American Journal of Emergency Medicine 44 (2021) 441–451

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American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Evaluation and management of the critically ill adult asthmatic

in the emergency department setting
Brit Long, MD a,⁎, Skyler Lentz, MD b, Alex Koyfman, MD c, Michael Gottlieb, MD d
a
Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States
b
Division of Emergency Medicine, Department of Surgery, Larner College of Medicine, University of Vermont, Burlington, VT, United States
c
The University of Texas Southwestern Medical Center, Department of Emergency Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States
d
Department of Emergency Medicine, Rush University Medical Center, United States

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Asthma is a common reason for presentation to the Emergency Department and is associated with
Received 13 November 2019 significant morbidity and mortality. While patients may have a relatively benign course, there is a subset of pa-
Received in revised form 8 March 2020 tients who present in a critical state and require emergent management.
Accepted 16 March 2020 Objective: This narrative review provides evidence-based recommendations for the assessment and management
of patients with severe asthma.
Discussion: It is important to consider a broad differential diagnosis for the cause and potential mimics of asthma
Keywords:
Asthma
exacerbation. Once the diagnosis is determined, the majority of the assessment is based upon the clinical exam-
Obstruction ination. First line therapies for severe exacerbations include inhaled short-acting beta agonists, inhaled anticho-
Pulmonary linergics, intravenous steroids, and magnesium. Additional therapies for refractory cases include parenteral
Lung epinephrine or terbutaline, helium‑oxygen mixture, and consideration of ketamine. Intravenous fluids should
Beta agonist be administered, as many of these patients are dehydrated and at risk for hypotension if they receive positive
Glucocorticoids pressure ventilatory support. Noninvasive positive pressure ventilation may prevent the need for endotracheal
Critical intubation. If mechanical ventilation is required, it is important to avoid breath stacking by setting a low respira-
Severe
tory rate and allowing permissive hypercapnia. Patients with severe asthma exacerbations will require intensive
care unit admission.
Conclusions: This review provides evidence-based recommendations for the assessment and management of se-
vere asthma with a focus on the emergency clinician.
Published by Elsevier Inc.

1. Introduction
Asthma is an obstructive pulmonary disease affecting a wide range
of ages [1-3]. Asthma results in over two million Emergency Depart-
ment (ED) visits and close to 4000 deaths in the United States every
year [1-3]. Even in the current era with improved chronic asthma con-
troller medications, asthma exacerbation remains a major cause of
death in patients with chronic asthma. Older patients have a 5-fold in-
creased rate of mortality compared to younger patients, and African
American patients have a higher mortality rate when compared with
Caucasian and Hispanic patients [3,4]. Tobacco use, low income, living
in an urban setting, low education status, and poor healthcare access
also portend a worse prognosis [1,3,5].
Asthma severity varies significantly among patients. Some patients
may have minimal symptoms and rarely require ED evaluation, while
others experience frequent and severe exacerbations requiring
⁎ Corresponding author.
E-mail address: brit.long@yahoo.com (B. Long). ⁎ Corresponding author.
intensive care unit (ICU) admission and airway support [6-11]. Approx-
imately 10% of patients who are admitted for an asthma exacerbation
require ICU care, with 2% of patients requiring intubation [12]. While
more common among those with poorly-controlled asthma, severe ex-
acerbations can also affect those with mild or moderate baseline sever-
ity of disease [7-10]. Therefore, it is important for Emergency Medicine
(EM) clinicians to be aware of the unique management of the critically
ill asthmatic.
2. Methods
This narrative review provides a focused overview of severe adult
asthma for EM clinicians. As such, this manuscript will not review
mild exacerbations or chronic asthma management. The authors
searched PubMed and Google Scholar for articles using a combination
of the keywords “asthma”, “severe”, and “critical”. The search was con-
ducted from the database's inception to September 1, 2019. PubMed
yielded over 600 articles. The first 200 articles in Google Scholar were
also searched as recommended by Bramer et al. [13] Authors evaluated

https://doi.org/10.1016/j.ajem.2020.03.029
0735-6757/Published by Elsevier Inc.

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B. Long, S. Lentz, A. Koyfman et al.
case reports and series, retrospective and prospective studies, system-
atic reviews and meta-analyses, and other narrative reviews. Authors
also reviewed guidelines and supporting citations of included articles.
The literature search was restricted to studies published in English,
with focus on the EM and critical care literature. Authors decided
which studies to include for the review by consensus. When available,
systematic reviews and meta-analyses were preferentially selected.
These were followed sequentially by randomized controlled trials, pro-
spective studies, retrospective studies, case reports, and other narrative
reviews when alternate data were not available. A total of 214 resources
were selected for inclusion in this narrative review. Of these, there were
34 systematic reviews and meta-analyses, 41 randomized controlled
trials, 45 prospective studies, 25 retrospective studies, 26 case reports
or case series, and 43 narrative reviews or expert consensus documents.
3. Discussion
3.1. Pathophysiology
Asthma is a chronic form of reactive airway disease characterized by
bronchial hyperresponsiveness resulting in smooth muscle spasm, in-
flammatory mediator release, and vascular permeability leading to
narrowing of the airways [1,14]. This results in airway obstruction and
lung hyperinflation and hypoventilation, which in severe exacerbations
can result in hypercarbia, hypoxemia, and death if uncorrected
[8-10,17].
There are two main types of severe exacerbation: rapid- and slow-
onset [18-26]. These types differ in terms of symptom severity and
likelihood of treatment success with beta-agonist and glucocorticoid
therapy. Rapid-onset asthma is generally associated with an onset to se-
vere symptoms of b6 h and accounts for up to 20% of severe exacerba-
tions [24-26]. The underlying pathophysiology of rapid-onset asthma
primarily involves smooth muscle bronchospasm with neutrophil pre-
dominance [18,19]. Slow-onset asthma accounts for the majority of crit-
ical exacerbations, with 80–85% of patients experiencing symptoms for
at least 12 h prior to presentation, though some symptoms can last as
long as 1–3 weeks [17,20]. The slow-onset form is associated with eo-
sinophilic inflammation resulting in airway obstruction [20-23]. While
both forms can lead to severe asthma exacerbations, the courses can dif-
fer significantly. Rapid-onset asthma exacerbations provide a shorter in-
terval to initiate treatment before they become severe, but are often
more rapidly reversible if aggressively treated. Slow-onset exacerbation
has a longer interval before it reaches critical severity, but can require a
much more prolonged treatment duration to reverse the symptoms
[18-26].
3.2. History and physical examination
In critically ill patients, resuscitation is needed during the initial eval-
uation including history and physical examination, as delays in therapy
can lead to worse outcomes. History may be limited in critically ill pa-
tients, but if able to obtain, history should include time of symptom
onset, precipitating cause, symptom severity compared to prior exacer-
bations, and treatments attempted prior to ED presentation
[9,10,14,17,27,28]. Clinicians should screen for symptoms that suggest
an alternate etiology, such as anaphylaxis, congestive heart failure,
pneumonia, and pulmonary embolism, as well as other conditions that
may result in wheezing and respiratory distress (Table 1) [29–49]. In-
creasing use of short-acting beta agonist therapy, recent glucocorticoid
use, recent ED visit or hospital admission for asthma, and any prior air-
way interventions for asthma (e.g., non-invasive positive pressure ven-
tilation [NIPPV] and endotracheal intubation) may suggest a more
severe exacerbation [9,10,14,17,27,28]. Other symptoms reflective of a
severe exacerbation include inability to speak more than a few words,
respiratory distress, agitation, and a sensation of air hunger [14,17].
442
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American Journal of Emergency Medicine 44 (2021) 441–451
The physical examination should assess mental status, cyanosis, re-
spiratory distress, and wheezing, as well as for other causes of dyspnea
or wheezing [9,10,14,17,29–49]. Signs suggestive of severe exacerbation
include tachypnea, tachycardia, accessory respiratory muscle use, in-
ability to speak in full sentences, inability to lie flat, and tripoding posi-
tion [14-17,50,51]. However, these findings possess a sensitivity of b50%
for severe airway obstruction, and thus their absence should not be used
to exclude the diagnosis of severe exacerbation [14,52]. Evidence of im-
minent cardiorespiratory arrest includes cyanosis, inability to maintain
respiratory effort, bradycardia, and decreased mental status [16,17]. It
is important for clinicians to note that wheezing and respiratory distress
are nonspecific findings that may also be found in a variety of other con-
ditions (Table 1).
3.3. Evaluation
Pulse oxygen saturation testing should be performed as soon as pos-
sible. Oxygen saturations b90% are markers for more severe obstruction
and require early and aggressive treatment [9,10,14,16,17]. However, as
asthma is predominantly an issue with ventilation rather than oxygen-
ation, saturations may appear normal despite severe exacerbations, so
providers should not be falsely reassured by a normal oxygen
saturation.
While guidelines recommend use of spirometry for diagnosis and
classification of asthma [14,50], spirometry is not beneficial in the undif-
ferentiated patient with shortness of breath. Moreover, spirometry re-
lies on the patient's ability to perform the test and reproduce it to
monitor response to therapy [9,10,16,17]. Critically ill patients are un-
likely to be able to perform peak flow measurements in the ED due to
the effort required.
End tidal capnography can be used to assess the severity of the air-
way obstruction and treatment response [53-59]. When severe small
airway bronchoconstriction is present, the capnography waveform
will have an increased slope during phase III and an increased alpha
angle, resembling a shark fin due to delayed emptying of regions with
obstruction (Fig. 1) [53-55,59]. Several studies have demonstrated
that inhaled beta agonist therapy decreases the slope during phase III,
which is correlated with improvements in the patient's air movement
and respiratory status [53-59].
Several guidelines discuss the use of arterial blood gas (ABG) assess-
ment to evaluate partial pressure of carbon dioxide (pCO2) and partial
pressure of oxygen (pO2); most recommend reserving blood gas sam-
pling for severe cases or those that fail to respond to initial therapies
[14,50]. In early exacerbation hyperventilation predominates; pCO2
will be low and pO2 normal-to-high [14,16,17,70-72]. As the disease
progresses in severity and the tidal volume decreases, the pCO2 and
pO2 begin to normalize. A rising or high pCO2 (N45 mmHg) and a low-
to-normal pO2 can suggest worsening hypoventilation and airway ob-
struction, which should prompt consideration of escalation of therapy
or NIPPV [16,17]. A venous blood gas (VBG) is an effective screening
tool for hypercarbia and can be drawn easily with other labs. A venous
Table 1
Differential diagnosis of wheezing.
Acute coronary syndrome
Anaphylaxis
Bronchiectasis
Carcinoid syndrome
Congestive heart failure
Cystic fibrosis
Foreign body aspiration
Interstitial lung disease
Lung mass
Pneumonia
Pneumothorax
Pulmonary embolism
Vocal cord dysfunction
B. Long, S. Lentz, A. Koyfman et al. American Journal of Emergency Medicine 44 (2021) 441–451

Fig. 1. Waveform capnograph depicting normal waveform (A) and waveform suggesting bronchoconstriction (B).

PCO2 of b45 mmHg rules out hypercarbia [64-66]. A VBG to screen for
hypercarbia and pulse oximetry to evaluate oxygenation is an alterna-
tive to an ABG in most cases [65]. Studies suggest that blood gas mea-
surements in patients with respiratory failure cannot accurately
predict need for intubation or mortality [60-69]. Therefore, a blood gas
may not be needed in every patient, and the focus should remain on
the clinical examination. In those that fail to respond to treatment or
have clinical signs suggestive of hypercarbia (i.e. somnolence) or visible
respiratory muscle fatigue, a blood gas is helpful to assess for ventilation
perfusion mismatch and the presence of hypercarbia in severe exacer-
bations [14,63-69]. The trend in pCO2, along with the trend in clinical
examination may demonstrate response to therapy, or more ominously
the failure to respond, particularly in those severe enough to require
treatment with non-invasive ventilation.
While chest radiographs are typically unrevealing in mild or moder-
ate acute exacerbations [60,73-77], they should be obtained in patients
with severe exacerbation or patients with significant respiratory dis-
tress, fever, chest pain, hypoxemia, or if there is concern for an alternate
etiology for patient symptoms (e.g., pleural effusion, heart failure, pneu-
monia, pneumothorax) [17].
In patients with undifferentiated shortness of breath, point-of-care
ultrasound (POCUS) can provide valuable information with regard to al-
ternate etiologies and potential causes of the exacerbation [78-82]. This
offers several advantages over radiographs, including the ability to
obtain information rapidly while avoiding the need for the unstable pa-
tient to leave the ED.
3.4. Management
The initial goals of the critical patient with severe exacerbation are
stabilization and reversal of the airflow obstruction (Fig. 2 and
Table 2), as well as any associated hypoxemia and hypercarbia. Admin-
istration of supplemental oxygen is recommended for hypoxemia
[14,17,83-85]. Asthmatic patients are often significantly dehydrated
due to respiratory losses and decreased oral intake from the illness
[9,10,14,17]. While they may have a normal blood pressure or even be
hypertensive on initial presentation, much of this is due to the adrener-
gic stimulus. Intubation or NIPPV can further reduce blood pressure
[16,17]. Therefore, intravenous fluid resuscitation should be given em-
pirically to most patients with asthma who are critically ill to reduce
risk of hemodynamic decompensation [9,10,16].
3.4.1. Beta agonists
Short-acting beta agonists (SABA) work by relaxing the smooth
muscle in the bronchioles of the lung and possess significant literature
support as a first-line therapy in asthma exacerbation (Table 2)
[9,10,14,17]. The most commonly used SABA is albuterol [86-90]. The
time of onset for SABAs is seconds to minutes, with a peak action at

Fig. 2. Severe asthma exacerbation management.

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Table 2
Medications utilized in severe asthma exacerbation [86-173]
Medication Dose
Albuterol nebulized – 2.5–5 mg every 20 min up to 3 doses, then
2.5–10 mg every 1–4 h
– For continuous, use 10–20 mg/h
Ipratropium – 0.5–2 mg every hour
bromide – Use 2.5 mL every 6 h after initial dose
nebulized
Epinephrine – IM is first line for critical patients; use
parenteral 0.3–0.5 mg every 20 min up to 3 doses
– For patients refractory to IM, use
10–20 μg IV boluses
Terbutaline – 0.25 mg every 20 min up to 3 doses SC
Magnesium – 2 g IV every 20 min up to 3 doses
Ketamine – 0.1–0.3 mg/kg IV, then 0.5 mg/kg/h for 2 h
for bronchodilation
– 1–2 mg/kg IV for dissociation
Methylprednisolone – 40–125 mg IV
Prednisolone – 40–80 mg/day
Dexamethasone – Maximum 16 mg once (IV, IM, or PO)
h — hour, mg — milligrams, min — minutes, IV — intravenous, IM – intramuscular, PO — per os, ED — emergency department, SC — subcutaneously, L — liters.
30 min and a half-life of 4–6 h [14,17,86-93]. In severe exacerbations,
continuous nebulized albuterol (10–20 mg per hour) is recommended,
as continuous nebulization among these patients has been found to re-
duce hospitalizations with a number needed to treat (NNT) of 10
[17,94]. Most patients with severe exacerbations will improve after 3
separate therapies or 1 h of continuous nebulization [95-97].
Inhaled epinephrine has been proposed to assist patients who do not
benefit from other beta agonists, as its alpha agonist activity may reduce
airway edema [98]. However, literature evaluating inhaled epinephrine
has failed to demonstrate improved efficacy when compared with stan-
dard inhaled beta agonist therapy [99-103]. Nebulized terbutaline has
also not demonstrated improved efficacy when compared to other
beta agonists [99]. Therefore, albuterol remains the inhaled beta agonist
agent of choice in this population.
Providers should understand that use of inhaled beta agonists is as-
sociated with lactic acid elevation N2 mmol/L in over 50% of patients,
which may reach N4 mmol/L. [104-108] This lactic acid elevation associ-
ated with inhaled beta agonists is primarily due to altered cellular me-
tabolism, rather than patient decompensation, airway obstruction, or
poor oxygen delivery [104-108].
3.4.2. Anticholinergics
Ipratropium bromide produces bronchodilation by inhibiting mus-
carinic acetylcholine receptors in pulmonary smooth muscle and is
often combined with inhaled albuterol among critically ill asthmatic pa-
tients [14,17]. Its onset of action is approximately 15 min, with peak ac-
tivity at 60–90 min and a half-life of 4–8 h [14,16,17,109-124]. Thus, it is
slower in onset but lasts longer compared to SABAs [14,16,17].
Ipratropium is given as 0.5–2 mg for the first hour via nebulization
[9,10,14,16,17]. The addition of an inhaled anticholinergic to a SABA sig-
nificantly improves pulmonary function and reduces the likelihood of
hospital admission, particularly in patients with severe exacerbation,
with an NNT of 10 to prevent 1 hospitalization [109-124].
3.4.3. Glucocorticoids
Glucocorticoids are a key component of treatment, as they improve
lung function through upregulation of beta receptors and reduction of
airway inflammation [9,10,14,16,17]. Guidelines recommend their use
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American Journal of Emergency Medicine 44 (2021) 441–451
Pharmacokinetics Comments
– Onset of action: Seconds to minutes – Continuous nebulization recommended for severe
– Peak effect: 30 min exacerbation
– Duration: 4–6 h – Gas flow should be at least 4 L/min
– Onset of action: 15 min – Mix with albuterol for initial therapy
– Peak effect: 60–90 min
– Duration: 4–8 h
– Onset of action: 5–10 min – May be used for patients refractory to inhaled beta
– Peak effect: b20 min for IV; b1 h for IM – agonist therapy
Duration: b1 h for IV; 4 h for IM or SC
– Onset of action: b15 min – Not proven to be more effective than inhaled beta
– Peak effect: 1–3 h agonist therapy
– Duration: 3–4 h
– Onset of action: seconds to minutes – Use in severe exacerbation; no benefit in mild to
– Duration: 30 min moderate exacerbation
– Onset of action: seconds to minutes – Slowly infuse over 5–10 min to reduce psychiatric
– Duration: 10–30 min complications
– Onset of action: several hours – Doses over 125 mg IV do not improve outcomes and
– Peak effect: 1–2 h may be associated with adverse events
– Duration: 30–36 h
– Onset of action: several hours – Can be administered orally and as prescription if
– Peak effect: 1 h discharged
– Duration: 18–36 h
– Onset of action: several hours – Can provide 1 dose in ED and another in 2 days if
– Peak effect: 1–2 h discharged
– Duration: 36–54 h
in patients with moderate-to-severe exacerbation and patients who
do not respond to initial SABA therapy within the first hour of presenta-
tion [9,10,14,127-131]. While the onset of action is typically within the
first 6 h after administration, studies suggest that glucocorticoids ad-
ministered early in the management of patients with severe exacerba-
tion (specifically within the first hour) reduce the overall need for
hospital admission [127-131]. In severe exacerbations, methylpredniso-
lone 80–125 mg intravenous (IV) may be administered [9,10,14,130-
133]. Doses higher than this are not recommended, as higher doses do
not reduce duration of stay, reduce duration of endotracheal intubation,
or improve respiratory function, while increasing risk of complications
such as hyperglycemia, neurologic side effects (e.g., anxiety, delirium),
myopathy, infection, and gastrointestinal bleeding [134,135]. While glu-
cocorticoids possess a high degree of oral bioavailability, the IV formula-
tion is recommended in those with severe asthma exacerbation, oral
(PO) intolerance, and respiratory distress or failure, as critically ill pa-
tients with asthma often experience splanchnic hypoperfusion and de-
creased gastrointestinal absorption secondary to increased adrenergic
stimulus [9,10,16,17].
3.4.4. Magnesium sulfate
In patients with severe asthma exacerbation, magnesium sulfate can
improve bronchodilation by inhibiting calcium influx in the airway
smooth muscle and by activating adenylate cyclase [10,14,17,136-
148]. Magnesium sulfate is typically dosed at 2 g IV, given rapidly over
20 min and can be repeated twice [9,10,14,17]. Studies suggest that IV
magnesium improves pulmonary function and reduces hospital admis-
sions in severe asthma [136-148]. A systematic review of 7 randomized
controlled trials (RCTs) found reduced admissions and improved pul-
monary function among those with severe exacerbation, while a subse-
quent 2014 Cochrane review of 14 RCTs (n = 1769 patients) suggested
magnesium sulfate reduced admission rates by 25% in patients with se-
vere asthma [136,139]. Of note, while it has been shown to reduce ad-
missions, it has not been demonstrated to improve mortality or
reduce need for airway interventions such as NIPPV or intubation
[136,139,140,145,147]. While beneficial in pediatric patients, the data
on inhaled magnesium in adult patients are more limited, with a few
studies suggesting benefit [145,148].
444
B. Long, S. Lentz, A. Koyfman et al.
3.4.5. Parenteral beta agonist therapy
Parenteral beta agonists via the subcutaneous (SC), intramuscular
(IM), or IV route are typically reserved for patients with severe exacer-
bations who are unresponsive to other therapies or in those who are un-
able to tolerate inhaled bronchodilators [9,10,16,17,149-161].
Terbutaline is the most common beta agonist administered via the SC
route and is given at doses of 0.25 mg [9,10,16,17]. However, the litera-
ture has not consistently demonstrated an improvement in patient out-
comes among patients with severe exacerbations [14,16,17,149-161].
For patients with anaphylaxis or severe, refractory status asthmaticus,
epinephrine 0.3–0.5 mg IM can also be given [14,16,17]. In hypotensive
patients or those with respiratory distress and reduced skin circulation
due to hyperadrenergic state, IM epinephrine may be preferable over
the SC route.
Intravenous administration should be considered in patients who
are profoundly hypotensive or refractory to IM dosing [16,17]. The
most common beta agonist administered via the IV route is epinephrine
[9,10,16,17]. Intravenous epinephrine boluses can be given in doses of
5–20 μg every 2–5 min. A continuous IV infusion of 0.1–0.5 μg/kg/min
should follow these IV boluses, titrating to symptomatology. While
some clinicians may be concerned about side effects with the parenteral
route, the literature has not demonstrated an increased risk of adverse
cardiovascular or neurologic events, and the resulting reduction in
bronchospasm can reduce tachycardia, lower hypertension, and im-
prove pulmonary function [155-161].
3.4.6. Ketamine
Ketamine is a dissociative anesthetic with an onset of action of 60 s
and half-life of 10–15 min [161-163]. Ketamine has been proposed to
reduce bronchoconstriction by lowering nitric oxide production, reduc-
ing the inhibition of beta agonist reuptake, and blocking the N-
Methyl‑d-aspartic acid (NMDA) receptors [162-165]. Ketamine also re-
duces macrophage recruitment and cytokine production, leading to de-
creased pulmonary inflammation [163-166]. A 2013 systematic review
found that ketamine may improve pulmonary function, reduce oxygen
requirements, and decrease need for invasive ventilation in patients un-
responsive to conventional therapies [163]. Other studies have also sug-
gested that ketamine may improve pulmonary function in patients with
severe bronchospasm unresponsive to traditional therapy [164-173].
There are two main dosing strategies for ketamine. Subdissociative
dose ketamine is intended to help improve pulmonary function while
keeping the severely distressed patient awake and comfortable [162-
173]. As discussed below in “non-invasive positive pressure ventila-
tion”, dissociative dosed ketamine may be used to facilitate non-
invasive positive pressure ventilation or for induction of rapid sequence
intubation. Importantly, ketamine may increase bronchial secretions,
which can help relieve mucous plugs, but may transiently increase the
work of breathing [162,163,173].
3.4.7. Helium-oxygen
Helium‑oxygen mixtures (70–80% helium and 20–30% oxygen) have
been used in patients who are refractory to other therapies.
Helium‑oxygen mixtures have been proposed to decrease airway resis-
tance, lower the work of breathing, and improve ventilation due to the
lower density of helium when compared with other molecules [174-
179]. As a result, the lower density mixture may be able to deliver bron-
chodilators and anticholinergic agents more effectively than with oxy-
gen alone or room air [174-181]. Studies suggest that helium‑oxygen-
driven nebulized bronchodilator therapy improves pulmonary function
compared to air-driven nebulization in patients with severe asthma
[174-181]. A 2014 meta-analysis of 10 trials suggested that
helium‑oxygen-driven therapies improved pulmonary function and re-
duced hospital admission in those with severe asthma (odds ratio 0.49,
95% confidence interval 0.31–0.79) [180]. However, limited availability
in most EDs and a lower concentration of oxygen (20–30%) in the gas
mixture limit its widespread use [174-181].
445
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American Journal of Emergency Medicine 44 (2021) 441–451
3.4.8. Antibiotics
Most respiratory infections associated with asthma exacerbations
are viral in nature [9,10,14,16,17]. A 2018 Cochrane review found lim-
ited evidence that antibiotics given during an exacerbation may im-
prove symptoms or pulmonary function, but findings were limited by
significant heterogeneity between the studies [182]. Therefore, antibi-
otics should be reserved for when pneumonia is diagnosed based on
chest x-ray and clinical assessment.
3.4.9. Non-invasive positive pressure ventilation
NIPPV, including continuous positive airway pressure (CPAP) or
bilevel positive airway pressure (BPAP), should be attempted in those
with severe asthma exacerbation and a respiratory rate N 30 breaths
per minute, significant work of breath, or when refractory to first-line
therapies to avoid or optimize the patient for endotracheal intubation
[183-193]. The literature suggests that NIPPV can reduce the need for
intubation, improve patient ventilation, recruit alveoli, and improve
ventilation-perfusion mismatch [185-189]. Authors of this review rec-
ommend using BPAP compared to CPAP as this is more consistent
with the pathophysiology of airway obstruction and ventilatory failure
in asthma. In asthma, the additional benefit of the pressure support of
BPAP can improve air movement [194].
NIPPV should be initiated using inspiratory pressure support of
5–10 mmHg, with a positive end-expiratory pressure (PEEP) of
3–5 mmHg [189,190,195]. When titrating the BPAP, it is preferable to
increase the inspiratory pressure (i.e., pressure support) to improve
ventilation while maintaining expiratory pressure (i.e., PEEP)
[189,195]. If using NIPPV, clinicians should directly monitor and fre-
quently reassess the patient's work of breathing and respiratory rate.
Tidal volume should aim for at least 5 cm3/kg, as lower tidal volumes
are associated with ineffective ventilation, while the minute ventilation
should approximate 4–5 liters per minute (LPM) [189,195]. In-line neb-
ulized beta agonists and anticholinergic medications should be contin-
ued during NIPPV [9,10,17]. A 2012 Cochrane review found that
patients with severe asthma exacerbations who were treated with
NIPPV versus no NIPPV had a shorter hospital length of stay and reduced
need for endotracheal intubation; however, there was no reduction in
mortality [191].
Relative contraindications to NIPPV include recent esophageal sur-
gery or trauma, upper airway deformities, copious secretions, signifi-
cant facial hair preventing an adequate seal, or lack of patient
cooperation [17,185,192,193]. Hypercarbia, pH b 7.25, and altered men-
tal status are not contraindications for NIPPV [17,189,195]. While al-
tered mental status will require more close monitoring of the patient,
it is not an absolute contraindication to NIPPV as long as a provider is
closely watching the patient [17]. NIPPV may actually improve the men-
tal status in patients with severe asthma exacerbation associated with
hypercarbia or hypoxemia.
Patients who are unable to cooperate with NIPPV may benefit from
procedural sedation agents, such as ketamine or dexmedetomidine,
with a goal of improving oxygenation and ventilation with NIPPV,
though the patient should be prepared for intubation if the patient
does not tolerate or fails NIPPV [196,197]. Ketamine is an optimal
agent, as patients can retain their respiratory drive and airway reflexes
in their dissociated state [198,199], while facilitating tolerance of NIPPV.
One study of ketamine utilized for preoxygenation before endotracheal
intubation in patients with altered mental status preventing
preoxygenation found that patients improved their oxygenation by
8.9% on average with ketamine, from 89.9% to 98.8% [196]. Two patients
with severe asthma improved sufficiently enough to avoid intubation
[196]. Dexmedetomidine is a titratable alpha-2 agonist medication
that provides sedation while also preserving the respiratory rate [200].
Dexmedetomidine may have bronchodilatory effects, but its onset of ac-
tion is slower compared to ketamine with 10–15 min [200]. Boluses of
dexmedetomidine can result in hypotension and bradycardia and
should be avoided.
B. Long, S. Lentz, A. Koyfman et al.
Fig. 3. Management of acute ventilator decompensation.
3.4.10. High-flow nasal cannula
High-flow nasal cannula (HFNC) provides heated, humidified oxy-
gen with flow rates of up to 60 LPM and may be used as an alternative
to NIPPV in patients with relative contraindications or those with poor
tolerance to the facemask [201-203]. HFNC reduces anatomic dead
space by increasing airway pressures and reducing expiratory flow re-
sistance, but it does not significantly improve tidal volumes [204,205].
Currently, there is limited evidence directly assessing this in adult
asthma, with the majority of the adult literature pertaining to acute
hypoxemic respiratory failure from other etiologies, such as acute respi-
ratory distress syndrome and community-acquired pneumonia [201-
203]. HFNC has been shown to be beneficial in pediatric patients with
severe asthma [205,206], but further study in adult severe asthma is re-
quired before routine use.
3.4.11. Endotracheal intubation
Endotracheal intubation is associated with increased morbidity and
mortality, with mortality rates approaching 20% among intubated pa-
tients admitted to the intensive care unit [207]. Therefore, intubation
should be avoided when possible in asthmatic patients [9,10,14,17].
However, intubation and mechanical ventilation may be necessary in
patients with severe respiratory distress that does not improve with
the aforementioned interventions [9,10,14,17,208,209]. Other relative
indications include worsening mental status with inability to protect
their airway, inability to maintain respiratory effort, and refractory hyp-
oxia [9,10,17,209]. If patients require intubation, continuous adminis-
tration of oxygen via nasal cannula during the intubation attempt is
recommended, as well as pre-intubation administration of IV fluids to
improve preload [9,10,17,189,210]. Ketamine is recommended for in-
duction, with succinylcholine or rocuronium as a paralytic
[9,10,14,17,189,211]. If rocuronium is used, a dose of 1.2 mg/kg IV is rec-
ommended, as this has been demonstrated to have a similar time to
onset as succinylcholine [211,212]. When possible, a larger endotra-
cheal tube should be used (i.e., 8.0 mm) to reduce airway resistance
[9,10,189,195].
Fig. 4. A high peak pressure with a reassuringly normal plateau pressure (in this case 69 cm H2O and 18 cm H2O, respectively) suggests an airway resistance problem such as
bronchospasm.
446
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American Journal of Emergency Medicine 44 (2021) 441–451
3.4.12. Mechanical ventilation
While ventilated, patients require scheduled inhaled bronchodila-
tors [9,10,17]. When the patient is placed on the mechanical ventilator,
permissive hypercapnia by allowing for a respiratory acidosis with a pH
of N7.15–7.20, is recommended to avoid barotrauma and reduce auto-
PEEP [189,195,207]. This is generally performed by limiting the tidal
volume and respiratory rate [189,195,207]. Initial ventilator settings
should include volume control with a respiratory rate of 6–10 breaths
per minute, tidal volume of 6–8 cm3/kg of ideal body weight, and inspi-
ratory flow rate of 80–120 L/min [189,195,207]. A longer expiratory
time is recommended (inspiration-to-expiration ratio of N1:4), and
PEEP should begin at 0–5 mmHg. A small amount of PEEP can reduce
work of breathing by stenting open the airways during exhalation, re-
duce the risk of ventilator-induced pulmonary injury, and reduce the ef-
fort required to trigger the ventilator [189,195,207].
A variety of causes may result in rapid decompensation of the me-
chanically ventilated patient. Etiologies include displaced endotracheal
tube, obstruction of the endotracheal tube (patient biting, kink, mucous
plug), pneumothorax, equipment failure, and stacking of breaths or
auto-PEEP [189,195]. A treatment strategy for managing acute ventila-
tor decompensation is demonstrated in Fig. 3.
A patient who is decompensating while mechanically ventilated
should be assessed with determination of peak and plateau pressures
[189,195,207]. Peak pressures can be obtained directly from the ventila-
tor. Plateau pressure can be assessed with an end-inspiratory breath
hold maneuver in a passive patient. The plateau pressure estimates
the average pressure in the alveoli at end inspiration and reflects the
compliance of the respiratory system [195,207]. Clinicians should target
a goal plateau pressure of b30 cm H2O [195]. High peak pressures with
normal plateau pressures suggest an issue with airway resistance
(Fig. 4), such as bronchoconstriction or mucous plug, and may benefit
from more aggressive beta-agonist therapy. However, patients with
high peak and plateau pressures may be experiencing an issue with pul-
monary compliance or overdistension (e.g., breath stacking, pneumo-
thorax, acute respiratory distress syndrome). Auto-PEEP should be
suspected if the plateau pressure N 30 cm H2O or if there is incomplete
B. Long, S. Lentz, A. Koyfman et al. American Journal of Emergency Medicine 44 (2021) 441–451

Fig. 5. Waveform capnography demonstrating normal versus inadequate exhalation.

exhalation of the flow waveform (Figs. 5 and 6). Patient-ventilator
dyssynchrony can occur for multiple reasons including air hunger
from inadequate flow delivery or from difficulty triggering a breath
due to auto-PEEP. Different treatment strategies include increasing the
flow rate or adjusting the flow pattern (i.e. decelerating) to match the
patient's desired flow, adjusting trigger settings, treating auto-PEEP, or
deeper sedation if these adjustments fail [195]. Patients will often at-
tempt to breath over the set rate, resulting in worsening auto-PEEP if
there is incomplete exhalation of the inspired volume. This is treated
by decreasing the respiratory rate, decreasing the inspiratory time,
using a higher flow rate, and decreasing the tidal volume [189,195].
Deep sedation and paralysis will likely be needed in patients with a
rapid respiratory rate or ventilator dyssynchrony. Plateau pressures
that remain elevated despite sedation and appropriate ventilator set-
tings may require inhalational anesthetics or extracorporeal membrane
oxygenation [9,10,16,17,213-215].
3.4.13. Extracorporeal life support
Patients with asthma that is refractory to other therapies may re-
quire extracorporeal life support. Several case series and retrospective
studies suggest extracorporeal life support may benefit patients with
severe asthma associated with pulmonary hyperinflation leading to re-
duced cardiac preload and output [213-215]. This should also be consid-
ered in patients receiving mechanical ventilation with inadequate
oxygenation or a refractory respiratory acidosis. The largest study in-
cludes a registry of 272 patients receiving extracorporeal life support
for asthma [214]. Authors of this study found airway exchange and ox-
ygenation on mechanical ventilator improved with extracorporeal life
support, with a survival-to-discharge rate of 83.5% [214]. However,
complications occurred in 65.1%, with hemorrhage being the most com-
mon (28.3%) [214]. Extracorporeal life support also requires significant
support staff and equipment that is possible in only select centers. If ox-
ygenation and ventilation are unable to be managed by mechanical ven-
tilation, referral to an extracorporeal life support center should be
considered.
4. Conclusions
Asthma is a common condition managed in the ED and can be asso-
ciated with significant morbidity and mortality. It is important to con-
sider a broad differential diagnosis for the etiology and potential
mimics of asthma exacerbation. The majority of assessment is based
upon the clinical examination with a focus on the patient's respiratory
and hemodynamic status. First-line therapy for severe exacerbations in-
cludes inhaled short acting beta agonists and anticholinergics combined
with intravenous steroids and magnesium. Patients refractory to these
treatments may benefit from parenteral beta agonists, inhaled
helium‑oxygen mixture, and ketamine. As many of these patients are
dehydrated, intravenous fluids are recommended. NIPPV can be
attempted and may improve patient respiratory function and avoid in-
tubation. If mechanical ventilation is required, permissive hypercapnia
is recommended to avoid breath stacking.

Fig. 6. A high peak and plateau pressure (42 cm H2O and 35 cm H2O, respectively) suggest an issue with lung compliance or rising auto-PEEP.

447

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B. Long, S. Lentz, A. Koyfman et al.
Conflicts of interest
None.
Credit author statement
MG, BL, SL, and AK conceived the idea for this manuscript and con-
tributed substantially to the writing and editing of the review.
Acknowledgements
This manuscript did not utilize any grants or funding, and it has not
been presented in abstract form. This clinical review has not been pub-
lished, it is not under consideration for publication elsewhere, its publi-
cation is approved by all authors and tacitly or explicitly by the
responsible authorities where the work was carried out, and that, if ac-
cepted, it will not be published elsewhere in the same form, in English
or in any other language, including electronically without the written
consent of the copyright-holder. This review does not reflect the views
or opinions of the U.S. government, Department of Defense, U.S. Army,
U.S. Air Force, or SAUSHEC EM Residency Program.
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