What is the role of epinephrine (adrenaline) during cardiac arrest?

Role of Epinephrine During Cardiac Arrest

Epinephrine significantly increases return of spontaneous circulation (ROSC) and survival to hospital discharge during cardiac arrest primarily through its α-adrenergic effects, which increase coronary and cerebral perfusion pressure during CPR. 1

Mechanism of Action

Epinephrine acts through multiple mechanisms during cardiac arrest:

• α-adrenergic effects: Primary beneficial mechanism that causes peripheral vasoconstriction, increasing coronary and cerebral perfusion pressures during CPR 2, 3
• β-adrenergic effects: Increases heart rate (positive chronotropic) and contractility (positive inotropic) but may have detrimental effects including:
  • Increased myocardial oxygen demand
  • Reduced subendocardial perfusion
  • Potential for post-ROSC arrhythmias 2, 3

Evidence for Efficacy

Meta-analysis of randomized controlled trials shows epinephrine significantly improves:

• ROSC (RR 3.09,95% CI 2.82-3.39)
• Survival to hospital admission (RR 2.88,95% CI 2.57-3.22)
• Survival to hospital discharge (RR 1.44,95% CI 1.11-1.86) 1

The effects are particularly pronounced in patients with non-shockable rhythms:

• Improved survival to hospital discharge in non-shockable rhythms (RR 2.56,95% CI 1.37-4.80)
• Increased ROSC in non-shockable rhythms (RR 4.45,95% CI 3.91-5.08) 1

Dosing and Timing

• Standard dose: 1 mg IV/IO every 3-5 minutes during CPR 1
• For non-shockable rhythms: Administer as soon as feasible (Class 2a recommendation) 1
• For shockable rhythms: Administer after initial defibrillation attempts have failed (Class 2b recommendation) 1
• High-dose epinephrine: Not recommended as it shows no benefit and potential harm 4

Potential Concerns

While epinephrine improves ROSC and short-term survival, there are important considerations:

• The impact on neurological outcomes remains uncertain 1, 5
• Higher cumulative doses of epinephrine (>5 mg) are associated with increased risk of cardiocirculatory death in patients who achieve ROSC 5
• The β-adrenergic effects may be detrimental post-ROSC by increasing myocardial oxygen demand 3

Clinical Application

1. For non-shockable rhythms (PEA/asystole):

   • Administer epinephrine 1 mg IV/IO as soon as feasible
   • Continue every 3-5 minutes during resuscitation

2. For shockable rhythms (VF/pVT):

   • Focus first on high-quality CPR and defibrillation
   • Administer epinephrine 1 mg IV/IO after initial defibrillation attempts have failed
   • Continue every 3-5 minutes during resuscitation

Common Pitfalls

• Delayed administration: Earlier administration of epinephrine is associated with better outcomes, particularly in non-shockable rhythms 1
• Excessive dosing: Higher cumulative doses may worsen post-resuscitation syndrome and increase risk of cardiocirculatory death 5
• Route of administration: IV/IO is preferred; if unavailable, consider alternative routes but expect delayed or diminished effect

In conclusion, epinephrine remains a cornerstone of cardiac arrest management with a strong recommendation for its use (Class 1, Level B-R) 1. The primary benefit is increased ROSC and short-term survival through α-adrenergic-mediated increases in coronary and cerebral perfusion pressure, though the impact on long-term neurological outcomes requires further study.