What is the maximum dose of epinephrine (adrenaline) considered safe in cardiac arrest?

Maximum Epinephrine Dosage in Cardiac Arrest

Standard-dose epinephrine (1 mg every 3 to 5 minutes) is recommended for cardiac arrest, with no defined maximum cumulative dose, though doses exceeding 3 mg may be associated with worse neurological outcomes. 1

Standard Dosing Recommendations

• The American Heart Association (AHA) guidelines recommend administering 1 mg of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest (Class IIb, LOE B-R) 1
• This dosing regimen is supported by evidence showing improved return of spontaneous circulation (ROSC) and survival to hospital admission compared to placebo 1
• There is no officially defined maximum cumulative dose or number of doses in the current guidelines 1

High-Dose vs. Standard-Dose Epinephrine

• High-dose epinephrine (0.1 to 0.2 mg/kg) is not recommended for routine use in cardiac arrest 1
• While high-dose epinephrine may increase ROSC rates, studies have not demonstrated any benefit for:
  • Survival to hospital discharge 1
  • Neurologically favorable survival 1
  • Survival with good neurologic recovery 1
• The adverse effects of higher doses in the post-arrest period may negate potential advantages during the arrest 1

Emerging Evidence on Cumulative Dosing

• Recent research suggests that cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurological outcomes, particularly in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) 2
• This association persisted after adjusting for age (odds ratio 4.6,95% CI 1.3-18.0) 2
• However, this finding requires further investigation before changing standard practice 2

Special Considerations

• High-dose epinephrine may be considered in exceptional circumstances such as:
  • β-blocker overdose 1
  • Calcium channel blocker overdose 1
  • When titrated to real-time physiologically monitored parameters 1

Epinephrine Administration Interval

• Multiple studies have examined whether changing the epinephrine administration interval affects outcomes:
  • Neither shorter (<3 minutes) nor longer (>5 minutes) dosing intervals were associated with improved neurologically favorable survival compared to the standard 3-5 minute interval 3, 4
  • This supports maintaining the current recommended interval of every 3-5 minutes 3

Pediatric Dosing

• For pediatric cardiac arrest, the recommended dose is 0.01 mg/kg (0.1 mL/kg of 1:10,000 concentration), with a maximum single dose of 1 mg 1
• This dose should be repeated every 3-5 minutes 1
• High-dose epinephrine is not recommended for routine use in pediatric patients 1

Common Pitfalls

• Delaying CPR and defibrillation while preparing epinephrine 5
• Using high-dose epinephrine routinely without specific indications 1
• Administering epinephrine at incorrect intervals (too frequent or too infrequent) 3
• Failing to recognize when epinephrine may be harmful, such as in cardiac arrest associated with sympathomimetic drug overdose 5

While there is no defined maximum number of doses in the guidelines, clinicians should be aware that higher cumulative doses may be associated with worse neurological outcomes, and the decision to continue administering epinephrine should be integrated into the overall resuscitation strategy.