High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: a prospective, randomized study

Abstract

Objective: To determine whether high-dose epinephrine (0.2 mg/kg) during cardiopulmonary resuscitation (CPR) results in improved outcome, compared with standard-dose epinephrine (0.02 mg/kg).

Design: A prospective, randomized, blinded study.

Setting: Research laboratory of a university medical center.

Subjects and interventions: Thirty domestic swine were randomized to receive standard- or high-dose epinephrine during CPR after 15 mins of fibrillatory cardiac arrest. Three minutes of CPR were provided, followed by advanced cardiac life support per American Heart Association guidelines. Animals that were successfully resuscitated were supported for 2 hrs in an intensive care unit (ICU) setting, and then observed for 24 hrs.

Measurements and main results: Electrocardiogram, aortic blood pressure, right atrial blood pressure, and end-tidal CO2 were monitored continuously until the intensive care period ended. Survival and neurologic outcome were determined. Return of spontaneous circulation was attained in 14 of 15 animals in each group. Four of 14 high-dose epinephrine pigs died during the ICU period after return of spontaneous circulation vs. zero of the 14 standard-dose pigs (p < .05). Six standard-dose pigs survived 24 hrs vs. four high-dose pigs. Twenty-four-hour survival rate and neurologic outcome were not significantly different. Within 10 mins of defibrillation, severe hypertension (diastolic pressure > 120 mmHg) occurred in 12 of 14 high-dose pigs vs. two of 14 standard-dose pigs (p < .01). Severe tachycardia (heart rate > 250 beats/min) occurred in seven of 14 high-dose pigs vs. zero of 14 standard-dose pigs (p < .01). All four high-dose epinephrine pigs that died during the ICU period experienced both severe hypertension and tachycardia immediately postresuscitation.

Conclusions: High-dose epinephrine did not improve 24-hr survival rate or neurologic outcome. Immediately after return of spontaneous circulation, most animals in the high-dose epinephrine group exhibited a hyperadrenergic state that included severe hypertension and tachycardia. High-dose epinephrine resulted in a greater early mortality rate.