Managing an acute asthma exacerbation in children

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Definition, epidemiology, and background

Asthma is a common, chronic inflammatory disorder of the airways characterized by paroxysmal or persistent symptoms and is associated with airflow limitation and airway hyper-responsiveness ^[1][2]. Canadian experts have proposed that asthma can be diagnosed in children as early as 1 year of age, if presenting with frequent asthma-like symptoms or recurrent ^[2] exacerbations reversible with salbutamol with no other alternative diagnosis ^[1]. Asthma is the most common chronic disease in young people. The general prevalence of asthma in Canada has been estimated at 10%, but is higher (up to 20%) in children and youth, including their Indigenous peers ^[3]-[8]. Asthma exacerbations are a frequent cause of emergency department (ED) visits ^[9][10] and hospitalizations in children ^[11], and asthma is the leading cause of absenteeism from school ^[5]. Preschool age children with asthma represent more than 50% of consultations in the ED ^[9]. In one Alberta study, nearly 10% of paediatric ED visits resulted in admission, with one death for every 25,000 ED visits ^[10].

For this statement, asthma exacerbation is defined as an acute or subacute deterioration of symptom control causing respiratory distress or health risk ^[2] that requires a visit to a health care provider (HCP), and when self-management by the patient with a written asthma plan is insufficient. The most common trigger for asthma exacerbations in children and youth is viral respiratory tract infection, which is also associated with significant risk for treatment failure in the ED ^[12]. Other triggers include exposure to aeroallergens, air pollution, seasonal changes, and poor adherence to inhaled corticosteroids ^[13].

Many health care centres, along with national and international associations, have developed practice guidelines for the assessment and management of acute asthma exacerbations ^{[1][2][14]-[17]}. This statement specifically addresses the management of acute asthma exacerbations in paediatric patients with a known diagnosis of asthma, including preschoolers whose pattern of symptoms suggests likelihood for asthma or suspected asthma ^[1][18].

Emergency department management objectives for acute asthma exacerbations include:

1. A rapid and objective assessment of symptom severity (including consideration of alternative diagnoses for acute respiratory distress).
2. Prompt and effective medical intervention to decrease respiratory distress, improve oxygenation, and reduce the risk of recurrence.
3. Appropriate disposition.
4. Proper follow-up.

1. Assessment of respiratory distress

Effective treatment depends on an accurate and rapid assessment of disease severity and the elimination of other differential diagnoses (See reference ^[2], Boxes 1–5 and 6–3) ^{[2][16][19][20]}. Assessment should include:

• Signs and symptoms of respiratory distress and airway obstruction, including documentation of vital signs. Pulse oximetry should be used in all patients. Pulse oxygen saturation (SpO₂) of 92% or less on presentation is associated with higher morbidity ^[21] and ED management failure (50% versus 12%) ^[12].
• A focused asthma history recording triggers for exacerbation, previous medications and risk factors for ICU admission and death ^[2][22][23]:
  • Previous life-threatening events, admissions to an intensive care unit (ICU), intubation
  • Hospitalizations or ED visits for asthma in the last year
  • Deterioration while on, or recently after stopping, systemic steroids
  • Using >1 canister of salbutamol per month
  • Lack of an asthma action plan or poor adherence to treatment
  • Comorbidities (e.g., food allergy, obesity)
  • Low socioeconomic status, psychosocial concerns

Particularly when risk factors are identified, prompt and aggressive treatment is indicated, and caution should be used in determining readiness for discharge. Early consultation with a tertiary care paediatric ED and/or paediatric intensive care unit (PICU) specialist to discuss patient management and transport when response to treatment is insufficient is advised.

• A focused physical examination to estimate the functional severity of airway obstruction. Different clinical tools for assessing disease severity in patients with acute asthma exacerbation have been developed and assessed ^[24]-[27]. Independent of the method of assessment, the same parameters used to estimate disease severity at baseline should be used after each treatment and at discharge. The PRAM score (Table 1), which assesses severity by oxygen saturation, use of accessory muscles, air entry in both lungs, and wheezing, was considered the most valid in one study ^[28] and is currently used in several Canadian paediatric EDs ^[16]. Higher PRAM scores at presentation are associated with increased risk for outpatient management failure ^[12]. Additional indicators of severity include:
  • Nasal flaring
  • Reduced activity level, inability to feed (infant) or inability to speak in full sentences
  • Decreased level of alertness, mental agitation, drowsiness, or confusion. These are clinical features of cerebral hypoxemia and should be considered signs of impending respiratory failure.

Table 1. Classification of asthma severity using the PRAM score
Paediatric Respiratory Assessment Measure (PRAM) scoring table
Oxygen saturation	≥ 95%	0
	92% to 94%	1
	<92%	2
Suprasternal retraction	Absent	0
	Present	2
Scalene muscle contraction	Absent	0
	Present	2
	Normal	0
Air entry*	Normal	0
	↓ At the base	1
	↓ At the apex and the base	2
	Minimal or absent	3
Wheezing†	Absent	0
	Expiratory only	1
	Inspiratory (± expiratory)	2
	Audible without stethoscope or silent chest (minimal or no air entry)	3
PRAM score (maximum 12)
Score	0 to 3	4 to 7	8 to 12
Severity	Mild	Moderate	Severe
Source: Reference [25]   *In case of asymmetry, the most severely affected (apex to base) lung field (right or left, anterior or posterior) will determine the rating of this criterion. †In case of asymmetry, the two most severely affected auscultation zones, irrespective of location (i.e., right upper lobe, right middle lobe, right lower lobe, left upper lobe, left lower lobe), will determine the rating of this criterion.

• Spirometry can be a useful objective measure of airway obstruction. Airflow can be measured by the FEV₁ (forced expiratory volume in 1 second) ^[17][29], with values above 80% of predicted generally considered normal. When well-performed, the FEV₁ is >70% in mild, 50% to 70% in moderate, and <50% in severe exacerbations. Of note, spirometry is difficult to perform in children <6 years old or during a severe exacerbation. Peak flow meters may be more readily available but are a less sensitive measure of airway obstruction and may be unreliable, especially in children <10 years old ^[30].
• Ancillary tests are not routinely recommended.
  • Chest x-rays are rarely indicated for typical asthma exacerbations but may be useful to exclude complications (e.g., pneumothorax, pneumonia) or other pathology (e.g., foreign body, cardiac insufficiency), particularly in patients with significant chest pain, hypoxemia, prolonged fever, or persisting asymmetry, or when a patient has failed to improve with maximal conventional treatment ^[31]. In the absence of suggestive clinical features, chest x-rays increase the risk of overdiagnosis of pneumonia ^[32].
  • Blood gases are not routinely required unless no clinical improvement is seen with maximal aggressive therapy. A normal capillary carbon dioxide level despite persistent respiratory distress may indicate impending respiratory failure.

2. Medical management

Treatment of acute asthma includes:

• Treatment of hypoxemia
• Administration of bronchodilators: inhaled short-acting beta2-agonists ± ipratropium bromide
• Administration of corticosteroids
• Assessment of response
• Consideration of other treatments, including transfer to a tertiary facility

Treatment should be instituted as soon as a rapid assessment is completed. Patients should be monitored closely to assess their response to initial management.

Patients who are acutely distressed, have signs of severe respiratory impairment, or show signs of impending respiratory failure (e.g., silent chest, altered level of consciousness) should be treated in the resuscitation room with initial attention to ABCs ^[2][20]. Anaphylaxis can present with severe respiratory distress, mimicking a severe asthma attack ^[33]. If anaphylaxis is suspected (e.g., acute respiratory distress combined with urticaria), treat immediately with intramuscular (IM) epinephrine.

Figure 1 shows a pathway for the assessment and management of children and youth with an asthma exacerbation. Establishing an order set to facilitate rapid initiation of treatment with salbutamol and steroids in children with known asthma presenting with respiratory distress can reduce unnecessary treatment delays and reduce variation in treatment ^{[16][17][19][34]}.

Figure 1. Clinical pathway for asthma exacerbation is available as a supplementary file.

Oxygen: Hypoxemia (SpO₂ <92%) must be treated urgently with oxygen delivered by face mask or nasal cannulae. While there is no strong evidence in support of a specific goal for SpO₂ in the context of acute respiratory distress, a SpO₂ ≥92% to 94% appears adequate ^[2][16][17].

Short-acting beta2-agonists: Salbutamol (albuterol) is the bronchodilator of choice ^[2][20]. A metered-dose inhaler (MDI) with an aerochamber is the preferred device for salbutamol administration because it is more efficient than a nebulizer for bronchodilator delivery ^[2][16][35], reducing length of stay and side effects in children (e.g., tachycardia, tremor) ^[31][36]. An MDI can be used in almost all situations except very severe cases associated with impending respiratory failure. In the presence of hypoxemia, oxygen can be administered by nasal cannula at the same time that salbutamol is given. The dose (Table 2) and frequency of intermittent salbutamol therapy depend on the severity of presentation and the response to treatment (Figure 1). In patients having a severe asthma attack, the continuous administration of nebulized beta2-agonists may have a better and more prolonged bronchodilator effect compared with intermittent therapy ^[37][38]. Side effects of salbutamol include tachycardia, hyperglycemia, and hypokalemia, which are generally well tolerated. Increased lactic acid can be seen in children receiving inappropriately escalating doses of salbutamol, causing compensatory hyperventilation, which can be confused with asthma deterioration ^[39]. There is no evidence of clinically significant arrhythmias following treatment with nebulized bronchodilators ^[40].

Table 2. Medications and dosages for acute asthma treatments by health care providers in children older than 1 year is available as a supplementary file.

Inhaled anticholinergics: Inhaled ipratropium bromide should be used as an adjunctive therapy to beta2-agonists in moderate-severe to severe crisis ^[16][17][41]. This combination has been shown to reduce hospital admission rates, improve lung function and reduce risk of nausea and tremor, compared with beta2-agonists used alone ^[42][43]. The dose may be repeated every 20 to 30 minutes for the 60 to 90 minutes, mixed with beta2-agonists ^[44]. There are no clinical trials supporting ipratropium use beyond the initial treatments in children and there is currently no evidence for its use in hospitalized children ^[45] or upon discharge.

Per os (PO)/IV corticosteroids: Children who have a moderate to severe asthma exacerbation should receive systemic steroids as part of their initial treatment. This medication should be administered as early as feasible ^[46], ideally by mouth, and within the first hour of arrival ^[2]. Steroids appear to reduce the need for hospitalization, risk for relapse after initial treatment and may also facilitate an earlier discharge from the hospital ^[46]-[48]. Recent systematic reviews suggest it is unclear which dose of corticosteroids is more effective (see Table 2 for dose range) ^[49][50].

For patients with mild asthma exacerbations, clear evidence is lacking to support routine use of oral corticosteroids ^[16]. Depending on the history (e.g., if requiring repeated doses of salbutamol at home), their use may be considered.

Children with severe asthma with vomiting, and who are not responding to initial therapy, or with impending respiratory failure, should receive IV steroids. The drug of choice is methylprednisolone (Table 2). In the adult literature, higher doses of methylprednisolone do not seem more effective than lower doses ^[51], and a dose of 80 mg used once a day could be sufficient. Some guidelines repeat doses every 6 h in patients with severe asthma who are not responding to initial therapy ^[17][41], but evidence-based data for this practice is lacking ^[52].

IV magnesium sulphate: Meta-analyses have suggested that IV magnesium sulphate is effective in children with moderate to severe exacerbations, by improving respiratory function and decreasing hospital admissions ^[53][54]. This adjunctive IV treatment was found to be more effective with fewer side effects than IV terbutaline (a beta2-agonist) and IV aminophylline ^[55]. IV magnesium sulphate should be considered for patients with incomplete response to conventional therapy during the first 1 to 2 h ^[53]. Children require cardiorespiratory monitoring during treatment because magnesium sulphate may cause hypotension and bradycardia. Consultation with a paediatric emergency physician or a paediatric intensive care unit physician is suggested.

The evidence is currently insufficient to suggest the use of inhaled magnesium sulfate in addition to standard treatment ^[56]. A multicentre study of inhaled magnesium sulphate in paediatric EDs in Canada showed that it did not decrease hospitalizations and did not improve other outcomes ^[57][58].

IV salbutamol infusion: IV salbutamol can be used in patients with severe asthma who fail to respond to other treatments, mainly to prevent intubation ^[59]. In patients with severe attacks, there is very limited evidence that IV beta2-agonists reduce recovery time ^[60][61] or improve pulmonary function ^[59]. The rationale to support IV salbutamol is that inhaled drugs may have a limited effect in patients with nearly complete airway obstruction and have practical limitations in ventilated patients. Cardiac responses, such as arrhythmia and tachycardia, increased lactate and anxiety are significant side effects, which may increase respiratory workload and exacerbate respiratory failure ^[61]. Patients receiving IV salbutamol should be in a PICU setting.

Heliox: Using a helium-oxygen gas mixture is generally reserved for children in a PICU setting, with severe exacerbation, who have failed to improve despite maximal therapy ^[62]. One systematic review showed a significant decrease in acute asthma severity with heliox-driven beta2-agonist nebulization as well as decreased hospital admission rates in children ^[63].

IV aminophylline: Most guidelines do not recommend use of IV aminophylline because of its low efficacy and safety profiles ^[2]. If used, this bronchodilator should be reserved solely for children with a severe asthma exacerbation, who have failed to improve despite maximal therapy (continuous inhaled beta2-agonists, IV corticosteroids, IV magnesium sulfate) and generally in a PICU setting ^[59][64]. A systematic review comparing use of IV aminophylline with IV beta2-agonists found no difference in clinical outcomes measured (i.e., improved length of stay or pulmonary function) but favoured beta2-agonists in terms of side effects ^[65]. The risk-benefit balance of IV aminophylline is unfavourable ^[66], and recent guidelines do not support its use ^[2].

Non-invasive ventilation (BiPAP, CPAP) or high-flow nasal cannulae: Non-invasive positive pressure ventilation in children with asthma exacerbations may reduce asthma symptom scores ^[67][68] and be an option for children unresponsive to optimized standard treatments ^[69]. However, reviews on this topic have concluded the evidence is of low quality and is not conclusive ^[2][67][69]. Further studies are required for both non-invasive ventilation and high-flow nasal cannulae use in children with acute asthma ^[31][68].

Endotracheal intubation and ventilation: Intubation and mechanical ventilation can be life-saving interventions but their use in paediatric patients with asthma has been associated with significant adverse effects. Up to 45% of patients intubated due to asthma have complications, including pneumonia, pneumothorax, pneumomediastinum, and cardiovascular collapse ^[70][71]. While invasive mechanical ventilation is infrequent (used in approximately 0.55% of paediatric admissions for status asthmaticus), it is associated with high in-hospital mortality ^[72]. This risk highlights the importance of adequate, rapid, and aggressive initial management of acute exacerbations. Intubation and mechanical ventilation should be initiated only when there is failure to respond to optimized initial care, only by the most experienced person available, and preferably in conjunction with a PICU specialist. In these situations, ketamine is generally considered the agent of choice for induction and ongoing sedation ^[73].

3. Disposition

Admission should be considered in the following cases: ^[2][16]

• Ongoing need for supplemental oxygen
• Increased work of breathing, with moderate or severe distress, PRAM ≥4, 4 to 6 h after receiving corticosteroids
• Ongoing need for beta2-agonists more often than every 4 h, after 4 to 6 h of conventional treatment
• Factors affecting adherence or capacity for close follow-up (e.g., comorbid conditions, diagnostic uncertainty, anaphylaxis, recent acute exacerbation, distance to the health facility or adherence and parental capacity concerns).

ICU admission or referral to a tertiary care centre should be considered when:

• A patient in severe distress fails to improve after the initial 1 to 2 h of therapy (i.e., persisting PRAM of 8 to 12). Call a tertiary care paediatric ED and/or PICU specialist to discuss patient management and transport. Intermittent inhaled or continuous nebulized salbutamol and ipratropium (if not already given) and IV magnesium sulfate should be administered while awaiting transport.

Discharge criteria include:

• A reading of SpO₂ ≥92% in room air
• Minimal or no signs of respiratory distress, PRAM score ≤3, sustained 1 to 2 h after the last bronchodilator treatment
• Improved air entry
• Expected or anticipated need for beta2-agonist treatment not greater than every 4 h

4. Discharge plan

Children and youth should be prescribed daily inhaled corticosteroids (ICS) when:

• Presenting with symptoms or waking up due to asthma 2 times per month or more, or
• Presenting with moderate or severe exacerbations and have required oral steroids within the last 12 months ^{[2][15][74][75]}.

In preschoolers, regular ICS are recommended for:

• Persistent symptoms ≥8 days per month
• Moderate or severe exacerbations requiring PO steroids at presentation ^[1].

ICS are the cornerstone of regular preventive anti-inflammatory treatment to reduce exacerbations and chronic morbidity. The literature does not support short-term intermittent ICS therapy in children. However, decreasing ICS to the lowest effective dose once asthma is well-controlled, with some authors suggesting a 3-month interval without symptoms, is advised ^[1][2]. ICS at low to medium dose (200 mcg/day of HFA-fluticasone equivalent, see Table 3) are safe and efficacious, despite having a small, non-clinically significant impact on final height. Although there is the rare risk for adrenal suppression with doses higher than 200 mcg/day to 250 mcg/day of ICS (fluticasone propionate equivalent) over prolonged periods ^[76], it can be reduced with use of lower dose ICS and, potentially, the use of newer molecules, such as ciclesonide.

The failure to achieve asthma control on medium-dose ICS suggests the needs for diagnostic and co-morbidity re-evaluation, evaluation of environmental triggers, technique verification, and assessment of compliance ^[2][15][77]. When the patient is already properly taking low-dose ICS:

• If <12 years old: The low ICS dose should be increased to a medium dose. Children who fail to achieve control on a medium dose of ICS should be referred to a specialist. For children 5 to 11 years old, a low to medium dose ICS with a long-acting beta2-agonist (LABA) or with anti-leukotrienes could also be an option ^[2][15].

• If ≥12 years old: A LABA can be added in combination with a low to medium dose ICS (low to medium daily dose ICS-LABA) ^[2][14][15]. In children taking low-dose ICS-formoterol PRN as their rescue medication instead of salbutamol, a regular dosing that provides a low to medium daily ICS dose as an ICS-formoterol combination should be initiated. These children should continue to use ICS-formoterol as their rescue medication (to a maximum total use of 8 puffs per day) until follow-up by their treating physician ^[2].

There is no evidence that doubling (or otherwise increasing) the dose of ICS for one week is more effective than the usual daily dose. Also, there is some evidence of harm in children from the adverse effects of repeated or prolonged use of high-dose ICS (i.e., adrenal suppression, growth suppression). Therefore, increasing the dose temporarily is not recommended, either pre-emptively at home (at the onset of an exacerbation) or on discharge from the ED.

In addition to ICS, it is recommended to:

• Complete a short course (generally 1 to 5 days) of oral steroids, depending on the severity of the illness at presentation and the type of steroids. Systemic corticosteroids reduce relapse of acute asthma in children discharged from an acute care setting. It is unclear whether a longer course of prednisolone is safer and more effective than a shorter course of dexamethasone ^[49], but one meta-analysis concluded that one or two dose(s) of dexamethasone could be an alternative to a 5-day regimen of prednisone or prednisolone, as dexamethasone is less associated with vomiting ^[50], and more associated with increased compliance and caregiver preference ^[31]. Further research is needed to support a strong recommendation for one therapy over another. 
• Continue to use a short-acting beta2-agonist every 4 h until the exacerbation resolves, then as needed, with directions to see a health care professional if therapy is required more often than every 4 h. Youth >12 years old who take ICS-formoterol as their control therapy should also use it as their rescue medication (to a maximum total use of 8 puffs per day). 
• Review techniques for administering inhaled asthma medications with children and youth. Use an age-appropriate device and spacer (for metered-dose inhalers), and include techniques for cleaning and maintaining their devices.
• Review environmental triggers, including tobacco smoke (passive and active in teenagers), allergens such as dust mites (in soft toys, mattresses, carpets), pollen, animals (e.g., cats), mold ^[77], and air pollution ^[2]. Recommend vaccination against seasonal influenza ^[31].
• Prepare a written, collaborative asthma action plan with family, and discuss when and where to go for help, which can be reviewed with HCP at follow-up. These resources can be used as starting points:
  • Asthma Canada. Asthma Action Plan
  • Lung Health Foundation. Pediatric Asthma Action Plan
  • Santé et Services sociaux Québec. Plan d’action pour l’asthme
• Encourage follow-up with either the patient’s primary care physician or an asthma educator at a local asthma clinic to review asthma control, environmental history, and symptom recognition within 4 weeks of discharge. If severe exacerbations lead to PICU admission, or the patient presents with recurrent (≥2) moderate to severe exacerbations despite moderate dose ICS, referral to an asthma specialist is recommended ^[1].

Table 3. Inhaled daily dose of corticosteroids (ICS) for asthma therapy in children is available as a supplementary file.

Acknowledgements

This position statement was reviewed by the Adolescent Health and Community Paediatrics Committees, and the Respiratory Health and Allergy Section Executives, of the Canadian Paediatric Society. It has also been reviewed by the Canadian Thoracic Society, with our thanks. Particular thanks are due to Dr Francine M. Ducharme, for her thorough review of both this statement and the tables. Thanks also to Ms Pascal Bedard and Christopher Marquis, pharmacists, for reviewing Table 2, and to Dr Charlotte Moore-Hepburn for her editing inputs.

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CANADIAN PAEDIATRIC SOCIETY ACUTE CARE COMMITTEE

Members: Carolyn Beck MD, Kevin Chan MD (Chair), Laurel Chauvin-Kimoff MD (Past Chair), Kimberly Dow MD (Board Representative), Karen Gripp MD, Kristina Krmptoic MD, Marie-Pier Lirette MD (Resident member), Kyle C McKenzie MD (past member), Evelyne D. Trottier MD
Liaisons: Laurel Chauvin-Kimoff MD, CPS Paediatric Emergency Medicine Section; Sidd Thakore MD, CPS Hospital Paediatrics Section

CANADIAN PAEDIATRIC SOCIETY PAEDIATRIC EMERGENCY MEDICINE SECTION

Section Executive: Laurel Chauvin-Kimoff MD (President), April Kam MD (Member-at-large), Michelle Long MD (Vice-president), Andrea Robb MD (Member-at-large), Kevin Chan MD (Past-president), Dayae Jeong MD (Resident member)
Principal authors: Evelyne D. Trottier MD, Kevin Chan MD, Dominic Allain MD, Laurel Chauvin-Kimoff MD

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References

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.