When is epinephrine (adrenaline) indicated in acute asthma attacks?

When to Use Epinephrine in Acute Asthma Attacks

Epinephrine should be used in acute asthma attacks only when there is concomitant anaphylaxis or angioedema, or in cases of acute severe or life-threatening asthma that is unresponsive to first-line therapies. 1

Primary Indications for Epinephrine in Asthma

• Epinephrine is indicated when acute asthma is accompanied by anaphylaxis or angioedema 1
• Epinephrine may be considered in acute severe or life-threatening asthma unresponsive to repeated courses of inhaled beta-agonist therapy 1, 2
• Epinephrine is commonly recommended in many prehospital ambulance guidelines for severe or life-threatening asthma, though this practice differs from international asthma guidelines 1

Route of Administration and Dosing

• Subcutaneous epinephrine (concentration 1:1000) can be given at 0.01 mg/kg, divided into 3 doses of approximately 0.3 mg administered at 20-minute intervals 1
• Intravenous epinephrine may be considered in life-threatening cases at 0.25-1 mcg/min continuous infusion, though this carries a 4% risk of serious side effects 1, 3
• Nebulized racemic epinephrine has been used successfully in some cases of severe asthma unresponsive to standard therapies 4

Efficacy Compared to Standard Treatments

• Current evidence suggests epinephrine and selective β2-agonists have similar efficacy in acute asthma, with a pooled odds ratio for treatment failure of 0.99 (95% CI 0.75 to 1.32) 1
• Studies recruiting adults-only showed lower odds of treatment failure with epinephrine compared to selective β2-agonists 1
• There is insufficient evidence to determine whether adding epinephrine to selective β2-agonists improves outcomes 1

Safety Considerations

• Despite concerns about cardiovascular side effects, epinephrine appears to be well-tolerated even in patients over 35 years of age 1, 5
• The nonselective adrenergic properties of epinephrine may cause increased heart rate, myocardial irritability, and increased oxygen demand 1
• A study of intravenous epinephrine in younger adults with life-threatening asthma showed no significant adverse effects beyond sinus tachycardia 3
• In older adults (>40 years), subcutaneous epinephrine did not show increased risk of ventricular arrhythmias compared to younger patients 5

Clinical Decision Algorithm

1. First-line treatment: Use inhaled selective β2-agonists and systemic corticosteroids for all acute asthma exacerbations 1

2. Add-on therapies: Consider adding ipratropium bromide and IV magnesium sulfate for severe exacerbations 1

3. Consider epinephrine when:

   • Patient has features of anaphylaxis or angioedema 1
   • Patient has severe or life-threatening asthma unresponsive to repeated courses of inhaled β2-agonists 1, 2
   • Patient is in a prehospital setting with severe respiratory distress 1

4. Route selection:

   • Subcutaneous: 0.01 mg/kg (1:1000), divided into 3 doses of ~0.3 mg at 20-minute intervals 1
   • Intravenous: Consider only in extreme cases at 0.25-1 mcg/min continuous infusion 1, 3

Important Caveats

• The overall quality of evidence regarding epinephrine in asthma is low, with significant heterogeneity among studies 1
• There is clinical equipoise regarding whether adding epinephrine to selective β2-agonists improves outcomes 1
• Current international asthma guidelines recommend against epinephrine use except with concomitant anaphylaxis or angioedema, which conflicts with many prehospital guidelines 1
• When using epinephrine in older patients or those with cardiovascular risk factors, careful monitoring is essential despite evidence of general safety 1, 5