Abstract

Introduction: The optimal timing of epinephrine administration in shockable initial rhythm out-of-hospital cardiac arrest (OHCA) is unclear. Hypothesis: Early compared to late epinephrine following first electrical defibrillation attempt is associated with better outcomes in shockable initial rhythm OHCA. Methods: We conducted a retrospective study in adults with shockable initial rhythm OHCA from 2011-2015 in North America. We used multivariable logistic regression to assess associations between timing of epinephrine and prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and hospital discharge with favorable neurological outcome (modified Rankin Scale score≤3). We used propensity-score-matching and subgroup analyses to assess robustness of associations. Results: Of 6416 patients, median age was 64 (IQR: 54-74) years, 5136 (80%) were men, 2226 (35%) received epinephrine within four minutes after first defibrillation, 5119 (80%), 1237 (19%), and 996 (16%) had prehospital ROSC, survival to hospital discharge, and favorable neurological outcome at discharge respectively. Adjusted for confounders, we observed lower odds of prehospital ROSC (OR=0.95, 95%CI 0.94-0.96; p<0.001), survival to hospital discharge (OR=0.91, 95%CI 0.89-0.92; p<0.001), and favorable neurological outcomes at discharge (OR=0.92, 95%CI 0.90-0.93; p<0.001) per minute later epinephrine administration. Compared to epinephrine administration within four minutes following first defibrillation attempt, later epinephrine was associated with lower odds of prehospital ROSC (OR=0.58, 95%CI 0.51-0.68; p<0.001), survival to hospital discharge (OR=0.50, 95%CI 0.43-0.58; p<0.001), and favorable neurological outcome at discharge (OR=0.51, 95%CI 0.43-0.59; p<0.001). Associations remained significant in a well-balanced propensity score matched cohort and subgroup analyses by witness status, EMS response time, and total epinephrine dose. Conclusion: In shockable initial rhythm OHCA, early compared to late epinephrine administration following first defibrillation attempt was associated with better odds of prehospital ROSC, survival to hospital discharge, and hospital discharge with favorable neurological outcome.

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