Airway management in acute severe asthma for emergency medicine and critical care

INTRODUCTION — Most patients with a severe asthma exacerbation can be managed successfully with aggressive use of beta-agonists, anticholinergics, glucocorticoids, and other medications. Infrequently, such medical interventions are insufficient to reverse the immediate course of disease and endotracheal intubation is required.

The medications and techniques used to perform advanced airway management, particularly endotracheal intubation, in the patient with a severe asthma exacerbation will be reviewed here. An algorithm for the management of asthma exacerbations in adults is provided (algorithm 1). Other aspects of the diagnosis and management of severe asthma and of emergency airway management are discussed separately:

●Medical management of severe asthma in adults (see "Acute exacerbations of asthma in adults: Home and office management" and "An overview of asthma management")

●Management of mechanical ventilation in patients with asthma (see "Invasive mechanical ventilation in adults with acute exacerbations of asthma")

●Management of severe asthma in children, including mechanical ventilation (see "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management")

●Evaluation of severe asthma (see "Evaluation of severe asthma in adolescents and adults" and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management")

●Assessment and management of the difficult airway and the performance of rapid sequence intubation (See "Approach to the difficult airway in adults for emergency medicine and critical care" and "Rapid sequence intubation in adults for emergency medicine and critical care".)

PATHOPHYSIOLOGY OF SEVERE ASTHMA — Severe asthma exacerbations have several important pathophysiologic effects. Among the most important are:

●Increased work of breathing from severe airflow resistance due to bronchial mucosal inflammation and edema, constriction of bronchial smooth muscle, and mucus in the bronchial lumen

●Increased intrathoracic pressure from air trapping, which further increases the work of breathing, decreases preload, and increases afterload

●Depletion of catecholamines during prolonged exacerbations

●Dehydration through insensible losses (more important in children)

The pathophysiology of asthma is discussed separately. (See "Pathogenesis of asthma".)

THE DECISION TO INTUBATE — The decision to intubate is a clinical one. A patient with an asthma exacerbation in obvious respiratory distress that the clinician judges to be unsustainable requires prompt intubation. Beyond that, there are no studies or consensus guidelines that predict precisely when intubation is necessary for an asthma exacerbation.

The clinical assessment that a patient in respiratory distress requires intubation involves the patient's appearance, vital signs including oxygen saturation, and the response to therapy. As an example, the patient who is clearly tiring, speaking only in one- or two-word phrases, and demonstrating either increased distress or declining mental status should be intubated prior to the inevitable respiratory arrest of which these findings warn. It is a combination of the severity of bronchoconstriction and the exhaustion of the patient trying to overcome it that sets the stage for respiratory arrest. When the clinician decides that respiratory failure is advanced, progressing, and unlikely to be reversed by further pharmacologic therapy, intubation should be performed expeditiously, before crisis ensues.

Unlike other conditions in which intubation essentially "solves the problem," the dynamic hyperinflation potentially caused or exacerbated by mechanical ventilation for a severe asthma exacerbation can have devastating consequences, including cardiovascular collapse and barotrauma. Therefore, intubation of a patient with acute status asthmaticus should be undertaken only when judged clinically necessary. (See "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Complications' and "Invasive mechanical ventilation in adults with acute exacerbations of asthma", section on 'Adverse effects of dynamic hyperinflation'.)

In most patients (including those with asthma), a simple assessment consisting of three clinical evaluations distinguishes those who require intubation:

●Is there failure of airway maintenance or protection?

●Is there failure of oxygenation or ventilation?

●Is deterioration, particularly of the airway, anticipated? (ie, what is the expected clinical course?)

This general approach to emergency intubation is discussed in detail separately. (See "The decision to intubate" and "Technique of emergency endotracheal intubation in children", section on 'Indications'.)

In the patient with severe acute asthma, the most important indication for intubation is anticipation of the patient's continued deterioration. Without prompt intervention this can lead to severe hypoxemia or respiratory arrest. Irreversible failure of oxygenation or clinical suspicion of ventilatory failure may also develop, prompting emergent intubation.

Clinical findings that portend imminent respiratory arrest in a patient with an asthma exacerbation may include:

●Inability to maintain respiratory effort (ie, extreme fatigue)

●Depressed mental status

●Cyanosis

Note that these findings are not sensitive indicators of severe attacks; many patients with severe airway obstruction will not manifest these signs.

Signs associated with a severe asthma exacerbation may include:

●Accessory muscle use; chest wall retractions

●Brief, fragmented speech

●Inability to lie supine

●Profound diaphoresis

●Agitation

●Rapid, shallow breathing (respiratory rate >25 to 30 breaths/minute)

Although a peak expiratory flow rate (PEFR) or forced expiratory volume in one second (FEV1) less than 40 percent of predicted (less than 200 L/minute in all but the smallest adolescent and adults or based upon height in children over six years of age (table 1)) indicates severe disease, such evaluations are often difficult to obtain, highly variable, and unreliable in patients with severe asthma exacerbations. Arterial blood gases are also rarely helpful in determining the need for intubation in the emergency setting. End-tidal carbon dioxide (EtCO₂) monitoring is noninvasive and provides additional evidence of worsening respiratory function and airway obstruction, and correlates with FEV1 and the partial pressure of carbon dioxide (pCO₂) concentrations obtained by blood gas [1,2]. (See "Carbon dioxide monitoring (capnography)", section on 'Acute respiratory distress'.)

Patients with asthma with coronavirus disease 2019 (COVID-19) are more likely to be intubated and likely to be ventilated longer compared with patients without asthma, particularly those who are younger and obese. Despite this, the overall mortality is unchanged in patients with asthma when adjusting for comorbidities. In general, clinicians should try to maintain a higher threshold for intubation in patients with severe asthma with coexisting COVID-19 [3-5]. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Advice related to Covid-19 pandemic'.)

RESPIRATORY THERAPIES FOR PATIENTS NOT REQUIRING IMMEDIATE INTUBATION — In addition to the administration of bronchodilators and other medical therapies, several respiratory treatments can be used in a patient suffering from a severe, acute asthma exacerbation but who is not on the brink of respiratory failure.

Noninvasive positive pressure ventilation — Endotracheal intubation and mechanical ventilation can lead to severe complications in patients with asthma. One possible alternative in patients who are not on the brink of respiratory failure and do not have other contraindications is noninvasive positive pressure ventilation (NPPV) using bilevel positive airway pressure (BLPAP). BLPAP offers positive airway pressure on inspiration and a lower level of continuous positive airway pressure on expiration.

In some patients with severe respiratory distress, NPPV reduces the work of breathing, decreases airway resistance and the feeling of dyspnea, re-expands collapsed alveoli, and provides rest for the thoracic muscles of respiration. Although evidence is limited, NPPV may reduce the need for invasive mechanical ventilation in patients with asthma. Therefore, a trial of BLPAP prior to invasive mechanical ventilation is reasonable in patients experiencing a severe, persistent exacerbation despite maximal bronchodilator therapy, if they do not already require immediate intubation [6,7]. NPPV is discussed in detail separately. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Noninvasive positive pressure ventilation' and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Asthma exacerbation'.)

Heliox — Heliox may help a patient with a severe asthma exacerbation who needs time to respond to conventional therapy. Heliox has a lower density than oxygen, causing decreased airway resistance and a consequent reduction in the work of breathing. Heliox has been shown to improve respiratory distress and decrease hospital admissions in patients with severe asthma exacerbations [8,9]. It generally comes in a ratio of 70:30 or 80:20 percent helium to oxygen. Heliox has demonstrated greatest benefit for improving symptoms when used as a nebulizing gas for a beta-2 agonist medication [9]. Benefit is generally seen within minutes after the initiation of therapy. The role of heliox in treating severe asthma is reviewed in detail separately. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Helium-oxygen' and "Physiology and clinical use of heliox" and "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Heliox'.)

Oxygen by high flow nasal canula — Oxygen delivered via high-flow nasal cannula (HFNC) can be helpful for patients in severe respiratory distress, particularly those who are alert but hypoxemic and expected to respond to conventional therapy. HFNC provides continuous warmed and humidified oxygen, decreases inspiratory resistance, and reduces the work of breathing. Flows of up to 60 L/minute can wash out carbon dioxide and decrease anatomic dead space. In addition, HFNC may produce positive end-expiratory pressure (PEEP) and increase end-expiratory lung volume. The results of several clinical trials suggest that HFNC reduces respiratory distress early in the treatment of moderate to severe asthma [10] and reduces the need for intubation in children [11,12]. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Preintubation therapies' and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

If intubation is necessary, HFNC can improve preoxygenation and decrease the risk of early desaturation. (See "Rapid sequence intubation in adults for emergency medicine and critical care", section on 'Preoxygenation' and "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications".)

RAPID SEQUENCE INTUBATION

Approach — A patient with a severe asthma exacerbation who is in need of endotracheal intubation is often exhausted with little physiologic reserve and at high risk of sustaining a rapid decline in oxygen saturation and blood pressure after receiving sedating medications and neuromuscular blocking agents. For these reasons, it is important to plan for and achieve intubation as early as possible once the determination has been made that intubation is necessary. Rapid sequence intubation (RSI) is the preferred approach in such cases because it is the most rapid method for securing the airway with the highest likelihood of success [13].

Aspects of RSI of special relevance to patients with severe asthma are discussed below. The general performance of RSI is reviewed separately. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Preoxygenation — Achieving adequate preoxygenation in a patient experiencing a severe asthma exacerbation is extremely difficult, if not impossible, due to their high residual volume and functional residual capacity [14]. The clinician must anticipate rapid oxygen desaturation when performing RSI in such patients, despite maximal efforts at preoxygenation. Patients who do not achieve a SpO₂ above 93 percent have a much faster rate of SpO₂ decline during intubation attempts [15]. General measures to improve preoxygenation, including oxygen delivered by high-flow nasal cannula, are reviewed separately. (See "Rapid sequence intubation in adults for emergency medicine and critical care", section on 'Preoxygenation'.)

If the patient will tolerate it, preoxygenation via active breathing through a bag valve mask provides significantly higher inspiratory oxygen concentrations than a typical nonrebreather mask. The use of noninvasive positive pressure ventilation may also improve preoxygenation, even if it does not successfully reverse the patient's respiratory failure. (See 'Noninvasive positive pressure ventilation' above.)

Many patients with status asthmaticus require positive pressure ventilation either before or between attempts at intubation. Such ventilation should be delivered by bag and mask using a small tidal volume and high inspiratory flow rate with a prolonged expiratory phase, mimicking the approach used during mechanical ventilation. If a normal tidal volume is delivered at a normal rate, breath stacking and increasing auto-positive end-expiratory pressure (PEEP) may lead to further declines in oxygenation and impair the ability to ventilate the patient. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma" and "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Ventilator settings' and "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Ventilation strategy'.)

Positioning and ETT placement — Medications for RSI should be administered to the patient while they maintain the position of greatest comfort, which is generally sitting upright. Once the patient loses consciousness, place the patient in a supine position and perform laryngoscopy and intubation.

Placement of a large endotracheal tube (8 to 9 mm) is desirable in order to minimize airway resistance and facilitate aggressive pulmonary toilet during mechanical ventilation in adults, but tube size should be selected to achieve the most rapid possible intubation [16]. If necessary, the tube can be changed later to one of a larger diameter.

In children between one and eight years of age, the tube size can be calculated based upon age (table 2) (calculator 1). A cuffed endotracheal tube is preferable for all age groups and a cuff pressure should be measured, especially in pediatric patients. Older children and adolescents should have the largest possible tube placed (up to 9 mm internal diameter).

Although cricoid pressure is now considered optional during RSI, it may reduce the flow of air into the stomach should bag-mask ventilation be necessary, particularly given the increased airway resistance from a severe asthma exacerbation.

Pretreatment — Pretreatment should be viewed as a supplementary but nonessential step in RSI. A detailed discussion of RSI pretreatment for reactive airway disease is found separately. (See "Pretreatment medications for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Asthma (elevated airway resistance)'.)

Choice of induction agent — Studies suggest that ketamine and propofol have bronchodilatory properties and thus are suitable induction agents in a patient with a severe asthma exacerbation [13]. Ketamine is preferable because it aids bronchodilation through both direct and indirect mechanisms and helps to maintain blood pressure. Barbiturates, such as thiopental, should be avoided because they can exacerbate bronchospasm through histamine release.

Ketamine is a dissociative anesthetic that provides several benefits for a patient with a severe asthma exacerbation. It acts directly as a smooth muscle dilator, increases circulating catecholamines (thus indirectly dilating smooth muscle), inhibits vagal outflow, decreases production of vasodilatory nitric oxide, and does not cause histamine release. Ketamine is discussed in greater detail separately. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Ketamine' and "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Ketamine'.)

Large, randomized trials to assess the effectiveness of ketamine in the intubation of patients with asthma are lacking. A systematic review of ketamine for children with severe asthma found that ketamine decreased respiratory rate and increased peak expiratory flow and oxygen saturation; adverse effects included increased tracheobronchial secretions and hallucinations that seemed to be dose dependent [17]. A number of studies and case reports suggest that ketamine improves pulmonary function and is of benefit in severe asthma [18-21]. In addition, multiple case series suggest that infusions of ketamine improve pulmonary function in patients with severe asthma.

Not all studies of ketamine have been favorable [22-24]. One randomized, placebo-controlled trial of IV ketamine (0.2 mg/kg bolus followed by an infusion of 0.5 mg/kg per hour) in 53 consecutive nonintubated adults with acute asthma failed to demonstrate benefit [23]. However, the rate of dysphoric reactions, a well-known side effect of ketamine, led the investigators to reduce the initial bolus to 0.1 mg/kg after the first nine patients. In another randomized controlled trial of 68 nonintubated children, IV ketamine showed no benefit compared with placebo in ameliorating severe acute asthma exacerbations during the two-hour infusion period [22].

The use of anticholinergic premedication (eg, glycopyrrolate, atropine) for ketamine induction is not routinely necessary. Even though anticholinergic agents may decrease secretions from ketamine, a consortium study found that the use of these agents during pediatric sedation increased the risk of serious adverse events such as laryngospasm and aspiration [25]. If an anticholinergic agent is felt to be required, we prefer atropine since it is associated with less vomiting and fewer airway and respiratory adverse events during pediatric sedation [26]. The evidence is discussed in detail separately. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Ketamine' and "Pediatric procedural sedation: Pharmacologic agents", section on 'Ketamine'.)

Observational studies suggest that propofol has bronchodilatory effects and is therefore a suitable induction agent in the patient with severe asthma [27,28]. However, propofol can cause hypotension, so it is less ideal than ketamine in these patients, who are predisposed to drop their blood pressure after intubation. There is no high-quality evidence assessing propofol's role in the emergency intubation of patients with severe asthma. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Propofol'.)

Ketofol (ketamine/propofol admixture) has been associated with favorable hemodynamics during intubation and is a reasonable alternative for induction, although few data involving emergency intubation of patients with asthma are available. Ideal ratios appear to be ketamine:propofol 1:3 or 1:4 [29].

Rapid sequence intubation in a patient with asthma — RSI for a patient with asthma includes induction with 1 to 1.5 mg/kg IV ketamine (preferred drug) or 2 mg/kg IV propofol over two minutes. This is followed immediately by 1.5 to 2 mg/kg succinylcholine given by IV push [30]. In patients with contraindications to succinylcholine (eg, hyperkalemia, neuromuscular disease, rhabdomyolysis, or burn or stroke over 72 hours old), rocuronium 1.2 to 1.5 mg/kg IV is used. (See "Rapid sequence intubation in adults for emergency medicine and critical care".)

POST-INTUBATION MANAGEMENT — Mechanical ventilation in a patient with severe asthma can be difficult to manage and is fraught with potential complications, including cardiovascular collapse and barotrauma. Minimizing airway pressures while maintaining adequate oxygenation is the primary goal of management. Mechanical ventilation in patients with asthma exacerbations is discussed in detail separately. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma" and "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Endotracheal intubation and mechanical ventilation'.)

An intubated patient with an asthma exacerbation is usually hypercapnic with a severe acidosis from the elevated partial pressure of carbon dioxide (pCO₂) and lactic acidosis, due to their increased work of breathing and beta-agonist use. To avoid subsequent tachypnea and loss of synchronization with the ventilator, patients should be deeply sedated and receive parenteral opioid analgesia with a non-histamine releasing opioid (eg, fentanyl) in order to achieve complete relaxation and comfort for mechanical ventilation. Whenever possible, sedation and pain scores should be used to determine whether treatment is adequate. In a few instances, neuromuscular blockade may be required to optimize treatment of patients with severe disease. In addition, minimizing hyperinflation by reducing minute ventilation, lengthening expiration time, and using a low level of positive end-expiratory pressure (PEEP) is recommended. (See "Mechanical ventilation of adults in the emergency department", section on 'Sedation and analgesia for the ventilated patient' and "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal" and "Neuromuscular blocking agents in critically ill patients: Use, agent selection, administration, and adverse effects".)

Pharmacologic management of severe asthma exacerbations, which includes short-acting beta-2-selective adrenergic agonists and systemic glucocorticoids, is discussed separately. Use of nonstandard therapies for severe and refractory airflow obstruction, such as biologic agents that target specific pathways in inflammation (eg, IL-5 and IgE), has been described [31,32]; these therapies and agents are also discussed separately. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Emergency department management' and "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Elements of treatment' and "Treatment of severe asthma in adolescents and adults", section on 'Persistently uncontrolled asthma' and "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Nonstandard therapies'.)

The management of acute hypoxemia (such as from pneumothorax, air trapping, mucus plugging, atelectasis, or pneumonia) in an intubated patient with an asthma exacerbation is discussed separately. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma", section on 'Troubleshooting hypoxemia' and "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Complications'.)

In a patient with a severe asthma exacerbation complicated by refractory respiratory acidosis, severe hypoxemia, or hemodynamic instability in the setting of maximal medical management and ventilation settings (ie, "near-fatal" asthma), oxygenation and carbon dioxide removal through an artificial membrane (extracorporeal life support [ECLS]) may be beneficial as a temporizing measure. Use of extracorporeal membrane oxygenation (ECMO) or extracorporeal CO₂ removal (ECCO₂R) for severe asthma has been associated with good outcomes, reduced mortality, and less ventilator-associated lung injury [33,34]. For example, in a retrospective study of 24 patients with near-fatal asthma who were started on ECLS, 83 percent survived to hospital discharge [35]. Survival with ECLS following cardiac arrest from asthma has also been reported [36]. ECLS is discussed in detail separately. (See "Extracorporeal life support in adults in the intensive care unit: Overview" and "Extracorporeal life support in adults: Extracorporeal carbon dioxide removal (ECCO2R)" and "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Extracorporeal membrane oxygenation'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Airway management in adults".)

SUMMARY AND RECOMMENDATIONS

●Decision to intubate – The decision to intubate a patient with a severe asthma exacerbation is a clinical one and can be difficult. Patients in obvious respiratory distress that the clinician judges to be unsustainable require prompt intubation. (See 'the decision to intubate' above.)

●Signs of respiratory distress – Signs of respiratory distress in a patient with an asthma exacerbation may include:

•Inability to maintain respiratory effort (ie, extreme fatigue)

•Depressed mental status

•Cyanosis

•Accessory muscle use; chest wall retractions

•Brief, fragmented speech

•Inability to lie supine

•Profound diaphoresis

•Agitation

•Rapid, shallow breathing (respiratory rate >25 to 30 breaths/minute)

●Potential dangers of mechanical ventilation – Following intubation, the dynamic hyperinflation potentially caused or exacerbated by mechanical ventilation of in a severe asthma exacerbation can have devastating consequences, including cardiovascular collapse and barotrauma. Intubation and mechanical ventilation must be managed with great care.

●Treatments for patients not at immediate risk of respiratory failure – Treatments that may help a patient with a severe, acute asthma exacerbation but not on the brink of respiratory failure include noninvasive positive pressure ventilation (NPPV), helium-oxygen (heliox) gas, and oxygen delivered by high-flow nasal cannula. (See 'Respiratory therapies for patients not requiring immediate intubation' above.)

●Rapid sequence intubation – Rapid sequence intubation (RSI) is the preferred approach for securing the airway. A patient with severe asthma in need of tracheal intubation has little physiologic reserve and is at high risk of sustaining a rapid decline in oxygen saturation and blood pressure after receiving sedating medications and neuromuscular blocking agents. Therefore, it is important to maximize preoxygenation, achieve intubation expeditiously, and be prepared for oxygen desaturation or hypotension immediately following RSI. (See "Approach to the difficult airway in adults for emergency medicine and critical care" and "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

•Preoxygenation – Achieving adequate preoxygenation in a patient experiencing a severe asthma exacerbation can be extremely difficult. Many patients with severe acute asthma require positive pressure ventilation either before or between attempts at intubation. Such ventilation should be delivered by bag and mask using a small tidal volume and high inspiratory flow rate with a prolonged expiratory phase. (See 'Preoxygenation' above.)

•Ketamine is preferred induction agent – We suggest that ketamine (1 to 2 mg/kg IV) be used as the induction agent for RSI in patients with severe asthma (Grade 2C). Ketamine aids bronchodilation and helps to maintain blood pressure. Propofol can be used and possesses bronchodilatory effects but can cause hypotension. (See 'Choice of induction agent' above.)

●Mechanical ventilation – Mechanical ventilation in a patient with severe asthma is fraught with potential complications, including cardiovascular collapse and barotrauma. Minimizing airway pressures while maintaining adequate oxygenation is the primary goal of management. Mechanical ventilation in patients with severe asthma exacerbations is discussed in detail separately. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma" and "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Endotracheal intubation and mechanical ventilation'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Peter Shearer, MD, who contributed to an earlier version of this topic review.