Invasive mechanical ventilation in adults with acute exacerbations of asthma

INTRODUCTION — Intensive therapy with inhaled bronchodilators and systemic glucocorticoids is usually sufficient to reduce airflow obstruction and ameliorate symptoms in patients with acute asthma exacerbations [1]. However, 3 to 5 percent of all patients hospitalized for acute asthma exacerbation develop respiratory failure and require invasive mechanical ventilation [2-5]. Although potentially life-saving, mechanical ventilation and its associated interventions (eg, sedatives, paralytics) can also cause morbidity and mortality [6-10].

In this topic review, the indications, management, and adverse effects of invasive mechanical ventilation in patients with severe acute asthma exacerbation will be reviewed. The pharmacologic treatment of acute exacerbations of asthma and the role of noninvasive positive pressure ventilation are discussed separately. (See "Acute exacerbations of asthma in adults: Home and office management" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

INDICATIONS — The primary indication for mechanical ventilation in an acute asthma exacerbation is acute respiratory failure (ie, insufficient oxygenation or alveolar ventilation). The decision to initiate mechanical ventilation should be based on serial clinical evaluations that consider the severity of airflow limitation (eg, peak expiratory flow), degree of respiratory difficulty (eg, respiratory rate >40/minute, inability to talk), clinical findings (eg, accessory muscle use, intercostal retractions, fatigue, somnolence), hypoxemia, hypercapnia (elevated arterial tension of carbon dioxide [PaCO₂]), and response to therapy [11,12]. Bronchoconstriction can worsen abruptly after placement of an endotracheal tube, so the need for ventilatory support must be weighed against the potential for initial worsening of ventilation. Nonetheless, intubation and mechanical ventilation should not be delayed until the need becomes emergent.

Generally, acute asthma exacerbations are associated with mild hyperventilation and a low PaCO₂. However, with worsening airflow limitation, the high work of breathing leads to fatigue, a resultant decrease in the minute ventilation, and an increase in PaCO₂. Thus, during an acute asthma exacerbation, a PaCO₂ of 42 mmHg or greater, while technically "normal," may suggest incipient respiratory failure. On the other hand, hypercapnia alone is not an indication for mechanical ventilation in the absence of decreased mental status or exhaustion.

NONINVASIVE VENTILATION — The optimal role of noninvasive ventilation (NIV, also called noninvasive positive pressure ventilation [NPPV]), including biphasic positive airway pressure and continuous positive airway pressure ventilation, in acute asthma exacerbations is unclear [4,13-18]. However, a brief trial of NIV may be reasonable in selected patients with impending respiratory failure with careful attention to comorbid conditions [4,18-21]. Failure of NIV to improve oxygenation would be an indication for invasive mechanical ventilation. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Asthma exacerbation'.)

GENERAL APPROACH — The goals of mechanical ventilation during an acute asthma exacerbation are to maintain adequate oxygenation, reduce the work of breathing, and prevent barotrauma due to airtrapping, while waiting for bronchodilator and glucocorticoid medications to reverse the airway edema, inflammation, and bronchoconstriction. While maintenance of a normal arterial tension of carbon dioxide (PaCO₂) is generally a goal of mechanical ventilation, this is not always desirable or achievable in respiratory failure due to asthma, as the amount of ventilation needed to normalize PaCO₂ may contribute to hyperinflation and barotrauma.

Intubation — Intubation should be approached cautiously in patients with severe acute asthma exacerbations because manipulation of the airway can cause laryngospasm and worsening of bronchoconstriction [11]. Venous access and noninvasive monitoring should be in place prior to intubation. The clinician most experienced with airway management should intubate the patient, preferably with a large-bore (≥8 mm) endotracheal tube to minimize airway resistance and enable suctioning [19,22,23]. Oral intubation is preferred over nasal intubation. Issues related to preoxygenation and patient positioning are discussed separately. (See "Airway management in acute severe asthma for emergency medicine and critical care" and "The decision to intubate" and "Direct laryngoscopy and endotracheal intubation in adults".)

Resolution of wheezing and absence of an elevated airway pressure immediately after intubation are clues to an upper airway cause of respiratory failure. Patients with severe asthma exacerbation typically have increased airway pressures; the absence of elevated airway pressures after intubation suggests that upper airway obstruction (eg, vocal cord dysfunction, laryngeal malignancy) may have been contributing to wheezing and respiratory distress. (See "Evaluation of wheezing illnesses other than asthma in adults".)

Induction agents — Once the decision has been made to proceed with intubation, most patients receive rapid sequence induction [24,25]. The most commonly used agents are etomidate, ketamine, and propofol [26]. Etomidate is least likely to cause hemodynamic instability, while ketamine and propofol have more bronchodilating characteristics; however, the optimal agent has not been determined. Most patients will also receive a neuromuscular blocking agent (eg, succinylcholine or rocuronium), unless they have a contraindication [24,25]. The use of induction agents in patients with asthma and general considerations for rapid sequence induction are discussed separately. (See "Airway management in acute severe asthma for emergency medicine and critical care", section on 'Rapid sequence intubation' and "Rapid sequence intubation in adults for emergency medicine and critical care" and "Pretreatment medications for rapid sequence intubation in adults for emergency medicine and critical care" and "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care".)

Opiate medications are avoided due to the risk of histamine release exacerbating bronchoconstriction.

Ventilator mode — Volume-limited modes of ventilation are commonly used for patients with respiratory failure due to acute asthma exacerbation, although the optimal mode is not known and may vary from one patient to another and over the course of a single patient's illness. We typically select one of the following volume-limited modes: assist control ventilation (ACV), synchronized intermittent mandatory ventilation (SIMV), or SIMV with pressure support ventilation (SIMV/PSV) and adjust as needed to achieve synchrony between the patient and the ventilator. Pressure support and pressure-limited modes are less suitable for patients with airflow limitation. If a pressure-limited mode is employed, careful attention must be paid to tidal volume and gas exchange, as the volume delivered varies with airway resistance and lung compliance. (See "Modes of mechanical ventilation" and "Invasive mechanical ventilation in acute respiratory failure complicating chronic obstructive pulmonary disease", section on 'Ventilator modes'.)

Initial ventilator settings — The following are reasonable initial ventilator settings for adults with acute severe asthma [1,24,25,27]:

●Respiratory rate: 10 to 12 breaths/min

●Tidal volume: 6 to 8 mL/kg (ideal body weight) (calculator 1)

●Minute ventilation (respiratory rate multiplied by tidal volume): less than 115 mL/kg/min

●Inspiratory flow: We advise an initial inspiratory flow of 60 L/min, which can be increased if needed to decrease inspiratory time and prolong expiratory time in patients with more severe airflow obstruction. We use 75 L/min as an upper limit. Given the possibility of increased bronchoconstriction at increased flow rates, the impact of changes in flow rate on ventilation should be carefully monitored.

●Allow increased expiratory time by decreasing I:E ratio (1:3 or 1:4 up to 1:5)

●Extrinsic positive end-expiratory pressure (extrinsic PEEP, also known as applied PEEP) less than 80 percent of the intrinsic PEEP, or 5 cm H₂O if intrinsic PEEP is <10 cm H₂O (see 'Adding extrinsic PEEP to offset intrinsic PEEP' below)

●Set the fraction of inspired oxygen (FIO₂) at 100 percent initially and then titrate downwards as tolerated to maintain the pulse oxygen saturation (SpO₂) above 90 percent or the arterial oxygen tension (PaO₂) above 60 mmHg

●Set the sensitivity for triggering a ventilator-assisted breath at -2 L/min

The sensitivity setting determines the inspiratory effort (inspiratory air flow) that the patient needs to generate to trigger a machine-assisted breath. We typically use flow triggering of ventilator-assisted breaths for patients on SIMV, as this appears to decrease the work of breathing compared with pressure triggering. Greater sensitivity of the trigger (eg, -1 cm H₂O) can lead to over-ventilation; lower sensitivity (eg -3 cm H₂O) can increase work of breathing.

Continuing medical management — Administration of inhaled bronchodilator medication (eg, albuterol, levalbuterol, ipratropium) remains an important therapeutic modality during mechanical ventilation. Inhaled medications can be delivered via the ventilator tubing using either a metered dose inhaler (MDI) with a specialized adaptor or a jet or mesh nebulizer. Methods for delivery of inhaled medication during mechanical ventilation and the medical management of acute asthma exacerbations are discussed separately. Pretreatment with bronchodilators prior to intubation can mitigate the increase in airway resistance often seen in asthmatics after tracheal intubation [12]. (See "Delivery of inhaled medication in adults", section on 'Mechanically ventilated patients' and "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Inhaled beta-agonists'.)

Other interventions to treat acute asthma, such as intravenous magnesium and glucocorticoids, should continue during ventilatory support. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management".)

TROUBLESHOOTING HIGH PEAK PRESSURES — For patients requiring mechanical ventilation for a severe asthma exacerbation, several processes can cause high peak pressures (eg, >30 cm H₂O), which in turn can increase the risk of barotrauma. Causes of high peak pressure include airway obstruction, decreased lung/pleural elasticity (eg, hyperinflation, pneumonia, pneumothorax), and patient-ventilator asynchrony.

Differentiating airway and lung parenchymal causes of high pressures — Mechanical ventilators normally display the peak pressure (Ppeak), which is the highest airway pressure measured during each respiratory cycle and reflects the sum of resistive pressure of airways + elastic pressure of lungs + positive end-expiratory pressure (PEEP). The plateau pressure (Pplat) is measured at end-inspiration and represents the pressure in the small airways and alveoli after flow has ceased. To measure Pplat, an inspiratory hold (0.5 to 1 second) is applied at end-inspiration and the airway pressure displayed by the ventilator drops from the peak pressure to the plateau pressure.

●An increase in both Ppeak and Pplat (with less than a 5 cm H₂O difference between them), suggests a lung parenchymal, pleural, or chest wall/diaphragmatic process (eg, asynchrony, hyperinflation, pneumonia, pleural effusion, pneumothorax).

●A large difference between Ppeak and Pplat indicates more airway resistance (eg, bronchoconstriction, airway mucus, endotracheal tube obstruction).

Dyssynchrony — Patient-ventilator dyssynchrony exists if the phases of breath delivered by the ventilator do not match those of the patient (eg, machine breath on top of patient-directed inspiration or machine breath before exhalation complete) and is manifest by agitation, tachypnea, tachycardia, use of accessory muscles, uncoordinated thoracic wall or abdominal movement, or deterioration in gas exchange. Common causes among patients with asthma include ineffective triggering of machine-assisted breaths (eg, due to insufficient trigger sensitivity or auto-PEEP as described below) (figure 1), intolerance of a slow inspiratory flow rate, and cough. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit", section on 'Follow-up' and "Acute respiratory distress syndrome: Ventilator management strategies for adults", section on 'Treat dyssynchrony'.)

Sedation (eg, with a combination of propofol and fentanyl) may help the patient to breathe in synchrony with the ventilator, but some patients are unable to breathe in synchrony with the ventilator even with sedation. Paralytic agents may be necessary in this setting. Adequate sedation and analgesia must be maintained if paralysis is used [22]. Neuromuscular blockade in patients receiving high-dose glucocorticoids increases the risk of post-paralytic myopathy and should be used sparingly [28,29]. (See "Neuromuscular blocking agents in critically ill patients: Use, agent selection, administration, and adverse effects" and "Neuromuscular weakness related to critical illness", section on 'Critical illness myopathy'.)

Dynamic hyperinflation — Dynamic hyperinflation occurs when the expiratory time is insufficient to completely exhale and inadequate emptying of the lungs between breaths causes progressive hyperinflation and increases Pplat (figure 2). Dynamic hyperinflation is a common problem in patients who require mechanical ventilation for severe asthma exacerbations. Bronchospasm, airway inflammation, airway edema, and mucus plugging dramatically decrease expiratory flow and prolong the time needed to complete exhalation prior to the onset of the next breath. (See "Invasive mechanical ventilation in acute respiratory failure complicating chronic obstructive pulmonary disease", section on 'Dynamic hyperinflation'.)

Assessment — When assessing whether an individual patient has excessively high intrathoracic pressures due to dynamic hyperinflation, use of Pplat (at end-inspiration) is preferred to use of Ppeak. A high Ppeak is not a reliable indicator of lung overdistension since Ppeak can be elevated due to increased airway resistance or high inspiratory flow rates, even in the absence of overdistension. A safe upper limit of Pplat has not been established; however, most clinicians aim for a Pplat below 30 cm H₂O [25] and an intrinsic PEEP under 10 cm H₂O.

Adverse effects of dynamic hyperinflation — Dynamic hyperinflation, which can be induced or exacerbated by mechanical ventilation, is common in patients with severe asthma exacerbation and its consequences can be devastating. Sequelae of dynamic hyperinflation include cardiovascular collapse, barotrauma, and increased work of breathing [27,30]. There are numerous other adverse effects associated with mechanical ventilation that are discussed in detail separately. (See "Clinical and physiologic complications of mechanical ventilation: Overview".)

●Cardiovascular collapse – Hyperinflation increases intrathoracic pressure, which increases pulmonary vascular resistance and decreases venous return. The net effect is reduced cardiac output. Progressive cardiovascular collapse culminating in cardiac arrest with pulseless electrical activity may ensue if not treated quickly [31]. Intravascular volume depletion and sedatives can accelerate the deterioration. Successful treatment requires volume resuscitation and alleviation of the hyperinflation, usually by temporarily disconnecting the ventilator circuit from the endotracheal tube [32].

Pneumothorax is in the differential and should be excluded by examining the patient (eg, for subcutaneous emphysema, unilateral decrease in breath sounds, deviation of the trachea), using a bedside ultrasound, and/or obtaining a portable chest radiograph. (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax".)

●Barotrauma and pneumothorax – Barotrauma refers to alveolar rupture due to elevated transalveolar pressure and is caused by progressive hyperinflation with overdistension of alveoli and subsequent loss of alveolar structural integrity. Interstitial emphysema, pneumothorax, pneumomediastinum, subcutaneous emphysema, and/or pneumoperitoneum can result. A pneumothorax in patients receiving positive pressure ventilation usually requires evacuation via tube thoracostomy. Unrecognized, it can rapidly increase in size, impair venous return, and lead to refractory hypotension ("tension pneumothorax") complicated by cardiac arrest due to pulseless electrical activity [33,34]. (See "Diagnosis, management, and prevention of pulmonary barotrauma during invasive mechanical ventilation in adults", section on 'Ventilator management' and "Thoracostomy tubes and catheters: Indications and tube selection in adults and children".)

●Increased work of breathing – Dynamic hyperinflation creates intrinsic PEEP, which increases the magnitude of the drop in airway pressure that the patient must generate to trigger a breath (figure 3), thereby increasing the patient's workload. Careful application of extrinsic PEEP at levels less than the intrinsic PEEP will reduce this gradient and the work of breathing [30]. Extrinsic PEEP should not exceed 80 percent of the measured intrinsic PEEP in order to avoid worsening the dynamic hyperinflation [35]. (See 'Adding extrinsic PEEP to offset intrinsic PEEP' below and "Positive end-expiratory pressure (PEEP)".)

Adjustments to decrease dynamic hyperinflation — Dynamic hyperinflation creates intrinsic PEEP and elevates the Pplat, which can lead to cardiovascular collapse and barotrauma, as well as increase the work of breathing.

Initial steps — Adjustments of the ventilator settings should aim for an inspiratory Pplat less than 30 cm H₂O and an intrinsic PEEP less than 10 cm H₂O. The following adjustments may help achieve these goals with the most important adjustments aiming to decrease minute ventilation [11,24,36]:

●Decreasing the tidal volume allows a shorter inspiratory time and decreases the volume that the patient needs to exhale prior to the next breath.

●Decreasing the respiratory rate also increases the expiratory time, allowing the patient more time to exhale.

●Ensuring that the trigger for machine supported breaths is not overly sensitive decreases potential breath-stacking due to extra machine breaths.

●Increasing the inspiratory flow will shorten the inspiratory time and allow the patient more time in the expiratory phase to fully exhale (assuming respiratory rate remains unchanged). However, increased inspiratory flow may trigger bronchoconstriction in patients with bronchial hyperresponsiveness.

Of note, some evidence suggests that increasing the inspiratory flow rate has less of an ameliorative effect on dynamic hyperinflation at lower levels of minute ventilation (eg, <10 L/min) [36]. Also, increasing inspiratory flow may lead to an increase in the spontaneous respiratory rate and thus not achieve a decrease in dynamic hyperinflation [24].

Adding extrinsic PEEP to offset intrinsic PEEP — Increased intrinsic positive end-expiratory pressure (also known as auto-PEEP) is a manifestation of breath-stacking and dynamic hyperinflation. Normally, the end-expiratory pressure is zero or equal to any extrinsic PEEP (also known as applied PEEP) delivered by the ventilator. One consequence of intrinsic PEEP is that initiation of the next breath by the patient requires sufficient negative pressure to overcome the intrinsic PEEP and trigger the ventilator. (See "Positive end-expiratory pressure (PEEP)", section on 'Auto (intrinsic) PEEP'.)

Intrinsic PEEP can be detected by using ventilator-generated flow versus time graphs to determine whether inspiratory flow begins before expiratory flow reaches zero (figure 4). To obtain a numeric value for intrinsic PEEP, the extrinsic PEEP is subtracted from airway pressure measured during a breath-hold at end-expiration (waveform 1). Ideally, the intrinsic PEEP should be <10 cm H₂O. (See "Positive end-expiratory pressure (PEEP)", section on 'Assessment'.)

A small amount of applied PEEP (3 to 5 cm H₂O) is used in most mechanically ventilated patients to mitigate end-expiratory alveolar collapse. Increasing the extrinsic PEEP (eg, up to 80 percent of the intrinsic PEEP) can offset the adverse effects of intrinsic PEEP and reduce the effort necessary to trigger inspiration during patient-initiated breaths. However, the amount of intrinsic PEEP must be measured accurately to avoid administering excess extrinsic PEEP and exacerbating air-trapping and high inspiratory pressures. The following are examples of clinical scenarios in which the measurement of auto-PEEP may be inaccurate:

●During severe asthma exacerbations, widespread airway closure due to luminal secretions and airway edema/inflammation can impede measurement of end-expiratory alveolar pressure, resulting in a falsely low intrinsic PEEP measurement [37]. As a consequence, marked hyperinflation may be unrecognized.

●Persistent expiratory muscle activity at end-expiration can also cause a falsely high measurement of intrinsic PEEP by the ventilator. This is recognized at the bedside by observing expiratory muscle activity during the breath-hold at end-expiration. In this situation, addition of extrinsic PEEP could be deleterious and lead to increased work of breathing. (See "Positive end-expiratory pressure (PEEP)", section on 'Assessment'.)

The patient's airway pressures and gas exchange should be monitored closely after addition of extrinsic PEEP. (See "Positive end-expiratory pressure (PEEP)".)

Additional methods to decrease intrinsic PEEP include prolonging the expiratory phase, reducing minute ventilation, and administering medications to promote bronchodilation. (See 'Adjustments to decrease dynamic hyperinflation' above.)

Permissive hypercapnia — The strategies of decreasing the respiratory rate and tidal volume to prevent barotrauma can lead to an increase in the arterial tension of carbon dioxide (PaCO₂). Permissive hypercapnia refers to the acceptance of the elevated PaCO₂ and associated respiratory acidosis. The effects of respiratory acidosis are generally better tolerated than the consequences of barotrauma, such as pneumothorax. The indications, contraindications, and technique of permissive hypercapnia are discussed separately. (See "Permissive hypercapnia during mechanical ventilation in adults".)

TROUBLESHOOTING HYPOXEMIA — In patients with acute asthma exacerbations, adequate oxygenation is usually achieved without difficulty (eg, with an FIO₂ ≤50 percent) after intubation, as the main problem is typically failure of the patient to maintain the necessary work for ventilation. However, some patients develop hypoxemia due to processes such as mucus plugging, atelectasis, air trapping, ventilation/perfusion (V/Q) mismatch, pneumonia, or pneumothorax.

The first step is to determine the cause of hypoxemia by examination at the bedside and review of a chest radiograph and/or use of bedside ultrasound. Examination at the bedside should include interrogation of the ventilator, looking for high peak (Ppeak) and plateau (Pplat) airway pressures, and breath-stacking.

●Audible wheezing and higher peak pressures (with a gap between peak and plateau pressures more than 5 cm H₂O) can indicate that bronchoconstriction or airway secretions are contributing to V/Q mismatch. Adequate dosing of inhaled bronchodilator and systemic glucocorticoids should be ensured along with suctioning to remove secretions.

●Increasing extrinsic positive end-expiratory pressure (extrinsic PEEP), which is often helpful for hypoxemia due to acute respiratory distress syndrome (ARDS), must be done cautiously in an acute asthma exacerbation, because excess extrinsic PEEP (above 80 percent of intrinsic PEEP) may contribute to air trapping and poor ventilation. Careful measurement of intrinsic PEEP is needed to guide any addition of extrinsic PEEP. (See 'Adding extrinsic PEEP to offset intrinsic PEEP' above.)

●Does the patient have a pneumonia or pneumothorax? Review chest radiograph and/or ultrasound for features of pneumonia or pneumothorax (eg, asymmetric opacities on imaging, deep sulcus sign, absence of "lung sliding" on ultrasound). (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax" and "Clinical presentation and diagnosis of pneumothorax", section on 'Diagnostic imaging'.)

●Consider adjunctive/experimental therapies to improve ventilation. (See 'Additional and unconventional therapies' below.)

ADDITIONAL AND UNCONVENTIONAL THERAPIES — Rarely, airflow obstruction is so severe and refractory that sufficient ventilation cannot be achieved despite maximal standard therapy, including deep sedation, paralysis, intravenous glucocorticoids, and inhaled bronchodilators. In this circumstance, general anesthesia or heliox may permit ventilation and extracorporeal life support may act as a substitute gas exchanger. The routine use of these adjunctive therapies cannot be recommended on the basis of existing clinical studies.

General anesthesia — Induction of general anesthesia, either by intravenous infusion (eg, ketamine) or inhalation (eg, isoflurane), can reduce bronchospasm and airway resistance [38-42]. This approach should not be undertaken lightly, due to the risk of profound hypotension [43]. An anesthesiologist is required for the duration of the anesthesia and bronchoconstriction may recur when anesthesia is withdrawn. The duration of general anesthesia typically ranges from 2 to 12 hours. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Anesthetic agents'.)

Heliox — Heliox is a blend of helium and oxygen that has a lower density than air. Heliox is rarely necessary, but can reduce resistance to airflow, enhance delivery of nebulized bronchodilators, and improve oxygenation compared with standard nitrogen-oxygen mixtures [44-48]. However, it can also cause ventilator malfunction, including inaccurate measurement of tidal volume and oxygen concentration [49]. (See "Physiology and clinical use of heliox".)

Extracorporeal life support — Oxygenation and carbon dioxide removal through an artificial membrane may be beneficial as a temporizing measure for patients with severe asthma exacerbation complicated by refractory respiratory acidosis, although evidence based on clinical trials is lacking [50-56]. (See "Extracorporeal life support in adults in the intensive care unit: Overview".)

EXTUBATION — Patients who have been intubated for respiratory failure due to severe asthma exacerbation can usually wean quickly once airway edema and inflammation and bronchoconstriction respond to medical therapy. Specific weaning and extubation criteria have not been established for acute asthma exacerbation. One approach is to perform a spontaneous breathing trial once the patient is awake and has normal vital signs, minimal audible wheezes, a normal arterial tension of carbon dioxide (PaCO₂), intrinsic positive end-expiratory pressure (auto-PEEP) less than 10 cm H₂O, and no evidence of neuromuscular weakness. (See "Extubation management in the adult intensive care unit".)

After extubation, observation in an intensive care unit is recommended for an additional 12 to 24 hours.

PROGNOSIS — Patients with severe asthma exacerbation who require mechanical ventilation have increased in-hospital mortality compared with patients who do not require mechanical ventilation (7 versus 0.2 percent) [2,3]. Patients who survive to hospital discharge remain at high risk of death; this excess risk is only beginning to be recognized and may be worse than some malignancies. As an example, one study assessed the long-term outcome of 145 survivors of severe asthma exacerbation who required mechanical ventilation [57]. The one-, three-, and six-year mortality rates were 10, 14, and 23 percent, respectively. Most of the deaths were due to recurrent asthma. Close medical follow-up may be a key to long-term survival (table 1). (See "Identifying patients at risk for fatal asthma".)

Poor perception of illness severity and depression can contribute to the risk of near-fatal asthma episodes. Survivors of near death due to asthma often demonstrate a lot of denial regarding their illness, and anxiety appears to be more common among close family members than the patients themselves [58]. Denial is an understandable psychological mechanism for dealing with fear. The challenge is to demonstrate to such patients that they can manage their illness. This requires a coordinated team approach involving the inpatient and outpatient medicine and nursing services, and the use of community resources like asthma support groups. (See "Identifying patients at risk for fatal asthma", section on 'Identifying high-risk patients' and "Identifying patients at risk for fatal asthma", section on 'Prevention'.)

Depression is strongly associated with an increased risk of asthma mortality, and suspicion of depression in a survivor of a near-fatal asthma attack warrants formal evaluation and treatment [21]. (See "Trigger control to enhance asthma management", section on 'Emotional factors' and "Unipolar depression in adults: Assessment and diagnosis".)

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: Asthma in adolescents and adults".)

SUMMARY AND RECOMMENDATIONS

●Among patients hospitalized for an acute severe asthma exacerbation, approximately 3 to 5 percent require mechanical ventilation. (See 'Introduction' above.)

●Acute respiratory failure (ie, insufficient oxygenation and/or alveolar ventilation) is the primary indication for mechanical ventilation. The decision to initiate mechanical ventilation should be based on clinical judgment that considers the entire clinical situation, including clinical and physiologic derangements and clinical course. (See 'Indications' above.)

●The role of noninvasive ventilation (NIV), including biphasic positive airway pressure and continuous positive airway pressure ventilation, in patients with acute asthma exacerbations is not well-defined. However, a brief trial of NIV may be reasonable in selected patients prior to intubation and mechanical ventilation. (See 'Noninvasive ventilation' above.)

●Intubation should be approached cautiously in patients with severe asthma exacerbation because manipulation of the airway can cause increased airflow obstruction due to exaggerated bronchial responsiveness. While evaluating the need for intubation, the patient's airway is examined for traits associated with potential difficulty. If a difficult intubation is anticipated, the necessary assistance (personnel, equipment, airway devices) for management of a difficult airway should be obtained in case intubation becomes necessary. (See 'Intubation' above and "Direct laryngoscopy and endotracheal intubation in adults" and "Approach to the difficult airway in adults for emergency medicine and critical care", section on 'Identifying the anatomically difficult airway'.)

●Once the decision has been made to intubate, the majority of patients are given rapid sequence induction using sedation with etomidate, ketamine, or propofol and neuromuscular blockade with succinylcholine or rocuronium. The optimal agent has not been determined. The clinician most experienced with airway management should intubate the patient, preferably with a large-bore (≥8 mm) endotracheal tube. (See 'Intubation' above and 'Induction agents' above and "Airway management in acute severe asthma for emergency medicine and critical care", section on 'Rapid sequence intubation'.)

●Reasonable initial ventilator settings include a respiratory rate from 10 to 12 breaths/min, a tidal volume of 6 to 8 mL/kg, a minute ventilation less than 115 mL/kg, and an inspiratory flow of 60 to 75 L/min. Positive end-expiratory pressure (PEEP) is usually initiated at 5 cm H₂O. (See 'Initial ventilator settings' above.)

●Dynamic hyperinflation is a common problem in patients with a severe asthma exacerbation. It refers to progressive hyperinflation due to inadequate emptying between breaths, a consequence of expiratory airflow limitation. Dynamic hyperinflation creates intrinsic PEEP (auto-PEEP) and elevates the plateau pressure (Pplat), which places the patient at risk for cardiovascular collapse, barotrauma, and increased work of breathing. (See 'Dynamic hyperinflation' above.)

●To assess whether dynamic hyperinflation is occurring, measurement of Pplat is performed during a brief breath-hold at end-inspiration. Pplat is felt to be a more accurate measure of lung overdistension, than measurement of peak airway pressure (Ppeak). (See 'Assessment' above.)

●Initial ventilator settings may need further adjustment to maintain Pplat less than 30 cm H₂O and intrinsic PEEP less than 10 cm H₂O. Adjustments that may help achieve these goals include increasing the inspiratory flow (to allow longer expiratory time), decreasing the tidal volume, and/or decreasing the respiratory rate. Decreasing the tidal volume or respiratory rate may require the acceptance of elevated arterial tension of carbon dioxide (PaCO₂), a strategy known as permissive hypercapnia. (See 'Adjustments to decrease dynamic hyperinflation' above and "Permissive hypercapnia during mechanical ventilation in adults".)

●Increased intrinsic-PEEP is a manifestation of breath-stacking and dynamic hyperinflation. The intrinsic PEEP is equal to the airway pressure measured during a breath-hold at end-expiration, minus the amount of extrinsic PEEP (also known as applied PEEP). Increasing the amount of extrinsic PEEP (eg, up to 80 percent of the intrinsic PEEP) can offset the effects of intrinsic PEEP and reduce the effort necessary to trigger inspiration during patient-initiated breaths. The accurate measurement of intrinsic PEEP is essential to avoid adding excess extrinsic PEEP. (See 'Adding extrinsic PEEP to offset intrinsic PEEP' above.)

●Hypotension due to dynamic hyperinflation and poor venous return is treated with fluid resuscitation and prompt alleviation of hyperinflation, usually by temporarily disconnecting the ventilator circuit from the endotracheal tube. Ventilator settings are adjusted to prevent a recurrence when mechanical ventilation is resumed. (See 'Adverse effects of dynamic hyperinflation' above.)

●Rarely, airflow obstruction is so severe that sufficient ventilation cannot be achieved despite maximal standard therapy. Benefit has been reported with use of general anesthesia, heliox, or extracorporeal life support in these circumstances, although formal study is lacking. (See 'Additional and unconventional therapies' above.)

●Patients with severe asthma exacerbation who require mechanical ventilation have increased in-hospital and long-term mortality. Vigorous efforts to improve asthma control after discharge may help prevent recurrent episodes. (See 'Prognosis' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Carlos Camargo, Jr, MD, DrPH, and Jerry Krishnan, MD, PhD, who contributed to earlier versions of this topic review.