[ Asthma How I Do It ] Z CHEST

Management of Life-Threatening Asthma (@ e

Severe Asthma Series
Orlando Garner, MD; James Scott Ramey, MD; and Nicola A. Hanania, MD, FCCP

Asthma exacerbations can be life-threatening, with 25,000 to 50,000 such patients per year
requiring admission to an ICU in the United States. Appropriate triage of life-threatening
asthma is dependent on both static assessment of airway function and dynamic assessment
of response to therapy. Treatment strategies focus on achieving effective bronchodilation with
inhaled p,-agonists, muscarinic antagonists, and magnesium sulphate while reducing inflam-
mation with systemic corticosteroids. Correction of hypoxemia and hypercapnia, a key in
managing life-threatening asthma, occasionally requires the incorporation of noninvasive me-
chanical ventilation to decrease the work of breathing. Endotracheal intubation and mechanical
ventilation should not be delayed if clinical improvement is not achieved with conservative
therapies. However, mechanical ventilation in these patients often requires controlled hypo-
ventilation, adequate sedation, and occasional use of muscle relaxation to avoid dynamic hy-
perinflation, which can result in barotrauma or volutrauma. Sedation with ketamine or propofol
is preferred because of their potential bronchodilation properties. In this review, we outline
strategies for the assessment and management of patients with acute life-threatening asthma
focusing on those requiring admission to the ICU. CHEST 2022; 162(4):747-756
KEY WORDS: critical care medicine; life-threatening asthma; mechanical ventilation; respiratory
failure; sedation

Introduction mechanical ventilation. In one study, of

Patients with asthma often experience severe 33,000 patients with acute asthma
exacerbation of the disease that, on occasion, exacerbation requiring hospital care,
‘may be life-threatening." Although the 10.1% required admission to the ICU and
prevalence of asthma generally has increased 2.1% required intubation and invasive
in most countries, the incidence of life- mechanical ventilation (IMV).” Therefore, it
threatening exacerbations has decreased is imperative for clinicians working in an ICU
because of the improvement in management to be familiar with the proper assessment and
strategies, therapies, and health-care access.” management strategies of life-threatening
It is estimated that of 2 million patients with asthma exacerbation (LTAE).
asthma exacerbations seeking treatment at
the ED in the United States every year, Case Presentation
approximately 25,000 to 50,000 patients will A 41-year-old man with history of asthma
require ICU admission, with some requiring was seen in the ED reporting shortness of

ABBREVIATIONS: DHI = dynamic hyperinflation; ECMO = extracor- AFFILIATIONS: From the Section of Pulmonary, Critical Care and
poreal membrane oxygenation; HENC = high-flow nasal cannula; Sleep Medicine (O. Garner and N. A. Hanania), and the Department of
IMV = invasive mechanical ventilation; LTAE = life-threatening Medicine (. S. Ramey), Baylor College of Medicine, Houston, TX.
asthma exacerbation; NIV = noninvasive ventilation; NMB = neuro- CORRESPONDENCE T0: Orlando Garner, MD; email: oege311986@
muscular blockade; PEEP = positive end-expiratory pressure; PEF = gmail.com
peak expiratory flow; Ppaw = peak airway pressure; SA = static Copyright © 2022 American College of Chest Physicians. Published by
assessment; SABA = short-acting f,-agonist; SpO, = oxygen saturation Elsevier Inc. All rights reserved.
DO https://doi.org/10.1016/j.chest.2022.02.029

chestjournal.org 747
breath, productive cough, and wheezing that began based on six parameters obtained by clinical evaluation
3 days previously. He did not report fever, sick contacts, and classifies patients according to mild, moderate, and
chest pain, nausea, vomiting, or reflux, but had nasal severe exacerbations. Severe and moderate exacerbation
congestion and postnasal drip of 1 year’s duration. He groups have an OR for hospitalization of 12.2 (95% CI,
disclosed that he recently was discharged from the 7.5-19.9) and 5.6 (95% CI, 3.5-8.9), respectively, when
hospital after experiencing another asthma exacerbation, compared with the mild exacerbation group. A
but had not filled the prescription given to him on simplified severity score may aid in disposition of
discharge for controller medication and had been using patients in the ED and in the decision for ICU
only his rescue medication multiple times during the day admission.
and night. He has five dogs at home and has a 10-pack-
year history of smoking. On examination, temperature
Static assessments (SAs) and dynamic assessments of
acute asthma exacerbation in the ED also can help to
was 36 °C, heart rate was 116 beats/min, respiratory rate
triage patients. SA looks at severity at presentation,
was 28 breaths/min, and BP was 164/79 mm Hg, with an
which in turn determines the aggressiveness of initial
oxygen saturation (SpO,) of 90% on room air. He was
treatment. SA includes obtaining history of treatment
sitting upright, using accessory muscles, and could not
adherence, severity of current exacerbation compared
speak in complete sentences. Cardiac examination
with previous episodes, and prior hospitalization or need
revealed tachycardia without any extra heart sounds.
for mechanical ventilation. Physical examination also
Diffuse wheezes were heard throughout both lung fields.
can help to determine severity of illness. Tripoding and
In the ED, he was started on albuterol nebulization every
use of accessory muscles correlate with increased
20 min along with oxygen 3 L by nasal cannula,
severity. Similarly, the absence of breath sounds (silent
improving SpO, to 93%. However, the work of breathing
lungs) and presence of abdominal paradox breathing are
did not improve, and abdominal paradox was observed
red-flag features of an underlying life-threatening
at bedside. Chest radiography showed hyperinflation,
asthma episode. Objective SAs include the measurement
but no infiltrates, and venous blood gas revealed a pH of
of peak expiratory flow (PEF), FEV}, or both. A severe
7.28 and Pco, of 54 mm Hg. The patient received
exacerbation usually is defined as a PEF or FEV of less
125 mg of methylprednisolone intravenously and an
than 50% to 60% of predicted normal values.
infusion of 2 g of magnesium sulfate and was started on
high-flow nasal cannula. Dynamic assessment is more helpful because it gauges
response to treatment. A lack of improvement in
How We Do It expiratory flow rates after initial bronchodilator therapy
with continuous or worsening symptoms suggests the
Triaging need for hospitalization.” Ventilation and perfusion
Appropriate disposition is vital in the management of mismatch is very common in acute asthma, and
acute asthma to avoid complications and to prevent significant hypoxemia and hypercapnia may occur
death. Danker et al' proposed a simplified severity score during an acute severe episode. However, depending on
for asthma evaluation in the ED. This score (Table 1)" is oxygen saturation alone sometimes may be misleading,

TABLE 1 ] Simplified Severity Score for Acute Asthma®

Severity Score
Sign or Symptom Severe
Pulse rate, beats/min <90 91-119 > 120
Wheezing Absent Present Present
Rales Absent Present Present
Prolonged expirium Absent Present Present
Oxygen saturation, % 95-100 90-94 <89
Use accessory muscles Absent Present Present
Minimal no. of parameters Any 3 of the above Any 3 of the above or the use Any 3 of the above or oxygen
required to qualify for of accessory muscles only saturation of < 89% only
categories

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and therefore blood gas examination or end-tidal administered in combination with SABAs, and it seems
capnography often are valuable tools for complete that its benefit is limited to patients with severe
assessment. ICU admission should be considered in
;
disease.' 213
”"
patients with hypoxemia (SpO, < 92%) despite the use Systemic Corticosteroids: Systemic corticosteroids
of supplemental oxygen, worsening hypercarbia,
improve outcomes in patients with acute asthma and
encephalopathy, presence of arrhythmia, or evidence of
reduce the likelihood of repeat exacerbation. They
barotrauma (pneumothorax or pneumomediastinum) or
should be administered as soon as possible, because
for those who require oxygen by high-flow nasal cannula
clinical effects may take 6 to 12 h to take effect.'*
(HENC), noninvasive ventilation (NIV), or IMV.®
Although no significant difference in efficacy exists
between oral and IV corticosteroids, the degree of
Pharmacologic Management of Acute Asthma
respiratory distress may dictate the route of
The main therapeutic goals for acute asthma are reversal administration.'” We recommend starting with IV
of bronchospasm and correction of hypoxemia. In methylprednisolone in those with severe respiratory
addition, implementing plans to prevent recurrence is distress who are being admitted to the hospital or ICU.
crucial. The cornerstone, initial, conventional The potential role of inhaled corticosteroids in
pharmacologic management of acute asthma includes managing acute asthma has not been evaluated fully in
the administration of repeated doses of inhaled short- large trials, although some studies in children and adults
acting B,-agonists (SABAs), inhaled short-acting suggest a benefit."”
anticholinergics (short-acting muscarinic antagonists),
systemic corticosteroids, and on occasion, IV Magnesium Sulphate: Magnesium sulphate acts as a
‘magnesium sulfate. bronchodilator by inhibiting calcium channels and
blocking parasympathetic tone.'” The role of IV
Inhaled SABAs: SABAs are the first-line treatment for magnesium in the treatment of acute asthma has been
acute asthma. Continuous nebulization of albuterol is a studied as an adjunct therapy to SABAs, ipratropium
safe approach, but intermittent dosing also is reasonable bromide, and corticosteroids. Evidence has shown that
and is implemented more commonly (Table 2). Use of this intervention reduced hospital admissions in severe
metered-dose inhalers with spacers allows for targeted asthma and improved pulmonary function, but it has
albuterol dosing, but offers no significant advantage over not been found to reduce mortality or need for NIV."
nebulization.”* Also a high-dose strategy (7.5 mg) offers The use of nebulized magnesium sulphate is much less
no benefit over a low-dose (2.5 mg) of albuterol.” IV f,- clear, and studies have not shown consistent benefit."*
agonists should be reserved for when inhaled therapy is
not feasible.” Controlled Oxygen Therapy: Acute asthma is
associated with significant V/Q mismatch with perfusion
B,-Agonists with higher intrinsic efficacy (full agonists), of nonventilated areas causing hypercarbia and
such as formoterol and isoproterenol, may offer a hypoxemia.'”* If concomitant hypoxemia occurs
theoretical advantage over a partial agonist such as (Pao, < 55 mm Hg or SpO, < 90%), oxygen therapy
albuterol, especially when the latter does not yield a should be initiated with a goal SpO, of > 92%.
significant response. For example, the full agonist Hyperoxia may be harmful in some patients and should
isoproterenol demonstrated superiority to albuterol in be avoided whenever possible.””” A randomized
improvement of lung function and symptoms in asthma controlled trial found that patients who received
exacerbations. However, the potential for systemic 28% oxygen, compared with 100% oxygen, showed a fall
adverse effects by activating receptors on nontarget sites in Paco,, and those in the latter group showed an
such as the heart is higher."" increase.”’ Therefore, conservative SpO, targets should
be pursued in patients with acute severe asthma and
Inhaled Short-Acting Muscarinic Antagonists:
those with impending respiratory failure.
Ipratropium bromide relaxes bronchial smooth muscle
by antagonizing the muscarinic M3 receptor on smooth HENC: Although HENC is useful in patients with
muscle of the airway, alleviating airway obstruction. respiratory failure such as acute lung injury and ARDS,
Compared with SABAs, it has a slower onset of action its role in acute severe asthma has not been well
(60-90 min) coupled with an average potency established. A study of 36 patients assigned to either
(15% increase in PEF) and unsustained benefits after ED HENC or conventional oxygen therapy did not
admission. When used, ipratropium bromide should be demonstrate any difference in clinical response,

chestjournal.org 749
TABLE 2] Pharmacotherapy in Asthma Exacerbation

Medication Comments
Inhaled bronchodilators
Albuterol nebulization 2.5-5 mg every 20 min for 3 doses, then
2.5-10 mg every 1-4 h as needed or
10-15 mg/h continuously
MDI (90 ig/puff) 4-8 puffs every 20 min up to 4 h, then every
1-4 h as needed
Isoproterenol nebulization 7.5 mg/h for 2 h No longer available in the United
States
Ipratropium bromide 0.5 mg every 20 min for 3 doses, then as
nebulization needed
MDI 8 puffs every 20 min as needed up to 3 h
Systemic bronchodilators
Epinephrine
IM 1:1,000 (1 mg/mL) 0.3-0.5 mg IM every 20 min up to 3 doses
Subcutaneous 1:1,000 0.3-0.5 mg subcutaneously every 20 min up
(1 mg/ml) to 3 doses
Intravenous 0.1 pg/kg/min
Terbutaline Titrate by 0.1-0.2 ug/kg/min based
on response or toxicity
Subcutaneous 0.25 mg subcutaneously every 20 min for
3 doses
Intravenous Bolus 4-10 pg/kg followed by continuous
infusion of 0.2-0.4 jg/kg/min
Albuterol Not available in the United States
Intravenous 10-15 pg/kg (maximum, 250 ig) over 5-10
min, which can be repeated every 5 min
Aminophylline Not recommended by current
guidelines
Intravenous 6 mg/kg over 30 min followed by an infusion Serum levels should be checked and
of 0.5 mg/kg/h kept between 8 and 12 jg/mL
Corticosteroids
Methylprednisolone 40-60 mg IV every 6 h for 24 h, taper to
40-60 every 12 h if improved
Prednisone 40 mg po daily for 5 d
Other medications
Magnesium sulfate 1-2 g IV over 20 min
Sedatives and muscle relaxants
Ketamine May cause laryngospasm
Subanesthetic dosing infusion 0.1-0.5 mg/h
Dissociative dosing infusion 1-4 mg/h
Dexmedetomidine May cause myocardial depression
Infusion 0.2-0.7 ug/kg/h
Propofol
Infusion 5-50 ug/kg/min
Cisatracurium
1V bolus followed by infusion Loading 0.1-0.2 mg/kg followed by infusion
of 1-3 ug/kg/min
MDI = metered-dose inhaler.

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although a signal of improved heart and respiratory rate Heliox has two preparations, 70:30 and 80:20, which can
was found in the HFNC group.”* HENC can be used in be delivered via face mask, nebulizer, or nonrebreather
acute severe asthma, but it should not delay the use of mask or through IMV.*" A meta-analysis found that
NIV or endotracheal intubation. heliox was associated with improvement in PEF,
especially in severe (PEF > 50% predicted) and very
Case Presentation: Update
severe (PEF < 50% predicted) exacerbations.”’ Heliox
The patient was admitted to the ICU; however, can be used in patients with severe bronchospasm who
respiratory distress worsened despite treatment. He do not respond to conventional therapies to facilitate
became unable to speak and continued to assume a medication delivery, and it has been reported to decrease
tripod posture, and subcostal retractions became dynamic hyperinflation (DHI), reducing the work of
notable. He became hemodynamically unstable, with breathing and hypercarbia. Its effects in reducing
minimal tachypneic and lung sounds. The patient intubation remain unknown. We favor using heliox over
progressed to LTAE, prompting a move to the ICU, and not using it. If intended effects are not seen within 15
warranted consideration for other avenues of treatment min, the therapy should be abandoned.””
and respiratory support.
Biologics
Pharmacologic Management of LTAE
Interest has been expressed in the use of biologics to
Systemic f3,-Agonists: When inhaled SABA treatment
reduce eosinophils in those with asthma. Benralizumab
is not possible, IV albuterol is recommended by some
national guidelines, although it is not available in the
is an IL-5 receptor antibody that has been able to
United States.””*’ Epinephrine has bronchodilating
produce eosinopenia after a single dose. Nowak et al I
effects and can be used with various presentations
demonstrated that single-dose benralizamab coupled
(Table 2). Systemic terbutaline is another B,-agonist that
with steroids reduces the rate and severity of
exacerbations in those seeking treatment at the ED and
can be used for asthma refractory to inhaled
therapeutics. Although strong evidence of superiority of
suggested possible efficacy in patients with asthma
exacerbations with contraindications to steroids.
its use is lacking, it can be useful in patients who are not
responding to conventional therapy. Caution is advised
However, the usefulness of other biologics in treating
acute asthma has not been evaluated, and none of them
in patients with tachyarrhythmias and hypokalemia.”*
is approved for treatment of acute exacerbations.
Side effects include those commonly seen with inhaled
albuterol, including hypokalemia, hyperlactatemia, Ventilation in LTAE
hyperglycemia, tachycardia, and tremors.”
NIV: Few studies have examined the effect of NIV
Methylxanthines: Aminophylline is a methylxanthine (either biphasic positive pressure ventilation or CPAP)
that traditionally has been used as an infusion in acute in patients with LTAE. A Cochrane review concluded
asthma. It is a nonselective phosphodiesterase inhibitor. that the use of NIV with standard of care may be
However, aminophylline is an inferior bronchodilator to beneficial. Although no clear benefit in mortality or rate
SABA monotherapy. Furthermore, aminophylline is of intubation was found, statistically significant
associated with an increased risk of nausea, vomiting, improvements occurred in respiratory rate, PEF, FEV;,
and tachyarrhythmias. Because of the safety profile of number of hospital admissions, and length of ICU and
aminophylline, its use is no longer recommended in the hospital stays.™
treatment of acute asthma.””
CPAP at 10 cm H,O can be used as a rescue therapy
Heliox (Helium Plus Oxygen) from intubation, although we favor the use of biphasic
Normal airflow in the medium and small airways is positive pressure ventilation.” Biphasic positive
laminar; during a life-threatening asthma episode, pressure ventilation allows use of expiratory positive
airflow in these airways often becomes turbulent, airway pressure to match autopositive end-expiratory
increasing the work of breathing. Helium has a lower pressure (PEEP) and inspiratory positive airway
density and higher viscosity than regular air, and thus pressure to create a driving pressure to support the work
can improve airflow through narrow airways. Heliox is a of breathing. We recommend starting at an expiratory
combination of helium and oxygen that reduces positive airway pressure of 5 cm H,O and an inspiratory
turbulent flow and promotes laminar flow. However, positive airway pressure of 10 cm H,0 and titrating Fio,
Fio, requirements need to be < 30% for its proper use. for a goal SpO, of approximately 92%. Inspiratory

chestjournal.org 751
positive airway pressure should be titrated for pneumothoraces. Detection of pneumothorax on point-
improvement in the work of breathing, Intubation is of-care ultrasound depends on the lack of movement of
recommended if no improvement in the work of the parietal pleural on the visceral pleura, which is seen
breathing, PEF, FEV, or Pco, occurs within 30 to in patients with asthma exacerbation."’
60 min of initiation. Invasive mechanical ventilation goals in LTAE are to
IMV: Endotracheal intubation remains a rare event in improve delivery of inhaled bronchodilators, to improve
patients with asthma, due in part to the improved work of breathing, and to reduce DHI while preventing
therapeutics and reversible nature of the disease but volutrauma and barotrauma. IMV can be detrimental in
some patients will require IMV. This is especially true in LTAE because it adds positive pressure to an already
patients with refractory bronchospasm. Ideally most high airway pressure, exacerbating DHI further.
patients can be rescued from intubation, but those who Excessive DHI affects preload through high
present with frank respiratory distress, encephalopathy intrathoracic pressure, resulting in hemodynamic
or are hemodynamically unstable should be intubated. instability. Efforts must be made to relieve airway
Airway management of patients with LTAE is crucial pressure and to decompress DHI with the ventilator
because they usually have poor reserve, bag-mask settings.
ventilation can further worsen DHI, acidosis can
Mechanical ventilation can be achieved with either
precipitate cardiac arrest, and hemodynamic instability
assisted and controlled volume-cycled ventilation or
may arise from insensible losses. Patients with LTAE
with assisted and controlled pressure-cycled ventilation.
should always be considered as difficult airways due to
The focus of initial ventilator settings should be to
potential complications that may arise peri-intubation.
reduce DHI and to prevent lung injury. This is
A large endotracheal tube (> 8 mm) is favored to relieve achievable by manipulating the minute ventilation,
the airway resistance generated through IMV."® Delayed inspiratory to expiratory ratio, and peak airway pressure
sequence intubation is an alternative to rapid sequence (Ppaw). Initially a low respiratory rate (8-10 breaths/
intubation that can be beneficial in LTAE. Delayed min) should be set to allow a prolonged expiration
sequence intubation intends to separate the induction (Fig 1). Monitoring DHI response to low minute
agent from the paralytic to resuscitate, preoxygenate and ventilation can be seen in flow-time scalar. The
denitrogenate better. Peri-intubation resuscitation can expiratory portion of this scalar should come back to
prevent hemodynamic instability in patients who might baseline before a new breath is initiated, suggesting
have become hypovolemic from insensible losses.”” The resolution of DHI. If breath stacking continues (ie, flow-
shock index is a simple bedside calculation (heart rate/ time curve does not return to 0 before a new breath is
systolic BP) that can help to identify occult shock and is started), decreasing the inspiratory time will allow for a
predictive of peri-intubation cardiac arrest. If a patient faster breath to be delivered and for more time to be
has a shock index of > 1, pre-emptive resuscitation with spent in expiration at the expense of increased Ppaw.
fluids or vasopressors is needed.” Ketamine should be Ideally, the inspiratory to expiratory ratio should be set
used as an induction agent because it does not cause at 1:2, but in LTAE, a ratio of 1:3 or 1:4 is acceptable. If
hemodynamic instability.”” As soon as the SpO, goal is breath stacking persists, disconnection from the
achieved, paralysis with rocuronium is favored. ventilator circuit while gently compressing the chest for
Rocuronium will allow patients to be passive while 30 to 60 s can be performed. Gentle chest compressions
receiving IMV after intubation, facilitating ventilator at end expiration during IMV has been reported as a
management. Bag-mask ventilation should be avoided maneuver to improve DHI. Deep sedation, or
because it can worsen DHI or cause barotrauma. neuromuscular blockade (NMB), may be needed."'
Barotrauma occurs as a result of high pressures in distal The tidal volume should be set approximately 6 to 8 mL/
airways. Pneumomediastinum or pneumothorax must kg of ideal body weight. Careful attention should be paid
be suspected in patients with tracheal deviation, crepitus, to plateau pressure, with a goal of < 30 cm H,O while
or sudden loss of breath sounds. Imaging studies are adjusting tidal volume or respiratory rate to avoid lung
required to make the diagnosis. Portable chest injury. Ventilation may be limited because of high Ppaw
radiographs may be used, but may not be readily and plateau pressure, but usually hypercarbia is well
available. Point-of-care ultrasound can be useful, but tolerated up to Paco, of 90 to 100 mm Hg. Permissive
hyperinflated lungs may be confounded by hypercarbia should be allowed to a pH of > 7.20 in those

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 Shortness of Breath
Tachypnea
Wheezing

SABA, SAMA, SCS, oxygen

Mild: Any 3 mild symptoms from Table 1
Moderate: Any 3 moderate symptoms
Calculate from Table 1 or accessory muscle use
Simplified Severity
Sc ore. Severe: Any 3 severe symptoms from
Table 1 or SpO, < 89%

Mild
Symptom
Improvement

Consider MgSO, Gonsider discharge home

Glinical Improvement?
No Yes

Icu
Evidence of Hypercapneic Inpatient admission
Respiratory Failure or
Diaphragmatic Fatigue

IPAP 10 cmH20 Consider

EPAP 5 cm H20 Systemic Bronchodilators.
Tolerated? Heliox

Encephalopathy
Delayed Sequence RR > aowt:rea?:s/r)vlfin
Intubation pH <7.20, Pco, > 90

Mechanical Ventilation Ketamine

Initial Settings: Propofol
AC, Fio, 100%, RR 8-10 breaths/min NMB|
PEEP < 5 cmH20, TV 6-8 kg of IBW
Keep Pplat < 30 cmH20 Worsening dynamic hyperinflation Decrease Ti
Volutrauma or barotrauma Temporary Disconnect from MV
Mechanical Chest Compression
Consider
Bronchoscopy + NAC if atelectasis® *In extremis situations.
Gas Anesthesia / ECMO/ECCO2-R"
Figure 1 -~ Flowchart showing a management of life-threatening asthma exacerbation algorithm. AC = assist control; ECCO-R = extracorporeal
carbon dioxide removal; ECMO = extracorporeal membrane oxygenation; EPAP = expiratory positive airway pressure; IBW ideal body weight;
MV = mechanical ventilation; MgSO, = magnesium sulphate; Mod = moderate; NAC = N-acetylcysteine; NMB = neuromuscular blockade; PEEP =
positive end-expiratory pressure; RR = respiratory rate; SABA = short-acting 8 -agonist; SAMA = short-acting muscarinic antagonist; SCS = systemic
corticosteroid; SpO, = oxygen saturation; Ti = inspiratory time; TV = tidal volume.

patients without any contraindication (eg, myocardial pressure gradient needed to overcome the auto-PEEP.
depression or intracranial pathologic features). Measuring auto-PEEP should occur at least every 6 h.
Extrinsic PEEP should be set at a low level in intubated Fio; initially should be set at 100%, but then rapidly
patients (< 5 cm H,0). Spontaneously breathing patients titrated down for a goal SpO, of > 92%. If hypoxia
may benefit from matching the auto-PEEP with the extrinsic persists, a workup for alternative causes, including
PEEP. This improves the work of breathing by decreasing the pulmonary shunting, should ensue.”**

chestjournal.org 753
Nonventilatory Strategies for LTAE Infusions should be avoided to prevent myopathy from
Sedation: Patients with LTAE exhibit a degree of the combination of steroids and NMB. Monitoring
breathlessness and feeling of imminent death that are during NMB infusions includes train-of-four and serial
detrimental to NIV use or inhaled medication delivery. creatinine kinase evaluations."
Light sedation can be used to help patients tolerate NIV Inhaled Anesthetics: Inhaled anesthetics can be used in
and to deliver inhaled bronchodilators effectively. Deep patients with LTAE with high Ppaw, excessive
sedation, with or without neuromuscular blockade, may hypercarbia, and refractory bronchospasm who are
be warranted in those requiring IMV. Use of sedatives receiving IMV. Isoflurane or halothane can reduce
should warrant an admission to the ICU because bronchospasm, and evidence of improvement should be
patients will require frequent monitoring. seen quickly, but only while the gases are being
In a nonintubated patient, intermittent dosing of short- administered because their effect is short-lived. These
acting opioids can decrease breathlessness and can anesthetics are delivered through an anesthesia
depress respiratory drive. Boluses of fentanyl can be ventilator, and their use may be limited by the
used because it has a rapid onset of action and a short experience of the ICU staff. Inhaled anesthetics can
half-life. If a favorable response occurs, doses can be cause hemodynamic instability by reducing venous and
repeated every 30 min as needed. Morphine should be vascular tone.””**
avoided because it can cause histamine release.
Extracorporeal Membrane Oxygenation: LTAE is a
Dexmedetomidine is an ¢,-agonist that can be used if reversible condition in which extracorporeal membrane
more sedation is needed. It does not suppress the oxygenation (ECMO) can serve as a bridge to recovery.
respiratory drive and causes appropriate anxiolysis. Although ECMO is required seldomly, those with severe
Effects will be seen within 5 to 15 min, which may be too respiratory acidosis (pH < 7.2) with hemodynamically
long in some patients. unstable DHI can benefit from it. Venovenous ECMO
can be used with ultraprotective lung ventilation. As
Ketamine is an N-methyl-D-aspartate receptor
soon as bronchospasm and respiratory acidosis resolve,
antagonist that can be used at subanesthetic dosing or at
patients can undergo decannulation and extubation.’”"”
dissociative dosing. Ketamine works within seconds, will
not cause respiratory depression, and can have a
The use of ECMO is very limited in acute asthma,
although a recent retrospective study demonstrated
bronchodilation effect. Infusions are started at
benefit for those who required it.”" ECMO potentially
subanesthetic dosing and titrated slowly up to effect.
can increase the risk of sepsis, multiorgan failure, acute
Side effects include bronchorrhea, sialorrhea, and
kidney injury, stroke, bleeding, thrombosis, and
laryngospasm. Benzodiazepines should be avoided
cannula-related complications. Also, its complexity
because they are associated with worse outcomes. As
warrants its implementation in high-volume centers and
soon as ketamine or dexmedetomidine infusions are
may be cost prohibitive, and therefore may not be
started, equipment and induction medications for
feasible in smaller hospitals.”
intubation should be available readily at bedside.
Extracorporeal CO, removal is a form of extracorporeal
Propofol is a good first choice for patients receiving
IMV. It allows for deeper sedation and synchronization gas exchange designed to remove CO; from the blood
across a gas exchange membrane at low blood flow rates
with the ventilator and has bronchodilatory properties. (200-1,500 mL/min). This is performed without a
Using ketamine concomitantly also can potentiate the
clinically relevant effect on oxygenation, as opposed to
bronchodilation and can reduce propofol and opioid ECMO, which is used mainly for oxygen delivery at high
requirements, possibly decreasing the number of days of blood flow rates (2,000-7,000 mL/min). Extracorporeal
IMV.
CO, removal has been referred to as low-flow ECMO
Some patients still may show high ventilator and respiratory dialysis by some clinicians.”* Although
dyssynchrony despite high levels of sedation, depending its role in LTAE remains to be defined, the Protective
on ventilator strategy. These patients may benefit from Ventilation with Veno-venous Lung Assist in
NMB to tolerate the low respiratory rates required to Respiratory Failure (REST) trial did not find a mortality
allow for complete exhalation. This can be facilitated by benefit in patients with acute hypoxic respiratory failure
a bolus of cisatracurium after adequate sedation. compared with those receiving usual care.”’

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Bronchoscopy and Mucolytics: Airflow limitation in Rodrigo GJ, Rodrigo C, Hall JB. Acute asthma in adults: a review.
Chest. 2004;125(3):1081-1102,
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