Is epinephrine (epi) appropriate in pre-hospital cardiac arrest?

Is Epinephrine Appropriate in Pre-Hospital Cardiac Arrest?

Yes, epinephrine is recommended for pre-hospital cardiac arrest and should be administered at 1 mg IV/IO every 3-5 minutes. 1

Strength of Recommendation

The American Heart Association provides a Class 1 (strong) recommendation for epinephrine administration in cardiac arrest based on Level B-R evidence. 1 This recommendation applies to both in-hospital and out-of-hospital settings, though the evidence base primarily derives from out-of-hospital cardiac arrest trials. 1

Evidence Supporting Use

Proven Benefits

• Return of Spontaneous Circulation (ROSC): Epinephrine significantly increases ROSC rates, with 151 more patients per 1,000 achieving ROSC compared to placebo (RR 2.80,95% CI 1.78-4.41). 1

• Survival to Hospital Admission: Epinephrine increases survival to admission by 124 more patients per 1,000 (RR 1.95% CI 1.34-2.84). 1

• Survival to Hospital Discharge: Meta-analyses demonstrate epinephrine significantly improves survival to discharge. 1

Neurological Outcome Uncertainty

• At 3 months post-arrest, epinephrine showed a non-significant increase in both favorable AND unfavorable neurological outcomes. 1

• The PARAMEDIC 2 trial (>8,000 patients) found no definitive improvement in survival with favorable neurological outcome, though there was an increase in short-term survival with unfavorable neurological outcome. 1

• The very low survival rate with favorable neurological outcome (1.9-2.2%) in major trials may reflect the prolonged time to drug administration (median 21 minutes from arrest). 1

Dosing Protocol

Standard Dosing

• 1 mg IV/IO every 3-5 minutes during ongoing cardiac arrest 1
• Operationally, administering epinephrine every second cycle of CPR after the initial dose is also reasonable 1
• No maximum cumulative dose is defined in current guidelines 2

High-Dose Epinephrine

• High-dose epinephrine (0.1-0.2 mg/kg) is NOT recommended for routine use (Class 3: No Benefit) 1, 2
• While high doses may increase ROSC rates, they fail to improve survival to discharge and may cause harm through excessive beta-adrenergic stimulation 1, 2
• Consider high-dose only in exceptional circumstances: beta-blocker overdose, calcium channel blocker overdose, or when titrated to real-time physiological parameters 2

Timing Considerations

Rhythm-Specific Timing

• Non-shockable rhythms (PEA/asystole): Administer epinephrine as soon as feasible (Class 2a, Level C-LD) 1

  • All 16 observational studies found an association between earlier epinephrine and ROSC for non-shockable rhythms 1
  • Epinephrine may be particularly effective for non-shockable rhythms 1

• Shockable rhythms (VF/pVT): It may be reasonable to administer epinephrine after initial defibrillation attempts have failed (Class 2b, Level C-LD) 1

  • Witnessed arrests with shockable rhythms may be treatable without epinephrine, especially if a reversible cause is identified 1

The Time-to-Drug Problem

• Observational data consistently suggest better outcomes when epinephrine is given sooner 1, 3
• The median 21-minute delay from arrest to epinephrine in out-of-hospital trials likely contributes to poor neurological outcomes 1
• Any drug that increases ROSC and short-term survival but is given after several minutes of downtime will likely increase both favorable AND unfavorable neurological outcomes 1

Critical Nuances and Pitfalls

The Neurological Outcome Dilemma

The guideline writing groups acknowledge a fundamental challenge: determining the likelihood of favorable versus unfavorable neurological outcome at the time of arrest is currently not feasible. 1 Therefore, the recommendation prioritizes using a drug proven to increase survival while focusing efforts on shortening time-to-drug for all patients. 1

Pre-Hospital vs. In-Hospital Context

• No randomized trials exist for epinephrine in in-hospital cardiac arrest 1
• Time to drug is markedly shorter in-hospital, suggesting epinephrine may be more beneficial in this setting, particularly for non-shockable rhythms 1
• The applicability of out-of-hospital trial results to in-hospital arrests remains uncertain 1

Route of Administration

• Intravenous or intraosseous routes are standard 1
• The impact of delivery mode (IV vs. IO) on outcomes remains unknown and requires further research 1
• Recent research suggests intramuscular administration may have potential benefits, though this is not yet guideline-supported 3

Dose-Response Concerns

• Lower-dose protocols (0.5 mg) showed no significant difference in outcomes compared to standard 1 mg dosing 4
• Cumulative doses above 3 mg may be associated with unfavorable neurological outcomes in patients receiving ECPR (OR 4.6,95% CI 1.3-18.0) 5
• However, no threshold dose of benefit or harm has been definitively established for standard cardiac arrest 1

Common Pitfalls to Avoid

• Delaying epinephrine administration in non-shockable rhythms—give as soon as feasible 1
• Using high-dose epinephrine routinely without specific indications (beta-blocker/calcium channel blocker overdose) 2
• Administering epinephrine in sympathomimetic drug overdose-related cardiac arrest, where it may be harmful 2
• Extravasation: Monitor IV sites closely; blanching along the vein may progress to tissue necrosis. Treat extravasation with phentolamine 5-10 mg infiltrated into affected area 6

The Bottom Line

Despite uncertainty about neurological outcomes, epinephrine remains the standard of care for pre-hospital cardiac arrest because it significantly improves ROSC, hospital admission, and survival to discharge. 1 The focus should be on administering it as early as possible, particularly for non-shockable rhythms, while maintaining high-quality CPR and early defibrillation as the foundation of resuscitation. 1, 7