PEDIATRIC ALLERGY, IMMUNOLOGY, AND PULMONOLOGY SHORT COMMUNICATION/

Volume 35, Number 4, 2022

ª Mary Ann Liebert, Inc.
DOI: 10.1089/ped.2022.0126 BRIEF REPORT

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Children with Near-Fatal Asthma:

The Use of Inhaled Volatile Anesthetics
and Extracorporeal Membrane Oxygenation

Chasity M. Custer, MD,1 Erika R. O’Neil, MD,2 Janaki Paskaradevan, MD,3

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Brian J. Rissmiller, MD,2 and Maria C. Gazzaneo, MD2,3

Background and Purpose: The use of extracorporeal membrane oxygenation (ECMO) has been described for
near-fatal asthma that continues to be refractory despite maximal medical therapy.
Methods: Patients admitted to the pediatric intensive care unit at Texas Children’s Hospital from 2012 to 2020
with the diagnosis of asthma who were supported on ECMO or isoflurane were included in the study. Patient
demographics, medication usage, and complications were compared between the case group (ECMO, n = 12)
and the control group (isoflurane only, n = 8).
Results: All patients survived to discharge. ECMO patients received shorter durations of albuterol (12 versus
104 h, P = 0.0002) and terbutaline (13.3 versus 31.5 h, P = 0.0250). There were no differences in complication
rates between the 2 groups.
Conclusion: ECMO is a reasonable and safe support method for patients with near-fatal asthma and may lead to
less bronchodilator medication exposure when compared with inhaled volatile anesthetic use.

Keywords: extracorporeal membrane oxygenation, status asthmaticus, social determinants of health, intensive
care units, pediatric

Introduction mechanical ventilation. Isoflurane has become more preva-

A sthma is one of the most common chronic diseases of
childhood affecting an estimated 6.2 million individu-
als under the age of 18 in the United States. It remains the
most common cause of hospitalization and emergency
department visits in children with rates highest among Afri-
can Americans. In 2020, 204 pediatric deaths were attrib-
uted to asthma in the United States.1,2
Near-fatal asthma (NFA) is a life-threatening condition
of acute respiratory failure and the most severe survivable
clinical presentation of status asthmaticus. In addition to
first-line therapies such as bronchodilators and systemic cor-
ticosteroids, it often requires mechanical ventilation with
inhaled volatile anesthetics and paralysis with neuromuscu-
lar blockade.3–7 Inhaled anesthetics have direct and indirect
bronchodilator effects and provide sedation to facilitate
lent in pediatrics compared with other inhaled anesthetics
due to its safety profile.8 Yet despite maximal medical ther-
apy, some cases of NFA will have persistent hypercapnic
respiratory acidosis.
In these situations, the use of extracorporeal membrane
oxygenation (ECMO) has been described to support patients
with NFA.9–14 ECMO provides temporary cardiorespiratory
support, which allows lung rest and time for airway smooth
muscle relaxation and inflammation to reverse. It also pro-
vides the ability to perform aggressive airway clearance and
an avenue for controlled bronchoscopy. ECMO support for
asthmatics in case reports and small retrospective studies
report high survival rates.9–14
Although the National Institutes of Health have devel-
oped classification and therapy guidelines to address asthma,
these guidelines do not address management options for

Departments of 1Pediatrics, 2Pediatric Critical Care Medicine, and 3Pulmonology, Baylor College of Medicine, Houston, Texas, USA.

170
 ECMO SUPPORT FOR NEAR-FATAL ASTHMA 171

children with asthma severe enough to require admission
to the pediatric intensive care unit (PICU).15 We aimed to
describe demographics, medical management, and outcomes
of children who received inhaled volatile anesthetics or
ECMO for the management of NFA.
Methods
We conducted a retrospective review of children, ages
18 years or less, with NFA admitted to the PICU at Texas
Children’s Hospital between 2012 and 2020. Patients were
included if they had an admission diagnosis of asthma and
received inhaled volatile anesthetics or ECMO. This study
was approved by Baylor College of Medicine (BCM) IRB
(approval #H-39153, Date: 4/20/2018 Original title: Life
threatening asthma management in the PICU). Informed
consent was waived and all procedures were followed in
accordance with the ethical standards of BCM IRB and the
Helsinki Declaration of 1975.
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Statistical analyses were carried out using JMP (version
14; SAS, Cary, NC). Dichotomous variables were ana-
lyzed using Fisher’s exact or Pearson’s chi-square tests and
expressed as exact numbers with percentages. Continuous
variables were analyzed with Student’s t-test if normally dis-
tributed or Wilcoxon–Mann–Whitney test for non-normally
distributed continuous variables and are expressed as median
with 25th–75th interquartile ranges (IQRs). Statistical signifi-
cance was defined as a P value <0.05. Significant associations
are reported in odds ratios with 95% confidence intervals.
Results
A total of 20 patients with NFA were admitted to the
PICU and supported with either inhaled volatile anesthet-
ics or ECMO (Table 1). Males (60%), African Americans
(52%), and patients with Medicaid insurance (45%) were
over-represented in this patient population. The majority of
patients had a previous diagnosis of asthma (80%), 50% of

Data were collected from the electronic medical record
(EMR), including demographic information, pre-ECMO
comorbidities including asthma severity, pre-ECMO respi-
ratory and hemodynamic support, and pre-ECMO bio-
chemical, ventilation, and hemodynamic data. Asthma
therapies (albuterol, ipratropium bromide, terbutaline, sys-
temic corticosteroids, and magnesium sulfate) used before
and while on ECMO were included. Type and duration of
inhaled volatile anesthetics were included. ECMO-specific
variables were collected to include mode, duration of ECMO,
cannula type, and size and any complications sustained
while on ECMO. Social determinants of health and financial
concerns were obtained from social work notes found in the
EMR. Missing data were excluded from analysis.
Our primary outcome was survival to hospital discharge.
Secondary outcomes included hospital length of stay, ICU
length of stay, duration of invasive mechanical ventilation,
exposure to medications, and complications.
patients had a diagnosis of severe asthma and had been
prescribed controller medications before this admission
(Supplementary Data, Table 3). Almost all patients (90%)
were discharged with controller medications.
Eight patients received inhaled volatile anesthetics only,
whereas 12 patients received ECMO support. Nine patients
received isoflurane and ECMO and were analyzed in the
ECMO cohort (Table 1). All patients supported on ECMO
received venovenous support and were cannulated with a
dual-lumen cannula in the right internal jugular vein (Sup-
plementary Data, Table 4). Median duration of ECMO was
71 [46.9–126.9] h. Patients who received ECMO were more
likely to have a higher oxygenation index (24.2 versus 9.95,
P = 0.0022) compared with patients who only required inha-
led volatile anesthetics (Supplementary Data, Table 5).
When comparing patients who received ECMO to
those who received only inhaled volatile anesthetics, ECMO
patients received shorter durations of albuterol (12 versus

Table 1. Characteristics of Intubated Asthmatics Supported with Inhaled Volatile Anesthetics

(Isoflurane, ISO) and Extracorporeal Membrane Oxygenation
All patients (n = 20) ECMO (n = 12) ISO only (n = 8)
Characteristics No. (%) or median-IQR P
Male 12 (60%) 7 (58%) 5 (63%) 1.0000
Age (years) 5.5 [2–9] 7.5 [3.3–11] 2 [1–7.5] 0.0325
Weight (kg) 24.4 [12.6–32.5] 27.9 [17.4–36.4] 11.9 [10.8–26.0] 0.0136
Black, non-Hispanic 10 (50%) 8 (67%) 2 (25%) 0.1698
Medicaid or no insurance 12 (60%) 9 (75%) 3 (38%) 0.1675
Financial concerns 10 (50%) 7 (58%) 3 (38%) 0.6499
History of severe asthma 10 (50%) 6 (50%) 4 (50%) 1.0000
Controller medication use 10 (50%) 6 (50%) 4 (50%) 1.0000
Inpatient parameters No. (%) or median-IQR P
Infectious trigger identified 13 (65%) 9 (75%) 4 (50%) 0.2508
Viral infection 11 (85%) 8 (89%) 3 (75%) 1.0000
ICU length of stay (days) 7 [6–10.8] 7.5 [6–14.3] 7 [6–8] 0.4355
Hospital length of stay (days) 10 [8–14.8] 12 [8.0–25] 9.5 [7.25–10] 0.2127
Discharged home 20 (100%) 10 (83%) 8 (100%) —
Discharged with controller medications 18 (90%) 8 (89%) 8 (100%) 1.0000
Readmission within 30 days 0 0 0 —
Values in bold represent statistically significant findings P £ 0.05.
IQR, interquartile range; ECMO, extracorporeal membrane oxygenation.
 172 CUSTER ET AL.

Table 2. Medication Usage of Intubated Asthmatics Supported with Inhaled Volatile Anesthetics
(Isoflurane, ISO) and Extracorporeal Membrane Oxygenation
All patients (n = 20) ECMO (n = 12) ISO only (n = 8)
Medications No. (%) or median-IQR P
Continuous albuterol 20 (100%) 12 (100%) 8 (100%) —
Duration of continuous albuterol (hours) 27.3 [10.5–92.5] 12 [8.3–24.8] 104 [47.5–132.8] 0.0002
Terbutaline 19 (95%) 11 (92%) 8 (100%) 1.000
Duration of terbutaline (hours) 23.5 [4.8–33.3] 13.3 [4.0–25.3] 31.5 [24–112.5] 0.0250
Steroids 20 (100%) 12 (100%) 8 (100%) —
Ipratropium bromide 20 (100%) 12 (100%) 8 (100%) —
Magnesium 20 (100%) 12 (100%) 8 (100%) —
Subcutaneous epinephrine 6 (30%) 4 (33%) 2 (25%) 1.000
Ketamine 15 (75%) 9 (75%) 6 (75%) 1.0000
Isoflurane 17 (85%) 9 (75%) 8 (100%) 0.2421
Isoflurane duration (hours) 10.4 [5.1–39.1] 5.7 [1.1–11.7] 29 [13.5–51.5] 0.0166
Neuromuscular blockade 16 (80%) 10 (83%) 6 (75%) 1.0000
Values in bold represent statistically significant findings P £ 0.05.
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104 h, P = 0.0002) and terbutaline (13.3 versus 31.5 h,
P = 0.0250) (Table 2). There were no significant differences
in invasive mechanical ventilation parameters or duration
between the 2 groups. PICU length of stay (7.5 versus 7 days,
P = 0.4255) and hospital length of stay were not significantly
different between the groups (12 versus 9.5 days, P = 0.2127).
All patients were discharged home and there were no
readmissions within 30 days. A total of 6 complications oc-
curred in the ECMO group: neurological (1), arrhythmias (4),
and pneumomediastinum with bronchoscopy (1). One com-
plication was reported for the isoflurane group: bleeding (1).
There was no statistically significant difference in complica-
tions between the 2 cohorts (Supplementary Data, Table 5).
Discussion
Overall, our study showed high survival for children
with NFA with minimal complications during their treat-
ment course. Patients supported on ECMO received less
cumulative bronchodilator medication exposure. In addition,
this study highlighted the socioeconomic factors present in
the most severe asthmatics.
All patients survived and there were no statistically
significant complications identified between the cohorts.
Similar to previous studies, our data demonstrated that
ECMO support for asthmatics is safe.11–14 The most com-
monly reported complication in our study was arrhythmia,
which occurred at the time of cannulation. We suspect this
is related to the insertion of a wire near a myocardium that
is overstimulated with beta-agonist exposure rather than a
direct effect of the beta-agonist medication given that these
arrhythmias were not sustained postcannulation. Cardiac
complications have been reported with ECMO use, and pre-
viously, no difference was noted in cannulation techniques
between dual-site versus single-site double lumen.16 How-
ever, cannulation technique for asthmatics may be an area of
future research.
Although a descriptive study, we examined differences in
medical therapy while on ECMO support for NFA. At our
institution there is no protocol for escalation of therapy
regarding anesthetics usage or ECMO support for near-fatal
asthma. Upon review, there were no statistically significant
differences in mechanical ventilator parameters, blood gas
parameters, or oxygen index values; indicating the severity
of illness in both groups was similar. All patients with
NFA admitted to the PICU received albuterol, ipratropium
bromide, magnesium sulfate, and methylprednisolone, and most
received inhaled volatile anesthetics before initiation of ECMO.
Interestingly, when compared with the isoflurane-only
group, patients who were supported on ECMO received
less exposure to albuterol, terbutaline, and isoflurane, and
potentially the side effects associated with bronchodilatory
medications. Myocardial toxicity from beta 2-agonist expo-
sure has been reported, in particular in patients with hyper-
carbia and hypoxemia and with the use of older generation
beta-agonists.17 Limiting exposure to these medications in
NFA may be beneficial; however, future research is required.
Finally, racial and socioeconomic disparities in asthma
outcomes have been well documented in previous litera-
ture. Black Americans are 3 times more likely to die from
asthma.18–20 In this study, the patient population was reflec-
tive of this national trend, with 50% of patients enrolled
identifying as Black Americans. Lack of consistent health
insurance has been shown to result in higher rate of emer-
gency department visits, higher rate of hospitalizations,
and a higher mortality rate.18,21,22 Of the patients in this
study, 45% had Medicaid and 15% of patients lacked
insurance. Fifty percent of patients had a prior diagnosis of
asthma and 3 patients reported being prescribed a control-
ler medication but not having access to their inhaler. These
results highlight the need for better and more consistent
access to care, for better community outreach programs, and
for a higher focus on social determinants of health in the
outpatient and hospital setting.
Our descriptive study is limited by its retrospective
nature and small numbers of children with NFA. In addition,
some patients received isoflurane and were supported with
ECMO; given the small numbers we could not analyze these
groups separately and those patients were included in the
ECMO only cohort. Finally, given limitations in our EMR we
were not able to capture vasoactive medication information.
Conclusion
With appropriate treatment, children with NFA have
high survival. ECMO is a reasonable and safe support
 ECMO SUPPORT FOR NEAR-FATAL ASTHMA
method for patients with NFA and may lead to less medi-
cation exposure. In addition, there is a significant need for
further research and public health interventions to address
the socioeconomic disparities that exist among this patient
population.
Author Disclosure Statement
The authors of this article do not have any financial
disclosures or conflicts of interests to disclose.
Funding Information
No funding was received for this article.
Supplementary Material
Supplementary Data
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Address correspondence to:
Chasity M. Custer, MD
Department of Pediatrics
Baylor College of Medicine
Houston, TX 75390-9096
USA
E-mail: chasity.custer@gmail.com
Received for publication July 28, 2022; accepted after
revision October 29, 2022.