Hagihara: Prehospital epinephrine use and survival among patients without-of-hospital cardiac arrest

Hagihara. JAMA 2012;(307)11:1165-1168

Clinical Question

  • In patients with out-of-hospital (OOH) cardiac arrest is the use of adrenaline, compared to not using adrenaline, associated with an improved mortality?


  • Prospective
  • Non-randomised
  • Cohort study with concurrent control group


  • Pre-hospital services, Japan
  • 01.01.2005-31.12.2008


  • Inclusion: adult patients who had an OOH cardiac arrest prior to arrival of emergency services
  • Exclusion: >60 minutes elapsed from call to scene arrival or >480 minutes from call to hospital arrival; missing data on adrenaline administration
  • 417 188 patients


  • Patients treated with epinephrine
    • From April 2006 certified paramedics were permitted to use adrenaline which led to the development of the intervention and the control group


  • Patients not treated with adrenaline


  • Comparing patients who received adrenaline with patients who did not receive adrenaline:
    •  the Odds Ratios (95% C.I.) were the following for:
      • Return of spontaneous circulation (ROSC) before hospital arrival
        • unadjusted OR 3.75 (3.59-3.91)
        • adjusted OR 2.36 (2.22-2.5)
      • Survival at 1 month
        • unadjusted OR 1.15 (1.07-1.23)
        • adjusted OR 0.46 (0.42-0.51)
      • Good neurological outcome (CPC 1 or 2)
        • unadjusted OR 0.61 (0.53-0.7)
        • adjusted OR 0.31(0.26-0.36)
    • Similar results were found in a propensity matched subgroup (n=26,802)

Authors’ Conclusions

  • Use of prehospital adrenaline was significantly associated with increased ROSC but decreased chance of survival and good functional outcome


  • Huge numbers of patients
  • Similar results found when analysed with different models


  • Non-randomised
  • Baseline characteristics generally favour adrenaline group with greater rates of bystander CPR (45% vs. 36%), use of public AED (0.8% vs. 0.4%), VF/VT (13.7% vs. 7.2%)
  • Data on in-hospital CPR not included in analysis
  • Number of adrenaline doses given not recorded
  • Included pre-hospital cardiac arrests only
  • One month survival influenced by in-hospital care which varies between centres

The Bottom Line

  • This study found an association between the use of adrenaline for cardiac arrest, and decreased survival as well as a poor neurological outcome. It is a non-randomised study, but with >400,000 patients included it needs to be taken seriously. If this was a ‘new drug’ it would not be included in any guideline, and is perhaps currently still only in the guidelines because it is something that ‘we have always done’!


Full text pdf / abstract / doi: 10.1001/jama.2012.294

Editorial, Commentaries or Blogs


Summary author: @davidslessor
Summary date: 14 May 2014
Peer-review editor: @stevemathieu75

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