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A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest
Gavin D Perkins1, Chen Ji1, Charles D Deakin1
1From the Warwick Clinical Trials Unit (G.D.P., C.J., C.S., S.R., J.L., S.P., S.G., R.L.) and Warwick Medical School (A.S., N.S.), University of Warwick, Coventry, University Hospitals Birmingham (G.D.P.) and the Cancer Research U.K. Clinical Trials Unit, University of Birmingham (S.G.), Birmingham, South Central Ambulance Service NHS Foundation Trust, Otterbourne (C.D.D., H.P., J.J.M.B.), Southampton Respiratory Biomedical Research Unit, National Institute for Health Research, Southampton (C.D.D.), Kingston University and St. George's, University of London (T.Q.), and the London Ambulance Service NHS Trust, (F.M., R.T.F.), London, Bristol Medical School, University of Bristol, Bristol, and Royal United Hospital, Bath (J.P.N.), Oxford University Hospitals NHS Foundation Trust, Oxford (J.J.M.B), South East Coast Ambulance Service, Crawley (F.M.), Welsh Ambulance Services NHS Trust, Swansea (N.R., L.O.), West Midlands Ambulance Service NHS Foundation Trust, Brierley Hill (M.D., I.G.), and North East Ambulance Service NHS Foundation Trust, Newcastle Upon Tyne (K.H., K.C.) - all in the United Kingdom; and Curtin University, Perth, WA (J.F.), and Monash University, Melbourne, VIC (J.F.) - both in Australia.
Background:
Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients.
Methods:
In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]).
Results:
At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]).
Conclusions:
In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024 .).
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