Why is epinephrine administered during adult cardiac arrest in ACLS?

Why Epinephrine is Administered in ACLS Cardiac Arrest

Epinephrine is administered during cardiac arrest primarily because its alpha-1-adrenergic effects increase coronary perfusion pressure and aortic diastolic pressure, which are critical determinants of achieving return of spontaneous circulation (ROSC), even though its impact on long-term survival and neurological outcomes remains controversial. 1

Primary Mechanism of Action

Epinephrine works through peripheral vasoconstriction via alpha-1-adrenergic receptor stimulation, which increases:

• Coronary perfusion pressure during chest compressions 2, 3
• Aortic diastolic pressure, improving blood flow to vital organs 4
• Cerebral and myocardial blood flow through increased systemic vascular resistance 3

The drug's beta-adrenergic effects (increased heart rate, contractility, and myocardial oxygen demand) are actually considered potentially harmful, but the alpha effects are deemed essential for successful resuscitation 4, 3.

Evidence Supporting Its Use

Short-Term Benefits (Well-Established)

• ROSC rates increase dramatically: 151 more patients per 1,000 achieve ROSC with epinephrine versus placebo (RR 2.80,95% CI 1.78-4.41) 1
• Survival to hospital admission improves: 124 more patients per 1,000 survive to admission (RR 1.95% CI 1.34-2.84) 1
• These benefits form the basis for the AHA Class 1 (strong) recommendation for epinephrine use 1

Long-Term Outcomes (Controversial)

The evidence reveals a troubling paradox:

• No randomized trials have demonstrated improved survival to hospital discharge when comparing epinephrine to placebo 4
• Large observational studies suggest epinephrine may actually reduce long-term survival and functional recovery, particularly in patients with shockable rhythms 3, 5
• One major cohort study found adjusted odds ratios for intact survival of 0.48 for 1mg, 0.30 for 2-5mg, and 0.23 for >5mg of epinephrine compared to no epinephrine 5

Current Guideline Recommendations

Standard dosing: 1 mg IV/IO every 3-5 minutes during ongoing cardiac arrest 4, 1

Timing Based on Rhythm

• Non-shockable rhythms (PEA/asystole): Administer epinephrine as soon as feasible (Class 2a recommendation) 1
• Shockable rhythms (VF/pVT): May be reasonable to give after initial defibrillation attempts fail (Class 2b recommendation) 1

What NOT to Do

• High-dose epinephrine (0.1-0.2 mg/kg) is NOT recommended for routine use (Class 3: No Benefit) 1, 6
• Despite improving coronary perfusion pressure more than standard doses 2, high-dose regimens have not improved survival to discharge and may worsen post-arrest myocardial dysfunction 4, 6

Critical Physiological Considerations

The Duration Paradox

Research reveals that epinephrine's effects change as cardiac arrest progresses:

• Early in arrest (2 minutes): Epinephrine may actually improve post-ROSC cardiac function 7
• Mid-duration arrest (4 minutes): Cardiac function returns to baseline after ROSC 7
• Prolonged arrest (6+ minutes): Epinephrine becomes increasingly necessary for ROSC but causes progressively worse post-ROSC myocardial depression 7

Diminishing Returns with Repeated Dosing

• The hemodynamic augmentation from epinephrine decreases with each successive dose during prolonged CPR 8
• Maximum blood pressure elevation occurs 78-97 seconds after administration 8
• This suggests the current 3-5 minute dosing interval may not be optimally timed, though no alternative has proven superior 8

Why We Continue Using It Despite Concerns

The fundamental clinical reality is:

• Without epinephrine, very few patients achieve ROSC from cardiac arrest 1, 5
• While epinephrine may harm some patients who would have survived anyway, it enables ROSC in many who would otherwise have no chance 4, 1
• The AHA acknowledges the challenge of determining at the time of arrest which patients will have favorable versus unfavorable neurological outcomes 1

In the absence of a superior alternative (vasopressin shows no difference in outcomes 4, 9, and no other vasopressor has proven benefit 4), epinephrine remains the standard of care because some chance of survival with potential neurological impairment is considered preferable to certain death 1.

Common Pitfalls to Avoid

• Delaying epinephrine in non-shockable rhythms - it should be given immediately, not after multiple rounds of CPR 1
• Using high-dose epinephrine routinely without specific indications like beta-blocker or calcium channel blocker overdose 4, 6
• Giving epinephrine too early in shockable rhythms before adequate defibrillation attempts 1
• Administering epinephrine in sympathomimetic drug overdose where it may be harmful 6