Respiratory Care

Volume 00, Number 00, 2025

ª Daedalus Enterprises
DOI: 10.1089/respcare.12597
Published by Mary Ann Liebert, Inc.

CONFERENCE PROCEEDINGS

Invasive Respiratory Support in Critical Pediatric Asthma

Christopher J. L. Newth1,2,* and Patrick A. Ross2,3
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Introduction
Severity Assessment
Intubation
Strategies for MV [Mechanical Ventilation]
High-Frequency Oscillatory Ventilation
Administration of Other Inhaled Agents
and Intravenous Bronchodilators
Heliox
Nitric oxide
Mucolytics
Magnesium
b2 agonists
Theophylline
Administration of Inhalational Anesthetic Agents
ECMO
Mortality
Complications of Severe Status Asthmaticus
in Children
Summary

Abstract
In the United States and Canada, severe asthma requiring mechanical ventilation has declined over the
past decade reflecting a rise in noninvasive therapies. When aggressive noninvasive therapies fail, endo-
tracheal intubation and mechanical ventilation are lifesaving and should be planned for in advance. As
speed is important, the most experienced practitioner should intubate and rapid correction of hypercar-
bia and respiratory acidosis should be avoided. An elevated minute ventilation may cause pulmonary
hyperinflation leading to air-leak syndrome and/or hemodynamic instability. Patients with severe air
flow obstruction in asthma typically have near-normal respiratory system compliance. Therefore, an
increase in plateau pressure (Pplat) usually reflects dynamic hyperinflation. A suggested upper limit for
Pplat is 25–30 cm H2O. Intrinsic PEEP (PEEPi) is measured with an expiratory hold and is valuable in that

1
Dr. Newth is affiliated with Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital Los Angeles, Los Angeles,
California, USA.
2
Drs. Newth and Ross are affiliated with Keck School of Medicine University of Southern California, Los Angeles, California, USA.
3
Dr. Ross is affiliated with Divisions of Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital Los Angeles,
Los Angeles, California, USA.
Dr. Newth presented a version of this paper at the 61st RESPIRATORY CARE Journal Conference, Pediatric Asthma: Management Across the Continuum of Care, held June 19–21,
2024 in Tampa, Florida.

*Address correspondence to: Christopher Newth, MD, ACCM, MS #12, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA, Email:
[email protected]

1
 2 NEWTH AND ROSS

PEEP set on the ventilator can be lower than PEEPi. A reasonable ventilation strategy involving low ventilator
rates and PEEP without quick correction of blood gases should be adopted. Alternative modalities to conven-
tional mechanical ventilation are limited and unless very experienced with high-frequency oscillatory ventila-
tion, the risk likely outweighs benefit. Heliox may be beneficial but cannot be delivered by every ventilator
and this varies by manufacturer. Inhaled anesthetics are direct bronchodilators and likely beneficial but as
no conventional ICU ventilator can deliver them, close cooperation with Anesthesiology is needed.
Extracorporeal membrane oxygenation (ECMO) is a rescue therapy that is particularly useful in cases of
severe air-leak syndrome. As with mechanical ventilation, ECMO does not reverse the asthma disease process
but allows support of the patient until there is improvement with other therapies. Most children who die
experience cardiac arrest prior to hospitalization. Otherwise, most mechanically ventilated children survive to
hospital discharge but there is a suggestion of additional mortality from asthma in the following decade.
Keywords: severe asthma, antiasthmatic agents, intubation, inhalation anesthetics, mechanical ventilation,
extracorporeal life support, mortality
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Introduction therapy for delivery of inhaled b2 agonists. The ease of

There is reasonable evidence that after increasing for application of HFNC and better acceptance without sedation
decades, the incidence of severe asthma requiring inter- makes it more attractive, particularly in younger children.
vention with mechanically assisted ventilation has declined Unfortunately, HFNC does not provide airway pressure as
over the past 10 years, at least in the United States and opposed to CPAP or NIV, which are likely more effective
Canada. The decline was from approximately 10% of for aerosolized drug delivery and overcoming the elevated
patients with severe asthma requiring mechanical ventila- intrinsic PEEP (PEEPi) associated with the obstructed air-
tion during 2004–20081 to 5.3% in the 2012–2021 era.2 ways of severe asthma. This topic is reviewed in depth in
This decline in mechanical ventilation was concomitant this issue of the Journal by Miller and Rotta.5
with a marked increase in noninvasive respiratory support The presence of an air leak in the form of pneumome-
including high-flow nasal cannula (HFNC) oxygen ther- diastinum, subcutaneous emphysema, or pneumothorax is
apy, CPAP, noninvasive ventilation (NIV),2 and also not necessarily a sign of severity. In the 5-year retrospective
the application of extracorporeal membrane oxygen- chart abstraction of 261 intubated children with severe
ation (ECMO). Although lifesaving, endotracheal intu- asthma exacerbations across the 8 tertiary care PICUs of
bation and mechanical ventilation carry significant risk the Collaborative Pediatric Critical Care Research Network,
in children with asthma. This may be because of the 15 subjects (6%) had experienced pulmonary barotrauma
lack of understanding of the pathophysiology of asthma before PICU admission, including 10 with pneumomedias-
in intubated children but also through the lack of experi- tinum, 6 with subcutaneous emphysema, and 4 with pneu-
ence in providing this modality of treatment. Therefore, mothorax. Although all the latter subjects required a chest
prevention of endotracheal intubation and mechanical venti- tube be placed while invasively ventilated, the others expe-
lation has been the most important goal of in-patient ther- rienced resolution spontaneously. Pneumoperitoneum is
apy of asthma. However, when failing aggressive rare and the most difficult to manage in our experience
noninvasive therapies, there are instances when the risks with even large bore abdominal drainage tubes becoming
of respiratory failure outweigh the potential complications blocked readily by abdominal contents. Management is
of intubation and mechanical ventilation. addressed further in the ECMO section.
Again, despite aggressive use of medications and non-
Severity Assessment invasive respiratory support, there are some children
Despite sophisticated monitoring equipment and the with severe asthma who do not respond. There are lim-
close clinical observation available in the pediatric ICU ited data but anecdotally we have found that patients at a
(PICU), there are no validated PICU severity of illness high risk of failing NIV are those that require significant
scores that predict the need for escalation of therapy sedation to tolerate a mask or where the mask does not
(such as invasive ventilation, inhaled anesthetics, and fit well. In addition, there are those patients who present
ECMO) for pediatric asthma. Gorelick3 (ED) and Miller4 late and are in extremis as NIV is initiated. These types
(PICU) provide the most commonly used assessments. of patients may well require intubation for respiratory
Thus, the assessment of response, or lack thereof, to thera- failure. When reaching this stage, it is necessary to define
pies is largely clinical observation and by following serial a management plan to anticipate events needed to sup-
blood gases. Compounding the lack of a severity score, there port the patient with a severe asthma exacerbation on
has been a shift toward an overreliance on HFNC oxygen through to recovery (see Fig. 1).
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 3

Intubation Return of SBT / ERT

spontaneous Extubation
respiration

Spontaneous Breathing Mechanical Ventilation Pressure Support/PEEP Spontaneous Breathing

(Acute Respiratory Failure) or CPAP (Post-extubation)
Patient Management

▪ NIV or CPAP to decrease ▪ Limit hyperinflation: ▪ Moderate PEEP to ▪ Consider prophylactic

WOB low V and longer T offset PEEPi to reduce HFNC O2 therapy to
Conventional

▪ Continuous inhaled β2 ▪ I:E ratio of 1:3 - 1:4 effort to trigger ventilator prevent re-intubation
agonists ▪ Apply zero PEEP or ▪ Apply moderate PS in selected cases
▪ Heliox to decrease WOB PEEP only up to 80% levels and assess tidal
and lower trapped gas PEEPi volumes delivered
volume ▪ Do not normalize blood ▪ Frequent assessments
gases quickly of weaning PEEP and PS
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▪ CPAP or NIV on transport ▪ Isoflurane or sevoflurane ▪ Consider changing from ▪ Consider preventive
Other Approaches

▪ Consider Helium 70% / general anesthesia in pressure to volume CPAP or NIV to

Exploratory

Oxygen 30% to improve selected cases control modes of ventilation prevent re-intubation
the efficacy of NIV and ▪ Consider HFOV to avoid high tidal volumes in selected cases
provide better drug ▪ Consider VV ECMO in as asthma resolves
delivery selected cases (e.g. ▪ NAVA to provide
pneumoperitoneum) proportional ventilation
assistance

Fig. 1. Conventional and exploratory approaches to patient management for pediatric status asthmaticus.
SBT, Spontaneous Breathing Trial; ERT, Extubation Readiness Test.

Intubation of fentanyl and midazolam. It is our experience that this

The likely indications for intubating a child with severe combination of medication requires a longer onset time
asthma are declining or altered level of consciousness, to be effective and does not reach the depth of anesthesia
exhaustion, persistent or worsening hypoxia, particularly necessary to limit further bronchospasm. We believe that
if related to pneumothoraces, progressive hypercapnia, other induction drugs that may be better alternatives
circulatory collapse, apnea, and cardiac arrest. include ketamine and propofol. Our reasoning for the
If any of these circumstances pertain, careful preparation potential choice of these medications follows. Ketamine
for induction of anesthesia for intubation is paramount. A has sedative, analgesic, anesthetic, and bronchodilator
detailed airway assessment should be performed. Physical properties. It is associated with a lower incidence of
examination of the airway is essential and the history of hemodynamic complications when used for intubation in
any prior intubations should be reviewed. While it is critically ill children.8,9 Previously reported concerns
unusual in most pediatric asthma episodes to have sig- about ketamine contributing to hypertension and tachy-
nificant dehydration,6 if there is fluid-related hypoten- cardia or raising intracranial pressure by sympathetic
sion it should be quickly corrected before any attempted stimulation have been disproven.10 Ketamine will, how-
intubation. Many children with severe asthma will have ever, cause an increase in laryngeal secretions and lower
been on HFNC or some form of noninvasive respiratory the seizure threshold if the child has epilepsy. To address
support for hours before failure of these modalities is the increased secretions, some practitioners will pretreat
acknowledged. Subsequent intubation under these cir- with glycopyrrolates. Ketamine is a dissociative anes-
cumstances may be associated with a worse outcome.7 thetic that may be associated with dysphoria. Therefore,
There is a tendency to clinically underestimate the amount we also choose to use a dose of midazolam to reduce
of inspiratory work the patient is doing prior to the decision those adverse effects. Propofol is an equally preferred
to intubate. Thus, any prolonged periods of apnea during initial agent for its induction of anesthesia for intubation
intubation may result in severe hypoxemia and cardiac because of its rapid onset of action and ease of titration.
arrest. For these reasons, we advise that the most experi- Propofol can achieve deep sedation without paralytic
enced practitioner available perform the intubation. drugs and has mild bronchodilator effects. Propofol is
There are several drugs that might be used to induce associated with some discomfort on injection in a periph-
anesthesia for the intubation. All of these have their posi- eral IV. A greater concern is that propofol may result in
tive and negative factors. Some would recommend vasodilation and hypotension, as increased intrathoracic
choosing the induction method that is most common in pressures may decrease venous return. Assuring an
each ICU. However, in many ICUs this might be the use adequate volume status is helpful (vide supra). The use
 4 NEWTH AND ROSS

of muscle relaxation may be beneficial as it greatly If patient-ventilator asynchrony occurs despite sedation
reduces the amount of induction medication that is nec- or if the ventilator application is likely to cause barotrauma,
essary. If there is concern about returning to spontane- dynamic hyperinflation, or PEEPi, the ongoing use of
ously triggered ventilation as soon as possible, the choices muscle relaxants may be needed. There has been a recent
for muscle relaxation are the use of succinylcholine or small study in adult subjects with ARDS showing that
rocuronium followed by a reversal agent. There is less there was no difference in the risk for ICU myopathy
clinical experience with succinylcholine in pediatric prac- between the use of vecuronium and cisatracurium.16
tice compared with adults. Succinylcholine use rarely may However, for ongoing muscle relaxation, cisatracurium
result in hyperkalemia and can provoke malignant hyper- remains our preferred agent of choice because it is elimi-
thermia. Therefore, if neuromuscular blockade is deemed nated independent of renal and hepatic function by Hof-
necessary for intubation, we prefer rocuronium over mann degradation, has no active metabolites, and
vecuronium for its more rapid onset. The reversal agent, appears to have direct anti-inflammatory properties.
sugammadex, has resulted in near immediate return to With either medication, for prolonged muscle relaxation
full muscular strength in emergency situations.11
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use in the ICU, the train-of-four (a peripheral nerve stim-

A cuffed endotracheal tube (ETT) of appropriate inter- ulator) should be monitored. This is commonly used in
nal diameter ([age in years/4] + 3.5)12 and length ([height the ICU to assess neuromuscular transmission when neu-
in cm/8] + 3.5)13 for the patient should be selected. Mod- romuscular blocking agents are given to block musculo-
ern cuffed ETTs of appropriate size are safe and neces- skeletal activity. It counts the number of twitches
sary to provide markedly increased airway pressures elicited by electrodes placed along a nerve pathway. The
without leak, if necessary (vide infra). The integrity of number of twitches indicates the level of neuromuscular
the balloon should be tested beforehand, and a stylet and blockade. By assessing the depth of neuromuscular
end-tidal carbon dioxide (CO2) sensor utilized to aid blockade, peripheral nerve stimulation can ensure proper
accurate placement. As routine, suction should be checked. medication dosing and thus decrease the incidence of
Video laryngoscopy results in higher rates of first pass suc- adverse effects.
cess and shorter periods of apnea.14 If it is available and is
part of the ICU’s practice, it should be used. Strategies for MV [Mechanical Ventilation]
It is important not to underestimate the inspiratory Pediatric intensivists have slowly evolved over recent
work that the patient has been doing prior to being medi- years to lung-protective ventilation, adopting the pre-
cated for intubation. After being given induction medica- cepts of high levels of PEEP while limiting VT and hence
tions with or without a neuromuscular blocking agent, as delivering smaller driving pressures (DP = plateau pres-
soon as the patient can tolerate manual ventilation, it sure minus PEEP).17 This also has the secondary effect
should be instituted with sufficient inspiratory pressures. of limiting minute ventilation and allowing permissive
We find that peak pressures of ‡35– 40 cm H2O are nec- hypercapnia. In status asthmaticus, however, there is
essary to achieve an appropriate tidal volume (VT) in often a desire to correct respiratory acidosis and hyper-
many circumstances. Evidence of worsening hypoxemia carbia quickly by increasing minute ventilation and this
by pulse oximetry suggests that the operator is assisting may lead to extreme pulmonary hyperinflation with the
ventilation with insufficient pressure or is having a prob- attendant risks of tension pneumothorax and hemody-
lem with the technique, such as not lifting the jaw namic collapse.18 While there have been no prospective,
adequately or inadequate face mask seal. Successful intuba- randomized trials of controlled hypoventilation in chil-
tion outcomes are improved by maintaining hand ventila- dren or adults with severe asthma, it is likely that
tion with 100% oxygen until the moment of the intubation accepting hypercarbia as the cost of avoiding excessive
attempt and having the shortest apnea time possible. dynamic hyperinflation will lead to better outcomes. A
Following intubation ongoing sedation is necessary. If debate continues as to the relative virtues of pressure
propofol is used for intubation, it redistributes quickly control and volume control modes of ventilation, while
and will have a much shorter clinical half-life than rocuro- most pediatric experience continues to be with the for-
nium. Options for sedation that we have used include keta- mer.19 Conversely, most adult experience is with volume-
mine with or without lorazepam. A combination of fentanyl cycled modes of ventilation.20
and lorazepam or dexmedetomidine and lorazepam are sat- Spontaneously breathing patients with severe asthma
isfactory alternatives. The use of propofol for continuous undergo tidal ventilation near their total lung capacity.
sedation in children raises the concern of propofol infusion During mechanical ventilation, lung volumes may
syndrome. However, the use of propofol in circumstances increase further, and dynamic hyperinflation is initiated
of a severe asthma exacerbation is usually only for a day or when there is insufficient time during expiration for
two and high doses are not needed, thus mitigating the risk complete exhalation of the delivered VT resulting in an
of propofol infusion syndrom.15 increase in end-expiratory lung volume and positive
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 5

Airway obstruction
Lung Progressive dynamic hyperinflation VT
Volume
VEI

Vtrapped
Normal or ARDS lungs
FRC
Insp. Exp.
TI TE Time

Fig. 2. Dynamic hyperinflation. During conventional mechanical ventilation of normal or ARDS lungs (shown in
red), all tidal volume (VT) is exhaled with return of lung volume to functional residual capacity (FRC) before arrival
of the next VT. In airway obstruction (shown in green), slow expiratory flow causes incomplete exhalation of VT
during expiratory time (TE) and results in progressive dynamic hyperinflation. Reprinted with permission from
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Tuxen.21

end-expiratory alveolar pressure (auto PEEP or Pplat is usually the result of dynamic hyperinflation. This
PEEPi).21 The volume of gas that is trapped in the method does require an end-inspiratory hold on the
dynamically hyperinflated lungs is Vtrapped (see Fig. 2). ventilator as spontaneous breathing will often interfere
The volume of gas at end-inspiration (VEI) is the sum- with accuracy. Hence, neuromuscular paralysis, or at
mation of VT and Vtrapped (VEE). With subsequent least heavy sedation, is more commonly required. It
breaths, a progressive increase in lung volume leads to can be obtained in both pressure and volume controlled
an improvement in expiratory gas flow because of breaths.23 Although the threshold Pplat that predicts
higher elastic recoil pressure and an increase in the air- increased risk of barotrauma is not well-defined in sta-
way diameter, permitting the entire VT to be exhaled. tus asthmaticus, an acceptable upper limit of 25–30 cm H2O
This continues until a lung volume is reached where all has been suggested.24 At the same time, an end-expiratory
VT is exhaled during TE. hold can also be obtained, which will show a characteristic
There are two principal methods of monitoring the increase above ventilator-set PEEP to the PEEPi level. The
severity of flow obstruction in status asthmaticus. The first difference between Pplat and PEEPi is the driving pressure
is using a measurement of total exhaled volume during a
prolonged apnea beginning at end inspiration. Tuxen et al22
used this method where the total amount of gas exhaled
during apnea represents the volume above functional Dynamic Hyperinflation
residual capacity at end-inspiration. The volume at end- Lung Tidal Ventilation Apnea
Volume
expiration is calculated by subtracting VT from the total VT
VT
amount of gas exhaled during apnea VEI and this represents A
VTrapped VEI
FRC
the increase in lung volume caused by dynamic hyperin- PEEP
B (VEE)
flation (Vtrapped). If this volume is >20 mL/kg body FRC
Time
weight, the risk of air-leak syndrome and cardiac com- Volumetrapped = Volume at end
promise was deemed to be high (see Fig. 3). exhalation = VEE = VEI – VT
A more common method to monitor the severity of
flow obstruction is by the assessment of airway pres- Fig. 3. Measurement of trapped gas and
sures. However, peak pressure is highly dependent on dynamic hyperinflation by a prolonged apnea.
the inspiratory flow-resistive properties and therefore The amount of gas trapped (VEE) is the total vol-
does not reliably reflect the degree of hyperinflation. The ume (VEI) from peak pressure to FRC minus the
combination of markedly increased airways resistance initial VT. FRC, functional residual capacity; VT,
and use of high inspiratory flow commonly results in
tidal volume; VEI, volume (above FRC) at end
peak pressures >50 cm H2O but without increased risk of
inspiration; (VEE), trapped volume (above FRC)
barotrauma. Unlike peak pressure, plateau pressure
caused by dynamic hyperinflation. A trapped vol-
(Pplat) is not affected by inspiratory flow-resistive proper-
ume of greater than 20 mL/kg body weight is
ties and is likely a better parameter for monitoring lung
linked to barotrauma and hemodynamic instabil-
hyperinflation in status asthmaticus. Because patients
with severe air flow obstruction typically have near- ity. Reprinted with permission from Tuxen.22
normal respiratory system compliance, an increase in
 6 NEWTH AND ROSS

A PIP
Resistance
to air flow PRES
PALV (PIP – Pplat)

Pressure
PPLAT
Compliance
(Pplat - ΔΡ
PEEP) (Pplat - PEEPi)

Auto-PEEP
PEEP
(PEEPi)
0

B
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Flow

Inspiratory Expiratory
Pause Pause

Fig. 4. Schematic representation of airway pressure (A) and flow (B) during controlled mechanical
ventilation. Note that flow persists at end-expiration in severe asthma, indicating that end-expiratory
alveolar pressure exceeds circuit pressure (ie, auto-PEEP or PEEPi is present). The dotted line represents
alveolar pressure. There is a marked difference between peak pressure (PIP) and plateau pressure (Pplat),
which is because of the resistive properties of the lung. The alveoli do not see this pressure. The compli-
ance of the lung is determined by the pressure and volume changes between Pplat and PEEPi. DP is the
driving pressure. PRES - resistive pressure. Reprinted with permission from Leatherman.23

(DP), and if maintained below 15 cm H2O, it has been (pressure control). Although this strategy produces a
shown to be associated with lowering mortality in ARDS. more favorable inspiratory:expiratory (I:E) ratio, the
Ideally, the same goal should be attempted in status asthma- effect on dynamic hyperinflation in a patient whose
ticus. The decrease between peak and Pplat is a way of meas- minute ventilation already has been restricted will be
uring response to therapy (see Fig. 4). modest.27 Thus, high inspiratory flows and square wave-
Ventilator settings: In severe asthma, three key factors forms offer no significant advantage over a decelerating
determine the degree to which the volume associated waveform in patients with severe asthma whose minute
with hyperinflation will increase during mechanical ven- ventilation already has been limited.
tilation. Resistance to air flow during expiration, VT that Applied external PEEP is used often during mechani-
must be exhaled, and the time available for expiration. cal ventilation to decrease the effort required to trigger
Tuxen and Lane examined various ventilator settings in the ventilator and does not increase lung volume as long
severe asthma in adults and found that minute ventilation as applied PEEP is less than PEEPi.28 However, there is
was the most important determinant of dynamic hyperin- no clear-cut rationale for the use of external PEEP when
flation.25 They clearly demonstrated the potential risk of the patient is receiving controlled mechanical ventilation
progressively increasing minute ventilation (whether by under the influence of deep sedation or paralysis. Thus, it
rate or VT) to correct hypercapnia quickly. Available is recommended that low (£5 cm H2O) PEEP levels
data suggest that very high breathing frequencies (and should be applied in this setting.
very short expiratory times) should be avoided (see Because the ability to correct hypercapnia by manipu-
Fig. 5).18,26 lation of minute ventilation is often limited and fraught
At any given breathing frequency, shortening of with potential hazards, a reasonable approach is to
inspiratory time using a high inspiratory flow, of neces- reduce the breathing frequency below 12–14 breaths/
sity, will lengthen the expiratory time. Similarly, inspira- min, keeping an inspiratory time of 1.0–1.2 s, which
tory time will be shorter when the inspiratory waveform allows an I:E ratio between 1:3 and 1:4, PEEP £ 5 cm
is square (volume control) rather than decelerating H2O, and accepting a VT of 6–8 mL/kg. In severe cases,
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 7

Pplat Ppeak (cm H2O)

80 * P < 0.02
** P < 0.001
**
60 * *

**
40 ** **

20
3
**
**
** VT
2
VEI (L)

Vtrapped
n = 6 adults
1 VC mode
FRC PEEP VT = 1.0 L
TI constant
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0
PEEP (cm H2O) 0 5 10 15 0 5 10 15 0 5 10 15
Ventilator rate 10 16 22
(breaths/min)

Fig. 5. Detrimental effects of PEEP and ventilator rate during mechanical ventilation in severe air flow
obstruction. The effects of PEEP on lung volumes and airway pressures at each level of minute ventila-
tion (altered by ventilator rate). Ppk, peak inspiratory airway pressure; Pplat, plateau pressure; VR, ventilator
rate (breaths/min); VT, tidal volume; Vtrapped, volume of gas trapped above FRC; FRCPEEP, increasing FRC with
VR—see Figure 2. Reprinted with permission from Tuxen & Lane.25

the patient will usually be heavily sedated and under neu- the CO2 waveform will suggest a positive response to
romuscular blockade and will accept the resulting hyper- therapy. Flow-volume loops are also frequently misleading
capnia and respiratory acidosis. Under other circumstances in severe asthma in children (see Fig. 6). In most ventila-
in PICU management, such as diabetic ketoacidosis, we find tors, flows, volumes, and pressures are measured back in
that pH values down to 6.8 appear to be well-tolerated if the ventilator itself, which is separated from the patient by
being controlled and relatively short-lived. Similarly, in one tubing that is often quite compliant, especially when faced
small study, several days of supercarbia did not appear to with a severe downstream resistive force as in asthma.
have any long-term adverse effects on children.29 In general, As the patient’s condition improves with PaCO2 declin-
unless there is some compelling reason to correct underlying ing and pH climbing, heavy sedation can be lessened
respiratory acidosis quickly, such as hyperkalemia, it is and neuromuscular blockade weaned off. Irrespective of
probably reasonable to wait for air flow obstruction to whether pressure or volume control ventilation is applied
improve with pharmacotherapy and forego direct attempts during the acute phase, consideration should be given to
to correct serum pH. Most patients experience substantial using volume-targeted ventilation during weaning and
improvement in their hypercapnia during the first 12–24 h spontaneous ventilation. As airway resistance decreases
of intubation and ventilation, and the majority are ventilated and spontaneous breathing frequency increases, dynamic
for <72 h.30 If bicarbonate therapy is given, ideally it should hyperinflation can occur during this phase unless pres-
be administered by slow infusion over 15–30 min rather sures are modified quickly. At this point, PEEP can also
than by rapid bolus administration because the latter might be increased up to near the level of PEEPi to compensate
lead to an acute increase in CO2 production and a transient for its effect on effort of breathing. Expiratory holds to
fall in intracellular pH as a consequence of rapid diffusion determine PEEPi are difficult to obtain on a spontane-
of CO2 into cells. ously breathing patient but it is usually sufficient to
Observation of ventilator and end-tidal CO2 wave- increase the PEEP and observe the patient reaching a com-
forms is academically interesting and useful for teaching fortable level of inspiratory effort of breathing31,32 and set-
physiology but provides little direct help in patient man- ting their own frequency (see Fig. 7).
agement. In severe asthma, the flow waveform using the High-Frequency Oscillatory Ventilation
ventilator settings suggested (vide supra) will very infre- High-frequency oscillatory ventilation has been recom-
quently come back to zero before the onset of the next mended by some for the management of patients with
breath. However, its ability to go to zero, along with a asthma requiring ventilation. Although there have been
decrease in the upward slope of the alveolar “plateau” of some case reports about this modality in children,33,34
 8 NEWTH AND ROSS
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Fig. 6. Flow and volume measurements recorded at different sites on the ventilator circuit. Left panel:
The measurements are taken in the ventilator. The ventilator circuit tubing is distensible with pressure. The
inspiratory limb (red) shows mild overshoot, whereas the expiratory limb (yellow) is passive and shows much
more overshoot with concavity, strongly suggesting air flow obstruction. This also causes overestimation
of volumes and the tidal volume is noted to be 12.3 mL/kg body weight. Right panel: Here the measure-
ments are taken at the connection of the Y-piece to the endotracheal tube and the distensible circuit tubing is
excluded. Note the different character of the inspiratory limb (red) and the lack of any concavity to the expira-
tory limb as opposed to the appearance in the left panel. Flows and volumes obtained at the Y-piece give a
much more accurate measurement of the VT which is now shown to be only 4 mL/kg body weight.

there have been no published series or randomized con- hyperinflation. Unfortunately, the data supporting the use of
trolled studies. There are protocols (eg, Beatrix Children’s these adjunct therapies are often unclear, conflicting, or
Hospital, Groningen, Netherlands) for this modality (see absent.
Supplementary File S1—protocol provided with permis-
sion and translated by Professor M. Kneyber). Nonethe-
Heliox
less, unless very experienced, considerable caution
The lower gas density of heliox reduces frictional resist-
should be used when undertaking this modality, which
ance where the gas flow is turbulent and encourages lam-
delivers ultrashort I:E respiratory ratios to patients who
inar flow by lowering the Reynolds number. Virtually all
have moderately prolonged inspiratory times and often
our knowledge about heliox in mechanically ventilated
extremely prolonged expiratory times.
patients with asthma exacerbations is gleaned from stud-
Administration of Other Inhaled Agents ies of adult patients either with asthma or COPD, the lat-
and Intravenous Bronchodilators ter having high airway resistance to expiratory flow, as is
A great majority of ventilated patients with severe asthma found in asthma. One study reported that heliox pro-
respond to standard treatment with inhaled bronchodilators duced a rapid fall in peak airway pressure and PaCO2 of
and corticosteroids. Occasionally, patients with very ventilated subjects with asthma but the important effects
severe asthma may need to be considered for nontraditional on Pplat and PEEPi were not reported.35 Studies on sub-
approaches to reduce marked hypercapnia and extreme jects with COPD have found that a 70:30 mixture of
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 9

Tier 1: Increasing PS, Tier 2: Increasing PEEPe, Tier 3: Increasing PS,

Constant Zero PEEP Constant PS Constant PEEPc
20 28 28
PS PS PS

Alrway pressure

Alrway pressure

Alrway pressure
24 24
16 Zero PEEP PEEPe PEEPc
20 20
12 16 16
8 12 12
8 8
4
4 4
0 0 0
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5
Tier Subsection Tier Subsection Tier Subsection

800 n = 9 children 700 n = 9 children 350 n = 9 children

Pressure rate product

700 600 300

(cm H2O/min)

(cm H2O/min)

(cm H2O/min)
600
500 250
500
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400 200
400
300 150
300
200 200 100

100 100 50

0 0 0
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
PS (cm H2O) above zero PEEP PS (cm H2O) with constant PS PS (cm H2O) above compensatory
PEEPc
PEEPc = compensatory PEEP which minimized PEEPe specific to each patient
PEEPe = extrinsic (ventilator circuit) PEEP applied to minimize effect of PEEPi

Fig. 7. Application of PEEP to offset intrinsic PEEP (PEEPi) decreases patient work of breathing much
more than pressure support. Upper panels: Three tiers of algorithm. Tier 1, PEEP maintained fixed at 0,
pressure support (PS) increased from 0 to 16 cm H2O in increments of 4 cm H2O. Tier 2, PS maintained at
8 cm H2O; PEEPe raised from 0 to 16 cm H2O in increments of 4 cm H2O. Tier 3, end-expiratory pressure
maintained at patient’s PEEPc, as determined from Tier 2 measurements; pressure support increased from 0
to 16 cm H2O in increments of 4 cm H2O. Lower panels: Pressure-rate product (PRP) changes during each
tier. PRP is the measurement of change in esophageal pressure (Pes) with tidal breathing multiplied by the
breathing frequency (PRP = PES · f). PRP is a measure of the patient’s work of breathing at different levels of
support. First tier with end-expiratory pressure fixed at 0 (zero PEEP): PRP decreases as PS increases. Second
tier, PS is fixed at 8 cm H2O: PRP decreases by 59% as PEEPe increases. Third tier, PEEPc determined from
the second tier remained fixed: PRP decreased with increasing PS to its lowest value of the series. Note that
the Y-axis is expanded in this tier for symmetry. Reprinted with permission from Graham et al.31

heliox significantly reduced PEEPi and dynamic hyperin- subgroup requiring mechanical ventilation and found no
flation during mechanical ventilation.36 differences in median duration of ventilation for those
Conversely, in a small but carefully performed study with or without heliox.39 Nonetheless, if a decision is
of eight adult subjects with asthma and five adult sub- made to use heliox in the ventilated patient, prior to its
jects with COPD,37 it was concluded that large airways application, it is critical to understand the performance
(ETT, trachea, mainstem bronchi) have turbulent flow, capabilities of the ventilator to be used. Some ventilators
so heliox decreases inspiratory resistance. However, become inoperable with heliox, whereas others have soft-
smaller bronchi are many and flow slower and are more ware that allows the ventilator pneumotachograph to inter-
laminar; therefore, there is little enhancement of expira- pret exhaled VT accurately when heliox rather than a
tory flow by heliox with minor consequent reduction in nitrogen:oxygen gas mixture is used. For example, the
expiratory resistance. Thus, heliox caused no reduction
Hamilton G5 ventilator (Hamilton Medical, Bonaduz, Swit-
of the indices of dynamic hyperinflation, PEEPi, and
zerland) can deliver heliox, but its more recent cousin, the
Pplat and little reduction of PaCO2.
C6, will not.
It has become evident that the use of heliox in asthma
exacerbations has declined over the last decade irrespective
of whether patients are mechanically ventilated or not.38 Nitric oxide
A retrospective cohort study using the Virtual Pediatric Inhaled nitric oxide is a very weak bronchodilator. How-
Systems database (Los Angeles, California) assessed the ever, it was reported to be of significant benefit in one small
 10 NEWTH AND ROSS

and uncontrolled series of pediatric subjects with very not available in the United States. IV terbutaline52–54
severe asthma.40 Unfortunately, the mechanism of action (1 mg/mL) can be used as a bronchodilator but the vol-
is unknown, and further studies have not been reported. ume of drug required to achieve effective drug levels at
10 lg/kg body weight/min can lead to fluid overload in
ventilated patients if extended use over several days is
Mucolytics
required. Epinephrine IV infusion is also available as an
Unlike adult patients with severe asthma episodes, chil-
alternative, and although not a selective b2 agonist, epi-
dren rarely have problems with mucus plugging. However,
nephrine causes less increase in oxygen consumption and
there are anecdotal case reports of N-acetylcysteine41 and
minute ventilation than terbutaline55 and has the advantage
recombinant human deoxyribonuclease (rhDNase)42 being
of a short half-life if (rare) serious cardiac arrhythmias are
helpful in the removal of mucus plugs. The former has a
encountered.
known but infrequent adverse effect of worsening bron-
chospasm. In theory, N-acetylcysteine functions by break-
ing down the sulfur bonds making mucus less viscous but Theophylline
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the true method of action is unclear. RhDNase liquefies Aminophylline and theophylline were at one time the
mucus by breaking down polymerized DNA strands in primary therapy for severe asthma exacerbations. In
the airway secretions of patients, which reduces the vis- more recent times they have fallen out of favor because
cosity of mucus. Its benefit in severe childhood asthma of the higher incidence of adverse effects and their nar-
treatment is unclear as it has not been widely studied, par- row therapeutic range. However, a Cochrane database
ticularly in the PICU.43,44 review of IV aminophylline for acute severe asthma in
children over 2 years of age receiving inhaled bronchodi-
lators and glucocorticoids concluded that the drug
Magnesium
improved lung function in 6 h even though there was no
No large multi-center studies evaluating inhaled versus
overall improvement in hospital stay.56 Nonetheless, a
intravenous (IV) magnesium have been performed in the
randomized controlled trial was carefully conducted by
PICU. Schuh and co-workers, in a seven-center random-
Yung and South in 1998 utilizing an asthma severity
ized controlled trial in Canada, did not find that nebu-
score in 163 children receiving inhaled b2 agonists (and
lized magnesium reduced the need for hospitalization
including some children who received IV salbutamol as
from the emergency department in severe refractory
well) comparing IV aminophylline versus placebo.
pediatric asthma.45 In a further post hoc analysis of this
This study showed the same improvement in pulmo-
trial that allowed IV magnesium administration under
nary function in the aminophylline group. Further,
protocol for children not responding to nebulized magne-
there were five children intubated in the placebo group
sium, after adjustment for patient-level characteristics,
versus none in the aminophylline group.57 Yung and
receipt of IV magnesium therapy after initial asthma
South also noted serum drug concentrations well within
treatment in the ED was associated with subsequent hos-
the therapeutic range, albeit with a higher incidence of
pitalization only.46 Goodacre et al conducted a large
adverse effects—mainly vomiting but no other serious
randomized controlled trial in adults with severe asthma
issues. Unfortunately, there has been a dearth of subse-
and concluded that neither inhaled nor IV magnesium
quent randomized controlled trials of aminophylline.
was particularly helpful in exacerbations but inhaled was
However, the extended clinical experience with amino-
probably inferior to IV magnesium.47
phylline suggests that in the population of children
with severe asthma and respiratory failure, methylxan-
b2 agonists thines continue to play a role in those children incom-
When children are intubated, the initial preferred method pletely responsive to other bronchodilator therapies.
of administering b2 agonists remains as continuous inha-
lation through the inspiratory limb of the ventilator cir- Administration of Inhalational Anesthetic Agents
cuit. This can also be achieved by intermittent inhalations Inhalational anesthetics have potent bronchodilating proper-
using a pressurized metered-dose inhaler or by an ultra- ties and many anecdotal reports have described their use in
sonic mesh nebulizer placed in line. Sometimes, the contin- status asthmaticus.58–63 However, no clinical trials exist
uous inhalation method is insufficient to improve the comparing this therapy with other adjunct therapies. Retro-
patient’s status and IV bronchodilators can be added with spective reviews demonstrate that the initiation of these
some benefit. While the evidence available for the use of gases is consistently associated with an improvement in
IV b2 agonist therapy in critical asthma continues to be of blood gases within a few hours of administration.
low quality and quantity, isoproterenol48 and albuterol (sal- Isoflurane and sevoflurane have equal bronchodilator
butamol)49–51 have both been judged as effective in small potency. Inhaled anesthetics can cause hypotension sec-
studies. Isoproterenol is expensive and IV salbutamol is ondary to peripheral vascular effect, which may be
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 11

exacerbated if the patient has dynamic hyperinflation and Looking to the future, there is the potential for use of
poor venous return. Generally, liberal administration of inhaled anesthesia with dual-limb critical care ventila-
fluid will reverse these effects. Malignant hyperthermia tors. One device that is available in Europe, Canada,
is a rare but potentially fatal complication of inhaled and many other countries (and in the USA for research
gases of this nature. purposes) is the SedaConDa Anesthetic Conserving
Unfortunately, it appears that there is no currently Device (ACD, Sedana Medical, Sweden). This device
produced intensive care ventilator that has a low- is typically positioned between the patient’s ETT and
pressure port to which an anesthesia vaporizer can be the Y-piece of the ventilator circuit. Sevoflurane or iso-
attached. Furthermore, none have internal scavenging flurane can be continually injected in the liquid form into
systems for anesthetic gases. Prior versions of anesthe- the ACD and there is a reflective filter that prevents the
sia workstations used in the operating room were not anesthetic vapor that results from being flushed out of the
able to deliver the high airway pressures and flow of circuit. This reflective filter also traps moisture and
gases needed for severe obstructed airways disease. humidifies the circuit. The drawback of the typical posi-
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Newer commercially available anesthesia workstations tioning of the ACD is that it will greatly increase the
are improving in their ability to ventilate patients in mechanical dead space of the patient’s breathing circuit.
general and potentially those with obstructed airways The version for pediatric patients (ACD-S) requires a VT
disease. Successful use of inhaled anesthesia in most of >200 mL, which limits its use potentially to patients
cases will require expert advice from and close cooper- weighing 25–30 kg. There is an alternative placement of
ation with Anesthesiology colleagues. The time to cre- the ACD-S on the inspiratory limb of the ventilator. This
ate policies and workflow maps to quickly transition to position permits use in infants and children with VT
inhaled anesthesia is before any patient may need this between 30 and 200 mL. Unfortunately, the ACD then
degree of support. Inhaled anesthesia for severe asthma no longer recycles the volatile agent exhaled by the
has the potential to prevent patients from requiring patient and does not provide effective humidification.
ECMO. Inhaled anesthesia is likely associated with Nonetheless, when paired with commercially available
lower risks than ECMO and its use does not preclude charcoal-based scavenging cannisters on the expiratory
the initiation of ECMO if the clinical situation contin- ventilator limb, it is reported to function very effec-
ues to deteriorate. Again, it will take time to identify an tively64 (see Fig. 8).
Anesthesiology colleague who can support an ICU
patient, moving an anesthesia workstation, and prepar- ECMO
ing ICU nursing staff and respiratory therapists. Having Invasive mechanical ventilation in a patient with severe
a policy to accomplish this therapy in the ICU will limit asthma can be challenging. Despite understanding the
all these delays and in the first instance should be far physiological barriers and using careful ventilation strat-
quicker than instituting ECMO. egies, gas trapping with dynamic hyperinflation can lead

1
7

6 5 1. Syringe pump with

isoflurane syringe
2. ACD-S
8 3. Humidifier (with water,
4 set to invasive mode)
4. Inspiratory ventilator
circuit limb
10 2 5. Test lung
6. Expiratory circuit limb
7. Ventilator
9 3 8. Ventilator exhaust
outlet with scavenge
37.1
tubing
9. Deltasorb canister
10. Suction

Fig. 8. A representation of the ventilator configuration with the SedaConDa ACD-S. The ACD-S is on
the inspiratory limb, with active humidity and test lung. Arrows indicate the direction of gas flow
through the system. The gas absorbing canister is attached to the expiratory outlet of the ventilator with
low standard wall suction actively scavenging. Reprinted with permission from Reise et al.64
 12 NEWTH AND ROSS

to high risks of hemodynamic instability and barotrauma. survived to hospital discharge. Most of the children who
As mentioned earlier, unless there has been prudent prior died experienced cardiac arrest before admission.30
planning, it is often easier and quicker for the PICU team The data from the Extracorporeal Life Support Orga-
to arrange ECMO than inhalational anesthesia for con- nization (ELSO) registry for the years 2013–2023 include
tinuing management. Similar to mechanical ventilation, 676 cases of status asthmaticus supported on ECMO,
ECMO provides respiratory support (usually by the which is an average of 67 cases per year. This increased
venovenous route because poor ventilation with hyper- use contrasts with the ELSO report of 64 cases from
carbia rather than hypoxemia is the predominant feature 1986–2007 (an average of three cases per year).30 There
of severe status asthmaticus) while the patient recovers were 137 deaths for a 20% mortality. Although it is note-
over time and from the application of pharmacologic worthy that this population has failed other therapies for
therapies. As with mechanical ventilation, ECMO does not status asthmaticus and therefore might be expected to
cure or reverse the underlying disease process of the have a high mortality, it is extremely unusual for patients
asthma exacerbation. However, ECMO does allow clini- with asthma to have a cardiac arrest after reaching medi-
cal care in a hospital.30 In the reports of Pineda63 and
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cians to adequately oxygenate and ventilate the patient dur-

ing the acute asthma episode that is usually a short-term Kolli,62 a high proportion of the subjects were very
disease. Although numerous case reports describe success- hypoxemic before transitioning to ECMO, suggesting
ful use of ECMO for refractory status asthmaticus,65,66 that other factors were at play rather than just asthma.
there is limited evidence evaluating the efficacy of this The real mortality for patients placed on ECMO for respira-
therapy, especially against inhalational anesthetics, which tory failure from status asthmaticus alone is likely much
are much safer.62,63 lower than 20%, and certainly low when compared with the
Another option for extracorporeal support that is 44% mortality for all pediatric respiratory ECMO patients.72
attractive for asthma patients is pumpless extracorpor- Severe asthma may also be a lifelong disease and
eal lung assist (extracorporeal CO2 removal). With can contribute to mortality beyond the acute hospitali-
these devices, the patient’s own arterial pressure is zation. Recently, Melbourne investigators interviewed
used to drive blood through the gas exchange mem- the families of 410 of the 684 patients admitted to their
brane, which can remove CO2 and return oxygenated PICU with asthma over a 15-year period (mean
blood to the patient’s venous system. This strategy has follow-up, 10.3 years). Asthma persisted in 88%, and
advantages that include no requirement of a mechani- 5% of the children who received mechanical ventila-
cal pump and the reduced need for anticoagulation. tion during their index admission died within 10 years
Data in children are lacking, although there are a few of discharge.73 These data are also in line with the expe-
case reports.67,68 rience in adults with asthma23 and suggest that children
Severe air-leak syndromes as a complication of severe who receive mechanical ventilation for asthma are a
asthma are a relatively strong indication for ECMO. high-risk group and should be studied prospectively,
Spontaneous pneumothoraces can occur in patients with a view to evaluating longer-term outcomes.
with asthma even before receiving medical attention,30 In a retrospective review of the Virtual Pediatric Sys-
whereas air leaks severe enough to require multiple chest tems database, Pineda and co-workers reviewed 221 sub-
tubes are rare in mechanically ventilated asthma cases. jects from 2010 to 2020, 149 of whom had received
However, when severe air-leak syndromes occur, partic- ECMO and 62 received inhaled anesthetics, whereas 10
ularly pneumoperitoneum, the early consideration of received both interventions.63 They failed to identify an
ECMO should be entertained. association between ECMO versus inhaled anesthetic
Similar to inhaled anesthetics, extracorporeal lung use and survival to hospital discharge. However, ECMO
support is clinically indicated only for patients with was associated with longer duration of intervention and
asthma failing other therapies. Unfortunately, some of PICU stay. There were caveats in that the data did not
these patients are probably failing secondary to subopti- exclude the possibility that inhaled anesthetic use was
mal understanding and management of mechanical venti- associated with a more than five-fold greater odds of sur-
lation and the pharmacologic interventions. vival. It was also clear that ECMO versus inhaled anes-
thetics was associated with a lower preintervention PaCO2
Mortality and high utilization of high-frequency oscillatory ventilation.
There have been several reports of death from asthma in
children over the past few decades but only a few analy- Complications of Severe Status Asthmaticus
ses of PICU management and deaths, with most from in Children
single centers.69–71 In a more recent multi-center 5-year Despite the risks inherent in mechanically ventilating a
review of the children ventilated in the Collaborative patient with severe status asthmaticus and the use of
Pediatric Critical Care Research Network PICUs, 96% adjuvant therapies such as inhaled anesthetic gases and
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 13

ECMO, the majority of patients will do well. As dis- widely and rapidly. Again, because there are few cases
cussed earlier, most asthma episodes are short-lived of pediatric asthma requiring ventilation (secondary to
when appropriately managed and mortality is low com- better care and improved medications), it is difficult to
pared with other respiratory diseases. Most deaths are study these patients under protocol. For that reason, we
associated with a cardiorespiratory arrest prior to reach- will probably always be dependent upon the adult expe-
ing a hospital. However, there are a number of complica- rience and research with their greater numbers of
tions associated with asthma to be considered when patients and must be prepared to learn from them (see
managing these cases. Most are rarely seen. Fig. 1—suggested management plan for pediatric status
asthmaticus). However, while we have very few research
1. Hypotension—usually secondary to excessive hyper-
inflation from ventilation practices or pneumothorax. studies of good or high quality in the area of drug thera-
2. Pulmonary edema is usually noncardiogenic in ori- pies, excluding the relatively few children requiring
gin occurring secondary to the effect of high (nega- mechanical ventilation, we certainly have enough pediat-
tive) inspiratory pressures, inflammation, or large ric patients to do collaborative studies on drugs to deter-
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volumes of IV b2 agonist (usually terbutaline). mine best delivery modalities, best doses, interactions,
3. Barotrauma in the form of pneumothorax and, and toxicities. Collectively, in this area, we could do
infrequently, pneumoperitoneum can occur sponta- better.
neously but also secondary to ventilation practices.
4. Cardiac complications such as arrhythmias (except- Author Disclosure Statement
ing sinus tachycardia) are infrequent even after car- No competing financial interests exist.
diac arrest.
5. Rhabdomyolysis has been conjectured to occur sec- Funding Information
ondary to the extreme muscle exertion associated No funding was received for this article.
with asthma, but there is little reported evidence.
Rhabdomyolysis could occur as a direct compli- Supplementary Materials
cation of inhaled anesthetic gases or indirectly Supplementary File S1

from malignant hyperthermia but this would be

extremely rare.74,75 References
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Study Group. Intravenous salbutamol bolus compared with an amino- intensive care unit: Occupational health and safety assessment. Can J
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52. Bogie AL, Towne D, Luckett PM, Abramo TJ, Wiebe RA. Comparison of Fortenberry JD. Experience with use of extracorporeal life support for
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continuous high-dose nebulized albuterol for status asthmaticus. R29; doi: 10.1186/cc7735
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Panel Discussion Newth: It could be a good device for giving continu-

Miller: This is more of a comment, but the AnaConDa ous albuterol or epinephrine.
device is available. I’m not sure it’s FDA-approved but Miller: Absolutely, or maybe inhaled anesthetics are
there are hospitals that have it and have used it in their the better drug to give. You can’t give it safely noninva-
ICUs. sively, but for inhaled in an intubated patient where you
Newth: Any of us can get anything for research pur- can give isofluorane easily, maybe that’s the right drug
poses (often needing an IND or IDE), but it’s not FDA- to give if you’re intubated.
approved for asthma in children. It is fast track approved Newth: It’s an interesting point you bring up because
for exploration of isoflurane as sedation in adults, as I one of the things about intubation in patients with asthma
understand. is most of them are done outside the receiving children’s
Miller: They’re using it for research. There are some hospital. The tubes are taken out fairly quickly and peo-
companies that are studying inhaled sedation. Not so ple say, ‘well they didn’t really need to be intubated.’
much in kids yet, but once that is approved then poten- The other thing is maybe they got the inhaled drugs
tially there’s an off-label use for that. more quickly and hence recovered faster.
 16 NEWTH AND ROSS

Grunwell: We have an Apollo ventilator in our ICU short-term thing. Most of us get them off the ventilator
and an RT who can sit one-on-one with each patient for in 2 or 3 days at most. I think it’s a lot cheaper to do it
that shift. We have an anesthesia consult who comes up that way than to get out the ECMO machine.
and they’re usually pretty impressed with the fact that Grunwell: Completely agree. I would put the kid on
we’re not really needing anesthesia support and they’re the Apollo ventilator and avoid ECMO at all costs with
intrigued by this because they don’t typically care for the ensuing problems we all know can happen. The strat-
these kids in status asthmaticus unless something is egy is to put them on the anesthesia workstation for the
really going wrong and they’re in the operating room. day or two it takes to break their asthma and get them off
You bring up isofluorane, it works really well when you the ventilator, or at least moved to conventional
need it. It avoids ECMO. The kids that go on to ECMO ventilation.
typically have some other processes happening, they Abu-Sultaneh: The Canadian group obtained funding
have bad pneumonia, they have ARDS, they have some to perform a randomized, controlled trial to use inhaled
contraindication to being on isofluorane. Malignant anesthesia for sedation in pediatric patients.7,8
Newth: Samer, I want to respond to your kind com-
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hyperthermia or family history and people don’t want to

do that. ment about experience. You might remember that experi-
Newth: Are some of these comments made in your ence for most of us, or many of us anyway, you have
paper? 40 years of experience but that could be one year
Grunwell: We did most of them as a case series. In repeated 40 times. We tend to remember what finally
the isofluorane paper I described1 some of the ECMO worked and then we carry it on. And that stops us from
stuff is in the supplementary materials but I reported thinking about these things, we’re not doing the studies
these things. I think I did comment that a lot of these we need to do or developing the things we need to do to
kids really had severe hypoxemia and gave the reasons look after things like asthma in the ICU. We need to con-
why they may not have done well on isofluorane at first. centrate on trials.
Newth: I take your word for it. Certainly in the table Miller: For the inhaled sedation trial in adults, they
you could see this one had hypoxemia, and so forth. You cut it off after 48 hours. They don’t get more than that.
could exclude them from failing their asthma therapy. They are trying to get FDA approval. My question for
Grunwell: Exactly. Kit is more back to mechanical ventilation in general,
Abu-Sultaneh: Great talk, Kit. It’s nice to hear all how do we get people to actually measure Pplat and
your experience in summarizing the evidence. I would intrinsic PEEP? It’s not just a problem in asthma it’s a
like to refer readers again to one of your studies from problem with lots of other diseases.
Newth: Not too many places do it, I agree. If you can
2007, it’s a very elegant study and people need to look at
get the patients sedated so they have a period at zero
it.2 Maybe this will help settle the debate on how we
flow they actually do a pretty good job finding of Pplat
should manage PEEP in critical asthma. On inhaled
with the fancy mathematical algorithm. We need to test
anesthesia, there was a review paper3 published this year
them for accuracy in pediatrics to see that they are real.
talking about non-anesthesia uses for inhaled anesthetics.
But when they’re on neuromuscular blockade on a mod-
The two big uses are status asthmaticus and status epilep-
ern ventilator.
ticus. I hope that there will be more interest in introduc-
Miller: We’re in the process of updating our ventila-
ing more viable options for us to use inhaled anesthesia
tor protocol. We’re going to push hard for Pplat but I
in PICU, because there’s value for some of these kids.
don’t think it’s going to go down smoothly. It will be a
We can use ECMO more easily now but using inhaled challenge because it’s a big change trying to get and use
anesthesia for status asthmaticus may help save patients Pplat measurements instead of PIP. You can also get
from other treatments like ECMO or medications that Pplat measurements in spontaneously breathing patients
might not work. but it’s trickier.
Grunwell: You can do that but there is some anesthesia Newth: We are doing esophageal manometry for
literature4–6 with expectation of neural toxicity with pro- Pplat along with esophageal measurement of PEEP, but
longed use of inhaled anesthetics or general anesthesia. I it is hard.9,10 The other thing is if any of you want to use
think in the developing brain that’s one thing we should heliox, you need to be aware that not all ventilators can
definitely consider. And these are really sick kids, if you do it. I learned recently that the newer Hamilton C6
are in status ellipticus you brain is clearly not working, but won’t do it whilst the earlier G5 will.
I don’t know that we need to add insult to injury. There is
some literature about that although it’s imperfect. References
Newth: There are some adult ICUs who use inhaled 1. Kolli S, Opolka C, Westbrook A, et al. Outcomes of children with life-
threatening status asthmaticus requiring isoflurane therapy and extracor-
anesthetics for sedation. I probably wouldn’t go for poreal life support. J Asthma 2023;60(10):1926–1934; doi: 10.1080/
inhaled anesthetics for days on end, but asthma is a 02770903.2023.2191715
 INVASIVE RESPIRATORY SUPPORT IN CRITICAL PEDIATRIC ASTHMA 17

2. Graham AS, Chandrashekharaiah G, Citak A, et al. Positive end-expiratory 7. Effect and safety of inhaled isoflurane vs iv midazolam for sedation in
pressure and pressure support in peripheral airways obstruction: work of mechanically ventilated children 3-17 years old (IsoCOMFORT). https://
breathing in intubated children. Intensive Care Med 2007;33(1):120–127; clinicaltrials.gov/study/NCT04684238 Accessed Sept 17, 2024.
doi: 10.1007/s00134-006-0445-6 8. Canadian Institutes of Health Research. Advancing brain outcomes in
3. Gorsky K, Cuninghame S, Jayaraj K, et al. Inhaled volatiles for status asth- pediatric critically ill patients sedated with volatile anesthetic agents
maticus, epilepsy, and difficult sedation in adult ICU and PICU: a system- (ABOVE). https://clinicaltrials.gov/study/NCT05867472 Accessed Sept 17,
atic review. Crit Care Explor 2024;6(2):e1050; doi: 10.1097/CCE 2024.
.0000000000001050
9. Kyogoku M, Shimatani T, Hotz JC, et al. Direction and magnitude of
4. McCann ME, Soriano SG. Does general anesthesia affect neurodevelop-
ment in infants and children? Bmj 2019;367:l6459; doi: 10.1136/bmj.l6459 change in plateau from peak pressure during inspiratory holds can iden-
5. Kamat PP, Simon HK, Sulton C, et al. Neurotoxicity outside the operating tify the degree of spontaneous effort and elastic workload in ventilated
room: an evolving challenge for pediatricians and pediatric subspecial- patients. Crit Care Med 2021;49(3):517–526; doi: 10.1097/CCM
ists. Acad Pediatr 2022;22(2):193–195; doi: 10.1016/j.acap.2021.10.001 .0000000000004746
6. Raper J, Simon HK, Kamat PP. Long-term evidence of neonatal anaesthe- 10. Hotz JC, Sodetani CT, Steenbergen JV, et al. Measurements obtained
sia neurotoxicity linked to behavioural phenotypes in monkeys: where from esophageal balloon catheters are affected by the esophageal bal-
do we go from here? Br J Anaesth 2021;127(3):343–345; doi: 10.1016/j.bja loon filling volume in children with ARDS. Respir Care 2018;63(2):
.2021.06.005 177–186; doi: 10.4187/respcare.05685
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