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Standard dose epinephrine versus placebo in out of hospital cardiac arrest: A systematic review and meta-analysis

Published:January 11, 2019DOI:https://doi.org/10.1016/j.ajem.2018.12.055

      Abstract

      Introduction

      Out of hospital cardiac arrest (OHCA) is a time critical and heterogeneous presentation. The most appropriate management strategies remain an issue for debate. The aim of this systematic review and meta-analysis was to determine the association of epinephrine versus placebo with return of spontaneous circulation, survival to hospital admission, survival to hospital discharge and neurological outcomes in out of hospital cardiac arrest.

      Methods

      A systematic review of five databases was performed from inception to August 2018. Only randomised controlled trials were considered eligible for inclusion. The primary outcome was survival to hospital discharge. Secondary outcomes were ROSC, survival to hospital admission, neurological function on discharge and three-month survival. All studies were assessed for level of evidence and risk of bias.

      Results

      Five randomised controlled trials with 17,635 patients were identified for inclusion. Use of epinephrine was associated with increased ROSC (OR = 3.10; 95% CI = 2.16 to 4.45; I2 = 74%; p < 0.0001) and increased survival to hospital admission OR = 2.52; 95% CI = 1.63 to 3.88; I2 = 94%; p < 0.0001). However, epinephrine was not associated with increased survival to discharge (OR = 1.09; 95% CI = 0.48 to 2.47; I2 = 77%; p = 0.84) or differences in neurological outcomes (OR = 0.81; 95% CI = 0.34 to 1.96).

      Discussion

      This study was a systematic review and meta-analysis of epinephrine versus placebo in OHCA. The use of epinephrine was associated with improved ROSC and survival to hospital admission. However, use of epinephrine was not associated with a significant difference in survival to hospital discharge, neurological outcomes or survival to 3 months. Further research is required to control for the confounders during inpatient management.

      Keywords

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      References

        • Sasson C.
        • Rogers M.A.
        • Dahl J.
        • Kellermann A.L.
        Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis.
        Circ Cardiovasc Qual Outcomes. 2010; 3: 63-81
        • Valenzuela T.D.
        • Roe D.J.
        • Nichol G.
        • Clark L.L.
        • Spaite D.W.
        • Hardman R.G.
        Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos.
        N Engl J Med. 2000; 343: 1206-1209
        • Chowdhury A.
        • Fernandes B.
        • Melhuish T.M.
        • White L.D.
        Antiarrhythmics in cardiac arrest: a systematic review and meta-analysis.
        Heart Lung Circ. 2017; 27: 280-290
        • Perkins G.D.
        • Cottrell P.
        • Gates S.
        Is adrenaline effective in out of hospital cardiac arrest?.
        BMJ. 2014; 348: g1763
        • Abraham J.
        • Mudd J.O.
        • Kapur N.
        • Klein K.
        • Champion H.C.
        • Wittstein I.S.
        Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists.
        J Am Coll Cardiol. 2009; 53: 1320-1325
        • Ristagno G.
        • Tang W.
        • Huang L.
        • et al.
        Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.
        Crit Care Med. 2009; 37: 1408-1415
        • Lin S.
        • Callaway C.W.
        • Shah P.S.
        • et al.
        Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials.
        Resuscitation. 2014; 85: 732-740
        • Higgins J.P.
        • Altman D.G.
        • Gotzsche P.C.
        • Juni P.
        • Moher D.
        • Oxman A.D.
        • et al.
        The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Review Manager (RevMan)
        Version 5.
        vol. 3. The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen2014
        • Atiksawedparit P.
        • Rattanasiri S.
        • McEvoy M.
        • Graham C.A.
        • Sittichanbuncha Y.
        • Thakkinstian A.
        Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis.
        Crit Care. 2014; 18: 463
        • Patanwala A.E.
        • Slack M.K.
        • Martin J.R.
        • Basken R.L.
        • Nolan P.E.
        Effect of epinephrine on survival after cardiac arrest: a systematic review and meta-analysis.
        Minerva Anestesiol. 2014; 80: 831-843
        • Jacobs I.G.
        • Finn J.C.
        • Jelinek G.A.
        • Oxer H.F.
        • Thompson P.L.
        Effect of adrenaline on survival in out-of-hospital cardiac arrest: a randomised double-blind placebo-controlled trial.
        Resuscitation. 2011; 82: 1138-1143
        • Nordseth T.
        • Olasveengen T.M.
        • Kvaloy J.T.
        • Wik L.
        • Steen P.A.
        • Skogvoll E.
        Dynamic effects of adrenaline (epinephrine) in out-of-hospital cardiac arrest with initial pulseless electrical activity (PEA).
        Resuscitation. 2012; 83: 946-952
        • Olasveengen T.M.
        • Sunde K.
        • Brunborg C.
        • Thowsen J.
        • Steen P.A.
        • Wik L.
        Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
        JAMA, J Am Med Assoc. 2009; 302: 2222-2229
        • 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
        • Woodhouse S.P.
        • Cox S.
        • Boyd P.
        • Case C.
        • Weber M.
        High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest.
        Resuscitation. 1995; 30: 243-249
        • Ajam K.
        • Gold L.S.
        • Beck S.S.
        • Damon S.
        • Phelps R.
        • Rea T.D.
        Reliability of the Cerebral Performance Category to classify neurological status among survivors of ventricular fibrillation arrest: a cohort study.
        Scand J Trauma Resusc Emerg Med. 2011; 19: 38
        • Rittenberger J.C.
        • Raina K.
        • Holm M.B.
        • Kim Y.J.
        • Callaway C.W.
        Association between cerebral performance category, modified Rankin scale, and discharge disposition after cardiac arrest.
        Resuscitation. 2011; 82: 1036-1040
        • The Hypothermia After Cardiac Arrest Study Group
        Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.
        N Engl J Med. 2002; 346: 549-556
        • Hansen M.
        • Schmicker R.H.
        • Newgard C.D.
        • et al.
        Resuscitation outcomes in consortium investigators. Time to epinephrine administration and survival from nonshockable out-of-hospital cardiac arrest among children and adults.
        Circulation. 2018; 137: 2032-2040