Does increased epinephrine (adrenaline) administration during cardiac arrest worsen patient outcomes?

From the Guidelines

Increased epinephrine administration during cardiac arrest does not improve patient outcomes and may worsen them, therefore standard dosing of epinephrine 1mg IV/IO every 3-5 minutes remains the recommended approach for cardiac arrest management. The use of epinephrine in cardiac arrest has been extensively studied, with the most recent and highest quality evidence coming from the 2023 American Heart Association focused update on adult advanced cardiovascular life support 1. This update highlights that epinephrine increases return of spontaneous circulation (ROSC) and short-term survival, but its impact on long-term survival with favorable neurological outcomes remains uncertain.

The evidence suggests that higher doses of epinephrine do not improve survival to hospital discharge or neurological outcomes, and may actually be harmful 1. The alpha-adrenergic effects of epinephrine can increase coronary and cerebral perfusion pressure, but its beta-adrenergic effects can simultaneously increase myocardial oxygen demand and cause post-ROSC myocardial dysfunction. Additionally, epinephrine may worsen cerebral microcirculation, potentially leading to worse neurological outcomes.

Key points to consider in the administration of epinephrine during cardiac arrest include:

• The timing of epinephrine administration, with earlier administration (within 3-5 minutes of cardiac arrest) generally associated with better outcomes than delayed administration 1
• The use of standard dose epinephrine (1 mg IV/IO every 3-5 minutes) as the recommended approach for cardiac arrest management 1
• The avoidance of increasing epinephrine doses beyond standard recommendations, as the potential harms may outweigh any short-term benefits in achieving ROSC 1
• The consideration of the patient's initial rhythm, with epinephrine administration recommended as soon as feasible in cardiac arrest with nonshockable rhythms, unless there is a clearly reversible cause that can be addressed rapidly 1.

Overall, the current evidence supports the use of standard dose epinephrine in cardiac arrest management, with careful consideration of the timing and potential risks and benefits of its administration.

From the FDA Drug Label

5.3 Cardiac Arrhythmias and Ischemia Epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially patients with coronary artery disease, or cardiomyopathy 10. OVERDOSAGE Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation

The administration of increased epinephrine during cardiac arrest may worsen patient outcomes due to the potential for:

• Cardiac arrhythmias and myocardial ischemia
• Pulmonary edema
• Cerebrovascular hemorrhage
• Cardiomyopathy These potential adverse effects are associated with the use of epinephrine, especially in patients with pre-existing coronary artery disease or cardiomyopathy 2 2.

From the Research

Epinephrine Administration During Cardiac Arrest

• The use of epinephrine during cardiac arrest is a common practice, but its effectiveness in improving patient outcomes is still a topic of debate 3, 4, 5.
• Studies have shown that epinephrine may improve return of spontaneous circulation (ROSC), but it does not necessarily improve survival to discharge or neurologic outcome 3, 4, 5.
• The optimal dose and timing of epinephrine administration are still unknown, and current guidelines are based on limited animal data and expert opinion 6, 4.

Outcomes of Epinephrine Administration

• Research suggests that high-dose epinephrine is harmful and not recommended 3.
• A systematic review and meta-analysis found that the epinephrine administration interval (EAI) during cardiopulmonary resuscitation (CPR) was not associated with better hospital outcomes 6.
• Another study found that reducing the dose of epinephrine administered during out-of-hospital cardiac arrest was not associated with a change in survival to hospital discharge or favorable neurological outcomes 7.

Key Findings

• Epinephrine may improve ROSC, but its effect on long-term survival and functional recovery is still unclear 3, 4, 5.
• Basic Life Support measures, including adequate chest compressions and early defibrillation, provide the greatest benefit for patient survival 3.
• Further clinical trials are necessary to determine the optimal dosing interval and patient selection for epinephrine in cardiac arrest 6, 4.