A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest

Abstract

Objective: To determine the relative efficacy of high- vs standard-dose catecholamines in initial treatment of prehospital cardiac arrest.

Design: Randomized, prospective, double-blind clinical trial.

Setting: Prehospital emergency medical system of a major US city.

Patients: All adults in nontraumatic cardiac arrest, treated by paramedics, who would receive epinephrine according to American Heart Association advanced cardiac life support guidelines.

Interventions: High-dose epinephrine (HDE, 15 mg), high-dose norepinephrine bitartrate (NE, 11 mg), or standard-dose epinephrine (SDE, 1 mg) was blindly substituted for advanced cardiac life support doses of epinephrine.

Main outcome measures: Restoration of spontaneous circulation in the field, admission to hospital, hospital discharge, and Cerebral Performance Category score.

Results: Of 2694 patients with cardiac arrests during the study period, resuscitation was attempted on 1062 patients. Of this total, 816 patients met study criteria and were enrolled. In the entire cardiac arrest population, 63% of the survivors were among the 11% of patients who were defibrillated by first responders. The three drug treatment groups were similar for all independent variables. Thirteen percent of patients receiving HDE regained a pulse in the field vs 8% of those receiving SDE (P = .01), and 18% of HDE patients were admitted to the hospital vs 10% of SDE patients who were admitted to the hospital (P = .02). Similar trends for NE were not significant. There were 18 survivors; 1.7% of HDE patients and 2.6% of NE patients were discharged from the hospital compared with 1.2% of SDE patients, but this was not significant (P = .37; beta = .38). There was a nonsignificant trend for Cerebral Performance Category scores to be worse for HDE (3.2) and NE patients (3.7) than for SDE patients (2.3) (P = .10; beta = .31). No significant complications were identified. High-dose epinephrine did not produce longer hospital or critical care unit stays.

Conclusions: High-dose epinephrine significantly improves the rate of return of spontaneous circulation and hospital admission in patients who are in prehospital cardiac arrest without increasing complications. However, the increase in hospital discharge rate is not statistically significant, and no significant trend could be determined for neurological outcome. No benefit of NE compared with HDE was identified. Further study is needed to determine the optimal role of epinephrine in prehospital cardiac arrest.