Anesthesia for the child with asthma or recurrent wheezing

INTRODUCTION — Asthma is a chronic inflammatory lung disease characterized by symptoms of cough, wheezing, dyspnea and chest tightness, partially or completely reversible airway narrowing, and increased airway responsiveness to a variety of stimuli. Increased airway responsiveness is also seen in children with recurrent acute wheezing due to causes other than asthma (eg, allergies, viral infections). Asthma and recurrent wheezing are common childhood illnesses; pediatric patients with these conditions commonly present for anesthesia and surgery and can pose challenges for the anesthesiologist. Children with these conditions are at increased risk for perioperative respiratory adverse events, including laryngospasm and bronchospasm.

Wheezing can occur at any time during anesthesia, most commonly during induction of general anesthesia after endotracheal intubation. If it occurs, it is usually transient and without sequelae if treated. However, bronchospasm can be severe and can result in significant morbidity and mortality.

This topic will discuss preoperative assessment and preparation of pediatric patients with asthma and recurrent wheezing, as well as intraoperative management. Evaluation and management of asthma in children is discussed in more depth separately.

●(See "Asthma in children younger than 12 years: Initial evaluation and diagnosis".)

●(See "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control".)

●(See "Evaluation of wheezing in infants and children".)

PREOPERATIVE EVALUATION — When possible, we prefer to assess patients with asthma one to two weeks prior to elective surgery to allow time for modification of treatment, if necessary. The goal of preoperative preparation is optimization of therapy to reduce the risk of perioperative respiratory adverse events (PRAE).

Asthma severity and control — The history given by the patient or caregiver at the time of preoperative evaluation can help determine the severity and level of medical control of asthma and predict the likelihood of perioperative bronchospasm. Important historical points to emphasize during preoperative evaluation, in addition to a complete preoperative history, include:

●Severity of asthma as assessed by patient or caregiver

●Triggering factors

●Personal or family history of allergies and atopy

●Passive or active cigarette smoke inhalation

●Frequency and type of asthma medication use for maintenance and rescue

●Dose, frequency, and most recent use of oral glucocorticoids

●History of hospitalizations, intubations, and/or emergency department visits

●Recent upper respiratory infection (URI), sinus infection, nocturnal cough, or fever

●Baseline and current peak expiratory flow or FEV₁ if applicable

Using this information, the level of control of asthma is classified as well controlled, not well controlled, or very poorly controlled. (See "An overview of asthma management", section on 'Adjusting controller medication'.)

Any patient with asthma that is not well controlled should be referred to the appropriate clinician, primary care physician, or asthma specialist for treatment optimization prior to elective surgery. Further information about the assessment of asthma control is presented in detail separately. (See "An overview of asthma management", section on 'Symptom and risk assessment'.)

National and international organizations have developed guidelines that suggest a stepwise approach to the treatment of asthma in children. Patients are placed on a step that prescribes preferred and alternative medications, based on severity and control of symptoms, and can move up or down steps as disease worsens or improves.

Medical management typically starts with intermittent or daily inhaled glucocorticoids whenever a short acting beta₂ agonist is used, progressing as necessary with increasing doses of inhaled glucocorticoids and the addition of long-acting beta₂ agonists (LABA), long-acting muscarinic agonists, anti-IgE, anti-IL5/5R, antiIL4R, leukotriene receptor antagonists, methylxanthines, and oral glucocorticoids.(See "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control".)

Wheezing is a known risk factor for PRAE. In a large cohort study of 9287 children undergoing general anesthesia, perioperative bronchospasm and laryngospasm were encountered in 2.1 and 3.8 percent, respectively [1]. A positive respiratory history (URI in the last two weeks, nocturnal dry cough, wheezing during exercise, or wheezing more than three times in the past 12 months) was associated with an increased risk of bronchospasm, perioperative cough, desaturation, or airway obstruction. URI was associated with PRAE only if present at the time of anesthesia or less than two weeks prior to the procedure. A history of current or past eczema as well as a family history of two family members with asthma, eczema, hayfever, or smoking increased the risk of PRAE as well. Risk factors for PRAE are shown in table (table 1). (See "Anesthesia for the child with a recent upper respiratory infection".)

Physical examination — Preoperative physical examination for patients with asthma should focus on respiratory rate, wheezing, signs of lung infection, and air movement. The patient should ideally not be wheezing at the time of anesthesia. Baseline pulse oximetry value should be noted.

Preoperative testing — Patients who have well controlled asthma that is not steroid-dependent generally do not need additional testing beyond that which is performed for patients without asthma.

●Pulmonary function testing – Younger children (eg, younger than five years) are often not capable of performing most techniques necessary for pulmonary function testing. Spirometry and measurement of peak flow rate can be used in the office setting for older children and may be useful preoperatively if the degree of asthma control is in question.

●Laboratory testing – Preoperative blood tests are rarely required and should only be performed as they would be for patients without asthma. However, patients who have taken oral glucocorticoids may be at risk for suppression of the hypothalamic pituitary axis (HPA) and adrenal insufficiency with the stress of surgery. Children who have been taking more than 5 mg/day of prednisone for more than three weeks in the past year should either have the hypothalamic pituitary axis evaluated or, more commonly, should receive stress dose steroids prior to induction of anesthesia. HPA suppression in patients taking glucocorticoids and stress dose glucocorticoids are discussed in more detail separately. (See "Treatment of adrenal insufficiency in children", section on 'Surgical procedures' and "The management of the surgical patient taking glucocorticoids".)

Therapy with inhaled glucocorticoids can also affect HPA function, but the effects seem to be infrequent and largely subclinical. For children receiving inhaled glucocorticoid therapy within the recommended ranges, the risk of symptomatic adrenal suppression or acute adrenal crisis appears to be very small. Adrenal suppression with use of inhaled glucocorticoids is discussed more fully separately. (See "Major side effects of inhaled glucocorticoids", section on 'Adrenal suppression'.)

●Arterial blood gas testing – Preoperative arterial blood gas testing is not routinely indicated, though it may be useful during a severe asthma attack.

●Chest radiograph – Chest radiograph may show signs of hyperinflation but is not routinely indicated unless looking for signs of pulmonary infection or barotrauma.

PREOPERATIVE MEDICATION MANAGEMENT

Maintenance medications — Patients with asthma should continue all of their usual medication up to and including the day of surgery. The exception is theophylline, which should be discontinued the evening prior to surgery because of the risk of cardiac arrhythmias [2]. Continuation of inhaled medications, including inhaled glucocorticoids, has been shown to reduce the incidence of postoperative pulmonary complications [3]. (See "Perioperative medication management", section on 'Pulmonary agents'.)

Supplemental glucocorticoids — Supplemental glucocorticoids should be given in consultation with a pulmonary or primary care clinician. Preoperative inhaled glucocorticoids should be administered for children with not well controlled asthma and who are not currently receiving inhaled glucocorticoids.

For children with very poorly controlled asthma requiring endotracheal intubation, we suggest a course of supplemental systemic glucocorticoid. In this setting, we usually administer prednisone or prednisolone orally 1 mg/kg (maximum 50 mg) once a day for 3 to 10 days. Intravenous (IV) hydrocortisone (4 mg/kg, maximum 100 mg, every six hours) or methylprednisolone (1 to 2 mg/kg, maximum 125 mg, once daily) are acceptable alternatives for patients unable to tolerate oral medications.

In adults, preoperative systemic glucocorticoids may improve lung function and reduce the bronchoconstrictive response to endotracheal intubation [4]. In addition, a number of studies have shown that systemic glucocorticoids do not increase postoperative wound infections, delayed wound healing, or asthma exacerbations [4-6]. However, there are no specific pediatric data.

PREMEDICATION — Bronchodilators are routinely administered to children with asthma prior to endotracheal intubation. We do not routinely premedicate children with asthma with sedatives.

●Inhaled bronchodilators – Children with asthma should receive inhaled short-acting beta₂ agonist (SABA) treatment 20 to 30 minutes prior to induction of anesthesia (albuterol, via nebulizer 2.5 mg if <20 kg, 5 mg if >20 kg, or via metered dose inhaler [MDI] with spacer, two to eight puffs) [7,8].

Additionally, preoperative SABA may reduce perioperative respiratory adverse events (PRAE) in children undergoing tonsillectomy [9]. (See "Anesthesia for tonsillectomy with or without adenoidectomy in children", section on 'Preoperative inhaled short-acting beta-2 agonist (SABA)'.)

●Benzodiazepines – Although benzodiazepines may be used in patients with asthma to reduce anxiety, they do not reduce the incidence of laryngospasm or bronchospasm with general anesthesia and are associated with an increased risk for desaturations and airway obstruction [1]. We prefer to use distraction techniques (eg, toys, video games, stickers) prior to anesthesia for most pediatric patients, including those with asthma, rather than administration of sedatives.

●Alpha agonists – There are conflicting data regarding the use of alpha agonists, such as clonidine and dexmedetomidine, for patients with asthma. Alpha agonists have been shown in animal studies to blunt reflex bronchoconstriction and might therefore be beneficial as premedication for children undergoing general anesthesia [10-12]. In contrast, two small clinical trials in adults showed an increase in histamine-induced airway resistance following oral clonidine [13,14]. Intranasal dexmedetomidine (3 mcg/kg) has been successfully used in agitated children with asthma [15].

REGIONAL VERSUS GENERAL ANESTHESIA — Airway management, particularly the use of an endotracheal tube, is a very potent stimulus for bronchoconstriction. When possible, avoidance of endotracheal intubation and instead the use of noninvasive airway devices (eg, supraglottic airway devices) decrease the chance of intraoperative bronchospasm and laryngospasm.

While regional anesthesia avoids the need to manipulate the airway, it is rarely used in the pediatric population. When possible in older children, regional anesthesia is a good choice as it avoids the need to manipulate the airway. Regional anesthesia is discussed more fully separately. (See "Anesthesia for adult patients with asthma", section on 'Regional anesthesia'.)

General anesthesia is associated with increased risk of bronchospasm and laryngospasm compared with regional anesthesia. In this setting bronchospasm occurs most commonly because of mechanical stimulation of the airway. In addition, bronchospasm can result from histamine release, an allergic reaction to administered medication, or from vagal stimulation during surgery (eg, peritoneal insufflation during laparoscopy, manipulation of viscera, or endoscopy).

STRATEGY FOR GENERAL ANESTHESIA — The risk of perioperative respiratory adverse events (PRAE), particularly for bronchospasm and laryngospasm, decreases with increasing experience in pediatric airway management [1,16,17]. As such, we suggest that children with asthma are best managed by an experienced pediatric anesthesiologist. This is particularly true for those with additional risk factors for PRAE (table 1).

Airway management — One goal of induction of anesthesia in the patient with asthma is to minimize the risk of a bronchoconstrictive response to airway management. Since the risk of bronchospasm is lower with a laryngeal mask airway (LMA) or mask ventilation when compared with endotracheal intubation [1,18-20], these less invasive devices should be used when possible rather than an endotracheal tube.

If endotracheal intubation is planned, we use a cuffed endotracheal tube (ETT) as opposed to an uncuffed ETT for all children, but particularly if a child has an increased risk of developing bronchospasm or has poorly controlled asthma. The cuffed ETT allows the use of higher peak airway pressures during mechanical ventilation with less leakage around the ETT [21,22]. A further advantage, irrespective of the presence of asthma, is that cuffed ETTs (when cuff pressure is well monitored) are associated with less perioperative laryngospasm, bronchospasm, and severe persistent coughing as well as less postoperative sore throat and hoarse voice [22,23]. (See "Airway management for pediatric anesthesia", section on 'Cuffed versus uncuffed endotracheal tubes'.)

If endotracheal intubation is planned, we suggest the use of neuromuscular blocking agents for children with asthma, as this is associated with less PRAEs [17].

Induction of anesthesia — Induction must achieve a depth of anesthesia sufficient to prevent physiologic response to airway manipulation. This is particularly important in the patient with asthma.

Most intravenous (IV) and inhalation anesthesia induction agents blunt airway reflexes and produce bronchodilation in varying degrees. During induction of anesthesia and airway manipulation, the ability of a medication to suppress airway reflexes is of particular value. During maintenance of anesthesia, the bronchodilatory effect of a drug may be more important.

Intravenous versus inhalation induction — When possible and tolerated by the child, we suggest IV induction rather than inhalation induction for children at risk for PRAE, including children with asthma. Traditionally, inhalation induction has been performed in pediatric anesthesia; however, IV induction has gained widespread acceptance.

The preponderance of available evidence suggests that IV induction is associated with reduced risk of perioperative PRAE in at risk children. In a single-center randomized trial including 300 children with two or more risk factors for PRAE (upper respiratory infection [URI] ≤2 weeks, wheezing ≤12 months, wheezing at exercise, nocturnal dry cough, past/present eczema, passive smoking, family history of hay fever/asthma/eczema) who underwent general anesthesia with a supraglottic airway, children who were assigned to inhalation induction with sevoflurane were twice as likely to experience PRAE (ie, bronchospasm, laryngospasm, coughing, desaturation to <95 percent, airway obstruction, or stridor) compared with those who were induced with propofol (43 versus 26 percent, relative risk [RR] 1.7, 95% CI 1.2-2.3) [24].

In support of these results, two large observational studies in children with and without risk factors for PRAE undergoing anesthesia found that IV induction was associated with fewer respiratory complications [1,17]. In a single-center prospective observational study of PRAE (ie, bronchospasm, laryngospasm, coughing, desaturation to <95 percent, airway obstruction, or stridor) in more than 9000 pediatric anesthetics, inhaled induction was associated with an increase in PRAE (20 versus 10 percent, RR 1.97, 95% CI 1.78-2.18) [1]. Similarly, in the Anaesthesia PRactice In Children Observational Trial (APRICOT) study, a large prospective multi-institutional study of critical events in over 31,000 pediatric anesthetics, inhalation induction was associated with an increase in severe respiratory critical events, defined as laryngospasm, bronchospasm, or postoperative stridor (2.2 versus 3.6 percent, RR 0.85, 95%CI 0.74-0.98]) [17].

A meta-analysis of four randomized trials including 588 children with and without known risk factors for PRAE who underwent general anesthesia did not demonstrate superiority of IV over inhaled induction with regards to rates of PRAE (RR 2.9, 95% CI 0.2-36.4) [25]. There was high risk of bias due to lack of blinding in all studies, high clinical heterogeneity among studies, and high statistical heterogeneity for all outcomes.

Lidocaine — We do not routinely use IV lidocaine prior to endotracheal intubation of children with asthma. In adults, IV lidocaine (1 to 2 mg/kg) and inhaled lidocaine (nebulized 5 mg/kg in saline) have been shown to attenuate bronchial hyperreactivity, including in patients with asthma [26-28], and in children, IV lidocaine (2 mg/kg IV) has been shown to transiently reduce the incidence of laryngospasm with vocal cord irritation [29]. However, inhaled lidocaine initially causes bronchoconstriction in patients with asthma and can cause cough and laryngospasm [30-32]. We do not recommend the use of topical lidocaine in children prior to endotracheal intubation without neuromuscular blockade, as this has been shown to increase desaturations without reducing the incidence of bronchospasm or laryngospasm [33].

Intravenous induction agents — While propofol is the induction agent of choice for most children with asthma, certain clinical scenarios may warrant the use of other agents. Both propofol and ketamine are bronchodilatory agents. IV induction of anesthesia in children is discussed in detail separately. (See "General anesthesia in neonates and children: Agents and techniques", section on 'IV induction'.)

●Propofol – We suggest using propofol for induction for the hemodynamically stable patient with asthma, as it has been shown to attenuate the bronchospastic response to intubation in both patients with and without asthma [34,35]. There are a number of case reports of significant bronchospasm with propofol use in patients allergic to the active components of the drug, the soybean oil or egg phosphatide in the propofol preparation, or, in some preparations, the sodium metabisulfite used as a preservative [34,36,37]. However, propofol appears safe even in children with egg allergy if there is no history of anaphylaxis [38].

●Ketamine – Ketamine has sympathomimetic bronchodilatory properties and blocks reflex bronchoconstriction, making it useful for induction, particularly in the hemodynamically unstable patient [39]. Ketamine-induced bronchodilation may not be as pronounced as that of propofol [40,41], though this has not been studied in children. The use of ketamine in addition to standard asthma treatment has not been shown to be of benefit in children with acute asthma exacerbation in the emergency department setting [42,43].

●Etomidate – Etomidate can be used for induction in patients with asthma, but it lacks the bronchodilatory effects of propofol [34]. Etomidate might be useful for induction of hemodynamically unstable patients. However, there is a risk of adrenal insufficiency in critically ill patients after an induction dose of etomidate [44]. Etomidate is not available in some countries (eg, Australia).

●Barbiturates – Thiopental, which is no longer available in the United States, releases histamine and has been shown to cause higher airway resistance compared with ketamine and propofol [34,41]. Methohexital does not release histamine and can be used as an alternative to the induction agents discussed. However bronchoconstriction in response to endotracheal intubation is more common with induction with methohexital than with propofol [41].

Maintenance of anesthesia

Anesthetic agents — For most patients with asthma, total IV anesthesia (TIVA), sevoflurane, isoflurane, or halothane can safely be used for maintenance of anesthesia.

Inhalation agents — Most potent or volatile inhalation anesthetic agents (eg, isoflurane, sevoflurane, and halothane) are bronchodilators, decrease airway responsiveness, and attenuate bronchospasm [45]. However, volatile anesthetic agents only have a limited ability to blunt reflex bronchoconstriction [46,47]. Attenuation of these reflexes is particularly important in children with asthma in order to avoid PRAE [46,47]. Volatile anesthetic agents have been used to treat status asthmaticus [48]. (See "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Delivery of inhaled medications'.)

Of the volatile agents, sevoflurane is generally preferred for patients with asthma because it is the most effective bronchodilator. Where available, halothane is an acceptable alternative. Desflurane is an extremely pungent volatile anesthetic and can produce an increase in secretions, coughing, airway resistance, and laryngospasm [49-51]. Desflurane should not be used in children with asthma or risk factors for PRAE since it significantly increases airway resistance and the incidence of PRAE in the pediatric population.

Nitrous oxide is a relatively weak inhaled anesthetic that is often used in conjunction with other anesthetics for general anesthesia in much higher concentration than the volatile agents. It is not an airway irritant but is also not a bronchodilator [45]. It can be used safely in patients with asthma who have no other contraindication to its use and who do not require 100 percent oxygen.

Intravenous agents — IV anesthetic medications may be used by either bolus or infusion along with inhalation agents, or as part of a TIVA. Combinations of propofol, ketamine, clonidine, and dexmedetomidine, as well as a variety of opioids, are used in this way. There are no studies that establish the benefits of combinations of these medications in asthma, but each of them in isolation has been shown to be safe or beneficial. Dexmedetomidine, an alpha₂ agonist, has been shown to protect against histamine-induced bronchoconstriction in dogs [12].

Neuromuscular blocking agents — Neuromuscular blocking agents are the most common cause of intraoperative allergic (IgE-mediated) and nonallergic reactions, which may cause bronchospasm through histamine liberation. Mivacurium and atracurium release histamine, though bronchospasm as a result is very rare [52]. The more commonly used relaxants (rocuronium, vecuronium, and cisatracurium) and the less commonly used pancuronium do not release appreciable amounts of histamine. Rocuronium and succinylcholine are the most commonly used agents associated with IgE-mediated allergic reactions [53]. Succinylcholine releases low levels of histamine and has been used safely in patients with asthma [54].

Reversal of neuromuscular blocking agents with anticholinesterase agents such as neostigmine can cause an increase in bronchial secretions and airway reactivity and can trigger bronchospasm [55], though this is rare. Neostigmine is administered with anticholinergic medication, either glycopyrrolate or atropine, to block the muscarinic receptors responsible for this effect.

Sugammadex, a newer drug used for the reversal of muscle relaxants, works by encapsulation of steroidal neuromuscular blockers and is devoid of muscarinic and bronchial smooth muscle effects [56]. However, a study of the use of sugammadex in patients with pulmonary disease showed a 2.6 percent incidence of bronchospasm and should therefore be used cautiously [57,58]. Sugammadex is also associated with a dose dependent incidence of anaphylaxis [59].

Opioids — Synthetic opioids are generally preferred for patients with asthma, though data are lacking to suggest that any particular opioid is safer for children with asthma. Almost all opioids release some amount of histamine and can thus theoretically cause bronchospasm. Morphine in particular can release histamine and cause bronchospasm, especially if given rapidly and in large doses [60,61], though in some patients morphine has been shown to blunt reflex bronchoconstriction [62]. Synthetic opioids (ie, fentanyl, sufentanil, remifentanil, and hydromorphone) tend to release much less histamine, and have all been used safely in patients with asthma [63,64]. An exception is meperidine, a synthetic opioid which can release relatively high levels [65].

Beta blockers — Beta blockers are only rarely used in pediatric anesthesia and should be used cautiously in patients with asthma. When required, the lowest possible dose of a beta₁-selective agent should be administered.

Beta blockade with nonselective drugs, which are those that block both beta₁ and beta₂ receptors, can cause bronchospasm because of their beta₂-blocking effects and may reduce the efficacy of beta agonist medication.

Esmolol and metoprolol, two beta₁-selective drugs that are commonly used under anesthesia, are much less likely to cause bronchospasm, though at high doses their selectivity may diminish. [66] Labetalol, a combined beta and alpha blocker, is even less likely to cause bronchospasm [67]. The use of beta blockers in patients with asthma is discussed in more detail separately. (See "Major side effects of beta blockers", section on 'Increased airways resistance'.)

Ventilation during anesthesia — Ventilatory strategy for patients with asthma during anesthesia that requires controlled ventilation should be designed to reduce air trapping [68,69]. Even during bag mask ventilation, patients with airflow obstruction need prolonged expiration. Stacked breaths, which occur when a breath starts before the prior exhalation is complete, can result in air trapping, hyperinflation, and, in the extreme, barotrauma. Reduction of the inspiratory/expiratory ratio is an important strategy to reduce air trapping, but the most effective maneuver is to reduce minute ventilation by reducing both rate and tidal volume [68]. This strategy may require permissive hypercapnia; ie, acceptance of a higher than normal end-tidal CO₂ or PCO₂. (See "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Ventilation strategy'.)

For children with well controlled asthma and no signs of bronchospasm under anesthesia, ventilatory strategy should be the same as for children without asthma. If there are any signs of bronchospasm, the following initial ventilator settings should be used, modified in response to the clinical situation (see 'Identification' below):

●Tidal volume of 6 to 8 mL/kg

●Respiratory rate near or below physiologic rate

●I:E ratio to prevent breath stacking, approximately 1:4

●Positive end-expiratory pressure (PEEP) of 3 to 5 cm H₂O

●Peak airway pressure <50 cm H₂O; plateau pressure <35 cm H₂O

Increased alveolar pressure is associated with an increased incidence of barotrauma, but peak inspiratory pressures do not reliably reflect plateau pressures or alveolar pressures in the presence of severe airflow obstruction.

If possible, the flow time curve should be assessed and the ventilator settings (eg, respiratory rate and expiratory time) should be modified to allow expiratory flow to return as close to baseline as possible [70,71].

INTRAOPERATIVE BRONCHOSPASM

Incidence — The reported incidence of intraoperative bronchospasm in children is between 0.3 and 3.2 percent [1,17]. In the Anaesthesia PRactice In Children Observational Trial (APRICOT) study, a prospective observational study of critical events in 30,874 children <15 years of age who underwent anesthesia in 261 hospitals throughout Europe, there was wide variation in the incidence of bronchospasm across centers, between 0.3 to 3.2 percent [17]. Ninety six percent of cases of bronchospasm occurred in the operating room, rather than in the post-anesthesia care unit.

Identification — Signs of bronchospasm under anesthesia include:

●Wheezing on chest auscultation

●Slow or incomplete expiration on inspection

●Change in end-tidal carbon dioxide (EtCO₂)

•Upsloping EtCO₂ waveform

•Severe: decreased value, or absent EtCO₂ waveform

●Decreased tidal volume

●High inspiratory pressure

●Decreasing oxygen saturation

Nonbronchospastic causes of the above findings should be ruled out, while setting FiO₂ to 100 percent and changing to hand ventilation to assess compliance and exhalation. During bronchospasm, compliance is decreased, and exhalation is prolonged. The following may mimic bronchospasm and are suggested by these clinical findings:

●Endobronchial intubation – Decreased breath sounds on one side (usually left) and a deep endotracheal tube; asymmetric chest rise.

●Pneumothorax – Decreased breath sounds on one side; asymmetric chest rise; tracheal deviation away from pneumothorax, particularly if high respiratory rate in combination with high tidal volumes have been used or clinical scenario, making pneumothorax likely (eg, trauma, diaphragm injury).

●Pulmonary edema – Frothy secretions in the endotracheal tube; crackles on pulmonary exam.

●Kinked or obstructed endotracheal tube – Difficulty passing suction catheter and/or removal of secretions upon suctioning.

Bronchospasm may be part of an anaphylactic reaction. Signs that suggest anaphylaxis include hypotension, tachycardia, and rash. The management of anaphylaxis is presented separately (table 2). (See "Anaphylaxis: Emergency treatment", section on 'Immediate management'.)

Management — When bronchospasm is suspected, initial management includes administration of 100 percent oxygen and careful hand ventilation (slow respiratory rate and sufficient expiratory time to avoid barotrauma). Mild bronchospasm is commonly treated by deepening the anesthetic. This can be accomplished by administering a bolus of propofol or ketamine or by deepening the level of inhaled anesthetic.

Patients with bronchospasm that persists after deepening the anesthesia should receive short-acting beta agonist therapy. A rapidly acting beta₂ agonist such as albuterol (salbutamol) should be administered by metered dose inhaler (MDI) via the endotracheal tube with an adapter. Eight to 10 puffs of short-acting beta₂ agonist (SABA) therapy should be used since much of the medication will condense in the endotracheal tube.

In spontaneously breathing, unintubated children, the optimal method for administration of inhaled medication for the treatment of bronchospasm is via a pressurized MDI (pMDI) with a spacer, while the optimal method for aerosol delivery in mechanically ventilated patients is less clear [72-74]. Much of the medication delivered by MDI condenses in the endotracheal tube or breathing circuit. In addition, the use of a small-sized ETT reduces the amount of drug reaching the lungs. A 10-fold greater dose of aerosol is required to provide a clinical effect when an MDI is used in an intubated patient, as compared with the doses used in an unintubated patient. It has been estimated that <3 percent of the drug dose is delivered to the bronchial site of action with use of an MDI when an endotracheal tube is in place [75]. Aerosol administration via the actuator of an MDI directly connected to the ETT may result in greater drug delivery to the lower airways compared with the use of an inline adaptor or a 50 mL Luer-Lok syringe [76].

More severe bronchospasm requires further intervention with one or more of the following:

●Volatile anesthetic agents – Except for desflurane, volatile anesthetic agents are excellent bronchodilators and have been successfully used to treat status asthmaticus [48]. The fastest and easiest intraoperative treatment is to increase the concentration of volatile anesthetics. (See "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Delivery of inhaled medications'.)

●Anticholinergics – Glycopyrrolate (4 mcg/kg intravenous [IV]), atropine (20 mcg/kg IV), and ipratropium (250 to 500 mcg by nebulizer or four to eight puffs 18 mcg/puff via MDI) have bronchodilatory properties. When compared with atropine, glycopyrrolate produces bronchodilation of longer duration (>4 hours versus 3 to 4 hours) [77]. Onset of effect takes 20 to 30 minutes, so anticholinergic use should be combined with a more rapidly acting treatment, such as albuterol. IV anticholinergics often cause significant tachycardia.

●Epinephrine – For refractory bronchospasm, and especially if anaphylaxis is suspected, epinephrine should be administered. Standard dosing for intramuscular (IM) administration is 0.01 mL/kg of a 1 mg/mL solution, maximum dose 0.4 mg or 0.4 mL administered IM into the mid-outer thigh (vastus lateralis muscle), which can be repeated at 5 to 15 minute intervals. When IV access has been established, an epinephrine infusion may be started at 0.1 to 1 mcg/kg/minute via infusion pump, monitoring for tachycardia and hypertension. If continued infusion is required, central venous access should be established for administration. (See "Anaphylaxis: Emergency treatment", section on 'Dosing and administration'.)

For cases of severe, refractory bronchospasm when cardiac arrest is imminent, epinephrine should be administered by IV bolus, starting with 10 mcg IV, escalating as needed.

●Intravenous SABA – In cases of severe bronchospasm refractory to other therapies, we administer IV albuterol (salbutamol) 10 mcg/kg over 10 minutes followed by 1 to 5 mcg/kg/minute. IV albuterol is not available in the United States [78,79]. IV terbutaline can be administered. Bolus with 10 mcg/kg IV over 10 minutes, then 0.1 to 10 mcg/kg/minute; infusion may be increased by 0.1 to 1 mcg/kg/minute every 30 minutes to a maximum of 5 mcg/kg/minute. Side effects of IV SABA include tachycardia and dysrhythmias, hypotension, hyperglycemia, hypokalemia, and myocardial ischemia. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management", section on 'Bronchodilators'.)

●Glucocorticoids – High-dose glucocorticoids hydrocortisone 4 mg/kg IV (maximum 100 mg) or IV methylprednisolone (1 to 2 mg/kg, maximum 125 mg) will not be effective for four to six hours and should be combined with rapidly acting medication. Perioperative steroids have not been shown to increase surgical complications [5].

●Neuromuscular blocking agents – In cases of severe bronchospasm, neuromuscular blocking agents (NMBAs) may improve mechanics of ventilation and lower peak inspiratory pressures [70,80]. An NMBA that does not release histamine should be chosen in this situation. (See 'Intravenous agents' above.)

●Magnesium sulfate – Magnesium sulfate (40 mg/kg up to 2 g IV over 20 minutes in children >2 years) may be helpful with difficult cases of bronchospasm, especially when given with inhaled beta₂ agonist and glucocorticoids. A meta-analysis supports its use in acute exacerbations of asthma [81,82]. High doses and blood levels of magnesium produce skeletal muscle weakness and central nervous system depression. Magnesium may cause hypotension because of a reduction in systemic vascular resistance.

Some interventions are controversial or have been described only in case reports for the adult population but are not commonly employed by anesthesiologists. These include:

●Theophylline – In a systematic review, IV theophylline had no benefit over IV SABAs [79]. In contrast to volatile anesthetic agents, theophylline has narrow therapeutic window and is not readily available in the operating room environment.

●Heliox – Mixtures of helium and oxygen (heliox) have occasionally been used in cases of acute, severe bronchospasm. However, heliox can only provide a fraction of inspired oxygen (FiO₂) of 21 to 30 percent and does not reverse bronchospasm, so it is used as a temporizing measure while bronchospasm is treated [83]. In addition, technical constraints limit the ability to use heliox during anesthesia. (See "Physiology and clinical use of heliox".)

●Extracorporeal membrane oxygenation is reserved for the most severe bronchospasm that is refractory to maximal medical and mechanical ventilatory therapy. (See "Acute severe asthma exacerbations in children younger than 12 years: Endotracheal intubation and mechanical ventilation", section on 'Extracorporeal membrane oxygenation'.)

COMPLICATIONS OF BRONCHOSPASM — Patients with asthma are at risk for significant respiratory and cardiovascular complications during mechanical ventilation.

Respiratory deterioration — Hypoxemia can develop as a result of worsening airflow obstruction, tension pneumothorax, or atelectasis.

●Tension pneumothorax – Tension pneumothorax can occur with positive pressure ventilation, with mask ventilation, through a supraglottic airway device, or with an endotracheal tube. Signs of tension pneumothorax include asymmetrical breath sounds and chest rise, dullness to percussion, tracheal deviation away from pneumothorax, and high airway pressures, though these may not be sensitive signs in children. Hypotension can occur as a result of tension pneumothorax because of decreased venous return to the heart. If tension pneumothorax is suspected and the patient is unstable, a needle should be inserted in the second intercostal space in the midclavicular line to release the air. (See "Pneumothorax in adults: Epidemiology and etiology".)

If the patient is hemodynamically stable, chest radiograph should be performed to confirm the diagnosis of pneumothorax prior to chest tube placement.

●Atelectasis – Atelectasis is frequent in children with asthma due to mucus plugging in relatively small airway calibers. If atelectasis and hypoxia are severe, the patient might benefit from endobronchial suctioning. Suctioning should be done only when absolutely necessary, as it is a potent mechanical stimulus for bronchospasm. Recruitment maneuvers should be used to open up atelectasis.

Cardiovascular deterioration — Hypotension can occur for many reasons under anesthesia (eg, hypovolemia or blood loss, vasodilation, myocardial depression), but some are more likely in children with asthma. The following should be considered in the event of cardiovascular deterioration:

●Reduced venous return – High airway pressures can result in reduced venous return. Treatment of bronchospasm or, if necessary, brief disconnection of the ventilator to relieve high intrathoracic pressure may help in this situation [84].

●Anaphylaxis – Hypotension may result from anaphylaxis. Epinephrine is a mainstay of treatment of anaphylaxis, along with H₁ and H₂ blockers and glucocorticoids. Treatment of anaphylaxis is discussed more fully separately. (See "Anaphylaxis: Emergency treatment", section on 'Pharmacologic treatments' and "Anaphylaxis in infants", section on 'Epinephrine for first-aid treatment of anaphylaxis in the community'.)

●Adrenal insufficiency – Insidious hypotension in a child who has been taking oral or inhaled glucocorticoids may be due to adrenal insufficiency as a result of suppression of hypothalamic pituitary axis. Hyponatremia and hyperkalemia might be present. If adrenal insufficiency is suspected, stress dose glucocorticoid should be administered (0 to 3 years: hydrocortisone 25 mg IV; 3 to 12 years: hydrocortisone 50 mg IV; 12 years and older: hydrocortisone 100 mg IV). Treatment of adrenal insufficiency in children is discussed more fully separately. (See "Causes of central adrenal insufficiency in children" and "Treatment of adrenal insufficiency in children", section on 'Surgical procedures' and "Causes of central adrenal insufficiency in children", section on 'Chronic high-dose glucocorticoid therapy'.)

EMERGENCE AND EXTUBATION — Bronchospasm can occur on emergence from anesthesia when the endotracheal tube (ETT) is in place and level of anesthesia is reduced. The goal should be to achieve a smooth, controlled emergence. In our clinical practice, we commonly perform deep removal of the airway (ETT or supraglottic airway [SGA]) in children who are at increased risk of perioperative respiratory adverse events (PRAE).

Awake removal of the ETT in children has been shown to increase the incidence of persistent coughing and oxygen desaturation, while deep removal of the ETT increases the incidence of partial airway obstruction. Such obstructions are easily overcome by simple airway maneuvers (eg, chin lift or jaw thrust) and are not associated with desaturations [1,85], as long as post-anesthesia care unit staff are competent in these simple airway maneuvers.

Whereas deep removal of airway devices may result in a smoother emergence than awake removal, the risk of PRAEs may be similar.

●In a single-center randomized trial that compared awake versus deep extubation of the trachea in 100 children with increased airway susceptibility undergoing adenotonsillectomy, the rate of PRAEs were similar in the two groups [85]. Children who were extubated awake showed a tendency toward more and longer episodes of very brief (<10 seconds) desaturations to <95 percent, but overall there was no evidence for an increased risk of oxygen desaturation following either technique. There was also no difference in the occurrence of laryngospasm or bronchospasm between children who were extubated awake as compared with those who were extubated while still at a surgical level of anesthesia.

●In a single center randomized trial including 290 children with at least one risk factor for PRAE who underwent tonsillectomy with a supraglottic airway, the incidence of PRAEs was similar in children who had the SGA removed while deeply anesthetized versus removed when awake [86].

POSTOPERATIVE MANAGEMENT — The intraoperative course for the child with asthma dictates the postoperative course. If the intraoperative course is uneventful and pain, nausea, and pulmonary status are well controlled, the postoperative management is similar to the child without asthma.

●Postoperative pulmonary management – Maintenance oral and inhaled asthma medications should be continued postoperatively. In some cases, oral steroids will have to be replaced by intravenous (IV) steroids. Nebulized bronchodilators and glucocorticoids should be prescribed if the patient is unable to use a metered dose inhaler (MDI) in the postoperative period.

Adequate pain control, bronchodilator therapy, incentive spirometry for children who can cooperate, deep breathing maneuvers, and early mobilization are important to avoid postoperative pulmonary complications. (See "Strategies to reduce postoperative pulmonary complications in adults".)

If severe bronchospasm has occurred during anesthesia, delayed extubation and postoperative ventilation may be considered to allow time for maximal medical treatment, return of airway function, and perhaps recovery from neuromuscular blocking agents (NMBAs) without the need for reversal.

If a child with ongoing severe wheezing is extubated, recovery in a pediatric intensive care unit or a step-down unit should be considered. A trial of high-flow humidified oxygen or noninvasive ventilation (NIV) may be beneficial in children with asthma who are wheezing after extubation. This is discussed in more detail separately. (See "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management".)

●Postoperative pain management – Postoperative epidural analgesia may be beneficial, especially for patients having upper-abdominal and thoracic surgery. Effective epidural analgesia may reduce splinting, reduce atelectasis, maintain respiratory muscle function, and provide superior pain control [87]. Nerve blocks (eg, intercostal or paravertebral blocks) may achieve similar goals in patients who cannot have epidural placement. (See "Approach to the management of acute perioperative pain in infants and children".)

Nonsteroidal antiinflammatory drugs (NSAIDs) should be used with caution in children with a history of aspirin-exacerbated respiratory disease (ie, asthma, chronic rhinosinusitis, and nasal polyposis). NSAIDs increase leukotriene production by cyclooxygenase inhibition and have been associated with bronchospasm, laryngospasm, rhinorrhea, and periorbital edema in susceptible children (see "NSAIDs (including aspirin): Allergic and pseudoallergic reactions" and "Aspirin-exacerbated respiratory disease"). However, the risk of postoperative NSAIDs causing bronchospasm is small [88-90].

Acetaminophen/paracetamol use has been postulated to be a risk factor for asthma because this agent induces depletion of the antioxidant glutathione in lung tissue [91]. However, a randomized controlled trial in 300 children with mild persistent asthma reported that as-needed use of acetaminophen was not associated with a higher incidence of asthma exacerbations or worse asthma control than as-needed use of ibuprofen [92]. The possible association between prenatal exposure to acetaminophen and asthma is discussed more fully separately. (See "Risk factors for asthma", section on 'Acetaminophen'.)

SPECIAL POPULATIONS

Emergency surgery — Induction of anesthesia for an emergency procedure in the patient with asthma undergoing general anesthesia requires a balance between the need for rapid control of the airway and the avoidance of bronchospasm with intubation.

Except in truly life-threatening emergencies, there is usually time to conduct a basic evaluation, to administer an inhaled bronchodilator, and to potentially administer perioperative systemic glucocorticoids, if required (see 'Supplemental glucocorticoids' above). A rapid preoperative assessment of the patient presenting for emergency surgery should at least include a brief history including identification of precipitating factors, medical management of asthma, degree of pulmonary disability, and previous episodes of bronchospasm under anesthesia.

Patients who have sustained trauma may be hemodynamically unstable, making it difficult to achieve a deep level of anesthesia for endotracheal intubation. We usually perform a modified rapid sequence induction for children using cricoid pressure with gentle bag and mask ventilation, which is of particular importance in children with lung disease to avoid hypoxia. The bronchodilatory properties of ketamine and propofol make a combination (sometimes referred to as "ketofol") of these drugs useful in this situation, depending upon patient hemodynamic stability. (See 'Induction of anesthesia' above.)

Injuries of the chest and airway can mimic the onset of bronchospasm. Conditions such as tension pneumothorax, tracheobronchial disruption, pulmonary hemorrhage, and ball-valve obstruction of the endotracheal tube by foreign bodies or blood clots should be quickly ruled out by Advanced Trauma Life Support (ATLS) survey. (See "Thoracic trauma in children: Initial stabilization and evaluation".)

Patients with asthma and with increased intracranial pressure — Ventilation for the child with asthma and with increased intracranial pressure (ICP) can be especially challenging. Hyperventilation to decrease ICP may be difficult and may result in hyperinflation and barotrauma. Volatile anesthetics, especially in higher concentrations and without hyperventilation, can decrease cerebral perfusion pressure and increase ICP.

Similar to patients without increased ICP, propofol is the induction agent of choice in the hemodynamically stable patient if measures are used to maintain blood pressure and therefore cerebral perfusion pressure. Etomidate and ketamine are alternative induction agents for patients who are hemodynamically unstable; the effects of ketamine on cerebral physiology are uncertain. Choice of induction agents is discussed separately. (See 'Intravenous induction agents' above and "Anesthesia for craniotomy in adults", section on 'Choice of induction agents'.)

Ambulatory surgery — Children with well controlled asthma and compliance with medications and treatments are suitable candidates for ambulatory surgery. If the surgery and anesthetic course are uneventful and pain, nausea, and respiratory status are well controlled, the child with asthma can be discharged to home without further intervention.

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: Pediatric anesthesia".)

SUMMARY AND RECOMMENDATIONS

●Preoperative management – Asthma control should be optimized prior to anesthesia. If possible, we assess patients with asthma one to two weeks prior to elective surgery to allow time for modification of treatment, if necessary. Patients should continue usual asthma treatment through the perioperative period. (See 'Induction of anesthesia' above and 'Preoperative medication management' above.)

For children with very poorly controlled asthma requiring endotracheal intubation, we suggest a course of supplemental glucocorticoids (Grade 2C). In consultation with an asthma specialist or primary care clinician, we usually administer prednisone or prednisolone orally 1 mg/kg (maximum 50 mg) once a day for four days. (See 'Supplemental glucocorticoids' above.)

●Induction and airway management – For most children with asthma, we suggest intravenous (IV) induction rather than inhalation induction as this may reduce the risk of perioperative respiratory adverse events (PRAE) in at-risk children (Grade 2B). For most hemodynamically stable children undergoing general anesthesia, we suggest induction with propofol rather than other agents, since propofol prevents bronchospasm in response to intubation (Grade 2B). Ketamine or etomidate may be preferred for patients who are hemodynamically unstable. Unlike etomidate, ketamine has bronchodilatory properties. (See 'Induction of anesthesia' above.)

Endotracheal intubation is a potent stimulus for bronchospasm, especially under light levels of anesthesia. When possible, we suggest use of mask ventilation or a supraglottic airway for airway management for general anesthesia rather than endotracheal intubation (Grade 2C). Endotracheal intubation is associated with a higher risk of PRAE. (See 'Airway management' above.)

●Maintenance anesthetics – For most children with asthma, total IV anesthesia or sevoflurane, isoflurane, or halothane can be used for maintenance of anesthesia. Desflurane is an airway irritant and should not be used in asthmatic children or children at an increased risk for PRAE . (See 'Inhalation agents' above.)

•Neuromuscular blocking agents (NMBAs) – For children with asthma, NMBAs that do not release appreciable amounts of histamine (eg, rocuronium, cisatracurium, and vecuronium) are preferred over those that do (eg, atracurium and mivacurium). Neostigmine used for reversal of muscle relaxants can rarely cause bronchospasm. We suggest the use of an NMBA for endotracheal intubation, rather than intubation without an NMBA (Grade 2C), as intubation with an NMBA is associated with less PRAEs. (See 'Airway management' above and 'Neuromuscular blocking agents' above.)

•Opioids – Morphine and meperidine can release histamine when given in high doses or very rapidly. Other synthetic opioids are preferred in children with asthma because they do not release clinically relevant amounts of histamine. (See 'Opioids' above.)

•Ventilation – Ventilation for patients with asthma during anesthesia should include controlled hypoventilation with low respiratory rates, reduced inspiratory time, increased expiratory time, moderate tidal volumes, and cautious use of positive end-expiratory pressure, aiming to avoid hyperinflation, air trapping, and barotrauma. (See 'Ventilation during anesthesia' above.)

●Treatment of intraoperative bronchospasm – If bronchospasm occurs during anesthesia, treatment should include:

•FiO₂ 100 percent

•Cautious hand ventilation (low frequency allowing adequate expiration)

•Deepened anesthesia

Patients with bronchospasm that persists after deepening the anesthesia (preferentially with volatile anesthetic agents) should receive short-acting beta₂ agonist therapy (eg, albuterol 8 to 10 puffs via metered dose inhaler or 2.5 mg via nebulizer). More severe bronchospasm may require intervention with IV albuterol, glycopyrrolate or atropine, epinephrine, magnesium, and steroids. (See 'Management' above.)

●Emergence from anesthesia – Aim for smooth emergence from anesthesia. We often perform extubation or removal of an SGA with the child still deeply anesthetized (as opposed to awake) to avoid bronchospasm during emergence. Patients with a complicated intraoperative course may benefit from continued postoperative intubation and ventilation. Postoperative noninvasive positive pressure ventilation can be used for extubated patients who need ventilatory support. (See 'Emergence and extubation' above.)