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Acad Emerg Med. 2012 Jul;19(7):782-92. doi: 10.1111/j.1553-2712.2012.01387.x.

Association between timing of epinephrine administration and intact neurologic survival following out-of-hospital cardiac arrest in Japan: a population-based prospective observational study.

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St. Marianna University School of Medicine, Kawasaki, Japan.



This study aimed to investigate whether early epinephrine administration in out-of-hospital cardiopulmonary arrest (OHCA) patients was associated with improved outcomes and to address the selection bias inherent in observational studies (more severe cases are more likely to receive epinephrine).


This was a retrospective analysis of prospectively collected population-based data of adult bystander-witnessed OHCA patients from a nationwide Japanese registry between January 2007 and December 2008. To address selection bias, those who attained early return of spontaneous circulation (ROSC) without epinephrine administration were excluded, leaving 49,165 patients in the analysis. The outcomes were intact neurologic survival, defined as survival with cerebral performance category score 1 or 2, and any survival at 1 month or at discharge (whichever was earlier). The primary predictor was the time from the start of cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) to first epinephrine administration, with early epinephrine defined as within 10 minutes.


Multivariate logistic regression analysis showed that cardiac origin OHCA patients who received early epinephrine (≤ 10 minutes) had significantly higher rates of intact neurologic survival (odds ratio [OR]=1.39, 95% confidence interval [CI]=1.08 to 1.78) and any survival (OR=1.73, 95% CI=1.46 to 2.04) than those who did not receive early epinephrine, after adjusting for potential confounders. Results for noncardiac OHCA patients were similar.


Early epinephrine administration may be associated with higher rates of intact neurologic survival and any survival in adult bystander-witnessed OHCA patients. This article provides a potential method to address the selection bias inherent in observational studies that examine the effects of drug administration in OHCA patients.

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