Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study Yosuke Homma a,b, ⁎, Takashi Shiga a,c , Hiraku Funakoshi a , Dai Miyazaki d , Atsushi Sakurai e , Yoshio Tahara f , Ken Nagao g , Naohiro Yonemoto h , Arino Yaguchi i , Naoto Morimura j , SOS-KANTO 2012 Study Group a Department of Emergency Medicine and Critical Care, Tokyo Bay Urayasu Ichikawa Medical Center, Chiba, Japan b Center for Clinical Epidemiology, St. Luke's International University, Tokyo, Japan c Department of Emergency Medicine, International University of Health and Welfare, Tokyo, Japan d Advanced Emergency Medical and Critical Care Center, Japanese Redcross Maebashi Hospital, Gunma, Japan e Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan f Department of Cardiovascular Medicine, National Cerebral and Cardio-vascular Center Hospital, Suita, Osaka, Japan g Cardiovascular Center, Nihon University Surugadai Hospital, Chiyoda-ku, Tokyo, Japan h Department of Biostatistics, School of Public Health, Kyoto University, Yoshida-konoe, Kyoto, Japan i Department of Critical Care and Emergency Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan j Department of Emergency and Critical Care Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan abstract article info Article history: Received 11 April 2018 Received in revised form 15 May 2018 Accepted 20 May 2018 Available online xxxx Objective: This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms. Methods: This was a post-hoc analysis of a multicenter prospective cohort study (SOS-KANTO 2012), which reg- istered OHCA patients in the Kanto region of Japan from January 2012 to March 2013. We included consecutive adult OHCA patients who received epinephrine. The primary result included 1-month favorable neurological out- comes defined as cerebral performance category (CPC) 1 or 2. Secondary results included 1-month survival and return of spontaneous circulation (ROSC) after arrival at the hospital. Multivariable logistic regression analysis determined the association between delay per minute of the time from call to first EA in both pre- or in- hospital settings and outcomes. Results: Of the 16,452 patients, 9344 were eligible for our analyses. In univariable analysis, the delay in EA was associated with decreased favorable neurological outcomes only when the initial rhythm was a non-shockable rhythm. In multivariable analyses, delay in EA was associated with decreased ROSC (adjusted odds ratio [OR] for one minute delay, 0.97; 95% confidence interval [CI], 0.96–0.98) and 1-month survival (adjusted OR, 0.95; 95% CI, 0.92–0.97) when the initial rhythm was a non-shockable rhythm, whereas during a shockable rhythm, delay in EA was not associated with decreased ROSC and 1-month survival. Conclusions: While assessing the effectiveness of epinephrine for OHCA, we should consider the time-limited ef- fects of epinephrine. Additionally, consideration of early EA based on the pathophysiology is needed. © 2018 Published by Elsevier Inc. Keywords: Out-of-hospital cardiac arrest Cardiopulmonary resuscitation Advanced cardiac life support Epinephrine Emergency medical services Heart arrest 1. Introduction Out-of-hospital cardiac arrest (OHCA) is an increasing public health problem in most countries. Approximately, 300,000, 280,000, and 100,000 OHCAs occur annually in the USA [1], Europe [2], and Japan [3], respectively. Epinephrine administration (EA) was recommended for all OHCAs before 1974 [4] and is still recommended in the 2015 guidelines [5-7]. Unlike the confirmed usefulness of early defibrillation and uninterrupted chest compressions [8], the effectiveness of EA for fa- vorable neurological outcomes in OHCA has been controversial [9-11]. Recently, much attention has been paid to the time-dependent asso- ciation between EA and outcomes in OHCA, and studies have shown that early EA was associated with the increased return of spontaneous circulation (ROSC) after arrival at the hospital. However, survival till dis- charge and neurological outcomes remained controversial [12-17]. Nev- ertheless, the following knowledge gaps have not been adequately examined: (i) actual EA time for in-hospital settings and (ii) classifica- tion into initial rhythms. The SOS-KANTO 2012 study [18] distinctly American Journal of Emergency Medicine xxx (2018) xxx–xxx ⁎ Corresponding author at: Department of Emergency Medicine and Critical Care, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32, Todaijima, Urayasu-city, Chiba, Japan. E-mail address: yousukeh@jadecom.jp (Y. Homma). YAJEM-57539; No of Pages 8 https://doi.org/10.1016/j.ajem.2018.05.037 0735-6757/© 2018 Published by Elsevier Inc. Contents lists available at ScienceDirect American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem Please cite this article as: Homma Y, et al, Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.05.037