A Comparison of Standard-Dose and High-Dose Epinephrine in Cardiac Arrest outside the Hospital

Experimental and uncontrolled clinical evidence suggests that intravenous epinephrine in doses higher than currently recommended may improve outcome after cardiac arrest. We conducted a prospective, multicenter study comparing standard-dose epinephrine with high-dose epinephrine in the management of cardiac arrest outside the hospital. Adult patients were enrolled in the study if they remained in ventricular fibrillation, or if they had asystole or electromechanical dissociation, at the time the first drug was to be administered to treat the cardiac arrest. Patients were randomly assigned to receive either 0.02 mg of epinephrine per kilogram of body weight (standard-dose group, 632 patients) or 0.2 mg per kilogram (high-dose group, 648 patients), both given intravenously. In the standard-dose group 190 patients (30 percent) had a return of spontaneous circulation, as compared with 217 patients (33 percent) in the high-dose group; 136 patients (22 percent) in the standard-dose group and 145 patients (22 percent) in the high-dose group survived to be admitted to the hospital. Twenty-six patients (4 percent) in the standard-dose group and 31 (5 percent) in the high-dose group survived to discharge from the hospital. Ninety-two percent of the patients discharged in the standard-dose group and 94 percent in the high-dose group were conscious at the time of hospital discharge. None of the differences in outcome between the groups were statistically significant. In this study, we were unable to demonstrate any difference in the overall rate of return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, or neurologic outcome between patients treated with a standard dose of epinephrine and those treated with a high dose. (N Engl J Med 1992;327: 1051–5.), RECENT experimental studies of cardiac arrest have demonstrated that, as compared with standard doses of epinephrine (0.01 to 0.02 mg per kilogram of body weight), a larger dose (0.2 mg per kilogram) improves cerebral and myocardial blood flow, the balance between myocardial oxygen supply and demand, and rates of resuscitation.^{1 2 3 4 5 6 7} As a result of these investigations, larger doses of epinephrine have been evaluated in several uncontrolled clinical trials.^{8 9 10 11 12} These studies have found improvement in arterial diastolic pressure,⁸ coronary perfusion pressure,⁹ rates of resuscitation,¹⁰ and neurologic outcome^{11 , 12} with high doses of epinephrine. To compare the efficacy of high-dose epinephrine (0.2 mg…