What is the role of adrenaline (epinephrine) in acute exacerbation of asthma?

Intramuscular Adrenaline in Acute Asthma Exacerbation

Based on the highest quality evidence, intramuscular epinephrine should NOT be routinely used in acute asthma exacerbations, as it offers no benefit over selective β2-agonists and has a worse side effect profile—reserve it only for concomitant anaphylaxis/angioedema or the rare patient with catastrophic sudden-severe asthma unresponsive to first-line therapies. 1, 2

Current Evidence on Efficacy

The most recent systematic review and meta-analysis from 2022 analyzing 17 RCTs with 1,046 patients demonstrates that:

• Epinephrine and selective β2-agonists have similar efficacy for treatment failure (OR 0.99,95% CI 0.74 to 1.34), meaning no clinically meaningful difference 1
• The overall quality of evidence is very low due to serious risk of bias, significant inconsistency between studies, and imprecision in effect estimates 1
• Epinephrine has a worse side effect profile compared to selective β2-agonists, including increased heart rate, myocardial irritability, and increased myocardial oxygen demand 1, 2

Important Nuance in the Data

While the overall pooled analysis shows no benefit, there is one intriguing finding: studies recruiting adults-only showed lower odds of treatment failure with epinephrine compared to selective β2-agonists 1, 2. However, this subgroup analysis is limited by small numbers and the overall low quality of evidence, making it insufficient to change practice 1

When to Consider IM Epinephrine

Clear Indications (Guideline-Supported)

Use IM epinephrine when:

• Concomitant anaphylaxis or angioedema is present 1, 2, 3
• Pre-identified high-risk patients with catastrophic sudden-severe (brittle) asthma who have a mutually agreed management plan and carry preloaded epinephrine syringes 3

Possible Consideration (Controversial)

May consider in severe/life-threatening asthma when:

• Patient is unresponsive to repeated courses of inhaled β2-agonists 2
• Patient is unable to cooperate with inhaled therapy (altered mental status, extreme distress) 2
• This remains controversial as it conflicts with international asthma guidelines but is included in many prehospital ambulance protocols 1, 2

Dosing and Administration

If epinephrine is indicated:

• Subcutaneous route: 0.01 mg/kg of 1:1000 concentration, divided into 3 doses of approximately 0.3 mg at 20-minute intervals 2
• Intramuscular route: Alternative in prehospital settings for rapid absorption 2
• Intravenous route: 0.25-1 mcg/min continuous infusion for life-threatening cases, though this carries a 4% risk of serious side effects 2, 4

Standard First-Line Treatment Algorithm

Never delay these proven therapies while considering epinephrine:

1. High-flow oxygen (40-60%) to maintain SaO2 >90% 3
2. Nebulized selective β2-agonists (salbutamol 5 mg or terbutaline 10 mg) via oxygen 2, 3
3. Systemic corticosteroids (prednisolone 30-60 mg PO OR hydrocortisone 200 mg IV) 2, 3
4. For life-threatening features, add:
   • Nebulized ipratropium 0.5 mg 2, 3
   • IV magnesium sulfate 2
   • IV aminophylline (250 mg over 20 minutes) OR IV salbutamol/terbutaline (250 µg over 10 minutes) 3

Critical Pitfalls to Avoid

• Do not use IM epinephrine routinely in standard acute severe asthma—it is not part of evidence-based stepwise management 3
• Do not delay first-line therapies (oxygen, nebulized β2-agonists, systemic steroids) while considering epinephrine 3
• Recognize the discrepancy between international asthma guidelines (which recommend against routine epinephrine use) and many prehospital ambulance protocols (which still recommend it for severe asthma) 1, 2
• Be aware of cardiovascular risks: While epinephrine appears well-tolerated even in patients over 35 years, it can cause tachycardia, arrhythmias, and increased myocardial oxygen demand 2, 4

The Bottom Line on Clinical Practice

The disconnect between prehospital guidelines and hospital-based asthma guidelines creates confusion. The evidence clearly shows no benefit from adding epinephrine to standard therapy in most acute asthma cases 1. The theoretical advantages of alpha-agonist activity (reducing microvascular leakage and airway edema) do not translate into clinically meaningful improvements in bronchodilation or outcomes 5.

High-quality RCTs are urgently needed to definitively answer whether adding IM epinephrine to inhaled selective β2-agonists improves outcomes in severe/life-threatening asthma 1. Until such evidence exists, the safest approach is to reserve epinephrine for anaphylaxis or the rare catastrophic brittle asthma patient with a pre-established plan 2, 3.