Acute asthma exacerbation in children

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Exacerbations represent an acute or subacute worsening of symptoms and lung function from a patient’s baseline (i.e., "flare-ups") and may be the first presentation for some patients.[7][57][72] Early recognition and assessment of the severity of an acute asthma exacerbation is crucial for effective management.[7][57]

Initial therapy focuses on correcting hypoxemia and reversing or preventing airflow obstruction. An inhaled, short-acting beta-2 agonist (SABA) is the first-line therapy of choice to reverse airflow limitation rapidly. Supplemental oxygen and a short course of a systemic corticosteroid may be required in more severe exacerbations. Good treatment response will be characterized by resolution of wheeze and tachypnea. Antibiotics are rarely required and should not be given routinely.[7][74]

The management approach detailed here focuses on guidance from the Global Initiative for Asthma (GINA) and applies to children 11 years or younger.[7] Children 12 years or older are treated the same as adults. See Acute asthma exacerbation in adults.

Life-threatening exacerbation or impending respiratory failure

Children with signs of a life-threatening exacerbation (e.g., drowsiness, confusion, silent chest) are admitted to the pediatric intensive care unit for treatment and respiratory support (e.g., high-flow humidified nasal cannulae, noninvasive ventilation, or intubation and mechanical ventilation).[7][75] The partial pressure of carbon dioxide (PaCO₂) from arterial (or venous) blood gases will reveal impending respiratory failure as tachypnea (low PaCO₂) gives way to fatigue, hypoventilation, and CO₂ retention (normal or high PaCO₂) and respiratory acidosis.[7][62]

Initially, all children should receive a nebulized SABA, controlled oxygen therapy (maintaining saturations of 94% to 98%), and systemic corticosteroids (intravenous or oral).[7] Children ages 6-11 years are also routinely given a nebulized anticholinergic.[7] A nebulized anticholinergic may be considered in a child 5 years or younger with poor response to initial treatment.[7] [ ] An intravenous SABA may be given when inhaled therapy cannot be used reliably.[7][57]

Nebulized magnesium sulfate can be added to a nebulized SABA and anticholinergic in the first hour of treatment for children 2 years and older with severe asthma (e.g., oxygen saturation <92%), particularly if symptoms have lasted <6 hours.[7][57] However, this may not be as effective as intravenous therapy.[7][76][77] [ ]

In patients with life-threatening asthma exacerbations, an intravenous bronchodilator is considered if there is poor response to first-line nebulized bronchodilators and corticosteroids.[7][57][59][78][79] [ ] Magnesium sulfate is preferred by GINA (children 6-11 years old) and BTS/NICE/SIGN (children 2-11 years old) in this setting.[7][80] BTS/NICE/SIGN also recommend intravenous SABAs and methylxanthines as second-line options.[7][80] Nebulized magnesium sulfate can be considered if there is no intravenous access, but this offers only modest benefit in severe exacerbations.[7][80][81][82][83] [ ]

Any severe exacerbations should prompt further assessment to reduce future risk, which may include optimizing treatment, assessing risk factors for exacerbations, and considering specialist referral; assessment should not focus on symptom control alone.[7]

Severe exacerbation

All patients with severe exacerbations should be admitted to hospital and the anesthetic or pediatric intensive care team involved early. If children with severe asthma develop signs of impending respiratory failure (confusion or marked agitation, loss of respiratory effort, pulsus paradoxus, cyanosis, hypoxemia, or respiratory acidosis) despite aggressive treatment (e.g., intravenous bronchodilators and magnesium sulfate), they may require intubation and mechanical ventilation with 100% oxygen.

Children with a severe exacerbation should receive a nebulized SABA, controlled oxygen therapy (maintaining saturations of 94% to 98%), and systemic corticosteroids (intravenous or oral).[7] Children ages 6-11 years are also routinely given a nebulized anticholinergic.[7] A nebulized anticholinergic may be considered in a child 5 years or younger with poor response to initial treatment.[7] [ ] There is a lack of evidence to support the use of spacers in this setting. [ ] An intravenous SABA may be given when inhaled therapy cannot be used reliably.[7][57] [ ]

Nebulized magnesium sulfate can be added to a nebulized SABA and anticholinergic in the first hour of treatment for children 2 years and older with severe asthma (e.g., oxygen saturation <92%), particularly if symptoms have lasted <6 hours.[7][80] However, this may not be as effective as intravenous therapy.[7][76][77] [ ]

In patients with severe exacerbations, an intravenous bronchodilator is considered if there is poor response to first-line nebulized bronchodilators and corticosteroids.[7][57][59][78][79] [ ] Magnesium sulfate is preferred by GINA (children 6-11 years old) and BTS/NICE/SIGN (children 2-11 years old) in this setting.[7][57] BTS/NICE/SIGN also recommend intravenous SABAs and methylxanthines as second-line options.[7][57]

Mild to moderate exacerbation

Mild exacerbations do not usually require hospital admission and can be treated appropriately at home using the child's personalized asthma action plan. However, some moderate exacerbations may require hospital admission.[7][57][75]

All patients should receive an inhaled SABA immediately, be reassessed 15-20 minutes after treatment, and receive a further dose if response is inadequate (up to three doses in the first hour).[7] The response to treatment should be immediate and sustained for 3-4 hours. A metered-dose inhaler plus a spacer is just as effective as a nebulizer for mild to moderate exacerbations, with a face mask used for children ages <3 years and a mouthpiece used for older children.[7][84] [ ]

An inhaled anticholinergic can be added to the SABA if there is a poor response to initial treatment in children with a moderate to severe exacerbation.[7][57] [ ] [ ]

Oxygen may be required in some children to maintain oxygen saturation at a target of 94% to 98%.[7][57]

Oral corticosteroids are not usually required in a mild exacerbation, but may be needed to prevent deterioration when response to inhaled SABA therapy is incomplete. For children 5 years and younger with mild to moderate exacerbations, a systemic corticosteroid should only be given if symptoms recur within 3-4 hours of treatment with a SABA.[7] There is good-quality evidence to suggest that administration of oral corticosteroids within the first hour of arrival reduces admission rates in children with acute asthma compared with placebo.[85]

Any increase in exacerbation frequency or severity should prompt further assessment to reduce future risk; this should not focus on symptom control alone.[7]

Inhaled short-acting bronchodilators

An inhaled SABA is the first-line therapy used to rapidly reverse airflow limitation. Frequent administration of a beta-2 agonist can cause transient decreases in potassium, magnesium, and phosphate levels. Potassium levels should be monitored when giving beta-2 agonist therapy very frequently (i.e., severe exacerbations), and replaced as required.[57]

In children with moderate to severe exacerbations and poor response to initial treatment after the first hour, an inhaled short-acting anticholinergic can be added to the SABA and given every 20 minutes for 1 hour only.[7][57] [ ] [ ] This approach has been shown to reduce the likelihood of hospital admission and the risk of nausea and tremor.[86][87] [ ] [ ] Cardiac stimulation occurs but is less marked than that produced by beta-2 agonists. Anticholinergics produce a weaker bronchodilation response with a slower onset of action (30-90 minutes) than beta-2 agonists (5-15 minutes).[88] Routine use of an anticholinergic in children with asthma <2 years of age is not recommended, except for those with bronchiolitis or chronic lung disease of prematurity.[89]

GINA recommends using a pressurized metered-dose inhaler and spacer with either a tightly fitting face mask or mouthpiece, depending on the child’s age.[7][84] Nebulizers are useful if the patient is unable to coordinate use of a metered-dose inhaler or if oxygen is required.

Oxygen-driven nebulizers are used to deliver short-acting bronchodilators in patients with severe or life-threatening exacerbations.[7][57] Continuous SABA nebulization is superior to intermittent administration.[90][91] Be vigilant for further oxygen desaturation due to pulmonary vasodilation in areas of poorly ventilated lung.[7][57] Caution is also needed in children with preexisting cardiac disease.

Inhaled corticosteroids (ICS)

Adjusting the ICS dose is not recommended in children. There is no good evidence to support either increasing the maintenance dose of an ICS or using a high-dose ICS from the onset of an exacerbation; this approach may stunt linear growth in children with severe exacerbations.[92][93][94] [ ] Increased doses of an inhaled ICS are considered inferior to systemic corticosteroid therapy, and are unlikely to reduce the need for oral corticosteroids in children with mild to moderate asthma.[94][95] In children ages 0-4 years, clinicians may consider adding a short course of daily ICS to a SABA reliever at the onset of a respiratory illness.[7][55]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.

The role of ICS in the emergency department management of acute asthma is unclear, but on balance, is not recommended, given that the optimal drug, dose, and treatment duration have yet to be determined.[7][96] Despite this, need for hospitalization may be reduced following administration of a high-dose ICS given in the first hour for patients not receiving systemic corticosteroids, or by the use of high-dose (nebulized) ICS and a systemic corticosteroid within the first few hours.[97][98] GINA guidelines suggest that this approach only be used on a case-by-case basis.[7]

Systemic corticosteroids

The choice of an oral or parenteral corticosteroid is dictated by the ability of the patient to tolerate oral therapy. Intravenous or intramuscular corticosteroids are often required in severe and life-threatening exacerbations, but oral corticosteroids have comparable effectiveness and are preferred when tolerated.

Oral dexamethasone and oral prednisone have comparable outcomes, although oral dexamethasone is associated with lower noncompliance and vomiting rates.[99] Concerns about metabolic adverse effects limit the use of oral dexamethasone to no more than two days, at which point changing to prednisone should be considered (i.e., if symptoms persist or relapse).[7][99]

Consider parenteral corticosteroids when patients are too dyspneic to swallow, are vomiting, or require noninvasive ventilation or intubation.[7] Parenteral corticosteroids may also be considered when adherence is a significant concern (e.g., intramuscular dexamethasone as an alternative to a short course of oral corticosteroids).[100]

Corticosteroids produce a treatment response by 4-6 hours.[7] There is good-quality evidence to suggest that administration of oral corticosteroids within the first hour of arrival reduces admission rates in children with acute asthma compared with placebo.[85] Trials have found comparable outcomes when using different doses of systemic corticosteroids; uncertainty exists about the optimal dose of systemic corticosteroid.[7][57][101][102][103]

Systemic corticosteroids have the potential to cause severe adverse effects (e.g., gastrointestinal bleeding, sepsis, pneumonia, and adrenal suppression), with systemic adverse effects more common with intramuscular long-acting corticosteroids.[104][105] Systemic corticosteroids may also be overused or underused.[104][106] These risks have led to calls to reduce inappropriate use of systemic corticosteroids in asthma, and to improve stewardship.[107] In general, however, concern regarding long-term cumulative adverse effects should not affect decisions to treat patients appropriately with corticosteroids during severe exacerbations.[7]

International guidelines support oral courses of systemic corticosteroids, typically with prednisone for three to five days. Reviewing the child on day 3, and only extending the course of corticosteroid therapy if necessary, is a reasonable approach.[7][57][108][109][110] Where intravenous or intramuscular corticosteroids are required for severe and life-threatening exacerbations, they should be continued for at least 3 days and increased to a maximum of 10 days with regular review.[107]

Inhaled magnesium sulfate

Nebulized magnesium sulfate can be added to a nebulized SABA and anticholinergic in the first hour of treatment for children 2 years and older with severe asthma (e.g., oxygen saturation <92%), particularly if symptoms have lasted <6 hours.[7][57] It is also an option if there is no intravenous access.[7][57]

Nebulized therapy offers only modest benefit in severe asthma exacerbations, and research outcomes are not consistent.[81][82][83] [ ] In one randomized placebo-controlled trial of 816 children, nebulized magnesium sulfate with albuterol did not significantly reduce the rate of hospitalization among children with refractory acute asthma.[76]

Intravenous bronchodilators

In patients with severe or life-threatening asthma exacerbations, consider intravenous bronchodilator therapy if there is poor response to inhaled bronchodilators and corticosteroids.[7][57][59] Criteria for starting include no response to initial therapies, persistent hypoxemia, and an FEV₁ <60% predicted at 1 hour.[7]

Intravenous magnesium sulfate is preferred by GINA (children 6-11 years old) and BTS/NICE/SIGN (children 2-11 years old) for exacerbations unresponsive to first-line therapy.[7][57][59][78][79] [ ] High-certainty evidence shows that its use can reduce the length of hospital stay.[87] It may also reduce the need for admission in some patients with moderate to severe exacerbations.[111] It does not have an established role in children 5 years and younger due to a lack of evidence. A trial of 61 children ages 6 months to 4 years concluded that a single dose of magnesium sulfate by slow infusion was ineffective for treating acute severe viral-induced wheeze.[112]

Intravenous SABA (albuterol or subcutaneous terbutaline where intravenous albuterolis is not available) or a methylxanthine (aminophylline or theophylline) are listed as second-line intravenous bronchodilators by the BTS/NICE/SIGN guideline for use in children 2-11 years old, but only under expert supervision and with extreme caution.[57][59] Neither approach is recommended by GINA.[7] Improved clinical outcomes have been reported with intravenous beta-2 agonists in individual randomized controlled trials, but not confirmed by meta-analyses.[113][114][115][116][117] [ ] Intravenous methylxanthines are limited in use because they are unlikely to offer additional bronchodilation and are associated with potentially fatal adverse effects that require continuous ECG monitoring.[57][59][118] One Cochrane review failed to find any consistent evidence favoring either intravenous beta-2 agonists or intravenous aminophylline for patients with acute asthma.[119] [ ]

Treatment with intravenous magnesium sulfate requires close monitoring for respiratory depression. During intravenous treatment with beta-2 agonists, monitor and replace potassium levels as required.[57] If patients receive intravenous aminophylline, adverse effects are more likely in those taking sustained-release theophylline as part of their chronic management.[7] Serum theophylline levels should be checked regularly and the dose adjusted accordingly if patients receive continuous therapy.

Intramuscular epinephrine

Administer intramuscular epinephrine if signs of angioedema or anaphylaxis are present.[7][120]

Ventilation

Noninvasive ventilation has a role in the management of acute asthma exacerbations in children and may help to avoid the subsequent need for invasive ventilation.[121]

Humidified high-flow nasal cannulae (HFNC) are well tolerated and may be appropriate in some settings, but their use is not supported by data from randomized controlled trials and they may offer no benefits over aerosol masks.[122][123][124]

The application of positive pressure in the setting of severe acute bronchospasm may prevent airway collapse and reduce the mechanical load on already tired respiratory muscles.[123] Noninvasive positive pressure ventilation (NPPV) may be used as a rescue therapy to avoid intubation. Continuous positive airways pressure (CPAP) or bi-level noninvasive ventilation can be applied using either a nasal or full-face mask interface. However, one Cochrane review found that current evidence is insufficient to recommend for or against the use of NPPV in children with acute asthma.[125] Sedation is occasionally necessary for patient tolerance, but should be used with caution.

Clinical symptoms of exhaustion, cyanosis, or drowsiness with hypoxemia and hypercapnia are indications for intubation and mechanical ventilation.The pediatric intensive care team and/or anesthetist with pediatric training should be alerted early; intubation is preferred before the onset of respiratory arrest. If intubation is required, the ventilation strategy should ensure adequate expiratory time to aid gas exchange. Muscle relaxation may be necessary. Fluid replacement will be required because these patients are often fluid depleted and the initiation of positive pressure ventilation may trigger hypotension.

Patients with fever and purulent sputum or radiographic evidence of pneumonia

Most acute asthma exacerbations are triggered by viral infection.[6][57]

Antibiotics are not given routinely unless there is fever, purulent sputum, or radiographic evidence of pneumonia.[7][50][74] If bacterial pneumonia is diagnosed, antibiotic selection and dosing should be according to local institutional protocols. Mycoplasma pneumoniae is the most common bacterial infection. See Mycoplasma pneumoniae infection.

Arrange ongoing treatment

In the acute care setting, patients are assessed for hospitalization or discharge based on their clinical status (including the ability to lie flat), oxygen saturation, and lung function 1 hour after starting treatment. These outcomes more reliably predict the need for hospitalization than the patient’s status on arrival.

If recorded, peak expiratory flow (PEF) and/or forced expiratory volume in the first second of expiration (FEV₁) can inform decisions about hospitalization and discharge from acute care.[7]

Hospitalization recommended: pretreatment FEV₁ or PEF is <25% predicted or personal best; posttreatment FEV₁ or PEF is <40% predicted or personal best.
Discharge possible: posttreatment lung function 40% to 60% predicted.
Discharge recommended: posttreatment lung function is >60% predicted or personal best.

Irrespective of the reason, discharge should only be considered after assessing the patient’s risk factors and the availability of follow-up care. Other factors associated with increased likelihood of need for admission include: female sex, older age, and non-white race; use of >8 beta-2 agonist puffs in 24 hours; life threatening or severe exacerbations (may be considered if moderate); past history of severe exacerbations (e.g., intubations, asthma admissions); and previous unscheduled office and emergency department visits requiring oral corticosteroids.[7]

Discharge for admitted patients can be considered when the child is:[57]

stable on inhaled bronchodilators every 3-4 hours that can be used at home, and
PEF and/or FEV₁ (if recorded) >75% of best or predicted, and
oxygen saturation >94% in room air.

Before hospital discharge or when an exacerbation has resolved, consider starting an ICS-containing controller or increasing the dose of an existing ICS-containing treatment for 2-4 weeks while transitioning back to as-needed rather than regular use of their reliever medication.[7] Take the opportunity to review inhaler technique, stress the importance of adherence to regular medications, and give advice about both trigger avoidance and early recognition. This may include reviewing an existing asthma management plan or drafting a new plan if the patient does not have one. Ensure patients have appropriate follow-up arrangements, ideally within 2 days.[7]

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