What is the preferred medication between epinephrine (Epi) and levophed (Norepinephrine) in the setting of cardiac arrest?

Epinephrine vs. Norepinephrine in Cardiac Arrest

Epinephrine is the recommended first-line vasopressor medication during cardiac arrest, while norepinephrine is preferred for post-ROSC hypotension management. 1

During Active Cardiac Arrest

Epinephrine Recommendations

• The 2023 American Heart Association (AHA) guidelines strongly recommend epinephrine administration for patients in cardiac arrest (Class 1, Level B-R) 1
• Standard dosing: 1 mg IV/IO every 3-5 minutes during CPR 1
• Timing recommendations:
  • For non-shockable rhythms (PEA/asystole): Administer as soon as feasible (Class 2a, Level C-LD) 1
  • For shockable rhythms (VF/pVT): Consider after initial defibrillation attempts have failed (Class 2b, Level C-LD) 1

Evidence Supporting Epinephrine in Cardiac Arrest

• Epinephrine increases return of spontaneous circulation (ROSC) and short-term survival through its α-adrenergic effects, which increase coronary and cerebral perfusion pressure during CPR 1
• Meta-analyses of randomized trials showed epinephrine significantly increases:
  • 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

Norepinephrine in Cardiac Arrest

• Current guidelines do not recommend norepinephrine as a first-line agent during active cardiac arrest
• No evidence supports norepinephrine over epinephrine during the cardiac arrest phase

Post-ROSC Management

Norepinephrine Preference After ROSC

• Norepinephrine is the preferred vasopressor for post-ROSC hypotension management 2
• Recent survey of emergency medicine pharmacists found 81% use norepinephrine as first-choice vasopressor for post-ROSC hypotension, while only 17% use epinephrine 2

Evidence Supporting Norepinephrine Post-ROSC

• Patients receiving epinephrine infusions after ROSC experience significantly higher rates of re-arrest compared to norepinephrine:
  • 55% vs 25% re-arrest rates (adjusted OR 3.28,95% CI 2.25-5.08) 3
  • Meta-analysis showed 63% lower odds of recurrent arrest with norepinephrine (OR 0.47,95% CI 0.24-0.92) 4

Clinical Algorithm

1. During active cardiac arrest:

   • Use epinephrine 1 mg IV/IO every 3-5 minutes
   • For non-shockable rhythms: Give as soon as possible
   • For shockable rhythms: Consider after initial defibrillation attempts fail

2. After achieving ROSC:

   • Switch to norepinephrine infusion for blood pressure support
   • Initial dose: 2-4 mcg/min, titrate to maintain adequate perfusion 5
   • Target systolic BP 80-100 mmHg (or no more than 40 mmHg below baseline in previously hypertensive patients) 5

Important Considerations

• High-dose epinephrine is not recommended during cardiac arrest (Class 3: No Benefit) 1
• Vasopressin may be considered but offers no advantage over epinephrine (Class 2b) 1
• Early administration of epinephrine is associated with better outcomes in observational studies 1
• The β-adrenergic effects of epinephrine may be detrimental post-ROSC, potentially increasing myocardial oxygen demand and promoting arrhythmias 1

Common Pitfalls to Avoid

1. Delaying epinephrine administration in non-shockable rhythms - give as soon as possible
2. Using high-dose epinephrine - no evidence of benefit and potential for harm
3. Continuing epinephrine infusions post-ROSC - associated with higher re-arrest rates compared to norepinephrine
4. Abrupt discontinuation of vasopressors - taper gradually to avoid rebound hypotension 5
5. Inadequate fluid resuscitation before or during vasopressor therapy - always consider occult hypovolemia 5