Acute severe asthma exacerbations in children and adolescents: Endotracheal intubation and mechanical ventilation

INTRODUCTION — Children with severe asthma exacerbations requiring hospital admission are often admitted to the pediatric intensive care unit (PICU). PICU-level care allows for continuous monitoring and rapid escalation of respiratory support in addition to the core asthma therapies (ie, systemic glucocorticoids and bronchodilatory agents) [1].

Endotracheal intubation and mechanical ventilation of children and adolescents with acute severe asthma exacerbation (ie, status asthmaticus) are discussed here. General intensive care unit (ICU) management, primarily pharmacotherapy, as well as non-ICU inpatient management are discussed in detail separately. Mechanical ventilation for adults with severe asthma is also reviewed separately. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management" and "Acute asthma exacerbations in children younger than 12 years: Inpatient management" and "Invasive mechanical ventilation in adults with acute exacerbations of asthma".)

Pharmacologic management of acute asthma exacerbations and management of chronic childhood asthma are discussed separately as well. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management" and "Asthma in children younger than 12 years: Initial evaluation and diagnosis" and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies" and "Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms".)

GENERAL PRINCIPLES — For children requiring pediatric intensive care unit (PICU) admission for a severe asthma exacerbation, airway management and mechanical ventilatory support should be considered early. Preventing intubation is an important goal as there are significant risks associated with intubation and invasive mechanical ventilation (IMV) [2-4]. Avoidance of intubation is best achieved with early and rapid escalation of bronchodilatory therapies and use of noninvasive positive pressure ventilation (NPPV). By providing positive pressure, NPPV can help to reduce the patient's work of breathing while awaiting maximal therapeutic effects of pharmacotherapy. NPPV is now widely used in the treatment of severe asthma exacerbations, with many centers opting for early initiation in the emergency department [5]. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Preintubation therapies' and "Noninvasive ventilation for acute and impending respiratory failure in children".)

The decision to intubate a patient to prevent severe hypoxia should be made with great care as tracheal stimulation itself can worsen bronchospasm and frequently worsens airway obstruction and hypercapnia. Mechanically ventilating a child with asthma can be challenging as the disease-associated airway obstruction impairs exhalation, resulting in air trapping, which can increase the risk of barotrauma and extrapulmonary air leak. IMV is generally reserved for patients with respiratory failure despite maximal medical therapy and NPPV. For children with severe asthma exacerbations, rates of intubation and IMV vary. Several single-center studies have reported IMV rates of 1 to 4 percent [6,7], whereas a review of the Pediatric Health Information Systems registry, a multiinstitutional PICU database, showed an overall IMV rate of 12.5 percent for children admitted to US PICUs for severe asthma between 2010 and 2019 [8]. In the context of asthma exacerbations, several morbidities have been associated with IMV, including barotrauma and neuromyopathy, but mortality is rare [2,3,9-11]. (See 'Endotracheal intubation and mechanical ventilation' below and 'Complications' below and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Prognosis'.)

In addition, IMV and intravenous pharmacotherapy may not be sufficient to sustain oxygenation and ventilation in some refractory cases, and adjunctive therapies including inhaled anesthetics and extracorporeal support may be necessary. (See 'Complications' below and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Pharmacotherapy' and 'Adjunctive therapies' below.)

SEDATION AND PARALYSIS

Overview — Supportive measures for children with asthma requiring invasive mechanical ventilation (IMV) include sedation, analgesia, and often paralysis [2,12-14]. Sedation in children with asthma who require intubation and invasive mechanical ventilation (IMV) is reviewed here. A more general review of medications for rapid sequence intubation (table 1) and other supportive measures are discussed in detail separately. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis" and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Supportive care'.)

●Intubation – For intubation, several agents can be used to sedate a child with severe asthma. Those typically considered include fentanyl, midazolam, ketamine, propofol, and etomidate. Morphine can stimulate histamine release and exacerbate asthma symptoms and is therefore generally avoided [15]. Neuromuscular blocking agents, including rocuronium, vecuronium and cisatracurium, are often employed to optimize intubating conditions.

●Postintubation – Once patients are intubated, sedation and sometimes paralysis are continued to promote patient/ventilator synchrony, reduce tachypnea, and reduce breath stacking, a term used to refer to incomplete exhalation resulting from early patient-triggered ventilator breath delivery. Most patients will also require intravenous fluids to treat dehydration and optimize cardiac preload following the transition to positive pressure ventilation.

Sedation

●Ketamine – Of the sedative agents that are available to facilitate intubation, ketamine, a synthetic derivative of phencyclidine, is often used because of its additional bronchodilatory effect. Unlike other sedative agents, respiratory drive and response to partial pressure of carbon dioxide (PaCO₂) are preserved with low-dose infusions of ketamine [16]. When used in this fashion, a loading dose of 2 mg/kg is followed by an infusion of 20 to 60 micrograms/kg/min [1]. In children with severe asthma, ketamine has been used for patients supported with noninvasive positive pressure ventilation (NPPV) or IMV [16]. There is limited evidence to suggest that ketamine is superior to other sedative agents used for children with severe asthma requiring IMV. A small, single-center study showed improved oxygenation parameters and lung compliance in a group of children with bronchospasm receiving ketamine and IMV [17]. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Sedation (induction) agents'.)

●Propofol – Propofol is another agent used to facilitate intubation. It is a potent hypnotic/anesthetic agent that directly activates gamma-aminobutyric acid (GABA) receptors, resulting in global central nervous system depression [18]. Propofol decreases cerebral metabolic demand and oxygen consumption and lowers intracranial pressure. While there are documented reports of propofol-induced bronchoconstriction in some patients with atopy, propofol is generally thought to act as a bronchodilator [19]. It also carries antiinflammatory properties. For these reasons, it is commonly used to facilitate intubation in patients with status asthmaticus [18].

In pediatric patients, prolonged use of propofol (>48 hours) is associated with propofol infusion syndrome (PIS). The symptoms of PIS can include myocardial depression, kidney failure, rhabdomyolysis, hepatomegaly, hyperkalemia, hypertriglyceridemia, and metabolic acidosis [19-21]. PIS is rare but occurs more commonly in critically ill children also receiving glucocorticoids and catecholamines. For this reason, the US Food and Drug Administration (FDA) recommends against the use of propofol for continuous sedation in the pediatric intensive care unit (PICU) [22,23]. However, several studies have documented uneventful use of propofol for sedation of children in the PICU, suggesting that it is safe for this population at doses of <4 mg/kg/hour for under 48 hours [24-26].

●Dexmedetomidine, fentanyl, and midazolam – Other medications without known bronchodilatory effects are also used for induction and, more often, maintenance of sedation of children with severe asthma requiring IMV. Fentanyl and midazolam are frequently used in the PICU [27]. Dexmedetomidine, a selective alpha-2-receptor agonist, is approved as a continuous agent in adults. There are multiple reports of its safety and efficacy in children [28], with dosing largely extrapolated from adult literature. Patients are typically loaded with 0.5 to 1 microg/kg over 10 to 20 minutes, followed by an infusion. Some pediatric centers forego the loading dose to avoid associated hypotension and bradycardia, which are the more commonly encountered adverse effects of dexmedetomidine in children. Reported infusion doses range from 0.2 to 0.7 microg/kg/hour. However, literature suggests that infusion doses of up 2 microg/kg/hour can be used beyond the recommended limit of 24 hours. Like ketamine, dexmedetomidine is also used to facilitate tolerance of NPPV [29].

Paralysis — Neuromuscular blockade may be used to facilitate safe intubation and eliminate tachypnea and ventilator dyssynchrony in sedated patients on IMV. However, efforts should be made to discontinue neuromuscular blocking agents as soon as is feasible as their use in combination with glucocorticoids is associated with an increased risk of myopathy of critical illness [3,30-36]. Also, the benefits of pressure support modes of mechanical ventilation (ie, improved patient comfort and reduced peak airway pressures) are not available in the paralyzed patient. The choice and use of these medications are discussed in greater detail separately. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Paralytic agents'.)

ENDOTRACHEAL INTUBATION AND MECHANICAL VENTILATION

Indications — The decision to intubate and mechanically ventilate a patient with status asthmaticus is made based upon clinical findings (eg, inability to speak, confusion or somnolence, hypoxemia despite supplemental oxygen) and physiologic changes (eg, moderate-to-severe hypercapnia). Care must be taken to control the airway before the patient suffers a respiratory arrest or hypoxic insult. (See "Technique of emergency endotracheal intubation in children".)

Indications for intubation and mechanical ventilation in patients with acute severe asthma despite maximal medical therapy and/or oxygen delivery include:

●Hypoxemia (partial pressure of oxygen [pO₂] <60) despite provision of high concentrations of oxygen via nonrebreather face mask, high flow nasal cannula (HFNC), or noninvasive positive pressure ventilation (NPPV)

●Severe and unremitting increased work of breathing (eg, inability to speak)

●Altered mental status

●Respiratory or cardiac arrest

Hypercapnia alone is not an indication for intubation [3,37]. However, intubation is warranted if a patient demonstrates a progressively rising arterial partial pressure of carbon dioxide (PaCO₂) despite maximal therapy and if hypercapnia is causing significant respiratory acidosis or altered mental status.

Precautions — Intubation should be approached cautiously in patients with status asthmaticus because manipulation of the airway can exaggerate bronchial hyperresponsiveness and worsen airflow obstruction. Adequate venous access, frequent noninvasive blood pressure monitoring, and sedation should be optimized before intubation. The clinician most experienced with airway management should perform the intubation. (See "Technique of emergency endotracheal intubation in children" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Clinicians must be prepared to manage acute deterioration due to tube malposition, tube obstruction, pneumothorax, equipment failure, and/or hypotension [38,39]. (See 'Complications' below.)

Goals — The goals of endotracheal intubation and mechanical ventilation for children with status asthmaticus and respiratory failure are to [40]:

●Relieve work of breathing from the exhausted patient and allow respiratory muscle rest

●Ensure adequate oxygenation (see 'Strategies to achieve adequate oxygenation' below)

●Ensure sufficient (not necessarily normal) gas exchange (initial hypercarbia is tolerated) until airway obstruction can be reversed (see 'Strategies to limit risk of hyperinflation and barotrauma' below)

●Minimize adverse effects (see 'Complications' below)

Rapid sequence intubation — Children intubated for severe asthma exacerbations should undergo rapid sequence intubation. The approach is reviewed in the rapid overview table (table 1) and is discussed in greater detail separately. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Approach" and "Technique of emergency endotracheal intubation in children".)

Strategies to achieve adequate oxygenation — Adequate oxygenation is usually achieved without difficulty in most patients with asthma since the airways, not the alveoli, are the primary targets of inflammation and bronchospasm. However, mucus plugging, atelectasis, hyperinflation, and ventilation/perfusion (V/Q) mismatch may contribute to hypoxemia. In mechanically ventilated patients, oxygenation is affected primarily by the fraction of inspired oxygen (FiO₂) and mean airway pressure. (See 'Ventilator settings' below.)

Atelectasis can be treated with judicious application of positive end-expiratory pressure (PEEP) (see 'Ventilator settings' below). Mucus plugging may also be significant, necessitating aggressive pulmonary clearance [41], including bronchoscopy to remove mucus plugs. Bronchoscopy and bronchoalveolar lavage can have therapeutic benefit and can also be useful for diagnosis of concurrent infection. Though the literature is sparse, retrospective reviews have shown that bronchoscopy is safe in children with asthma requiring invasive mechanical ventilation (IMV) [42]. One study of children with asthma receiving IMV found that children who received bronchoscopy experienced reduced length of IMV [43].

Strategies to limit risk of hyperinflation and barotrauma — For children with severe asthma requiring IMV, safe and effective mechanical ventilation depends upon limiting the risk of hyperinflation and barotrauma. The risk of hyperinflation is decreased by dropping the respiratory rate while maintaining a normal (constant) inspiratory time. This increases the expiratory time, thereby decreasing the ratio of inspiratory-to-expiratory time (I:E ratio). The risk of barotrauma is decreased by minimizing hyperinflation and peak inspiratory pressures (PIP). For these reasons, many consider pressure support ventilation (PSV) the ideal mode of ventilation for the intubated patient with asthma. However, pressure control and volume control are also used. There is no evidence to support one mode of ventilation over another. (See 'Dynamic hyperinflation' below and 'Barotrauma' below and 'Ventilatory modes' below.)

Diminishing the risk of hyperinflation and barotrauma requires acceptance of an initial PaCO₂ that is higher than normal with an accompanying respiratory acidosis, a strategy that is called "permissive hypercapnia" or "controlled hypoventilation" [4,44]. A slow increase in PaCO₂ (approximately 10 mmHg/hour) permits intracellular buffering mechanisms to accommodate the decreasing serum pH. This strategy is widely used in patients with asthma [4,45]. Permissive hypercapnia is well tolerated by children with normal cardiac function. However, those with concurrent chronic conditions, such as cyanotic heart disease, cardiomyopathy, or pulmonary hypertension, will probably not tolerate this strategy. Other potential contraindications to permissive hypercapnic ventilation include increased intracranial pressure, poor myocardial function, and coexistent metabolic acidosis (eg, patients with kidney disease).

Ventilatory modes — A variety of ventilatory modes have been successfully employed in the management of patients with asthma who require intubation [46]. These include pressure control ventilation (PCV), pressure support ventilation (PSV), volume control ventilation (eg, pressure-regulated volume control [PRVC]), and synchronized intermittent mandatory ventilation (SIMV), which is delivered with pressure control (SIMV/PC) or volume control (SIMV/VC). These ventilatory modes are reviewed in greater detail separately. (See "Initiating mechanical ventilation in children".)

Volume control ventilation (eg, PRVC or SIMV/VC) allows for consistent minute ventilation (respiratory rate [RR] x tidal volume [TV]) in the face of changing airway resistance and lung compliance. PRVC assures that the patient receives the desired/set TV at the lowest peak pressure possible, making it the optimal mode in the setting of severe asthma, where assuring minute ventilation and reducing risk of barotrauma are the main priorities.

Ventilator settings — The choice of mechanical ventilator settings (table 2) must take into account the physiologic derangements of acute severe asthma, including airflow obstruction and atelectasis [12], but also serve to minimize hyperinflation and barotrauma.

Determining initial settings — The patient should be given breaths with a bag and in-line manometer prior to initiating mechanical ventilation. Careful noting of the inherent expiration time can help to avoid breath stacking. In the setting of airway obstruction, positive pressure can exacerbate air trapping leading to increased lung volumes during both inspiration and expiration. The result is increased risk of barotrauma and extrapulmonary air leak along with increased pulmonary vascular resistance and decreased venous return; the last two can lead to decreased cardiac output. The respiratory rate on the ventilator should be sufficiently low to permit a normal inspiratory time and a generous expiratory time. (See 'Complications' below.)

Setting adjustment — Initial ventilator settings are adjusted as necessary to maintain adequate ventilation, as assessed by chest auscultation and measurement of arterial blood gases, and to prevent complications. The placement of an indwelling arterial catheter facilitates obtaining frequent arterial blood samples and continuous arterial pressure monitoring. However, many children intubated outside of the pediatric intensive care unit (PICU) setting will require IMV for <24 to 48 hours and therefore may not require invasive vascular pressure monitors [2,5,9,47]. (See 'Strategies to limit risk of hyperinflation and barotrauma' above and 'Complications' below and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Monitoring' and "Arterial puncture and cannulation in children".)

Setting parameters

●Fraction of inspired oxygen – The FiO₂ should be set at 1.0 upon intubation. FiO₂ is then decreased as tolerated to concentrations of 0.5 or lower to maintain oxygen saturation >92 percent. Use of an FiO₂ of 1.0 for prolonged periods in patients with asthma predisposes them to resorption atelectasis and should therefore be avoided.

●Respiratory rate – The respiratory rate should be set near or below physiologic rates (8 to 12 breaths per minute) [4], keeping the minute ventilation under 115 mL/kg per minute. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma".)

●Tidal volume – The delivered TV should initially be 6 to 8 mL/kg. The PIP and plateau pressure (Pplat) attained with these volumes should be noted and kept under 40 cm H₂O and 30 to 35 cm H₂O, respectively. Maintaining these limits helps to minimize dynamic hyperinflation and barotrauma. The TV may need to be reduced if the peak pressure limit exceeds 40 cm H₂O. Reducing the TV will result in increased PaCO₂. (See 'Dynamic hyperinflation' below and 'Barotrauma' below and 'Strategies to limit risk of hyperinflation and barotrauma' above.)

●Inspiratory and expiratory times and inspiratory flow – Inspiratory times should be normal to slightly low for patient age (0.75 to 1.2 seconds) and the respiratory rate sufficiently low so that the expiratory time prevents breath stacking. Thus, the cycle time is six seconds if the respiratory rate is 10, and the I:E ratio is 1:5 if the inspiratory time is one second.

Expiratory time should be maximized to allow complete exhalation, avoid hypercapnia, and prevent dynamic hyperinflation and increased intrinsic PEEP (elevation of alveolar pressure above atmospheric pressure or set PEEP at the end of exhalation, also called auto-PEEP).

To this end, inspiratory flow should be set at the highest rate the patient can tolerate without generating excessively high peak pressures. Flow rates of 4 to 10 L/kg per minute, with a maximum of 80 to 100 L/minute, are typically employed in children during PCV.

●Positive end-expiratory pressure – We suggest setting PEEP at a minimum of 3 to 5 cm H₂O initially. Some degree of extrinsic PEEP is necessary to compensate for the external resistance added to the respiratory tract by the endotracheal tube (eg, PEEP of 3 to 5 cm H₂O). PEEP may be increased in increments of 1 cm H₂O to determine whether additional PEEP improves ventilation. Most patients with asthma can be successfully managed with PEEP in the range of 3 to 8 cm H₂O. Care must be taken to ensure that extrinsic PEEP does not exceed intrinsic PEEP. At the author's institution, PEEP is carefully titrated by senior clinicians present at the bedside assessing plateau pressures, intrinsic PEEP, work of breathing, and ventilator graphics (flow-time loops in particular). PEEP should be adjusted or diminished if adverse effects occur (eg, dynamic hyperinflation). (See 'Dynamic hyperinflation' below.)

The utility of extrinsic PEEP beyond physiologic settings (5 cmH₂O) is debated [12,13,48,49]. In theory, extrinsic PEEP can help to splint the airways, reducing airflow obstruction and gas trapping. This can serve to reduce auto-PEEP and the work of breathing needed to overcome auto-PEEP [48]. Low levels of PEEP also facilitate ventilator triggering and synchronization for intubated patients capable of taking spontaneous breaths [48,49]. Higher levels of PEEP (5 to 8 cm H₂O) may be beneficial for children demonstrating persistent and severe hypercapnia despite appropriate TV (6 to 10 mL/kg) and expiratory times that permit complete exhalation.

Monitoring — Mechanically ventilated patients may require arterial and central venous access for hemodynamic monitoring, in addition to standard cardiorespiratory monitoring. Of the graphics available on most modern ventilators, the flow time curve is one parameter that allows for relatively easy assessment of air trapping. If the patient has sufficient time to exhale, the expiratory flow should to return to zero before the next breath begins (figure 1). (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Monitoring'.)

Delivery of inhaled medications — There are a variety of ventilator-compatible nebulization systems that allow for the continuous delivery of inhaled bronchodilators through the ventilator circuit. Children requiring PICU care often receive intravenous bronchodilator therapies. There is considerable practice variation in the use of bronchodilators across PICUs [50]. For children requiring IMV, despite preintubation use of inhaled bronchodilators, intravenous therapy may be helpful to ensure bronchodilator delivery. Some intensivists will apply therapies in a stepwise approach, switching to intravenous formulations once inhaled therapies have proven ineffective, while others will continue both inhaled and intravenous until there is clinical evidence of reduced bronchospasm (ie, improved aeration with auscultation, return or improvement of audible wheeze, or reduced arterial PaCO₂) [51].

ADJUNCTIVE THERAPIES

When to consider — In extreme cases, airflow obstruction is so severe that sufficient ventilation cannot be achieved despite intensive bronchodilator therapy, intravenous glucocorticoids, ventilatory support, sedation, and paralysis. In such cases, adjunctive therapies, such as extracorporeal membrane oxygenation (ECMO) or inhalational anesthetics, may be successful rescue measures. There are limited observational data on the use of these therapies in children with extremely refractory severe asthma exacerbations.

Extracorporeal membrane oxygenation — ECMO support is increasingly used in the treatment of asthma refractory to medical therapy and conventional invasive mechanical ventilation (IMV) [52]. Several case reports describe safe use of ECMO in this patient population [53-55]. Given the risk associated with cannulation and systemic anticoagulation, ECMO is generally reserved for cases of worsening hypercapnia with onset of hemodynamic instability suggesting pending cardiopulmonary arrest [52]. There are not well-established criteria for ECMO use in children with severe asthma, and the timing/decision to cannulate is usually center dependent.

Inhalational anesthetics — The use of inhalational anesthetics may be tried as a rescue maneuver in children with acute severe asthma exacerbations who have continued ventilatory failure despite appropriate IMV with aggressive medical therapy. Practical limitations to the use of inhalational anesthetics include the abrupt return of bronchoconstriction after discontinuation and the need for delivery via an anesthesia machine with proper scavenging of anesthetic gas (to avoid the second-hand inhalation of aerosolized anesthetic by health care personnel or other patients). This usually requires the bedside presence of an anesthesiologist, who can provide guidance regarding the dose, duration, and discontinuation of inhalational anesthetic.

The inhalational anesthetics, halothane, isoflurane, and sevoflurane, are potent bronchodilators. The positive effects of isoflurane for status asthmaticus have been described in a few case series [56-58]. The ventilator used to deliver these agents must have a scavenger system to prevent staff exposure to the anesthetic agents. Their mechanisms of action are unknown but are purported to include direct smooth muscle relaxation, reduction of vagal tone, and synergy with catecholamines. Inhalation anesthetics can generate hypotension. Delivery in some pediatric intensive care units (PICUs) may be difficult given lack of familiarity with anesthesia machines by pediatric intensivists [56,59-61]. In addition, use of these agents is associated with substantially increased hospital costs. A majority of PICUs never use volatile agents [53].

COMPLICATIONS

Causes, types, and frequency of complications — Complications can result from the asthma exacerbation itself or the treatments. Patients with an acute severe asthma exacerbation are at risk for progressive air trapping and alveolar hyperinflation, which may lead to alveolar rupture and hemodynamic compromise. Endotracheal intubation with mechanical ventilation in the child with asthma can be associated with significant morbidity including hypotension, barotrauma (including pneumothorax), and myopathy. These complications occur in 10 to 26 percent of children who are ventilated for asthma [4,5,10], and more than one-half of complications occur during or immediately after intubation [62]. Delayed recognition and mitigation of these adverse events can result in hemodynamic instability. Common causes of acute deterioration in intubated patients include tube displacement or malposition, tube obstruction, pneumothorax, and equipment failure [63]. (See "Initiating mechanical ventilation in children", section on 'Approach to decompensation'.)

Dynamic hyperinflation — Airflow obstruction during expiration slows lung emptying and may lead to increased lung volume. Expansion of lung volume may increase airway caliber and can reduce the resistive work of breathing. However, this physiologic response becomes maladaptive in patients with severe asthma because it increases mechanical load and elastic work of breathing [30]. Obstruction to expiratory airflow may lead to initiation of inspiration before the preceding exhalation is complete (ie, before the lung has reached the static equilibrium volume, leaving lung volume above functional residual capacity [FRC]), often called breath stacking. The result is gas trapping with elevated intrinsic positive end-expiratory pressure, known as auto-PEEP. This phenomenon is called dynamic hyperinflation (figure 1) [30,64].

●Consequences of dynamic hyperinflation – Dynamic hyperinflation increases the magnitude of the drop in airway pressure that the patient must generate to trigger a breath, thereby increasing the patient's workload (figure 2). It can also cause alveolar overdistention resulting in hypoxemia, hypotension, or alveolar rupture. Dynamic hyperinflation can occur in patients with asthma in the absence of positive pressure, but it is more common, and potentially more difficult to manage, in ventilated patients due to the use of positive pressure.

●Assessing for dynamic hyperinflation – There are several ways to assess for the presence of dynamic hyperinflation. These include measurement of the end-inspiratory plateau pressure (Pplat), end-inspired volume (VEI) above apneic functional residual capacity, or intrinsic or auto-positive end-expiratory pressure (intrinsic PEEP or auto-PEEP) [30]. The Pplat measure is obtained by pausing ventilation briefly (0.4 seconds) at end inspiration and measuring the airway pressure. Keeping Pplat below 30 cm H₂O can decrease complications. Whether this measure is valid in children is unknown. The last two measurements have limitations and are less commonly used. (See "Invasive mechanical ventilation in adults with acute exacerbations of asthma".)

●Interventions – Interventions to correct air trapping include decreasing the respiratory rate (functionally increasing expiratory time), increasing inspiratory flow rates (functionally decreasing the inspiratory time), and lowering the tidal volume (TV). Limiting minute ventilation is the key to avoiding dynamic hyperinflation. Keeping the minute ventilation under 115/mL/kg is a recommended goal in children (table 2). (See 'Ventilator settings' above and "Invasive mechanical ventilation in adults with acute exacerbations of asthma".)

Barotrauma — Pulmonary barotrauma in the mechanically ventilated patient is the result of alveolar rupture and is characterized by the development of extra-alveolar air. Barotrauma occurs when the transalveolar pressure increases to a degree that disrupts the structural integrity of the alveolus. This leads to alveolar rupture and interstitial emphysema. This can further progress by dissection of air along facial planes. (See "Diagnosis, management, and prevention of pulmonary barotrauma during invasive mechanical ventilation in adults".)

●Pneumothorax – Pneumothorax, the most common complication resulting from pulmonary barotrauma, results if the interstitial emphysema dissects along perivascular sheaths into the mediastinum and then the mediastinal parietal pleura ruptures. A pneumothorax should be suspected if the patient becomes hypoxemic and hypotensive following intubation and does not respond to alteration in ventilator settings and fluid administration [3,9]. A chest radiograph should be performed promptly so that treatment can be provided expeditiously. Needled decompression may be required prior to radiographic confirmation if the patient has or is about to suffer cardiovascular collapse. The most experienced clinician should perform needle decompression or insertion of a chest tube for pneumothorax [63]. (See "Causes of acute respiratory distress in children", section on 'Tension pneumothorax'.)

●Other pulmonary barotrauma – Dissection of air elsewhere along fascial planes can result in pneumomediastinum, pneumoperitoneum, or subcutaneous emphysema [65]. Other clinical manifestations of pulmonary barotrauma include bronchopleural fistula, tension pneumothorax, tension lung cysts, hyperinflation of the left lower lobe, systemic gas embolism, and subpleural air cysts [66].

Hypotension — Hypotension is a risk in any patient who is transitioned from negative- to positive-pressure ventilation. This risk is increased in patients with asthma who are mechanically ventilated. The hyperinflation that is intrinsic to asthma and the increased intrathoracic pressure associated with positive-pressure ventilation impede venous return to the heart. This effect may be compounded by the administration of sedatives and paralytics, which act as vasodilators and myocardial depressants. (See 'Sedation and paralysis' above.)

Several steps can be taken to minimize the risk of hypotension in patients with asthma who require mechanical ventilation. These include measures to limit peak pressure and avoid hyperinflation, as described above. Patients also may benefit from the administration of intravenous fluids to improve and optimize intravascular volume. Optimization of intravascular volume may help to blunt the tachycardia that results from vasodilation associated with systemic absorption of bronchodilators. Continuous cardiopulmonary monitoring is advised to detect hypotension. (See 'Dynamic hyperinflation' above and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Fluid support'.)

Empiric fluid may be administered before intubating, or fluid boluses may be made immediately available prior to sedation in anticipation of the hypotension that may be generated by sedative administration or the conversion to positive pressure ventilation. An extreme measure that can be taken if blood pressure fails to respond to volume resuscitation is to transiently disconnect the patient from the ventilator or manual resuscitator (bag valve mask or Ambu bag). This permits complete evacuation of the lung and, in turn, appropriate venous return to the heart. (See "Hypovolemic shock in children in resource-abundant settings: Initial evaluation and management", section on 'Fluid resuscitation'.)

Other complications — Other complications seen in children with severe asthma exacerbations managed in the intensive care unit (ICU), particularly those who require mechanical ventilation, include:

●Nosocomial infection (eg, ventilator-associated pneumonia [VAP], pneumonitis, sinusitis, tracheobronchitis, central line-associated blood stream infection [CLABSI])

●Gastrointestinal bleeding (see "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention")

●Myopathy and prolonged weakness; the risk increases with neuromuscular blockade and glucocorticoid use [31-36] (see 'Sedation and paralysis' above)

●Subglottic stenosis

●Aspiration at the time of intubation

OUTCOMES — Mechanical ventilation is associated with increased morbidity, mortality, and resource utilization in children with acute severe asthma exacerbations.

In a population-based study using the largest all-payer hospital discharge database in the United States (Nationwide Inpatient Sample, 2009 to 2010), mechanical ventilation was infrequently required by children admitted to hospitals for status asthmaticus (0.55 percent incidence) but was associated with higher mortality rate and increased resource utilization [11]. Over the study period, an overall in-hospital mortality rate of 0.03 percent was seen among over 250,000 children and adolescents admitted for status asthmaticus, but a mortality rate of 4 percent was found among children receiving mechanical ventilation. In a separate study that reviewed asthma management in 1528 children who were treated in 11 pediatric ICUs (PICUs), the mortality rate for ventilated children with asthma was 2 to 3 percent [9]. In a subsequent study published in 2012, reported mortality varied from 0.1 to 3 percent across pediatric centers for children admitted to the ICU [67].

WEANING FROM MECHANICAL VENTILATION — The primary goals for mechanical ventilation are to ease the patient's work of breathing and allow time for the bronchospasm and airway obstruction to improve. The majority of patients intubated prior to intensive care unit (ICU) care are extubated within a day [2], while children who have a trial of noninvasive positive pressure ventilation (NPPV) prior to intubation in the ICU are usually ventilated for two to three days [67,68]. Longer ventilation times are often required if the exacerbation is accompanied by pneumonia or other systemic illness. (See 'General principles' above.)

Positive response to therapy is indicated by:

●Improvement in and normalization of arterial blood gas measurements

●Decrease in the amount of peak inspiratory pressure (PIP) necessary to deliver the desired tidal volume (TV)

●Decreased wheezing in the expiratory phase of respiration

●Decreased need for supplemental oxygen (indicating improvement in ventilation/perfusion [V/Q] mismatch)

As the clinical status improves, the patient can be permitted to breathe spontaneously. Spontaneous modes such as pressure support allow the patient to determine the inspiratory and expiratory times. (See 'Ventilatory modes' above.)

A trial of extubation can be performed when the patient is comfortably achieving adequate oxygenation and effective ventilation. This is indicated by maintenance of a normal or near-normal partial pressure of carbon dioxide in arterial blood (PaCO₂) or normal pH with minimal settings (positive end-expiratory pressure [PEEP] and pressure support of 5 cm H₂O each) and a peripheral capillary oxygen saturation (SpO₂) >95 percent with a fraction of inspired oxygen (FiO₂) of ≤0.4 or less. Once the patient demonstrates readiness for extubation, sedation should be held until the patient demonstrates appropriate strength and wakefulness. Patients should be observed in the ICU for at least 24 hours following extubation to monitor for signs of respiratory embarrassment including tachypnea, dyspnea, increased work of breathing, hypoxia, and atelectasis.

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 children".)

SUMMARY AND RECOMMNEDATIONS

●Indications and approach to endotracheal intubation – The decision to intubate a patient with status asthmaticus is made clinically based upon clinical findings and physiologic changes. Care must be taken to control the airway before the patient suffers a respiratory arrest or a hypoxic insult. Intubation is performed by rapid sequence intubation (table 1). The clinician most experienced with airway management should perform the intubation. (See 'Indications' above and "Technique of emergency endotracheal intubation in children" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

●Sedation and paralysis – Supportive measures that help to prevent tachypnea, breath stacking, and ventilator dyssynchrony include analgesia, sedation, and paralysis. Ketamine and propofol are sedative agents with bronchodilatory properties that can be used for induction but also ongoing sedation, though use of propofol for sedation in the pediatric intensive care unit (PICU) carries the risk of propofol infusion syndrome (PIS) and is generally limited to <24 hours. Fentanyl, dexmedetomidine, and midazolam are also used for sedation. To minimize the risk of myopathy, neuromuscular blocking agents should be discontinued once sedation alone is sufficient to facilitate patient ventilator synchrony. (See 'Sedation and paralysis' above.)

●Limiting risk of hyperinflation and barotrauma – Successful mechanical ventilation in patients with asthma depends upon limiting the risk of hyperinflation and barotrauma. This requires acceptance of an initial partial pressure of carbon dioxide in arterial blood (PaCO₂) that is higher than normal with an accompanying respiratory acidosis, a strategy called "permissive hypercapnia" or "controlled hypoventilation." (See 'Strategies to limit risk of hyperinflation and barotrauma' above.)

●Ventilator settings – Initial ventilator settings (table 2) should be adjusted as necessary to maintain adequate exhalation, as assessed by chest auscultation and measurement of arterial blood gases, and to prevent complications. (See 'Ventilator settings' above.)

●Medical therapy – Patients are continued on maximal medical therapy. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Pharmacotherapy'.)

●Adjunctive therapies – Extracorporeal membrane oxygenation (ECMO) and inhalational anesthetics are rarely used adjunctive therapies that are reserved for patients who are not adequately oxygenated or ventilated despite appropriate mechanical ventilation and maximal pharmacotherapy. (See 'Adjunctive therapies' above.)

●Complications – Complications can result from the asthma exacerbation itself or the treatments. Complications of mechanical ventilation in patients with asthma include hyperinflation, barotrauma, and pneumothorax. Delayed recognition and mitigation of these adverse events can result in hemodynamic instability. Continuous cardiopulmonary monitoring is advised to detect hypotension. Dynamic hyperinflation can be recognized with ventilator hold maneuvers, which will reveal elevated end-expiratory pressure and elevated plateau pressure. Chest radiographs are useful when pneumothorax is suspected.

Other complications of invasive mechanical ventilation (IMV) include myopathy, nosocomial infection, gastrointestinal bleeding, and subglottic stenosis. (See 'Complications' above.)

●Mortality – The mortality rate for ventilated children with acute severe asthma exacerbations is approximately 1 to 5 percent. (See 'Outcomes' above.)