How Epinephrine Works During CPR
Epinephrine increases return of spontaneous circulation (ROSC) and short-term survival during cardiac arrest primarily through alpha-adrenergic-mediated peripheral vasoconstriction that raises coronary perfusion pressure, though its impact on long-term neurological outcomes remains uncertain. 1, 2
Mechanism of Action
Epinephrine acts on both alpha and beta-adrenergic receptors to produce three critical hemodynamic effects during CPR 3:
- Alpha-1 adrenergic vasoconstriction increases aortic diastolic pressure, which is the primary mechanism for improving coronary perfusion pressure (calculated as aortic diastolic pressure minus right atrial pressure) 4, 5
- Positive inotropic effect (beta-1) increases the strength of ventricular contraction 3
- Positive chronotropic effect (beta-1) increases heart rate 3
The alpha-adrenergic effects are what actually restore spontaneous circulation—the beta effects do not aid in restoration of circulation or defibrillation 4. In fact, beta-adrenergic stimulation increases myocardial oxygen consumption during fibrillation, which is potentially harmful 4.
Clinical Benefits and Evidence
Proven Short-Term Benefits
- Increases ROSC across all cardiac rhythms with high certainty evidence 2
- Improves survival to hospital discharge in patients with non-shockable rhythms (PEA/asystole) with moderate certainty evidence (RR 2.56; 95% CI 1.37-4.80) 2
- Increases 30-day survival compared to placebo (RR 1.40) based on the PARAMEDIC 2 trial 1, 2
Uncertain Neurological Outcomes
- Does NOT improve survival with favorable neurological outcome at 3 months in high-quality randomized trials 1, 2
- The larger PARAMEDIC 2 trial (8,000 patients) found no difference in survival with favorable or unfavorable neurological outcomes at 3 months 1
- There was an increase in survivors with poor neurological function in the epinephrine group 6
Timing of Administration
For Non-Shockable Rhythms (PEA/Asystole)
- Administer epinephrine as soon as feasible after establishing vascular access (strong recommendation) 2
- Earlier administration is associated with improved outcomes compared to delayed administration 2
- Delaying epinephrine in non-shockable rhythms worsens outcomes 2
For Shockable Rhythms (VF/pVT)
- Administer epinephrine after initial defibrillation attempts have been unsuccessful (weak recommendation) 1, 2
- The optimal timing or number of shocks before epinephrine administration remains unclear 1
- Meta-analysis shows epinephrine's effects on ROSC are greater for non-shockable rhythms than shockable rhythms 1
Dosing
- Standard dose: 1 mg IV/IO every 3-5 minutes during CPR 1, 2
- High-dose epinephrine (>1 mg) increases ROSC but does not improve survival to discharge or neurological outcomes 2
- Infuse into a large vein to avoid extravasation and tissue necrosis 3
Potential Harmful Effects
Microvascular Compromise
- Epinephrine reduces cerebral microvascular blood flow through its alpha-1 adrenergic effects, which may increase cerebral ischemia during CPR 5
- This reduction in microvascular perfusion may offset the beneficial increase in arterial blood pressure 7
Cardiovascular Complications
- May induce cardiac arrhythmias and myocardial ischemia, particularly in patients with underlying coronary artery disease 3
- Can cause severe hypertension requiring blood pressure monitoring 3
- Risk of pulmonary edema from increased cardiac output and peripheral vasoconstriction 3
Common Pitfalls to Avoid
- Do not delay epinephrine in non-shockable rhythms while attempting other interventions—give it as soon as vascular access is established 2
- Avoid extravasation by checking the infusion site frequently; blanching along the vein indicates vasa vasorum constriction and potential tissue necrosis 3
- Do not use vasopressin as a substitute for epinephrine or in combination with it—it offers no benefit over epinephrine alone 1, 2
- Do not stop chest compressions to administer epinephrine—all medications should be given during ongoing CPR 8