The Association of the Average Epinephrine Dosing Interval and Survival With Favorable Neurologic Status at Hospital Discharge in Out-of-Hospital Cardiac Arrest

      Study objective

      For patients with out-of-hospital cardiac arrest, the recommended dosing interval of epinephrine is 3 to 5 minutes, but this recommendation is based on expert opinion without data to guide optimal management. We seek to evaluate the association between the average epinephrine dosing interval and patient outcomes.


      In a secondary analysis of the Resuscitation Outcomes Consortium continuous chest compression trial, we identified consecutive patients treated with greater than or equal to 2 doses of epinephrine. We defined average epinephrine dosing interval as resuscitation duration after the first dose of epinephrine divided by the total administered epinephrine, and categorized the dosing interval in minutes as less than 3, 3 to less than 4, 4 to less than 5, and greater than or equal to 5. We fit a logistic regression model to estimate the association of the average epinephrine dosing interval category with survival with favorable neurologic status (modified Rankin Scale score ≤3) at hospital discharge.


      We included 15,909 patients (median age 68 years [interquartile range 56 to 80 years], 35% women, 13% public location, 46% bystander cardiopulmonary resuscitation, and 19% initial shockable rhythm). The median epinephrine dosing interval was 4.3 minutes (interquartile range 3.5 to 5.3 minutes). Survival with favorable neurologic status occurred in 4.7% of patients. Compared with the reference dosing interval of less than 3 minutes, longer epinephrine dosing intervals were associated with lower survival with favorable neurologic status: dosing interval 3 to less than 4 minutes, adjusted odds ratio 0.44 (95% confidence interval 0.32 to 0.60); 4 to less than 5 minutes, adjusted odds ratio 0.26 (95% confidence interval 0.18 to 0.36); and greater than or equal to 5 minutes, adjusted odds ratio 0.21 (95% confidence interval 0.15 to 0.30).


      In this out-of-hospital cardiac arrest series, a shorter average epinephrine dosing interval was associated with improved survival with favorable neurologic status.
      To read this article in full you will need to make a payment
      ACEP Member Login
      ACEP Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Go A.S.
        • Mozaffarian D.
        • Roger V.L.
        • et al.
        Heart disease and stroke statistics—2014 update: a report from the American Heart Association.
        Circulation. 2014; 129: e28-e292
        • Link M.S.
        • Berkow L.C.
        • Kudenchuk P.J.
        • et al.
        Part 7: adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.
        Circulation. 2015; 132: S444-S464
        • Ornato J.P.
        Optimal vasopressor drug therapy during resuscitation.
        Crit Care. 2008; 12: 123
        • Hansen M.
        • Schmicker R.H.
        • Newgard C.D.
        • et al.
        Time to epinephrine administration and survival from nonshockable out-of-hospital cardiac arrest among children and adults.
        Circulation. 2018; 137: 2032-2040
        • Warren S.A.
        • Huszti E.
        • Bradley S.M.
        • et al.
        Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: a retrospective review of prospectively collected data for the American Heart Association’s Get With the Guidelines–Resuscitation (National Registry of CPR) Investigator.
        Resuscitation. 2014; 85: 350-358
        • Wang C.H.
        • Huang C.H.
        • Chang W.T.
        • et al.
        The influences of adrenaline dosing frequency and dosage on outcomes of adult in-hospital cardiac arrest: a retrospective cohort study.
        Resuscitation. 2016; 103: 125-130
        • Hoyme D.B.
        • Patel S.S.
        • Samson R.A.
        • et al.
        Epinephrine dosing interval and survival outcomes during pediatric in-hospital cardiac arrest.
        Resuscitation. 2017; 117: 18-23
        • Nichol G.
        • Leroux B.
        • Wang H.
        • et al.
        Trial of Continuous or Interrupted Chest Compressions During CPR.
        N Engl J Med. 2015; 373: 2203-2214
        • Morrison L.J.
        • Nichol G.
        • Rea T.D.
        • et al.
        Rationale, development and implementation of the Resuscitation Outcomes Consortium Epistry–Cardiac Arrest.
        Resuscitation. 2008; 78: 161-169
        • von Elm E.
        • Altman D.G.
        • Egger M.
        • et al.
        The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
        J Clin Epidemiol. 2008; 61: 344-349
        • Kudenchuk P.J.
        • Brown S.P.
        • Daya M.
        • et al.
        Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest.
        N Engl J Med. 2016; 374: 1711-1722
        • Perkins G.D.
        • Jacobs I.G.
        • Nadkarni V.M.
        • et al.
        Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: a statement for healthcare professionals from a task force of the International Liaison Committee.
        Resuscitation. 2015; 96: 328-340
        • Daya M.
        • Leroux B.
        • Rea T.
        • et al.
        Survival after intravenous vs intraosseous amiodarone, lidocaine or placebo in out-of-hospital ventricular fibrillation cardiac arrest.
        Circulation. 2018; 138: e777
        • Kawano T.
        • Grunau B.
        • Scheuermeyer F.
        • et al.
        Intraosseous vascular access is associated with lower survival and neurological recovery among patients with out-of-hospital cardiac arrest.
        Ann Emerg Med. 2018; 71: 588-596
        • Perkins G.D.
        • Ji C.
        • Deakin C.D.
        • et al.
        A randomized trial of epinephrine in out-of-hospital cardiac arrest.
        N Engl J Med. 2018; 379: 711-721
        • Grunau B.E.
        • Reynolds J.C.
        • Scheuermeyer F.X.
        • et al.
        Comparing the prognosis of those with initial shockable and non-shockable rhythms with increasing durations of CPR: informing minimum durations of resuscitation.
        Resuscitation. 2016; 101: 50-56
        • Reynolds J.C.
        • Grunau B.E.
        • Rittenberger J.C.
        • et al.
        Association between duration of resuscitation and favorable outcome after out-of-hospital cardiac arrest: implications for prolonging or terminating resuscitation.
        Circulation. 2016; 134: 2084-2094
        • Cantrell C.L.
        • Hubble M.W.
        • Richards M.E.
        Impact of delayed and infrequent administration of vasopressors on return of spontaneous circulation during out-of-hospital cardiac arrest.
        Prehosp Emerg Care. 2013; 17: 15-22

      Linked Article