Expert Review of Respiratory Medicine

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Respiratory monitoring in Adult Intensive Care

Unit

Pongdhep Theerawit, Yuda Sutherasan, Lorenzo Ball & Paolo Pelosi

To cite this article: Pongdhep Theerawit, Yuda Sutherasan, Lorenzo Ball & Paolo Pelosi (2017):
Respiratory monitoring in Adult Intensive Care Unit, Expert Review of Respiratory Medicine, DOI:
10.1080/17476348.2017.1325324

To link to this article: http://dx.doi.org/10.1080/17476348.2017.1325324

Accepted author version posted online: 28

Apr 2017.

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Publisher: Taylor & Francis

Journal: Expert Review of Respiratory Medicine

DOI: 10.1080/17476348.2017.1325324
REVIEW

Respiratory monitoring in Adult Intensive Care Unit

Authors
1) Pongdhep Theerawit1, M.D. , [email protected]
2) Yuda Sutherasan1, M.D. , [email protected]
3) Lorenzo Ball2 M.D. , [email protected].
4) Paolo Pelosi2, Professor, M.D., FERS, [email protected]

1
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of
Medicine Ramathibodi Hospital, Mahidol University, Bangkok
2
IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics,
University of Genoa, Genoa, Italy

Corresponding author: Yuda Sutherasan, M.D.

[email protected]

Address for correspondence: Division of Pulmonary and Critical Care Medicine,

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, 270 Rama VI road,
Ratchathewi, Bangkok, Thailand ,10400 Tel: +6622011619 Fax: +6622011629 ext. 2

1
2
Abstract

Introduction: The mortality of patients with respiratory failure has steadily decreased with

the advancements in protective ventilation and treatment options. Although respiratory

monitoring per se has not been proven to affect the mortality of critically ill patients, it plays

a crucial role in patients’ care, as it helps to titrate the ventilatory support. Several new

monitoring techniques have recently been made available at the bedside. The goals of

monitoring comprise of alerting physicians to detect the change in the patients’ conditions, to

improve the understanding of pathophysiology to guide the diagnosis and provide cost-

effective clinical management.

Area covered: We performed a review of the recent scientific literature to provide an

overview of the different methods used for respiratory monitoring in adult intensive care

units, including bedside imaging techniques such as ultrasound and electrical impedance

tomography.

Expert commentary: Appropriate respiratory monitoring plays an important role in patients

with and without respiratory failure as a guiding tool for the optimization of ventilation

support, avoiding further complications and decreasing morbidity and mortality. The

physician should tailor the monitoring strategy for each individual patient and know how to

correctly interpret the data.

Keywords: respiratory monitoring, Acute Respiratory Distress Syndrome, ventilator-induced

lung injury, respiratory mechanics, mechanical ventilation

3
1. Introduction

The mortality of patients receiving mechanical ventilation is slowly but steadily

decreasing [1]. Although respiratory monitoring has not been proven to affect the mortality

per se, it plays a crucial role in patient care, both for a better risk stratification and potentially

leading to a better setting of ventilatory support.

Respiratory monitoring can be defined as the process of continuously assessing the

cardiopulmonary status of patients. The goals of monitoring comprise alerting physicians to

detect the change in the patients’ conditions and to improve the understanding of

pathophysiology to guide the diagnosis and a cost-effective clinical management.

Appropriate respiratory monitoring in the intensive care unit (ICU) is a guiding tool for

providing an appropriate management of ventilatory support, avoiding complications and

potentially reducing morbidity and mortality.

The authors performed a review of the recent scientific literature to provide an

overview of various methods for respiratory monitoring in adult ICU. Furthermore, the role

of bedside imaging techniques such as ultrasound and electrical impedance tomography is

discussed.

4
2. Gas exchange monitoring

2.1 Monitoring oxygenation

2.1.1 Partial pressure of oxygen and derived parameters

Partial pressure of oxygen (PaO2) is the standard parameter to monitor oxygenation in

patients with respiratory failure. Its target values are about 80-100 mmHg, and higher levels

of PaO2 does not result in any clinical benefit [2] and might be associated with oxygen

toxicity [3].

The PaO2 over fraction of inspired oxygen(FiO2) ratio, is the most commonly used

parameter in respiratory failure patients and correlates with the shunt fraction in Acute

Respiratory Distress Syndrome (ARDS) [4]. Currently, the Berlin definition of ARDS [5]

stratifies the severity of ARDS according to the PaO2/FiO2 ratio assessed with a positive end

expiratory pressure (PEEP) level of at least 5 cm H2O. However, the criteria for the diagnosis

of ARDS include onset of disease, chest imaging characteristics and exclusion of cardiogenic

pulmonary edema, as low PaO2/FiO2 ratios can be found in other causes of respiratory failure.

The PaO2/FiO2 ratio is aimed at standardizing the PaO2 based on the amount of administered

oxygen. However, Whiteley et al. demonstrated the PaO2/FiO2 ratio is not constant when the

FiO2 is increased in a model of inhomogeneous lungs [6]. Another study by Gowda MS. et al.

showed that the PaO2/FiO2 ratio was changed by an increase in FiO2 in ARDS patients with

shunt < 30% and the direction of change was different at low and high FiO2 [7].

The gradient between the alveolar oxygen tension (PAO2) and PaO2 (PA-aO2) is a

useful parameter for determining hypoxemia, but more complex to calculate, as the PAO2 is

affected by the FiO2, humidity, and the carbon dioxide tension inside the alveoli. The latter

parameter must be derived from the partial pressure of carbon dioxide in the blood (PaCO2)

and the respiratory quotient (RQ), namely the ratio between eliminated CO2 and consumed

O2. When approximating relative humidity to 100%, the formula is PA-aO2 = (760-47) ✕ FiO2

5
- PaCO2/RQ – PaO2. This relation is affected unpredictably by FiO2 changes in conditions of

relevant ventilation-perfusion mismatch[8]. When assessing oxygenation in room air, PA-aO2

can be approximated, at a FiO2 of 0.21 and an estimated RQ of 1, as 150 – (PaCO2 + PaO2),

easier to be calculated at the bedside.

The PaO2/PAO2 ratio is more robust to changes in FiO2 compared to the PaO2/FiO2

ratio: in a study conducted by Gilbert et al. [8] the stability of PaO2/PAO2 at increasing FiO2

was verified in subjects with healthy and injured lungs, while the , PA-aO2 increased.

Another study in mechanically ventilated patients, showed similar results, confirming the

stability of PaO2/PAO2 when increasing of FiO2 [9]. As a result, PaO2/PAO2 ratio performed

better than PaO2/FiO2 ratio and PA-aO2 gradient, both to compare oxygenation in patients

receiving different FiO2 and to monitor changes in illness evolution when changing FiO2.

However, PaO2/PAO2 is more difficult to calculate compared to PaO2/FiO2 ratio.

Another derived PaO2 parameter is the oxygen index. It is calculated as the product of

FiO2 and mean airway pressure divided by PaO2, but limited evidence is available concerning

this index in adult. Dechert et. al. demonstrated that an increased oxygen index is associated

with mortality in ARDS patients [10]. The reciprocal of oxygen index is referred to as

oxygenation factor, it was proposed by El-Khatib et. al. and is inversely correlated with the

shunt fraction in patients undergoing open-heart surgery [11].

2.1.2 Pulse oximetry

Peripheral oxygen saturation (SpO2), also referred to as pulse oximetry, is a non-

invasive method to assess oxygenation. It estimates indirectly the arterial oxygen saturation

(SaO2), measuring the light absorption at two different wavelengths, visible red and infrared,

through skin areas with a high vascular density, such as the finger, nose, ear lobe, or forehead

6
[12]. The mechanism relies on the different absorption spectra of oxygenated and de-

oxygenated hemoglobin.

SpO2 is used to estimate SaO2, but several conditions can affect the reliability of this

measurement. Among the other, common causes of unreliable SpO2 measurement in the ICU

are poor tissue perfusion, nail polish, hyperbilirubinemia, vasoconstriction, excessive motion,

anemia, carbon monoxide poisoning and dyshemoglobinemia. Septic and vasodilatory shock

can produce either falsely low or high SpO2, but in most cases this difference is rather small,

around ±3% [13, 14]. Factor influencing the accuracy of pulse oximetry include: 1) fluid

therapy; 2) peripheral tissue perfusion; 3) cardiac function; 4) type of probe and 5)

vasopressor use [15]. Patient motion can misplace the probe, especially when placed in a

finger, causing either overestimation or underestimation of SaO2 [15]. Typically, excessive

movement such as in seizures can lead to a low SpO2 measurement.

Different types of sensors influence the accuracy of SpO2. To reduce the motion error,

adhesive sensor or forehead sensor can be employed. In an hypoperfusion state worsened by

vasopressor administration in critically ill patients, SpO2 measured from forehead sensors

was reported to be more accurate than finger sensors [16]. Interestingly, a study conducted by

MacLeod DB. et al. demonstrated a significantly higher desaturation response time (DRT)

with finger sensors than with forehead sensors during hypothermic state. The authors also

observed that the DRT of finger sensors was shortened by vasodilators administration. These

findings suggest that vasoconstriction affects the accuracy of SpO2 measured with finger

sensors, therefore SpO2 should be interpreted cautiously under vasoconstriction conditions

[17].

In addition to the control of potential sources of inaccuracy of SpO2 measurement,

interpretation should be based on a deep understanding of the oxygen dissociation curve.

When the actual PaO2 ranges from 100 mmHg to 500 mmHg, as occurs in patients with

7
healthy lungs ventilated with a high FiO2, the SpO2 is constantly elevated, ideally 100%.

Therefore, monitoring SpO2, shown 100% in case of a significant reduction of PaO2, but not

below 100 mmHg, is potentially misleading physicians having less awareness to patients at

risk. Furthermore, SpO2 monitoring is unable to detect hyperoxia, as all values of PaO2 over a

certain threshold will result in an SpO2 of 100%.

The ratio of SpO2 over FiO2 must also be interpreted with caution. The relationship

between the SpO2 and the PaO2 is not linear, but has a sigmoid shape as it is linked to the

oxygen dissociation curve, comparing the SpO2/FiO2 with the PaO2/FiO2 is not

straightforward. However, in some country, where measurement of arterial blood gas is not

routinely available, the SpO2/FiO2 ratio has been proposed to screen patients for hypoxemia,

as suggested in the Kigali modification of Berlin definition of ARDS: a ratio below 315 in

conjunction with bilateral lung anomalies at the lung ultrasound has a high positive predictive

value for the diagnosis of ARDS [18].

2.1.3 Near infrared spectroscopy

Monitoring oxygenation at the tissue level is also important to characterize cellular

oxygenation especially during poor tissue perfusion state, as it occurs during sepsis or other

types of shock.

The assessment of tissue oxygenation can be performed by near-infrared spectroscopy

(NIRS). Cerebral oxygenation monitoring by NIRS is used in major surgeries such as cardiac

surgery during cardio-pulmonary bypass [19], caesarean section under spinal-epidural

anesthesia [20], or carotid endarterectomy to prevent brain injury from hypotension or

hypoperfusion. However, the agreement between cerebral oxygenation monitoring by NIRS

and invasive brain tissue oxygenation measurement is poor[21].

8
 Tissue oxygenation monitoring at thenar muscle using the occlusion technique (StO2)

is applied either in shock or respiratory failure. The occlusion test is performed inducing a

brief transient ischemia, applying a blood pressure cuff on the forearm inflated at 50 mmHg

above the systolic blood pressure for 3 minutes, then releasing the cuff allowing reperfusion.

The occlusion test provides information concerning the descending slope after occlusion,

representing local oxygen consumption, and the ascending slope, reflecting perfusion

pressure and endothelial integrity at reperfusion [22]. In septic shock, the persistence of low

ascending slope of StO2 is associated with poorer outcome [23]. A lower ascending slope of

StO2 is a negative prognostic factor in patients with ARDS, and this change can be observed

within 24 h from diagnosis [24]. A reduction of StO2 can be observed in patients failing a

spontaneous breathing trial (SBT) and its value is significantly correlated with the SaO2 [25].

The main limitations of StO2 are linked to its susceptibility to interferences from the

environment, temperature, age, obesity, tissue edema, vascular tone, including the use of

vasoactive drugs [22]. Moreover, the heterogeneity present in septic shock can make local

StO2 assessed in a single site not representative of the overall microcirculation function.

2.1.4 Mixed venous oxygen

Tissue hypoxia is caused by following mechanisms: 1) imbalance between global

oxygen delivery and oxygen consumption; 2) decrease of oxygen transport at the tissue level;

or 3) impairment of cellular oxygen uptake and utilization. Mixed venous oxygen (SvO2) is

the amount of oxygen in the systemic circulation remaining after utilization by the peripheral

organs and tissues of the body, it is measured performing a blood gas analysis on a blood

sample drawn from the distal lumen of a pulmonary artery catheter. The name “mixed” refers

to the fact that the blood sampled from the pulmonary artery contains a mixture of venous

blood coming from all the body districts, both via the superior and inferior vena cava. It is an

indicator of the balance between oxygen delivery and consumption and therefore is an

9
indicator of the degree of oxygen extraction. Figure 1 shows the relationship between the

oxygen delivery (DO2), oxygen consumption (VO2), and SvO2. The SvO2 is affected by

several parameters. If the SaO2, hemoglobin level, and PaO2 are constant, the SvO2 is

modified by the balance between DO2 and VO2. If the DO2 decreases at a constantly elevated

VO2, the SvO2 will be low, while the arterial lactates level will be increased. However, SvO2

measured from blood drawn from the pulmonary artery catheter is not routinely used at

bedside. The central venous oxygen saturation (ScvO2) from superior vena cava may be

considered as a surrogate marker of SvO2 [26]. Typically, a ScvO2 drawn from a catheter in

the internal jugular or subclavian vein overestimates SvO2.

In septic shock, despite high global oxygen delivery, impaired regional distribution of

blood flow and low cellular oxygen uptake may occur and lead to paradoxically high ScvO2

[27]. Arterial lactates must be measured frequently to determine maldistribution of regional

blood flow, as their value raises when the peripheral organs, in a state of intracellular

hypoxia, switch their metabolism to anaerobic glycolysis. For example, a high DO2, low VO2,

and high ScvO2, but with high arterial blood lactate indicate a low peripheral oxygen uptake,

despite possibly good values of PaO2 and SpO2.

In conclusion, the PaO2 is a fundamental parameter for the assessment of

oxygenation. To determine the degree of ARDS severity, the PaO2/FiO2 ratio should be used.

However, when comparing degree of hypoxemia in non-ARDS patients, the PaO2/PAO2 ratio

is more reliable than PaO2/FiO2 ratio. Indirect assessments such as SpO2, StO2, or SvO2 are

available at the bedside, but physicians should know in depth their limitations interpret

carefully their values in specific conditions.

10
2.2 Monitoring carbon dioxide

Changes of PaCO2 are caused by a modification in minute ventilation and/or dead

space ventilation. The carbon dioxide retention occurs in low minute ventilation conditions,

such as neuro-muscular diseases or from high dead space ventilation, such as chronic

obstructive airway disease (COPD) or pulmonary embolism. The correct interpretation of

PaCO2 must consider the minute ventilation. Minute ventilation is the product of patient’s

respiratory rate(RR) and exhaled tidal volume in mechanically ventilated patients. In

spontaneously breathing normal subjects at rest, minute ventilation is about 3-5 L/min,

keeping PaCO2 within a physiological range. In a healthy subject ventilated with a tidal

volume of 6-8 mL/kg of predicted body weight (PBW) with a RR of 12 breaths/min, minute

ventilation is approximately 7-9 L/min, therefore PaCO2 should be lower than normal.

Therefore, if the PaCO2 is higher than 45 mmHg with these previously mentioned ventilator

setting, if the gas exchange capability of the lung are normal, the hypercarbia must be

explained by an increase in dead space ventilation. The physiologic dead space, namely the

combination of alveolar and anatomical dead space, can be measured by analyzing PCO2

from expired gas (PECO2) and calculated from this equation [28]:

Vd PaCO − PECO
=
Vt PaCO

However, the original technique for analyzing expired CO2 requires the collection of expired

gases in a Douglas bag to calculate the Vd/Vt ratio [29]. This technique is time-consuming

and not practical at the bedside. To date, the alveolar dead space can be measured by analysis

of capnography at the bedside, as described in detail in the next section.

Another parameter derived from the partial pressure of carbon dioxide is the veno-

arterial carbon dioxide tension difference (Pv-aCO2), which is calculated from the partial

pressure of carbon dioxide in mixed venous blood (PvCO2) minus the PaCO2. A value higher

11
than 6 mmHg reflects inadequacy of venous blood flow (e.g. due to low cardiac output) in

eliminating the total CO2 produced by the peripheral tissues, which reflects microcirculation

alteration [30, 31]. It can be used for monitoring adequacy of tissue perfusion in sepsis [32,

33].

2.3 Capnography

2.3.1 Time-based capnography

Time-based capnography is a simple, non-invasive, method providing an estimation

of PaCO2 by measuring the concentration of CO2 in the exhaled gases continuously. The

clinician can infer information from the end-tidal CO2 (PetCO2) and by the shape of the CO2

waveform breath by breath during inspiration and expiration. In subjects with healthy lungs,

the PetCO2 measured from time-based capnography is about 2-5 mmHg lower than PaCO2

and changes according to the CO2 production and to the ventilation-perfusion mismatch [34].

In patients with respiratory failure, the gap between PaCO2 and PetCO2 can vary significantly

[35]. Thus, PaCO2 should not be replaced with PetCO2 in those patients, but rather used to

monitor its trend and variation. However, the gap between PaCO2 and PetCO2 can be used to

estimate the alveolar dead space fraction [36]. In a model described by Jonathan et al. a good

relationship between the dead space calculated by Vd/Vt ratio and PaCO2-PetCO2 gap was

reported [37].

Additional information can be derived from the real-time visual inspection of the

CO2-time waveform. The shape of such waveform is typically trapezoidal, with a modest

elevation of the curve during the progression of expiration. A change of this shape to a

curved “shark fin” aspect can be seen in obstructive airway disease [38, 39] or acute lung

injury [40], and partial normalization of the shape can be seen with the use of bronchodilators

in airway obstruction and with lung recruitment and PEEP in ARDS, respectively. Deflection

of the waveform during the plateau phase can be due to patient-ventilator asynchrony [41].

12
Small negative deflections suggest ineffective triggering, while a deep wave deflection

followed by sudden increase of end-tidal CO2 wave might indicate excessive spontaneous

inspiratory effort during mandatory ventilation. In addition, it can be used to identify

rebreathing (upward deflection of the baseline level), weaning failure (chaotic waveform), or

water retention in the expiratory limb (flutter waveform) [42].

2.3.2 Volumetric capnography

Volumetric capnography [43] is a method to quantify dead space by measuring partial

pressure of expired CO2 in relation to expired gas volume, obtained plotting CO2 against

expiratory lung volume. Analysis of the curve plotted between the expired fraction of CO2

against exhaled tidal volume provides an estimation of physiologic and alveolar dead space

as illustrated in figure 2.

Volumetric capnography may be used for PEEP titration [43]: in addition to the

common goal of obtaining the highest dynamic respiratory compliance and SpO2, the

improvement of the elimination of CO2 per breath and improvement dead space can be taken

into account as criteria to select the so-called “best PEEP” [44]. Siobal et al. demonstrated a

good correlation between the volumetric capnography obtained with a commercial ventilator

(Dräger XL; Dräger Medical, Telford, Pennsylvania) and a metabolic analyzer in patients

recovering from ARDS [45]. Moreover, monitoring percent alveolar dead space has a

clinical relevance because it is correlated with mortality in ARDS [43]. In addition,

volumetric capnography is an excellent tool for monitoring the efficacy of thrombolytic

therapy in patients with major pulmonary embolism [46].

In summary, measurement of PaCO2 remains the gold standard for assessment of

ventilation. Nonetheless, end-tidal CO2 monitoring is a convenient non-invasive technique,

but cannot be considered a replacement of PaCO2 measurement. Volumetric capnography is

beneficial for the assessment of physiologic dead space, and can be useful in ARDS.

13
3. Monitoring respiratory mechanics

3.1 Respiratory system compliance and resistance

Respiratory mechanics refers to the interaction between the lung and chest wall.

Within the lung, both airways and alveolar structures must be considered. The airway

opening pressure (PAO) or peak inspiratory pressure (PIP) is the pressure that overcomes total

airway resistance and elastic recoil of the total respiratory system. To assess respiratory

system mechanics during mechanical ventilation, the PAO must be split into two distinct

components: the resistive pressure (Raw) and the static or plateau pressure (Pplat), the latter

being the pressure in the airways when flow is zero. Notably, to measure these parameters

patients require neuromuscular blockade and volume-controlled ventilation: during constant

inspiratory flow, the Raw and Pplat can be measured setting an inspiratory pause, and the

Raw is represented by the difference between PAO and Pplat. High Raw from total respiratory

system could be caused by either bronchospasm or obstruction of the endotracheal tube. The

gases delivered through the airways will create different pressures according to the

inspiratory flow and inspiratory resistance. Patients with narrowing of airways, e.g., due to

retained secretion or bronchospasm, are characterized by high PIP during mechanical

inflation, and the gradient between the PIP and plateau pressure is elevated: effective

suctioning of secretions or bronchodilator drugs decrease the gradient.

The respiratory system compliance can be measured to assess the pathological

changes in lung structure due to various diseases such as ARDS, cardiogenic pulmonary

edema, and pulmonary fibrosis. Low respiratory system compliance is also caused by high

Pplat level associated with increased end-expiratory lung volume (EELV) from dynamic

hyperinflation secondary to intrinsic PEEP (PEEPi). The end-expiratory occlusion technique

can be used to measure PEEPi.

14
 Total respiratory system compliance measurement is simpler compared to the

measurement of the lung compliance as it does not require the measurement of esophageal

pressure [47]. The respiratory system compliance is calculated as the ratio of tidal volume to

the driving pressure, namely plateau pressure minus total PEEP. In pulmonary ARDS, after

recruitment maneuver (RM), a decremental PEEP test until reaching the PEEP associated

with the highest respiratory system compliance has been proposed as a method to set PEEP.

Several studies have reported that airway driving pressure equal or higher than 15 cmH2O is

strongly associated with mortality [48] and identifies a group of patients with lung stress

above 24-26 cmH2O [49].

3.2 Static Pressure-Volume curve

In ARDS, modern ventilators have the capability to perform a quasi-static automated

pressure–volume curve at slow flow, where the lower and upper inflection points can be

identified. Hysteresis is calculated as the area between the inflation and deflation limb of the

pressure-volume (PV) curve. A higher area is observed in ARDS because of the high opening

pressure. The lower inflection point (LIP) is the point of the inspiratory limb at which

alveolar recruitment begins. The upper inflection point (UIP) is associated with the presence

of alveolar strain which should be avoided during protective ventilation. The LIP was

proposed as the pressure at the intersection between the extrapolated line drawn from the

portion of the PV curve at low lung volume and from the steep portion of the PV curve [50].

In a study by Amato et al, the mechanical ventilation(MV) strategy that included setting

PEEP at 2 cmH2O above the LIP on the static PV curve was shown to be associated with

better survival [51]. In absence of circuit leaks, the volume increase due to a RM can be

measured by the integration of flow during 10 second sustained inflation at 40 cmH2O. The

additional volume needed to maintain the pressure is an estimation of the recruited lung

volume [52].

15
 PEEP levels above the LIP and plateau pressure below the UIP of the static PV curve

were recommended to minimize tidal derecruitment and tidal hyperinflation. Although

several studies investigated the PV curve-guided ventilator strategy in ARDS, there is poor

evidence regarding its efficacy to affect outcome [52, 53].

3.3 Dynamic Pressure–Time and Pressure-Volume Curve

3.3.1 Dynamic airway pressure time curve (Stress index)

During constant inspiratory flow inflation, volume controlled ventilation, the rate of

change of slope of airway pressure-time curve is related to the rate of change of intra-tidal

compliance of the respiratory system. The stress index is a numeric parameter describing this

phenomenon. A gradual decrease of slope during tidal inflation characterized by downward

concavity in the pressure-time waveform indicates a progressive increase of the respiratory

system compliance. The stress index analyzed from this curve would be below 1, namely

occurrence of tidal recruitment over time: applying additional PEEP in this case could be

helpful to obtain further alveolar recruitment. Conversely, a progressive increase of slope

(upward convexity) has a stress index above 1, representing tidal hyperinflation. Therefore,

the maximal airway pressure should be reduced. Ideally, the presence of a straight line, where

the stress index is exactly 1, should be considered an optimum ventilator setting, as illustrated

in figure 3 [54].

In lung lavage experimental models of ARDS, during a constant flow of tidal

inflation, the shapes of airway pressure-time curve correspond to tidal recruitment and

inflation assessed by computed tomography (CT) [54]. Nevertheless, in ARDS with a

decrease of chest wall compliance in which the airway pressure is not a good surrogate for

lung compliance such as in the presence of pleural effusion, abdominal hypertension or

obesity, the stress index is a misleading indicator for tidal inflation. Formenti et al. showed

that extensive tidal recruitment was present with CT findings despite the stress index value

16
being more than 1 [55]. Thus, the interpretation of stress index should be applied with caution

when the extrapulmonary environment is abnormal [56].

3.3.2 Dynamic pressure-volume curve

Dynamic PV curves has been proposed as a real-time tool for tidal volume and PEEP

titration. The percentage E2 (%E2), or distension index, is the ratio between the volume-

dependent part of the respiratory system elastance and total elastance which is strongly

correlated with the driving pressure following PEEP titration. The % E2 is derived from a

multiple linear regression analysis of airway pressure and flow that includes the nonlinear

and volume dependent parts of the PV loop. Positive values of %E2 and an upward concavity

of the dynamic inspiratory PV curve indicate tidal overdistension, and negative values and a

downward concavity of dynamic inspiratory PV curve indicate tidal recruitment [57, 58, 59]

(Figure 3). A %E2 above 30 indicates lung hyperinflation in ARDS [57, 60].

In summary, although some commercially available ventilators provide many of the

mentioned parameters, including stress index and %E2, there is few evidence about the

improvement in outcome with the monitoring of those parameters; thus, tidal volume and

PEEP setting in ARDS should be set on an individual basis according to the clinical

evaluation of the patients, and several parameters should be integrated for decision making.

3.4 Esophageal pressure monitoring

The respiratory system elastance (ERS) is the sum of the elastance of the lung (EL) and

chest wall (ECW). In some circumstances, such as the extra-pulmonary ARDS, intra-

abdominal hypertension and morbidly obese patients. Ecw is primarily increased and to reach

the same transpulmonary pressure (Ptp), thus the same tidal volume, higher pleural pressure

swings are necessary [61]. The measurement of ECW requires pleural pressure (Ppl) during

passive mechanical ventilation [62].

17
 The esophageal catheter placement can estimate Ppl, work of breathing (WOB) and

intrinsic PEEP [63]. Gastric pressure can be measured simultaneously with available double

balloon catheters, and its value approximates intra-abdominal pressure (IAP).

Esophageal pressure (Peso) is an estimation of Ppl obtained placing a balloon in the

lower third of esophagus. In deeply sedated mechanically ventilated patients, the catheter

should be progressively inserted into the stomach and positioning tested by observation of the

transient increase in the balloon pressure during abdominal compression. Then the catheter is

progressively withdrawn until the point where the cardiac beat can be detected in the

waveform, marking the transition into thorax. External chest compression can be applied after

airway occlusion. A ΔPeso/Δ airway pressure ratio ranging from 0.8 to 1.2 indicates an

accurate placement of the esophageal balloon; this usually occurs when the catheter tip is

about 35– 45 cm from the nares and the procedure is referred to as “Baydur maneuver” [62].

Nevertheless, it remains discussed whether the value of measured esophageal pressure

can effectively replace Ppl, especially in supine position, where the surrounding organs

compress the esophagus. Furthermore, the Peso reflects only the pressure at mid lung region,

while not representing the entire lung condition. In an ARDS experimental model, with high

potential for recruitment, there were good correlations between the variations of invasive

pleural pressure measurement and esophageal pressure regardless of the dependent,

nondependent, or middle lung regions [64].

Talmor et al. reported the advantage of PEEP titration guided by end-expiratory Ptp in

ARDS. Oxygenation and compliance were improved compared with the conventional

ARDSnet protocol [65]. The EPVent2 is a phase II multi-centered, RCT of mechanical

ventilation directed by Peso measurement, is investigating the impact of mechanical

ventilation targeted at maintaining a positive end-expiratory Ptp on a composite outcome of

28-day mortality and time off the ventilator in patients with moderate to severe ARDS [66].

18
 Other investigators have proposed the use of an approach based on PEEP titration to

target an elastance-derived end inspiratory Ptp of 26 cm H2O [62]. In patients with H1N1

influenza-associated ARDS referred for extracorporeal membrane oxygenation (ECMO), the

PEEP titration targeting an elastance-derived end inspiratory Ptp of less than 25 cmH2O

instead of plateau pressure of 30 cmH2O avoided the use of ECMO in half of the patients

[67].

Obesity affects respiratory mechanics, causing a restrictive pattern due to the

accumulation of adipose tissue, compromising both chest wall and lung compliance as well as

an increase in airway resistance. The lung volume is decreased in obese patients,

predominantly due to a reduction of functional residual capacity (FRC). Severely obese

patients are more likely to develop ARDS than non-obese patients. Indeed, the decrease in

respiratory system compliance in obese patients with healthy lungs results from an increase in

the chest wall elastance. The Peso measurement could help to better optimize the pressure

required for alveolar recruitment, the tidal volume and safe plateau pressure as well as the

PEEP level in obese patients [68].

In conclusion, the authors recommend monitoring of Ptp and intraabdominal pressure

during mechanical ventilation titration in moderate to severe ARDS, especially when caused

by extrapulmonary disease, in high-risk postoperative abdominal surgical patients who have

abdominal hypertension, and in obesity.

3.5 Ventilator–patient asynchrony

The resistive load caused by airflow obstruction increases WOB and is a common

cause of patient-ventilator asynchrony [69]. The PEEPi resulting from flow limitation can

lead to ineffective trigger, which can be detected by a negative deflection in the pressure-time

waveform and by a positive change of flow during expiration phase in flow-time waveform

[38, 70, 71] (figure 4). In the flow-volume loop, the expiratory limb appears truncated.

19
 Ineffective triggering can be reduced by applied PEEP [70], titrated depending on

PEEPi. However, estimating PEEPi by rapid end-expiratory airway occlusion may

underestimate the actual PEEPi due to unmeasurable pressure in alveoli connected to closed

airway [72]. On the other hand, in patients with diffuse airway narrowing, PEEP might even

worsen the lung overdistension [38].

Asynchrony from inspiratory flow mismatch occurs when the ventilator delivers

insufficient flow rate to the patient’s demand, which could be detected by the presence of

concave distortion in pressure-time waveform. Increasing inspiratory flow rate or switch to

pressured-preset mode can minimize this type of asynchrony. However, increasing flow rate

in volume assisted/controlled mode shortens the inspiratory time, which may be

inappropriate. In this case, switching to pressure-preset, such as pressure controlled

ventilation or pressure support ventilation may be helpful.

Assuming that the inspiratory time is appropriately set, pressure support ventilation

(PSV) and assisted pressure-controlled ventilation (A-PCV) should lead to similar patient-

ventilator synchrony. Asynchronies during A-PCV can often be explained by an

inappropriate inspiratory time setting. During PSV, too high support level, despite decrease

of respiratory muscle workload, can affect patient’s breathing patterns, increasing PEEPi and

interference with the neural drive causing termination asynchrony. In case of early

termination, a positive deflection wave would be observed at the beginning of the expiratory

flow-time waveform, as consequence of a too short mechanical inspired time. Meanwhile,

delayed termination, characterized by a pressure spike at end inspiration, results from too

long mechanical inspiratory time, which often occurs in obstructive airway disease patients

[38, 69].

20
 In conclusion, a precise waveform analysis is required to detect patient–ventilator

asynchrony. Focusing on the abnormalities of ventilator waveforms can be helpful to prevent

dynamic hyperinflation, trigger asynchrony and optimize PEEP levels, particularly in COPD

exacerbation.

4. End-expiratory lung volume measurement

Measuring FRC or EELV during the application of PEEP can measure lung recruitability

and PEEP-induced lung strain (tidal volume to FRC ratio). The FRC is the volume of gas in

the lung at the end of a physiologic expiration without PEEP, while the EELV is the volume

of gas during expiration in MV with PEEP. The gold standard bedside technique for the

measurement of EELV is the simplified helium dilution method, this method is complex and

requires the interruption of mechanical ventilation for a short period. Alternative methods to

measure EELV are the nitrogen wash-out/wash-in technique, [73] which has good accuracy,

and the continuous measurement of end-tidal O2 and CO2 during a sudden change of FiO2 of

0.1, which has recently been validated [74], and commercially available on some ICU

ventilators.

Strain is the ratio of changes of EELV to functional residual capacity (EELV/FRC). In

mechanically ventilated patients with normal lungs, the EELV is reduced to 66% of the

predicted sitting FRC which is probably because of a loss of muscle tension attributed to the

use of sedation [75], as well as supine positioning. In ARDS, the calculated EELV is 31-42%

of expected FRC [76]. Dellamonica et al. demonstrated that the variation of EELV correlated

with recruited volume measured by PV curves [76]. The change in EELV should be

interpreted with caution; the increase of EELV by the application of PEEP leads to increased

EELV values because of either recruitment of previous collapsed lung or hyperinflation of

previously open alveoli. EELV changes should be combined with compliance values to

21
differentiate between recruitment and overdistension. The increase of EELV and dynamic

lung compliance should be used to identify the successful recruitment [38].

An alternative measurement of strain is the driving pressure, namely the difference

between plateau pressure and total PEEP. Driving pressure represents the tidal volume/

compliance of the respiratory system ratio or, alternatively, the transpulmonary driving

pressure is the ratio between tidal volume and the compliance of the lungs. Assuming that the

compliance of the respiratory system is correlated with the EELV, the driving pressure

estimates the strain of the respiratory system or of the lung. Recent studies showed that

higher driving pressure is associated with increased mortality in ARDS [48] and during

ECMO [77] and with higher risk to develop post-operative pulmonary complications in

patients undergoing different type of surgery [78].

5. Monitoring work of breathing

5.1 Esophageal pressure derived method

The main aim of mechanical ventilation is to reduce the WOB and inspiratory effort.

However, many patients still have inspiratory effort despite mechanical ventilator support.

The inspiratory effort can create reduction of pleural pressure, which may cause high Ptp and

promotes damage to the lungs [79, 80, 81]. In addition, it can generate intra-thoracic pressure

swing, which increases the left ventricle afterload by increasing the left ventricular ejection

pressure [82], and mean arterial pressure, which may lead to hemodynamic compromise due

to decreasing of cardiac output [83]. Therefore, when assisted ventilation effectively reduce

inspiratory effort and WOB, high Ptp are less present, which may minimize ventilator

induced lung injury(VILI) and improve patient-ventilator asynchrony [81, 84]. Monitoring of

WOB, appropriate selection of ventilator modes and titration of inspiratory effort should

guide physicians to choose the optimum ventilation settings.

22
 Work is the product of force and length. Applied to the lungs, force is the pressure

generated from the respiratory muscle power that changes the dimension of alveoli to acquire

the volume of gas to the lungs. Therefore, WOB is the product of pressure created by

respiratory muscles (Pmus) and changes of lung volume [85]. During controlled mechanical

ventilation, the WOB is work that ventilator use to expand the respiratory system, which is

the result of airway pressure(Paw) multiplied by tidal volume (pressure-volume loop area)

[85]. During assisted ventilation, patients use their own respiratory muscle as well; thus, in

this circumstance, we need to know Pmus to calculate WOB during assisted ventilation

(WOBassist). Physiologically, the reduction of Ppl from inspiratory effort is generated from

the net force between Pmus and recoil pressure of chest wall (Pcw) in opposite direction.

Therefore, the relationship among these variables is shown in below expression [63]:

Pmus = Pcw − Ppl

The Pcw can be measured during passive ventilation, where the Pcw would be equal to the

Ppl, thus approximated by Peso.

During volume controlled ventilation, the Ppl changes according to Paw. Thus, the

WOB can be analyzed by the difference of the area under the Paw-time waveform during

passive and active mechanical ventilation [86]. Conversely, the changes of Ppl and Paw in

pressure mode are not correlated. Necessarily, estimation of Ppl by Peso is needed and the

WOB is the area difference in the waveform of Ppl during passive and active respiration [87].

The WOB is associated with the oxygen cost of breathing which is the difference between

the VO2 measured during assisted spontaneous breathing and the VO2 during controlled

mechanical ventilation. However, the stronger correlation is seen between oxygen

consumption and the pressure-time product (PTP) [88, 89].

23
 The PTP is independent to the inspired volume but affected by the time spent during

inspiration. In the presence of asynchrony, inspiratory effort does not always generate

inspired volume, thus the calculated WOB does not represent all the work used by the patient.

The pressure-time parameters include the PTP, pressure-time index (PTI) and tension-time

index (TTI). The PTP is the integral of Pmus and inspired time (Ti) according to the

following equation:

PTPmus = (Pcw − Peso) ∙ Ti

This measurement requires an estimation of the Pcw [90] and measurement of the Ppl by

esophageal pressure. The area between the waveform of Pcw and Ppl during Ti is the PTP

(Figure 5). The following equations are the PTI and TTI, those need the measurement of

transdiaphragmatic pressure (Pdi) and maximal transdiaphragmatic pressure (Pdimax)[91]

where Ttot is a total respiratory cycle time.

PTI = Pdi × Ti⁄Ttot

TTI = Pdi⁄Pdimax × Ti⁄Ttot

To determine the pressure generated by the diaphragm, a key muscle for inspiration,

the measurement of transdiaphragmatic pressure (Pdi) is indicated, which requires

measurement of gastric pressure and Peso [91].

5.2. Electrical activity of diaphragm

The measurement of the electrical activity of diaphragm (EAdi), is available at

bedside during neurally adjusted ventilatory assist(NAVA) or using catheter for direct

measurement [92]. Pmus is strongly related to EAdi [93]. The ratio of Pmus/EAdi index is

stable within each patient. The derivation of the Pmus/EAdi index from EAdi and airway

24
pressure during an expiratory occlusion enables a continuous estimate of patient's inspiratory

effort [94].

Regarding neuro-ventilatory coupling, triggering of mechanical ventilator by sensing

EAdi occurs by diaphragmatic excitation, which is earlier than sensing by airway pressure or

flow. It makes the assisted breath from mechanical ventilator synchronous with patients’

inspiratory effort despite the presence of intrinsic PEEP or leakage. Thus, this type of sensing

mechanical ventilation improves patients-ventilator synchronization. It reduces triggering and

cycling delay [95, 96].

Compared to the aforementioned methods to assess WOB, the EAdi is more practical

at bedside, but requires a specific ventilator with expensive single-patients disposable

catheters, which may be not available in some hospitals. Besides the measurement of EAdi,

diaphragmatic ultrasound, can be employed to assess inspiratory effort, and will be

mentioned in the next section.

6. Imaging in ICU for respiratory monitoring

Several imaging techniques have been proposed for assessing lung aeration and strain

during mechanical ventilation, especially in ARDS. Although the quantitative CT scan

analysis is the gold standard, for determining lung aeration, the degree of lung injury and the

potential for lung recruitment, the routine use and quantitative analysis of CT scans are

limited due to the harmful radiation exposure and to difficulties in transporting unstable

critically ill patients to the CT facility. In this article, the authors provide an overview of

available bedside imaging techniques that can be used in clinical practice, namely ultrasound

and electrical impedance tomography (EIT).

25
6.1 Lung ultrasound

The ultrasound waves are not able to transmit through gas-filled anatomical

structures, thus preventing direct lung visualization. In normal aeration or in hyperinflated

lungs, air generates artifacts creating the specific artifacts feature: the A-lines. On the other

hand, partial loss of aeration creates longitudinal laser-like artifacts called B-lines. Table 1

illustrates examples of ultrasound images with particular focus on patterns useful for

respiratory monitoring.

Ultrasound can visualize directly pleural effusion and consolidation, as they both can

transmit sound waves. Alveolar consolidation is characterized by the presence of dynamic air

bronchograms, while bronchopneumonia or atelectasis are characterized as either hypoechoic

tissue structures that are poorly defined and wedge-shaped or dynamic air bronchograms [97,

98] (Table 1).

The lung ultrasound (LUS) has very high diagnostic accuracy for pneumothorax.

Pneumothorax is diagnosed observing the abolition of lung sliding sign and confirmed by the

presence of the lung point sign [99]. LUS can also early diagnose ventilator associated

pneumonia (VAP) by the presence of subpleural consolidation and dynamic air bronchogram.

The combination of dynamic bronchogram or ≥ 2 areas with subpleural consolidations and a

positive finding on gram stain examination strongly increase the likelihood of VAP [100].

However, subpleural consolidation and dynamic air bronchogram can also be seen in

atelectasis.

In ARDS, LUS allows the bedside optimization of MV by determining lung

morphology and lung recruitability. The changes in LUS aeration patterns can be used for

PEEP titration in ARDS. During RM, the attenuation of atelectasis observed by LUS images

in the dependent area confirms the response of RM. Then, a step-wise decrease in PEEP can

detect the lowest level of PEEP that prevents the alveolar derecruitment, appearing as the re-

26
appearance of LUS consolidation pattern [101]. Furthermore, after applying the protective

ventilation, with low tidal volume and appropriate level of PEEP, the clinician can use

ultrasound to assess lung aeration. In ARDS, consolidated regions may variably influence to

the degree of hypoxemia depending on the hypoxic vasoconstriction and the amount of

intrapulmonary shunt: color Doppler ultrasound may be used to identify the vessels in

consolidation part corresponding to intrapulmonary shunt [100].

Bouhemad et al. have compared the LUS and PV curve method for evaluating PEEP-

induced lung recruitment. There was a strong correlation between PEEP-induced lung

recruitment measured by the P-V curve and LUS re-aeration score, particularly when

recruitment caused changes in volume greater than 600 mL [102]. In ARDS patients with

septic shock, LUS can guide fluid resuscitation, potentially avoiding fluid overload. This

impairment correlates with the amount of extravascular lung water (EVLW) [103, 104]. A

recent study proposed computer-aided quantitative LUS to assess EVLW in mechanically

ventilated patients: the authors found that quantitative LUS correlated with pulmonary

capillary wedge pressure and EVLW[105].

The LUS has some limitations, as it is operator dependent and affected by patient’s

characteristics. The thickness of subcutaneous tissue around the rib cage in obese patients, the

presence of thoracic dressings and subcutaneous emphysema make LUS-image acquisition

difficult. Furthermore, LUS cannot be used as continuous monitoring device.

6.2 Diaphragmatic ultrasound

During acute respiratory failure and mechanical ventilation, diaphragmatic ultrasound

can be used to assess the respiratory effort. The diaphragmatic thickness fraction (TFdia) is

calculated as the difference in end-inspiratory diaphragmatic thickness and end expiratory

diaphragmatic thickness divided by the end-expiratory diaphragmatic thickness [106]. The

TFdia is correlated with the PTP of the diaphragm, and is able to detect changes in diaphragm

27
activity due to variations of the pressure support level [106, 107]. Moreover, a study by

Goligher et al. suggested that too high respiratory support, causing low TFdia, may be related

to a rapid decrease of diaphragmatic thickness overtime [108].

Diaphragmatic ultrasound can predict the weaning outcome. A diaphragmatic

excursion below 10 mm during SBT is associated with weaning failure [109] (Table 1). In

another study by DiNino et al., a percentage of thickness difference ≥ 30 % was associated

with success of extubation [110]. TFdia above 36% was associated with a successful SBT.

TFdia during SBT has a good correlation with maximal inspiratory pressure and a better

performance compared to rapid shallow breathing index [110, 111].

6.3 Electrical impedance tomography (EIT)

EIT is a bedside imaging technique which allows visualization of air distribution in

the lungs. The concept of EIT relies on the detection of changes in chest impedance,

measured with a low voltage electrical current applied with electrodes around the chest of the

patient. The impedance data is then reconstructed to obtain a low-resolution single-plane

image. The EIT has been expansively studied in both experimental and clinical studies to

monitor the regional lung ventilation as well as pulmonary perfusion. In ARDS, the loss of

regional ventilation is typically located in dorsal regions, with a compensatory increase in

regional ventilation at ventral region [98]. The increasing PEEP results in an increased end

expiratory lung volume, estimated by EIT which is mainly distributed to non-dependent lung

regions [112].The PEEP can induce alveolar recruitment, reflected as volume change by EIT

and derecruitment during the decrement PEEP titration. Nevertheless, lung EIT signals are

susceptible to interferences by multiple sources including high-frequency ventilation and

invasive hemodynamic monitoring.

28
 In summary, EIT is a monitoring modality offering real time imaging of lung ventilation.

Technological improvement is warranted to translate this technique in the daily clinical

practice.

7. Extravascular lung water monitoring

Extravascular lung water is the amount of fluid collected in the lungs outside of the

pulmonary vessels and comprises alveolo-interstitial fluid, lymphatic fluid, and intracellular

water. The transpulmonary thermodilution method is the only bedside technique providing an

easy measurement of EVLW at the bedside, validated in studies against gravimetric and

thermo-dye dilution methods in experimental and clinical studies [113, 114, 115].The patient

must have a central venous catheter and a thermistor-tipped arterial catheter in a large artery,

often via femoral access. Then, the thermodilution measurement is performed injecting cold

normal saline through the central venous catheter and the decrease of blood temperature is

detected at the thermistor tip in the arterial catheter, yielding the thermodilution curve. Since

transpulmonary thermodilution passes through the right heart, pulmonary circulation and left

heart, it permits additional measurements, including global end diastolic volume,

intrathoracic blood volume, EVLW index and pulmonary vascular permeability index(PVPI).

In normal lungs, the EVLW indexed to the body weight (EVLWI) is below 10 mL/kg.

The increase of EVLW was reported as an independent predictor of mortality in ARDS,

sepsis and critically ill patients [116]. PVPI is the ratio between EVLWI and pulmonary

blood volume, reflecting the integrity of the alveolar-capillary barrier.

In the clinical practice, EVLWI and PVPI can be used as guiding tools for fluid

management in ARDS with sepsis. A PVPI of 3 can discriminate between ARDS and

hydrostatic pulmonary edema [117]. Table 2 summarizes the various methods for respiratory

monitoring in ARDS.

29
8. Summary

In conclusion, appropriate respiratory monitoring plays an important role in patients

as a guiding tool for optimization of ventilation support, avoiding further complications and

decreasing morbidity and mortality. The physicians should decide which monitoring strategy

is optimal for the individual patient and know how to correctly interpret the acquired data.

9. Expert commentary (500-1000)

In the last decade, survival among patients with respiratory failure has increased

significantly with the advancement in monitoring, protective ventilation, resuscitation, and

treatment modalities.

Monitoring should be applied differently according to patients’ severity. For instance,

monitoring oxygenation in patients with pulmonary edema, SpO2 monitoring can be enough

in most circumstances. On the other hand, in ARDS patients the clinician needs to perform

arterial blood gas analysis for appropriate mechanical ventilator setting and to monitor the

oxygenation status.

The least invasive devices and techniques should always be considered as an initial

choice, including imaging. LUS is an appropriate option to quickly assess lung aeration, and

can be used to determine lung recruitment when computed tomography is not available. Also,

it can be used to detect lung edema, when the measurement of EWLW is difficult to perform.

However, physicians need to know its limitations and accuracy, and should carefully interpret

the findings.

The accuracy of monitoring devices varies significantly, therefore physicians need to

know which type of monitoring is a gold standard for a particular condition. For example, to

determine the WOB, physicians should measure the esophageal pressure.. Analysis of

30
alveolar dead space, physicians requires collecting bag. However, new technologies, such as

EAdi or volumetric capnography may replace the old technique with good performance

compared to the gold standard, being more practical at the bedside.

In several circumstances, physicians may have to choose between different monitoring

methods. For example, titration of PEEP in ARDS can be guided by several factors. To

determine which one provides an optimum PEEP level, physicians may need to combine

different parameters, such as PaO2, Vd/Vt, static compliance, EELV, or impedance change

from EIT.

Finally, using monitoring device without an accurate interpretation can be misleading.

Physicians need to know the basic principles of each monitoring technique, understanding

potentials, pitfalls, and limitations of different monitoring techniques to interpret correctly

data obtained from devices, in order to optimize the treatment.

10. Five-year view

Lung monitoring in the future will be tailored on an individual basis. The trend of

monitoring will be focused not on a single parameter, but integrating several parameters to

optimize ventilator settings for the specific patient. Currently, some commercially available

ventilators offer semi-automated ventilation setting.

Proportional assisted ventilation plus (PAV+) measures in real-time the compliance and

resistance of the respiratory system, to estimate the WOB and automatically adjust ventilator

support to keep WOB within a target range. Likewise, NAVA measures the EAdi to adjust

ventilator settings automatically. However, both modes are not totally automated, and

physicians must choose few settings, for example, the percentage of assistance in PAV or

NAVA to start ventilation. The INTELLiVENT Adaptive supportive ventilation(ASV) has

been designed to be an automated ventilator mode. It targets to an optimum SpO2 and PetCO2

31
monitoring lung mechanics and adjusting PEEP, FiO2, inspiratory pressure, inspiratory time,

tidal volume, and mandatory respiratory rate. However, none of these methods have been

tested in large randomized trials with clinical endpoints, and further investigation is

warranted before giving definitive recommendations.

Key issues

• Patients admitted to ICU requires appropriate respiratory monitoring depending on the

clinical conditions and hospital resources.

• Consider basic monitoring equipment first, unless patients really need more

complicated devices.

• Monitoring WOB would help physicians seek the optimum MV setting to prevent

potential harmful effects.

• LUS is helpful in assessing the optimal ventilator setting in ARDS patients, and as

early diagnosis tool in various pulmonary complication such as pneumonia and

pneumothorax.

• In ARDS, Ptp and/or IAP should be monitored, in ARDS especially when caused by

extrapulmonary disease, in patients who have abdominal hypertension and in obese

patients.

• In patients with airflow obstruction, precise waveform analysis is required to detect

patient-ventilator asynchrony.

Table 1 Ultrasound patterns and corresponding conditions

Table 2 Respiratory monitoring in Acute Respiratory Distress Syndrome

32
Funding
This paper was not funded.

Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the subject matter or materials
discussed in the manuscript. This includes employment, consultancies, honoraria, stock
ownership or options, expert testimony, grants or patents received or pending, or royalties.

33
Figure legend

• Figure 1 Oxygen transport diagram showing how the oxygen is delivered to cells and

returned to the lungs.

DvO2; oxygen delivery, VO2; oxygen consumption, CvO2; venous oxygen content,

CaO2;arterial oxygen content, SvO2mixed venous oxygen saturation, SaO2;arterial

oxygen saturation, PaO2 ; partial pressure of arterial oxygen

34
 • Figure 2 The waveform derived from volumetric capnography shows the relationship

between the alveolar volume and percentage of carbon dioxide concentration. The left

dashed vertical line is draw pass the point of airway-alveolar interface. The right

dotted vertical line is placed in order to make the two gray areas equal. The distance

from x to y and from y to z represent anatomical dead space and alveolar dead space,

respectively. Therefore, the physiologic dead space is the distance from x to z. PaCO2;

Partial pressure of carbon dioxide, PetCO2; end tidal CO2

35
 • Figure 3 Percentage E2 (left panel), Stress index (Right panel)

Left panel: percentage E2 or distension index is the ratio of the compliance of the last

20% of the dynamic pressure-volume curve to the total compliance.

Right panel: Airway pressure can be described as exponential function of time

(Airway pressure=atb +c) during constant flow controlled mechanical ventilation, in

which b is the stress index.

Modified from Sutherasan Y, D'Antini D, Pelosi P. Advances in ventilator-associated

lung injury: prevention is the target. Expert review of respiratory medicine.

2014;8:233-48. Epub 2014/03/08.with permission.

36
 • Figure 4 An example of ineffective trigger and auto-PEEP in a patient with

monitored esophageal pressure during pressure support ventilation, demonstrating a

negative deflection in pressure-time waveform and positive change of flow during

expiration phase in flow-time waveform (continuous arrow). The expiratory flow fails

to return to the baseline indicating auto-PEEP(Arrowhead). Peso; esophageal

pressure, Paw; airway pressure

37
 • Figure 5 Pressure-time product that calculated by the difference of area under the

pressure-time waveform of Pcw and Ppl. The Pcw is the Peso during passive

ventilation and the Ppl is estimated by Peso during active ventilation.

Peso; esophageal pressure, Ppl; pleural pressure, Pcw ; chest wall pressure, PTPmus;

pressure-time product.

38
References

Papers of special note have been highlighted as:

** of considerable interest

* of interest

1. Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Penuelas O, Abraira V, Raymondos K,

Rios F, Nin N, Apezteguia C, Violi DA, Thille AW, Brochard L, Gonzalez M, Villagomez AJ,

Hurtado J, Davies AR, Du B, Maggiore SM, Pelosi P, Soto L, Tomicic V, D'Empaire G, Matamis D,

Abroug F, Moreno RP, Soares MA, Arabi Y, Sandi F, Jibaja M, Amin P, Koh Y, Kuiper MA, Bulow

HH, Zeggwagh AA, Anzueto A. Evolution of mortality over time in patients receiving mechanical

ventilation. American journal of respiratory and critical care medicine. 2013;188:220-30.

2. Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, Morelli A, Antonelli M,

Singer M. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in

an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA : the journal of the

American Medical Association. 2016;316:1583-9. Epub 2016/10/19.

3. Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care,

emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Annals of intensive

care. 2015;5:42.

4. Covelli HD, Nessan VJ, Tuttle WK, 3rd. Oxygen derived variables in acute respiratory

failure. Critical care medicine. 1983;11:646-9. Epub 1983/08/01.

5. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L,

Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. Jama. 2012;307:2526-33.

Epub 2012/07/17.

6. Whiteley JP, Gavaghan DJ, Hahn CE. Variation of venous admixture, SF6 shunt, PaO2, and

the PaO2/FIO2 ratio with FIO2. Br J Anaesth. 2002;88:771-8.

7. Gowda MS, Klocke RA. Variability of indices of hypoxemia in adult respiratory distress

syndrome. Critical care medicine. 1997;25:41-5. Epub 1997/01/01.

39
8. Gilbert R, Keighley JF. The arterial-alveolar oxygen tension ratio. An index of gas exchange

applicable to varying inspired oxygen concentrations. The American review of respiratory disease.

1974;109:142-5. Epub 1974/01/01.

9. Gilbert R, Auchincloss JH, Jr., Kuppinger M, Thomas MV. Stability of the arterial/alveolar

oxygen partial pressure ratio. Effects of low ventilation/perfusion regions. Critical care medicine.

1979;7:267-72. Epub 1979/06/01.

10. Dechert RE, Park PK, Bartlett RH. Evaluation of the oxygenation index in adult respiratory

failure. The journal of trauma and acute care surgery. 2014;76:469-73. Epub 2014/01/25.

11. El-Khatib MF, Jamaleddine GW. A new oxygenation index for reflecting intrapulmonary

shunting in patients undergoing open-heart surgery. Chest. 2004;125:592-6. Epub 2004/02/11.

12. Mannheimer PD. The light-tissue interaction of pulse oximetry. Anesthesia and analgesia.

2007;105:S10-7. Epub 2007/12/06.

13. Wilson BJ, Cowan HJ, Lord JA, Zuege DJ, Zygun DA. The accuracy of pulse oximetry in

emergency department patients with severe sepsis and septic shock: a retrospective cohort study.

BMC emergency medicine. 2010;10:9. Epub 2010/05/07.

14. Secker C, Spiers P. Accuracy of pulse oximetry in patients with low systemic vascular

resistance. Anaesthesia. 1997;52:127-30. Epub 1997/02/01.

15. Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic principles facilitates

appreciation of its limitations. Respiratory medicine. 2013;107:789-99. Epub 2013/03/16.

16. Nesseler N, Frenel JV, Launey Y, Morcet J, Malledant Y, Seguin P. Pulse oximetry and high-

dose vasopressors: a comparison between forehead reflectance and finger transmission sensors.

Intensive care medicine. 2012;38:1718-22. Epub 2012/08/08.

17. MacLeod DB, Cortinez LI, Keifer JC, Cameron D, Wright DR, White WD, Moretti EW,

Radulescu LR, Somma J. The desaturation response time of finger pulse oximeters during mild

hypothermia. Anaesthesia. 2005;60:65-71. Epub 2004/12/17.

18. Riviello ED, Kiviri W, Twagirumugabe T, Mueller A, Banner-Goodspeed VM, Officer L,

Novack V, Mutumwinka M, Talmor DS, Fowler RA. Hospital Incidence and Outcomes of the Acute

40
Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition. American

journal of respiratory and critical care medicine. 2016;193:52-9. Epub 2015/09/10.

19. Brady K, Joshi B, Zweifel C, Smielewski P, Czosnyka M, Easley RB, Hogue CW, Jr. Real-

time continuous monitoring of cerebral blood flow autoregulation using near-infrared spectroscopy in

patients undergoing cardiopulmonary bypass. Stroke. 2010;41:1951-6. Epub 2010/07/24.

20. Sun S, Liu NH, Huang SQ. Role of cerebral oxygenation for prediction of hypotension after

spinal anesthesia for caesarean section. Journal of clinical monitoring and computing. 2016;30:417-

21. Epub 2015/07/19.

21. Kerz T, Beyer C, Huthmann A, Kalasauskas D, Amr AN, Boor S, Welschehold S.

Continuous-wave near-infrared spectroscopy is not related to brain tissue oxygen tension. Journal of

clinical monitoring and computing. 2016;30:641-7. Epub 2015/08/21.

22. Mesquida J, Gruartmoner G, Espinal C. Skeletal muscle oxygen saturation (StO2) measured

by near-infrared spectroscopy in the critically ill patients. BioMed research international.

2013;2013:502194. Epub 2013/09/13.

23. Creteur J, Carollo T, Soldati G, Buchele G, De Backer D, Vincent JL. The prognostic value of

muscle StO2 in septic patients. Intensive care medicine. 2007;33:1549-56. Epub 2007/06/19.

24. Orbegozo Cortes D, Rahmania L, Irazabal M, Santacruz C, Fontana V, De Backer D, Creteur

J, Vincent JL. Microvascular reactivity is altered early in patients with acute respiratory distress

syndrome. Respiratory research. 2016;17:59. Epub 2016/05/18.

25. Poriazi M, Kontogiorgi M, Angelopoulos E, Vasileiadis I, Tripodaki ES, Nanou V,

Fassoulaki A, Nanas S, Routsi C. Changes in thenar muscle tissue oxygen saturation assessed by near-

infrared spectroscopy during weaning from mechanical ventilation. Minerva anestesiologica.

2014;80:666-75. Epub 2013/11/15.

26. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich

M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England

journal of medicine. 2001;345:1368-77. Epub 2002/01/17.

27. Ince C, Mik EG. Microcirculatory and mitochondrial hypoxia in sepsis, shock, and

resuscitation. J Appl Physiol (1985). 2016;120:226-35.

41
28. Klocke RA. Dead space: simplicity to complexity. J Appl Physiol (1985). 2006;100:1-2. Epub

2005/12/17.

29. Douglas CG, Haldane JS. The capacity of the air passages under varying physiological

conditions. The Journal of physiology. 1912;45:235-8. Epub 1912/10/22.

30. Lamia B, Monnet X, Teboul JL. Meaning of arterio-venous PCO2 difference in circulatory

shock. Minerva anestesiologica. 2006;72:597-604. Epub 2006/05/10.

31. Ospina-Tascon GA, Umana M, Bermudez WF, Bautista-Rincon DF, Valencia JD, Madrinan

HJ, Hernandez G, Bruhn A, Arango-Davila C, De Backer D. Can venous-to-arterial carbon dioxide

differences reflect microcirculatory alterations in patients with septic shock? Intensive care medicine.

2016;42:211-21. Epub 2015/11/19.

32. Ospina-Tascon GA, Bautista-Rincon DF, Umana M, Tafur JD, Gutierrez A, Garcia AF,

Bermudez W, Granados M, Arango-Davila C, Hernandez G. Persistently high venous-to-arterial

carbon dioxide differences during early resuscitation are associated with poor outcomes in septic

shock. Critical care (London, England). 2013;17:R294. Epub 2013/12/18.

33. Mekontso-Dessap A, Castelain V, Anguel N, Bahloul M, Schauvliege F, Richard C, Teboul

JL. Combination of venoarterial PCO2 difference with arteriovenous O2 content difference to detect

anaerobic metabolism in patients. Intensive care medicine. 2002;28:272-7. Epub 2002/03/21.

34. Siobal MS. Monitoring Exhaled Carbon Dioxide. Respiratory care. 2016;61:1397-416. Epub

2016/09/08.

35. Yousuf T, Brinton T, Murtaza G, Wozniczka D, Ahmad K, Iskandar J, Mehta R, Keshmiri H,

Hanif T. Establishing a gradient between partial pressure of arterial carbon dioxide and end-tidal

carbon dioxide in patients with acute respiratory distress syndrome. Journal of investigative medicine

: the official publication of the American Federation for Clinical Research. 2016. Epub 2016/10/16.

36. Hardman JG, Aitkenhead AR. Estimation of alveolar deadspace fraction using arterial and

end-tidal CO2: a factor analysis using a physiological simulation. Anaesthesia and intensive care.

1999;27:452-8. Epub 1999/10/16.

37. Hardman JG, Aitkenhead AR. Estimating alveolar dead space from the arterial to end-tidal

CO(2) gradient: a modeling analysis. Anesthesia and analgesia. 2003;97:1846-51. Epub 2003/11/25.

42
38. Ball L, Sutherasan Y, Pelosi P. Monitoring respiration: what the clinician needs to know. Best

practice & research Clinical anaesthesiology. 2013;27:209-23. Epub 2013/09/10.

39. Nassar BS, Schmidt GA. Capnography During Critical Illness. Chest. 2016;149:576-85. Epub

2015/10/09.

40. Tusman G, Suarez-Sipmann F, Bohm SH, Borges JB, Hedenstierna G. Capnography reflects

ventilation/perfusion distribution in a model of acute lung injury. Acta anaesthesiologica

Scandinavica. 2011;55:597-606. Epub 2011/02/24.

41. Carlon GC, Ray C, Jr., Miodownik S, Kopec I, Groeger JS. Capnography in mechanically

ventilated patients. Critical care medicine. 1988;16:550-6. Epub 1988/05/01.

42. Thompson JE, Jaffe MB. Capnographic waveforms in the mechanically ventilated patient.

Respiratory care. 2005;50:100-8; discussion 8-9. Epub 2005/01/08.

43. Verscheure S, Massion PB, Verschuren F, Damas P, Magder S. Volumetric capnography:

lessons from the past and current clinical applications. Critical care (London, England). 2016;20:184.

Epub 2016/06/24.

44. Tusman G, Groisman I, Fiolo FE, Scandurra A, Arca JM, Krumrick G, Bohm SH, Sipmann

FS. Noninvasive monitoring of lung recruitment maneuvers in morbidly obese patients: the role of

pulse oximetry and volumetric capnography. Anesthesia and analgesia. 2014;118:137-44. Epub

2013/12/21.

45. Siobal MS, Ong H, Valdes J, Tang J. Calculation of physiologic dead space: comparison of

ventilator volumetric capnography to measurements by metabolic analyzer and volumetric CO2

monitor. Respiratory care. 2013;58:1143-51. Epub 2012/12/13.

46. Murias G, Blanch L, Lucangelo U. The physiology of ventilation. Respiratory care.

2014;59:1795-807. Epub 2014/10/16.

47. Rodriguez PO, Bonelli I, Setten M, Attie S, Madorno M, Maskin LP, Valentini R.

Transpulmonary pressure and gas exchange during decremental PEEP titration in pulmonary ARDS

patients. Respiratory care. 2013;58:754-63. Epub 2012/10/12.

*48. Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE,

Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival

43
in the acute respiratory distress syndrome. The New England journal of medicine. 2015;372:747-55.

Epub 2015/02/19.

The landmark study demonstrated that the decrease in driving pressure were associated with

increased rates of survival in ARDS patients.

49. Chiumello D, Carlesso E, Brioni M, Cressoni M. Airway driving pressure and lung stress in

ARDS patients. Critical care (London, England). 2016;20:276. Epub 2016/08/23.

50. Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M. Pressure-volume curve of total

respiratory system in acute respiratory failure. Computed tomographic scan study. The American

review of respiratory disease. 1987;136:730-6. Epub 1987/09/01.

51. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla

RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-

ventilation strategy on mortality in the acute respiratory distress syndrome. The New England journal

of medicine. 1998;338:347-54. Epub 1998/02/05.

52. Demory D, Arnal JM, Wysocki M, Donati S, Granier I, Corno G, Durand-Gasselin J.

Recruitability of the lung estimated by the pressure volume curve hysteresis in ARDS patients.

Intensive care medicine. 2008;34:2019-25. Epub 2008/06/26.

53. Godet T, Constantin JM, Jaber S, Futier E. How to monitor a recruitment maneuver at the

bedside. Current opinion in critical care. 2015;21:253-8. Epub 2015/04/02.

54. Grasso S, Terragni P, Mascia L, Fanelli V, Quintel M, Herrmann P, Hedenstierna G, Slutsky

AS, Ranieri VM. Airway pressure-time curve profile (stress index) detects tidal

recruitment/hyperinflation in experimental acute lung injury. Critical care medicine. 2004;32:1018-

27. Epub 2004/04/09.

55. Formenti P, Graf J, Santos A, Gard KE, Faltesek K, Adams AB, Dries DJ, Marini JJ. Non-

pulmonary factors strongly influence the stress index. Intensive care medicine. 2011;37:594-600.

Epub 2011/02/01.

56. Chiumello D, Gattinoni L. Stress index in presence of pleural effusion: does it have any

meaning? Intensive care medicine. 2011;37:561-3. Epub 2011/02/01.

44
57. Carvalho AR, Pacheco SA, de Souza Rocha PV, Bergamini BC, Paula LF, Jandre FC,

Giannella-Neto A. Detection of tidal recruitment/overdistension in lung-healthy mechanically

ventilated patients under general anesthesia. Anesthesia and analgesia. 2013;116:677-84. Epub

2012/05/01.

58. Carvalho AR, Bergamini BC, Carvalho NS, Cagido VR, Neto AC, Jandre FC, Zin WA,

Giannella-Neto A. Volume-independent elastance: a useful parameter for open-lung positive end-

expiratory pressure adjustment. Anesthesia and analgesia. 2013;116:627-33. Epub 2012/04/03.

59. Carvalho AR, Spieth PM, Pelosi P, Vidal Melo MF, Koch T, Jandre FC, Giannella-Neto A,

de Abreu MG. Ability of dynamic airway pressure curve profile and elastance for positive end-

expiratory pressure titration. Intensive care medicine. 2008;34:2291-9. Epub 2008/10/01.

60. Bersten AD. Measurement of overinflation by multiple linear regression analysis in patients

with acute lung injury. The European respiratory journal. 1998;12:526-32. Epub 1998/10/08.

61. Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercesi P, Lissoni A. Acute respiratory distress

syndrome caused by pulmonary and extrapulmonary disease. Different syndromes? American journal

of respiratory and critical care medicine. 1998;158:3-11. Epub 1998/07/09.

**62. Mauri T, Yoshida T, Bellani G, Goligher EC, Carteaux G, Rittayamai N, Mojoli F, Chiumello

D, Piquilloud L, Grasso S, Jubran A, Laghi F, Magder S, Pesenti A, Loring S, Gattinoni L, Talmor D,

Blanch L, Amato M, Chen L, Brochard L, Mancebo J. Esophageal and transpulmonary pressure in the

clinical setting: meaning, usefulness and perspectives. Intensive care medicine. 2016;42:1360-73.

Epub 2016/06/24.

Excellence review about the application of esophageal and transpulmonary pressure in clinical

practice.

63. Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor

D, Grasso S, Chiumello D, Guerin C, Patroniti N, Ranieri VM, Gattinoni L, Nava S, Terragni PP,

Pesenti A, Tobin M, Mancebo J, Brochard L. The application of esophageal pressure measurement in

patients with respiratory failure. American journal of respiratory and critical care medicine.

2014;189:520-31. Epub 2014/01/29.

45
64. Pelosi P, Goldner M, McKibben A, Adams A, Eccher G, Caironi P, Losappio S, Gattinoni L,

Marini JJ. Recruitment and derecruitment during acute respiratory failure: an experimental study.

American journal of respiratory and critical care medicine. 2001;164:122-30. Epub 2001/07/04.

65. Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH.

Mechanical ventilation guided by esophageal pressure in acute lung injury. The New England journal

of medicine. 2008;359:2095-104. Epub 2008/11/13.

66. Fish E, Novack V, Banner-Goodspeed VM, Sarge T, Loring S, Talmor D. The Esophageal

Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of

mechanical ventilation guided by transpulmonary pressure. BMJ open. 2014;4:e006356. Epub

2014/10/08.

67. Grasso S, Terragni P, Birocco A, Urbino R, Del Sorbo L, Filippini C, Mascia L, Pesenti A,

Zangrillo A, Gattinoni L, Ranieri VM. ECMO criteria for influenza A (H1N1)-associated ARDS: role

of transpulmonary pressure. Intensive care medicine. 2012;38:395-403. Epub 2012/02/11.

**68. Sutherasan Y, D'Antini D, Pelosi P. Advances in ventilator-associated lung injury: prevention

is the target. Expert review of respiratory medicine. 2014;8:233-48. Epub 2014/03/08.

Our review of pathophysiology of VILI, the possible prevention and treatment as well as

monitoring MV to minimize VILI.

69. Jolliet P, Tassaux D. Clinical review: patient-ventilator interaction in chronic obstructive

pulmonary disease. Critical care (London, England). 2006;10:236. Epub 2006/11/14.

*70. Blanch L, Bernabe F, Lucangelo U. Measurement of air trapping, intrinsic positive end-

expiratory pressure, and dynamic hyperinflation in mechanically ventilated patients. Respiratory care.

2005;50:110-23; discussion 23-4. Epub 2005/01/08.

The excellent review : the authors describe how to monitor PEEPi and dynamic hyperinflation

in mechanical ventilated patients.

71. Laghi F, Goyal A. Auto-PEEP in respiratory failure. Minerva anestesiologica. 2012;78:201-

21. Epub 2011/10/06.

72. Peigang Y, Marini JJ. Ventilation of patients with asthma and chronic obstructive pulmonary

disease. Current opinion in critical care. 2002;8:70-6. Epub 2002/09/03.

46
73. Dellamonica J, Lerolle N, Sargentini C, Beduneau G, Di Marco F, Mercat A, Richard JC,

Diehl JL, Mancebo J, Rouby JJ, Lu Q, Bernardin G, Brochard L. Accuracy and precision of end-

expiratory lung-volume measurements by automated nitrogen washout/washin technique in patients

with acute respiratory distress syndrome. Critical care (London, England). 2011;15:R294. Epub

2011/12/15.

74. Chen L, Brochard L. Lung volume assessment in acute respiratory distress syndrome. Current

opinion in critical care. 2015;21:259-64. Epub 2015/04/02.

75. Bikker IG, van Bommel J, Reis Miranda D, Bakker J, Gommers D. End-expiratory lung

volume during mechanical ventilation: a comparison with reference values and the effect of positive

end-expiratory pressure in intensive care unit patients with different lung conditions. Critical care

(London, England). 2008;12:R145. Epub 2008/11/22.

76. Dellamonica J, Lerolle N, Sargentini C, Beduneau G, Di Marco F, Mercat A, Richard JC,

Diehl JL, Mancebo J, Rouby JJ, Lu Q, Bernardin G, Brochard L. PEEP-induced changes in lung

volume in acute respiratory distress syndrome. Two methods to estimate alveolar recruitment.

Intensive care medicine. 2011;37:1595-604. Epub 2011/08/26.

77. Serpa Neto A, Schmidt M, Azevedo LC, Bein T, Brochard L, Beutel G, Combes A, Costa EL,

Hodgson C, Lindskov C, Lubnow M, Lueck C, Michaels AJ, Paiva JA, Park M, Pesenti A, Pham T,

Quintel M, Marco Ranieri V, Ried M, Roncon-Albuquerque R, Jr., Slutsky AS, Takeda S, Terragni

PP, Vejen M, Weber-Carstens S, Welte T, Gama de Abreu M, Pelosi P, Schultz MJ. Associations

between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia

and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data

analysis : Mechanical ventilation during ECMO. Intensive care medicine. 2016;42:1672-84. Epub

2016/10/21.

*78. Neto AS, Barbas CS, Simonis FD, Artigas-Raventos A, Canet J, Determann RM, Anstey J,

Hedenstierna G, Hemmes SN, Hermans G, Hiesmayr M, Hollmann MW, Jaber S, Martin-Loeches I,

Mills GH, Pearse RM, Putensen C, Schmid W, Severgnini P, Smith R, Treschan TA, Tschernko EM,

Melo MF, Wrigge H, de Abreu MG, Pelosi P, Schultz MJ. Epidemiological characteristics, practice of

ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive

47
care units from 16 countries (PRoVENT): an international, multicentre, prospective study. The Lancet

Respiratory medicine. 2016;4:882-93. Epub 2016/11/02.

Recent large prospetive study about the epidemiological characteristics of patients at risk of ARDS

79. Yoshida T, Fujino Y, Amato MB, Kavanagh BP. Spontaneous Breathing During Mechanical

Ventilation - Risks, Mechanisms & Management. American journal of respiratory and critical care

medicine. 2016. Epub 2016/10/28.

80. Yoshida T, Roldan R, Beraldo MA, Torsani V, Gomes S, De Santis RR, Costa EL, Tucci MR,

Lima RG, Kavanagh BP, Amato MB. Spontaneous Effort During Mechanical Ventilation: Maximal

Injury With Less Positive End-Expiratory Pressure. Critical care medicine. 2016;44:e678-88. Epub

2016/03/24.

81. Saddy F, Sutherasan Y, Rocco PR, Pelosi P. Ventilator-associated lung injury during assisted

mechanical ventilation. Seminars in respiratory and critical care medicine. 2014;35:409-17. Epub

2014/08/12.

82. Virolainen J, Ventila M, Turto H, Kupari M. Effect of negative intrathoracic pressure on left

ventricular pressure dynamics and relaxation. J Appl Physiol (1985). 1995;79:455-60. Epub

1995/08/01.

83. Jubran A, Mathru M, Dries D, Tobin MJ. Continuous recordings of mixed venous oxygen

saturation during weaning from mechanical ventilation and the ramifications thereof. American

journal of respiratory and critical care medicine. 1998;158:1763-9. Epub 1998/12/16.

84. Saddy F, Oliveira GP, Garcia CS, Nardelli LM, Rzezinski AF, Ornellas DS, Morales MM,

Capelozzi VL, Pelosi P, Rocco PR. Assisted ventilation modes reduce the expression of lung

inflammatory and fibrogenic mediators in a model of mild acute lung injury. Intensive care medicine.

2010;36:1417-26. Epub 2010/03/25.

85. Robertson CH, Jr., Foster GH, Johnson RL, Jr. The relationship of respiratory failure to the

oxygen consumption of, lactate production by, and distribution of blood flow among respiratory

muscles during increasing inspiratory resistance. The Journal of clinical investigation. 1977;59:31-42.

Epub 1977/01/01.

48
86. Kreit JW, Capper MW, Eschenbacher WL. Patient work of breathing during pressure support

and volume-cycled mechanical ventilation. American journal of respiratory and critical care medicine.

1994;149:1085-91. Epub 1994/05/01.

87. Van de Graaff WB, Gordey K, Dornseif SE, Dries DJ, Kleinman BS, Kumar P, Mathru M.

Pressure support. Changes in ventilatory pattern and components of the work of breathing. Chest.

1991;100:1082-9. Epub 1991/10/01.

88. Annat GJ, Viale JP, Dereymez CP, Bouffard YM, Delafosse BX, Motin JP. Oxygen cost of

breathing and diaphragmatic pressure-time index. Measurement in patients with COPD during

weaning with pressure support ventilation. Chest. 1990;98:411-4. Epub 1990/08/01.

89. Field S, Sanci S, Grassino A. Respiratory muscle oxygen consumption estimated by the

diaphragm pressure-time index. Journal of applied physiology: respiratory, environmental and

exercise physiology. 1984;57:44-51. Epub 1984/07/01.

90. Jubran A, Van de Graaff WB, Tobin MJ. Variability of patient-ventilator interaction with

pressure support ventilation in patients with chronic obstructive pulmonary disease. American journal

of respiratory and critical care medicine. 1995;152:129-36. Epub 1995/07/01.

91. Doorduin J, van Hees HW, van der Hoeven JG, Heunks LM. Monitoring of the respiratory

muscles in the critically ill. American journal of respiratory and critical care medicine. 2013;187:20-7.

Epub 2012/10/30.

92. Goto Y, Katayama S, Shono A, Mori Y, Miyazaki Y, Sato Y, Ozaki M, Kotani T. Roles of

neurally adjusted ventilatory assist in improving gas exchange in a severe acute respiratory distress

syndrome patient after weaning from extracorporeal membrane oxygenation: a case report. Journal of

intensive care. 2016;4:26. Epub 2016/04/09.

93. Beck J, Gottfried SB, Navalesi P, Skrobik Y, Comtois N, Rossini M, Sinderby C. Electrical

activity of the diaphragm during pressure support ventilation in acute respiratory failure. American

journal of respiratory and critical care medicine. 2001;164:419-24. Epub 2001/08/14.

94. Bellani G, Mauri T, Coppadoro A, Grasselli G, Patroniti N, Spadaro S, Sala V, Foti G,

Pesenti A. Estimation of patient's inspiratory effort from the electrical activity of the diaphragm.

Critical care medicine. 2013;41:1483-91. Epub 2013/03/13.

49
95. Spahija J, de Marchie M, Albert M, Bellemare P, Delisle S, Beck J, Sinderby C. Patient-

ventilator interaction during pressure support ventilation and neurally adjusted ventilatory assist.

Critical care medicine. 2010;38:518-26. Epub 2010/01/20.

96. Schmidt M, Dres M, Raux M, Deslandes-Boutmy E, Kindler F, Mayaux J, Similowski T,

Demoule A. Neurally adjusted ventilatory assist improves patient-ventilator interaction during

postextubation prophylactic noninvasive ventilation. Critical care medicine. 2012;40:1738-44. Epub

2012/05/23.

97. Arbelot C, Ferrari F, Bouhemad B, Rouby JJ. Lung ultrasound in acute respiratory distress

syndrome and acute lung injury. Current opinion in critical care. 2008;14:70-4. Epub 2008/01/16.

98. Pesenti A, Musch G, Lichtenstein D, Mojoli F, Amato MB, Cinnella G, Gattinoni L, Quintel

M. Imaging in acute respiratory distress syndrome. Intensive care medicine. 2016;42:686-98. Epub

2016/04/02.

99. Lichtenstein DA. Lung ultrasound in the critically ill. Annals of intensive care. 2014;4:1.

Epub 2014/01/10.

100. Mongodi S, Bouhemad B, Iotti GA, Mojoli F. An ultrasonographic sign of intrapulmonary

shunt. Intensive care medicine. 2016;42:912-3. Epub 2015/12/10.

*101. Tusman G, Acosta CM, Nicola M, Esperatti M, Bohm SH, Suarez-Sipmann F. Real-time

images of tidal recruitment using lung ultrasound. Critical ultrasound journal. 2015;7:19. Epub

2015/12/15.

The authors proposed algorithm to assess recruitment maneuver by ultrasound.

102. Bouhemad B, Brisson H, Le-Guen M, Arbelot C, Lu Q, Rouby JJ. Bedside ultrasound

assessment of positive end-expiratory pressure-induced lung recruitment. American journal of

respiratory and critical care medicine. 2011;183:341-7. Epub 2010/09/21.

103. Zhao Z, Jiang L, Xi X, Jiang Q, Zhu B, Wang M, Xing J, Zhang D. Prognostic value of

extravascular lung water assessed with lung ultrasound score by chest sonography in patients with

acute respiratory distress syndrome. BMC pulmonary medicine. 2015;15:98. Epub 2015/08/25.

104. Theerawit P, Touman N, Sutherasan Y, Kiatboonsri S. Transthoracic ultrasound assessment

of B-lines for identifying the increment of extravascular lung water in shock patients requiring fluid

50
resuscitation. Indian journal of critical care medicine : peer-reviewed, official publication of Indian

Society of Critical Care Medicine. 2014;18:195-9. Epub 2014/05/30.

105. Corradi F, Brusasco C, Vezzani A, Santori G, Manca T, Ball L, Nicolini F, Gherli T,

Brusasco V. Computer-Aided Quantitative Ultrasonography for Detection of Pulmonary Edema in

Mechanically Ventilated Cardiac Surgery Patients. Chest. 2016;150:640-51. Epub 2016/05/01.

106. Vivier E, Mekontso Dessap A, Dimassi S, Vargas F, Lyazidi A, Thille AW, Brochard L.

Diaphragm ultrasonography to estimate the work of breathing during non-invasive ventilation.

Intensive care medicine. 2012;38:796-803. Epub 2012/04/06.

107. Umbrello M, Formenti P, Longhi D, Galimberti A, Piva I, Pezzi A, Mistraletti G, Marini JJ,

Iapichino G. Diaphragm ultrasound as indicator of respiratory effort in critically ill patients

undergoing assisted mechanical ventilation: a pilot clinical study. Critical care (London, England).

2015;19:161. Epub 2015/04/19.

108. Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A,

Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND.

Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort.

American journal of respiratory and critical care medicine. 2015;192:1080-8. Epub 2015/07/15.

109. Kim WY, Suh HJ, Hong SB, Koh Y, Lim CM. Diaphragm dysfunction assessed by

ultrasonography: influence on weaning from mechanical ventilation. Critical care medicine.

2011;39:2627-30. Epub 2011/06/28.

110. DiNino E, Gartman EJ, Sethi JM, McCool FD. Diaphragm ultrasound as a predictor of

successful extubation from mechanical ventilation. Thorax. 2014;69:423-7. Epub 2013/12/25.

111. Ferrari G, De Filippi G, Elia F, Panero F, Volpicelli G, Apra F. Diaphragm ultrasound as a

new index of discontinuation from mechanical ventilation. Critical ultrasound journal. 2014;6:8. Epub

2014/06/21.

112. Lowhagen K, Lundin S, Stenqvist O. Regional intratidal gas distribution in acute lung injury

and acute respiratory distress syndrome--assessed by electric impedance tomography. Minerva

anestesiologica. 2010;76:1024-35. Epub 2010/12/24.

51
113. Katzenelson R, Perel A, Berkenstadt H, Preisman S, Kogan S, Sternik L, Segal E. Accuracy

of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water.

Critical care medicine. 2004;32:1550-4. Epub 2004/07/09.

114. Kirov MY, Kuzkov VV, Kuklin VN, Waerhaug K, Bjertnaes LJ. Extravascular lung water

assessed by transpulmonary single thermodilution and postmortem gravimetry in sheep. Critical care.

2004;8:R451-8. Epub 2004/11/30.

115. Michard F, Schachtrupp A, Toens C. Factors influencing the estimation of extravascular lung

water by transpulmonary thermodilution in critically ill patients. Critical care medicine.

2005;33:1243-7. Epub 2005/06/09.

*116. Jozwiak M, Teboul JL, Monnet X. Extravascular lung water in critical care: recent advances

and clinical applications. Annals of intensive care. 2015;5:38. Epub 2015/11/08.

A review; the authors focus on the measurement of EVLW and clinical applications of EVLW

monitoring.

117. Monnet X, Anguel N, Osman D, Hamzaoui O, Richard C, Teboul JL. Assessing pulmonary

permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary

edema from ALI/ARDS. Intensive care medicine. 2007;33:448-53. Epub 2007/01/16.

52
Table 1 Ultrasound
d patterns and
a corresp onding conditions
Ultrasound Pattern Con
nditions Images

Horizonttal artifacts (A-lines) parallel

p to Normal aeraation, Hyper-
ural lines, or no more than two B-
the pleu aeration.
lines

Moderate loss off aeration, multiple Interstitial syndrome

s
distinct B-lines (comet tail sign)

Multiplee coalescent B-line at a distance of Alveolar-interstitial

3 mm or less, arrising from a visible syndrome (ground glass)
pleural line
Severe loss of aeration

Complette loss of aerration Pneumonia,, Atelectasis

Lung con
nsolidation with
w or witho out air
bronchoogram
Hyperecchoic punctifform structures

Hypoech
hoic or anech hoic structurre Pleural effussion
between
n the visceraal and parietaal pleura

Bright ddiaphragm line easily detected Useful to assess

though tthe liver window diaphragmaatic excursion
n

Three eechogenic lines

l : in which
w the Diaphragm thickness
t and
thickening fraction durin
ng
caudal line represeents the diiaphragm- inspiration
mplex, the middle line the lung-
liver com
visceral pleura com mplex, and th
he rostral
line resu
ults from a mirror
m image artifact

53
Table 2 Respiratory monitoring in Acute Respiratory Distress Syndrome
Techniques/parameters Advantages Limitations

PaO2/FiO2 and PAO2/PaO2 Estimate severity and shunt fraction in Requires arterial blood gas analysis
ARDS
SvO2 or ScvO2 Reflect the balance of oxygen delivery Requires pulmonary artery catheter or central venous line
and consumption
Static respiratory system compliance At bedside, easy to assess Requires sedation and paralysis, does not represent actual lung
compliance in patients with increased chest wall elastance
Dynamic pressure-volume curve and Detect tidal recruitment and tidal Complex, overestimates hyperinflation
pressure-time curve analysis (stress overinflation
index)
Static pressure-volume curve Advocated for the titration of PEEP Needs sedation and paralysis, unclear meaning in lungs with high
level and measurement of PEEP- heterogeneity
induced recruited volume
Esophageal pressure Estimate transpulmonary pressure Invasive, complex interpretation
Volumetric capnography and PetCO2 Estimate dead space Complex
Intra-abdominal pressure Detect intra-abodominal hypertension Invasive
End expiratory lung volume Assess lung recruitability when Complex and need sedation
combined with compliance
Extravascular lung water measured Assess severity of ARDS Invasive
with transpulmonary thermodilution Guide fluid management in ARDS
Quantitative computer tomography Precise, gold standard Radiation exposure, requires transporting critically ill patients to the
radiology facility
Electrical impedance tomography Fast, noninvasive Complex, not widely available, low resolution
Lung ultrasound Assess lung recruitability and lung Operator dependent, poor acoustic window in some situation i.e. obesity,
collapse during PEEP titration subcutaneous emphysema
Estimation of extravascular lung water
Abbreviations: PaO2, arterial partial pressure of oxygen; FiO2, Fraction of Inspired Oxygen; PEEP, positive end expiratory pressure

PetCO2, End-tidal carbon dioxide; ARDS, Acute Respiratory Distress Syndrome; SvO2, Mixed venous saturation; ScvO2 , central venous
saturation

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