noninvasive Home Ventilation Users 729

5. Barnes M, McEvoy RD, Banks S, Tarquinio N, Murray CG, Vowles N, Pierce RJ. Efficacy of
positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea. Am J
Respir Crit Care Med. 2004;170(6):656–64.
6. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depres-
sion. Arch Gen Psychiatry. 1961;4:561–71.
7. McNair DM, Lorr M, Droppleman LF. POMS manual: profile of mood states. San Diego:
Educational and Industrial Testing Service; 1992.
8. Haensel A, Norman D, Natarajan L, Bardwell WA, Ancoli-Israel S, Dimsdale JE. Effect of a 2
week CPAP treatment on mood states in patients with obstructive sleep apnea: a double-blind
trial. Sleep Breath. 2007;11(4):239–44.
9. Lee IS, Bardwell W, Ancoli-Israel S, Loredo JS, Dimsdale JE. Effect of three weeks of con-
tinuous positive airway pressure treatment on mood in patients with obstructive sleep apnoea:
a randomized placebo-controlled study. Sleep Med. 2012;13(2):161–6.
10. Radloff LS. The CES-D scale: a self-report depression scale for research in the general popula-
tion. Appl Psychol Measur. 1977;1:385–401.
11. Derogatis L. BSI brief symptom inventory: administration, scoring, and procedure manual. 4th
ed. Minneapolis: National Computer Systems; 1993.
12. Carissimi A, Martinez D, Kim LJ, Fiori CZ. Factors influencing the response of psychological
symptoms to continuous positive airway pressure therapy. Sleep Breath. 2014;18(3):499–507.
13. Gold AR, Dipalo F, Gold MS, O’Hearn D. The symptoms and signs of upper airway resistance
syndrome: a link to the functional somatic syndromes. Chest. 2003;123(1):87–95.
Ambulatory Model of Noninvasive
Ventilation Adaptation: Implications 85
for Health Care, Organization,
and Outcome

Alessio Mattei, Cinzia Ferrero, and Giuseppe Tabbia

Contents
85.1 Introduction ................................................................................................................. 732
85.2 Effectiveness of HMV Ambulatory Adaptation.......................................................... 732
85.3 Requirements for Ambulatory HMV ......................................................................... 733
85.4 Adaptation to Ambulatory HMV ................................................................................ 733
85.5 Follow-Up ................................................................................................................... 734
References .............................................................................................................................. 735

Abbreviations

ABG Arterial blood gases

ALS Amyotrophic lateral sclerosis
BURR Back-up respiratory rate
COPD Chronic obstructive pulmonary disease
HMV Home mechanical ventilation
NIV Noninvasive ventilation
NMDs Neuromuscular diseases
OHS Obesity hypoventilation syndrome
PaCO2 Partial pressure of carbon dioxide in arterial blood
PEEP Positive end-expiratory pressure
PFTs Pulmonary function tests
PSG Polysomnography

A. Mattei (*) • C. Ferrero • G. Tabbia

Pulmonary Division, Cardiovascular and Thoracic Department,
Città della Salute e della Scienza, Molinette Hospital, C.so Bramante 88, Turin 10126, Italy
e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 731

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_85
732 A. Mattei et al.

PTCCO2 Transcutaneous CO2 pressure

QoL Quality of life
SpO2 Peripheral capillary oxygen saturation

85.1 Introduction

Noninvasive home mechanical ventilation (HMV) is an effective treatment for

hypercapnic respiratory failure due to restrictive thoracic diseases. It is also used in
hypercapnic respiratory failure resulting from obstructive pulmonary disease
(chronic obstructive pulmonary disease, COPD), although there is no strong evi-
dence of efficacy [1–3].
Long-term HMV improves survival and quality of life (QoL) and reduces health-
care costs. These effects are mainly due to a reduction in hospitalization for restric-
tive disorders [1, 4]. In Europe, about 6.6/100,000 inhabitants are ventilated, and
most of them initiate HMV as hospital inpatients [3]. Time spent adapting to venti-
lation in the hospital leads to a delay in starting HMV, augmented infective risk, loss
of work or study time for the patients and caregivers, increased health-care costs,
and inappropriate occupation of hospital beds [5, 6]. Although adapting to HMV in
the hospital is still considered the best approach for unstable patients, many studies
have demonstrated that, in stable patients, it is possible to start HMV as outpatients.

85.2 Effectiveness of HMV Ambulatory Adaptation

Chatwin et al. [6] carried out a study randomizing ambulatory versus hospital adap-
tation in patients with neuromuscular and chest wall disease with nocturnal
hypoventilation. They demonstrated the equivalence of the two groups for nocturnal
and diurnal arterial blood gases (ABG), ventilator compliance, health-care profes-
sional contact time, and length of hospitalization.
Pallero et al. [5] performed a similar study randomizing ambulatory versus hos-
pital adaptation in stable patients with chronic hypercapnic respiratory failure sec-
ondary to restrictive thoracic diseases, obesity hypoventilation syndrome (OHS),
and slowly progressive neuromuscular diseases (NMDs). Ambulatory adaptation
was as effective as hospital adaptation, however, its more accessible strategies
reduced waiting time for starting HMV. Ambulatory adaptation represents a cost
savings (71 % during initiation and 44 % during follow-up) and saves resources for
the population requiring hospitalization.
Lujàn et al. [7], in a prospective observational study of only 16 patients, demon-
strated the reduction in costs for ambulatory adaptation of HMV, with a cost savings
of 53 %, but did not consider costs in follow-up. The authors studied not only
patients with NMDs and OHS but also those with COPD with chronic hypercapnic
respiratory failure. They demonstrated that there was no difference in clinical effec-
tiveness or patient compliance.
85 Ambulatory Model of Noninvasive Ventilation Adaptation 733

Rabec et al. [8] proposed ambulatory initiation of HMV in stable patients with
COPD, confirming that clinical effectiveness, improvement in QoL, and adherence
to treatment are similar whether HMV is started in hospital or at home.
Sheers et al. [9] found better survival in patients with motor neuron disease in an
ambulatory model of HMV implementation. They correlated the survival advantage
in the ambulatory group to a shorter waiting period from the time of deciding to start
HMV.
Hazenberg et al. [10] showed that home initiation of HMV in patients with
chronic respiratory failure due to a neuromuscular or thoracic cage disease is as
effective as hospital initiation for gas exchange and quality of life. In addition, they
found that it is safe, technically feasible, and less expensive than hospital initiation.
However, HMV initiation at home requires a qualified team with the possibility of
home-telemonitoring.

85.3 Requirements for Ambulatory HMV

For ambulatory HMV, a pneumologist and respiratory nurses with experience in

ventilation and possibly a physiotherapist are need. It the presence of a nurse in the
role of case-manager to organize adaptation to ventilation, cough management,
maintenance of equipment, and follow-up is also beneficial. The presence of a respi-
ratory physiopathology laboratory is important, possibly integrated with the ambu-
latory ventilation, that performs pulmonary function tests (PFTs), ABG analysis,
nocturnal pulse oximetry, and nocturnal cardiorespiratory monitoring/polysomnog-
raphy (PSG). For HMV patients, it is also important to be able to perform fibrobron-
choscopy if necessary. Good infrastructure, adequate equipment, and staff able to
resolve any medical or technical problems that may arise will help to ensure the
success of HMV. The equipment needed for ambulatory HMV is in Table 85.1.

85.4 Adaptation to Ambulatory HMV

Patients who fulfill the inclusion criteria (Table 85.2) must have recently performed
PFTs, ABG analyses, and nocturnal pulse oximetry or PSG before starting ventila-
tion. Before beginning HMV, the proper and personalized interface, ventilator, and

Table 85.1 Equipment for HMV ambulatory

Wide availability of interfaces
Wide availability of various models of domiciliary ventilators for correct adaptation to the
characteristics of the patient
Possibility to use transcutaneous capnography (PTCCO2) for the monitoring of ventilation
during the adaptation and night monitoring in HMV
Built-in monitoring system to unload ventilation data (compliance, flow, pressure, leakages,
volumes, etc.) and electronic archive
734 A. Mattei et al.

Table 85.2 Inclusion and exclusion criteria for ambulatory adaptation to HMV
Inclusion criteria Exclusion criteria
Stable clinical condition Unstable clinical condition or respiratory
exacerbations
Residence in the urban area or within easy reach Living far away from the HMV ambulatory
Adequate caregiver support or sufficient degree Inadequate caregiver support and/or
of autonomy to allow daily attendance at hospital insufficient autonomy
Needs of frequent ambulatory controls

setting, including modality of ventilation, correct pressure support, positive

end-expiratory pressure (PEEP), back-up respiratory rate (BURR), and oxygen sup-
plementation, must be chosen. The patient should be monitored for peripheral oxy-
gen saturation (SpO2) and PTCCO2. After an hour from the start of NIV, an ABG
analysis should be performed. The session lasts about 2–3 h [5]. It is important to
take into account the patient’s tolerance to HMV. During the session of adaptation
to HMV, the instructions to patients and caregivers regarding the use of the ventila-
tor and interfaces are also carried out. Ventilation will be continued at home, with
the recommendation that the patient and caregiver gradually increase use of the
ventilator until reaching at least 4 h/night of ventilation.
The first ambulatory monitoring visit must be made within 30 days. During this
visit, compliance, gas exchange, and built-in monitoring of ventilation data will be
assessed. Before this visit, a nocturnal pulse oximetry or PSG during HMV should
have been executed. The objective of this visit is to ensure compliance and check
reduction of partial pressure of carbon dioxide in arterial blood (PaCO2) while
awake, increase in nocturnal saturation, and correction of nocturnal respiratory
events. If these goals are not achieved, the settings should be changed and the moni-
toring visit rescheduled. The ambulatory HMV team is responsible for prescribing
the ventilator and consumables at the end of adaptation.

85.5 Follow-Up

The follow-up should be modified according to the more or less progressive disease
of the patient and the clinical severity. It must also be based on the patient’s compli-
ance and the training of patient and caregiver. The SomnoNIV group [11] proposed
a decision flowchart for the follow-up of patients for optimizing HMV setting. They
proposed evaluating the built-in monitoring data of the ventilator, the ABGs, and
oximetry in NIV. Only if it is impossible to find solutions to the various problems in
NIV (leaks, nocturnal hypoventilation, central and/or obstructive nocturnal respira-
tory events, presence of asynchronisms) do they recommended domiciliary polyg-
raphy or PSG during NIV.
Follow-up is also useful to reinforce of patient and caregiver education, or to
change or prescribe new consumables based on the actual needs of the patient and
assessment of cough management. Above all, during follow up, any clinical insta-
bility in these patients requires accurate clinical evaluation to modify therapy if
necessary.
85 Ambulatory Model of Noninvasive Ventilation Adaptation 735

Key Recommendations
• Ambulatory adaptation of HMV is possible only in clinically stable
patients.
• Ambulatory adaptation of HMV may be carried out in all pathologies with
indication to initiate HMV.
• The presence of a case manager is important to organize adaptation to
ventilation.
• Ambulatory adaptation of HMV has efficacy equal to inpatient
adaptation.
• Ambulatory adaptation of HMV will likely reduce health-care costs.

References
1. Simonds AK, Elliott MW. Outcome of domiciliary nasal intermittent positive pressure ventila-
tion in restrictive and obstructive disorders. Thorax. 1995;50:604–9.
2. Consensus Conference. Clinical indications for noninvasive positive pressure ventilation in
chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventila-
tion – a consensus conference report. Chest. 1999;116:521–34.
3. Lloyd-Owen SJ, Donaldson GC, Ambrosino N, et al. Patterns of home mechanical ventilation
use in Europe: results from the Eurovent survey. Eur Respir J. 2005;25:1025–31.
4. Dave C, Turner A, Dretzke J, et al. Protocol for a systematic review and economic evalu-
ation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation
(NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure. Syst Rev.
2014;3:32.
5. Pallero M, Puy C, Güell R, et al. Ambulatory adaptation to noninvasive ventilation in restrictive
pulmonary disease: a randomized trial with cost assessment. Respir Med. 2014;108:1014–22.
6. Chatwin M, Nickol AH, Morrell MJ, et al. Randomised trial of inpatient versus outpatient
initiation of home mechanical ventilation in patients with nocturnal hypoventilation. Respir
Med. 2008;102:1528–35.
7. Luján M, Moreno A, Veigas C, et al. Non-invasive home mechanical ventilation: effective-
ness and efficiency of an outpatient initiation protocol compared with the standard in-hospital
model. Respir Med. 2007;101:1177–82.
8. Rabec C, Gonzalez-Bermejo J, Arnold V, et al. Mise en route d’une ventilation non invasive au
domicile: propositions du groupe de travail Casavni. Rev Mal Respir. 2010;27:874–89.
9. Sheers N, Berlowitz DJ, Rautela L, et al. Improved survival with an ambulatory model of
non-invasive ventilation implementation in motor neuron disease. Amyotroph Lateral Scler
Frontotemporal Degener. 2014;15:180–4.
10. Hazenberg A, Kerstjens HA, Prins SC, et al. Initiation of home mechanical ventila-
tion at home: a randomised controlled trial of efficacy, feasibility and costs. Respir Med.
2014;108(9):1387–95.
11. Janssens JP, Borel JC, Pépin JL. Nocturnal monitoring of home non-invasive ventilation: the
contribution of simple tools such as pulse oximetry, capnography, built-in ventilator software
and autonomic markers of sleep fragmentation. Thorax. 2011;66:438–45.
Chronic Obstructive Pulmonary Disease
and Obstructive Sleep Apnea, Known 86
as the Overlap Syndrome: Indications
for CPAP and BiPAP. Evidence and Key
Practical Recommendations

Philippe Jaoude and Ali A. El Solh

Contents
86.1 Introduction ................................................................................................................. 737
86.2 PAP Therapy in OSA and in COPD............................................................................ 738
86.3 CPAP and BiPAP in Overlap Syndrome ..................................................................... 739
86.3.1 Pulmonary Function Tests and Gas Exchange .............................................. 739
86.3.2 Exacerbations and Hospitalizations .............................................................. 740
86.3.3 Mortality ....................................................................................................... 740
86.3.4 Inflammation, Vascular Effect, and Pulmonary Hypertension...................... 742
86.3.5 Exercise and Quality of Life ......................................................................... 742
86.3.6 Other Considerations .................................................................................... 743
Conclusion ............................................................................................................................. 743
References .............................................................................................................................. 744

86.1 Introduction

Chronic obstructive pulmonary disease (COPD) is a condition that primarily affects

the lungs and is characterized by a progressive airway obstruction with ensuing air-
flow limitation. It is often associated with a variable degree of alveolar destruction and
pulmonary vasculature attrition. These pathological changes are linked to important
systemic features mediated by acute phase immune activation, leading, in some cases,

P. Jaoude, MD • A.A. El Solh (*), MD, MPH

The Veterans Affairs Western New York Healthcare System, Buffalo, NY, USA
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine,
State University of New York at Buffalo School of Medicine and Biomedical Sciences
and School of Public Health and Health Professions, Buffalo, NY, USA
Department of Social and Preventive Medicine, State University of New York at Buffalo
School of Medicine and Biomedical Sciences and School of Public Health and Health
Professions, Buffalo, NY, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 737

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_86
738 P. Jaoude and A.A. El Solh

to weight loss, malaise, and fatigue. In 1985, Flenly coined the term “overlap syn-
drome” to define the coexistence of both COPD and obstructive sleep apnea (OSA) in
a given patient. As may be intuitively expected, patients with overlap syndrome tend
to have more severe inflammation and worse cardiovascular outcomes compared with
patients with COPD or OSA alone. The daytime partial pressure of oxygen in arterial
blood (PaO2) is lower and nocturnal oxygen desaturation is greater in patients with
overlap syndrome compared with patients with OSA or COPD alone. Daytime hyper-
capnia is also more commonly observed in overlap patients [1–3]. Alveolar hypoven-
tilation is considered the prime culprit for most of the oxygen desaturation. Other
causes include decreased ventilation–perfusion matching, respiratory muscle dys-
function, and decreased end-expiratory lung volume. The presence of an additive car-
diovascular effect in overlap syndrome is reflected in an increased arterial stiffness
[4], an increased right ventricular (RV) remodeling and RV mass [5], a more prevalent
pulmonary hypertension, and a higher mortality compared with patients with COPD
or OSA only. The treatment of overlap syndrome mainly consists of treating its con-
stituents: COPD and OSA. Whereas treatment of COPD is essentially based on avoid-
ance of risk factors, along with oxygen and symptomatic therapy, positive airway
pressure (PAP) continues to be the mainstay of OSA treatment.

86.2 PAP Therapy in OSA and in COPD

Continuous positive airway pressure (CPAP) provides a constant airway pressure

throughout the respiratory cycle. It is associated with an improvement in OSA
symptoms such as snoring and excessive daytime sleepiness (EDS). There is also
evidence that the use of CPAP reduces inflammatory markers and improves endo-
thelial dysfunction in patients with OSA. Other research suggests that treatment of
OSA with CPAP may improve glucose intolerance and hypertension. Although
there are no randomized controlled trials to confirm a benefit in cardiovascular out-
comes and mortality, it has been suggested that severe untreated OSA may be asso-
ciated with increased mortality compared with treated severe or mild-to-moderate
OSA and with controls [6].
Although no outcome benefit has been shown for bi-level positive airway pres-
sure (BiPAP) compared with CPAP for treatment of OSA, BiPAP is still considered
an alternative to CPAP when OSA is associated with hypoventilation during sleep,
such as in obesity hypoventilation syndrome (OHS) or in neuromuscular disorders.
It is also considered in patients who require high PAP pressures to treat their OSA,
and who have difficulties tolerating such increased pressure [7].
The role of noninvasive positive pressure ventilation (NIPPV) in the manage-
ment of chronic respiratory failure secondary to COPD has been controversial [8].
More recent evidence, however, seems to favor a positive impact of NIPPV on out-
comes of hypercapnic patients with COPD. McEvoy and colleagues [9] randomized
144 stable hypercapnic patients with severe COPD to either long-term oxygen ther-
apy (LTOT) alone or to LTOT with noninvasive ventilation (NIV). COPD patients
who received the NIV + LTOT treatment had an improvement in adjusted mortality.
86 Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea 739

This benefit, however, was at the cost of a worsening in the quality of life. Similarly,
Windisch and colleagues [10] reported an improvement in blood gases and lung
function of patients with severe COPD and chronic hypercapnic respiratory failure
after using NIPPV. A mortality benefit was also reported compared with historical
controls. The PAP pressure used in the study, however, was very high and required
in-hospital acclimatization.

86.3 CPAP and BiPAP in Overlap Syndrome

Although there are no studies comparing BiPAP to CPAP in overlap syndrome, dif-
ferent authors have used one or the other of the two modalities in addressing the
effect of PAP on clinical outcomes.

86.3.1 Pulmonary Function Tests and Gas Exchange

Mansfield and Naughton [11] were among the first to examine the effect of CPAP in
overlap syndrome. A cohort of 10 patients with OSA and COPD who were compli-
ant with CPAP were followed for approximately 16.5 months. The average CPAP
pressure was 10.2 cmH2O with an estimated compliance of 4.8 h/night. The authors
noted an increase in the forced expiratory volume in 1 s (FEV1) from 0.96 ± 0.13 to
1.10 ± 0.13 l (p = 0.005), and an improvement in the levels of awake arterial partial
pressure of oxygen (PaO2) and of carbon dioxide (PaCO2). PaO2 increased from
54.8 ± 3.8 to 63.2 ± 1.8 mmHg (p = 0.015), and PaCO2 decreased from 58.0 ± 3.5 to
48.0 ± 2.9 mmHg (p = 0.015) on CPAP therapy.
A similar study included 55 patients, of whom 33 had hypercapnia (defined by
PaCO2 ≥45 mmHg) who were placed on appropriate CPAP based on a titration
study. After 6 months of PAP therapy, there were statistically significant increases
in PaO2, in FEV1, and forced vital capacity (FVC). There was also a statistically
significant decrease in PaCO2, in alveolar-arterial oxygen difference, and in serum
bicarbonate level. These changes were associated with a significant decrease in
body weight and body mass index (BMI). At 18 months follow-up, no further
changes were observed in body weight, arterial blood gases, or pulmonary function.
The response to CPAP was more prominent in the hypercapnic group. Although the
results of the study suggest a beneficial effect of CPAP on lung function and blood
gases in patients with overlap syndrome, these changes may have been related to
weight loss [12]. Conversely, in a retrospective study, O’Brien and Whitman [13]
reported worsening of FEV1 and FVC in patients with overlap syndrome who were
compliant with CPAP, compared with those who were not compliant with CPAP. The
results of this study could reflect a bias related to the fact that patients with most
progressive disease and symptoms may have used CPAP the most. More recently,
Toraldo et al. [16] examined the effect of PAP therapy in patients with coexistent
severe OSA (apnea hypopnea index (AHI) >30) and mild to moderate COPD. At
baseline, patients were hypercapnic, hypoxic, and obese, with a mean BMI of
740 P. Jaoude and A.A. El Solh

34.2 ± 0.2. The authors assessed different variables at baseline and at 3, 12, and 24
months after starting treatment with CPAP. The variables included pulmonary func-
tion, maximum inspiratory pressure (Pimax), arterial blood gases, and echocardio-
graphic mean pulmonary artery pressure (MPAP). Throughout the follow-up period,
the CPAP pressure was 12.67 ± 0.24, with a mean use of 5.06 ± 0.14 h/night. A sig-
nificant improvement was seen at 3 months and 12 months of CPAP therapy in
PaCO2, PaO2, MPAP, FEV1, functional residual capacity (FRC), Pimax, and
Epworth Sleepiness Scale (ESS). Whereas ESS, FEV1, and FRC continued to
improve at 24 months follow-up, the remainder of the measures remained stable
with no further improvement compared with 12 months prior.
The mechanism by which CPAP may improve pulmonary function and arterial
blood gases in patients with overlap syndrome is not fully understood. It has been
postulated that off-loading the respiratory muscles could decrease hypoventilation,
oxygen consumption, and carbon dioxide production by the respiratory muscles. By
improving upper airway irritation caused by recurrent airway collapse in OSA
patients, CPAP may improve lower airway resistance. Alternatively, CPAP may off-
set intrinsic PEEP in severe COPD [14]. The net effect may be a better respiratory
muscle function during wakefulness.

86.3.2 Exacerbations and Hospitalizations

The available data addressing the effect of CPAP on COPD exacerbations and hos-
pitalizations in patients with overlap syndrome is limited, but seems to support a
beneficial effect. In the study by Mansfield and Naughton [11], a decrease in the
number of admissions per annum was observed from 3.85 in the 4 years preceding
CPAP to 0.73 admissions per year following initiation of CPAP. The total inpatient
days was also reduced from 25.6 to 5.1 days per annum after starting CPAP. The
incidence of COPD exacerbations was reduced in those patients who were compli-
ant with CPAP treatment. This finding occurred when the baseline reports of exac-
erbation were compared with results over a 9-year monitoring period for CPAP and
non-CPAP groups. These groups were similar in many baseline characteristics
(including BMI, smoking history, alcohol use, cardiac and respiratory medications,
spirometry measurements, and AHI), and both groups received similar medical care
and medications over the course of time [15].
Similar findings were reported by Toraldo et al. [16], who noted a reduction in
the numbers of total COPD exacerbations per year, total hospital days, and in the
number of yearly outpatient visits 2 years after starting CPAP therapy in patients
with overlap syndrome.

86.3.3 Mortality

Long-term effects of CPAP treatment and particularly its effect on survival have
been reported more recently. CPAP treatment was shown to have beneficial survival
86 Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea 741

benefit, particularly in patients with moderate to severe OSA and concomitant

COPD with hypoxia.
After a median follow-up of 9.4 years (range, 3.3–12.7), Marin et al. [6] showed
a higher mortality in patients with overlap syndrome who were not treated with
CPAP compared with patients with COPD only (relative risk, 1.79; 95 % confidence
interval, 1.16–2.77). Patients with overlap syndrome treated with CPAP did not
experience an increased mortality risk and had similar mortality to the COPD-only
group. The most common cause of death in the untreated overlap patients was
related to cardiovascular events. The nonrandomized nature of the study however,
raises the issue that refusal of CPAP therapy may be a marker of noncompliance
with general medical care, which may have contributed to the higher mortality in
the untreated overlap syndrome group. The optimal prescription for CPAP was also
unclear. The issue of whether there is a true threshold for optimal CPAP use remains
unanswered by this study, as some patients had significant mortality reductions with
CPAP use <4 h/night, which has previously been suggested as a minimal level
needed for reductions in OSA morbidity. Nevertheless, recent studies have sug-
gested near-linear improvements in sleepiness and cognitive function with increas-
ing time on CPAP at night (2 versus 4 versus 6 h) [17]. This linear improvement on
CPAP has been confirmed more recently by Antic and colleagues [18].
Machado et al. [19] studied hypoxemic COPD patients who were on LTOT for
≥6 months. Hypercapnia was also present in the group. Although all subjects who
had moderate to severe OSA on polysomnography were prescribed CPAP therapy,
not all the patients were able to use CPAP. The studied population was divided into
two groups, those who used CPAP and those who did not use CPAP. The latter
group included patients who refused CPAP, those who could not afford it, and those
who were not adherent to CPAP. Adherence was defined as using CPAP ≥5 h per
night on ≥5 nights per week. During a median follow-up of 41 months (range,
6–106 months), death occurred in 39 patients (41 % mortality). The 5-year survival
estimate was 71 % (95 % confidence interval, 53–83 %) and 26 % (12–43 %) in the
CPAP-treated and non-treated groups, respectively (p < 0.01). The survival benefit
persisted even after adjusting for several confounders, including age, FEV1, and
comorbidities. Treatment with CPAP was associated with a significantly lower risk
of death (hazard ratio HR) of death versus non-treated, 0.19 (0.08–0.48)). The lack
of randomization of CPAP, and the fact that the group that did not use CPAP could
have had financial challenges, may introduce a potential source of selection bias
favoring the CPAP group.
A similar survival effect was reported by Stanchina et al. [20], who identified 227
patients with overlap syndrome, from an existing cohort database of 10,721 outpa-
tient records. Death was reported in 7.4 % of patients with overlap syndrome. In a
multivariate Cox proportional hazards analysis, only age (HR 1.14 (1.04–1.23),
p = 0.003) and CPAP nightly use (HR 0.71 [0.55–0.90], p = 0.004) were significant
predictors of mortality. Patients who used CPAP for an average 0–2 h per night had
a decreased survival compared with groups who used CPAP for more than 2 h per
night. The retrospective chart review nature of the study does not allow drawing of
definite conclusions on a mortality benefit with the use of CPAP, as it is possible that
742 P. Jaoude and A.A. El Solh

patients who used CPAP more frequently have a better compliance with the treat-
ment of other comorbidities, which may have affected their survival.
More recently, Jaoude et al. [21] examined all-cause mortality in 271 patients
with overlap syndrome who were followed for a median of 71 months. Hypercapnia
was present in 104 of the patients (PaCO2 = 51.6 ± 4.3 mmHg). Both normocapnic
and hypercapnic patients had comparable AHI and similar adherence rates to CPAP
(43 and 42 %, respectively, p = 0.9). Survival analysis revealed that hypercapnic
patients who were adherent to CPAP had reduced mortality compared with nonad-
herent hypercapnic patients (p = 0.04). In contrast, the cumulative mortality rate for
normocapnic patients was not significantly different between the adherent and the
nonadherent group (p = 0.42). The results of this study suggest that patients with
overlap syndrome who are hypercapnic may benefit the most from CPAP therapy.

86.3.4 Inflammation, Vascular Effect, and Pulmonary

Hypertension

Various inflammatory and endothelial function markers have been examined in

patients with overlap syndrome. Hypoxic and hypercapnic responses are reduced in
the affected patients. After 6 weeks of treatment with BiPAP, the hypoxic response
improved significantly but remained below normal range. In contrast to OSA
patients who had their hypercapnic response normalized after 6 weeks of BiPAP
use, there was no significant change in the hypercapnic response in patients with
overlap syndrome [22].
Inflammatory markers such as C-reactive protein (CRP) and tumor necrosis fac-
tor (TNF)-α are increased in patients with overlap syndrome, but CPAP treatment is
associated with an improvement in inflammation. The reduced inflammatory
response appears to be similar in both patients with overlap syndrome and those
with OSA only [23]. More importantly, there was an inverse relation between
increased compliance with CPAP and the levels of the inflammatory mediators.
The altered chemoresponsiveness and inflammatory response in overlap syn-
drome is thought to modify the homeostatic pathways, resulting in endothelial dys-
function. Institution of BIPAP therapy improved vascular dysfunction even after 1
month of therapy [24]. This interplay between overlap syndrome and vascular dys-
function was highlighted by Perimenis et al. [25], who studied the effect of CPAP
on erectile dysfunction (ED) in 48 men with overlap syndrome and concomitant
ED. The reported improvement of ED was noted in 25 % of patients who were
treated with CPAP.

86.3.5 Exercise and Quality of Life

There is scarce data on the effect of CPAP on exercise or quality of life. A small
study suggested that CPAP improved exercise tolerance by 17 % in patient with
overlap syndrome treated with CPAP [13]. Wang et al. [26] studied the effect of
86 Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea 743

CPAP on walking capacity in patients with COPD and patients with overlap syn-
drome. The sleep apnea in the study group was defined as an AHI >15, and the
COPD group included patients with concomitant mild OSA. Both groups were
treated with CPAP, and the incremental shuttle walking test (ISWT) was used to
determine maximal walking capacity at baseline and after 2 days of CPAP treat-
ment. Walking distance improved in both groups, but the improvement was signifi-
cantly greater in the overlap syndrome than in the COPD patients. In addition, in
patients with overlap syndrome, CPAP treatment significantly increased pre-
exercise oxygenation, and significantly decreased pre-exercise Borg scale and heart
rate. While the results are promising, the study did not address the long-term effects
of CPAP on exercise tolerance and quality of life.

86.3.6 Other Considerations

Although the American Academy of Sleep Medicine (AASM) does not consider
patients with significant lung disease as candidates for automatic CPAP titration, a
small study by Guerrero et al. [27] showed that auto-CPAP titration may be appro-
priate in OSA patients with COPD. Comparing auto-CPAP titration in two groups
of patients, one with OSA and COPD and the second with OSA only, no significant
difference was observed in the residual AHI and in the optimal pressure between the
two groups. There was, however, a significant increase in air leak in patients with
OSA and COPD. Air leak was associated with a higher percentage of the night spent
with oxygen saturation less than 90 % (CT90). Furthermore, the long-term effects
of auto-CPAP titration on patient outcome were not addressed in this study. If auto-
CPAP titration is to be used in patients with overlap syndrome, close attention
should be paid to minimizing air leak, and a follow-up on nocturnal oxygen satura-
tion should be conducted.
While NIPPV is often used to treat hospitalized patients presenting with COPD
exacerbation, and has been investigated in the treatment of stable COPD, there is no
evidence that BiPAP is superior to CPAP in treating patients with stable overlap
syndrome. Patient tolerance of either modality may, however, be affected by the
severity of the underlying COPD. Theerakittikul et al. [28] reported hyperinflation
on a chest radiograph as a marker of decreased adherence to CPAP therapy in
patients with overlap syndrome. When treating patients with overlap syndrome, the
choice of PAP treatment modality may need to take into account other factors that
could affect patients’ tolerance and adherence.

Conclusion
Overlap syndrome is associated with increased morbidity and mortality. In addi-
tion to improving OSA, treatment with CPAP or BiPAP seems to have a benefi-
cial effect on lung function and arterial blood gases. It may also improve survival
and reduce COPD exacerbations and hospitalizations. Other favorable effects
may be seen in inflammatory markers, vascular and endothelial function, pulmo-
nary artery pressure, and exercise tolerance. There is no data to favor BiPAP over
744 P. Jaoude and A.A. El Solh

CPAP in treatment of stable overlap syndrome, and the choice of PAP modality
should be based on patient’s tolerance and underlying factors such as the pres-
ence of lung hyperinflation or of hypoventilation during sleep. Future research
should address the underlying mechanism that leads to worse outcomes in
patients with overlap syndrome, compare BiPAP and CPAP in terms of effect,
tolerance, and compliance, and focus on ways to improve patients’ adherence to
PAP therapy.

Key Recommendations
• Screening for overlap syndrome should be considered in patients with
COPD, especially in the presence of worsening COPD symptoms, poor
sleep quality, or symptoms of sleep apnea (snoring, excessive daytime
sleepiness or fatigue).
• Discussion of potential benefits of PAP treatment on pulmonary function,
gas exchange, mortality, and quality of life should be incorporated in the
education process of patients with overlap syndrome.
• In-lab CPAP or BiPAP titration is the preferred modality for determining
the appropriate PAP settings. If auto-PAP titration is considered, measures
should be taken to minimize air leak, and nocturnal oxygen saturation
should be assessed once the patient is using the PAP machine.
• The choice of PAP treatment modality largely depends on the patient’s
tolerance and preference. CPAP is the standard of care. BiPAP should be
considered in patients with significant lung hyperinflation, who are not
able to tolerate CPAP, or in patients with signs of hypoventilation during
sleep.
• Patients with significant residual nocturnal oxygen desaturation on PAP
therapy, despite adequate control of apnea and hypopnea events, should
have combined nocturnal oxygen and PAP therapy.

Conflict of Interest None.

Financial Support Supported by a grant from the American Sleep Medicine Foundation (PJ) and
a Merit Review Grant (CX000478) from the Department of Veterans Affairs (AES). The views
expressed in this review do not communicate an official position of the Department of Veterans
Affairs.

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26. Wang TY, Lo YL, Lee KY, et al. Nocturnal CPAP improves walking capacity in COPD patients
with obstructive sleep apnoea. Respir Res. 2013;14:66.
27. Guerrero A, Montserrat JM, Farre R, Masa F, Duran J, Embid C. Automatic CPAP perfor-
mance in patients with sleep apnea plus COPD. COPD. 2012;9:382–9.
28. Theerakittikul T, Hatipoglu U, Aboussouan LS. Hyperinflation on chest radiograph as a
marker of low adherence to positive airway pressure therapy in the overlap syndrome. Respir
Care. 2014;59:1267–74.
Continuous Positive Airway
Pressure in Nonapneic Asthma 87
J. Navarro-Esteva and G. Juliá-Serdá

Contents
87.1 Introduction ................................................................................................................... 747
87.2 Animal Studies .............................................................................................................. 748
87.3 Human Studies .............................................................................................................. 749
87.4 Discussion ..................................................................................................................... 750
Conclusion ............................................................................................................................... 751
References ................................................................................................................................ 752

Abbreviations

AHR Airway hyperresponsiveness

ASM Airway smooth muscle
CPAP Continuous positive airway pressure
eNO Exhaled nitric oxide
FEV1 Forced expiratory volume in 1 s
PEFR Peak expiratory flow rate

87.1 Introduction

Airway smooth muscle (ASM) cells contribute in multiple ways to the pathogenesis
of asthma, including direct causation of airflow obstruction through contraction and
indirect promotion of airflow obstruction through airway remodeling and

J. Navarro-Esteva, MD (*) • G. Juliá-Serdá, MD, PhD

Department of Pulmonary Medicine, Hospital Universitario Gran Canaria “Dr. Negrín”,
Las Palmas, Spain
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 747

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_87
748 J. Navarro-Esteva and G. Juliá-Serdá

modulating airway inflammation. Each of these processes interacts with the other.
Among the contributing mechanisms to airway hyperresponsiveness (AHR), there
are increased dynamic muscle stiffness, increased vagal tone, and cytokine-potenti-
ated rises in intracellular free calcium. Studies at the micromechanic and molecular
levels have repeatedly shown that stretching reduces the tone of ASM by lowering
the number and cycling rate of cross bridges between actin and myosin filaments.
However, there are other potentially important features that play a role in airway
dynamics and include the nonlinear viscoelastic properties of the passive airway
wall structures, mechanical coupling between the ASM and extracellular matrix,
buckling of the epithelial basement membrane, and circumferential as well as radial
stress distribution in the airway wall [1, 2].
In healthy people and in a few patients with asthma there is a breathing-induced
reversal of bronchoconstriction and length adaptation likely due to perturbation in
actin-myosin interactions. In most patients with asthma, however, the ability of
deep breaths to reverse bronchoconstriction seems blunted [3]. One of the key
mechanisms regulating airway caliber is provided by the changes in lung volume
imposed by the respiratory pump. During lung inflation, airway caliber increases
because airways and lung parenchyma are mechanically interdependent [4]. In the
acute setting, there is evidence that bi-level positive airway pressure improves phys-
iological variables in patients with severe asthma attacks [5]. Likewise, in the
chronic setting, there is increasing interest in studying the effects of continuous
positive airway pressure (CPAP) on AHR and asthma control.

87.2 Animal Studies

Zue et al. [6, 7] designed several studies in rabbits, ferrets, and mice, where CPAP
versus sham CPAP was applied through a tracheostomy. In the first study, they
showed that 4 days of external mechanical strain applied to the lungs resulted in
lower AHR to acetylcholine in vivo. Decreased AHR was also observed in vitro.
In the second study, the authors found that ferrets subjected to CPAP during 14
days had increased luminal areas of intrathoracic trachea and intraparenchymal
airways and lower levels of myosin light-chain phosphorylation. These findings
could account for the decreased AHR observed in vivo. In a new study, the authors
proved that intermittent application of CPAP reduced AHR for at least 24 h. They
also showed that CPAP suppressed AHR caused by ovoalbumin-induced airway
inflammation. Two years later, the same authors showed that only 2 h of CPAP
decreased airway resistance in vitro in the following 6 h, and CPAP was associ-
ated with downregulation of Akt phosphorylation, a mediator involved in
AHR. This study led to speculation that, in humans, short application of CPAP
could improve asthma control and be more acceptable than prolonged or night-
time CPAP treatment. The same group of investigators published in an abstract
form that canine tracheal tissue stimulated with interleukin (IL)-13 produced sig-
nificantly lower levels of eotaxin measured in the media of submucosa when sub-
jected to CPAP.
87 Continuous Positive Airway Pressure in Nonapneic Asthma 749

87.3 Human Studies

Busk et al. [8] studied 16 patients with controlled mild asthma and performed base-
line and follow-up methacholine challenge after 1 week of nocturnal CPAP, set at
8–10 cmH2O. The control nonasthmatic group received sham CPAP. In the real
CPAP group, AHR was clearly decreased (2.7-fold increase in the concentration of
methacholine causing a 20 % fall in forced expiratory volume in 1 s (FEV1)). No
changes were found in FEV1 or exhaled nitric oxide (eNO), but this was not expected
since baseline FEV1 was similar in both groups (86 % vs 89 %), and the asthma
group was clinically stable from the outset. As a drawback, there are no data on
body mass index or exclusion of sleep apnea, as AHR can be potentially influenced
by those.
D’Amato et al. [9] studied 10 patients with noncontrolled severe asthma of lon-
ger than 25 years since diagnosis (mean FEV1: 68 %, mean asthma control test score
below 15). Automatic CPAP was applied during seven nights through a full face
mask. Sleep apnea was excluded by polysomnography. The primary objective of
this open unblinded pilot study was to determine the efficacy of automatic CPAP to
achieve control of symptoms, reduce PEF variability, and improve quality of life.
Measurements of lung function, asthma control, and quality of life were performed
at baseline, during the treatment period, and within 1 month from baseline. Mean
positive airway pressure applied was 5.3 ± 1.3 cmH2O. The authors found that the
variability of peak expiratory flow rate (PEFR) was reduced during treatment and
the week after – W0 and W1 (Fig. 87.1). The asthma control score also improved
significantly after automatic CPAP, mainly from decreased use of rescue beta2 ago-
nists. As limitations of this study, automatic CPAP was used instead of CPAP, and
there was no control group.
Finally, Rondinel et al. [10] found that two daily sessions of respiratory exercises
with incentive spirometry coupled to an expiratory airway pressure (EPAP) resistor

500
PEF

450

400

350

300

250

200

150

100

50

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
Days
W-2 W-1 W0 W+1 W+2

Fig. 87.1 Peak flow (individual) values measured throughout 5 weeks. CPAP was applied during
the W0 period (shown with permission from the publisher)
750 J. Navarro-Esteva and G. Juliá-Serdá

Table 87.1 Studies in humans with nonexacerbated asthma and positive airway pressure. All the
studies were carried on a limited number of patients
Study Design Intervention Results Commentary
Busk et al. Randomized Night CPAP CPAP decreases Sleep apnea not
(2013) [8] controlled 8–10 cmH2O AHR. No changes in ruled out
trial. Subjects: during 1 week. FEV1 or eNO
patients with Metacholine (expected)
mild asthma challenge, FEV1
and eNO before
and after
intervention
D’Amato Noncontrolled Night autoCPAP AutoCPAP (mean Effects of CPAP
et al. study. PEF values, 5.3 cmH2O) associated on PEFR
(2014) [9] Subjects: control of with higher PEF and beyond time of
nonapneic symptoms, and better asthma control application
patients with quality of life and reduced B2 agonist Limitation:
severe asthma before, during and use noncontrolled
after intervention study,
autoCPAP used
Rondinel Randomized Incentive EPAP titrated to Monitoring of
et al. controlled spirometry 15 cmH2O. Intervention compliance with
(2014) [10] trial. Subjects: coupled with group showed the device not
patients with EPAP. Twice daily improvement in asthma done
severe asthma sessions of 15 min control and quality of
during 5 weeks life

were associated with clinically significant improvements in asthma control and

quality of life. It was a randomized controlled trial that lasted 5 weeks on eight
patients with severely uncontrolled asthma and six controls. Although it was not
real CPAP, titration of EPAP from 5 to 15 cmH2O was performed in the intervention
group. In this case, no changes in pulmonary function were observed. As a limita-
tion of the study, objective monitoring of compliance with the device was not fea-
sible (Table 87.1).

87.4 Discussion

The available evidence suggests that CPAP may provide an effective therapy for
some patients with asthma. Even though CPAP during sleep does not seem to be a
reasonable solution for nonapneic patients with asthma, it could play a role in some
patients where the contribution of ASM to airway narrowing is uncontrolled by
pharmacological therapies. This could be the case of some obese patients with
asthma. It is known that obesity has effects on both inflammation and airway
mechanics, which might be important in asthma through the effects on airways’
smaller caliber, muscle stiffness, and hyperresponsiveness exacerbated by the
supine position. CPAP could be used as a “rescue” therapy in partially controlled or
uncontrolled asthmatics through intermittent daily and/or nightly use.
There may be also a role of CPAP to assist in inhaled therapy and achieve
a greater bronchodilation inasmuch as ventilation inhomogeneities are
87 Continuous Positive Airway Pressure in Nonapneic Asthma 751

minimized at increased lung inflation [4]. However, there are several unresolved
questions:

• It remains to be seen in humans whether application of CPAP induces reorgani-

zation of cytoskeletal and contractile proteins of ASM as well as extracellular
matrix junctions found in animal studies.
• Duration of asthma should be accounted for in future studies because airway
remodeling might blunt response to CPAP.
• Nasal intolerance is a frequent side effect occurring with CPAP, affecting as
many as 50 % of treated patients with sleep apnea. Rhinitis is common in patients
with asthma and might worsen with CPAP treatment.
• Potential interference of CPAP with sleep quality in the nonapneic patients with
asthma might be a reason for noncompliance.
• PEF or FEV1 may not be the most reliable tools to assess the effect of CPAP on
pulmonary function. They could have a role in some uncontrolled patients with
asthma, but other tools such as measures of airway resistance, namely forced
oscillometry or specific airway conductance, may be of help.
• Knowledge of the effects of CPAP in asthma’s related comorbidities, that is,
changes in inflammatory cytokines and gastroesophageal reflux, is limited.

Conclusion
Studies on induced AHR in animal models subjected to CPAP clearly indicate
that application of positive airway pressure reduces AHR and has a lasting
though limited effect. Results in human studies are hampered by the low number
of patients but also point to a therapeutic effect of CPAP in AHR, control of
symptoms, and possibly PEFR. A higher degree of evidence about the effects of
CPAP on nonapneic asthmatic patients is needed. The trial “Effect of Positive
Airway Pressure on Reducing Airway Reactivity in Patients with Asthma” is an
ongoing, 12-week, randomized multicenter study with three arms (nocturnal
sham CPAP, CPAP 5 cmH2O, CPAP 10 cmH2O) that will assess hyperrespon-
siveness to methacholine, clinical variables, and airway changes through com-
puterized tomography. The results of this study could shed light on the role of
this nonpharmacological treatment for asthma.

Key Major Recommendations

• Asthma is characterized by chronic airway inflammation and frequently
reversible bronchoconstriction, where ASM cells play a prominent role.
• In animal models, there is a consistent effect on airway function when
subjected to CPAP.
• In nonexacerbated patients with asthma, CPAP reduces the response to metha-
choline challenge and may improve control of asthma even after withdrawal.
• More studies are needed to explore both the effects of CPAP in stable
asthma and strategies for its application and tolerance.
752 J. Navarro-Esteva and G. Juliá-Serdá

References
1. Fredberg JJ, Inouye D, Miller B, et al. Airway smooth muscle, tidal stretches, and dynamically
determined contractile states. Am J Respir Crit Care Med. 1997;156:1752–9.
2. Doeing DC, Solway J. Airway smooth muscle in the pathophysiology and treatment of asthma.
J Appl Physiol. 2013;114:834–43.
3. Skloot G, Permutt S, Togias A. Airway hyperresponsiveness in asthma: a problem of limited
smooth muscle relaxation with inspiration. J Clin Invest. 1995;96:2393–403.
4. Pellegrino R, Pellegrino GM, Brusasco V. CPAP as a novel treatment for bronchial asthma? J
Appl Physiol. 2011;111:343–4.
5. Carson KV, Usmani ZA, Smith BJ. Noninvasive ventilation in acute severe asthma: current
evidence and future perspectives. Curr Opin Pulm Med. 2014;20:118–23.
6. Xue Z, Zhang L, Liu Y, Gunst SJ, Tepper RS. Chronic inflation of ferret lungs with CPAP
reduces airway smooth muscle contractility in vivo and in vitro. J Appl Physiol.
2008;104:610–5.
7. Xue Z, Yu Y, Gao H, et al. Chronic continuous positive airway pressure (CPAP) reduces air-
way reactivity in vivo in an allergen-induced rabbit model of asthma. J Appl Physiol.
2011;111:353–7.
8. Busk M, Busk N, Puntenney P, et al. Use of continuous positive airway pressure reduces air-
way reactivity in adults with asthma. Eur Respir J. 2013;41:317–22.
9. D’Amato M, Stanziola AA, de Laurentiis G, et al. Nocturnal continuous positive airway pres-
sure in severe non-apneic asthma. A pilot study. Clin Respir J. 2014;8:417–24.
10. Rondinel TZ, Corrêa IF, Hoscheidt LM, et al. Incentive spirometry combined with expiratory
positive airway pressure improves asthma control and quality of life in asthma: a randomised
controlled trial. J Asthma. 2014;2:1–7.
Chronic Heart Failure and Sleep-
Disordered Breathing: Evidence 88
for the Effect of Continuous Positive
Airway Pressure and Key Practical
Implications

Takatoshi Kasai

Contents
88.1 Introduction ................................................................................................................... 754
88.2 Pathogenesis of SDB in CHF........................................................................................ 754
88.3 Pathophysiology of SDB............................................................................................... 755
88.4 Effects of CPAP on OSA in CHF ................................................................................. 756
88.5 Effects of CPAP on CSA in CHF.................................................................................. 758
Conclusions .............................................................................................................................. 760
References ................................................................................................................................ 761

Abbreviations

AHI Apnea-hypopnea index

ASV Adaptive servo-ventilation
CANPAP Canadian Continuous Positive Airway Pressure for Treatment of
Central Sleep Apnea in Heart Failure
CHF Chronic heart failure
CPAP Continuous positive airway pressure
CSA Central sleep apnea
CSR Cheyne-Stokes respiration
LV Left ventricular
LVEF Left ventricular ejection fraction
OSA Obstructive sleep apnea
PaCO2 Arterial partial pressure of carbon dioxide

T. Kasai, MD, PhD

Cardiovascular Respiratory Sleep Medicine, Department of Cardiovascular Medicine,
Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo
113-8421, Japan
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 753

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_88
754 T. Kasai

REM Rapid eye movement

RV Right ventricular
SDB Sleep-disordered breathing
SNA Sympathetic nerve activity

88.1 Introduction

Patients with chronic heart failure (CHF) often have multiple concomitant diseases
that complicate management and may adversely affect outcomes. Sleep-disordered
breathing (SDB) is one of the common comorbidities in patients with CHF. More
than 50 % of CHF patients have SDB [1]. Two types of SDB can be seen in patients
with CHF: obstructive and central sleep apnea (OSA and CSA, respectively). OSA
results from upper airway collapse, whereas CSA arises from reductions in the cen-
tral respiratory drive in association with CHF. During OSA, the respiratory effort
generated to overcome the narrowed upper airway causes the rib cage and abdomen
to distort and move out of phase. In contrast, in CSA, respiratory movements are
absent or attenuated, but in phase. In patients with CHF, CSA usually occurs as
Cheyne-Stokes respiration (CSR), which is a form of periodic breathing character-
ized by a crescendo-decrescendo pattern of breathing followed by central apnea or
hypopnea.
In patients with CHF, SDB may worsen their condition by exposing the heart to
intermittent hypoxia, increased preload and afterload, and increased sympathetic
nervous activity (SNA), and, in fact, the coexistence of SDB is associated with a
poor prognosis [1–3]. However, clinical data suggest that treatment of SDB may
attenuate these detrimental effects [1]. Thus, SDB may be a potential therapeutic
target in patients with CHF. Continuous positive airway pressure (CPAP), which
keeps the airway open and abolishes obstructive apnea and hypopnea, can be used
for treating OSA in patients with CHF. In addition, several studies suggest that
CPAP can suppress CSA in half of patients with CHF, possibly through cardiac
unloading [4]. This chapter aims to highlight the effects of CPAP as a treatment for
SDB, either OSA or CSA, in patients with CHF, in addition to the pathogenesis and
pathophysiology of SDB. The discussion is confined to CHF due to left ventricular
(LV) systolic dysfunction.

88.2 Pathogenesis of SDB in CHF

Patients with OSA generally have a narrow pharynx related to fat accumulation in
the neck that compromises the pharyngeal lumen, to micrognathia, or to tonsillar
hypertrophy. At sleep onset, loss of pharyngeal dilator muscle tone causes complete
or partial pharyngeal collapse, causing obstructive apnea and hypopnea, respec-
tively. Fluid accumulation in nuchal and peripharyngeal soft tissues can also cause
pharyngeal narrowing and increase the likelihood of pharyngeal occlusion in
patients predisposed to OSA. In addition, fluid accumulated in the legs while upright
88 Chronic Heart Failure and Sleep-Disordered Breathing 755

during the day can shift into the neck when recumbent during sleep. Such shifted
fluid can cause edema of the peripharyngeal soft tissue that increases peripharyn-
geal tissue pressure, predisposing the patient to pharyngeal obstruction. These
mechanisms can be more prominent in patients with CHF who may be more likely
to have fluid overload [1]. A recent study, in which the craniofacial structures of
OSA patients with CHF and age-, body mass index-, and severity-matched OSA
patients without CHF were compared, found that OSA patients with CHF have
more airway space while awake and upright, but they also have a more enlarged
tongue, suggesting that an enlarged tongue may play a more prominent role in
patients with CHF than in patients without CHF, and that alterations in upper airway
condition during sleep or while recumbent may play a more prominent role in
patients with CHF than in patients without CHF [5].
CSA appears to arise secondary to CHF. Patients with CHF tend to hyperventi-
late chronically owing to stimulation of pulmonary vagal irritant receptors by pul-
monary congestion and to increased central and peripheral chemosensitivity [1].
When the arterial partial pressure of carbon dioxide (PaCO2) falls below the apnea
threshold because of an increase in the apnea threshold during the transition from
wakefulness to sleep or an acute increase in ventilation that is triggered by a spon-
taneous arousal, CSA ensues [1]. Apnea persists until the PaCO2 rises above the
apnea threshold, and then ventilation will resume and ventilatory overshoot occurs.
The PaCO2 then decreases below the apnea threshold in association with arousal
during the ventilatory phase and increased chemosensitivity, which is characteristic
of CHF patients with CSA [1]. The length of the ventilatory phase following CSA
is directly proportional to the lung-to-peripheral chemoreceptor circulation time,
and inversely proportional to cardiac output, reflecting delayed transmission of
changes in arterial blood gas tensions from the lungs to the chemoreceptors in asso-
ciation with impaired cardiac output in patients with CHF [1]. This could also con-
tribute to the pathogenesis of CSA with the CSR pattern by facilitating ventilatory
overshoot and undershoot. In addition to OSA, rostral fluid displacement from the
legs at night can contribute to the pathogenesis of CSA. Some of the fluid might be
redistributed into the lungs and cause pulmonary congestion that stimulates pulmo-
nary vagal irritant receptors to elicit reflex hyperventilation, predisposing the patient
to CSA [1].

88.3 Pathophysiology of SDB

In general, SNA, blood pressure (BP), heart rate (HR) fall and cardiac vagal activity
increase during non-rapid eye movement (non-REM) sleep, which constitutes
approximately 85 % of total sleep time [6]. In contrast, during REM sleep, intermit-
tent surges in SNA, BP, and HR occur. However, in general, REM comprises only
15 % of total sleep time, and average BP and HR remain below waking levels. Thus,
sleep is generally a state of cardiovascular quiescence [6]. SDB interrupts such car-
diovascular quiescence, such that the sufferer may not enjoy the restorative effect of
sleep.
756 T. Kasai

During obstructive apnea, negative inspiratory intrathoracic pressure generated

against the occluded pharynx increases LV transmural pressure (i.e., intracardiac
minus intrathoracic pressure) and, consequently, LV afterload. It also increases
venous return, augmenting right ventricular (RV) preload, while OSA-induced
hypoxic pulmonary vasoconstriction increases RV afterload [6]. Consequent RV
distension and leftward septal displacement during diastole impair LV filling [6].
The combination of increased LV afterload and diminished LV preload during
obstructive apneas causes a progressive reduction in stroke volume and cardiac out-
put [7]. This is a unique feature of OSA. Nevertheless, over months to years, these
stresses can contribute to the progression of CHF.
Autonomic cardiovascular dysregulation, characterized by elevated SNA and
parasympathetic withdrawal, is an important consequence of SDB, including both
OSA and CSA [1, 6]. Intermittent hypoxia induced by apnea and hypopnea, the
absence of breathing during apnea, which eliminates reflex inhibition of central
sympathetic nerve traffic arising from pulmonary stretch receptors that are activated
during normal breathing, and arousal from sleep augment SNA [1, 6]. In OSA, the
baroreceptor reflex stimulated by reductions in stroke volume and cardiac output
also augments SNA [1, 6]. Importantly, the adverse effects of SDB on the auto-
nomic nervous system are not confined to sleep, but they may persist into wakeful-
ness, although the mechanism of such daytime carryover effects remains unclear.
Nevertheless, SDB may contribute to a worse prognosis in CHF, at least partly
through autonomic dysregulation.

88.4 Effects of CPAP on OSA in CHF (Table 88.1)

CPAP is the standard treatment for OSA even in patients with CHF. As in patients
without CHF, CPAP splints the pharynx and maintains its patency, thereby prevent-
ing apnea and hypopnea. In addition, independent from treating OSA, CPAP may
have beneficial positive airway pressure effects on CHF, such as cardiac unloading.
For instance, CPAP reduces LV transmural pressure and afterload in patients with
CHF by increasing intrathoracic pressure. It also reduces LV preload and conse-
quently LV end-diastolic volume and pressure. The acute response of cardiac output
to CPAP therapy in awake patients with CHF is dependent on cardiac preload [8].
In patients with CHF and high LV filling pressure (i.e., ≥12 mmHg), CPAP of
5–10 cm H2O generally augments cardiac output, but in patients with CHF and low
LV filling pressure (i.e., <12 mmHg), it generally reduces cardiac output [8].
As an OSA treatment, in addition to the alleviation of OSA, one-night applica-
tion of CPAP caused abolition of negative intrathoracic pressure swings and reduc-
tions in nocturnal BP that caused a dramatic reduction in LV afterload that was
accompanied by a decrease in HR. [9] A recent study extended these findings by
demonstrating that treatment of OSA by CPAP reversed overnight decreases in
stroke volume and cardiac output and increases in peripheral resistance [7].
Other studies have shown that treatment of OSA by CPAP in CHF patients for
3–9 weeks improved the cardiac work metabolic index, indicating the energy-
sparing effect of CPAP [10]. In a study in which subjects were randomized to
88 Chronic Heart Failure and Sleep-Disordered Breathing 757

Table 88.1 Summary of clinical studies investigating the effects of OSA treatment by CPAP on
cardiovascular outcomes in patients with CHF
Author (year) Design Duration Outcome
Tkacova et al. (1998) [9] Self-controlled 1 night LV transmural pressure↓, systolic
BP↓, HR↓
Kasai et al. (2015) [7] Self-controlled 1 night Attenuate overnight reduction in
stroke volume and cardiac output
and overnight increase in total
peripheral resistance
Malone et al. (1991) Crossover 4 weeks LVEF↑, but ↓ 1 week after
[27] withdrawal of CPAP
Johnson et al. (2008) Pre-post 7 weeks LVEF↑, systemic vascular
[28] resistance index↓
Yoshinaga et al. (2007) Pre-post 3–9 weeks LVEF↑, trend for reduced cardiac
[10] oxidative metabolism, work
metabolic index↑
Kaneko et al. (2003) RCT 1 month LVEF↑, systolic BP↓, HR↓
[12]
Usui et al. (2005) [13] RCT 1 month MSNA↓, systolic BP↓, HR↓
Ryan et al. (2005) [29] RCT 1 month Nocturnal ventricular ectopy↓,
LVEF↑, systolic BP↓
Gliman et al. (2008) RCT 1 month HF-HRV during wakefulness↑,
[17] LVEF↑
Ruttanaumpawan et al. RCT 1 month Spontaneous BRS during
(2008) [18] wakefulness↑, LVEF↑, systolic
BP↓, HR↓
Hall et al. (2014) [11] RCT 6–8 weeks Improved myocardial
sympathetic nerve function
Mansfield et al. (2004) RCT 3 months LVEF↑, urinary norepinephrine↓,
[15] improved quality of life
Smith et al. (2006) [16] Randomized 6 weeks No differences in cardiovascular
crossover outcomes between CPAP and
sham-CPAP groups
Egea et al. (2008) [14] RCT 3 months LVEF↑
Ferrier et al. (2008) Controlled, 6 months LVEF↑, left ventricular systolic
[30] non-randomized volume↓, systolic BP↓
Wang et al. (2007) [2] Observational 2.9 years Trend for reduced mortality in
(mean) the CPAP group
Kasai et al. (2008) [19] Observational 2.1 years Lower death and hospitalization
(mean) risk in the CPAP group
BP blood pressure, BRS baroreflex sensitivity, CHF chronic heart failure, CPAP continuous posi-
tive airway pressure, HF-HRV high-frequency heart rate variability, HR heart rate, LVEF left ven-
tricular ejection fraction, MSNA muscle sympathetic nerve activity, OSA obstructive sleep apnea,
RCT randomized, controlled trial

receive either 6–8 weeks of CPAP therapy or not, cardiac positron emission
tomography-derived indices of oxidative metabolism and cardiac sympathetic nerve
presynaptic function were assessed in patients with CHF and OSA [11]. Although
significant improvement in cardiac sympathetic nerve presynaptic function was
758 T. Kasai

observed in patients randomized to CPAP, oxidative metabolism was not improved

with CPAP, probably due to the short time periods of CPAP treatment. However, it
should be noted that improvement in oxidative metabolism with CPAP was observed
in a subset of patients with more severe OSA.
In a 1-month randomized trial involving HF patients with severe OSA, fixed-
pressure CPAP increased the LV ejection fraction (LVEF) by 9 % in association
with reduced systolic BP and HR [12]. Considering that CPAP reduced sympathetic
vasoconstrictor activity [13], it was suggested that this was a mechanism by which
BP was lowered. Egea et al. [14] also reported that in 50 patients with CHF, fixed-
pressure CPAP improved the LVEF after 3 months. In a 3-month randomized trial
involving 40 patients with less severe CHF and OSA, Mansfield et al. [15] reported
that fixed-pressure CPAP reduced urinary norepinephrine concentration and
improved the LVEF and quality of life, but not BP. In another randomized trial,
Smith et al. [16] found no improvement in the LVEF in CHF patients with OSA
while on CPAP. In contrast to the previously mentioned trials, they used auto-
titrating CPAP, and they did not confirm that it eliminated OSA in a sleep study at
the end of the trial. Furthermore, short-term CPAP treatment increased high-
frequency heart rate variability and baroreflex sensitivity, indicating an increase in
parasympathetic modulation of the heart rate [17, 18].
These observations, along with the short-term beneficial effects on the LVEF and
autonomic nervous system, suggest that CPAP may have beneficial effects on long-
term clinical outcomes. In terms of long-term clinical outcomes, although there are
no randomized, controlled trials, two observational studies exist. In a study involv-
ing 218 patients with CHF, of whom 51 had OSA and an apnea-hypopnea index
(AHI) ≥15, there was a trend toward lower mortality in the 14 who accepted CPAP
therapy than in the 37 who did not (p = 0.07) over mean and maximum follow-up
periods of 2.9 and 7.3 years, respectively [2]. In another study of 88 CHF patients
with moderate to severe OSA, 65 CPAP-treated patients had significantly greater
hospitalization-free survival than 23 untreated patients over mean and maximum
follow-up periods of 2.1 and 4.8 years, respectively [19]. In the latter study, among
the 65 CPAP-treated patients, the hospitalization-free survival rate was significantly
higher in the more compliant group (N = 32), whose average nightly usage was more
than the median level (4.9 h), than in the less compliant group (N = 33), whose aver-
age nightly usage was 4.9 h or less [19].

88.5 Effects of CPAP on CSA in CHF (Table 88.2)

Because CHF patients with CSA have increased LV filling pressures, CPAP has
been used to augment cardiac output and improve hemodynamics. Indeed, some
studies showed that, in patients with CHF, CPAP suppressed CSA [8]. However, the
effects of CPAP on CSA have not been consistent. This is probably due to differ-
ences in how it is applied. When CPAP was applied acutely and at low pressure (i.e.,
5–7.5 cmH2O), CSA was not alleviated [8]. On the other hand, if CPAP were
88 Chronic Heart Failure and Sleep-Disordered Breathing 759

Table 88.2 Summary of clinical studies investigating the effects of CSA treatment by CPAP on
cardiovascular outcomes in patients with CHF
Author (year) Design Duration Outcome
Javaheri Self-controlled 1 night Ventricular ectopy↓
(2000) [31]
Davies et al. Randomized 2 weeks No differences in cardiovascular
(1993) [32] crossover outcomes between CPAP of 1.5 and
7.5 cm H2O
Naughton Controlled, 1 month PtcCO2↑, tidal volume↓ and minute
et al. (1994) non-randomized ventilation↓ during stage 2 sleep,
[20] LVEF↑, NYHA class↓
Naughton RCT 1 month Plasma and urine norepinephrine↓,
et al. (1995) LVEF↑, NYHA class↓
[21]
Takasaki Crossover 3 months LVEF↑, but ↓ 1 week after withdrawal of
et al. (1989) CPAP
[22] NYHA class↓
Naughton RCT 3 months LVEF↑, NYHA class↓, improved quality
et al. (1995) of life
[23]
Granton et al. RCT 3 months Maximal inspiratory pressure↑, LVEF↑,
(1996) [24] NYHA class↓
Tkacova et al. RCT 3 months Mitral regurgitant fraction↓, plasma
(1997) [25] atrial natriuretic peptide↓, LVEF↑,
NYHA class↓
Arzt et al. Controlled, 3 months Ventilatory efficiency during exercise
(2007) [33] non-randomized ( VE / VCO2 -slope)↓, LVEF↑
Sin et al. Subgroup analysis 2.2 years Better transplant-free survival rate in the
(2000) [26] of RCT (median) CPAP group
Bradley et al. RCT 2 years No difference in transplant-free survival
(2005) [34] (Multicenter) (mean) rate.
Plasma norepinephrine↓, LVEF↑,
distance in 6 min walk test↑ in CPAP
group.
Arzt et al. Post-hoc analysis 23 months LVEF↑, better transplant-free survival
(2007) [4] of RCT (mean) rate in patients whose AHI following
(Multicenter) CPAP was <15 compared with control
subjects. Lower death and
hospitalization risks in the CPAP group
BP blood pressure, BRS baroreflex sensitivity, CHF chronic heart failure, CPAP continuous posi-
tive airway pressure, CSA central sleep apnea, HR heart rate, LVEF left ventricular ejection frac-
tion, NYHA New York Heart Association, RCT randomized, controlled trial

gradually initiated with pressures of 8–12.5 cmH2O, the AHI was reduced by >50 %
[8]. In addition, CPAP alleviated CSA in association with an increase in the PaCO2
[20], a reduction in SNA [21], and improvements in cardiopulmonary functions,
including increases in the LVEF [22, 23], inspiratory muscle strength [24], reduc-
tions in functional mitral regurgitation, and daytime plasma atrial natriuretic peptide
760 T. Kasai

concentrations [25]. In one small randomized trial in HF patients with and without
CSA, CPAP had no effect on either the LVEF or the composite of mortality and
cardiac transplantation in those without CSA [26]. However, in those with CSA,
CPAP improved the LVEF at 3 months and showed a trend toward a reduced event
rate (p = 0.059, median follow-up period, 2.2 years). In particular, a subgroup of
patients who were compliant with CPAP had a significant reduction in the event rate
(p = 0.017).
The Canadian Continuous Positive Airway Pressure for Treatment of Central
Sleep Apnea in Heart Failure (CANPAP) trial sought to determine whether CPAP
would improve CSA, morbidity, mortality, and cardiovascular function in CHF
patients with CSA receiving contemporary medical therapy for CHF. The CANPAP
trial, which included 258 patients with CHF and CSA (130 in a control group and
128 in a CPAP-treated group), reproduced previous findings that CPAP attenuates
CSA, improves the LVEF, and lowers SNA. However, there were no significant dif-
ferences in transplant-free survival between the two groups (mean follow-up dura-
tion, 2-years). Because reversal of CSA itself appears to be one means by which
CPAP could improve cardiovascular outcomes, and as it was suggested that there
are some CHF patients whose CSA cannot be attenuated by CPAP, a post hoc analy-
sis of the CANPAP trial was carried out [4]. It suggested that patients whose AHI
was reduced below 15 by CPAP at 3 months have a significantly better transplant-
free survival rate compared with control groups. The results of the CANPAP trial do
not support routine use of CPAP for CHF, but the post hoc analysis implies the
potential for the effective suppression of CSA (i.e., AHI <15). Given this perspec-
tive, a newer type of noninvasive positive airway pressure, adaptive servo-ventilation
(ASV), which can suppress CSA more effectively than CPAP, has been the focus of
attention. A detailed description of ASV is beyond the scope of this chapter, and,
thus, it should be discussed elsewhere. Findings from the CANPAP trial also sug-
gest that if patients were successfully treated by CPAP (i.e., AHI <15), they could
show a significant improvement in transplant-free survival rate. Therefore, in CHF
patients with CSA, CPAP should be tried first, and then, if AHI ≥15 even for CPAP,
ASV may be considered.

Conclusions
In patients with CHF, OSA has adverse effects on cardiac function and could be
associated with progression of CHF, and CSA worsens the prognosis. In short-
term or non-randomized studies, treatment of SDB using CPAP appeared to have
beneficial effects on long-term outcomes in patients with CHF.
ASV, a newer type of noninvasive positive airway pressure, can more effec-
tively suppress SDB than CPAP in patients with CHF. Two ongoing, large-scale,
randomized trials investigating the effects of ASV in CHF patients with SDB on
long-term clinical events will provide further information on the SDB treatment
strategy in patients with CHF.
88 Chronic Heart Failure and Sleep-Disordered Breathing 761

Key Major Recommendations

• Because OSA is frequently observed in patients with CHF, and coexisting
OSA promotes the progression of cardiac dysfunction and increased mor-
tality through the generation of exaggerated negative intrathoracic pressure
during obstructive apnea and sympathetic nervous system overactivation,
in association with intermittent hypoxia and reoxygenation, identifying
OSA is recommended in patients with CHF.
• Because CSA is also frequently observed in patients with CHF, and coex-
isting CSA increases sympathetic nervous activity and is also associated
with an increased risk of death in patients with CHF, identifying CSA is
also recommended in patient with CHF.
• In CHF patients with OSA, abolition of OSA by CPAP improves underly-
ing cardiac dysfunction and may contribute to improvement of long-term
outcomes; therefore, CPAP therapy for OSA is recommended in CHF
patients with OSA.
• Although treatment options of CSA vary compared with OSA treatment, in
patients with CSA, CPAP can also improve underlying cardiac dysfunction
and may contribute to the improvement of long-term outcomes (if CSA is
suppressed as AHI <15). Thus, treatment of CSA by CPAP can be
considered.

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obstructive sleep apnea and left ventricular afterload in patients with heart failure. Circulation.
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on myocardial energetics in patients with heart failure and obstructive sleep apnea. J Am Coll
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 Part X
Non Invasive Ventilation in Long-Term
Applications
Long-Term Noninvasive Ventilation
Application in COPD: Determinants 89
and Lessons Learned

Nicolino Ambrosino

Contents
Conclusion ............................................................................................................................. 769
References .............................................................................................................................. 769

Chronic respiratory failure (CRF) is frequent in the end stage of the natural progres-
sion of chronic obstructive pulmonary disease (COPD). Among other factors, in
these patients, inspiratory muscle dysfunction caused by pulmonary hyperinflation
leads to ineffective alveolar ventilation, resulting in chronic hypercapnia [1]. Whether
chronic hypercapnia is adversely associated with overall prognosis is still the subject
of discussion, at least in patients on long-term oxygen therapy (LTOT) [2].
Long-term noninvasive positive pressure ventilation (NPPV) is well established
and increasingly used in patients with CRF cause by restrictive thoracic (RTD) and
neuromuscular diseases (NMD) as well as in those with obesity hypoventilation
syndrome. There is evidence that in COPD patients with chronic hypercapnia, long-
term (nighttime) NPPV may improve physiological and clinical parameters such as
daily arterial blood gases, exercise capacity, and, with conflicting results, health-
related quality of life (HRQL) when evaluated with appropriate questionnaires [3,
4]. Furthermore, it has been reported that, in these patients, compared with LTOT
alone, addition of long-term NPPV is associated with fewer hospital admissions [3]
and lower overall treatment costs [5]. Nevertheless, the role of NPPV in improving
survival in COPD patients with CRF remains uncertain [6].
As shown by a one meta-analysis [7], most of the earlier and more recent large
randomized controlled trials (RCTs) of addition of NPPV to LTOT did not show any
substantial improvement in survival compared with LTOT alone [3, 7, 8]. Although

N. Ambrosino
Auxilium Vitae, Volterra, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 767

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_89
768 N. Ambrosino

the small sample size of the evaluated studies prevents definite conclusions, in the
meta-analysis [7], nighttime home NPPV for at least 3 months in stable hypercapnic
patients with COPD showed no consistent clinically or statistically significant effect
on arterial blood gases, exercise tolerance, HRQL, lung function, respiratory mus-
cle function, or sleep efficiency. One RCT showed a small significant survival ben-
efit, which, however, was associated with worsening in HRQL [4].
The “negative” results in survival benefit reported by these studies have been
challenged by a German RCT and ascribed to the applied inspiratory pressures that
were considered “low” and, as such, unable to improve hypercapnia [9]. This one-
year randomized, prospective, multicenter RCT of NPPV addition to standard treat-
ment versus standard treatment alone was performed over many years in patients
with stable GOLD (Global Initiative on Obstructive Lung Disease) stage IV COPD
and daytime carbon dioxide tension (PaCO2) of 51.9 mmHg or higher. NPPV was
targeted to reduce baseline PaCO2 by at least 20 % or to achieve PaCO2 values lower
than 48.1 mmHg. One-year mortality was 12 % in the intervention group and 33 %
in the control group. The authors concluded that the addition of long-term NPPV to
standard treatment improves survival of patients with hypercapnic, stable COPD
when inspiratory pressure is targeted to greatly reduce hypercapnia [9].
The results of the study [9] differ from those of another study [8] that has inves-
tigated whether nighttime home NPPV in patients admitted to hospital for acute
respiratory failure (ARF) prolongs the time to readmission for respiratory causes or
death in the following 12 months. Although daytime PaCO2 was significantly
improved in NPPV versus standard treatment alone, as was night transcutaneous
PCO2, 1 year after discharge, 65 % of patients treated with NPPV versus 64 % of
patients in standard treatment were readmitted to hospital for respiratory causes or
had died, and time to event was not different. Furthermore, the number of exacerba-
tions, lung function, mood state, daily activity, and severity or dyspnea were not
significantly different. Only HRQL showed a trend in favor of NPPV. Therefore,
these authors could not demonstrate any improvement in time to readmission or
death by adding NPPV for 1 year in COPD patients with prolonged hypercapnia
after an episode of ARF treated with NPPV. This author agrees with these investiga-
tors that there is no reason to believe the NPPV was not effective, inasmuch as
daytime PaCO2 and nighttime PCO2 improved.
These two studies are conflicting. It seems that, despite the effectiveness in
reducing daytime PaCO2 and transcutaneous nighttime PCO2 in one study [8],
NPPV was unable to improve prognosis of these patients. In addition, the other
study [3] was unable to improve 2-year survival, despite the ability to improve day-
time PaCO2 (while breathing oxygen), and HRQL and to reduce readmissions.
Therefore, it is not probable that differences in 1-year survival between the German
study and the others is the result of the claimed “high inspiratory pressures” applied
or whatever ability to reduce PaCO2 levels was obtained in that study [9].
Furthermore, the control population of the German study suffered from a high mor-
tality rate, which was significantly higher than in population also treated with NPPV
[9]. This may indicate that severity of the patients’ disease rather than correction of
hypercapnia or any other supposed effect of “high inspiratory pressures” may be the
89 Long-Term Noninvasive Ventilation in COPD 769

reason for differences in survival in patients treated with NPPV in different studies.
The claim that chronic hypercapnia is associated with worse survival is question-
able, at least in the patients undergoing oxygen therapy [2], and should be evaluated
with specific studies. Furthermore, there is growing evidence that mortality of
patients with COPD is related to many other factors, such as exercise capacity,
comorbidities, and inflammatory status [10].

Conclusion
NPPV may reduce readmissions and, with less evidence, mortality in patients
with COPD after acute hypercapnic respiratory failure. The question of when to
select patients with prolonged hypercapnia needs further assessment. Once sta-
ble hypercapnia is proven, NPPV may improve survival and, again, with less
evidence, HRQL. As a consequence, in spite of studies that have added to the
comprehension of the role of long-term NPPV, this author believes that there is
not enough evidence for a widespread generalized use of this therapeutic
approach in stable hypercapnic patients with COPD. This modality should be
reserved for individual cases.

Key Points
• Chronic respiratory failure is frequently in the final stage of the natural
progression of COPD.
• Whether chronic hypercapnia is adversely associated with overall progno-
sis remains uncertain.
• The role of long-NPPV in improving survival in COPD patients with CRF
is still under discussion.
• Long-term nighttime noninvasive ventilation in these patients has some
physiological and clinical benefits.
• Long-term noninvasive ventilation should be reserved for individual
patients.

References
1. Ambrosino N, Guarracino F. Respiratory failure. In: Palange P, Simonds AK, editors. ERS
handbook of respiratory medicine. 2nd ed. Sheffield: ERS; 2013. p. 162–5.
2. Aida A, Miyamoto K, Nishimura M, et al. Prognostic value of hypercapnia in patients with
chronic respiratory failure during long-term oxygen therapy. Am J Respir Crit Care Med.
1998;158:188–93.
3. Clini E, Sturani C, Rossi A, et al. The Italian multicentre study on noninvasive ventilation in
chronic obstructive pulmonary disease patients. Eur Respir J. 2002;20:529–38.
4. McEvoy RD, Pierce RJ, Hillman D, et al. Nocturnal non-invasive nasal ventilation in stable
hypercapnic COPD: a randomized controlled trial. Thorax. 2009;64:561–6.
5. Clini EM, Magni G, Crisafulli E, et al. Home non-invasive mechanical ventilation and long-
term oxygen therapy in stable hypercapnic chronic obstructive pulmonary disease patients:
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770 N. Ambrosino

6. Ambrosino N. The history of home ventilation: what have we learned? The Buyer’s guide.
2014–2015, 31–4.
7. Struik FM, Lacasse Y, Goldstein R, et al. Nocturnal non-invasive positive pressure ventilation
for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev.
2013;(6):CD002878.
8. Struik FM, Sprooten RT, Kerstjens HA, et al. Nocturnal non-invasive ventilation in COPD
patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a
randomised, controlled, parallel-group study. Thorax. 2014;69:826–34.
9. Köhnlein T, Windisch W, Köhler D, et al. Non-invasive positive pressure ventilation for the
treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre,
randomised, controlled clinical trial. Lancet Respir Med. 2014;2:698–705.
10. Stolz D, Meyer A, Rakic J, et al. Mortality risk prediction in COPD by a prognostic biomarker
panel. Eur Respir J. 2014;44:1557–70.
Long-Term Noninvasive Ventilation
Among Chronic Respiratory Failure 90
Diseases (Cystic Fibrosis and Other
Diseases) Awaiting Lung
Transplantation: Key Determinants
and Practical Implications

Ana Souto Alonso, Pedro Jorge Marcos Rodriguez,

and Carlos J. Egea Santaolalla

Contents
90.1 Introduction ................................................................................................................. 771
90.2 Long-Term NIV in Patients with Chronic Respiratory Failure Diseases
Awaiting Lung Transplantation................................................................................... 773
90.2.1 Cystic Fibrosis ............................................................................................... 773
90.2.2 COPD ............................................................................................................ 775
90.2.3 NIV Modalities and Operating Procedures ................................................... 776
90.2.4 Advantages of NIV........................................................................................ 777
Conclusion ............................................................................................................................. 778
References .............................................................................................................................. 778

90.1 Introduction

Lung transplant prevalence continues to increase in spite of the recent advances

that have been made in the knowledge and treatment of lung diseases in recent
years. Today, it is a therapeutic option for patients with end-stage lung disease with
poor prognosis in 2 year’s time to improve their chance of survival and quality of
life.

A. Souto Alonso (*) • P.J. Marcos Rodriguez

Respiratory Service, Instituto de Investigación Biomédica de A Coruña (INIBIC),
Complejo Hospitalario Universitario de A Coruña (CHUAC), Sergas,
Universidade da Coruña (UDC), Corunna, Spain
e-mail: [email protected]
C.J. Egea Santaolalla
Sleep Unit, Araba University Hospital, Basque Country University, School of Medicine,
Ciberes, BioaAraba Project, Vitoria-Gasteiz, Spain

© Springer International Publishing Switzerland 2016 771

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_90
772 A. Souto Alonso et al.

In Spain in 2014, according to the National Transplantation Office Annual

Report [1], interstitial lung disease (ILD, 38 %), chronic obstructive pulmonary
disease (COPD, 35 %), and cystic fibrosis (CF, 11 %) are the three most frequent
principal diagnoses among patients awaiting lung transplantation. Other indications
include bronchiectasis, pulmonary hypertension, and retransplantation [1]. This dis-
tribution is similar in the international registry [2].
It is important to highlight the difference between the time the patient is referred
to evaluation by the multidisciplinary transplantation team and the time to be placed
to wait for lung transplantation [3, 4]. There are national and international consen-
sus recommendations to manage this situation, and we must acknowledge that the
decision to include a patient on the waiting list for lung transplant is complex and
involves taking into account specific program and regional factors that affect such a
decision [3, 4].
In 2014, 262 patients out of 601 listed underwent lung transplantation in Spain
[1]. The average and median number of days spent on the waiting list were 241
(standard deviation (SD) 221) and 178 (range 75–329), respectively. The waiting
list global mortality rate was 3.9 %. Nearly 1 out of 10 transplantation procedures
was under emergency code, and the most common diseases were ILD (45 %) and
CF (28 %). Mortality under emergency code has remained between 6 and 11 % dur-
ing the past few years.
Although every country has its own transplant waiting list management system,
territorial distribution criteria together with severity index and anthropometric fea-
tures are taken into account for most of them. The Lung Allocation Score (LAS) is
a statistical model used in some countries that considers both urgency and post-
transplant survival and prioritizes listing and transplantation for high risk patients.
The treatment of symptomatic chronic respiratory failure (CRF) continues to be
the cornerstone of the management of critically ill patients, and noninvasive ventila-
tion (NIV) is the key element to its success. Initially, it was used as a bridge to lung
transplantation strategy instead of invasive mechanical ventilation [5]. Gradually, its
use has adopted a long-term view with the aim of stabilizing critically ill patients to
improve access to lung transplantation as pre-transplant life expectancy increases,
and to improve the probability of success as the patient undergoes surgery in better
condition [3, 6–8]. Currently, the need for ventilatory support is an element of sever-
ity to be assessed while the patient is being evaluated to be a lung transplant candi-
date, and it is not considered as a contraindication [3, 4]. Nor does it bias the
prioritization scales used in some countries. What determines a change in consider-
ation and in priority is the beginning of invasive ventilation.
In spite of the spread of its use, the scientific evidence that supports long-term
NIV for patients awaiting lung transplantation relies on observational studies. This
is due to the ethical difficulty of designing a randomized trial for these patients.
This chapter reviews the most representative studies of long-term NIV within this
context.
90 Long-Term NIV Among CRF Diseases Awaiting Lung Transplant 773

90.2 Long-Term NIV in Patients with Chronic Respiratory

Failure Diseases Awaiting Lung Transplantation

The long-term NIV approach for patients on a waiting list lung for transplantation
is a situation that is mainly seen in patients with CF and COPD, as it is irrelevant to
the pathogenesis and course of lung interstitial and vascular diseases. The role of
invasive and noninvasive ventilation for CF patients was initially evaluated as a
bridge to lung transplantation in patients with respiratory failure and severe
advanced disease. It was then considered as a treatment option for respiratory fail-
ure in very advanced disease, irrespective of the patient’s status as a lung transplant
candidate. The difficulty of not having randomized studies means that the scientific
evidence for this approach is based on observational series alone. There are no data
about short-term NIV or treating exacerbations. There are no clinical guidelines for
how to start and adapt ventilation in these patients. Each team has its own program
based on the available evidence and on its proven experience.
The highest level of evidence to support the use of NIV is achieved in the treat-
ment of COPD patients with hypercapnic respiratory failure exacerbation. Benefits
in survival, less orotracheal intubation (OTI), and hospital length of stay have been
proven. However, its role in respiratory failure outside the context of an exacerba-
tion scenario is more controversial. Nevertheless, after several scientific studies
there is favorable evidence for its use in a group of patients with stable hypercapnic
chronic respiratory failure. We have not found any specific studies about long-term
NIV in COPD designed in the lung transplant context.

90.2.1 Cystic Fibrosis

Pulmonary alteration in patients with CF is characterized by bronchiectasis that

damages lung parenchyma and by progressive bronchial obstruction due to bron-
chial wall inflammation and mucous plugs. Hart et al. [9] observed that, in children
and young adults with CF and stable advanced lung disease, there was a correlation
between forced expiratory volume in 1 s (FEV1) fall and muscle respiratory load
rise. As a result, these patients develop a compensatory mechanism of rapid shallow
breathing pattern. Although this respiratory strategy succeeds in maintaining the
level of ventilation, pCO2 eventually increases, and the efficiency of the respiratory
muscle pump in eliminating CO2 diminishes. Supportive treatment with NIV allevi-
ates the muscle respiratory load and, therefore, respiratory muscle performance can
be preserved. Despite this physiopathological basis, more studies are required to
determine for whom, when, and how this therapy is proven to be beneficial.
In 2002, Madden et al. [6] produced the first and most extensive retrospective
report on 113 patients with end-stage CF receiving nasal ventilation. Indication for
ventilatory support was established when clinical condition and arterial blood gases
where judged to be a severe risk to survival. They studied 23 non-transplant candi-
dates and 90 patients who were either waiting for or being evaluated for a lung
774 A. Souto Alonso et al.

transplant. They looked after most patients on a general ward or at home. The mean
duration of NIV support was 61 days (range 1–600) for those on the lung transplant
waiting list, 53 days (range 1–279) for patients under evaluation and 45 days (range
0–379) among those patients who were not being considered for a lung transplant.
They described their experience in treating respiratory failure until transplantation
with NIV for advanced patients who are actually on the lung transplant waiting list
or being evaluated for it. They also recommend caution in its use among non-
candidate patients as it may unnecessarily delay the inevitable and prolong
suffering.
There are few references to long-term NIV therapy. This chapter focuses on two
more recent works. One is a French study based on the analysis of data from the CF
National Register Centre, and the second is an English study that reviewed 20 years
of clinical practice in a lung transplant center with a multidisciplinary team.
The aim of the study of Faroux et al. [7] was to evaluate the respiratory function
of patients with CF following 1 year of NIV. The study selected 41 out of 89 patients
who had initiated long-term NIV between 1999 and 2001 and had been monitored
during the following 2 years. Reasons for exclusion were lung transplantation,
death, no match available, and lack of follow-up. For each ventilated patient, a con-
trol match from the same center was included. They were comparable in terms of
age, anthropometric data, lung function (±10 % of pred%FEV1 (percentage of pre-
dicted value)), genotype, and equal follow-up period. Anthropometric data, lung
function, gas analyses, antibiotic prescription, inhaled and oral corticosteroid ther-
apy, insulin treatment, nutritional support, and oxygen therapy were compared
between both groups through 3 years of study. Initiation of NIV was based on func-
tional and clinical signs that reflected an accelerated decline of respiratory status,
with moderate hypercapnia at the beginning of therapy. Ventilated patients experi-
enced during the previous year of NIV a greater decline in pulmonary function than
the control group patients. After 1 year of NIV, the reduction in pulmonary function
was comparable in both groups. Thus, data has shown that long-term NIV was
related to the stabilization of pulmonary function in patients with advanced
CF. Nevertheless, the authors pointed out that in the year when treatment was initi-
ated and in the previous year, ventilated patients were treated in a more intensive
way and had received intravenous antibiotic for more days and were prescribed
nutritional support and oxygen more frequently, and this may have contributed to
their stabilization. The study was not designed to assess survival and the authors
mention that more studies with a larger number of patients and a longer follow up
period are needed.
Flight et al. [8] analyzed the data of all domiciliary NIV prescriptions in patients
with CF in their center between 1991 and 2010. Out of 47 patients, 10 had started
NIV between 1991 and 2000, and 37 since 2001. The average length of NIV was 16
months (range 2–90). Twenty-four (51 %) patients were on the lung transplant wait-
ing list while they were on NIV. Predicted %FEV1 was significantly lower in the 17
patients who underwent lung transplantation than in those who died while on NIV
(17.1 % vs 24.9 %; p = 0.0015). Nine out of 10 patients received pressure mode
(either spontaneous or controlled) and all of them used a nasal mask. Persistent
90 Long-Term NIV Among CRF Diseases Awaiting Lung Transplant 775

diurnal hypercapnia and/or inability to maintain oxygenation in a safe way with

available devices were the NIV starting criteria. The authors found a variable
response among patients, where those with more rapid decline suffering from the
most severe level of disease and the worst lung function were more likely to respond.
The main limitations of the study were related to its retrospective design, its limited
number of patients, and the absence of a control group, meaning that their results
cannot being generalized to the whole CF population. Considering the results and
the limitations of the study, they also suggest that NIV might slow down or even
reverse the decline of lung function in adults with advanced CF. Compared with the
previous year, and because every patient received the same intensive therapy for
their respiratory failure (physiotherapy, antibiotics, nebulized medication, diabetes
treatment, and nutritional support), and this care was maintained throughout the
years, the authors suggest that the improvement in pulmonary function is related to
the use of NIV. However, they highlighted the need for extensive multicenter pro-
spective studies to clarify the effects of NIV in CF and to determine the optimal
starting time.

90.2.2 COPD

COPD is the most frequent indication for lung transplantation worldwide [2].
However, it is still challenging to define which patients benefit from it and to define
the most accurate procedure time. Therefore, it is essential for these patients to be
evaluated within the framework of a multidisciplinary lung transplant program.
The main goal of transplantation is to increase survival rates and improve quality
of life. Thus, short- or medium-term survival probability supports the candidate
selection to referral and waiting list placing criteria. Tools such as the BODE (for
Body-mass index, airflow Obstruction, Dyspnea, and Exercise) score have been
developed to assess prognosis in COPD patients [10]. Despite not being designed in
the lung transplant setting, it has been used to guide the referral and listing time
[3, 4]. It is recommended that patients with BODE >5 should be referred to be
evaluated, and those with BODE >7 and holding another circumstance that affects
prognosis will be placed on the waiting list. These situations include any acute
hypercapnic exacerbation that needs hospital admission [3, 4]. Patients with BODE
between 7 and 10 have a 52-month overall mortality of 80 % [10], and a 2-year
survival after hospitalization for acute hypercapnic exacerbation of 49 % [11]. In
contrast, overall survival after transplantation from COPD is 5.5 years [2].
The worldwide utilization of NIV to treat hypercapnic respiratory failure in the
context of COPD exacerbation is based on strong scientific evidence that it is proven
to decrease mortality rates, OTI need, and hospital admission length [12, 13]. To
date, this level of evidence does not exist with regard to its use in hypercapnic stable
patients. However, some recent studies have shown beneficial effects that have led to
the inclusion of some suggestions in current clinical practice guidelines, such as the
one from the National Institute for Health and Care Excellence (NICE) [14]. Referral
to a specialized center is recommended for COPD patients with hypercapnic chronic
776 A. Souto Alonso et al.

respiratory failure disease who had ventilatory support during an exacerbation or

have hypercapnia or acidosis with long-term oxygen therapy (LTOT) [14].
In the latest Global Strategy for Diagnosis, Management and Prevention of
COPD update, the wide use of NIV in patients with stable, very severe COPD is
acknowledged [13]. The authors report that, in a subset of patients with pro-
nounced daytime hypercapnia, the combination of NIV and LTOT may be of some
use, although they also say that there is not sufficient evidence to make a
recommendation.
Patients with very severe disease for whom acute or chronic hypercapnia might
mean their inclusion on the lung transplant waiting list may be treated with NIV in
an attempt to decrease premature mortality and to increase transplantation survival.

90.2.3 NIV Modalities and Operating Procedures

NIV is a sign that objectively denotes the gravity of the disease. Therefore, the
sooner patients and their family have information about the possibility of starting
the therapy in the near future the better. This could occur in an acute exacerbation
context or it could be planned when the clinical condition recommends it. Sometimes,
in poor prognosis cases, if the transplant is not carried out in the short term, the line
between curative and palliative intention becomes blurred. So, patients must be sup-
ported throughout the whole process to decide on the measures they may want to
adopt.
Successful NIV requires that patients are appropriately selected and informed,
and that the selection of the kind of ventilation, interface, and accessories is suitable
for their specific clinical condition. Most of the studies refer to using nasal masks,
which usually interfere less with speech and oral intake, induce less gastric disten-
sion, and allow coughing and expectoration. In any case, different types of inter-
faces should be available to provide comfort and meet each patient’s needs, as these
will enhance long-term ventilation compliance.
Although most of the studies and series have used spontaneous or controlled
positive pressure ventilators, it is important to take into account that it may be nec-
essary to use another kind of respiratory support for a given patient. In addition, this
may vary over the months or years, thus close follow-up and monitoring is required.
It is crucial to establish the treatment goals at each stage, and to consider that
equipment with other functions might be needed. One must be prepared to deal with
different types of asynchrony that might be associated with the trigger sensitivity
and the respiratory cycling time, which may vary among different devices. If venti-
latory support is required for at least 16 h, it is recommended to have a backup
machine and an independent energy supply as well. In addition, the use of an appro-
priate humidification system in these patients is a valuable way to prevent the
adverse effects of cold, dry air in the epithelial wall [15].
It is essential that the starting clinical environment is adequate, usually in a hos-
pital ward, with a highly specialized team composed of doctors, nurses, and physio-
therapists with professional skills in the management of ventilation for these
90 Long-Term NIV Among CRF Diseases Awaiting Lung Transplant 777

patients. The standard operating procedure must include how to succeed in adapting
to NIV, the patient’s education, and the monitoring process. One fundamental aspect
that provides the guarantee of receiving adequate health care is the availability of
access to this professional team around the clock, 365 days of the year, if any
changes or decline occurs.

90.2.3.1 Clinical Key Points When Employing NIMV on These

Patients
It is preferable to start this therapy in an inpatient setting. However, if close moni-
toring and safety concerns can be addressed, an outpatient controlled initiation and
titration of NIV is possible When considering NIV, even in the clinically stable
patient, it is important to assess a very recent chest radiograph to identify any con-
traindications to ventilation (e.g., pneumothorax).
Initially, short daytime trials that increase gradually in duration are implemented
so that the patient becomes accustomed to the machine and the interface. Experienced
personnel should adjust the interface to assure a good seal with minimal air leakage,
which is necessary to achieve effective ventilation and to assure the well-being of
the patient and improve compliance. A nasal mask is usually tried first because it is
generally well tolerated. Oral-nasal masks are useful for patients who have exces-
sive oral air leaks or poorly fitting nasal masks, though it should be used with cau-
tion among patients with either high sputum volume or needs for intensive chest
physiotherapy, such as patients with CF.

90.2.4 Advantages of NIV

Although NIV has the drawbacks of an unprotected airway and it provides no

access for tracheal suction, we believe that the advantages outweigh the disadvan-
tages. When the patient is not ill enough to require special monitoring or treatment,
the use of NIV facilitates handling the patient outside the intensive care unit in a
regular ward, a respiratory care unit, or even at home, becomes a cost-effective
solution.
With NIV, patients are able to communicate, eat, be active during chest physio-
therapy and have their nutrition and general physical condition optimized while
receiving this treatment. Depending on patient condition, NIV will be applied in a
wide range of situations, from continuously, in more severe cases, to only at night
for nocturnal hypoventilation.
For selected patients, NIV provides a useful but limited period of extra time in
which suitable donor organs may be found. Moreover, it may also reduce the risk of
infection and ischemia of the airway after transplantation, classically associated
with patients under invasive mechanical ventilation.
Some patients will require NIV after lung transplantation, mainly after extuba-
tion, and so the employment of this treatment before the surgical procedure may
help the patient to become familiarized with it and to tolerate it better because NIV
is usually well tolerated when it is reintroduced [6].
778 A. Souto Alonso et al.

Conclusion
NIV appears to be a safe option for managing patients with hypercapnic respira-
tory failure awaiting lung transplantation. Most of the data comes from observa-
tional isolated experiences. In this context, although we understand that there are
ethical difficulties in carrying out randomized studies that could bring scientific
evidence to support the use of pretransplant NIV, more specific designed studies
are needed to determine in which circumstances and to which patients this ther-
apy should be offered.
An common international approaching procedure needs to be defined. This
should incorporate the evaluation and the positioning of all therapies that have
been developed so far to manage hypercapnic respiratory failure, such as extra-
corporeal lung assistance and NIV.

Key Recommendations
• NIV for candidates for a lung transplant allows them to avoid invasive
mechanical ventilation and increases the probability of receiving an organ
under optimal conditions.
• Long-term domiciliary NIV may be considered for COPD patients with
chronic hypercapnic respiratory failure who experience progressive desta-
bilization despite optimal non-ventilatory treatment and after a first hyper-
capnic exacerbation while awaiting lung transplantation.
• NIV is now an established treatment for CF patients with respiratory fail-
ure and plays a role in maintaining lung health while awaiting lung
transplantation.
• Most of the evidence for NIV effectiveness for patients with COPD or CF
awaiting lung transplantation comes from observational retrospective
studies.
• Extensive multicenter prospective studies are necessary to clarify the role
of NIV for patients with CF and COPD and to determine its optimum start-
ing time.

References
1. Organización Nacional de Trasplante. Memoria de actividad donación y trasplante pulmonar.
España. 2014.
2. Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, for the International
Society for Heart and Lung Transplantation. The Registry of the International Society for
Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report – 2014;
focus theme: retransplantation. J Heart Lung Transplant. 2014;33:1009–24.
3. Weill D, Benden C, Corris PA, Davies RD, et al. A consensus document for the selection of
lung transplant candidates: 2014 – an update from the Pulmonary Transplantation Council of
the International Society for Heart and Lung Transplantation. J Heart Lung Transplant.
2015;34:1–15.
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4. Roman A, Ussetti P, Solé A, Zurbano F, Borro JM, et al.; Normativa SEPAR. Normativa para
la selección de pacientes candidatos a trasplante pulmonar. Arch Bronconeumol.
2011;47(6):303–9.
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tilation for cystic fibrosis patients – a potential bridge to transplantation. Eur Respir J.
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6. Madden BP, Kariyawasam H, Siddiqi AJ, Machin A, et al. Noninvasive ventilation in cystic
fibrosis patients with acute or chronic respiratory failure. Eur Respir J. 2002;19:310–3.
7. Flight WG, Shaw J, Johnson S, Webb AK, et al. Long-term non-invasive ventilation in cystic
fibrosis – experience over two decades. J Cyst Fibros. 2012;11:187–92.
8. Faroux B, Le Roux E, Ravilly S, Bellis G, Clément A. Long-term noninvasive ventilation in
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ing disease severity in children and young adults with cystic fibrosis. Am J Respir Crit Care
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2004;350:1005–12.
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chronic obstructive pulmonary disease. N Engl J Med. 1995;333:817–22.
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Home Mechanical Ventilation
and Quality of Life in Neuromuscular 91
Patients During Noninvasive Mechanical
Ventilation: New Trends and Key
Practical Topics

Catarina Ferreira and Joaquim Moita

Contents
91.1 Introduction ................................................................................................................. 782
91.2 Discussion and Analysis Main Topic .......................................................................... 782
91.2.1 Chronic Respiratory Failure in Neuromuscular Diseases ............................. 783
91.2.2 Home Noninvasive Mechanical Ventilation in Patients with
Neuromuscular Disease ................................................................................. 784
91.2.3 NIV Versus Tracheostomy Ventilation .......................................................... 785
91.2.4 Duchenne Muscular Dystrophy..................................................................... 785
91.2.5 Amyotrophic Lateral Sclerosis ...................................................................... 786
91.2.6 Starting Home Mechanical Ventilation ......................................................... 787
91.2.7 Ventilators...................................................................................................... 787
91.2.8 Interfaces ....................................................................................................... 788
Conclusion ............................................................................................................................. 789
References .............................................................................................................................. 789

Abbreviations

ALS Amyotrophic lateral sclerosis

CO2 Carbon dioxide
DMD Duchenne muscular disease
FVC Forced vital capacity
NIV Noninvasive ventilation
NMD Neuromuscular disease
PaCO2 Partial pressure of carbon dioxide

C. Ferreira (*) • J. Moita

Pulmonology Department, Centro Hospitalar e Universitário de Coimbra – Hospital Geral,
Coimbra, Portugal
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 781

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_91
782 C. Ferreira and J. Moita

PaO2 Partial pressure of oxygen

PCF Peak cough flow
PEG Percutaneous endoscopy gastrostomy
PSG Polysomnography
REM Rapid eye movement
SpO2 Peripheral oxygen saturation
VC Vital capacity

91.1 Introduction

The neuromuscular respiratory system is divided into three main areas of function:
ventilator function determined predominantly by the inspiratory muscles; cough
function determined by inspiratory, expiratory, and bulbar muscles; and swallowing
and airway protection determined by glottic muscles [1]. Many chronic neuromus-
cular disorders (NMD) lead to progressive respiratory muscle dysfunction, which in
turn can lead to respiratory failure and death. When and how to ventilate these
patients are relevant issues in the evaluation and monitoring of neuromuscular dis-
ease. The answers are based on the knowledge of the natural history of respiratory
failure that in neuromuscular disease has specific contours [2].

91.2 Discussion and Analysis Main Topic

Patients with neuromuscular diseases can have rapidly progressive disease with
muscle impairment that worsens over months and results in death within a few
years, such as amyotrophic lateral sclerosis (ALS) and some forms of spinal muscu-
lar atrophy. Duchenne muscular disease (DMD) is considered a relatively rapidly
progressive NMD, resulting in muscle impairment within a few years and death in
young adulthood. Other myopathies, such as Becker muscular dystrophy, facioscapu-
lohumeral muscular dystrophy, limb-girdle muscular dystrophy, and myotonic dys-
trophy are slowly progressive diseases, resulting in slow reduction in muscular
function and only mildly reduced life expectancy. Respiratory failure is the most
common cause of morbidity and morbility in patients with chronic or rapidly pro-
gressive neuromuscular diseases [3].
Neuromuscular diseases are the oldest and one of the most successful indications
for noninvasive mechanical ventilation (NIV). Modern NIV, based in positive pres-
sure portable ventilators and noninvasive interfaces, emerged in the 1980s. The
expansion benefited from the technology developed to treat respiratory sleep disor-
ders, with modern masks and ventilators [2]. Respiratory failure is the most com-
mon cause of morbidity and mortality in patients with chronic or rapidly progressive
neuromuscular diseases [3].
Molecular biology now allows identification of the genetic defects present in
many neuromuscular conditions, and there is hope that, in the future, gene therapy
could be used for the treatment of some conditions such as DMD [4]. In parallel
91 Home Mechanical Ventilation and Quality of Life in Neuromuscular Patients 783

with the pharmacological research, we are witnessing today a quiet revolution pro-
vided by NIV. An increasing number of children with congenital NMDs reach
adulthood. And even when survival is not significantly prolonged, as in end-stage
ALS, NIV has a tangible palliative benefit [2].

91.2.1 Chronic Respiratory Failure in Neuromuscular Diseases

Chronic respiratory failure in neuromuscular diseases results from progressive

inspiratory muscle weakness (mainly the diaphragm), leading to restrictive ventila-
tory impairment with decreased inspiratory capacity and breathing pattern with low
tidal volumes and increased respiratory rate. There is an increased dead space ratio/
tidal volume, resulting in the inability to maintain alveolar ventilation at a level that
prevents the appearance of hypercapnia.
This progressive respiratory muscle weakness also results in mechanical respira-
tory system changes with reduced lung and chest wall distensibility (compliance)
and musculoskeletal chest deformation, with progressive decline in vital capacity
(VC) and increase in muscle work of breathing and increased risk of muscle fatigue.
A rapid-shallow breathing pattern is also associated with increased work of breath-
ing and inability to breathe deeply, leading to chronic microatelectasis and decreased
lung and thorax compliance. Furthermore, these patients may also present changes
in the respiratory center (drive), with loss of sensitivity of central and peripheral
chemoreceptors.
Alveolar hypoventilation in neuromuscular disease typically appears during the
rapid eye movement (REM) sleep stage. In REM sleep, there is respiratory muscu-
lar weakness with hypotonia of intercostal muscles and pharyngeal dilators, with
relative excess loading of the diaphragm, and also instability of the upper airway
due to weakness of the bulbar muscles. Breathing becomes asynchronous, faster,
and less effective. This phenomenon, which is physiological, is amplified with
decreased muscle strength and compliance seen in NMD, which may result in
severe alveolar hypoventilation leading to sustained oxygen desaturation and
hypercapnia.
NMD may also be associated with obstructive apneas particularly during REM
sleep. PaCO2 increases and PaO2 decreases, which is not compensated because, in
REM sleep, paradoxically, the response of the respiratory center (drive) to these
chemical stimuli is decreased. The possible adaptive response is in the form of fre-
quent arousals that allow regaining characteristic control of the wakefulness phase.
Arousals cause sleep fragmentation, with decreased sleep efficiency and sleep
deprivation; this in turn increases the hypotonia of the upper airway and further
reduces the capacity of the drive respond to respiratory stimuli.
Thus, a vicious circle is perpetuated, leading to a progressive and sustained
increase of hypercapnia, which in turn reduces the sensitivity of chemoreceptors to
subsequent changes in PaCO2 (with depression of the respiratory center). The
chronic respiratory failure that began in REM phase then extends progressively to
non-REM and finally to wakefulness. That is, the nighttime alveolar
784 C. Ferreira and J. Moita

hypoventilation, changes in control of ventilation, and change in breathing pattern

ultimately lead to daytime alveolar hypoventilation. The development of pulmonary
hypertension and premature death depend in part on the severity of desaturation
during sleep.
Chronic respiratory failure in NMD is predominantly hypercapnic. Hypoxia is a
secondary and late-onset alveolar hypoventilation manifestation but may be rele-
vant in the presence of changes in ventilation/ perfusion, with infections and atelec-
tasis (predominantly basal) being the most frequent causes of involvement of the
lung parenchyma in these patients. Frequently, respiratory failure occurs acutely in
the context of a respiratory infection secondary to retention of secretions by ineffec-
tive cough or aspiration. The weakness of the expiratory, abdominal, and intercostal
muscles results in ineffective cough, with failure to remove respiratory secretions,
affecting the pulmonary defense mechanisms and facilitating the emergence of
respiratory infections [1, 2, 4–7].

91.2.2 Home Noninvasive Mechanical Ventilation in Patients

with Neuromuscular Disease

Long-term NIV improves quality of life in most patients with neuromuscular dis-
ease and improves survival in some patients, allowing patients with slowly progres-
sive neuromuscular diseases to live to nearly normal life expectancy. It extends
survival by many years in patients with other conditions such as DMD. In patients
with forms of rapidly progressive disease, as happens in ALS, symptoms can be
palliated even if mortality is not reduced [4].
The best accepted indication to start nocturnal noninvasive ventilator assistance
in neuromuscular disease is symptomatic hypoventilation with diurnal hypercapnia
(PaCO2 >45 mmHg) or nocturnal desaturation with peripheral oxygen saturation
(SpO2) <88 % for 5 consecutive minutes. However, it is now recognized that inter-
national recommendations to initiate NIV in neuromuscular diseases are question-
able for other symptoms. In the early stage of the disease, the patient does not value
the symptoms consistent with sleep-disordered breathing and hypoventilation such
as nocturnal awakenings, nocturia, vivid nightmares, fatigue, morning headaches,
daytime sleepiness, depression, decreased concentration and/or memory and dimin-
ished daytime performance [1].
Symptoms become evident only when diurnal hypercapnia appears, and at
that time a poor outcome is expected. In patients with symptomatic hypercapnia
with advanced disease, NIV reduces the work of breathing muscles and corrects
alveolar hypoventilation, but the results of this late treatment, however, are lim-
ited in terms of quality of life and survival. Therefore, symptoms should be care-
fully researched and NIV during the sleep period should be scheduled earlier, in
normocapnic patients, when the nocturnal hypoventilation is identified. Under
these circumstances, NIV enhances chemosensitivity to CO2 changes, increasing
ventilatory response of the respiratory center and stabilizing the structure of
sleep [4].
91 Home Mechanical Ventilation and Quality of Life in Neuromuscular Patients 785

Some authors recommend starting NIV as soon as nighttime hypoventilation is

identified, which requires the systematic realization of a polygraph sleep study [2, 4].
Guidelines list severe restriction with forced vital capacity (FVC) <50 % of predicted
or maximum inspiratory pressure (MIP) <60 mmHg as a criterion for initiation of NIV.
Patients with slowly progressive conditions, such as limb-girdle muscular dys-
trophy, may not become symptomatic or hypoventilate until FVC falls well below
50 %. On the other hand, this criterion may be sensible for patients with rapidly
progressive neuromuscular syndromes such as DMD, allowing time to adapt to NIV
before impairment becomes severe. In ALS, NIV should be started early when FVC
is <70 % of predicted because, in this disease, when FVC is no longer normal its
decline is rapid and unpredictable. Volume loss is preceded by a decrease in muscu-
lar strength (MIP) [4].
Sleep-disordered breathing and nocturnal hypoventilation usually precede the
onset of diurnal hypoventilation in neuromuscular patients. Partly because of their
inability to maintain physical activity, patients with NMD are often unaware of
dyspnea or other respiratory symptoms, even when they have severe restriction [6].
For patients who have hypercapnia despite adequate nocturnal therapy, dyspnea
during the daytime or hypoxemia due to recurrent respiratory infections associated
with atelectasis, daytime ventilation may also be needed [1].
Noninvasive ventilation and cough-assist techniques may also be indicated to
manage some acute exacerbations of NMD caused by bronchitis and pneumonia
and acute respiratory failure in the home and to reduce the need for hospitalization.
Thus, the combination of NIV with cough-assist techniques decreases pulmonary
morbidity and hospital admissions [1].

91.2.3 NIV Versus Tracheostomy Ventilation

Consensus opinion consistently supports that home NIV is preferred to tracheos-

tomy and invasive mechanical ventilation for the long-term ventilatory support of
patients with neuromuscular disease. The reasons are many, including ease of
administration of care, less strain on caregivers, more comfort for patient, greater
portability, lower cost, more security, lower airway complications, fewer infections,
and reduced need for hospitalization. Tracheostomy ventilation may be necessary
when patients have severe bulbar dysfunction and intolerance to NIV or with copi-
ous secretions and uncontrolled aspiration, which is reflected in permanent desatu-
ration under NIV [1].

91.2.4 Duchenne Muscular Dystrophy

DMD is an X-linked recessive disease caused by a mutation of the dystrophin gene

and is the most common muscular dystrophy of childhood. Chronic respiratory fail-
ure is an expected complication of the disease and, without ventilatory support,
death occurred on average at 19 years. These arise as a result of progressive loss of
786 C. Ferreira and J. Moita

expiratory muscles strength, which occurs in parallel with the inspiratory muscle
weakness with respiratory insufficiency, ineffective cough, and inevitable accumu-
lation of secretions.
The well-conducted NIV, associated with assisted cough, changed the natural
history of the disease, and children with DMD are now surviving to adulthood with
the aid of ventilatory support. Today, patients tend to die of cardiac complications
of the disease: abnormal electrical conduction or decompensated cardiomyopathy,
associated with lack of dystrophin. The management of heart disease is the major
challenge in the future.
NIV should be initiated when there is nighttime hypoventilation, even if the
symptoms associated with it are not visible [5]. The slow vital capacity (VC) and
FVC are classic indicators of the evolution of DMD. Hypoventilation, predomi-
nantly in REM, can arise when the VC drops below 60 %. At this time, registration
of sleep-disordered breathing should be performed, ideally by polysomnography
(PSG), and at least with oximetry and capnography registration. PSG has the addi-
tional advantage of identifying obstructive apneas that are common in DMD, which
affect the way in which the ventilation is conducted. PSG is also helpful in deter-
mining pressure settings.
Patients with DMD have poor sleep quality, with fragmented sleep due to a high
number of arousals and low mean SpO2, even in the absence of relevant respiratory
events. Arousals can be seen as a compensatory mechanism to sleep hypoventilation
and may contribute to clinical diurnal manifestations, such as excessive daytime
sleepiness and poor quality of life [8].
The NIV, initiated and conducted based on the identification and characterization
of nocturnal hypoventilation, seems to stabilize the decline in FVC [9]. Thus, NIV
has clearly demonstrated its usefulness, significantly increasing the survival and
quality of life of these patients. NIV stabilizes vital capacity, increases PaO2,
decreases PaCO2, and improves the quality of sleep. The use of long-term home
NIV can significantly decrease pulmonary morbidity and the incidence of respira-
tory hospitalizations, reduce the number of days of hospitalization, and prolong
survival in DMD patients without resort to tracheostomy. These findings may
impact the decision to initiate NIV at earlier stages.

91.2.5 Amyotrophic Lateral Sclerosis

ALS is a disease characterized by signs of loss of function of the upper and lower
motor neurons at the spinal and bulbar level. ALS often affects the respiratory mus-
cles, including those for airway protection and cough [1]. Bulbar symptoms (drooling,
difficulty in speech, aspiration of secretions, and chronic respiratory failure) may not
be present at presentation but are invariably present in the late stage of the disease.
Respiratory infections and respiratory failure are the leading cause of death in
ALS. Sleep-disordered breathing associated with respiratory muscle weakness is
common in ALS and increases in frequency with the progress of the disease.
Monitoring pulmonary function is critical in these patients. In ALS patients, NIV
91 Home Mechanical Ventilation and Quality of Life in Neuromuscular Patients 787

should be considered when FVC is less than 70 % of predicted or sleep studies show
desaturation or sleep-disordered breathing. As in the other NMDs, sleep studies are
important to confirm hypoventilation overnight because nocturnal desaturation cor-
relates directly with mortality [8].
Home NIV increases survival and improves quality of life, sleep-related symp-
toms, and functional scores, especially in patients without bulbar dysfunction.
Patients with severe bulbar dysfunction are often intolerant to NIV and have no
survival benefit, but in tolerant patients, sleep-related symptoms and some domains
of quality of life improved. Thus, a trial of NIV is justified, even in these patients,
but when it is not effective tracheostomy and long-term invasive ventilation should
be considered.
More than in any other neuromuscular pathology, in ALS, NIV should be com-
plemented by other supportive measures [9]. The introduction of insufflation-
exsufflation cough-assist is mandatory when the peak cough flow (PCF) is less than
160 l/min, a level that reflects the patient's inability to mobilize bronchial secretions.
Some authors recommend its use with PCF below 270 l/min, because viral infec-
tions decrease muscle strength. Regular use of cough-assist significantly improves
the ability of cough. However, when there is deep bulbar involvement, it may have
the perverse effect of bringing about the dynamic collapse of the upper airway in
exsufflation phase [10].
Muscle cachexia and malnutrition are serious problems directly related with
mortality in patients with ALS. The situation is aggravated by frequent choking
(particularly liquid) and dysphagia in patients bulbar. Percutaneous endoscopic gas-
trostomy (PEG) should not be delayed in these patients. Its placement should pref-
erably be done in patients with higher FVC 50 %. It is a fast and safe procedure even
in severe patients and can be done with the support of NIV. Administration of botu-
linum toxin in the parotid glands and submaxillary is safe and effective, dramati-
cally reducing drooling [11].

91.2.6 Starting Home Mechanical Ventilation

Before starting NIV, the most appropriate type of noninvasive ventilator and inter-
faces should be chosed, based on the patient’s needs and lifestyle factors, the
patient’s preference, the patient’s tolerance of the treatment, the risk and possible
consequences of ventilator failure, the power supply required, including battery
back-up, how easily the patient can get to hospital, whether a humidifier is required,
and issues relating to secretion management.

91.2.7 Ventilators

There are two types of positive pressure ventilators for home use: volume-controlled
(volume target ventilators) and pressure-controlled (pressure target ventilators). Some
newer hybrid systems have the capacity for regulation of volume and pressure.
788 C. Ferreira and J. Moita

The bi-level ventilator is a type of pressurimetric ventilator that is widely used

for the treatment of chronic respiratory failure in patients with neuromuscular dis-
eases. At home, these ventilators are usually set to work in pressure-support and
assisted-controlled mode. The management is facilitated by algorithms that adapt
the ventilator to the patient's respiratory pattern and leak compensation. Inasmuch
as the objective is to maintain pressure during inspiration, if there is any leakage,
flow is automatically incremented to achieve pressurization. Pressurimetric ventila-
tors increase the patient’s comfort with sensitive triggers (especially when it is for
flow), deliver volume through a decelerating flow that fits the patient’s best effort,
and, finally, the breathing pattern is not as fixed. However, ventilation regulated by
pressure has a limited ability to ventilate patients with low thoracopulmonary com-
pliance [2].
Currently, there is some preference for volume-programmed ventilation. In this
type of ventilation, when a certain volume or a certain inspiratory time is reached,
the inspiratory valve is closed and the exhalation valve opens. No evidence has been
found of a difference between pressure and volume programmed ventilators in
patients with chronic respiratory failure. However, patient tolerance is better with
pressure-limited modes [6].
Hybrid ventilators allow the patient to be ventilated during the day in volume
mode and during the night in pressure mode. The ventilation in volume mode
ensures a predefined tidal volume ventilation to correct alveolar hypoventilation and
facilitates air stacking during the day. In sleep, pressure ventilation is more comfort-
able and the leaks are compensated [2].
AVAPS (average volume-assured pressure support) is a more recent additional
technology for bi-level NIV. AVAPS combines characteristics of ventilation regu-
lated by pressure and volume to effectively manage the ventilation of the patient and
to adapt to the evolution of the disease, automatically adapting pressure support to
the changing needs of the patient, to ensure a predefined tidal volume target.
Finally, the best ventilator is the one that responds to the individual needs of the
patient.

91.2.8 Interfaces

There are many interfaces used to deliver NIV: oronasal masks, full face masks,
nasal masks, nasal pillows, and mouth pieces, with different sizes and different
materials. Nasal masks are often better tolerated than oronasal masks for long-term
ventilation. Facial masks are indicated in the presence of uncontrollable leakage or
nasal obstruction.
In general, the complications and adverse effects of NIV are not serious and rela-
tively rare if patients are appropriately selected and managed. The most common
complications are related to the interface, airflow, pressure, or the ventilator itself
and are preventable. These include mask discomfort, claustrophobic reactions, nasal
or oral congestion or dryness and eye irritation due to air leakage, gastric insuffla-
tion, and nasal bridge redness and ulceration. These problems are treated with local
91 Home Mechanical Ventilation and Quality of Life in Neuromuscular Patients 789

measures, including refitting of masks or headgear, using alternative interfaces, or

adjusting delivered pressures or volumes [6].
The patient on permanent ventilation can combine more than one interface using
nasal or face mask during sleep and nasal pillows or mouthpieces during the day to
facilitate reading and social interaction. This solution also allows the variation of
pressure points and therefore prevents skin ulceration [2].

Conclusion
Patients with chronic neuromuscular disorders have progressive respiratory mus-
cle dysfunction with hypoventilation and respiratory failure, cough dysfunction,
and respiratory infections, leading to death. Home NIV as a treatment for neuro-
muscular disease has several benefits and improves quality of life. It has been
shown to decrease work of breathing and improve blood gases, symptoms of
fatigue, daytime sleepiness, and morning headaches. NIV should be started ear-
lier in the course of neuromuscular diseases. The future of NIV is to provide
more life to life.

Key Major Recommendations

• Patients with chronic NMDs have progressive respiratory muscle dysfunc-
tion with hypoventilation and respiratory failure, cough dysfunction, and
respiratory infections and eventual death.
• Noninvasive mechanical ventilation in neuromuscular diseases should be
started earlier in the course of the disease when patients present symptom-
atic hypoventilation with diurnal hypercapnia (PaCO2 >45 mmHg) or noc-
turnal desaturation with peripheral oxygen saturation (SpO2) <88 % for 5
consecutive minutes.
• In patients with DMD, NIV should be considered when FVC is <50 % of
predicted or MIP is <60 mmHg. In ALS, NIV should be started when FVC
is <70 % of predicted.
• Noninvasive mechanical ventilation in neuromuscular diseases improves
symptoms of fatigue, daytime sleepiness, and morning headaches as well
as blood gas exchange, thus improving quality of life.
• Appropriate selection of ventilators, ventilation mode and parameters, and
interfaces is crucial to the success of NIV and patient comfort.

References
1. Benditt JO, Boitano LJ. Pulmonary issues in patients with chronic neuromuscular disease. Am
J Respir Crit Care Med. 2013;187(10):1046–55.
2. Moita J, Martins V, Guimarães C. Ventilação mecânica não invasiva na patologia neuromuscu-
lar. In Princípios da Ventilação Mecânica Não Invasiva – do Hospital ao Domicilio. Ed.
Esquinas AM. Gasin Mèdica. Gasin Médica; 2011;196–203.
790 C. Ferreira and J. Moita

3. Ambrosino N, Carpenè N, Gherardi M. Chronic respiratory care for neuromuscular diseases in

adults. Eur Respir J. 2009;34:444–51.
4. Simonds AK. Recent advances in respiratory care for neuromuscular disease. Chest.
2006;130:1879–86.
5. Ward S, et al. Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal
hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia.
Thorax. 2005;60:1019–1024.
6. Hill NS. Ventilator management for neuromuscular disease. Semin Respir Crit Care Med.
2002;23(3):293–306.
7. Shneerson JM, Simonds AK. Non invasive ventilation for chest wall and neuromuscular disor-
ders. Eur Respir J. 2002;20:480–7.
8. Ferreira C, et al. How sleep studies are important to initiate noninvasive ventilation in
Duchenne muscular dystrophy. Sleep Med. 2013;14S:e123.
9. Marques A, et al. Pulmonary function in Duchenne muscular dystrophy patients before and
after noninvasive ventilation. Eur Respir J. 2005;26 Suppl 49:85s.
10. Miller RG, et al. Practice parameter update: the care of the patient with amyotrophic lateral
sclerosis: drug, nutritional and respiratory therapies (an evidence-based review): report of the
Quality Standards Subcommittee of the American Academy of Neurology. Neurology.
2009;73(15):1218–26.
11. Sancho J, et al. Efficacy of mechanical insufflation-exsufflation in medically stable patients
with amyotrophic lateral sclerosis. Chest. 2004;125(4):1400–5.
European Models of Home Noninvasive
Mechanical Ventilation: What Have 92
We Learned? Evidence and Key
Determinants

Francisco J. Ribas-Solís, Julia A. Garcia-Fuertes,

and Carlos J. Egea-Santaolalla

Contents
92.1 Introduction ................................................................................................................. 792
92.2 HMV Prevalence in Europe ........................................................................................ 792
92.3 HMV Models .............................................................................................................. 794
92.4 NIV Adaptation in HMV Programs ............................................................................ 794
92.5 HMV Programs Follow-Up ........................................................................................ 795
92.6 Telemonitoring ............................................................................................................ 795
Conclusions ............................................................................................................................ 796
References .............................................................................................................................. 796

Abbreviations

ALS Amyotrophic lateral sclerosis

COPD Chronic obstructive pulmonary disease
HMV Home mechanical ventilation
NIV Noninvasive ventilation

F.J. Ribas-Solís (*) • J.A. Garcia-Fuertes

Respiratory Department, Araba University Hospital, Vitoria-Gasteiz, Spain
e-mail: [email protected]; [email protected]
C.J. Egea-Santaolalla
Multidisciplinary Sleep Unit, Araba University Hospital, Vitoria-Gasteiz, Spain
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 791

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_92
792 F.J. Ribas-Solís et al.

92.1 Introduction

In the history of mechanical ventilation over the last 100 years, from 1928, when an
iron lung was first used at the Children’s Hospital of Boston (Massachusetts),
through its highest level of use in the 1940s and 1950s during the poliomyelitis
epidemics, until our current times, we realize it is a two-speed journey. The fast
track was taken in the 1950s, when iron lungs started to be replaced by positive
airway pressure through intubation, and the second track started when the facial
mask started to be used as a noninvasive ventilation method. Thus, the possibility of
avoiding long hospital stays became a reality with the creation of the first home
mechanical ventilation (HMV) programs.
The prevalence rate of HMV has considerably increased in Europe in recent
years, both in countries that traditionally had low prevalence rates like Switzerland
[1] and the Netherlands [2], in those that had the highest rates, such as France (data
source is ANTADIR) [3], and also in countries such as Australia and New Zealand
(9.9–12/100,000) [4].
In the beginning, most patients (70 %) were invasively ventilated with positive
pressure mechanical ventilators through a tracheostomy tube, and the rate of patients
whose ventilation was noninvasive was low. The interfaces used for these were
either mouth or nasal pieces (16 %), or negative pressure ventilators (14 %). In the
1980s, nasal masks started to be used in patients with Duchenne’s disease, and
negative pressure ventilators were limited to exceptional use [5].
After that time, the use of noninvasively implemented mechanical ventilators
spread quickly as the technique of choice among patients with restrictive respiratory
failure. Patients adapted to the ventilator in a hospital setting and there were later
followed-up in their homes; this is when the first positive pressure noninvasive ven-
tilation (NIV) home programs appeared. In 1994, Leger et al. [6] published the first
series of patients treated with positive pressure NIV at home, with a follow-up of
276 patients during 5 years. In this study, the benefit for patients with kyphoscolio-
sis or sequelae from tuberculosis or Duchenne’s disease was clear. Moreover, the
study showed that patients with chronic obstructive pulmonary disease (COPD) and
bronchiectasis also benefited from this method. In 1992, the first pressure support
ventilator was created and, since then, the technology has improved and different
ventilation methods have appeared.
HMV programs have evolved in recent years and, at the same time, technological
progress has allowed for an increase in home monitoring of patients on
NIV. Moreover, HMV program implementation aims to bring NIV as close to
patients’ homes as possible.

92.2 HMV Prevalence in Europe

HMV’s introduction into Europe has been uneven and has differed according to
country. In 2001 and 2002, to assess the pattern of HMV use in Europe, question-
naires were sent to 483 centers in 16 European countries. A total of 329 replied,
92 European Models of Home Noninvasive Mechanical Ventilation 793

which amounts to between 62 and 79 % of HMV users in Europe. This data was
published in the EUROVENT [7] study. The average prevalence in Europe was
estimated at 6.6 patients/100,000 citizens, although there was a large variation
between countries: France was the country with the highest prevalence
(17/100,000) whereas Poland had the lowest (0.1/100,000) (Table 92.1).
Prevalence variation could be related partly to the average years since NIV
started to be implemented. Differences in the relative proportion of patients with
obstructive disease, rib cage pathology, and neuromuscular disease were also
made clear.
In fact, it is highly likely that data obtained from EUROVENT is not up to date.
This is the case with Poland, which went from a 0.1/100,000 prevalence in 2002, to
2.5/100,000 in 2010, with a reduction from over 80 % of neuromuscular patients in
2002 to 51 % in 2010 as a result of the increase in the number of patients with respi-
ratory disease [8].
A similar case is that of the Spanish region of Valencia. Spain showed a preva-
lence of HMV in 1999 of 4.59/100,000 according to a study by De Lucas et al. [9],
and of 6.3/100,000 in 2002 according to the EUROVENT study (close to the
European average) [7]. In 1999, the Valencia region showed a prevalence of 4.83
[5]. In a study carried out in 2007 by Chiner et al. [10] in the Valencia region,
HVM prevalence was proven to have risen to 29/100,000. Although this is data
from just one region in Spain, it can probably be extrapolated to the rest of the
country.

Table 92.1 Estimated prevalence Estimated prevalence

of users in HMV programs in 16 per 100,000 (2001–2002)
European countries (2001–2002)
Austria 3.8
Belgium 5.0
Denmark 9.6
Finland 8.7
France 17.0
Germany 6.5
Greece 0.6
Ireland 3.4
Italy 3.9
Netherlands 5.6
Norway 7.8
Poland 0.1
Portugal 9.3
Spain 6.3
Sweden 10.0
United Kingdom 4.1
All countries 6.6
794 F.J. Ribas-Solís et al.

92.3 HMV Models

NIV use in patients with chronic respiratory failure is covered by national health
systems, however, only a few countries have clear guidelines about how NIV should
be started and in which patient groups. Public national health systems and private
insurance companies usually hire private home therapy companies to provide and
maintain NIV equipment prescribed by patients’ doctors to use when patients are at
home. These companies have paramedical staff that can train patients and their fam-
ilies to correctly use NIV. The frequency of visits depends on the type of ventilator
prescribed for each patient; the interface type can be adjusted and humidifiers can
be provided. In some cases, these companies can also offer other home services, for
instance SatO2 night monitoring can be provided. If problems arise at patients’
homes, they are communicated to the prescribing doctor; good coordination with
the reference hospital is key [11].
Sometimes, the relationship between these companies and the national health
systems is poor and often there is no formal infrastructure. Thus, a European study
that was carried out in 16 countries including more than 20,000 ventilated patients
showed that, in 62 % of centers, an external company carried out services provided
to patients. It also showed that the maintenance frequency ranged between 3 and 12
months; that interaction between the service-providing companies and the hospitals
was scarce; that the participation of hospitals in the quality control of equipment
was poor; and that there were important differences not only between countries but
also within the same country [10, 12].
An outstanding exception is France’s HMV program. The French model’s effi-
cacy is partly attributed to local and regional services, which get support from a
specialized center. The services network is effectively maintained as a result of the
national capacity to gather data to advance and support the service assessment and
research [13].

92.4 NIV Adaptation in HMV Programs

NIV adaptation can take place during a programmed hospital stay, although it can also
be effectively implemented in day hospitals, outpatient settings, and even at the
patient’s home. Pallero et al. [14] carried out a multicenter, randomized, prospective
study to compare efficacy and costs according to whether the HMV program was
started in a hospital setting or an outpatient setting, with patients who had stable
chronic respiratory failure with NIV indication. The main study variable was the
PaCO2 drop 6 months after NIV initiation. They found a significant decrease in both
groups, although they did not find significant differences between them. Direct costs of
both interventions were estimated. The hospital setting intervention was estimated to
have a cost of 2692 euros, whereas the outpatient setting intervention had a cost of
1500 euros. Therefore, the conclusion was that, because adapting NIV in the outpatient
setting is equivalent to doing it in the hospital setting from a therapeutic perspective,
adaptation in the outpatient setting could lead to cost-savings for the health system.
92 European Models of Home Noninvasive Mechanical Ventilation 795

92.5 HMV Programs Follow-Up

There are no data on how frequently patients should see their specialized center
doctor, and it depends on different factors such as the patient’s pathology, how they
adapt to NIV, and how easy it is for them to travel to the hospital. If a private home
services company is involved, some of the follow-up can be done in patients’ homes.
The information can be transmitted to the prescribing doctor who, every 3 months,
can systematically check the patients’ approximate symptoms, quality of life, ven-
tilation-related side effects, and compliance. After receiving this information, the
doctor will be able to determine whatever adjustments are needed.
Some of the tests can only be carried out in the hospital; therefore, it seems that
some kind of hospital follow-up is necessary. Generally, the average number of
outpatient visits per year is three. Follow-up complementary tests during these visits
include arterial blood gas, chest X-rays, and respiratory function tests. The noctur-
nal evaluation is carried out at home, if possible, or in the hospital to control ventila-
tion quality during the night, and, if possible, in the 3 months following NIV
initiation. Patient nocturnal follow-up during the HMV program’s first year includes
monitoring O2 saturation, if possible with capnography, respiratory polygraphy,
polysomnography, and arterial blood gas first thing in the morning. For many of the
more restrictive patients, once they are stable, the supervision required is minimal.
Unstable patients or patients who are insufficiently stabilized with NIV need closer
follow-up (e.g., those with rapidly progressing neuromuscular diseases such as
amyotrophic lateral sclerosis (ALS), and to a lesser extent, patients with muscular
dystrophy caused by Duchenne’s disease or COPD) [11].

92.6 Telemonitoring

Telemonitoring can be used to check a ventilator’s compliance and performance.

Although not widely available at the moment, the situation is likely to improve in
the future. In 2010, Pinto et al. [15] published a prospective study on 40 patients
with ALS who were divided into two groups. In the intervention group, the venti-
lator data was received by modem, whereas in the control group, compliance and
ventilator parameters were checked on official visits. The study did not find dif-
ferences between groups regarding compliance, although the number of visits to
the doctor and to the ER was significantly lower in the group in which telemoni-
toring was carried out (p < 0.0001). Moreover, although there were no significant
differences, survival showed a positive trend in the group with telemonitoring
(p = 0.13), the conclusion being that telemonitoring reduces the need to use health
services and probably has a favorable impact on costs, survival, and performance
status.
Telemonitoring might also be useful for patients other than those with ALS. In
2015, Borel et al. [16] published a study that observed that an increase in the breath-
ing rate and the percentage of respiratory cycles caused by the patient were predic-
tive of a COPD exacerbation. Both parameters can be registered by NIV software.
796 F.J. Ribas-Solís et al.

Conclusions
A progressive increase of the NIV prevalence rate by all European Union mem-
ber states demands cost-effective schemes to manage patients on HMV. Moreover,
telemonitoring these patients should be the first option to effectively solve this
public health issue, although prospective, multicenter studies that ensure its fea-
sibility are still needed.

Key Major Recommendations

• The exponential and global growth, in Europe, of patients on HMV pro-
grams generates a key area for development.
• There is a need for European guidelines on home assistance management
models.
• Unique quality indicators for the HMV model are needed.
• The cost-efficiency of telemonitoring programs requires assessment.

References
1. Janssens JP, Derivaz S, Breitenstein E, De Muralt B, Fitting JW, Chevrolet JC, Rochat
T. Changing patterns in long-term noninvasive ventilation: a 7-year prospective study in the
Geneva Lake area. Chest. 2003;123:67–79.
2. Hazenberg A, Cobben NA, Kampelmacher MJ, Rischen J, Wijkstra PJ. Home mechanical
ventilation in the Netherlands. Ned Tijdschr Geneeskd. 2012;156:A3609.
3. Antadir. www.antadir.com. 2014.
4. Garner DJ, Berlowitz DJ, Douglas J, Harkness N, Howard M, McArdle N, Naughton MT, Neill
A, Piper A, Yeo A, Young A. Home mechanical ventilation in Australia and New Zealand. Eur
Respir J. 2013;41:39–45.
5. Diaz Lobato S, Mayorales AS. Modern non-invasive mechanical ventilation turns 25. Arch
Bronconeumol. 2013;49:475–9.
6. Eger P, Bedicam JM, Cornette A, Reybet-Degat O, et al. Nasal intermittent positive pressure.
Long-term follow-up in patients with severe chronic respiratory insufficiency. Chest.
1994;105:100–5.
7. Lloyd-Owen SJ, Donaldson GC, Ambrosino N, et al. Patterns of home mechanical ventilation
use in Europe: results from the Eurovent survey. Eur Respir J. 2005;25:1025–31.
8. Nasiłowski J, Wachulski M, Trznadel W, et al. The evolution of home mechanical ventilation
in Poland between 2000 and 2010. Respir Care. 2015;60:577–85.
9. De Lucas Ramos P, Rodríguez González-Moro JM, Paz González L, et al. Estado actual de la
ventilación domiciliaria en España: resultados de una encuesta de ámbito nacional. Arch
Bronconeumol. 2000;36:545–50.
10. Chiner E, Llombart M, Martínez-García MA, Fernández-Fabrellas E, et al. Noninvasive
mechanical ventilation in Valencia, Spain: from theory to practice. Arch Bronconeumol.
2009;45:118–22.
11. Leger P, Laier-Groeneveld G. Infrastructure, funding and follow-up in a programme of nonin-
vasive ventilation. Eur Respir J. 2002;20:1573–8.
12. Farré R, Lloyd-Owen SJ, Ambrosino N, et al. Quality control of equipment in home mechani-
cal ventilation: a European survey. Eur Respir J. 2005;26:86–94.
92 European Models of Home Noninvasive Mechanical Ventilation 797

13. Stuart M, Weinrich M. Integrated health system for chronic disease management – lessons
learned from France. Chest. 2004;125:695–703.
14. Pallero M, Puy C, Güell R, et al. Ambulatory adaptation to noninvasive ventilation in restric-
tive pulmonary disease: a randomized trial with cost assessment. Respir Med.
2014;108:1014–22.
15. Pinto A, Almeida JP, Pinto S, Pereira J, Oliveira AG, de Carvalho M. Home telemonitoring of
non-invasive ventilation decreases healthcare utilisation in a prospective controlled trial of
patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatr. 2010;81:1238–42.
16. Borel JC, Pelletier J, Taleux N, et al. Parameters recorded by software of non-invasive ventila-
tors predict COPD exacerbation: a proof-of-concept study. Thorax. 2015;70:284–5.
Telemonitoring of CPAP Compliance: Key
Technical Topics and Clinical 93
Implications

Sevinc Sarinc Ulasli and Aylin Ozsancak Ugurlu

Contents
93.1 Introduction ................................................................................................................. 800
93.2 Discussion and Analysis ............................................................................................. 800
93.2.1 Definition and Types of Telemedicine and Telemonitoring .......................... 800
93.2.2 Telemonitoring for Respiratory Disorders .................................................... 801
93.2.3 Limitations of Telemonitorization ................................................................. 805
Conclusion ............................................................................................................................. 805
References .............................................................................................................................. 805

Abbreviations

AHI Apnea/hypopnea index

ALS Amyotrophic lateral sclerosis
APAP Automated positive airway pressure
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
HMV Home mechanical ventilation
NIV Noninvasive ventilation
NMD Neuromuscular disease

S.S. Ulasli, MD (*)

Faculty of Medicine, Department of Pulmonary Diseases,
Afyon Kocatepe University, Afyon, Turkey
e-mail: [email protected]
A.O. Ugurlu, MD
Department of Pulmonary Medicine, Baskent University Hospital, Istanbul, Turkey
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 799

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_93
800 S.S. Ulasli and A.O. Ugurlu

OSAS Obstructive sleep apnea syndrome

PaCO2 Arterial carbon dioxide pressure
TLC Telephone-linked communications

93.1 Introduction

Telemonitoring provides close follow-up of patients by ensuring transmission of

clinical and physiologic data and by supporting prompt medical intervention before
deteriorations of patients’ conditions occur. It has been used for the management
and close follow-up of several chronic diseases (such as diabetes, hypertension,
cardiac diseases, etc.) with improved access to health care, reduced waiting times
for appointments, and increased patient adherence to chronic illness treatment
plans [1]. In the setting of respiratory medicine, telemonitoring has been used in
the management of patients with asthma, chronic obstructive pulmonary disease
(COPD), obstructive sleep apnea syndrome (OSAS), and pulmonary transplanta-
tion [2]. In this chapter, the role of telemonitoring for improving the adherence of
patients with OSAS to continuous positive airway pressure (CPAP) therapy is
discussed.

93.2 Discussion and Analysis

93.2.1 Definition and Types of Telemedicine and Telemonitoring

Chronic diseases such as COPD, diabetes, hypertension, and OSAS represent a sig-
nificant burden of disease. These affect both the patients themselves and the health-
care systems with imposition of huge costs for management. Telemedicine, defined
as “the use of information and communication technology to deliver health services,
expertise and information over distance, geographic, time, social and cultural barri-
ers” [3], involves various technologies to potentially enhance quality of care and
reduce health-care costs, especially in these chronic disorders.
Telemedicine encompasses diverse patient care services such as telepsychiatry,
teleradiology, teledermatology, and teleophthalmology [2, 3]. The main roles of
telemedicine in management of chronic diseases includes providing education (to
improve self-care), enabling information transfer (e.g., telemonitoring), facilitating
contact with medical professionals (e.g., telephone interviews and follow-ups), and
improving medical records [4].
Three different models exist in telemedicine:

1. Store-and-forward telemedicine (asynchronous) involves acquiring medical data

(e.g., medical images, biosignals, etc.) and then transmitting recorded data to a
health professional at a convenient time for assessment offline. It does not require
the presence of both parts at the same time. A properly structured medical record,
preferably in electronic form, is the major component of this transfer. The store-
93 Telemonitoring of CPAP Compliance: Key Technical Topics and Clinical Implications 801

and-forward process requires the clinician to rely on a history report and audio/
video information in lieu of a physical examination.
2. Remote monitoring, also known as self-monitoring or testing, enables medical
professionals to monitor a patient remotely using various technological devices.
This method is primarily used for managing chronic diseases or specific condi-
tions, such as cardiovascular diseases, diabetes mellitus, or asthma.
3. Interactive telemedicine services (synchronous) provide real-time interactions
between patient and provider (e.g., telephone or videoconference, online com-
munication) with or without physiological monitoring, Many activities such as
history review, physical examination, psychiatric evaluations, and ophthalmol-
ogy assessments can be conducted comparably to those done in traditional face-
to-face visits [2, 3].

“Telemonitorization” is a rapidly evolving domain of telemedicine focused on

providing care in a home setting with the primary intent of supporting the patient
rather than the health professionals [5]. The term home telemonitoring is used in a
more restrictive sense and encompasses the use of audio, video, and other telecom-
munication technologies to monitor patient status at a distance.

93.2.2 Telemonitoring for Respiratory Disorders

Respiratory disorders have significant effects and burdens on society. In patients with
chronic respiratory diseases, underlying disorders, the level of dependency on caregiv-
ers, the hours spent under mechanical ventilation, the presence of tracheostomy, dis-
tance from home to hospital, and hospital access are parts of the care burden both for
the family and health-care systems. These patients need education, self-monitoring,
and close management to ensure better outcomes and improve survival. Patient-, ven-
tilator-, or interface-related problems (e.g., patient-ventilator asynchrony, re-breathing,
or leaks) should be detected so that the most appropriate ventilator settings and inter-
face in patients receiving home mechanical ventilation (HMV) can be selected. Home
telemonitoring presents an alternative tool for close follow-up of patients by ensuring
timely transmission of clinical and physiologic data to estimate detrimental events in
patients treated with HMV during day and night. Subsequent rapid troubleshooting of
potential problems may improve adherence to HMV therapy.

93.2.2.1 Types of Telemonitorization Used for Respiratory Diseases

Electronic diary and spirometer systems were widely used methods for telemonitor-
ing of respiratory diseases in the 1990s, whereas more recent studies introduced
more sophisticated technologies such as handheld devices, digital technology, and
wireless networks [6]. Telephone short messaging services, internet-based monitor-
ing systems and electronic diaries are commonly used methods for data transmis-
sion of patients with respiratory diseases. Despite variability in the technologies
used and their sophistication over the years, the modalities were similar across stud-
ies in relation to the types of transmitted data and frequency of transmission.
802 S.S. Ulasli and A.O. Ugurlu

Telemonitorization for Sleep-Related Breathing Disorders

OSAS is a highly prevalent sleep-related breathing disorder with high morbidity
and mortality, defined as presence of five or more predominantly obstructive respi-
ratory events per hour of sleep during polysomnography. This chronic disease
mainly leads to cardiovascular complications (e.g., coronary artery disease, heart
failure, arrhythmias, stroke, systemic and pulmonary hypertension), neuropsychiat-
ric complications (e.g., cognitive and memory impairment, depression), impotence,
socioeconomic problems, and metabolic complications. CPAP, the first-line medical
treatment in adults with OSAS, effectively improves sleep architecture, reduces the
apnea-hypopnea index (AHI), normalizes oxyhemoglobin saturation, and decreases
neurocognitive and cardiovascular sequences. However, adherence to CPAP limits
its overall effectiveness among all age groups [4].
CPAP adherence is defined as using CPAP for an average of 4 h a night for at
least 70 % of the nights. The importance of adherence to treatment has been dem-
onstrated with the return of sleepiness and impairment in simulated driving ability
in as little as one night off CPAP. Furthermore, CPAP withdrawal resulted in a rapid
recurrence of apneic events, daytime sleepiness, increased blood pressure, and
increased heart rate [7].
Factors affecting CPAP compliance include the severity of the disorder, air leak,
side effects, therapeutic response, claustrophobia, patient’s perception of disease
seriousness, family support, and cost. Strategies to improve adherence to CPAP that
have been tested are broadly categorized as educational, technological, psychoso-
cial, pharmacological, and multidimensional. Heated humidification, mask optimi-
zation, and topical nasal therapy can increase adherence.
Adherence can also be significantly improved by comprehensive support pro-
grams and timely interventions by health professionals. Therefore, to increase
patients’ understanding of the expected benefits of CPAP use, and to motivate using
this therapy, to determine side effects, and to monitor and promote adherence to
CPAP therapy at the beginning of use are needed to improve CPAP adherence.
CPAP adherence can be evaluated with self- report measures including diaries
and verbal recall, hour meter readings, and CPAP devices that measure night-by-
night and mask-on CPAP application at effective pressure over each 24-h period.
This recent CPAP technology allows CPAP adherence data to be transmitted to
practice sites by several vehicles, including modem, smartcard, or web portal,
depending on the manufacturer. In this way, CPAP adherence can be assessed more
reliably.
Previous studies related to different telemonitoring options have demonstrated
variable effectiveness in CPAP adherence of OSAS patients. Telephone-linked
communications (TLC) systems offer an effective, low-cost, and convenient way of
providing information, advice and counseling to improve patient adherence.
Sparrow et al. [8] revealed improvement of CPAP adherence with the use of a tele-
medicine intervention with TLC in a relatively large randomized controlled study
(250 patients with OSAS from two different centers); therefore, they indicated a
potentially useful role for telemedicine in the management of patients with
OSAS. Telemedicine intervention with an automated TLC system designed around
93 Telemonitoring of CPAP Compliance: Key Technical Topics and Clinical Implications 803

the concepts of motivational interviewing, a patient-centered approach to increase

motivation to engage in health behavior by addressing the themes of perceived
importance of using CPAP, was applied. Every week for the first month (beginning
from 3 days after initiating CPAP therapy) and every month thereafter for a 12-month
period, patients called the system and reported perceptions and experiences with
OSAS and CPAP (including compliance) from the previous week. The computer
system called the participants if they did not make a call at the expected times. The
intervention arm received tailored feedback and counseling to increase motivation
of patients to use CPAP. The control arm received general health information
through the TLC system. At 12 months, median CPAP use was significantly higher
in the telemedicine group (2.98 h vs 0.99 h/night).
Taylor et al. [9] randomized 114 patients with OSAS to either a telemedicine arm
or traditional care. In the intervention arm, questionnaires (including questions
related to CPAP use, hours of sleep, and quality of sleep) were sent to patients via
computer. The patients’ responses were monitored by the sleep medicine practitio-
ner, and the patient telephoned if required. They did not find a significant difference
in the hours of CPAP use between two groups (4.22 vs 4.29 h night; p = 0.87).
However, only self-reported data was provided to the health-care provider; objec-
tive compliance and detailed physiological information were lacking.
Fox et al. [10] randomized 75 patients with OSAS to either standard care with an
auto-titrating positive airway pressure (APAP) machine or an APAP machine that
transmitted physiologic information such as adherence, air leak, residual AHI daily
to a website that could be reviewed. If any problems were detected from informa-
tion on the website, the patient was contacted by phone. APAP adherence after 3
months was significantly higher in the intervention arm than the standard arm
(191 min per day vs 105 min per day; p = 0.006). On days when APAP was used,
mean adherence was 321 min in the telemedicine arm and 207 min in the standard
arm (difference = 113 min, 95 % CI: 62–164 min, p < 0.0001). So, APAP adherence
was improved with the use of a web-based telemedicine system at the initiation of
treatment.
From the patients’ point of view, telemedicine seems to be an effective time and
cost-saving method in the care of sleep medicine. A survey study investigating the
patients’ perspectives of telemonitoring in sleep medicine revealed that video tele-
medicine was considered as an option for care of patients with OSAS, despite the
fact that none of the respondents had any personal experience with video telemedi-
cine. Patients with OSAS described challenges about in-person visits, such as time
away from work or school and cost associated with travel, gas, parking, or missed
work [11].

Telemonitorization for Other Chronic Respiratory Disorders

Telemonitoring with home spirometry assists in early identification and treatment
of deterioration, organ rejection, and complications (e.g., bronchiolitis obliterans
syndrome, etc.) in the health-care status of patients after lung transplantation.
Home telemonitoring ensures the diagnosis of asthma and also improves the man-
agement of asthma with the identification of early signs of deterioration and
804 S.S. Ulasli and A.O. Ugurlu

control of acute exacerbations. Patients with COPD and respiratory failure also
seem to utilize telemonitoring [6]. Vitacca et al. [12] evaluated the effectiveness of
a tele-assistance program supported by the continuous availability of a 24-h call
center and pulse oxygen device, as compared with the usual outpatient follow-up
regimen in 240 patients requiring long-term oxygen therapy or home mechanical
ventilation. Reduction in home exacerbations, emergency room admissions, and
urgent general practitioner calls were tested. A nurse-centered tele-assistance pro-
gram in that study was found to be effective in preventing hospitalizations, home
acute exacerbations, and urgent general practitioner calls, and especially patients
with COPD and respiratory failure received more benefit from this program. These
positive outcomes can improve patients’ adherence to medical and long-term oxy-
gen treatment and NIV.
Telemonitoring, especially associated with remotely controlling the settings of
ventilator, may be useful in patients with neuromuscular diseases (NMD) receiving
NIV. In a prospective controlled trial by de Almeida et al. [13], compliance with
NIV in patients with amyotrophic lateral sclerosis (ALS) was assessed with a tele-
monitoring device that was able to act as a digital recorder of parameters exported
from the NIV device via wireless modem. The authors remotely monitored home-
ventilated ALS patients and tuned the settings of the respiratory ventilator accord-
ing to the patients’ needs. The number of office and emergency room visits and
in-hospital admissions was lower and daily hours of ventilation use was higher in
the telemonitoring intervention arm. So, it was useful to improve management and
compliance of ALS patients receiving NIV at home. Moreover, cost analysis
revealed that telemedicine was cost effective.
Finally, an important problem during the initiation of HMV has been the lack of
professional supervision in the home environment and nighttime observation during
sleep. Hazenberg et al. [14] investigated whether or not initiation of HMV at home
in a selective group of patients with chronic respiratory failure resulting from NMD
or thoracic cage disorder by using telemonitoring is non-inferior to an in-hospital
based setting. Patients were randomized into two groups (38 patients in the home
group; 39 patients in the hospital group) and the primary outcome measure was the
arterial carbon dioxide (PaCO2), and quality of life and costs were secondary out-
come measurements. Telemonitoring was performed every morning during the ini-
tiation period of HMV at home. The data of ventilator settings, respiratory rate, and
carbon dioxide and oxygen saturation levels were sent to the hospital. The nurse
practitioner receiving the anonymous digital data by email called the patient to eval-
uate the results. A software program especially developed for the study started the
data collection from the ventilator and transcutaneous monitor automatically, and
data was transferred to the hospital. PaCO2 and quality of life were not significantly
different between groups. Initiation of HMV at home, using telemonitoring, was
safe, feasible, and less expensive than the initiation of mechanical ventilation at the
hospital. From the patients’ view, initiation of HMV at home by using a mobile con-
nection without technical delays is an ideal treatment option; there is no need for
hospital admission and highly individualized care can be maintained at the begin-
ning of HMV.
93 Telemonitoring of CPAP Compliance: Key Technical Topics and Clinical Implications 805

93.2.3 Limitations of Telemonitorization

Many questions remain before telemedicine can be considered for broad applica-
tion. Multicenter studies of telemedicine technologies in a broad range of academic
and community sleep centers are needed to address this issue, and the cost implica-
tions of this technology (e.g., cost per additional quality-adjusted life year saved)
should be clarified. Most importantly, most crucial telemedicine components
improving adherence need to be better understood so that the most efficient system
can be designed. In addition, it is not known whether regular automated telephone
follow-ups or more advanced technology (monitoring CPAP pressures, leaks, and
objective compliance and sending this information to the practitioner on a daily
basis) will improve adherence the most. How to integrate telemedicine in the daily
practice of patients receiving NIV in the most cost-efficient way needs to be
determined.

Conclusion
Further exploration of methods of telemedicine are needed to improve NIV com-
pliance. The potential benefits of telemonitoring (such as early intervention for
problems, patient education, improving adherence, and outcomes) should be
considered more important than technology costs.

Key Major Recommendations

• Telemonitoring, supporting early identification of deteriorations in
patients’ conditions and increasing NIV adherence, represents a promising
patient management approach that is well received by patients.
• Initiation of HMV can be ensured by the use of telemonitoring to transmit
digital data and to provide clinical health care outside the hospital.
• Despite minimal evidence of its economic viability, preliminary studies
demonstrate promising results and the affordability of telemonitoring to
improve NIV compliance.

References
1. Chaudhry SI, Phillips CO, Stewart SS, et al. Telemonitoring for patients with chronic heart
failure: a systematic review. J Card Fail. 2007;13:56–62.
2. Darkins AW, Cary MA. Telemedicine and telehealth principles, policies, performance and
pitfalls. 1st ed. New York: Springer; 2000. p. 1–321.
3. Meystre S. Telemedicine and e-Health. Telemed J E Health. 2005;11(1):63–9.
4. Sawyer AM, Gooneratne N, Marcus CL, et al. A systematic review of CPAP adherence across
age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep
Med Rev. 2011;15:343–56.
806 S.S. Ulasli and A.O. Ugurlu

5. Paré G, Jaana M, Sicotte C. Systematic review of home telemonitoring for chronic diseases:
the evidence base. J Am Med Inform Assoc. 2007;14(3):269–77.
6. Jaana M, Paré G, Sicotte C. Home telemonitoring for respiratory conditions: a systematic
review. Am J Manag Care. 2009;15:313–20.
7. Schwab RJ, Badr SM, Epstein LJ, et al. An official American Thoracic Society statement:
continuous positive airway pressure adherence tracking systems. The optimal monitoring strat-
egies and outcome measures in adults. Am J Respir Crit Care Med. 2013;188:613–20.
8. Sparrow D, Aloia M, Demolles DA, Gottlieb DJ. A telemedicine intervention to improve
adherence to continuous positive airway pressure: a randomised controlled trial. Thorax.
2010;65:1061–6.
9. Taylor Y, Eliasson A, Andrada T, et al. The role of telemedicine in CPAP compliance for
patients with obstructive sleep apnea syndrome. Sleep Breath. 2006;10:132–8.
10. Fox N, Hirsch-Allen AJ, Goodfellow E, et al. The impact of a telemedicine monitoring system
on positive airway pressure adherence in patients with obstructive sleep apnea: a randomized
controlled trial. Sleep. 2012;35:477–81.
11. Kelly JM, Schwamm LH, Bianchi MT. Sleep telemedicine: a survey study of patient prefer-
ences. ISRN Neurol. 2012;135329. doi:10.5402/2012/135329.
12. Vitacca M, Bianchi L, Guerra A, et al. Tele-assistance in chronic respiratory failure patients: a
randomised clinical trial. Eur Respir J. 2009;33:411–8.
13. de Almeida JP, Pinto A, Pinto S, et al. Economic cost of home-telemonitoring care for BiPAP-
assisted ALS individuals. Amyotroph Lateral Scler. 2012;13:533–7.
14. Hazenberg A, Kerstjens HA, Prins SC, et al. Initiation of home mechanical ventilation at
home: a randomised controlled trial of efficacy, feasibility and costs. Respir Med.
2014;108:1387–95.
Psychological Factors as a Determinant
of Noninvasive Ventilation Compliance: 94
Key Practical Aspects and Topics

Marie-Christine Rousseau and Stéphane Pietra

Contents
94.1 Introduction ................................................................................................................. 807
94.2 Discussion ................................................................................................................... 808
Conclusion ............................................................................................................................. 809
References .............................................................................................................................. 809

94.1 Introduction

Noninvasive mechanical ventilation (NIV) is a useful procedure in the management

of patients with chronic respiratory failure with hypercapnia resulting from motor
neuron disease, spinal cord injury, neuromuscular diseases, or post-polio syndrome
[1–4]. NIV relieves respiratory symptoms and reduces energy expenditure in
patients with amyotrophic lateral sclerosis (ALS) [5]; several studies have sug-
gested that NIV leads to a longer survival time and better health-related quality of
life and physiological parameters in patients with ALS or chronic respiratory failure
[2, 3, 5–7]. In spite of these benefits, NIV is rejected by a large proportion of patients
because of psychological factors.

M.-C. Rousseau, MD (*) • S. Pietra

Hôpital San Salvadour (Assistance Publique Hôpitaux de Paris),
BP 30080, Hyeres 83407, France
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 807

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_94
808 M.-C. Rousseau and S. Pietra

94.2 Discussion

Outcome for patients with ALS who are dependent on mechanical ventilation is
similar to that of patients with locked-in-syndrome: both categories have a healthy
brain locked into a paralyzed body. Studies show that patients receiving NIV report
good perceived health, despite severe physical limitations, and NIV is becoming
more popular, considering the great benefits that it represents [7].
Several studies have demonstrated the positive effect of NIV on patients’ wellbe-
ing, including improvement in night sleep, tiredness, and daily activity, decrease of
shortness of breath and orthopnea, and amelioration of cognitive functions [4, 8].
NIV has a positive impact on social activities, too, and the physical benefits induced
by NIV have a positive impact patients’ psychological condition.
Contraindications for the use of NIV in motor neuron diseases are cognitive
impairment, neurobehavioral dysfunctions, social isolation, and rapidly progressive
disease [9]. Factors associated with acceptance of NIV are cognitive and educa-
tional status and level of executive functions.
Psychological factors have a great influence on patient compliance with NIV. Fear
of death has been reported to be a facilitator for the initiation of and the adherence
to NIV. Others psychological factors associated with NIV acceptance are a focus by
the patient on perceived benefits from NIV and a positive coping style. NIV may
also be used in patients who have declined tracheal intubation and is also applied in
other chronic encephalopathies with hypercapnia.
Patients’ NIV acceptance and compliance depends also on how family caregivers
can develop resilience and coping through the situation [10]. Although NIV
increases the caregivers’ burden and may negatively affect their physical function
(which appear through signs of exhaustion such as insomnia, anxiety disorders, or
loss of attention) it shows good acceptance by them [6]. This emphasizes the impor-
tance of informing caregivers regarding the effects and the value of NIV on survival,
respiratory symptoms, and patient’s quality of life (QOL). Caregivers should also be
involved in the planning of care and should receive therapeutic education training.
Psychological interventions for caregivers are necessary to help them to cope with
this challenge.
Although NIV can benefit survival and quality of life, it is rejected by a substan-
tial proportion of people with motor neuron disease [10]. However, its application
in chronically ill and dependent patients with chronic respiratory failure requires
taking into consideration a range of disorders and psychological mechanisms and
possible impact on patients’ QOL. Psychological factors in patients with life-threat-
ening situations are the consequence of a number of diverse psychological disor-
ders. These disorders are linked to a potentially fatal disease, or to a condition so
severe that, psychologically, it cannot be assumed because the evolution of the dis-
ease defeats the psychological defense mechanisms and can lead to a collapse of
these ones and a severe depression.
In the study of Ando et al. [8] on patients with motor neuron disease, about a
third of patients declined NIV ventilation. Psychological reasons for patient disen-
gagement with NIV include threat to the self, sense of loss of control, anxiety,
94 Psychological Factors as a Determinant of Noninvasive Ventilation Compliance 809

negative perceived impact of NIV on dignity and quality of life, and negative expe-
rience with health-care services. NIV may also not be accepted by patients for fear
of prolonged survival and increasing disability. This emphasizes the importance of
sustained psychological support for this category of patients.
In our experience, for patients with a significant level of anxiety when NIV is
proposed, the use of hypnosis sessions performed as the patient is wearing the mask
allow a reduction of anxiety and enhance the acceptance of NIV. Support with hyp-
notherapy treatment at the frequency of one session per day generally yields good
compliance after a week, on average.
In several studies, these factors (psychological support) were more important to
patients than prolonging life in its current form [8]. During long-term use of NIV in
patients with motor neuron disease, patients’ perceptions of NIV evolve over time
and have an impact in their adherence to NIV. The study of Ando et al. [8] suggested
that a positive coping style, adaptation, and hope are key factors for psychological
well-being of patients with NIV.

Conclusion
It is important to control psychological factors of NIV acceptance because better
compliance with NIV is related to better survival, and good QOL is associated
with the desire to live longer and consequently with NIV compliance.

Key Major Recommendations

• Caregivers should be involved in the planning of care of patients on NIV.
• Clinicians must inform patients of benefits from NIV on QOL, respiratory
symptoms, and survival.
• Psychotherapy support, performed before starting the NIV, helps to reduce
defense mechanisms.
• Sustained psychological support for patients on NIV should always be
provided.

References
1. Markström A, Sundell K, Lysdahl M, Andersson G, Schedin U, Klang B. Quality-of-life eval-
uation of patients with neuromuscular and skeletal diseases treated with noninvasive and inva-
sive home mechanical ventilation. Chest. 2002;122(5):1695–700.
2. Bach JR, Bakshiyev R, Hon A. Noninvasive respiratory management for patients with spinal
cord injury and neuromuscular disease. Tanaffos. 2012;11(1):7–11.
3. Aboussouan LS, Khan SU, Meeker DP, et al. Effect of non-invasive positive-pressure ventila-
tion on survival in amyotrophic lateral sclerosis. Ann Intern Med. 1997;127:450–3.
4. Piepers S, Van Den Berg JP, Kalmijn S, Van Der Pol WL, Wokke JHJ, Lindeman E, Van Der
Berg LH. Effects of non-invasive ventilation on survival, quality of life, respiratory function
and cognition: a review of the literature. Amyotroph Lateral Scler. 2006;7:195–200.
810 M.-C. Rousseau and S. Pietra

5. Georges M, Morélot-Panzini C, Similowski T, Gonzalez-Bermejo J. Noninvasive ventilation

reduces energy expenditure in amyotrophic lateral sclerosis. BMC Pulm Med. 2014;14:17.
6. Mustfa N, Walsh E, Bryant V, Lyall RA, Addington-Hall J, Goldstein LH, Donaldson N,
Polkey MI, Moxham J, Leigh PN. The effect of noninvasive ventilation on ALS patients and
their caregivers. Neurology. 2006;66(8):1211–7.
7. Tsolaki V, Pastaka C, Kostikas K, Karetsi E, Dimoulis A, Zikiri A, Koutsokera A, Gourgoulianis
KI. Noninvasive ventilation in chronic respiratory failure: effects on quality of life. Respiration.
2011;81(5):402–10. doi:10.1159/000317138.
8. Ando H, Williams C, Angus RM, Thornton EW, Chakrabarti B, Cousins R, Piggin LH, Young
CA. Why don't they accept non-invasive ventilation?: insight into the interpersonal perspec-
tives of patients with motor neurone disease. Br J Health Psychol. 2014;20:341–59.
9. O'Neill CL, Williams TL, Peel ET, McDermott CJ, Shaw PJ, Gibson GJ, Bourke SC. Non-
invasive ventilation in motor neuron disease: an update of current UK practice. J Neurol
Neurosurg Psychiatry. 2012;83(4):371–6.
10. Cousins R, Ando H, Thornton E, Chakrabarti B, Angus R, Young C. Determinants of accept-
ing non-invasive ventilation treatment in motor neurone disease: a quantitative analysis at
point of need. Health Psychol Behav Med. 2013;1(1):47–58.
 Part XI
Non Invasive Ventilation Pediatric
Interfaces for Acute and Long-Term
Noninvasive Positive Pressure 95
Ventilation in Children: Key Technical
Elements and Clinical Implications

Brigitte Fauroux, Adriana Ramirez,

and Alessandro Amaddeo

Contents
95.1 Introduction ................................................................................................................. 814
95.2 Interfaces for Children ................................................................................................ 814
95.3 Side Effects and Monitoring of the Interface .............................................................. 819
95.4 How to Choose the Optimal Interface? ....................................................................... 821
Conclusion ............................................................................................................................. 823
References .............................................................................................................................. 824

B. Fauroux, MD, PhD (*)

Pediatric Noninvasive Ventilation and Sleep Unit,
AP-HP, Hôpital Necker-Enfants Malades, Paris, France
Paris Descartes University, Paris, France
Inserm U 955, Team 13, Creteil, France
e-mail: [email protected]
A. Ramirez, MSc
ADEP Assistance, Suresnes, France
Pediatric Noninvasive Ventilation and Sleep Unit,
AP-HP, Hôpital Necker-Enfants Malades, Paris, France
e-mail: [email protected]
A. Amaddeo, MD
Pediatric Noninvasive Ventilation and Sleep Unit,
AP-HP, Hôpital Necker-Enfants Malades, Paris, France
Paris Descartes University, Paris, France
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 813

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_95
814 B. Fauroux et al.

Abbreviations

CPAP Continuous positive airway pressure

NPPV Noninvasive positive pressure ventilation
PICU Pediatric intensive care unit
OSAS Obstructive sleep apnea syndrome

95.1 Introduction

Noninvasive positive pressure ventilation (NPPV) is increasingly used in children,

both in the acute and the chronic setting. Indeed, acute or chronic respiratory failure
or various origins may be improved or cured by means of NPPV. NPPV is now
recommended as a first-line therapy in the pediatric intensive care unit (PICU) for
bronchiolitis [1–5], acute respiratory exacerbations caused by neuromuscular dis-
ease, cystic fibrosis [6–8], pneumonia [9, 10], or sickle cell disease [11], and upper
airway obstruction [12–14]. The number of children treated at home with long term
NPPV for neuromuscular or lung disease, or various causes of upper airway obstruc-
tion is also growing rapidly [15–17]. However, respiratory mechanics and maxillo-
facial development are different in children as compared to adults, which justify
age-adapted ventilators, interfaces, and headgears.
This chapter presents the different types of interfaces available for children in the
acute and chronic setting, their advantages and limitations, how to choose the opti-
mal interface, and how to monitor the tolerance of the interface.

95.2 Interfaces for Children

Noninvasive interfaces can be classified as follows (Figs. 95.1, 95.2, 95.3, 95.4,
95.5, 95.6, 95.7, 95.8, and 95.9):

• Nasal pillows or plugs (which occlude the outer part of the nostrils),
• Nasal masks, which cover the nose
• Nasobuccal masks, which cover the nose and the mouth
• Full face masks, which cover the mouth, the nose, and the eyes
• Mouthpieces or oral masks
• And the helmet, which covers the entire head.

Nasal pillows or plugs are minimal-contact interfaces that are available for
patients weighing more than 30 kg, but small sizes can be used in children of 6–8
years (Fig. 95.1). They have the major advantage of exerting no pressure contact on
the child’s face. The acceptance of these interfaces is generally excellent in school-
aged children in whom they are proposed as first-line interfaces for NPPV [18].
Because of the minimal dead space, the patient may sometimes have the impression
that the level of positive pressure is higher with nasal pillows than with another
95 Interfaces for NPPV in Children 815

Fig. 95.1 Nasal pillows or

plugs

Fig. 95.2 Nasal mask on

an infant

Fig. 95.3 Nasal mask on a

boy with Prader Willi
syndrome
816 B. Fauroux et al.

Fig. 95.4 Nasobuccal mask on a boy with Treacher Collins syndrome

Fig. 95.5 Full face mask

interface. The headgear may be a limitation in these interfaces that have been mainly
developed for adults.
Nasal masks are the most commonly used interfaces, with numerous different
models being available (Figs. 95.2 and 95.3). Models differ with regard to the pres-
ence or not of a forehead support, internal flap, and type of fixation. These masks
are the only industrially available interfaces for preschool children and, more
recently, infants and neonates (weight >3–3.5 kg) (Fig. 95.2). In young children,
nasal masks are preferred to larger masks because they have less static dead space,
are less claustrophobic, and allow communication and expectoration more easily
95 Interfaces for NPPV in Children 817

Fig. 95.6 Oral mask on a

child with severe
obstructive sleep apnea and
total obstruction of the
nasal airways

Fig. 95.7 Mouthpieces for

mouthpiece ventilation

than nasobuccal or full face masks. Nasal masks also allow the use of a pacifier in
infants, which may contribute to a better acceptance of NPPV and the reduction of
mouth leaks (Fig. 95.2). New models integrating thin internal flaps that inflate with
the airway pressure are associated with a better skin tolerance because of a reduc-
tion in the pressure forces.
Nasobuccal masks cover the nose and the mouth and are indicated in case of
mouth breathing during sleep (Fig. 95.4). These interfaces are larger, have a greater
818 B. Fauroux et al.

Fig. 95.8 Helmet on an

infant in the pediatric
intensive care unit

Fig. 95.9 Infant nasal

cannula

dead space, and are heavier than nasal masks. Some have a forehead support. These
interfaces are contraindicated in case of esogastric reflux and when the child is not
able to remove the interface by himself because of the potential risk of inhalation.
Full face masks cover the mouth, the nose, and the eyes (Fig. 95.5). They are
used as last-choice masks, in case of intolerance or non-acceptance of all the other
interfaces. They may cause claustrophobia and, as with the nasobuccal masks, are
not recommended in case of reflux.
Mouthpiece and oral masks allow ventilation through the mouth (Figs. 95.6 and
95.7). Mouthpieces are generally used on demand during daytime in patients with
neuromuscular disease as a daytime extension of nocturnal ventilation with another
interface [19, 20]. They have been exceptionally used in children with total nasal
obstruction and severe obstructive sleep apnea syndrome (OSAS) [21].
The helmet is a commonly used interface in the PICU (Fig. 95.8). This interface
is composed of a plastic transparent bag that covers the entire head of the patient
and that is sealed around the neck by a hermetic collar. Two ports act as an inlet
95 Interfaces for NPPV in Children 819

(upper) and outlet (lower) of the gas flows. This interface can be used for continuous
positive airway pressure (CPAP) or bilevel ventilation. Its use has been evaluated
during acute exacerbations of neuromuscular disease in children in the PICU [22,
23]. The helmet has proved to be an efficient alternative to a nasal or a face mask but
its large dead space and the risk of asphyxia in case of power failure or other techni-
cal problems restricts its use to the PICU. Also, the quality of the ventilatory sup-
port may be less optimal with this interface compared with a nasobuccal mask or a
tracheal cannula [24]. In premature infants or neonates, nasal cannula or nasal
masks can be used to deliver oxygen, CPAP, or humidified high-flow oxygen, which
creates a low CPAP level, in the neonatal ICU (Fig. 95.9).
Interfaces can be vented or non-vented, that is, with or without intentional leaks.
The choice of non-vented interfaces is more limited than that of vented interfaces.
Vented interfaces need a minimal positive end-expiratory pressure, which is gener-
ally 4 cmH2O. In adult patients, the importance of manufacturer intentional leaks on
the mask may influence the quality of NPPV. Indeed, a first bench study showed that
the type of interface and importance of leaks did not influence trigger performances
[25]. However, the ability to achieve and maintain inspiratory positive airway pres-
sure was significantly decreased with all ventilators and in all simulated lung condi-
tions when intentional leaks increased (especially when leaks > 40 l/min). Another
study showed that the importance of manufacturer intentional leaks on the mask
was able to modify patient-ventilator synchronization, ventilator performance, and
risk of rebreathing [26]. Such studies have not been performed in children. However,
a systematic clinical evaluation of every mask change is recommended, checking
and eventually adjusting the inspiratory trigger sensitivity and pressurization, and
checking the absence of rebreathing [27].
For all types of interfaces, the headgear is of crucial importance. Indeed, the face
and skull of children requiring ventilatory support differ from healthy children [18].
An inappropriate headgear may compromise the use of a well-adapted interface in
children. The most important qualities of a headgear are the appropriate size, stabil-
ity, and the ease with which it can be put on and removed.

95.3 Side Effects and Monitoring of the Interface

The interface represents a crucial determinant of the success of NPPV. The patient
will be unable to tolerate and accept NPPV in case of facial discomfort, skin injury,
or significant unintentional leaks. The evaluation of the short- and long-term toler-
ance of the nasal mask is thus an essential component of NPPV [28] (Figs. 95.10,
95.11 and 95.12).
Interfaces for NPPV need to be adapted to the facial anatomy and physiognomy
of children. In the chronic setting, a growing number of young patients are treated
with NPPV. These patients represent a heterogeneous group, not only with regard to
the underlying disease, but also with regard to age, weight, and maxillofacial physi-
ognomy [15, 18, 29–31]. Numerous children have genetic diseases associated with
facial deformities, such as, for example, Treacher Collins syndrome, Goldenhar
820 B. Fauroux et al.

Fig. 95.10 Skin injury caused by a nasal mask

Fig. 95.11 Maxilla retrusion in a boy ventilated since 3 years for severe laryngomalacia

syndrome, Pierre Robin syndrome, achondroplasia, or osteogenesis imperfecta.

Individually adapted interfaces are thus mandatory for these patients. In our experi-
ence, children with OSAS resulting from maxillofacial deformity represented the
group that needed the greatest number of mask changes [18].
The soft tissue beneath the skin is thinner in children compared with adults.
Children are thus at greater risk of skin injury during NPPV than adults (Fig. 95.10).
Skin injury occurs as a consequence of pressure sores, which are defined as a lesion
on any skin surface that occurs as a result of pressure. The principal causative fac-
tor is the application of localized pressure to an area of skin not adapted to the
magnitude and duration of such external forces. Tissue damage will occur if both a
95 Interfaces for NPPV in Children 821

critical pressure threshold and a critical time are exceeded. Because young children
may need NPPV during extended periods including nocturnal sleep and daytime
naps, they are at increased risk of skin injury [28]. The effect of repetitive loading
on skin and bone tissue is also of major importance, which is the case during
NPPV. The anatomy of the facial bones and the proportions between the facial ele-
ments differ in children compared with adults. The anatomy of the maxillofacial
structures changes continuously during growth, which is particularly rapid during
the two first years of life. Facial growth occurs predominantly in an anterior and
sagittal axis in children. NPPV hinders this normal facial growth and may cause
facial deformity (Figs. 95.11 and 95.12). Indeed, NPPV is always used during
sleep, which can represent the major part of the day in young infants. In these
young patients, there is thus a potential risk of facial flattening and maxilla retru-
sion, caused by the pressure applied by the mask on growing facial structures.
Facial flattening and maxilla retrusion are commonly observed in children receiv-
ing long-term NPPV by means of nasal or nasobuccal masks, which justifies a
systematic evaluation and follow-up by a pediatric maxillofacial surgeon before
and during NPPV [28]. When possible, alternative use of different interfaces to
vary the pressure forces may reduce these side effects.
Monitoring of the facial side effects of interfaces is of crucial importance in
young children in whom interfaces need to be changed frequently because of the
rapid growth of the facial structures. The caregivers and the child (if old enough)
should be informed about the need to alert the NPPV team about any facial side
effect or poor or non-tolerance of the interface.

95.4 How to Choose the Optimal Interface?

The choice of the interface depends on:

• The patient’s age and weight

• The facial (and skull) anatomy and adaptability of the headgear
• The presence of mouth breathing and nasal permeability
• The ventilatory mode, requiring a vented or non-vented interface
• The patient’s autonomy with regard to the removal of the interface (e.g., in
patients with neuromuscular disease)
• The patient’s comfort with the mask and the level of unintentional leaks
• The patient’s tolerance with regard to skin injury and facial deformity
• The clinical situation: in an acute setting, mouth breathing is common, which
explains the greater use of nasobuccal or full face masks in the PICU than in the
home setting. Pressure sores are also more common in the ICU because of the
greater instability of the patients.

Figure 95.13 shows an updated algorithm of mask choice. Indeed, because of the
availability of industrial nasal masks for newborns and infants, we did not need to
make any custom-made masks in our unit over the last year [18].
822 B. Fauroux et al.

Fig. 95.12 Facial

flattening in a girl with
spinal muscular atrophy
ventilated with a nasal
mask

Leak or no leak ventilation

Age > 6–8 years

No Yes

Nasal mask Nasal prongs

Failure or
preference
Failure or preference
in children >6–8
years

Nasobuccal mask

Fig. 95.13 Algorithm for mask choice

95 Interfaces for NPPV in Children 823

Compliance with NPPV can be excellent with any type of interface when the
choice of the interface is appropriate. Indeed, our experience, objective compliance
reached almost a mean night use of 8:30 in a consecutive cohort of 62 children
treated with long-term NPPV at home [18]. Objective compliance was not related to
the age, gender, duration of home NPPV, or type of interface. Of note, compliance
was similarly excellent in adolescents using nasal pillows or plugs, underlining the
interest in this type of interface for this age group.

Conclusion
Important improvements have been made in interfaces for children. Nasal masks
for young infants are now available and several comfortable nasal masks are
available for older children, Nasal plugs or pillows are well accepted by older
children. However, headgears could be improved and the availability of nasal
plugs or prongs and nasobuccal interfaces for young children would constitute
further progress (Table 95.1).

Table 95.1 Advantages, limitations, and side effects of the different types of interfaces available
for NPPV in children
Interface Advantages Limitations Side effects
Nasal Small, light Not available for infants Nasal irritation
pillows or plugs No pressure sores Not to be used when mouth
breathing
Nasal mask Small volume Not to be used when mouth Pressure sores
Large choice breathing
Nasobuccal Prevents Large volume Pressure sores
mask mouth leaks Not available for infants
Full face mask Prevents mouth leaks Large volume, claustrophobic Pressure sores
Helmet No pressure sores Large dead space, claustrophobic Noise, pressure
For the PICU only around the head
Can decrease the sensibility (eyes)
of the ventilator’s trigger
Abbreviations: PICU pediatric intensive care unit

Key Major Recommendations

• The choice of an interface should take into account the type of ventilation,
the child’s facial anatomy, the type of breathing, and the acceptance and
comfort of the child.
• A change in the interface can modify the efficacy of NPPV.
• The choice of headgear is as important as that of the interface.
• Every child on NPPV should be monitored closely for potential interface-
related side effects such as skin injury or facial deformity.
• Objective compliance with NPPV can be excellent with every type of
interface when appropriately chosen.
824 B. Fauroux et al.

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 Part XII
Non Invasive Ventilation, Epidemiology, Health
Care Organization, Education and Ethics
Epidemiology, Practice and New Trends
in Noninvasive Mechanical Ventilation: 96
What Are We Learning?

Claudia Crimi and Annalisa Carlucci

Contents
96.1 Epidemiology of Noninvasive Ventilation in the Acute-Care Setting ........................ 830
96.1.1 Introduction ................................................................................................... 830
96.1.2 Discussion and Analysis................................................................................ 830
96.1.3 New Trends in NIV ....................................................................................... 835
Conclusion ............................................................................................................................. 837
References .............................................................................................................................. 838

Abbreviations

AECOPD Acute exacerbation of chronic obstructive pulmonary disease

ACPE Acute cardiogenic pulmonary edema
ARF Acute respiratory failure
CHF Congestive heart failure
DNI Do-not-intubate
DNR Do-not-resuscitate
ED Emergency department
ICU Intensive care unit
NIV Noninvasive ventilation

C. Crimi, MD, PhD

Respiratory Intensive Care Unit,
Azienda Ospedaliera per l’Emergenza Cannizzaro, Catania, Italy
e-mail: [email protected]
A. Carlucci, MD (*)
Respiratory Intensive Care Unit and Pulmonary Rehabilitation,
Fondazione Salvatore Maugeri-IRCCS, Pavia, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 829

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_96
830 C. Crimi and A. Carlucci

96.1 Epidemiology of Noninvasive Ventilation in the Acute-

Care Setting

96.1.1 Introduction

Noninvasive ventilation (NIV) represents one of the most important advances in the
field of pulmonary and critical care medicine of the last 30 years. The efficacy of
NIV in appropriately selected patients with acute respiratory failure (ARF) has been
widely confirmed by several randomized controlled trials and meta-analyses. Strong
evidence supports the application of NIV as a first-line treatment in patients with
acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute
cardiogenic pulmonary edema (ACPE). Moreover, NIV has also been proven to be
beneficial in patients with respiratory failure following solid organ transplantation
and in those who are immunocompromised and to wean chronic obstructive pulmo-
nary disease (COPD) patients from invasive ventilation [1] (Table 96.1).
Although the compelling evidence for the benefit of NIV has been shown by the
literature, the implementation of this innovative tool in clinical practice found sev-
eral barriers, initially. The increasing number of research articles published on the
topic, year in and year out, highlighted physicians’ interest on this new tool that,
although very attractive, has a substantial learning curve and important prerequi-
sites for successful implementation.

96.1.2 Discussion and Analysis

96.1.2.1 The Surveys: How Much NIV Is Used in Real Life

Several surveys have explored the pattern of NIV use and awareness among clini-
cians at various institutions in different geographic areas. These studies overall,
showed a heterogeneous distribution of NIV practices among different countries
that has been changing over time [2].

Table 96.1 Patient selection for NIV

Absolute contraindications
Coma (not attributed to CO2 narcosis)
Cardiac arrest
Respiratory arrest (apnea or agonal respirations)
Any other condition requiring immediate intubation
Relative contraindications (exceptions should be reviewed on a case–by-case basis)
Cardiac instability (shock, vasopressor requirements, cardiac instability due to
dysrhythmias, complicated myocardial infarction)
Gastrointestinal bleeding (hemodynamic instability, hematemesis)
Potential upper airway obstruction (head and neck tumor, angioedema)
Inability to protect airway due to depressed sensorium, inability to cough or clear secretions
(cerebrovascular accident, advanced neuromuscular disease, severe drug overdose)
Status epilepticus
96 Epidemiology, Practice and New Trends in Noninvasive Mechanical Ventilation 831

One of the first surveys, conducted in 1998, assessed NIV use and availability in
268 acute care hospitals in the United Kingdom and found that, at that time, NIV
was available in only half of the surveyed hospitals (especially in the intensive care
units (ICUs)) and, when available, was underutilized (used >60 patients/year in only
7 % of hospitals). A similar result was highlighted by Vanpee and coworkers in
2002 when exploring the availability and use of NIV for the treatment of AECOPD
in an emergency department (ED) in Belgium[2].
The estimated utilization rate of NIV in acute care settings was also relatively
low (20 %) among North American (Massachusetts and Rhode Island) respiratory
therapists, with great regional variations, as pointed out by a survey published in
2006 [2]. In all of these studies, lack of physician knowledge or training, equipment,
and financial limitations were the main declared barriers to NIV use. Similar results
of a low penetration of NIV for the treatment of AECOPD throughout Canadian
urban hospitals were registered in another survey conducted during in 2004 [2]
(Table 96.2).

Table 96.2 Clinical conditions suitable for management with noninvasive ventilation
Established efficacy (for most patients, multiple studies)
Chronic obstructive pulmonary disease (COPD) exacerbations
Cardiogenic pulmonary edema (CPE)
Efficacy in selected patients (effective in subgroups or experience limited)
Asthma
Post-extubation; following discontinuation of mechanical ventilation (COPD and hypercapnia)
Community acquired pneumonia (and COPD)
Immunocompromised state and infiltrates (known cause of infiltrates)
Solid organ transplants
Febrile neutropenic patients
Postoperative respiratory distress and respiratory failure
Atelectasis
Postoperative lung resection
Rib fractures
Trauma with nonpenetrating chest injury; flail chest
Decompensated obstructive sleep apnea/cor pulmonale
Efficacy promising or limited (limited reports)
Acute respiratory distress syndrome (ARDS)
Do not intubate status
Cystic fibrosis
Interstitial lung disease
Neuromuscular respiratory failure (better in chronic than acute respiratory failure); best to
avoid if upper airway issues
Kyphoscoliosis
Muscular dystrophy
Post-polio syndrome
Severe acute respiratory distress syndrome (SARS)
Mild Pneumocystis jiroveci pneumonia
832 C. Crimi and A. Carlucci

The stunning dissemination of scientific literature on the utility of NIV has likely
been able to overcome the initial barriers to the technique, and NIV has started to
become more widely available in hospitals, but, again, important regional differ-
ences have been registered. In fact, a postal survey published in 2005 [2] aimed at
exploring physicians’ stated practices regarding the use of bi-level NIV for ARF in
Ontario, Canada, showed the availability of NIV and protocols or guidelines for its
application in 12 out of the 15 interviewed hospitals, with a great variation in NIV
utilization among physician specialties (critical care, pulmonology, and internal and
emergency medicine).
Devlin and coworkers, in their international web-based survey of intensivists
published in 2007, reported a marked regional variation in stated use of NIV in
ARF. Overall, Europeans were more likely to use NIV than North American physi-
cians and preferably in AECOPD, congestive heart failure (CHF), and obesity
hypoventilation syndrome. On the contrary, they pointed out that North American
physicians were more inclined to use sedatives (41 % vs 24 %), analgesics (48 % vs
35 %), and hand restraints (27 % vs 16 %) during NIV treatment compared with the
Europeans [2].
The results of a questionnaire distributed to North American physicians and
respiratory therapists working in EDs, published in 2009, pointed out that 90 % of
respiratory therapists and 64 % of physicians stated that they were very familiar
with NIV and that its use in the ED is more common for AECOPD and CHF; more-
over, the study confirms the already known barriers to a greater application of this
technique such as: physician familiarity, equipment availability in EDs, and the
human cost and raises the important problem of the availability of respiratory thera-
pists (RTs) [3]. Another study published in 2009 [4] showed a wide availability of
NIV in the American Veterans Affairs health-care system, where NIV can be acces-
sible in both monitored (ICU, step-down, EDs) and unmonitored settings; however,
its use and perceived efficacy among the interviewed clinicians was low, with a
success rate of >50 % noted by only 29 % of respondents.
The setting where the scientific evidence had largely influenced everyday clinical
practice, resulting in an extensive application of NIV in real life, seems to be with
patients with do-not-resuscitate (DNR) orders. The Canadian group of Sinuff and
coworkers [2] showed that NIV is a quite frequently considered option for this
cohort of patients and that >80 % of clinicians initiate NIV mainly in DNR patients
with COPD or CPE. Fewer (59 % of physicians, 69 % of RTs) stated using NIV for
DNR patients with underlying malignancy or for patients choosing comfort mea-
sures only (40 % of physicians, 51 % of RTs). The study also showed that pulmon-
ologists were more likely than intensivists to use NIV in the management of
do-not-intubate (DNI) patients.
Data on frequency of NIV use and availability of resources for its delivery were
also recorded in Spain [5] with a study published in 2008 showing quite high NIV
utilization rate among Spanish ICUs, respiratory medicine departments, and EDs
(100 %, 88 % and 69 % of respondents, respectively) and a relatively low percentage
of use in internal medicine departments (37 %) and other wards (11 %), with a great
heterogeneity in terms of type of patients and equipment and lack of protocols.
96 Epidemiology, Practice and New Trends in Noninvasive Mechanical Ventilation 833

Another European survey published in 2010 [6] showed a relatively high utiliza-
tion rate of NIV, with considerable differences based on the underlying disease of
respiratory failure (mainly AECOPD), with an overall greater utilization of the
technique mainly by pulmonologists (52.9 % reported >20 % of patients treated
with NIV/year vs 34.3 % of intensivists/anesthesiologists). The study showed that
pulmonologists were more likely to use NIV in the treatment of AHRF compared
with intensivists (58.9 % vs 35.2 %). Conversely the latter were more likely to use
NIV in patients with ACPE (18.7 % vs 7.2 %), hypoxic respiratory failure (19.1 %
vs 6.2 %), and weaning from invasive ventilation (14.4 % vs. 8.5 %) (p < 0.05). For
all the physicians interviewed, the preferred equipment for NIV was dedicated NIV
ventilators and an oronasal interface.
In conclusion, the clinical application of NIV has slowly but significantly
increased in the last 10 years in ICUs as well as in respiratory medicine departments
and EDs. Its use seems to be in line with scientific evidence. However, differences
between European and North American practices are still evident, the latter being
less prone to use NIV, even in clinical situations with strong evidence for its use.

96.1.2.2 Observational Studies: Clinical Results in Real-Life

The accumulating evidence for the efficacy of NIV has increased its use in clinical
practice over time, as shown by observational studies based on on-site data collec-
tion at selected hospitals rather than on clinicians’ estimates of use in response to
questionnaires [2].
In 2003, Girou et al. published a retrospective study analyzing the clinical data
of their 26-bed medical ICU from 1994 through 2001. The authors found a gradual
and significant increase in NIV for similar patients admitted for AECOPD or ACPE
over the 8-year period with a positive impact on patients’ outcome due to a reduc-
tion in complications related to invasive mechanical ventilation, such as nosocomial
infections, either pneumonia and urinary, and catheter-related infections. Also, mor-
tality rates in these subgroups of patients significantly improved over the years,
probably as a consequence of the reduction of infections [2].
A larger survey [2] involving 42 ICUs in Europe (France, Switzerland, Belgium,
and Spain) and Tunisia aimed to prospectively follow all consecutive admissions
for ARF over an observation period of 3 weeks. A total of 1,337 patients were
admitted over that period for ARF (hypoxic (48 %), hypercapnic (15 %), coma
(30 %), CHF (7 %)). Among the 689 patients requiring ventilatory support, NIV
was used as initial ventilation approach in 108 (16 %) and was discontinued in 52
(48 %) due to lack of arterial blood gas improvement (46 %), inability to manage
copious secretions in 32 %, patient’s refusal to continue NIV in 22 %, and full
dependence on ventilatory support in 11 %. The 28-days hospital mortality was
significantly higher in those who needed IMV, compared with those who received
NIV (41 % vs 22 %). The incidence of ventilator-associated pneumonia was as low
as 2 % in patients who were successfully managed with NIV compared with 19 %
in those who needed IMV.
Five years later, a new version of the same survey was performed in French ICUs
with the aim of evaluating a possible change in the NIV use and success rate over
834 C. Crimi and A. Carlucci

time [2]. The authors showed an increased utilization of NIV from 16 to 23 % of the
total ventilated patients and from 35 to 52 % of patients not intubated before ICU
admission. Significant increases in NIV use were noted mainly for acute-on-chronic
respiratory failure (50 % vs 64 %) and hypoxic respiratory failure (14 % vs 22 %),
with an unchanged success rate.
A similar trend in increasing use of NIV to treat ARF was also described in a large
survey on 349 ICUs in 23 countries. Comparing with a cohort study published in
1998, Esteban et al. showed a change in the use of NIV from 4 to 11 % in 2008.
Despite strong evidence coming from the literature, the absolute percentage of NIV
use remains low. As in the French survey, no differences in outcomes were found [2].
Similar results were shown in an epidemiological study performed in the United
States by Stefan and coworkers [7], who found a steady increase in the number of
hospitalizations over the period from 2001 to 2009 with a discharge diagnosis of
ARF identified using the ICD-9 coding system. The study highlighted a decrease in
inpatient mortality and a significant shift toward the use of NIV that increased sig-
nificantly from 3.8 to 10.1 %, with a decrease in the rates of invasive mechanical
ventilation use (Table 96.3).

96.1.2.3 NIV Outside the ICU

The majority of studies on NIV have been conducted in the ICU, which is certainly
the ideal setting for an effective and safe use of this technique in acute and poten-
tially fatal episodes of respiratory failure. Nevertheless, the emerging scientific evi-
dences on the benefit of NIV in several common clinical scenarios such as AECOPD,
ACPE, and acute respiratory failure in immunocompromised patients, also made
NIV an appealing and attractive tool in clinical practice outside the ICU setting,
especially in general wards [8].
Paus-Jenssen [9] described the feasible use of NIV outside the critical care set-
ting in a single center in Canada, observing all consecutive patients hospitalized for
ARF (AECOPD, hypoxic respiratory failure, hypercapnic respiratory failure, CHF,
and patients with shortness of breath) over a 5-month period. The author found no

Table 96.3 Predictors of Severity of illness (moderate to severe)

response to NIV
Hypercapnic respiratory acidosis (pH 7.20–7.34); lower
limit of effectiveness not known
APACHE II (Acute Physiology and Chronic Health
Evaluation) score <25
Glasgow Coma Scale >11
Respiratory rate ≤35
Combination may further identify poor candidates
Trial of therapy (response to 1–2 h trial)
Improvement in respiratory parameters (respiratory rate,
oxygenation, dyspnea)
Improvement in pH (increase by ≥0.06)
Improvement in PaCO2 (decline by ≥8 mmHg)
96 Epidemiology, Practice and New Trends in Noninvasive Mechanical Ventilation 835

difference in outcome and mortality compared with data from controlled studies
performed in more aggressively monitored patients.
An international survey published in 2015 explored the use of NIV outside the
ICU, in general non-monitored ward evaluating settings and modalities of NIV
application and monitoring, estimated outcomes, technical and organizational
aspects, and observed complications [10]. NIV application in general wards was
reported by nearly 66 % of the respondents and perceived as feasible and effective.
Limited training and economic resources were highlighted as possible limitations to
NIV application.
The possibility of using NIV even in the pre-hospital setting was studied by
Bruge et al., who reported the results of a 2-year prospective observational investi-
gation of NIV in pre-hospital care, in emergency-response vehicles equipped with
bi-level ventilators with favorable and appealing results [8].

96.1.3 New Trends in NIV

96.1.3.1 Bronchoscopy
The use of NIV during diagnostic and therapeutic bronchoscopy has been reported
as a feasible and safe strategy but further studies need to address its impact on mor-
tality and intubation rate in critically ill patients [11]. NIV-assisted bronchoscopy
may be useful in obtaining lung biopsy or bronchoalveolar lavage in patients with
severe hypoxemia and lung infiltrates, but, although there are several reports on the
feasibility of this application, NIV during bronchoscopy should be performed only
in centers with a wide experience (Table 96.4).

Table 96.4 Intubation Intubation criteria (any one of the following):

guidelines
Cardiac or respiratory arrest
Loss of consciousness
Hemodynamic instability with systolic blood pressure
<70 mmHg
PaO2 <45 mmHg despite oxygen
Intubation criteria (two or more in the context of respiratory
distress):
Respiratory rate >35/min or <6/min
Tidal volume <5 ml/kg
Oxygen desaturation <90 % despite adequate supplemental
oxygen
pH <7.20 and decreasing on NIV support
Hypercapnia (PaCO2 >10 mm increase) or acidosis
(pH decline >0.08) from baseline
Increase in encephalopathy or decreased level of
consciousness
Abdominal paradox
Modified from Refs. [1, 9]
836 C. Crimi and A. Carlucci

96.1.3.2 Interventional Procedures

NIV may represent a great opportunity for patients with a high risk of undergoing
general anesthesia due to old age and/or co-morbidity or orthopnea due to severe
lung-disease [11]. Boitano et al. [12] used bi-level NIV to support five patients with
amyotrophic lateral sclerosis and forced vital capacity that ranged from 21 to 44 %
of predicted during percutaneous endoscopic gastrostomy tube placement, without
experiencing any complications.
NIV advantages have also been described in case series, during the perfor-
mance of continuous transesophageal echocardiograph examination in lightly
sedated patients with severe aortic valve stenosis and orthopnea, through a modi-
fied face mask, avoiding intubation and general anesthesia without complications
[11]. In another report of the literature [13], patients with severe pulmonary dis-
ease and considerable orthopnea uneventfully underwent percutaneous implanta-
tion of an aortic bioprosthesis for severe valve stenosis during NIV with conscious
sedation.
A case report on the successful use of pressure support during urgent coronary
angiography and stent implantation in an 86-year-old women with ARF due to myo-
cardial infarction complicated by ACPE was published by Rucci and colleagues [14].

96.1.3.3 Chest Trauma

The use of NIV has also been reported in patients with chest trauma with the goal
of preventing or treating respiratory failure and a recent meta-analysis grouping 10
studies on chest trauma patients showed a significant benefit in the NIV group of
patients compared with the control group, with an improvement of oxygenation and
a reduction of endotracheal intubation, ICU length of stay, and mortality (3 % vs.
22.9 %) [11].

96.1.3.4 Palliative Treatment

NIV may represent a chance to reduce and alleviate respiratory symptoms, reducing
the amount of sedation need, in patients with a nonreversible cause of respiratory
failure. The use of NIV in patients with DNI orders was reported by almost 50 % of
European physicians [11].

96.1.3.5 Postoperative Respiratory Failure

The application of NIV after complex surgical procedures in patients with high
risk for postoperative acute respiratory failure (e.g., obesity) has been described.
Several studies showed that it may be helpful in preventing and treating ARF after
major surgery (abdominal and lung), reducing patients’ intubation rate compared
to oxygen treatment [11]. Jaber et al. suggested that the two potential goals of
NIV in the postoperative period are to prevent acute respiratory failure (prophy-
lactic treatment) and to treat acute respiratory failure and avoid re-intubation
(curative treatment). The use of prophylactic CPAP for at least 6 h following
extubation compare to standard treatment was tested by Zarbock et al. The authors
found a lower incidence of pneumonia, re-intubation rate, and ICU readmission in
the intervention group, suggesting a positive effect of CPAP in preventing postop-
erative atelectasis [11].
96 Epidemiology, Practice and New Trends in Noninvasive Mechanical Ventilation 837

96.1.3.6 Pandemics
Some reports on the successful use of NIV during major pandemics such as SARS
and H1N1 are available, but the safety of its use in these clinical situations has gen-
erated some concerns. Cheung et al. reported their experience with NIV and SARS
in Hong Kong, showing that NIV was able to avoid intubation and to reduce ICU
length of stay compared with intubated patients. The major debate is on the safety
of NIV, because, during exhalation, infectious droplets can be spread into the ambi-
ent air through the exhalation ports of the NIV mask or tubing, enhancing the risk
of contamination for the caregiver. A bench study of aerosol dispersion during NIV
showed a dispersion that ranged up to 0.5 m from the mask; therefore, clinicians
might be at high risk of contamination. We suggest that health-care workers provid-
ing NIV, working close to an infected patient, should have a higher level of respira-
tory protection. In fact, two reports showed no evidence of viral contamination to
caregivers when appropriate precautions were adopted [11].

Conclusion
NIV represents one of the major advances in pulmonary and critical care medi-
cine of the last three decades that has proven to change dramatically the outcome
of some patients with respiratory failure. Although there is striking evidence
proving its utility in clinical practice, its actual use in real life, as reported by
surveys and observational studies, is still heterogeneous. Nevertheless, the litera-
ture suggests that NIV use increases as clinicians become more familiar with its
use and human and economic resources are available. As with every innovation,
a more even dissemination of NIV requires hard work, problem solving, thinking
“outside the box,” not fearing failure, and being comfortable with unknown.
Moreover, undoubtedly NIV requires the knowledge of some technical aspects
that can appear complex to the naïve user. Educational programs in some places
are judged inadequate and need to be implemented.
Indeed, NIV is probably more art than science, and requires a considerable
learning curve, the need of team work and dedicated staff, and the possibility of
having a selection of devices and interfaces. Adequate training and educational
programs for medical students, residents, and attending physicians of different
specialties and also hospital staff on evidence-based learning objectives to guide
NIV instructions is strongly suggested to further expand the use of this valuable
technique in clinical practice and to optimize its success. We expect a more
widespread use in coming years, with the advances in ventilator and mask tech-
nology, and increasing experience and skill at acute care centers.

Key Major Recommendations

• NIV should always be used, when clinically indicated, as a first-line
method of ventilation, before invasive mechanical ventilation is consid-
ered, but in some institutions it remains underutilized.
• Barriers to greater use at low-utilizing institutions include lack of educa-
tion of the staff and lack of appropriate equipment.
838 C. Crimi and A. Carlucci

• Educational programs are likely to remove some of these barriers and fur-
ther expand NIV diffusion.
• Overall, the use of NIV in real life has been increasing over the past decade
both inside and outside the ICU, in selected subgroups of respiratory fail-
ure, according to data from the literature.
• New trends in the application of NIV are emerging and seem promising,
but further larger studies need to confirm its safety.

References
1. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet.
2009;374(9685):250–9.
2. Pierson DJ. History and epidemiology of noninvasive ventilation in the acute-care setting.
Respir Care. 2009;54(1):40–52.
3. Hess DR, Pang JM, Camargo Jr CA. A survey of the use of noninvasive ventilation in aca-
demic emergency departments in the United States. Respir Care. 2009;54(10):1306–12.
4. Bierer GB, Soo Hoo GW. Noninvasive ventilation for acute respiratory failure: a national sur-
vey of Veterans Affairs hospitals. Respir Care. 2009;54(10):1313–20.
5. Chiner E, Llombart M, Martinez-Garcia MA, et al. Noninvasive mechanical ventilation in
Valencia, Spain: from theory to practice. Arch Bronconeumol. 2009;45(3):118–22.
6. Crimi C, Noto A, Princi P, et al. A European survey of noninvasive ventilation practices. Eur
Respir J. 2010;36(2):362–9.
7. Stefan MS, Shieh MS, Pekow PS, et al. Epidemiology and outcomes of acute respiratory fail-
ure in the United States, 2001 to 2009: a national survey. J Hosp Med. 2013;8(2):76–82.
8. Boldrini R, Fasano L, Nava S. Noninvasive mechanical ventilation. Curr Opin Crit Care.
2012;18(1):48–53.
9. Paus-Jenssen ES, Reid JK, Cockcroft DW, Laframboise K, Ward HA. The use of noninvasive
ventilation in acute respiratory failure at a tertiary care center. Chest. 2004;126(1):165–72.
10. Cabrini L, Esquinas A, Pasin L, et al. An international survey on noninvasive ventilation use
for acute respiratory failure in general non-monitored wards. Respir Care.
2015;60(4):586–92.
11. Ambrosino N, Guarracino F. Unusual applications of noninvasive ventilation. Eur Respir J.
2011;38(2):440–49.
12. Boitano LJ, Jordan T, Benditt JO. Noninvasive ventilation allows gastrostomy tube placement
in patients with advanced ALS. Neurology. 2001;56(3):413–4.
13. Guarracino F, Cabrini L, Baldassarri R, Petronio S, De Carlo M, Covello RD, et al. Noninvasive
ventilation for awake percutaneous aortic valve implantation in high-risk respiratory patients:
a case series. J Cardiothorac Vasc Anesth. 2011;25(6):1109–12.
14. Rucci G, Casale T, Nava S. First use of noninvasive ventilation during urgent coronary stenting
in acute myocardial infarction complicated by pulmonary edema. Intensive Care Med.
39(6):1166–7.
Determinants of Utilization
of Noninvasive Mechanical Ventilation 97
in Hospitals: Key Technical
and Nontechnical Issues

Guy W. Soo Hoo

Contents
97.1 Patient Selection.......................................................................................................... 840
97.2 Location of Therapy.................................................................................................... 842
97.3 Trial of Therapy .......................................................................................................... 843
97.4 Health-Care Staff ........................................................................................................ 843
97.5 Technical Issues .......................................................................................................... 844
97.5.1 Masks ............................................................................................................ 844
97.5.2 Ventilators...................................................................................................... 845
97.5.3 Modes of Ventilation ..................................................................................... 845
97.5.4 Ventilator Settings ......................................................................................... 846
97.6 Medication Delivery ................................................................................................... 847
97.7 Complications of NIV ................................................................................................. 847
97.8 Discontinuation of NIV .............................................................................................. 848
97.9 Failure of NIV ............................................................................................................. 848
Conclusion ............................................................................................................................. 849
References .............................................................................................................................. 849

Positive pressure noninvasive ventilation (NIV) delivered through a mask interface

has become a mainstay in the management of patients with acute respiratory failure
since the initial reports of its efficacy a little more than 25 years ago [1]. Indications
have expanded beyond exacerbations of chronic obstructive pulmonary disease
(COPD) to most causes of acute respiratory failure [2, 3]. However, despite wide-
spread endorsement and evidence-based support for its efficacy, utilization of NIV
remains quite variable. In Europe, NIV use in respiratory failure due to COPD

G.W. Soo Hoo, MD, MPH

Pulmonary and Critical Care Section (111Q),
West Los Angeles VA Healthcare Center, VA Greater Los Angeles
Healthcare System, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 839

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_97
840 G.W. Soo Hoo

approaches 50 %, but the utilization in the United States has been reported to be in
the 5–15 % range. There is a similar disparity in NIV utilization within countries
and states where local or regional use has been high. Although there is an overall
trend of increasing NIV use, actual application of NIV remains lower than the pool
of potential candidates for treatment [4, 5]. Unlike some critical care interventions
that only require limited engagement, a successful NIV program requires coordina-
tion and the support of the entire critical care infrastructure.
The most basic description of NIV involves the provision of ventilatory support
for patients with acute respiratory distress or respiratory failure through a mask
interface, thereby avoiding the “invasive” introduction of an endotracheal or trache-
ostomy tube into the tracheal bronchial tree. This “noninvasive” approach virtually
eliminates the potential complications and discomforts associated with invasive
ventilation. Although NIV provides ventilatory support, it may not be viewed as the
same level of life support as invasive ventilation. Other advantages include the pres-
ervation of speech, oral function, and, in some cases, oral intake, while providing an
easier transition on and off ventilator support than invasive ventilation. On the other
hand, NIV requires a little more staff vigilance for signs of ineffective or failing
therapy. Patients who fail therapy may be candidates for intubation. The timing of
intubation is often imperfect and may increase the risk of adverse outcomes. The
following provides an overview of the critical clinical (nontechnical) and technical
elements that influence utilization of NIV in the hospitalized patient.

97.1 Patient Selection

Proper patient selection is crucial for successful application of NIV. This requires
recognition of the severity of illness as well as the disease conditions best suited for
NIV. NIV is not well suited for patients with immediately life-threatening critical
illness. Since it uses a removal mask interface to deliver ventilatory support, it is
ineffective for those who need airway protection or those with shock and multiorgan
dysfunction. Those critically ill patients are better treated with immediate endotra-
cheal intubation and mechanical ventilation, bypassing treatment with NIV. Other
concomitant conditions that are better suited for invasive ventilation through an
endotracheal tube include active gastrointestinal bleeding, those with upper airway
obstruction, and patients with an inability to protect their airway (Table 97.1).
Once it is determined that the patient does not require immediate intubation,
careful consideration should be made of the underlying disease causing respiratory
failure. The vast majority of success with NIV has been accumulated in patients
with exacerbations of COPD, and these patients remain the best suited for
NIV. Cardiogenic pulmonary edema is another condition that readily responds to
NIV. Although these are the two best-suited conditions for NIV, there has been
expansion of NIV use into other causes of respiratory failure and in circumstances
where NIV has not been traditionally applied (Table 97.2).
The next step in patient selection is to determine the severity of their respiratory ill-
ness because this may influence their ability to be managed with NIV. This has been
97 Determinants of Utilization of Noninvasive Mechanical Ventilation 841

Table 1 Patient selection for noninvasive ventilation (NIV)

Absolute contraindications
Coma (not attributed to CO2 narcosis)
Cardiac arrest
Respiratory arrest (apnea or agonal respirations)
Any other condition requiring immediate intubation
Relative contraindications (exception should be reviewed on a case-by-case basis)
Cardiac instability (shock, vasopressor requirements, cardiac instability due to dysrhythmias,
complicated myocardial infarction)
Gastrointestinal bleeding (hemodynamic instability, hematemesis)
Potential upper airway obstruction (head and neck tumor, angioedema)
Inability to protect airway due to depressed sensorium, inability to cough or clear secretions
(cerebrovascular accident, advanced neuromuscular disease, severe drug overdose)
Status epilepticus

Table 2 Clinical conditions suitable for management with noninvasive ventilation

Established efficacy (for most patients, multiple studies)
Chronic obstructive pulmonary disease (COPD) exacerbations
Cardiogenic pulmonary edema (CPE)
Efficacy in selected patients (effective in subgroups or experience limited)
Asthma
Post-extubation, following discontinuation of mechanical ventilation (COPD and
hypercapnia)
Community acquired pneumonia (and COPD)
Immunocompromised state and infiltrates (known cause of infiltrates)
Solid organ transplants
Febrile neutropenic patients
Postoperative respiratory distress and respiratory failure
Atelectasis
Postoperative lung resection
Rib fractures
Trauma with nonpenetrating chest injury; flail chest
Decompensated obstructive sleep apnea/cor pulmonale
Efficacy promising or limited (limited reports)
Acute respiratory distress syndrome (ARDS)
Do not intubate status
Cystic fibrosis
Interstitial lung disease
Neuromuscular respiratory failure (better in chronic than acute respiratory failure); best to
avoid if upper airway issues
Kyphoscoliosis
Muscular dystrophy
Post-polio syndrome
Severe acute respiratory distress syndrome (SARS)
Mild Pneumocystis jiroveci pneumonia
842 G.W. Soo Hoo

Table 3 Predictors or response to NIV

Severity of illness (moderate to severe)
Hypercapnic respiratory acidosis (pH 7.20—7.34); lower limit of effectiveness not known
*APACHE II score <25
*Glasgow Coma Scale >11
*Respiratory rate ≤35
*combination may further identify poor candidates
Trial of therapy (response to 1–2 h trial)
Improvement in respiratory parameters (respiratory rate, oxygenation, dyspnea)
Improvement in pH (increase by ≥0.06)
Improvement in PaCO2 (decline by ≥8 mmHg)

most extensively studied in patients with COPD exacerbations. NIV is best suited for
those with decompensated COPD who have a moderate to moderately severe illness,
defined by the severity of hypercapnic respiratory acidosis starting with a pH < 7.35.
Those with a pH ≥ 7.35 have not been demonstrated to derive any benefit from the
addition of NIV to standard therapy. However, increasing respiratory acidosis does
increase the possibility of intubation as it falls below 7.25 and especially below 7.20.
The lowest threshold of effectiveness is not well defined inasmuch as comatose
patients with severe hypercapnic respiratory acidosis, CO2 narcosis, and pH as low as
6.93 have been successfully treated with NIV. Although hypoxemia is one of the
hallmarks of cardiogenic pulmonary edema, those who also have a hypercapnic
respiratory acidosis may represent a group most responsive to management with
NIV. These and other factors used in patient selection are presented in Table 97.3.
None of these values are absolute contraindications to NIV, but should be factored
into the decision to institute NIV, as well as determining failure of therapy and need
for endotracheal intubation. Some have identified a combination of factors, including
severity of illness (Acute Physiology and Chronic Health Evaluation (APACHE) II),
neurologic status (Glasgow Coma Score), and respiratory rate as predictive of failure
and, therefore, patients who may be poorly suited for NIV [6].

97.2 Location of Therapy

NIV was restricted to the intensive care unit (ICU) when first used to treat patients
with respiratory failure. There was a learning curve that required frequent monitor-
ing by nursing and respiratory staff and the ventilator devices initially used for NIV
were not well suited for this application. There was also concern for possible respi-
ratory failure requiring intubation and, therefore, NIV was best administered in a
location where there would be rapid transition to invasive mechanical ventilation.
However, with staff education, experience, and smaller NIV dedicated ventilators, it
became evident that NIV could be provided in an unmonitored ward setting with
staff specially trained in the nuances of NIV. In the ensuing years, the location of
NIV has become less of an issue as NIV is routinely provided for patients in a
97 Determinants of Utilization of Noninvasive Mechanical Ventilation 843

step-down unit setting, emergency room, and even an unmonitored ward. The ward
still represents a third or fourth-line option for its applications (behind the ICU,
step-down unit, and emergency department), but this is changing as providers gain
experience and are more comfortable with NIV in a ward setting [7].

97.3 Trial of Therapy

The other approach that has been used to determine the utility of NIV has been a
time-limited trial of therapy. Most patients who are treated with NIV are able to
tolerate a trial of therapy. However, some patients fail NIV in minutes or within an
hour of initiation. This group represents about 15 % of all patients treated with
NIV. For the remainder, the response to a short 1–2 h trial of therapy is often predic-
tive of successful treatment. This is often clinically evident at the bedside, mani-
fested as a reduction in respiratory rate and accessory muscle use. Arterial blood
gases before and after the trial provide further evidence of efficacy with decreasing
PaCO2 and increasing pH, objective markers that reflect effective patient synchrony
and ventilation. A short trial is useful to identify not only those effectively treated
with NIV but also to identify those with a poor response to NIV, thereby invoking
consideration for intubation and mechanical ventilation [6, 8]. Extended trials with-
out significant improvement only delay intubation and mechanical ventilation with
a risk of other adverse events at the time of intubation. Failure of NIV usually occurs
early, within 4–12 h of initiation, but there are those that fail after 24–48 h and oth-
ers with late failure, after 48 h of NIV, some in spite of initial response to therapy.
Failure to improve sensorium or respiratory acidosis after 24 h of NIV is another
marker of eventual failure. Although this experience has been mostly accumulated
in COPD patients, this clinical experience should hold for other conditions treated
with NIV.

97.4 Health-Care Staff

Staff experience is another factor that can influence utilization of NIV. As with any
therapy, there is a learning curve for staff whenever NIV is introduced into use, and
this involves physicians, nurses, and respiratory therapists. Early experience with
NIV was tempered by some nursing and respiratory therapy staff who experienced
difficulties in its application, thereby limiting its effectiveness. These issues dissi-
pated with increasing staff education and experience, and NIV generally does not
require significantly more time for initiation and maintenance than invasive ventila-
tion using an endotracheal or tracheostomy tube. When surveyed, the vast majority
spend <30 min with initiation and maintenance of NIV, a good portion reported
<15 min, but, of course, some patients may require an hour of time for satisfactory
NIV. As may be expected, larger centers with more patients have more frequent use
of NIV and also report greater success rates. It is difficult to discern whether patient
volume or operator expertise best explains the differences in institutional utilization
844 G.W. Soo Hoo

and outcomes, as both factors are inexorably related. Prior education and experience
with NIV also influences its utilization, which may partially explain some of the
global differences in utilization between Europe and North America. NIV utilization
is much higher in Europe, where there has been long-standing experience with NIV.

97.5 Technical Issues

97.5.1 Masks

The mechanics of NIV application may also impact on its efficacy. Even though
NIV can be used to treat comatose, hypercapnic COPD patients, the ideal patient
needs to be sufficiently cooperative to allow proper mask fitting and synchroniza-
tion with the ventilator. Agitated and uncooperative patients are unlikely to tolerate
NIV. The type of mask interface between the patient and ventilator may facilitate
patient adherence to NIV. Nasal or face (oronasal) masks are the most common
types of masks used in NIV. The severity of illness may identify the mask best
suited for use, as less severely ill patients better tolerate the nasal mask, which
requires a little more cooperation, but are subject to more leaks, whereas the face
mask is better suited for the patient who may not be able to cooperate [2, 8]. There
has been no significant difference in the efficacy of NIV in head-to-head compari-
sons of the masks. On the other hand, there is individual variability and the optimal
mask interface is the one that is best tolerated by the patient.
The masks do have to be fitted tightly for proper administration of NIV and pres-
sure necrosis attributed to the mask can occur. Loosening of the mask without exac-
erbating leaks, changing the type of mask, using facial pads, and providing time off
NIV are the main approaches to address this complication. Sedation has been used
by some to assist in coordination and ventilator synchrony, but it is not clear whether
this uniformly facilitates tolerance to NIV, and there is always a risk for excessive
sedation and respiratory failure.
Other mask interfaces include mouthpieces, nasal pillows, full face mask, and
helmets [8]. These other masks were used or developed because patients were not
able to tolerate the more common nasal or oronasal mask or because of concerns
with facial pressure necrosis as a result of tight-fitting masks. Although all have
demonstrated efficacy, mouthpiece masks do require more cooperation by the
patient, especially to avoid excessive leaks in the ventilator system. Less patient
cooperation is required for application of the full face or helmet masks, and there
may be fewer instances of facial pressure necrosis with these masks.
The proper mask interface is crucial for successful NIV. A properly fitted mask
facilitates delivery of NIV, which in turn translates into effective treatment and
recovery from acute respiratory failure. The mask also facilitates the trial of therapy,
which is often used to gauge the potential success of NIV. It is self-evident that poor
mask fit or intolerance of the mask will doom NIV and is an important limitation to
its use.
97 Determinants of Utilization of Noninvasive Mechanical Ventilation 845

97.5.2 Ventilators

The ventilators used to provide NIV have evolved since the initial reports, which
primarily utilized the same bedside ventilators used in endotracheally intubated
patients using both volume- and pressure-cycled ventilation. Generally, these venti-
lators were not optimal for NIV and were often plagued by mask leaks and alarms.
Addressing these technical issues has led to the development of specialty ventila-
tors, specifically designed to deliver NIV [1, 9]. Over time there has been a blurring
of the distinction between these and bedside ventilators, as modern devices have the
versatility to support both NIV and traditional mechanical ventilation through an
endotracheal tube or tracheostomy tube. These ventilators have also expanded the
modes of ventilation that can be delivered to patients administered NIV as well as
traditional invasive ventilation.

97.5.3 Modes of Ventilation

The first devices designed for NIV were based on the continuous positive airway
pressure (CPAP) devices used to treat obstructive sleep apnea. This mode remains
available and has been demonstrated to be especially effective in treating patient
with cardiogenic pulmonary edema. CPAP effectively recruits lung for ventilation
and also has the dual effect of treating cardiogenic pulmonary edema by decreasing
cardiac preload and afterload. However, higher CPAP pressures can be difficult to
tolerate. Experience with traditional volume cycle ventilation was tempered by
leaks and often high pressures. Inefficient patient-ventilator coordination, dyssyn-
chrony, and breath stacking could limit effective ventilation. Pressure-cycled venti-
lators delivering pressure support ventilation provide comparable ventilatory
support but have advantages of better leak compensation and patient control of
inspiratory flow, which in turn produces better patient-ventilator synchrony. Volume
delivery was more variable, but better tolerance of pressure-cycled ventilators made
these more effective devices. It should be noted that neither mode has been demon-
strated to be superior to the other.
This led to a ventilator with a proprietary name of BiPAP, which has become
synonymous with NIV. Two levels of support are provided, one inspiratory posi-
tive airway pressure (IPAP) and the other expiratory positive airway pressure
(EPAP). The difference between the two represents the amount of pressure pro-
vided to the patient, and it can be considered similar to a bedside ventilator mode
of pressure support and PEEP. The ventilators have become more sophisticated,
with a focus on improving patient ventilator synchrony. This has produced
machines with improved signal processing technology and speed, which permits
faster response times.
The newer ventilator modes often have proprietary names, and nomenclature
can be confusing. Proportional assist ventilation (PAV) or proportional pressure
ventilation (PPV) has been used in NIV and provides ventilator support with
846 G.W. Soo Hoo

adjustments in inspiratory flow and pressure to match the patient’s spontaneous

efforts. This provides support proportional to the patient’s efforts and thereby bet-
ter matches their needs and facilitates patient-ventilator synchrony. Its efficacy is
comparable but has not been demonstrated to be superior to the more commonly
used BiPAP mode.
Another increasingly used variation of BiPAP is the average volume-assured
pressure support (AVAPS) mode. This adjusts for variations in inspiratory pressure
by changing pressure support levels to achieve a targeted tidal volume. This modal-
ity may be especially useful in patients with neuromuscular or thoracic cage respira-
tory disorder to deliver a target tidal volume and ensure a target minute ventilation.
It has also been used in COPD patients and may be better suited for the patient with
an advanced hypercapnic respiratory acidosis and CO2 narcosis.
Advances in mask interfaces and noninvasive ventilators have greatly
improved the patient’s ability to tolerate and respond to NIV. These no longer
limit optimal NIV, as may have been the case in the past, but there are still some
nuances to be aware of involving these devices that may impact a patient’s ability
to tolerate NIV.

97.5.4 Ventilator Settings

Irrespective of the mask interface and device, the goals of NIV remain adequate
ventilation with a reduction in work of breathing. Gas exchange disturbances must
be also be corrected. The approach to ventilator settings has remained relatively
unchanged. Fraction of inspired oxygen (FiO2) can be adjusted to achieve target
oxygen saturation, but blood gases are essential to track the overall response in gas
exchange. Because most NIV patients have a hypercapnic respiratory acidosis, ven-
tilator settings are set to achieve adequate tidal volume and minute ventilation to
achieve normocapnia. Inspiratory and end-expiratory pressures are the most com-
mon targets for ventilator settings. These pressure-cycled settings permit a target
volume of 5–7 ml/kg with inspiratory pressures increased to match that goal.
Generally, in patients with a hypercapnic respiratory acidosis, the inspiratory pres-
sures are increased to permit an increase in tidal volume to facilitate clearance of
CO2. This pressure also represents the amount of pressure support provided by the
ventilator. IPAP of 10 cmH2O and EPAP of 5 cmH2O are frequently used as initial
pressures. Further adjustments to the ventilator should be based on the response to
therapy. Persistent hypercapnia can be treated with increasing minute ventilation,
with an increase in frequency and/or tidal volume.
In hypoxemic patients without hypercapnia, changes in the ventilator settings are
made to both the inspiratory and expiratory pressures. This effectively increases the
positive end-expiratory pressure (PEEP) in the system and helps recruit lung and
improve oxygenation. Volume cycle ventilation can be used with NIV, but is tem-
pered by inadequate volume delivery in the setting of mask leaks or patient dyssyn-
chrony with the ventilator.
97 Determinants of Utilization of Noninvasive Mechanical Ventilation 847

97.6 Medication Delivery

Inasmuch as one of the goals of NIV is to avoid intubation in those with respiratory
distress and impending respiratory failure, optimizing medication delivery during
NIV may facilitate recovery. Because successful application of NIV will further its
utilization, it is important to recognize that there is the potential for enhanced bron-
chodilator therapy with NIV. NIV can increase patient tidal volume and decrease
respiratory rate, factors that can enhance aerosol delivery of bronchodilators. There
is evidence that demonstrates greater improvement in the measure of lung function
when bronchodilators are delivered with NIV compared with a standard nebulizer.
However, the magnitude of this benefit has not been extensively studied.

97.7 Complications of NIV

The spectrum of complications associated with NIV differs from invasive ventila-
tion but may still be of sufficient magnitude to limit its use. The most common
complications involve pressure necrosis associated with the mask at its contact
points with the skin. The pressure ulcers can be quite large and deep, thereby limit-
ing effective delivery of ventilatory support. Options in management have been pre-
viously outlined in the section on masks, and include the use of different types of
masks including large full face masks and helmets. Alternating the size of the mask
and type of mask is another option as well as dressings to minimize the pressure of
the mask on the face. The goal is to relieve and minimize the facial pressure by the
mask, thereby reducing the risk of pressure ulcers.
Other complications associated with NIV mirror the complications also seen
with invasive mechanical ventilation [10]. These include barotrauma, hemodynamic
compromise due to increased intrathoracic pressure, and infectious complications.
Barotrauma is related to the pressures used and generated during ventilator support.
The pressures delivered to the airway and eventually the alveoli are often limited to
less than 20 cmH2O, as higher pressures are typically not used or not tolerated dur-
ing NIV. Leaks inherent with any mask also limit pressure. Nevertheless, there are
instances during patient-ventilator dyssynchrony where the pressures may approach
or exceed plateau pressures of 30 cmH2O, which in turn places the lung at risk for
barotraumas. The treatment of complications that occur during NIV mirrors the
treatment of complications related to positive pressure ventilation during invasive
mechanical ventilation. Barotrauma that causes a pneumothorax typically warrants
tube thoracostomy. Barotrauma can be minimized by a reduction in airway pres-
sures with lower volume targets for ventilator support. Hemodynamic compromise
is also addressed with lower pressure setting, but patients can also be supported with
intravenous fluids, which will help ameliorate the adverse hemodynamic effects of
positive pressure ventilation. Nosocomial respiratory infections occur at a much
lower rate during NIV compared with invasive ventilation. However, patients may
be at risk for gastric insufflations and subsequent aspiration event. This specifically
848 G.W. Soo Hoo

differs from invasive ventilation as airflow in NIV is delivered to the entire orophar-
ynx with subsequent flow down the esophagus as well as the tracheobronchial tree.
Excess pressures can overcome the lower esophageal sphincter, generating gastric
distension and increasing the risk of reflux, aspiration, and pneumonia. Local mea-
sures such as head-of-bed elevation, breaks between NIV support, and frequent
breaks off NIV may reduce that risk. Antimicrobial therapy remains a mainstay of
therapy.
All of the aforementioned complications are manageable and should not pre-
clude the use of NIV in the appropriate patient. Utilization of NIV may require
some modification, but should not be limited by these complications.

97.8 Discontinuation of NIV

One of the advantages of NIV over invasive ventilation is its ease of application and
discontinuation. As noted previously, it is a noninvasive approach to ventilator sup-
port and requires less advanced technical skill than intubation and mechanical ven-
tilation for initiation. Similarly, the discontinuation of NIV is not as complicated as
with invasive ventilation. Extubation is always tempered by the possibility of recur-
rent respiratory distress and need for reintubation. The timing of extubation is an
imperfect science and may be preceded by several weaning trials. NIV is typically
provided as intermittent ventilator support and broken up by approximate hour
breaks over the course of a day. Each time it is discontinued, a patient’s clinical
status should be evaluated. Respiratory distress may have resolved and subjects may
no longer require ongoing ventilator support. Objective measures of response to
therapy include resolution of physical signs of increased work of breathing (acces-
sory muscle use, wheezing, tachypnea, diaphoresis, diaphragmatic paradox), along
with improvement or resolution of hypoxemia, hypercapnia, and hypercapnic respi-
ratory acidosis.

97.9 Failure of NIV

Conversely, patients may not respond to NIV and there may need to be consideration
for invasive ventilation. Of course, in some patients, because of advanced underlying
disease, NIV will represent the extent of life-support therapies. In the others, there
needs to be vigilance of findings that would portend progression of respiratory fail-
ure to a point where intubation would be indicated. Table 97.4 provides some objec-
tive findings that can be used to signify failure of NIV and the need to proceed with
intubation and mechanical ventilation. The early, sometimes preemptive intubation
in patients failing NIV is of the utmost importance as these patients have been dem-
onstrated to have worse outcomes and higher mortality than those who are success-
fully treated with NIV [5]. It is important to incorporate these measures of NIV
failure (as well as success) in written guidelines to minimize any confusion among
staff with respect to therapy as well as to standardize treatment [2].
97 Determinants of Utilization of Noninvasive Mechanical Ventilation 849

Table 4 Intubation guidelines

Intubation criteria (any one of the following):
Cardiac or respiratory arrest
Loss of consciousness
Hemodynamic instability with systolic blood pressure <70 mmHg
PaO2 <45 mmHg despite oxygen
Intubation criteria (two or more in the context of respiratory distress):
Respiratory rate >35/min or <6/min
Tidal volume <5 ml/kg
Oxygen desaturation <90 % despite adequate supplemental oxygen
pH <7.20 and decreasing on NIV support
Hypercapnia (PaCO2 >10 mm increase) or acidosis (pH decline >0.08) from baseline
Increase in encephalopathy or decreased level of consciousness
Abdominal paradox
Modified from Refs. [1, 9]

Conclusion
In summary, positive pressure NIV has dramatically changed the management of
patients with respiratory distress and respiratory failure. It is considered a first-
line option for the management of acute exacerbations of COPD with hypercap-
nic respiratory distress and cardiogenic pulmonary edema. The determinants for
utilization have been separated into clinical (nontechnical) and technical issues
associated with NIV. Each area is important and, along with provider education
and experience, are major factors in its utilization.

References
1. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive ventila-
tion for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med.
1995;333(13):817–22.
2. Soo Hoo GW. Noninvasive ventilation in adults with acute respiratory distress: a primer for the
clinician. Hosp Pract (Minneap). 2010;38(1):16–25.
3. Keenan SP, Sinuff T, Burns KE, Muscedere J, Kutsogiannis J, Mehta S, et al. Clinical practice
guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous
positive airway pressure in the acute care setting. CMAJ. 2011;183(3):E195–214.
4. Schnell D, Timsit JF, Darmon M, Vesin A, Goldgran-Toledano D, Dumenil AS, et al.
Noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes.
Intensive Care Med. 2014;40(4):582–91.
5. Walkey AJ, Wiener RS. Use of noninvasive ventilation in patients with acute respiratory fail-
ure, 2000–2009: a population-based study. Ann Am Thorac Soc. 2013;10(1):10–7.
6. Confalonieri M, Garuti G, Cattaruzza MS, Osborn JF, Antonelli M, Conti G, et al. A chart of
failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J.
2005;25(2):348–55.
850 G.W. Soo Hoo

7. Cabrini L, Esquinas A, Pasin L, Nardelli P, Frati E, Pintaudi M, et al. An international survey

on noninvasive ventilation use for acute respiratory failure in general non-monitored wards.
Respir Care. 2014;60(4):586–92.
8. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet.
2009;374(9685):250–9.
9. Bott J, Carroll MP, Conway JH, Keilty SE, Ward EM, Brown AM, et al. Randomised con-
trolled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways
disease. Lancet. 1993;341(8860):1555–7.
10. Carron M, Freo U, BaHammam AS, Dellweg D, Guarracino F, Cosentini R, et al. Complications
of non-invasive ventilation techniques: a comprehensive qualitative review of randomized tri-
als. Br J Anaesth. 2013;110(6):896–914.
Influence of Staff Training
on the Outcome of Noninvasive 98
Ventilation

Bárbara M.E.M.A. Seabra

Contents
98.1 Introduction ................................................................................................................. 851
98.2 Staff Training in Noninvasive Ventilation ................................................................... 852
98.2.1 NIV Staff Training – Definition .................................................................... 852
98.2.2 NIV Staff Training – Methods ...................................................................... 852
98.2.3 NIV Staff Training – Contents ...................................................................... 853
98.3 Current Evidence on Staff Training in NIV ................................................................ 853
98.3.1 NIV in the Chronic Respiratory Failure Setting............................................ 856
Conclusions ............................................................................................................................ 857
References .............................................................................................................................. 858

Abbreviations

AHRF Acute hypercapnic respiratory failure

COPD Chronic obstructive pulmonary disease
CRF Chronic respiratory failure
NIV Noninvasive ventilation

98.1 Introduction

Since its introduction into clinical practice, noninvasive ventilation (NIV) has pro-
gressively gained a major role in the treatment of acute and chronic respiratory
failure of multiple etiologies. Despite the “relative simplicity” of its concept and
mechanism, the generalized use of NIV does not guarantee overall treatment suc-
cess. Several studies have suggested the importance of staff training in the outcome
of NIV. However, training goes well beyond acquisition of theoretical knowledge.
In fact, its subtle specificities require, in addition to the latter, consistent “hands-on”

B.M.E.M.A. Seabra, MD
Department of Respiratory, Hospital Pedro Hispano, Matosinhos, Portugal
e-mail: [email protected]; [email protected]

© Springer International Publishing Switzerland 2016 851

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_98
852 B.M.E.M.A. Seabra and A.M. Esquinas

experience for increasingly efficient and speedy treatment adjustments, in accor-

dance with each particular setting. This chapter discusses and analyzes the role of
staff training in the outcome of NIV in its most commonly used modality: positive
pressure noninvasive ventilation.

98.2 Staff Training in Noninvasive Ventilation

There are several aspects of staff training in NIV that have not been clarified:

• Definition of adequate staff training in NIV or its aims

• Which teachings contribute to an efficient training program
• Adequate duration of initial training
• Desirable frequency and contents during “maintenance” training
• Objective influence of staff training in NIV both in acute and chronic settings

98.2.1 NIV Staff Training – Definition

Despite the fact that most, if not all, medical centers where NIV takes place have a
local NIV training protocol, the definition of adequate NIV staff training has not
been globally established. Staff training may be defined as all the educational prepa-
ration, both theoretical and practical, delivered to NIV team constituents with the
goal of improving the general and specific skills of each member. This allows the
delivery of progressively more efficient and correct patient treatment. Training
should probably be continuous and shaped according to local and individual needs.
Training may take place both actively (through active article and guideline research,
theoretical updates, participating in practical courses, etc.) and “passively” (through
daily handling of this technique).

98.2.2 NIV Staff Training – Methods

Efficient staff training has not been clearly established, although the generally
adopted and recommended formation includes [1, 2]:

• regular local educational courses for doctors, nurses, and physical therapists;
• elaborating and teaching local protocols of action in NIV;
• updates on locally available ventilators and interfaces, adequate use, and
maintenance;
• attending national and international NIV courses;
• “hands-on” experience in progressively more differentiated or acute settings; and
• discussion of local practical aspects and difficulties on a regular basis, searching
for learning and improvement opportunities.
98 Influence of Staff Training on the Outcome of Noninvasive Ventilation 853

98.2.3 NIV Staff Training – Contents

All members of the NIV team, especially the medical coordinator, should be
aware and ideally absolutely comfortable with different variables continuously
handled during this procedure: technical knowledge, staff roles and capabilities,
available ventilators and their potential, patient profile, current interactions
between the intervenients (patient–ventilator–staff–coordinator), and so on. Some
of these variables are briefly listed in Table 98.1. Generally speaking, addressing
this content in staff training may bring benefits to clinical practice and NIV
success.
Doctors, nurses, and physical therapists may share a common background but
should develop specific skills according to their activities in the NIV team.
Differentiated training and education according to the role played by each staff
member is desirable and may make a difference in critical patients. Once again, the
content and the duration of what is considered an adequate training program have
not been defined. As a general rule, each NIV center has developed its own training
programs according to what is considered locally needed.

98.3 Current Evidence on Staff Training in NIV

When handling a patient with either acute or chronic respiratory failure, NIV –
mainly positive pressure NIV – may be among several treatment options available
to a medical team. Having its benefits widely identified in specific settings, its gen-
eralized use should not be taken lightly.
NIV treatment consists of a complex network where the main actors – the patient,
the medical coordinator, staff (including doctors, nurses, and physical therapists),
and the NIV in itself – are dynamically interrelated (Fig. 98.1). Each intervenient
plays its specific role during this procedure, and the resulting method of ventilation
contributes largely to the patient’s acceptance and compliance with this treatment
option, which is essential for a positive outcome [3].
Staff training and expertise in NIV are essential for successful NIV treatment,
especially in the acute hypercapnic respiratory failure (AHRF) setting. However,
medical and paramedical expertise is generally difficult to evaluate and has been
poorly studied, including in NIV [4].
The complexity and subtlety of NIV demand generalized knowledge, both theo-
retical and practical, of several aspects of this treatment modality. It seems logical
to assume that respiratory physiopathology, NIV basic knowledge, and updated
NIV guidelines are the essential pillars on which all NIV techniques may be devel-
oped with regular clinical practice.
Available publications specifically addressing NIV staff training are scarce,
mainly approach positive pressure NIV and its use in AHRF, and have limited sta-
tistical evidence. However, the general importance of staff training in the outcome
of NIV has been repeatedly stressed.
 854

Table 98.1 Multiple variables handled by the medical coordinator and staff in NIV
Medical coordinator –
Technical knowledge (theoretical and Medical coordinator – staff/ventilator Ventilator/patient
practical) staff/patient interaction interaction interactions Other variables
Indications/contraindications for NIV Adequate Bilateral Knowledge of available Assure patient comfort Staff capabilities and
Intubation and mechanical ventilation communication – ventilators (potential Causes of disadaptation limitations
criteria understanding and and limitations, Patient/ventilator asynchrony Staff’s confidence in
NIV physiopathology meeting patients’ needs advantages and Adjusting: NIV results
NIV mechanisms Getting across a sense of disadvantages) Mask and headgear Patient profile
NIV particularities according to diagnosis safety and reassurance to General ventilator Leaks Proximity to the
Treatment aims the patient maintenance Trigger/cycling ICU
Alarm signs Early identification of Ventilation modes Humidification
alarm signs How to manipulate the
ventilator
How to adjust settings
Interpreting data and
pressure/flow
waveforms
B.M.E.M.A. Seabra and A.M. Esquinas
98 Influence of Staff Training on the Outcome of Noninvasive Ventilation 855

Patient

Coordinator

NIV
Staff

Fig. 98.1 Network of intervenients in NIV and respective interrelationships. Although successful
patient treatment is the main aim of this network, the medical coordinator holds the central role in
its attainment, observing, receiving continuous feedback, and coordinating all activity leading to
NIV success and better patient outcome

Although it is difficult to correctly evaluate staff training, several studies have

led to the conclusion that the level of experience of the team conditions the result
of NIV. Some studies aiming to identify the ideal location for NIV in the acute
setting reached the conclusion that the main factor associated with different loca-
tion treatment outcomes was local team expertise in NIV [1]. Lopez-Campos
et al. [4] suggested that the use of NIV by inexperienced personnel led to a high
NIV failure rate. On the other hand, with adequate staff training, earlier and ade-
quate NIV treatment may even be attained in a general ward, contributing to a
better patient prognosis (although this treatment location is not generally recom-
mended) [2].
Reports have shown that maintaining and, most of all, initiating NIV is time
consuming, usually demanding close attention and staff dedication for adequate
adaptation and treatment success. However, progressive staff training contributes to
consistently diminished time expenditure and patient/nurse and patient/doctor ratio
needs [1], favoring treatment of increasingly more severe patients without signifi-
cantly changing success rate [2, 4]. It is even suggested that the cumulative experi-
ence acquisition deriving from regular handling of NIV over the years may modify
clinical practice and improve patient outcome [2].
856 B.M.E.M.A. Seabra and A.M. Esquinas

Table 98.2 Possible consequences of inadequate staff training in NIV in the CRF setting
Short term Medium term Long term
Inability to reassure patient Patient disadaptation/discomfort More episodes of
initiating NIV ARF over CRF
Inability to motivate patient to Patient NIV low compliance More hospital
adhere to NIV admissions
Inability to correctly Patient NIV refusal Higher morbidity and
adjust NIV settings for mortality related to CRF
patient comfort

98.3.1 NIV in the Chronic Respiratory Failure Setting

There is a considerable range of patients with indications for NIV who may initiate
this treatment in an outpatient setting, during stable disease. Patients diagnosed with
obesity -hypoventilation syndrome, chest wall deformities, some neuromuscular
diseases, overlap syndrome, and certain patients with chronic obstructive pulmo-
nary disease are within this group.
Most publications and recommendations concentrate on the importance of
staff training in NIV in the acute respiratory failure setting, possibly due to the
more immediate consequences of its failure. Studies reflecting the importance of
staff training in chronic respiratory failure (CRF) are lacking. However, clinical
practice suggests that one may generally draw the same conclusions in this set-
ting. Although the negative consequences of lack of staff training in this setting
may not be as obvious in the short term, they may surface sooner or later
(Table 98.2).
As a general rule, one may deduce that inexperienced NIV teams, aware of their
own technical limitations, may have more difficulties in reassuring and motivating
a patient initiating NIV. If this is not the case, inability to correctly adjust the venti-
lator and interfaces may cause patient discomfort and disadaptation. In the short
term, this may lead to non-adherence to treatment which, in the long term, may
consequently lead to more episodes of acute respiratory failure over CRF, higher
hospital admission rates, and increased patient morbidity and mortality.
As the complexity of these patients, higher dependency, and specific require-
ments from NIV increase, the impact of staff training in better patient care may
be progressively higher. Patients with neuromuscular disease and amyotrophic
lateral sclerosis, in particular, are a paradigmatic example of this situation,
requiring progressively more differentiated and expert care as their disease and
needs evolve.
Once again, solid background theoretical knowledge and practical experi-
ence of each intervenient in NIV contributes to patients’ acceptance of NIV in
the chronic setting, to an adequate response to patients’ needs, and possibly to
the motivation of treatment adherence, preventing long-term consequences of
untreated CRF.
98 Influence of Staff Training on the Outcome of Noninvasive Ventilation 857

Conclusions
NIV involves continuously handling several complex variables, frequently in
borderline situations. Adequate staff training plays a major part in the success of
NIV. Its impact in NIV has been identified mainly in the AHRF setting, however,
its influence in CRF is probably not negligible.
Current evidence on NIV staff training suggests the followin:

• Medical and paramedical expertise is generally difficult to evaluate and has

been poorly studied, including in NIV.
• Staff training and expertise will influence the resulting method of ventilation,
largely contributing to the patient’s acceptance and compliance with this
treatment option.
• The main factor associated with different location treatment outcomes is local
team expertise in NIV.
• The use of NIV by inexperienced personnel may lead to a high NIV failure
rate.
• Progressive staff training contributes to consistently diminished time expen-
diture and patient/nurse and patient/doctor ratio needs and may allow for car-
ing for increasingly more severe patients without significantly changing the
treatment success rate.

Staff training should ideally include theoretical formation generously

complemented with regular NIV practice and learning experiences, although
training duration and contents have not yet been defined. Today, the multi-
tude of indications for NIV and the ever-growing number of ventilators, ven-
tilatory modes and settings, interfaces, and so on demand a continuous update
in this area.

Key Major Recommendations

• Staff training in NIV seems to improve general outcome of patients in
AHRF and to diminish time expenditure and doctor/patient and nurse/
patient ratios needs and should therefore be widely promoted. Staff
regularly handling patients in need of NIV should be adequately
trained.
• Theoretically, practical training and regular updates in NIV are essential to
provide the best treatment to patients and improve their prognosis.
• Staff training should be continuous and adapted to local and individual
needs.
• Objective NIV training protocols with proven efficacy (for both the acute
and chronic settings) are yet to be established and should be addressed in
future studies.
858 B.M.E.M.A. Seabra and A.M. Esquinas

References
1. Elliot MW, Confalonieri M, Nava S. Where to perform noninvasive ventilation? Eur Respir J.
2002;19:1159–66.
2. Nava S, Fracchia C, Rubini F, et al. Changes in the practice of non-invasive ventilation in treat-
ing COPD patients over 8 years. Intensive Care Med. 2003;29:419–25.
3. Nava S, Ceriana P. Causes of failure of noninvasive mechanical ventilation. Respir Care.
2004;49(3):295–303.
4. Lopez-Campos JL, Garcia Polo C, Leon Jimenez A, et al. Staff training influence on non-
invasive ventilation outcome for acute hypercapnic respiratory failure. Monaldi Arch Chest
Dis. 2006;3:145–51.
Quality of Life during Long-Term
Mechanical Ventilation in Hypercapnic 99
Respiratory Failure: Main Determinants
and Evidence

Graham T. Atkins and Alex H. Gifford

Contents
99.1 Introduction ................................................................................................................. 860
99.2 NIPPV for Hypercapnic Respiratory Failure .............................................................. 861
99.3 Hypercapnic Respiratory Failure Due to Neuromuscular Disease ............................. 861
99.4 Hypercapnic Respiratory Failure Due to Obesity Hypoventilation Syndrome........... 862
99.5 Hypercapnic Respiratory Failure Due to Cystic Fibrosis ........................................... 862
99.6 Hypercapnic Respiratory Failure Due to COPD ......................................................... 863
99.7 Cost of NIV and Admissions to Hospital ................................................................... 863
Conclusions ............................................................................................................................ 864
References .............................................................................................................................. 864

Abbreviations

ALS Amyotrophic lateral sclerosis

CF Cystic fibrosis
CFQ Cystic fibrosis questionnaire
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
DMD Duchenne muscular dystrophy
EPAP Expiratory positive airway pressure
ESS Epworth sleepiness scale
IPAP Inspiratory positive airway pressure

G.T. Atkins, MBChB, MRCP(UK) • A.H. Gifford, MD (*)

Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center,
One Medical Center Drive, Lebanon, NH, USA
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 859

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_99
860 G.T. Atkins and A.H. Gifford

NIPPV Noninvasive positive pressure ventilation

NMD Neuromuscular disease
OHS Obesity hypoventilation syndrome
PaCO2 Arterial partial pressure of carbon dioxide
QoL Quality of life
RCT Randomized controlled trial
SAQLI Calgary sleep apnea quality of life index
SF-36 Medical outcomes study Short Form 36 quality of life questionnaire
SGRQ St George’s respiratory questionnaire

99.1 Introduction

Considerable evidence supports the use of noninvasive positive pressure ventilation

(NIPPV) to manage acute hypercapnic respiratory failure. Questions remain regard-
ing the utility of NIPPV in chronic hypercapnic respiratory failure, including
whether it can improve quality of life (QoL) for all or certain subsets of patients.
Common causes of chronic hypercapnic respiratory failure include chronic obstruc-
tive respiratory disease (COPD), obesity hypoventilation syndrome (OHS), cystic
fibrosis (CF), and neuromuscular diseases (NMD) such as amyotrophic lateral scle-
rosis (ALS) and Duchenne muscular dystrophy (DMD). In this chapter, we review
selected studies that question whether NIPPV, usually administered nocturnally, can
improve QoL for these patients. Sleep-disordered breathing may co-exist with
COPD, inevitably occurs in NMD, and by definition is present in OHS. Most inves-
tigations in this area have sought to identify a mortality benefit of NIPPV in chronic
hypercapnic respiratory failure and employed dyspnea scores or health-related QoL
questionnaires as secondary outcome measures. Selected commonly used QoL and

Table 99.1 Selected quality of life and symptom scoring systems [1]
Medical Outcomes Study Short Form 36 question health related quality of life questionnaire
SF – 36 that scores from 0 to 100 in 8 categories. A mental health and
physical health summary score (MCS and PCS), also from 0 to
100, are generated. Higher scores indicate greater perceived quality
of life
St George’s Respiratory 50 items are measured to generate scores in two distinct areas:
Questionnaire (SGRQ) (1) symptoms and (2) activity and limitations. Scores are on a
0–100 scale with higher scores indicating worse symptoms and
limitations
Calgary Sleep Apnea 35 item measurement, scored 1–7 in 5 domains, including an
Quality of Life Index assessment of the negative quality of life impact that treatment may
(SAQLI) have
Epworth Sleepiness 8 questions on a 4 point scale to measure sleepiness
Scale (ESS)
Cystic Fibrosis Disease-specific instrument designed to measure impact on overall
Questionnaire – Revised health, daily life, perceived well-being, and symptoms
(CFQ/CFQ-R)
99 Quality of Life during Long-Term Mechanical Ventilation 861

symptom scoring systems are listed in Table 99.1 [1]. QoL, rather than mortality,
may be a more appropriate metric by which to evaluate the efficacy of NIPPV in
some patients with end-stage pulmonary or neurological diseases. The questions
regarding QoL and the use of NIPPV in hypercapnic respiratory failure that are
addressed in this chapter include:

• Does noninvasive ventilation (NIV) improve or preserve QoL for all patients
with hypercapnic respiratory failure, or only for patients with specific
diseases?
• Do patients need to have evidence of sleep-disordered breathing to benefit from
nocturnal NIPPV?
• Does NIPPV have any negative effects on QoL?
• Is normalizing the arterial partial pressure of carbon dioxide (PaCO2) important
and what NIPPV settings should be used for patients with chronic hypercapnia?

99.2 NIPPV for Hypercapnic Respiratory Failure

The disease-specific literature is reviewed below, but there is some evidence to

suggest that NIPPV can improve QoL for all patients with hypercapnic respira-
tory failure. In a prospective study, a cohort of 85 patients with mean
PaCO2 > 50 mmHg commenced 1 year of home NIPPV with the aim of normal-
izing PaCO2 [2]. The study population included those with COPD, restrictive
thoracic disease, NMD, and OHS. Mean inspiratory airway pressure (IPAP) and
expiratory airway pressure (EPAP) were > 20 cmH2O and 2 cmH2O, respectively.
Mean NIPPV use was 7.3 h per day, and mean PaCO2 was <45 mmHg after 1 year
of treatment. The authors found that health-related QoL had improved at 1 month
and that this improvement was sustained at 1 year, with an approximate 5-point
increase in the SF-36 mean MCS and PCS. Frequently reported adverse effects
(37–22 % of the study population) included dry throat, facial soreness, sleep
disruption, nasal congestion, and abdominal distension. Although there was no
control group in this study, the small but significant improvement in quality life
scores is striking.

99.3 Hypercapnic Respiratory Failure Due to Neuromuscular

Disease

A Cochrane review of nocturnal mechanical ventilation for chronic hypoventilation

due to neuromuscular or chest wall disorders showed that mechanical ventilation
improved symptoms up to 1 year after commencing NIPPV [3]. The two subgroups
for which the strongest evidence exists are patients with ALS and DMD. In both
disorders, patients develop sleep-disordered breathing followed by nocturnal hyper-
capnia and then daytime hypercapnia as respiratory muscle function deteriorates. A
862 G.T. Atkins and A.H. Gifford

randomized controlled trial (RCT) of NIPPV in 41 patients with ALS showed that
NIPPV preserved QoL scores (SAQLI and SF-36 MCS) at 75 % of baseline for
longer than supportive care (median comparisons: 173 vs 99 days for SAQLI and
168 vs 99 days for SF-36 MCS) [4]. Although statistically significant, this 11 week
greater preservation of QoL may not be clinically meaningful; however, in patients
with good bulbar function, QoL was preserved for around 6 months longer with
NIPPV [4]. A review of mechanical ventilation in patients with DMD considered
whether 24-h NIPPV or home ventilation via a tracheostomy might be more benefi-
cial to QoL [5]. Tracheostomy allows clearance of secretions, which is often
required as the disease progresses but may necessitate care in an institution rather
than at home. Patients with a tracheostomy expressed fewer positive statements
regarding QoL than those receiving NIPPV. The finding that those with milder dis-
ease derived a longer period of maintained QoL raises the question of when to com-
mence NIPPV in patients with ALS and DMD. Early initiation of NIPPV in
neuromuscular disease, for instance, when patients demonstrate nocturnal but not
daytime hypercapnia, is an approach that may improve quality of life based on the
results of a single RCT [6].

99.4 Hypercapnic Respiratory Failure Due to Obesity

Hypoventilation Syndrome

OHS is characterized by obesity, daytime hypercapnia (PaCO2 > 45 mmHg), and

sleep-disordered breathing. Japanese investigators compared the effect of nocturnal
continuous positive airway pressure (CPAP) in three groups of patients: those with
OHS, obese patients with obstructive sleep apnea (OSA) but daytime normocapnia,
and non-obese patients with OSA and daytime normocapnia [7]. The duration, com-
pliance, and the pressure settings of CPAP used were not specified but CPAP was
titrated to abolish apnea and maintain saturations of >90 %. Improvements in all
domains of the SF-36 QoL score and the ESS were seen post treatment [7]. All
improvements were statistically significant, with the exception of SF-36 bodily pain
scale in OHS patients and SF-36 physical function and emotional limitation scales
in non-obese patients with OSA. It is not known whether PaCO2 improvements
occurred for the OHS population during this study. These data suggest that noctur-
nal NIPPV can improve QoL for patients with OHS but that this improvement is
likely mediated through an improvement in OSA.

99.5 Hypercapnic Respiratory Failure Due to Cystic Fibrosis

Progressive decline in lung function and QoL is seen in patients with CF. Young
et al. [8] conducted a randomized crossover trial of nocturnal NIPPV in patients
with daytime hypercapnia and nocturnal hypoxia. They found that NIPPV with-
out supplemental oxygen, compared with air delivered at 2 l/min via nasal can-
nula, improved chest symptoms at 6 weeks as measured using the CFQ (71 vs 64)
99 Quality of Life during Long-Term Mechanical Ventilation 863

[7]. NIPPV use was not associated with significant changes in physical function-
ing or emotional response domains of the CFQ, nor did it affect scores on the
ESS or the MRC dyspnea scale. NIPPV was well tolerated during the 6-week
intervention period.

99.6 Hypercapnic Respiratory Failure Due to COPD

Tsolaki et al. [9] reported that hypercapnic patients without sleep-disordered breath-
ing, apnea hypopnea index (AHI) <10, showed a mean increase of 9 points on the
SF-36 score after 1 year with NIPPV. This was not a RCT, but the control group
patients who could not tolerate NIPPV had no change or even a decrease in their QoL
metrics at 1 year. The relatively high mean IPAP, 15.3 cmH20, and mean 9 h of daily
NIPPV use were notable. When RCTs were conducted, the beneficial effect of NIPPV
on QoL was not observed. A trial of 144 hypercapnic COPD patients by McEvoy et al.
[10] in Australia randomized to receive NIPPV with oxygen or oxygen alone showed
slightly lower SF-36 scores in patients receiving NIPPV. A 2014 Cochrane review of
RCTs (which included the study by McEvoy et al.) showed no significant differences
in quality of life when NIPPV was used for 3–12 months in hypercapnic patients with
COPD [11]. When the RCT of McEvoy et al. is compared to the study by Tsolaki
et al., the patients appear similar in terms of their degree of hypercapnia and airflow
obstruction, but the treatment intervention has significant differences. In the RCT by
McEvoy et al. the levels of IPAP are lower, there is no significant change in PaCO2,
and patients used NIPPV for a much shorter period of time each day (mean of 4.5 h vs
9 h). One could hypothesize that normalizing hypercapnia, through the use of rela-
tively high IPAP, is important to achieve a QoL improvement.
With this in mind, a European study by Köhnlein et al. [12] randomized 195
patients with COPD with mean PaCO2 of 58 mmHg to 1 year of NIV titrated to
reduce PaCO2 by 20 % or to <48 mmHg. There was no assessment or exclusion of
patients with sleep-disordered breathing. Mean IPAP was 21.6 cmH2O and mean
EPAP was 4.8 cmH2O. Mean daily NIPPV use was 5.9 h. There were small but
significant QoL differences between the NIPPV and control groups, in favor of
NIPPV treatment. There was an 8.6 point improvement in the SF-36 general health
perception subscale, a 6.2 point improvement in the SGRQ summary score, and a
5.6 point improvement in the SRI summary scale score, all statistically better than
changes in the control group (p < 0.05).

99.7 Cost of NIV and Admissions to Hospital

Some data suggest that in-home NIV for patients with hypercapnic respiratory fail-
ure may be a cost-effective therapeutic intervention. In a trial of 13 hypercapnic
patients with COPD, in-home NIPPV provided a cost saving by reducing the fre-
quency and duration of hospital admissions [13]. Admissions to hospital are associ-
ated with lower QoL scores for patients with hypercapnic respiratory failure [14].
864 G.T. Atkins and A.H. Gifford

Conclusions
NIPPV appears to improve QoL for hypercapnic patients with NMD, CF, and
OHS. The studies suggest that the majority of these patients have sleep-disor-
dered breathing, and an improvement in sleep quality is a contributor to the over-
all improvements in quality of life. There is conflicting literature regarding
NIPPV to improve QoL in hypercapnic COPD patients. If NIPPV is used for
patients with COPD, relatively high levels of support (i.e., IPAP > 15 mmHg), 6
or more hours of daily NIPPV use, and a ventilation strategy targeted to normal-
ize PaCO2 are the factors associated with increased QoL. It is notable that, in all
the studies of NIPPV, patients were hospitalized for 3–12 days to establish
NIPPV and that there was close follow-up throughout. It is not clear whether
strict adherence to this methodology is required for patients to derive improve-
ment from NIPPV in clinical practice. In one study, NIPPV appeared to be asso-
ciated with a reduced QoL and observed adverse effects from NIPPV include
skin breaks at the site of the mask, facial soreness, dry throat, and abdominal
distension. Thus, the possibility of these untoward events should be discussed
with patients and their families prior to the initiation of treatment.

Key Recommendations
To improve QoL for patients with hypercapnic respiratory failure we
recommend:

• Identify the etiology of hypercapnic respiratory failure, establish goals of

care, and screen for sleep-disordered breathing.
• Use a QoL measurement before initiating NIPPV and repeat at 4–6 weeks
to assess whether NIPPV is having a beneficial effect on QoL.
• Titrating IPAP to normalize daytime hypercapnia may lead to the greatest
improvements in QoL, and may be mandatory in patients with COPD to
improve QoL.
• Adjust mask fit and pressure settings as needed to reduce the adverse
effects of NIPPV that may occur, such as facial soreness, dry mouth, sore
throat, and abdominal distension.
• Treat patients at home rather than in a hospital setting if possible, as this is
associated with greater QoL scores.

References
1. American Thoracic Society. Quality of life resource 2007. http://qol.thoracic.org/sections/
instruments/index.html.
2. Windisch W, et al. Impact of home mechanical ventilation on health-related quality of life. Eur
Respir J. 2008;32:1328–36.
99 Quality of Life during Long-Term Mechanical Ventilation 865

3. Annane D, Orlikowski D, Chevret S. Nocturnal mechanical ventilation for chronic hypoventi-

lation in patients with neuromuscular and chest wall disorders. Cochrane Database Syst Rev.
2014;(12):CD001941.
4. Bourke SC, et al. Effects of non-invasive ventilation on survival and quality of life in patients
with amyotrophic lateral sclerosis: a randomized controlled trial. Lancet Neurol.
2006;5:140–7.
5. Toussaint M, Chatwin M, Soudon P. Mechanical ventilation in Duchenne patients with chronic
respiratory insufficiency: clinical implication of 20 years published experience. Chron Respir
Dis. 2007;4:167–77.
6. Ward S, et al. Randomized controlled trial of non-invasive ventilation (NIV) for nocturnal
hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia.
Thorax. 2005;60(12):1019–24.
7. Hida W, et al. Nasal continuous positive airway pressure improves quality of life in obesity
hypoventilation syndrome. Sleep Breath. 2003;7:3–12.
8. Young AC, et al. Randomised placebo controlled trial of non-invasive ventilation for hypercap-
nia in cystic fibrosis. Thorax. 2008;63:72–7.
9. Tsolaki V, et al. One-year non-invasive ventilation in chronic hypercapnic COPD: effect on
quality of life. Respir Med. 2008;102:904–11.
10. McEvoy RD, et al. Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a
randomized controlled trial. Thorax. 2009;64:561–6.
11. Struik FM, et al. Nocturnal non-invasive positive pressure ventilation for stable chronic
obstructive pulmonary disease. Cochrane Database Syst Rev. 2013;(6):CD002878.
12. Köhnlein T, et al. Non-invasive positive pressure ventilation for the treatment of severe stable
chronic obstructive pulmonary disease: a prospective, multicenter, randomized, controlled
clinical trial. Lancet Respir Med. 2014;2:698–705.
13. Tuggey JM, Plant PK, Elliott MW. Domiciliary non-invasive ventilation for recurrent acidotic
exacerbations of COPD: an economic analysis. Thorax. 2003;58:867–71.
14. López-Campos JL, et al. Factors related to quality of life in patients receiving home mechani-
cal ventilation. Respir Med. 2008;102:605–12.
Ethics: Decision Making in Noninvasive
Ventilation 100
Andrea Purro

Contents
100.1 Introduction ................................................................................................................. 867
100.2 Discussion and Main Topics ....................................................................................... 868
Conclusion ............................................................................................................................. 871
References .............................................................................................................................. 872

100.1 Introduction
Ethics: a set of principles that people use to decide what is right and what is wrong.

Invasiveness of interventions, complexity of diseases, and patients’ age are

increasing in intensive care medicine. Ethical and legal issues are particularly chal-
lenging at the end of life of critically ill patients. At the borderline between inten-
sive care and palliative medicine, a significant number of patients suffer from
respiratory failure. Modern modes of mechanical ventilation may be able to improve
ventilation and quality of life. On the other hand, they may oppose a dignified death
at the end of a long-lasting chronic disease and prolong the suffering.
In contrast to endotracheal intubation and invasive mechanical ventilation, non-
invasive ventilation (NIV) enables patients to participate in the decision making
process. Under normal circumstances, ethical standards dictate that patients them-
selves participate in the medical decision making process. Patients with indications
for NIV can be categorized into three groups: those who want all possible treat-
ments and life-support; those who have elected specific limits on life-support and

A. Purro, MD
Emergency Department, Gradenigo Hospital, Turin, Italy
e-mail: [email protected]

© Springer International Publishing Switzerland 2016 867

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9_100
868 A. Purro

treatments, such as patients with do-not-intubate (DNI) orders; and patients very
near the end of life who will receive comfort measures only (CMO) [1].

100.2 Discussion and Main Topics

Over the last 20 years, the majority of the literature on NIV for acute respiratory
failure (ARF) has focused on patients who want all possible life support and treat-
ments. Randomized controlled trials have described the settings where NIV is
effective.
Many patients who set limits on life support and treatments have had poor expe-
riences with intubation and have chronic disease and a poor prognosis. CMO
patients may desire only to minimize discomfort and ease the dying process.
Clearly, the goals of therapy differ in the three care categories. The main ethi-
cal concern about NIV for ARF in DNI and CMO patients is informed consent,
which is necessary but can be problematic, because not all patients with terminal
diseases have discussed end-of-life issues with their physicians, and many physi-
cians are reluctant to discuss advance directives with their patients. Johnston et al.
[2] surveyed 329 adult outpatients, 282 residents, and 272 practicing physicians
(response rates 75 %, 76 %, and 65 %, respectively) for their opinions about
advance directives. The patients believed that discussions regarding advance
directives should occur earlier in the course of disease and earlier in the patient-
physician relationship than did the physicians. Both physician and patients
thought it was the physician’s responsibility to initiate the discussions about
advance directives. Despite literature that indicates patients’ desire to discuss
advance directives and a mandate by regulatory agencies, many patients with end-
stage disease, and the elderly, have not formalized their treatment wishes with
advance directives. Many patients at end of life who are transferred to acute-care
hospitals do not have advance directives [3].
Because standard advance directives are not commonly found in patients’ med-
ical records, it can be difficult to know whether a patient at end of life has dis-
cussed NIV. Recent statements about palliative care from societies whose focus is
patients with chronic pulmonary diseases do not discuss NIV in the sections on
the standard of care for patients with cardiopulmonary disease at end of life [4].
Thus, it is up to the clinician to determine whether the patient has consented to
NIV. The patient should be educated to the fact that NIV is a form of life support,
but is noninvasive, and that the patient can discontinue NIV at any time. Ideally, a
discussion about NIV should occur long before the patient is near the end of life.
The ideal is to provide precise direction to all caregivers regarding the patient’s
wishes. NIV is an ethical approach to managing a patient at end of life if the
patient provides informed consent. The literature on the application of NIV to
DNI and CMO patients is limited, and there have been no randomized controlled
trials. In addition, underlying primary diagnosis was an important determinant of
survival. Patients with congestive heart failure had significantly better survival
than any of the other groups.
100 Ethics: Decision Making in Noninvasive Ventilation 869

Little information is available on clinicians’ perspectives on NIV in DNI and

CMO patients. Sinuff et al. [5] surveyed pulmonologists, intensivists, and respira-
tory therapists (RTs) in 18 Canadian and 2 US institutions on the use of NIV in
patients with ARF near the end of life. The survey asked about factors associated
with the use of NIV in DNI and CMO patients. Overall, 104 (57 %) of 183 physi-
cians and 290 (61 %) of 473 RTs responded. Sixty-two percent of the physicians
indicated that they include NIV in DNI discussions at least part of the time. Eighty-
seven percent of the RTs indicated that NIV should be included in these discus-
sions. Regarding CMO patients, fewer respondents thought NIV should be included
in the discussion. Forty-nine percent of the physicians indicated that at least some
of the time they include NIV in the discussion, whereas 41 % of the RTs thought
that NIV should be part of the discussion. The RTs indicated that they were asked
to initiate NIV on DNI and CMO patients more frequently than the physicians
indicated they ordered it. Both physicians and RTs indicated they used NIV more
frequently in DNI patients than in CMO patients. The physicians were more likely
than the RTs to believe that NIV relieves dyspnea and facilitates communication in
DNI and CMO patients. The RTs more commonly than physicians indicated that
NIV was used so that the patient’s family had time to come to terms with their
loved one’s death. Physicians more commonly than RTs indicated that NIV was
used so that patients would have time to get their personal affairs in order. Both
physicians and RTs indicated that NIV at end of life for either DNI or CMO was
more likely in patients with COPD or congestive heart failure than in patients with
end-stage cancer.
These data clearly indicate an inconsistency of practice between physicians and
RTs with regard to NIV at the end of life. Additional study is needed on the use of
NIV in DNI and CMO patients, and about those patients’ perspectives on NIV.
NIV has been well recognized as a palliative tool, merely aimed to treat dyspnea
when acute respiratory distress or failure ensues [6]. The need for mechanical sup-
port is theoretically the main intervention when an organ is failing beyond a point at
which any pharmacological intervention is ineffective or partially effective. This is
true for the kidney, lung, and even the heart. The problem is understanding in clini-
cal practice when mechanical support may be futile. Failure of weaning from inva-
sive mechanical ventilation is one of the major clinical problems in patients with
COPD. In one study [7], these “chronically critically ill” patients, representing only
3 % of the total number of patients admitted to the ICU, used almost 40 % of the
total patient days of care.
The manner in which this relatively small population cuts into hospital costs has
drawn the attention of experts in the field. Thus, Seneff et al. [7] have openly stated
that, “there is some level of costs of acute care that is beyond our society’s economic
capacity.” Does this mean that a patient with advanced COPD always “deserves” an
end-of-life care decision? The general perception is that the outcome of COPD
patients requiring mechanical ventilation is poor, despite several studies in which
invasive ventilation or NIV was employed to demonstrate an acceptable survival
rate. With the introduction of NIV to treat acute respiratory failure of different eti-
ologies 20 years ago, classical outcome measures such as hospital mortality, need
870 A. Purro

for endotracheal intubation, complications of invasive ventilation, and length of

hospital stay have been drastically improved. The feasibility and usefulness of NIV
in the palliative care of patients with acute respiratory failure near the end of their
lives is still not well demonstrated.
Frequently, NIV is also used for those patients with terminal diseases to help
alleviate respiratory distress and attempt to provide some additional time to say
goodbye to their relatives and friends or to solve some administrative issues, but
most clinicians are unclear about the goals of care. For example, it has been high-
lighted that NIV may be inappropriate in this context because of an increased use
of medical resources, prolongation of the dying process, and intensification of
suffering. So there is a need to facilitate the decision concerning NIV or any other
form of mechanical ventilation.
When patients are well informed, they are generally satisfied with the decision
that has been made and do not change their mind later. Therefore, the decision to
commence mechanical ventilation in end-stage COPD needs the active participation
of the patient. Physicians and educators should target patients with COPD to
improve patients’ education about diagnosis and the disease process, and to explain
the treatments, prognosis, what dying might be like, and advance care planning. To
address these issues, Dales et al. [8] developed and tested an aid to assist patients
with decisions about mechanical ventilation. A scenario-based decision aid was
developed, consisting of an audiocassette and a booklet describing intubation and
mechanical ventilation and its possible outcomes. From this study it may be con-
cluded that, when discussed and explained in detail, an end-of-life decision is stable
in time and the patients achieve satisfaction and confidence. Proxy decisions were
incongruent, especially when made by family members; however, the strong sex
effect suggested a call for further investigation.
When used as life-support, NIV for ARF should be applied in the intensive care
unit (ICU), in an intermediate care unit, or in the emergency department. Curtis
et al. [9] defined NIV as life support when the patient is unable to sustain spontane-
ous breathing for at least 1 h without NIV. However, DNI and CMO patients have
been successfully sustained on NIV outside the ICU. A general medical/surgical
unit’s staff must understand the risks and benefits of NIV, and patients must be
appropriately monitored, including alarms for ventilator disconnect, pressure-loss,
high airway pressure, pulse oximetry, and cardiovascular monitoring, which should
all annunciate in the hall and nursing station to rapidly alert staff of changes in
patient status or ventilator malfunction. All categories of patients who require NIV
can be safely and effectively managed on general medical units, given proper staff
training and patient monitoring.
The best setting for NIV in older patients with DNI orders is the subject of some
debate [10]. Whereas the use of NIV in patients with acute respiratory failure with-
out preset limitations on life-sustaining treatment may be implemented in different
settings (ICUs, respiratory ICUs (RICUs), and emergency rooms), depending on the
typology of acute syndrome and the likelihood of success, the ideal care for “DNI
patients” is likely to be more appropriate outside the ICU. In fact, for these patients
for whom endotracheal intubation is questionable or care is centered largely on
100 Ethics: Decision Making in Noninvasive Ventilation 871

symptom palliation or both, NIV failure requires to increase of comfort measures

only, adequately performed in totally or partially “open” environments. The option
of NIV in end-of-life decisions is emerging in European RICUs, where a large
majority of DNI patients are treated by pulmonologists. This is not surprising, as
RICUs differ substantially from ICUs in terms of patient population, staffing, moni-
toring, and use of NIV as the preferred ventilator approach [4]. Furthermore, a
recent American survey showed that the stated use of NIV and the confidence in its
utility in end-of-life patients were greater for pulmonologists than for intensivists.
A pulmonologist’s point of view may be influenced by caring for end-stage respira-
tory patients over the entire spectrum of the illness as opposed to the greater focus
on acute care among intensivists.
In conclusion, the assignment of older patients with DNI orders to an environ-
ment, such as the ICU, that was originally designed to treat patients without preset
limitations of care (i.e., invasive mechanical ventilation) raises financial and ethi-
cal concerns, namely (a) the questionable cost-utility ratio of allocating the pre-
cious, limited ICU resources for patients whose needs may be met by lower levels
of care (i.e., nurse workload) and (b) the inappropriateness of a “closed environ-
ment” for managing respiratory patients who would like to spend the end of their
lives near their friends and family. Hospital administrators should identify, in
expert pulmonology units, the optimal setting for implementing NIV within the
DNI and end-of-life context to achieve economic and ethical benefits that surpass
those of the ICU.

Conclusion
NIV can benefit patients who have elected specific limits on life support and
treatments (e.g., DNI) and patients who will receive comfort measures only.
The critical ethical issue with regard to NIV for DNI and CMO patients is
informed consent. The risks and potential benefits of NIV must be clearly dis-
cussed. Data from terminal cancer patients suggest that is important to patients
retaining control over end-of-life care decisions and having adequate time to
prepare for death. If control over care decisions is assured, NIV may be able to
reverse an ARF that is not necessarily a life-terminating event, or improve
patient comfort, or sustain life until the patient can put his or affairs in order.

Key Major Recommendations

• NIV can be useful in DNI and CMO patients.
• The critical ethical issue with regard to NIV for DNI and CMO patients is
informed consent.
• Hospital administrators should identify the optimal setting for implement-
ing NIV within the DNI and end-of-life context.
872 A. Purro

References
1. Kacmarek RM. Should noninvasive ventilation be used with the do-not-intubate patient?
Respir Care. 2009;54:223–9.
2. Johnston SC, Pfeifer MP, McNutt R. The discussion about advance directives. Patient and
physician opinions regarding when and how it should be conducted. Arch Intern Med.
1995;155(10):1025–30.
3. Selecky PA, Elisson AH, Hall RI, et al. Palliative and end of life care for patients with cardio-
pulmonary diseases: American College of Chest Physicians Position Statement. Chest.
2005;128:3599–610.
4. Carlucci A, Guerrieri A, Nava S. Palliative care in COPD patients: is it only an end-of-life
issue? Eur Respir J. 2012;21:347–54.
5. Sinuff T, Cook DJ, Keenan SP, et al. Noninvasive ventilation for acute respiratory failure near
the end of life. Crit Care Med. 2008;36(3):789–94.
6. Nava S, Sturani C, Hartl S, et al. End-of-life decision-making in respiratory intermediate care
units: a European survey. Eur Respir J. 2007;30:156–64.
7. Seneff MG, Wagener D, Thompson D, et al. The impact of long-term acute-care facilities on
the outcome and cost of care for patients undergoing prolonged mechanical ventilation. Crit
Care Med. 2000;28:342–50.
8. Dales RE, O’Connor A, Hebert P, Sullivan K, et al. Intubation and mechanical ventilation for
COPD: development of an instrument to elicit patient preferences. Chest. 1999;116:792–800.
9. Curtis JR, Cook DJ, Sinuff T, White DB, Hill N, Keenan SP, et al. The SCCM Palliative NPPV
Task Force. Noninvasive positive pressure ventilation in critical and palliative care settings:
understanding the goals of therapy. Crit Care Med. 2007;35(3):932–39.
10. Scala R, Esquinas A. Noninvasive mechanical ventilation for very old patients with limitations
of care: is the ICU the most appropriate setting? Crit Care. 2012;16:429.
Index

A NIV treatment
Absolute humidity (AH), 185 acute coronary syndrome, 356
ACPE. See Acute cardiogenic pulmonary vs. conventional treatment, 355
edema (ACPE) in general wards, 834
ACS. See Acute coronary syndrome (ACS) observational studies, clinical
Acute asthma (AA) results, 833
clinical sign, 314 utilization rate, 833
GINA, 314 pathophysiology, 385–386
NCPAP, 136–137 programming of, 371
NIV, 316–317, 634, 635 respiratory and hemodynamic effects,
physiological changes, 314 354–355
physiologic signs, 314–315 SMT, 368–369
prevalence, 314 Acute coronary syndrome (ACS)
steroid therapy, 316 ACPE, 356
Acute cardiogenic pulmonary edema (ACPE) FBO, 609
acute chronic cardiac exacerbations, heart failure, 384
377–379 Acute exacerbation of chronic obstructive
AHRF pulmonary disease (AECOPD),
bi-level NPPV vs. CPAP, 238–239 4–5, 153, 157
clinical practice, 239–240 early NIV failure
emergency department, 238 baseline ABG and inability, 254
hypertensive vs. nonhypertensive, 239 hypercapnic ARF, 254
literature and rationale, 238 respiratory rate, 254
BiPAP, 368, 370–372, 387 severity of disease, 254
cardiac procedures, 372 ETI, 251
CPAP, 368, 370, 371, 386–387 face mask, 251
diastolic dysfunction immediate NIV failure
computer-generated randomization coma, 253
sequence, 364 HES, 253
CPAP, 261, 262 intolerance and psychomotor
criteria, 262 agitation, 253
patients’ baseline characteristics, patient-ventilator asynchrony, 253
362, 363 weak cough reflex and excessive
ultrasound investigation, 363–364 secretions, 252
ventilator and interfaces, 362–363 intermittent mode of support, 251
heart-lung interactions, 376–377 late NIV failure, 254–256
HF (see Heart failure (HF)) NIV treatment
LUS, 593 availability and use of, 831–832
NCPAP, 134, 135 in general wards, 834

© Springer International Publishing Switzerland 2016 873

A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation: Theory, Equipment,
and Clinical Applications, DOI 10.1007/978-3-319-21653-9
874 Index

Acute exacerbation of chronic obstructive clinical and laboratory values, monitoring

pulmonary disease (AECOPD) of, 242
(cont.) clinical goals for, 240
observational studies, clinical CPAP, 416
results, 833 definitions, 414
NPPV, 5 ECMO, 630–631
patient-related predictors, 251 endotracheal intubation, 415
patient-related risk factors, 252 literature and rationale, 240
prevalence, 251 lung injury, 414
UMC, 256 LUS, 593
ventilation, 250 NIV, use of, 634, 635
weaning patients, 463, 466 NPPV trial, 241–242
Acute hypoxemic respiratory failure PaO2/FiO2 ratios, 415, 416
(AHRF), 246 PEEP, 242
ACPE prevalence, 414
bi-level NPPV vs. CPAP, 238–239 Acute respiratory failure (ARF), NIV
clinical practice, 239–240 ACPE, 355
emergency department, 238 adaptation process
hypertensive vs. nonhypertensive, 239 advantage, 692
literature and rationale, 238 implementation protocols, 692
ARDS, 240–242 practical explanation, 694–695
atelectasis, 244 sequential steps, 694
blunt chest trauma, 244 alveolar flooding, 305
drowning, 244–245 alveolar ventilation, 260
epidemiology of, 540 availability and use of, 831–832
immunocompromised patients, 541 bag valve mask ventilation, 261
NCPAP CAP, 407
acute asthma, 136–137 cardiac surgery, 502–503
chronic conditions, 137 chest trauma, 836
clinical practice, 132–133 clinical conditions, 831
criteria, 138 comorbidity, 296–297
immunocompromised patients, 137 COPD, 4, 5
indications and contraindications, CPAP, 306–307
138–139 DNI and CMO patients, 832, 836
success/failure, predictors for, 139, 140 advance directives, 868
treatment, 136 COPD patients, 869, 870
NIV, efficacy of, 634 general medical units, 870
NPPV informed consent, 868
benefits, 541 older patients, 870, 871
in cancer patients, 542–544 physicians and RTs, 869
complications, 544 RICUs, 871
management of, 541 terminal diseases, 870
RCTs, 540, 541 for DNR patients, 832
pneumonia, 242–243 emergency medical services,
Acute lung injury (ALI) 259–260
NIV, use of, 549–550, 634, 635 FBO and ppNIMV (see Flexible
TRALI (see Transfusion-related acute lung bronchoscopy (FBO))
injury (TRALI)) in general wards, 834–835
Acute Physiology and Chronic Health hematological malignancy (see
Evaluation II (APACHE II), Hematological malignancy)
254, 440 hypercapnic ARF, 320, 853
Acute respiratory distress syndrome (ARDS) hypoxemic (see Acute hypoxemic
Berlin definition of, 241 respiratory failure (AHRF))
cardiopulmonary interactions, 17 indications
Index 875

contraindications, 262–263 OSA patients, CPAP adherence in,

hospital setting, 261 692–694
oxygen toxicity, 263 physiotherapist’s role in, 700
patient outcomes, 262 Adaptive servo-ventilation (ASV), 389, 760
prehospital setting, 262 Adult respiratory distress syndrome (ARDS),
interventional procedures, 836 549, 645
neurological dysfunction Advance directives, 868
case-control methodology, 439–441 AeCOPD. See Acute exacerbation of chronic
cases series, patient, 438–439 obstructive pulmonary disease
encephalopathy scale, 437 (AECOPD)
GCS, 436 Aerosol therapy
Kelly-Matthay scale, 437 bronchodilators and steroids, 192
NIV security, 441–442 circuit-related factors, 194
prevalence of, 436 drug-related factors, 196
treatment of, 437 interface, 194
ventilation mode, 442 nebulizers, 195, 197
NPPV, 42, 621–622 patient-related factors, 196
observational studies, clinical results, physiology of, 192
833–834 pMDIs, 195, 196
older patients, 453–454 ventilator-related factors, 193–194
OSA, 524 AHI. See Apnea hypopnea index (AHI)
palliative treatment, 836 AHRF. See Acute hypoxemic respiratory
pandemics, 837 failure (AHRF)
patient selection, 830 Air-stacking, 336, 342
possible life support and AIRVO™ system, 101
treatments, 868 Airway clearance techniques
post-extubation period NIV, 298
curative, 515 respiratory failure
preventive, 514–515 cough, 217–218
postoperative respiratory failure, 836 IPV equipment, 218–219
SB (see Skin breakdown (SB)) manual vibration, 217
solid malignancies, patients with (see Solid orotracheal and nasotracheal aspiration,
malignancies, ARF in) 219–220
during surgery percussion, 216–217
caesarean section, 491 shaking, 217
deep sedation, 491 Airway smooth muscle (ASM) cells,
practical recommendations, 492 747–748, 750
respiratory diseases, 490 ALI. See Acute lung injury (ALI)
tracheal intubation, 491 ALS. See Amyotrophic lateral sclerosis
vaginal delivery, 491 (ALS)
utilization rate of, 831–833 Ambulatory HMV
weaning patients, 467–468 ABG analysis, 734
Adaptation, NIV chronic respiratory failure, 733
in acute RF COPD, 733
advantage, 692 equipment for, 733
implementation protocols, 692 health-care costs, reduction in, 732
practical explanation, 694–695 vs. hospital adaptation, 732
sequential steps, 694 inclusion and exclusion criteria, 733, 734
in chronic RF, 692 monitoring visit, 734
COPD patients, high-intensity motor neuron disease, 733
NIV for, 695–697 patients follow-up, 734
restrictive chronic RF, follow-up requirements for, 733
protocol for, 696, 698–699 American Academy of Neurology
equipment malfunctions, 700 (AAN), 340
876 Index

American Academy of Sleep Medicine Atrial fibrillation, 604–605

(AASM), 186, 674, 743 Auto-positive end-expiratory pressure
Amyotrophic lateral sclerosis (ALS), (auto-PEEP), 721
786–787 Average volume-assured pressure support
bulbar weakness, 340 (AVAPS), 37, 441, 659, 664, 788,
neurodegenerative disease, 340 846
NIPPV, 475, 476 Awake ECMO
NIV in, 298 activities, 629
AAN, 340 ARDS patients, 630–631
benefits, 807, 808 COPD, 629–630
contraindications, 808 diaphragm function, preservation of, 629
European guidelines, 341 lung transplantation, 629
monitor NIV titration, 341
PCF, 342
PEG placement, 342 B
psychological factors, 808–809 Back-up respiratory rate (BURR)
survival and quality of life, 341 bi-level pressure cycled ventilation,
oronasal interfaces, 340 675–677
telemonitoring, 804 built-in software, 678
Analgesia. See Sedation and analgesia, NPPV in COPD, 677, 678
Analgosedation, 623, 625 volume-cycled devices, 674
Anxiety, 727–728 BAL. See Bronchoalveolar lavage (BAL)
Aortic stenosis (AS), 601 Beck Depression Inventory, 727
Apnea hypopnea index (AHI), 389 Benzodiazepines, 623, 624
children, TNI, 108–109 Bi-level positive airway pressure (BiPAP)
OSA, 719 therapy, 329
UANP, 644 ACPE, 368, 370–372, 387
ventilator software, 87 asthma attack, 315
ARDS. See Acute respiratory distress CAP, 406
syndrome (ARDS) capnography, 180
ARF. See Acute respiratory failure (ARF), CSA, S- and ST-mode ventilation,
NIV 668, 669
Arterial blood gas analysis (ABG) endotracheal intubation, 583, 584, 586
monitoring, 170 leakage (see Noninvasive ventilation
NCPAP, 141 (NIV), leakage)
Artificial humidification, 184 overlap syndrome (see Overlap syndrome)
Aspiration reflex (AspR), 643, 644 PARF, 497–498
Asthma pre-hospital NIPPV systems, 268
acute (see Acute asthma (AA)) vs. servo-ventilation, complex sleep
airway inflammation, 748 apnea, 670
ASM cells, 747–748, 750 single-limb circuits, 194
bronchoconstriction, reversal of, 748 Blunt chest trauma
CPAP therapy, effects of causes, 426
animal studies, 748 lung injury, pathophysiology of, 427
human studies, 749–750 NIV, 244
inhaled therapy, 750 application of, 431
obese patients, 750 benefits of, 427–428
rhinitis, 751 endotracheal intubation, 428, 429
Atelectasis indications and contraindications, 430
CPAP/NIMV, 403 “low grade recommendation,” 426
critically ill patients, 403 pain management, 431
incidence of, 401 patient outcomes, 431–432
neuromuscular disorders, 403 randomized control trials, 428, 429
postoperative period, 402 severe and worsening hypoxemia, 430
Index 877

Body-mass index, airflow Obstruction, electrophysiological procedures, 604–605

Dyspnea, and Exercise mitral clip, 602
(BODE), 775 TAVI, 601
Boussignac CPAP system, 271, 529, 584, TEE examination, 602–604
586, 617 Cardiac surgery
Brief Symptom Inventory of Depression and and ARF, 502–503
Anxiety, 727 postoperative period
Bronchiectasis benefit, 504
complication, 304 fast-track cardiac anesthesia, 503
COPD/asthma, 304 intensive care unit, 503
CPAP (see Continuous positive airway myocardial oxygen delivery, 503
pressure (CPAP)) PPV, 504–505
infective exacerbations, 304 prophylactic nasal CPAP, 504
obstruction, 305 PVR, 505
PEP, 308 surgical complications, 505
prevalence of, 304 valve repair/replacement, 503
respiratory failure, 304 ventilator settings, 505–506
Bronchoalveolar lavage (BAL), 610–611, 613 Cardiogenic shock, 239, 356, 370
Bronchoscopy and NIMV Cardiopulmonary interactions
advantages and disadvantages of, 610 cardiac output, 9
FBO (see Flexible bronchoscopy (FBO)) clinical implications
ICUs and RICUs, application in, 607 cardiac diseases, 14–15
interventional RB procedures, 608, 609, pulmonary diseases, 15–17
615–616 dyspnea, 14
intubation guidelines, 835 intrathoracic cardiovascular system, 13
npNIMV, 608, 615 ITP, 8, 12–13
Bulbar syndrome, 295 PPV, 12
BURR. See Back-up respiratory rate pulmonary compliance, 9
(BURR) PVR, 10–11
spontaneous breathing, 11–12
time constant, 14
C transmural pressure, 9
Canadian Consensus Conference on ventilation/perfusion ratio, 9–10
TRALI, 421 ventricular interdependence, 9
Canadian Continuous Positive Airway Cardiovascular rehabilitation
Pressure for Treatment of Central COPD and HF, 226
Sleep Apnea in Heart Failure dynamic hyperinflation, 225–226
(CANPAP) trial, 760 functional performance, 225
CAP. See Community-acquired pneumonia hemodynamic parameters, 224–225
(CAP) Center for Epidemiologic Studies Depression
Capnography, 179–181 Scale, 727
Carbon dioxide (CO2) rebreathing Central sleep apnea (CSA), 667–668
dead space, interfaces, 230 bi-level-S-mode ventilation, 668, 669
FiCO2, 230 bi-level-ST-mode ventilation, 668, 669
helmet ventilation, 233 in CHF patients
mask ventilation ASV, 760
dual-limb circuit, 231 central respiratory drive, reductions
single-limb circuit, 231–232 in, 754
Cardiac procedures, NIV in CPAP therapy, effects of, 388–389,
cardiac catheterization laboratory 758–760
coronary angiography and PCI, pathogenesis, 755
600–601 pathophysiology, 756
septal defects, percutaneous closure respiratory movements, 754
of, 601 servo-ventilation, 668–669
878 Index

Chest physiotherapy techniques Chronic heart failure (CHF)

aims of, 216 central sleep apnea
airway clearance techniques ASV, 389–390, 760
cough, 217–218 central respiratory drive, reductions
IPV equipment, 218–219 in, 754
manual vibration, 217 CPAP therapy, effects of,
orotracheal and nasotracheal aspiration, 389, 758–760
219–220 CRT, 389
percussion, 216–217 pathogenesis, 755
shaking, 217 pathophysiology, 756
Chest trauma, 426, 834. See also Blunt respiratory movements, 754
chest trauma epidemiology and pathophysiology,
Chest wall disease 387–388
BIPAP device, 329 older patients, 453
NIV, 326–327 OSA patients
contraindications of, 330, 331 CPAP therapy, effects of, 388–389,
indications for, 328 756–758
mechanism of action, 325, 326 pathogenesis, 754–755
negative pressure ventilation, 329 pathophysiology, 756
NIPPV, 329–330 respiratory movements, 754
prophylaxis therapy, high-risk upper airway collapse, 754
patients, 328 Chronic hypercapnic respiratory failure
volume-targeted and pressure-targeted (CHRF)
modes, 328–329 ambulatory vs. hospital adaptation, 732
pregnancy in, 331 BURR, 675
respiratory failure, pathophysiology causes of, 860
of, 324–325 NIV, 454, 464
Cheyne-Stokes respiration (CSR), 388, 667, 754 Chronic obstructive pulmonary disease
CHF. See Chronic heart failure (CHF) (COPD)
Children acute exacerbations (see Acute
NIV-NAVA (see Noninvasive neurally exacerbation of chronic obstructive
adjusted ventilatory assist pulmonary disease (AECOPD))
(NIV-NAVA)) asthma, 316
NPPV, interfaces for AVAPS mode, 664
advantages and limitations, 823 awake ECMO, 629–630
compliance, 823 bronchiectasis, 304
facial flattening, 821, 822 bronchodilator medication in, 484
full face masks, 816, 818 dynamic hyperinflation, 225
headgear, 819 ECCO2R, 630
helmet, 818–819 encephalopathy, 440
infant nasal cannula, 818, 819 end-of-life care decisions, 869, 870
intentional leaks, 819 exercise training, 226
mask choice, 821, 822 exhalation devices, effects of, 117
maxilla retrusion, severe GCS, 440
laryngomalacia, 820, 821 high BURR, 677, 678
monitoring, 822 HVC contamination, 94
mouthpiece and oral masks, 817, 818 hypercapnic respiratory failure, 863
nasal masks, 815–817 iVAPS, 665
nasal pillows/plugs, 814–816 Kelly-Matthay scale, 439, 440
nasobuccal mask, 816–818 long-term NPPV, 767–769
neuromuscular/lung disease, 814 lung mechanics in, 154–155
skin injury, risk of, 820–821 lung transplantation, long-term NIV,
vented/non-vented, 819 775–776
with OSA, TNI, 108–109 malnutrition, 204
Index 879

nasal pillows, 29 Continuous positive airway pressure (CPAP),

NIOV, 101–102 267, 845. See also Noninvasive
NPPV continuous positive airway pressure
acute exacerbations, 4–5 (NCPAP)
cardiovascular effects, 4 ACPE patients, 261, 262, 355, 356
hypoventilation correction, 4 inspiratory failure, 371
respiratory center reset, 4 LUS for, 592
respiratory muscle unloading, 4 OMT, 386–387
reverting hypoventilation, 4 acute respiratory failure, 306–307
off-cycling criterion airway clearance, 307
delayed, 156–158 atelectasis, 403
flow and pressure curves, 155 blunt chest trauma, 428
patient-ventilator interaction, 156 CAP, 406
premature, 156 capnography, 180
ventilator performance, 155 chest physiotherapy, 307–309
older patients, 453, 454 during exercise, 309
PEEPi (see Intrinsic positive end- expiratory resistance, 684–685
expiratory pressure (PEEPi)) fiber-optic nasotracheal intubation, 582,
solid malignancies, 569 584, 586, 587
telemonitoring, 804 NIV-NAVA, 149–150
Chronic respiratory failure (CRF), 692 nonapneic asthmatic patients, effect on
COPD patients airway inflammation, 748
high-intensity NIV for, 695–697 animal studies, 748
long-term NPPV, 767–769 ASM, 747–748, 750
in DMD, 335 bronchoconstriction, reversal of, 748
humidification, 184 human studies, 749–750
inadequate staff training, consequences inhaled therapy, 750
of, 856 obese patients, 750
lung transplantation, long-term NIV (see rhinitis, 751
Lung transplantation) NPPV, 305–306
NPPV, 42 OSA patients (see Obstructive sleep apnea
older patients, 454 (OSA) syndrome)
restrictive chronic RF, follow-up protocol overlap syndrome (see Overlap syndrome)
for, 696, 698–699 PARF, 497–498
Claustrophobia, 710 pMDI, 193
Comfort measures only (CMO) patients pre-hospital use of
advance directives, 868 Boussignac, 271
COPD patients, 869, 870 Flow-Safe, 272
general medical units, 870 O2-RESQ, 273
informed consent, 868 O-Two Single-Use CPAP device,
physicians and RTs, 869 272–273
Community-acquired pneumonia Oxy-PEEP, 273–274
(CAP), 297 Rescuer Emergency (BLS
antimicrobial therapy, 406 Systems), 273
in ARF, 407 REM, 128
BiPAP, 406 solid malignancies, 568
CPAP, 406 WB, 132
criteria, 410, 411 COPD. See Chronic obstructive pulmonary
de novo group, 408, 409 disease (COPD)
incidence of, 406 CO2 rebreathing. See Carbon dioxide (CO2)
interfaces, 407 rebreathing
randomized controlled trials, Coronary angiography, 600–601
408, 409 CPAP. See Continuous positive airway
SAPS, 410 pressure (CPAP)
880 Index

CRF. See Chronic respiratory failure (CRF) iVAPS, 659, 664–665

CSA. See Central sleep apnea (CSA) leaks, tidal volume estimation, 659, 661
Cystic fibrosis (CF) PSV-VS/PSV-VG, 659
HVC contamination, 94, 95 PSV-VTG, 659, 661, 664
hypercapnic respiratory failure, 862–863 target tidal volume, 659
lung transplantation, long-term NIV, within-a-breath mode, 658–660
773–775 Duchenne muscular dystrophy (DMD),
NIOV, 102–103 782, 785–786
respiratory failure, 304 complications, 336
contraindications, 336
diurnal and nocturnal respiratory
D function, 334–335
Depression, 727–728 interfaces and settings, 336
Deventilation syndrome noninvasive mechanical ventilation
coexisting medical problems, 722 causes of NIV failure, 337
definition, 719 early initiation of, 335
patient-ventilator asynchrony goals of, 335
auto-PEEP, 721 pulmonary complication, 334
trigger asynchrony, 721–722 respiratory failure, 334
poor sleep pattern, 722 ventilator, 336
Dexmedetomidine, 623, 624 Dynamic hyperinflation (DH), 225–226
Diaphragm thickness (DT), 594–595
Diaphragm ultrasound, 594–595
DMD. See Duchenne muscular dystrophy E
(DMD) ECMO. See Extracorporeal membrane
Do-not-intubate (DNI) orders, 296 oxygenation (ECMO)
ARF, 455, 832 Emergency medical services (EMS), 260, 267
end-of-life care decisions End-expiratory lung volume (ΔEELV),
advance directives, 868 14, 154, 291
COPD patients, 869, 870 Endoscopy mask, 583, 584, 586
general medical units, 870 Endotracheal intubation (ETI), NIV in, 251
informed consent, 868 difficult intubation
older patients, 870, 871 acute respiratory failure, 579
physicians and RTs, 869 clinical deterioration, risk of, 578
RICUs, 871 complications, 578
terminal diseases, 870 definition of, 578
hematological malignancy, 558–559 LEMON mnemonic, 578, 579
NCPAP, 140–141 Mallampati classification, 578, 579
solid malignancies, 569–570 FBO and ppNIMV, 608, 614–615
Do-not-resuscitate (DNR), 832 limitations, 588
Downs Flow Generator, 270, 271 physiologic benefits
Drowning, 244–245 hemodynamic effects, 582–583
Drug overdose-associated respiratory failure oxygenation, 580–581
advantages and limitations, 397–398 patient comfort and safety, 583
aspiration syndromes/complications, 394 splinting upper airways, 581–582
bi-level ventilation, 394 ventilation, 580
characteristics, 394–396 procedural techniques
management, 394–396 BIPAP, 583, 584, 586
opioids, 394 bronchoscopic-guided intubation,
patient outcomes, 394–396 585–587
ventilatory support method, 398 CPAP, 583, 584, 586, 587
Dual-mode ventilators, 662–663 full face mask, 583
AVAPS, 659, 664 LMA, ILM and endoscopy mask, 583,
breath-to-breath mode, 659, 660 584, 586
Index 881

NOVA technique, 585, 587 F

remifentanil sedation, use of, 624 Flexible bronchoscopy (FBO)
EPAP. See Expiratory positive airway pressure acute coronary syndrome, 609
(EPAP) acute interstitial lung diseases, 607
Epworth sleepiness scale (ESS), 704, 860 cardiac arrhythmias, 609
Erectile dysfunction (ED), 742 cardiogenic pulmonary edema, 609
Ethics, decision making community- and hospital-acquired
definition, 867 pneumonia, 607
DNI and CMO patients, 867 and ppNIMV, in ARF patients
advance directives, 868 analgesic and sedative drugs, 617
COPD patients, 869, 870 arterial oxygen pressure, 608–609
general medical units, 870 BAL, 610–611, 613
informed consent, 868 bronchial biopsies, 613
older patients, 870, 871 bronchoaspirates, 613
physicians and RTs, 869 cardiopulmonary alterations, 610
RICUs, 871 cardiopulmonary pathophysiological
terminal diseases, 870 effects, 608, 609
possible life support and treatments, 868 complications, 618
ETI. See Endotracheal intubation (ETI), NIV in contraindications, 618
European-American Consensus Conference COPD patients, 611, 614
(EACC) CPAP Boussignac system, 611, 613,
Exhalation ports and interface 616, 617
bioaerosols, dispersion of, 119–120 ETI, 614–615
CO2 elimination failure rate, 609
built in devices, 114, 115 mean duration of, 618
connectable devices, types of, 114, 115 nasal mask, 613, 617
intentional leak rates, 115, 116 nosocomial pneumonia, 613
laboratory and clinical investigations, orofacial masks, 616–617
117–118 OSAS patients, 615
position, 118–119 pressure-support ventilation, 616
product specification, 115 PSB, 613
separate devices, 114 in semi-recumbent position, 618
ICU type ventilators, 119 setting adjustments, 617
Expiration reflex (ExpR), 643, 644 in supine decubitus, 618
Expiratory positive airway pressure (EPAP), synergistic application, 610, 611
321, 497–498, 845 TBLB, 613–614
aerosol drug, 194 total face mask, 613, 617
dynamic hyperinflation, 225 Flow-Safe®, 272
mouthpiece ventilation, 25 Forced expiratory volume in 1 second
myasthenic crisis, 346, 347 (FEV1), 485
Extracorporeal CO2 removal (ECCO2R), 630 Fractional inspired oxygen (FiO2), 185
Extracorporeal membrane oxygenation Fraction of inspiratory CO2 (FiCO2), 230
(ECMO) Functional residual capacity (FRC), 305,
awake ECMO 580–581
activities, 629
ARDS patients, 630–631
COPD, 629–630 G
diaphragm function, preservation Glasgow Coma Score (GCS), 320
of, 629 acute lung injury, 549
lung transplantation, 629 hypercapnic hypoxic coma, 436
ECCO2R, 630 Global Initiative for Asthma (GINA), 314
partial extracorporeal support systems, 629 Global Initiative for Chronic Obstructive
refractory respiratory failure, patient | Lung Disease (GOLD),
with, 629 102, 686, 768
882 Index

H inclusion and exclusion criteria, 733, 734

Haldane effect, 253 monitoring visit, 734
Heart failure (HF) motor neuron disease, 733
definition, 384 patients follow-up, 734
exercise, 226 requirements for, 733
management of, 384 BURR
SDB (see Sleep-disordered breathing bi-level pressure cycled ventilation,
(SDB)) 675–677
systolic function, 384 built-in software, 678
Heat-and-moisture exchanger (HME), in COPD, 677, 678
187–188 cystic fibrosis, 677
Helmet, 818–819 volume-cycled devices, 674
Hematological malignancy equipment, 90
ARF in Europe
diagnostic and therapeutic approach, follow-up, 795
557–558 France’s HMV program, 794
DNI, 558–559 national health systems, 794
drawback, 559 NIV adaptation, 794
flow chart, 560 prevalence rate, 792–793
NIV failure, 558 private insurance companies, 794
patients outcome, 556–557 telemonitoring, 795
timing and place, 557 hospital inpatients, 732
noninvasive vs. invasive ventilation in HVC (see Home ventilation circuits
patients (HVC))
ALI/ARDS, 549, 550 for hypercapnic respiratory failure, 732
CPAP, 549, 550 vs. ICU ventilators, 60
data collection, 549 monitoring
equipment technology, 549 built-in software, 174
gas exchange, 548 compressible volume, 177–178
PaO2:FiO2, 549 drawbacks of, 174
pediatric patients, 550 expiratory leak port, 176
PICU, 551 native flow-time graph, 174–176
risk factors, 550 unintentional leak, 177
Society of Critical Care Medicine, 551 neuromuscular disease, 787
Hering-Breuer inflation reflex, 642 pressure-controlled PV 403, 124
HES. See Hypercapnic encephalopathy software for
syndrome (HES) AHI, 87
High-flow nasal cannula oxygen compliance, 82–84
(HFNC), 581 RR and %Trigg, 85–87
CPAP, 306–307 unintentional leaks, 84–86
during ETI, 581 VT and minute ventilation, 83–85
vs. NIV, bronchoscopy, 571 volume-controlled PLV 102, 124
High-flow therapy (HFT), 101 Home ventilation circuits (HVC)
HME. See Heat-and-moisture exchanger cleaning instructions, 91
(HME) dirtiness and contamination, 90
Home mechanical ventilation (HMV) infections, sensitivity to, 91
AASM guidelines, 674 maintenance, 90–91
ambulatory adaptation obstructive disorders, 93–95
ABG analysis, 734 restrictive disorders, 92–93
chronic respiratory failure, 733 Humidification
COPD, 733 adverse effects, 186
equipment for, 733 epidemiological studies, 186
health-care costs, reduction in, 732 heated humidifiers, 186–188
vs. hospital adaptation, 732 HME, 187–188
Index 883

inefficient gas conditioning, 184–186 of patients receiving NIV, 282

settings, 188–189 staff, 278
HVC. See Home ventilation circuits (HVC) Intrapulmonary percussive ventilation (IPV),
Hypercapnic coma, 436, 441 218–219, 252
Hypercapnic encephalopathy syndrome Intrathoracic pressure (ITP), 11–13, 376,
(HES), 253, 436, 438, 441 505, 527
Hypercapnic respiratory failure Intrinsic positive end-expiratory pressure
hypercapnic ARF, 320, 853 (PEEPi)
NIPPV, QoL scores artificial ventilation, 288
COPD, 863 CPAP, 309
cost and admissions, 863 dynamic
cystic fibrosis, 862–863 arterial blood gases, 289
mean PaCO2, 861 ΔP, 291
neuromuscular disease, 861–862 inhomogeneous time constant
OHS, 861, 862 distribution, 289
symptom scoring systems, 860–861 NPPV, 289, 290
Hypoxemic ARF. See Acute hypoxemic sick inhomogeneous lung, 288
respiratory failure (AHRF) ZEEP, 288, 290
off-cycling criterion, 157, 158
pulmonary disease, 16
I static
ILD. See Interstitial lung disease (ILD) arterial blood gases, 289
Incremental shuttle walking test (ISWT), 743 ΔP, 291
Informed consent, 868 homogeneous gas distribution, 288
Injury severity scores (ISS), 428 NPPV, 289, 290
Inspiratory positive airway pressure (IPAP), ZEEP, 288
295, 321, 845 weaning failure, 459
aerosol drug, 194 Intubating laryngeal mask (ILM),
humidification, 185 583, 584, 586
myasthenic crisis, 346, 347 IPAP. See Inspiratory positive airway
Integrative weaning index (IWI), 461 pressure (IPAP)
Intelligent volume-assured pressure support IPV. See Intrapulmonary percussive
(iVAPS), 659, 664–665 ventilation (IPV)
Intensive care unit (ICU) ventilators ITP. See Intrathoracic pressure (ITP)
central gas source, 124 iVAPS. See Intelligent volume-assured
characteristics of, 43–45 pressure support (iVAPS)
flow rates, 125
gas sources, 125
vs. home ventilators, 60 J
oxygenation, 125 Janus full face mask, 603–604
pneumatic principles of, 124
PSV of, 124
technical features of, 124 K
Intermediate ventilators, 43–45 Kelly-Matthay scale, 439, 440
Intermittent positive-pressure ventilation Kyphoscoliosis
(IPPV), 22, 23 acute respiratory failure, 327
Interstitial lung disease (ILD) pregnancy, 331
lung transplantation, 772 thoracic deformity, 325
NIOV system, 101, 102
Intra-hospital transport
elements of, 280, 281 L
equipment, 279 Laryngeal mask airway (LMA), 583, 584, 586
noninvasively ventilated patients, 278 Limb-girdle muscular dystrophy, 782, 785
patient monitoring, 279–280 Locked-in-syndrome, 808
884 Index

Lung Allocation Score (LAS), 772 Motor neuron disease. See Amyotrophic
Lung transplantation lateral sclerosis (ALS), NIV in
CRF patients, long-term NIV in Mouthpiece ventilation (MPV)
advantages, 777 advantages and disadvantages, 24, 25
CF patients, 773–775 chronic conditions, patients with, 22
COPD patients, 775–776 complications, 22, 24
critically ill patients, 772 EPAP, 25
modalities and operating procedures, hypoxemic and hypercapnic ARF, 22
776–777 IPPV, 22, 23
end-stage lung disease, patients with, 771 Lipseal/Oracle, 22–24
indications, 772 neuromuscular disease, 22
LAS, 772 sleep-related breathing disorders, 22
waiting list global mortality rate, 772 Multiple sleep latency test (MSLT), 704
Lung ultrasound (LUS) Myasthenic crisis (MC)
advantages of, 592 gas exchange, 347
and alveolar recruitment IPAP and EPAP, 346, 347
ACPE, CPAP treatment, 593 myasthenia gravis, 346
ARDS, 593 patient history, 347
dynamic air bronchogram, 593 respiratory fatigue, 346
interstitial syndrome, diagnosis of, 592 respiratory infection, 346
lung consolidations, 592, 593
pressure-volume curve, 593
re-aeration score, 593 N
SAPS II, 594 Nasal high flow (NHF)
diaphragm thickness, measurement of, CPAP, 684–685
594–595 dead-space ventilation, reduction
and weaning, 595 in, 685
expiratory resistance, 684–685
hypercapnic respiratory failure, 686
M medical devices, 683
MAC. See Mechanically assisted coughing NIV, 685
(MAC) obesity hypoventilation, 686, 687
MACS CPAP System, 274 overlap syndrome, 687–688
Mallampati classification, 578, 579 pursed-lip breathing, 683–684
Malnutrition sleep-disordered breathing, 682
ALS patients, mortality in, 787 technical and medical requirements, 682
in respiratory disease tracheal gas insufflation, 685
nutritional depletion, 204–205 upper airway obstruction, effects on,
nutritional intervention, 205 684–686
oral nutrition support, 205–206 wakefulness ventilatory responses, 683
Maximal transdiaphgramatic pressures Nasal Oxygenation and Ventilation of the
(Pdimax), 325 Airway (NOVA) technique,
Mechanical insufflation-exsufflation (MI-E) 585, 587
device, 210–212 Nasal pillows
Mechanically assisted coughing (MAC) for children, 814–816
MI-E device, 210–212 NIOV™ system, 98, 99
peak cough flow, 210, 212 OSA syndrome
secretion mobilization techniques, 210 clinical evidence, 28
SMT, 212 collapse, risk of, 29
two-stage axial compressor, 210 COPD, 29
Mental distress, 727–728 CPAP therapy, 28–29
Microstream (MST), 180 patients requirement, 29
Midazolam, 624 National Association of EMS Physicians
Mitral regurgitation (MR), 601 (NAEMSP), 267
Index 885

National Heart Lung and Blood Institute NPPV, 135

Working Group on TRALI, 421 RCCTs, 135, 139
NCPAP. See Noninvasive continuous positive vs. SO2T, 133
airway pressure (NCPAP) success case, criteria to stop in, 141
Negative-pressure NIMV (npNIMV), 608, 615 Noninvasive neurally adjusted ventilatory
Negative pressure ventilation (NPV), assist (NIV-NAVA)
56–57, 329 Edi catheter, 146–148
Neuromuscular disease (NMD) Edi signal, 146, 147
chronic respiratory failure, 782–784 publications, 149–150
gene therapy, 782 respiratory reflexes, neural integration
hypercapnic respiratory failure, 861–862 with, 147, 149
muscle impairment, 782 ventilator control, 147–149
noninvasive ventilation Noninvasive open ventilation (NIOV™)
ALS patients, 786–787 therapy
AVAPS, 788 breathing apparatus, 98, 99
cough-assist techniques, 785 compressed gas source, 98
DMD patients, 785–786 COPD patients, efficiency in, 101–102
home mechanical ventilation, 787 cystic fibrosis, 102–103
hybrid ventilators, 788 ILD, 101, 102
interfaces, 788–789 lung simulator, 100–101
nocturnal hypoventilation, 784–785 microprocessor-controlled ventilator, 98
pressurimetric ventilators, 788 nasal pillows interface, 98, 99
vs. tracheostomy ventilation, 785 sensing ports, 98, 99
volume-programmed ventilation, 788 SpO2 levels, 102
rapidly progressive, 782 technical specifications, 100
telemonitoring, 804 Venturi effect, 99, 100
Neuromuscular respiratory system, 782 Noninvasive positive pressure ventilation
NHF. See Nasal high flow (NHF) (NPPV)
NIOV™ therapy. See Noninvasive open ACPE, 355, 356
ventilation (NIOV™) therapy ARDS (see Acute respiratory distress
NIV. See Noninvasive ventilation (NIV) syndrome (ARDS))
NIV-NAVA. See Noninvasive neurally adjusted ARF patients, 621–622, 624
ventilatory assist (NIV-NAVA) blunt chest trauma, 428
NMD. See Neuromuscular disease (NMD) chest wall disease, 329–330
Noninvasive continuous positive airway children, interfaces for (see Children)
pressure (NCPAP) COPD patients (see Chronic obstructive
ABG, 141 pulmonary disease (COPD))
ACPE, 134, 135 CPAP, 305–306
AHRF and FBO (see Flexible bronchoscopy
acute asthma, 136–137 (FBO))
chronic conditions, 137 hypercapnic respiratory failure, QoL scores
clinical practice, 132–133 (see Hypercapnic respiratory
criteria, 138 failure)
immunocompromised patients, 137 hypoxemic ARF
indications and contraindications, benefits, 541
138–139 in cancer patients, 542–544
success/failure, predictors for, 139, 140 complications, 544
treatment, 136 management of, 541
complications, 134, 136 RCTs, 540, 541
DNI orders, patients with, 140–141 MAC (see Mechanically assisted coughing
failure case, criteria to stop in, 142 (MAC))
high-flow generators vs. ventilators, NIOV, 103
133–134 OSA, 529–530
interface characteristics, 134, 135 PEEPi,dyn/PEEPi,stat, 289, 290
886 Index

Noninvasive positive pressure ventilation chest trauma, 634, 635

(NPPV) (cont.) community-acquired pneumonia,
pneumonia, 243 634, 635
in pre-hospital setting (see Pre-hospital contraindications, 634
NIPPV systems) COPD exacerbation, 634
psychological factors, 474 mortality reduction, 634
ALS, 475, 476 neuromuscular and neurologic
children, 477 diseases, 634
clinician influences, 475–476 percentage of, 634
older patients, 476–477 post-extubation respiratory failure, 635
sedation and analgesia, use of (see guidelines, 294
Sedation and analgesia, NPPV) hospitalized patient, utilization in
ventilators (see Ventilators) complications, 847–848
Noninvasive ventilation (NIV), 628 discontinuation, 848
acute respiratory failure (see Acute failure, 848–849
respiratory failure (ARF), NIV) location, 842–843
adaptation process (see Adaptation, NIV) mask interfaces, 844
advantages, 840 medication delivery, 847
aerosol therapy (see Aerosol therapy) patient selection, 840–843
airway clearance, 298 staff experience, 843–844
atelectasis (see Atelectasis) therapy trial, 843
blunt chest trauma (see Blunt chest trauma) ventilation, modes of, 845–846
capnography, 179–181 ventilators, 845, 846
cardiac procedures (see Cardiac interfaces, manipulation of, 127
procedures, NIV in) leakage
cardiac surgery, patients after (see Cardiac auto-triggering, 32
surgery) dedicated NIV ventilators, 34, 35
cardiopulmonary function interactions estimation and compensation, 32–33
(see Cardiopulmonary interactions) expiratory leaks, 32
cardiovascular rehabilitation (see ICU ventilator, 34, 35
Cardiovascular rehabilitation) pressure-targeted ventilation, 36, 37
chronic respiratory failure, 295 venting leaks, 32
comorbidities and age groups, 297 volume (average) assured pressure
COPD (see Chronic obstructive pulmonary support, 36, 37
disease (COPD)) volume-targeted ventilators, 36
CO2 rebreathing (see Carbon dioxide (CO2) LUS (see Lung ultrasound (LUS))
rebreathing) metabolic comorbidities and
CPAP (see Continuous positive airway obesity, 299
pressure (CPAP)) misconnections, 126–127
in difficult endotracheal intubation nasal mask, 128, 644
(see Endotracheal intubation (ETI), NIOV system (see Noninvasive open
NIV in) ventilation (NIOV™) therapy)
and ECMO (see Extracorporeal membrane in older patients
oxygenation (ECMO)) ARF, 453–454
exhalation devices (see Exhalation ports CRF, 454
and interface) ICU admissions, 452
facial oronasal comorbidities, 297 palliative use, 455
full face mask, 128, 644 pathophysiology, 452
general wards, use in ventilation, 454–455
acute asthma, 634, 635 oral mask (see Mouthpiece ventilation
acute cardiogenic pulmonary (MPV))
edema, 634 OSA (see Obstructive sleep apnea (OSA)
AHRF, 634 syndrome)
ALI/ARDS, 634, 635 oxygenation, 125–126
Index 887

PARF (see Postoperative acute respiratory gastric distension, 711

failure (PARF)) heart-lung interaction, 526
patient monitoring heated humidification, 705–706
alarms, 171 indication for, 528
arterial blood gas analysis, 170 in-laboratory titration, 707
interface device, 165, 166 ITP, 527
patient-ventilator interaction, 166–169 left ventricular performance, 526
position and comfort, 164–165 limitations, 106
pressure-flow graph interpretation, manual CPAP titration, 651
166–169 mask intolerance and claustrophobia, 710
vital signs and clinical status, 169–170 mask leakage, 710–711, 720
perioperative period, 486 nasal bridge redness/ulceration, 711
in post-extubation period (see Post- nasal congestion, dryness, and
extubation period, NIV in) rhinorrhea, 711
postoperative period, 485 nasal mask-related side effects, 28
preoperative period, 484 optimal pressure, 652, 720
pressure constancy, 127 oxygenation, 526
psychological factors, 646 patients’ characteristics and disease
REM rebound, 128 features, 705
side effects of, 646 predictive equations, 653
single-circuit ventilation system, 126 pressure relief CPAP, 706
staff training (see Staff training) psychological and social factors, 706–707
ventilators (see Ventilators) psychological symptoms after, 726–728
NPPV. See Noninvasive positive pressure recommendations, 528–529
ventilation (NPPV) respiratory arousals, 650
respiratory muscles, 525
self-reports, 707
O sleep breathing pattern, effects on, 650
Obesity hypoventilation syndrome (OHS) supportive interventions, 693, 708
AVAPS mode, 664 tracking systems, 708
BURR, 675–676 unassisted autotitration, 652–653, 707
diagnostic criteria, 319 work of breathing, 526
hypercapnic respiratory failure, 861, 862 definition, 106, 726
NIV, 82 FBO and ppNIMV, 615
patien positioning, 321 intraoperative management, 523–524
post-extubation respiratory distress, 321 mild OSA, 719
preoxygenation, 321 moderate OSA, 719
Obstructive sleep apnea (OSA) syndrome nasal pillows (see Nasal pillows)
AHI, 719 oral masks, children, 817, 818
apneas and hypopneas, 718 overnight PSG, 719
in CHF patients (see Chronic heart failure perioperative NPPV, 529–530
(CHF)) polysomnography, 321
consequences of, 726 postoperative management, 524–525
CPAP, 709–710 preoperative evaluation, 521–523
arterial blood gases, 526 RERAs, 718
autotitration, 651–652, 667, 706, 720 risk factors, 718
behavioral therapy, 693, 708–709 severe OSA, 719
bi-level turbine-driven ventilator, 528 symptoms, 718, 719
blood pressure control, 653 telemonitoring, 802–803
blower-driven devices, 57 therapeutic mechanism, 106–107
compliance, 704–705 TNI
deventilation syndrome adult patients, 107, 109–110
(see Deventilation syndrome) airway pressure, 107–108
educational interventions, 693, 708 in children, 108–109
888 Index

Obstructive sleep apnea (OSA) syndrome Percutaneous endoscopic gastrostomy

(cont.) (PEG), 342
high flow rates, 107 Pneumonia, 242–243
nasal cannula, 107 CAP (see Community-acquired pneumonia
nasopharynx, 107 (CAP))
for respiratory failure, 107 NPPV for, 243
stroke patients, 109–110 PortO2Vent Oxygen Delivery System, 274
work of breathing, 107, 108 Positive end-expiratory pressure (PEEP), 581
OHS. See Obesity hypoventilation syndrome ARDS, 242
(OHS) cardiovascular effects, 354
Oracle Fisher oral mask, 22, 23 CO2 elimination, 117, 118
Oral nutritional supplements (ONS), 205 OHS, 321
O2-RESQ™, 273 PEEPi (see Intrinsic positive end-
OSA syndrome. See Obstructive sleep apnea expiratory pressure (PEEPi))
(OSA) syndrome Positive expiratory pressure (PEP)
Overlap syndrome bronchiectasis, 308
cardiovascular outcomes, 738 mouthpiece ventilation, 25
CPAP and BiPAP therapy, 738 Positive-pressure NIMV (ppNIMV). See
auto-CPAP titration, 743 Noninvasive positive pressure
erectile dysfunction, 742 ventilation (NPPV)
exacerbations and hospitalizations, 740 Positive pressure ventilation (PPV), 9, 12, 504
exercise tolerance, 742–743 Post-extubation period, NIV in
inflammatory markers, 742 ARF
mortality rate, 740–742 curative, 515
pulmonary function tests and gas preventive, 514–515
exchange, 739–740 benefit of, 515
quality of life, 743 clinical rationale, 512
vascular dysfunction, 742 objectives, 511
daytime hypercapnia, 738 physiopathological rationale, 511–512
NHF and oxygen, effects of, 687–688 strategies for, 510
weaning/extubation, MV
definition, 510–511
P epidemiology and impact, 511
ParaVent, 645 randomized controlled trials, 512–513
PARF. See Postoperative acute respiratory Postoperative acute respiratory failure (PARF)
failure (PARF) abdominal surgery, 497
Patient-controlled analgesia (PCA), 429 cardiac surgery, 496
Patient-ventilator asynchrony (PVA) CPAP/BIPAP modes, 497–498
AECOPD, 253 thoracic surgery, 497
deventilation syndrome, 677 Prader Willi syndrome, 815
auto-PEEP, 721 Pregnancy
trigger asynchrony, 721–722 ACPE patients, 362
Patil mask. See Endoscopy mask chest wall disease, 331
PAV. See Proportional assist ventilation Pre-hospital NIPPV systems
(PAV) adequate inspiratory flow rates, 269
Peak cough flow (PCF), 210, 298, 342, 787 anti-asphyxia capabilities, 269
Peak expiratory flow rate (PEFR), 749 BiPAP, 268
Peak tracheal pressure (Ptr,max), 290–291 capnography/capnometry, 269
PEEP. See Positive end-expiratory pressure CPAP, 268
(PEEP) demand flow
PEEPi. See Intrinsic positive end-expiratory MACS CPAP System, 274
pressure (PEEPi) PortO2Vent Oxygen Delivery
Percutaneous coronary intervention (PCI), System, 274
600–601 disposable CPAP devices
Index 889

Boussignac, 271 cost and admissions, 863

Flow-Safe, 272 cystic fibrosis, 862–863
O2-RESQ, 273 mean PaCO2, 861
O-Two Single-Use CPAP device, neuromuscular disease, 861–862
272–273 OHS, 861, 862
Oxy-PEEP, 273–274 symptom scoring systems, 860–861
Rescuer Emergency, 273 long-term HMV, 732
EMS, 267 with LTOT plus NPPV, 4
fraction of inspired oxygen, 269
manometer, 268–269
medical devices, 268 R
nebulized medications, 269 Rapid eye movement (REM) sleep
oxygen consumption, 269 CPAP, 128, 651
parts/compact, 269 NMD, 783
patient interface, 268 Rapid shallow breathing index (RSBI), 460
pressure pop-off/relief, 269 Remifentanil, 624
transport ventilators, 275–276 Rescuer Emergency CPAP system, 273
Vital Signs CPAP systems, 270 Resident volume of expired air (RVEA), 117
WhisperFlow, 270, 271 Respiratory disturbance index (RDI),
Pressure control ventilation (PCV), 48, 253 73, 109, 675
Pressure support ventilation (PSV), Respiratory effort-related arousals
61, 462, 601 (RERAs), 718
expiratory cycling, 48 Respiratory failure
ICU ventilators, 124 ARF, NIV in (see Acute respiratory failure
Pressure support ventilation-volume (ARF), NIV)
guaranteed (PSV-VG), 659 chest physiotherapy techniques (see Chest
Pressure support ventilation-volume security physiotherapy techniques)
(PSV-VS), 659 CRF (see Chronic respiratory failure
Pressure support ventilation with guaranteed (CRF))
volume (PSV-VTG), 659, 661, 664 drug overdose
Pressurized metered-dose inhaler (pMDI), advantages and limitations, 397–398
195, 197 aspiration syndromes/complications,
Profile of Mood States (POMS), 727 394
Propofol, 623–625 bi-level ventilation, 394
Proportional assist ventilation (PAV), 468, characteristics, 394–396
572, 668, 845 management, 394–396
Proportional pressure ventilation (PPV), 845 opioids, 394
Protected specimen brush (PSB), 607, 613 patient outcomes, 394–396
Psychological distress, 727–728 ventilatory support method, 398
Pulmonary function tests (PFTs), 677, 733, hypercapnic respiratory failure (see
739–380 Hypercapnic respiratory failure)
Pulmonary vascular resistance (PVR) Respiratory intensive care units (RICUs)
cardiac surgery, 505 bronchoscopy and NIMV, 607
cardiopulmonary interactions, 10–11 end-of-life care decision, 871
hypoxic pulmonary vasoconstriction, 11 Respiratory therapists (RTs), 869
and lung volume, 10–11 Respironic®, 604
PVA. See Patient-ventilator asynchrony (PVA) Rhinitis, 751
Rigid bronchoscopy (RB), 608, 609, 615–616

Q
Quality of life (QoL) S
CPAP, effect of, 742–743 SBT. See Spontaneous breathing trial (SBT)
hypercapnic respiratory failure Scoliosis, 295
COPD, 863 SDB. See Sleep-disordered breathing (SDB)
890 Index

Sedation and analgesia, NPPV causes of, 564, 565

analgosedation, 623, 625 comorbid diseases, treatment of, 569
benzodiazepines, 623, 624 DNI, 569
dexmedetomidine, 623, 624 ICU, 571–572
doses of, 624 NIV success and failure, predictors
European physicians, 623 of, 567–568
guidelines, 622 patients outcome, 564–567
mask intolerance/patient agitation, pressure-limited mode, 572
622, 623 surgery, 570
midazolam, 624 volume limited mode, 572
North American physicians, 623 Spinal cord injury
patient tolerance and acceptance, 622–623 acute respiratory insufficiency, 447
propofol, 623–625 air stacking, 447
remifentanil, 624 chest wall recoil pressure, 447
scales and protocols, use of, 623 decannulation, 448
sufentanil, 624 electrophrenic nerve stimulation, 448
Sequential Organ Failure Assessment (SOFA) lung function of, 446–447
score, 550 neuromuscular disorder, 446
Servo-ventilation symptoms of, 446
algorithms, 670–671 ventilator setting, 447
central sleep apnea, 668–669 Spontaneous breathing trial (SBT),
complex sleep apnea, 670 212, 461–462
goal of, 670 Staff training, 857
outcomes, 670 in AHRF setting, 853
Severe acute respiratory syndrome (SARS), contents, 853, 854
119, 831, 837 CRF setting, 856
Severe sleep apnea hypopnea syndrome definition, 852
(SAHS), 644–645 diminished time expenditure, 855
Simplified Acute Physiology Score (SAPS) II doctor/patient and nurse/patient ratios
score, 254, 410, 417, 594 needs, 855
Skin breakdown (SB) intervenients, network of, 853, 854
classification, 200 local team expertise, 855
frequency of, 200–201 methods, 852
treatment-related risk factors, 201–200 theoretical formation, 857
Sleep-disordered breathing (SDB) Standard medical treatment (SMT), 212,
in CHF patients (see Chronic heart failure 368–369
(CHF)) Standard oxygen therapy (SO2T), 133, 355,
diagnostic criteria, 319 514, 515
NHF, 682 Sufentanil, 624
polysomnography, 321 Synchronized intermittent mandatory
symptoms of, 334 ventilation (SIMV), 69, 462
TNI, 110
upper airways, valvular function
of, 644–645 T
SMT. See Standard medical treatment TBLB. See Transbronchial lung biopsy
(SMT) (TBLB)
Society of Critical Care Medicine, 551 TEE. See Transesophageal echocardiography
Society of National Adult Cardiac Surgery (TEE)
Database Thoracic Surgeons, 506 Telemedicine
Solid malignancies, ARF in definition, 800
acute hypercapnic respiratory interactive telemedicine services, 801
failure, 569 patient care services, 800
acute hypoxic respiratory failure, 568 remote monitoring, 801
bronchoscopy, 571 store-and-forward process, 800–801
Index 891

Telemonitoring, 795 adult OSA patients, 107, 109–110

home telemonitoring, 801 airway pressure, 107–108
limitations of, 805 children with OSA, 108–109
for respiratory disorders high flow rates, 107
ALS patients, 804 nasal cannula, 107
asthma, 803–804 nasopharynx, 107
COPD and respiratory failure, 804 for respiratory failure, 107
electronic diary and spirometer stroke patients, 109–110
systems, 801 work of breathing, 107, 108
NMD, 804 Treacher Collins syndrome, 816–818
OSAS patients, CPAP adherence,
802–803
telemedicine U
definition, 800 Upper airway negative pressure (UANP), 643
interactive telemedicine services, 801 Upper airways (UA)
patient care services, 800 anatomically imposed mechanical
remote monitoring, 801 loads, 642
store-and-forward process, 800–801 AspR and ExpR, 643–645
Telephone-linked communications (TLC) cough reflex, 644–645
systems, 802–803 negative intrathoracic pressure, 642–643
Temporary positive expiratory pressure neuromuscular factors, 642
(TPEP), 308 patency/collapsibility, 643–644
Terminal dyspnea, 455 SAHS patients, 644–645
Thickening fraction (TF), 594 SDB, 644–645
Thoracic cage deformities. See Chest wall structural anatomical changes, 642
disease tracheal and nasal occlusion, 642
Three Interventions in Cardiogenic Pulmonary UANP reflex, 643
Oedema (3CPO trial), 355 valvular function, 642
Tidal volume (VT), 83–85 Usual medical care (UMC), 251, 256
TNI. See Transnasal insufflation (TNI)
Tracheostomy ventilation, 785
TRALI. See Transfusion-related acute lung V
injury (TRALI) VAPS. See Volume-assured pressure support
Transbronchial lung biopsy (TBLB), 607, (VAPS)
613–614 Ventilation/perfusion ratio (V/Q), 9–10
Transcatheter aortic valve implantation Ventilator-induced lung injury (VILI),
(TAVI), 601 240, 629
Transdiaphragmatic pressure-time product Ventilators
(PTPdi), 594 air leak compensation, 46, 49–50
Transesophageal echocardiography (TEE), alarms, 46, 50
602–604 back-up respiratory rate, 46, 49
Transfusion-associated circulatory overload battery, 46, 50
(TACO), 422 bi-level, 43, 44
Transfusion-related acute lung injury (TRALI) blower-driven micro ventilators, 57, 74
clinical presentation, 421 characteristics, 57, 75
diagnostic criteria, 421–422 choice and optimal settings, 76
management, 422 circuit, 45–47
NIV controversial issues, 53
in ARDS, 422–423 dual-mode ventilators (see Dual-mode
physiological basis for, 422 ventilators)
ventilation modes, 423 exhalation device and connecting circuits,
pathogenesis of, 420 59–60
risk factors, 420, 421 expiratory cycling, 46–48
Transnasal insufflation (TNI) history of, 124–125
892 Index

Ventilators (cont.) W
HMV (see Home mechanical ventilation Weaning
(HMV)) assessment tools
ICU ventilators (see Intensive care unit diaphragm ultrasonography, 461
(ICU) ventilators) IWI, 461
ideal ventilator, 77 RSBI, 460
inspiratory flow, 46, 48–49 classification of, 459
inspiratory trigger, 46–48 criteria for, 459, 460
intermediate ventilators, 44, 45, 74 failure, 463
monitoring systems, 46, 50–52 definitions, 458
NPV, 56–57 pathophysiology of, 459
oxygen supply, 45, 46 and lung ultrasound, 595
patient ventilator synchrony mechanical ventilation (MV)
assist-control (A/C) mode, 61–62 definitions, 510–511
assist mode, 61 epidemiology and impact, 511
control mode, 62–64 randomized controlled trials, 512–513
EPAP levels, 69 noninvasive ventilation
inspiration to expiration cycling, 66–68 acute hypoxemic respiratory failure,
inspiratory pressure level, 66 466–467
measures, 69, 70 acute-on-chronic respiratory
PEEP level, 67, 69 illness, 467
pressurization, 65–66 acute respiratory failure, 467–468
spontaneous mode, 61 AECOPD, 463, 466
triggering function, 62, 64–65 practical approach, 468, 469
ventilatory cycle, 62, 64 randomized controlled trials (RCTs),
pressure vs. volume-targeted ventilators, 463–465
72–74 in progress, 459
PTM, 71 PSV, 462
source of gases, 45, 46 SBT, 461–462
types of, 125 SIMV, 462
unintentional leaks, 57–58 WhisperFlow®, 270, 271
upper airway, variable resistance, 58 Whisper Swivel exhalation port, 118, 119
volume-controlled home ventilators, 43, 44 Work of breathing (WOB), 305
volume targeting pressure mode, 73 acute COPD exacerbations, 4, 5
VTM, 70–71 BURR, 677
Ventricular arrhythmias, 604 CPAP, 132
Ventricular interdependence (VI), 9 pulmonary diseases, 16
Vital Signs CPAP systems, 270
Volume-assured pressure support (VAPS), 43,
327, 664 Z
Volume-targeted mode (VTM), 70–71, 73 Zero end-expiratory pressure (ZEEP),
Volume-target ventilators, 43, 44 187, 288, 290