{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:56:59Z","timestamp":1787677019515,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T00:00:00Z","timestamp":1736553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Academic Emergency Medicine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study aimed to clarify the appropriate timing for epinephrine administration in adults with out\u2010of\u2010hospital cardiac arrest (OHCA), particularly those cases with nonshockable rhythms, by addressing resuscitation time bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective observational study utilizing a multicenter OHCA registry involving 95 hospitals in Japan between June 2014 and December 2020. We included patients with OHCA and nonshockable rhythms who received epinephrine during resuscitation. The primary and secondary outcomes were favorable 30\u2010day neurological status and survival, respectively. A favorable neurological outcome was defined as a cerebral performance category score of 1 or 2. The time from emergency medical service (EMS) personnel contact to epinephrine administration was categorized in 5\u2010min intervals. We used the Fine\u2013Gray regression to calculate the time\u2010dependent propensity score in each group. After risk set matching, we employed a generalized estimating equation (GEE) to adjust for within\u2010patient clustering.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 36,756 patients were included in the analysis. When involving timing variables and GEE, epinephrine administration significantly affected favorable 30\u2010day neurological status at 1\u20135 and 6\u201310\u2009min, with risk ratios (RR; 95% confidence intervals [CIs]) of 9.36 (1.19\u201373.7) and 3.67 (1.89\u20137.14), respectively. Epinephrine administration significantly affected 30\u2010day survival at 1\u20135, 6\u201310, 11\u201315, and 16\u201320\u2009min, with RRs (95% CIs) of 2.33 (1.41\u20133.85), 2.09 (1.65\u20132.65), 1.64 (1.32\u20132.05), or 1.70 (1.29\u20132.25), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Epinephrine administration within 10\u2009min of EMS personnel contact may be associated with favorable neurological outcomes in patients with OHCA and nonshockable rhythms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acem.15089","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T10:51:16Z","timestamp":1736592676000},"page":"659-667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Optimal timing for epinephrine administration in adult patients with out\u2010of\u2010hospital cardiac arrest: A retrospective observational study"],"prefix":"10.1111","volume":"32","author":[{"given":"Kenta","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Saitama Medical Center Jichi Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-1595","authenticated-orcid":false,"given":"Hideto","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Saitama Medical Center Jichi Medical University  Saitama Japan"},{"name":"Department of Clinical Research Education and Training Unit Keio University Hospital Clinical and Translational Research Center (CTR)  Tokyo Japan"},{"name":"School of Nursing, Midwifery and Social Work, UQ Centre for Clinical Research The University of Queensland  Herston Queensland Australia"},{"name":"School of Nursing and Midwifery, Alliance for Vascular Access Teaching and Research Griffith University  Nathan Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Shinzato","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Saitama Medical Center Jichi Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-1466","authenticated-orcid":false,"given":"Yuki","family":"Kishihara","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Saitama Medical Center Jichi Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-1507","authenticated-orcid":false,"given":"Shunsuke","family":"Amagasa","sequence":"additional","affiliation":[{"name":"Department of Emergency and Transport Medicine National Center for Child Health and Development  Tokyo 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