{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:13:55Z","timestamp":1793916835001,"version":"4.8.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Epinephrine is the most common medication used in cardiac arrest. Although the medication has been a mainstay of treatment over the last century, the utility and efficacy of epinephrine has been re-evaluated in recent years. This study aims to evaluate the literature describing the efficacy, timing, and dosing of epinephrine use in cardiac arrest. We utilized an extensive PubMed and SCOPUS search that included randomized control trials, prospective observational studies, and secondary analysis of observational data. These articles evaluated the administration of epinephrine in cardiac arrest and reported patient outcomes, including survival rates, neurological function, and return of spontaneous circulation. Dosing of epinephrine has been standardized at 1 mg per administration in adults and studies show that higher doses may not have better outcomes and can potentially be harmful. Research on the optimal timing of epinephrine has shown that earlier administration of epinephrine in cardiac arrest is more likely to have improved outcomes compared to later administration and longer intervals, although there are still conflicting results on the improvement of neurological outcomes. Intravenous is the preferred route of administration for epinephrine, but new research suggests intramuscular administration may be beneficial. While epinephrine has been shown to improve the rates of return of spontaneous circulation and even survival to hospital discharge in several studies, epinephrine use may not provide patients who survive cardiac arrest with a meaningful neurological recovery.<\/jats:p>","DOI":"10.3390\/medicina60111904","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:14:38Z","timestamp":1732094078000},"page":"1904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Use of Epinephrine in Cardiac Arrest: Advances and Future Challenges"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-5799","authenticated-orcid":false,"given":"Caitlin A.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah E.","family":"Fairley","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7774-154X","authenticated-orcid":false,"given":"Quincy K.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Program in Trauma, The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8440-8454","authenticated-orcid":false,"given":"Ali","family":"Pourmand","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart Disease and Stroke Statistics\u20142023 Update: A Report From the American Heart Association. American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1912208","DOI":"10.1001\/jamanetworkopen.2019.12208","article-title":"Assessment of Hospital Readmission Rates, Risk Factors, and Causes After Cardiac Arrest: Analysis of the US Nationwide Readmissions Database","volume":"2","author":"Yeo","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_3","unstructured":"(2024, September 12). Adult Basic and Advanced Life Support. American Heart Association. Available online: https:\/\/cpr.heart.org\/en\/resuscitation-science\/cpr-and-ecc-guidelines\/adult-basic-and-advanced-life-support."},{"key":"ref_4","unstructured":"Dalal, R., and Grujic, D. (2024, September 12). Epinephrine, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK482160\/."},{"key":"ref_5","unstructured":"(2024, September 08). Algorithms. American Heart Association. Available online: https:\/\/cpr.heart.org\/en\/resuscitation-science\/cpr-and-ecc-guidelines\/algorithms."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s00134-021-06548-2","article-title":"Brain injury after cardiac arrest: Pathophysiology, treatment, and prognosis","volume":"47","author":"Sandroni","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jjcc.2020.03.007","article-title":"The Sequential Organ Failure Assessment (SOFA) score predicts mortality and neurological outcome in patients with post-cardiac arrest syndrome","volume":"76","author":"Matsuda","year":"2020","journal-title":"J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.resuscitation.2011.06.029","article-title":"Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial","volume":"82","author":"Jacobs","year":"2011","journal-title":"Resuscitation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1001\/jama.2012.294","article-title":"Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest","volume":"307","author":"Hagihara","year":"2012","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.resuscitation.2011.11.011","article-title":"Outcome when adrenaline (epinephrine) was actually given vs. not given\u2014Post hoc analysis of a randomized clinical trial","volume":"83","author":"Olasveengen","year":"2012","journal-title":"Resuscitation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1016\/j.jacc.2014.09.036","article-title":"Is Epinephrine During Cardiac Arrest Associated With Worse Outcomes in Resuscitated Patients?","volume":"64","author":"Dumas","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1806842","article-title":"A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest","volume":"379","author":"Perkins","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1111\/aas.12184","article-title":"Effects of adrenaline on rhythm transitions in out-of-hospital cardiac arrest","volume":"57","author":"Neset","year":"2013","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1056\/NEJM199210083271503","article-title":"A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group","volume":"327","author":"Brown","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1056\/NEJM199210083271502","article-title":"High-dose epinephrine in adult cardiac arrest","volume":"327","author":"Stiell","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJM199811263392204","article-title":"A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group","volume":"339","author":"Gueugniaud","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1001\/jama.1992.03490190067033","article-title":"A Randomized Clinical Trial of High-Dose Epinephrine and Norepinephrine vs Standard-Dose Epinephrine in Prehospital Cardiac Arrest","volume":"268","author":"Callaham","year":"1992","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"(2000). Part 6: Advanced Cardiovascular Life Support. Circulation, 102, 1\u201386.","DOI":"10.1161\/01.CIR.102.suppl_1.I-86"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ajem.2024.03.013","article-title":"Cumulative epinephrine dose during cardiac arrest and neurologic outcome after extracorporeal cardiopulmonary resuscitation","volume":"80","author":"Garcia","year":"2024","journal-title":"Am. J. Emerg. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.resuscitation.2017.04.014","article-title":"A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: An observational study and propensity analysis","volume":"117","author":"Lamhaut","year":"2017","journal-title":"Resuscitation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"g3028","DOI":"10.1136\/bmj.g3028","article-title":"Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: Retrospective analysis of large in-hospital data registry","volume":"348","author":"Donnino","year":"2014","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1161\/CIRCULATIONAHA.117.033067","article-title":"Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults","volume":"137","author":"Hansen","year":"2018","journal-title":"Circulation"},{"key":"ref_23","first-page":"1639","article-title":"Impact of early intravenous epinephrine administration on outcomes following out-of-hospital cardiac arrest","volume":"76","author":"Hayashi","year":"2012","journal-title":"Circ. J. Off. J. Jpn. Circ. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1097\/SHK.0000000000001731","article-title":"Timing of Intravenous Epinephrine Administration During Out-of-Hospital Cardiac Arrest","volume":"56","author":"Fukuda","year":"2021","journal-title":"Shock"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2120176","DOI":"10.1001\/jamanetworkopen.2021.20176","article-title":"Association of Timing of Epinephrine Administration With Outcomes in Adults With Out-of-Hospital Cardiac Arrest","volume":"4","author":"Okubo","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.resuscitation.2013.03.023","article-title":"Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest","volume":"84","author":"Koscik","year":"2013","journal-title":"Resuscitation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s00134-019-05836-2","article-title":"The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial | Intensive Care Medicine","volume":"46","author":"Perkins","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.annemergmed.2019.04.031","article-title":"The Association of the Average Epinephrine Dosing Interval and Survival With Favorable Neurologic Status at Hospital Discharge in Out-of-Hospital Cardiac Arrest","volume":"74","author":"Grunau","year":"2019","journal-title":"Ann. Emerg. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.resuscitation.2015.12.008","article-title":"The influences of adrenaline dosing frequency and dosage on outcomes of adult in-hospital cardiac arrest: A retrospective cohort study","volume":"103","author":"Wang","year":"2016","journal-title":"Resuscitation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.resuscitation.2013.10.004","article-title":"Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: A retrospective review of prospectively collected data","volume":"85","author":"Warren","year":"2014","journal-title":"Resuscitation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"i1577","DOI":"10.1136\/bmj.i1577","article-title":"Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: Propensity score matched analysis","volume":"353","author":"Andersen","year":"2016","journal-title":"BMJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.resuscitation.2021.02.010","article-title":"European Resuscitation Council Guidelines 2021: Adult advanced life support","volume":"161","author":"Soar","year":"2021","journal-title":"Resuscitation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e066534","DOI":"10.1136\/bmj-2021-066534","article-title":"Epinephrine before defibrillation in patients with shockable in-hospital cardiac arrest: Propensity matched analysis","volume":"375","author":"Evans","year":"2021","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100651","DOI":"10.1016\/j.resplu.2024.100651","article-title":"Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm","volume":"18","author":"Kawakami","year":"2024","journal-title":"Resusc. Plus"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.resuscitation.2007.10.017","article-title":"Cardiovascular response to epinephrine varies with increasing duration of cardiac arrest","volume":"77","author":"Angelos","year":"2008","journal-title":"Resuscitation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1161\/01.CIR.92.10.3089","article-title":"Epinephrine increases the severity of postresuscitation myocardial dysfunction","volume":"92","author":"Tang","year":"1995","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.resuscitation.2020.11.019","article-title":"Clinical evaluation of intravenous alone versus intravenous or intraosseous access for treatment of out-of-hospital cardiac arrest","volume":"159","author":"Tan","year":"2021","journal-title":"Resuscitation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1007\/s00134-019-05920-7","article-title":"Intraosseous versus intravenous administration of adrenaline in patients with out-of-hospital cardiac arrest: A secondary analysis of the PARAMEDIC2 placebo-controlled trial","volume":"46","author":"Nolan","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110266","DOI":"10.1016\/j.resuscitation.2024.110266","article-title":"Early intramuscular adrenaline administration is associated with improved survival from out-of-hospital cardiac arrest","volume":"201","author":"Palatinus","year":"2024","journal-title":"Resuscitation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114058","DOI":"10.1016\/j.jpeds.2024.114058","article-title":"Use of Initial Endotracheal Versus Intravenous Epinephrine During Neonatal Cardiopulmonary Resuscitation in the Delivery Room: Review of a National Database","volume":"271","author":"Halling","year":"2024","journal-title":"J. Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1097\/00003246-200006000-00022","article-title":"Endotracheal versus intravenous epinephrine and atropine in out-of-hospital \u201cprimary\u201d and postcountershock asystole","volume":"28","author":"Niemann","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0140-6736(01)05328-4","article-title":"Vasopressin versus epinephrine for inhospital cardiac arrest: A randomised controlled trial","volume":"358","author":"Stiell","year":"2001","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1056\/NEJMoa025431","article-title":"A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation","volume":"350","author":"Wenzel","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.resuscitation.2012.02.005","article-title":"A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department","volume":"83","author":"Ong","year":"2012","journal-title":"Resuscitation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/s13054-022-04248-x","article-title":"Augmented-Medication CardioPulmonary Resuscitation Trials in out-of-hospital cardiac arrest: A pilot randomized controlled trial","volume":"26","author":"Kim","year":"2022","journal-title":"Crit. Care"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chander, S., Parkash, O., Luhana, S., Lohana, A.C., Sadarat, F., Sapna, F., Raja, F., Rahaman, Z., Mohammed, Y.N., and Shiwlani, S. (2024). Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients\u2014A systematic review and meta-analysis. BMC Cardiovasc. Disord., 24.","DOI":"10.1186\/s12872-024-03962-4"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJMe1808255","article-title":"Testing Epinephrine for Out-of-Hospital Cardiac Arrest","volume":"379","author":"Callaway","year":"2018","journal-title":"N. Engl. J. Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1904\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:36:05Z","timestamp":1760114165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["medicina60111904"],"URL":"https:\/\/doi.org\/10.3390\/medicina60111904","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}