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Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry

BMJ 2014; 348 doi: (Published 20 May 2014) Cite this as: BMJ 2014;348:g3028
  1. Michael W Donnino, director, center for resuscitation science12,
  2. Justin D Salciccioli, clinical research coordinator1,
  3. Michael D Howell, associate professor of medicine3,
  4. Michael N Cocchi, director, critical care quality 14,
  5. Brandon Giberson, clinical research coordinator1,
  6. Katherine Berg, instructor of medicine2,
  7. Shiva Gautam, associate professor of medicine5,
  8. Clifton Callaway, executive vice chair of emergency medicine6
  9. for the American Heart Association’s Get With The Guidelines-Resuscitation Investigators
  1. 1Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, W/CC 2, MA, 02215, USA
  2. 2Department of Medicine, Division of Critical Care, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA
  3. 3Center for Quality, University of Chicago Medicine, 850 E 58th Street, Chicago, IL, 60637, USA
  4. 4Department of Anesthesia Critical Care, Division of Neurological/Trauma/Surgical Critical Care, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA, 02215, USA
  5. 5Department of Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA, 02215, USA
  6. 6Department of Emergency Medicine, University of Pittsburgh, 3600 Forbes Avenue, Iroquois Building, Suite 400A, Pittsburgh, PA, 15261, USA
  1. Correspondence to: M W Donnino, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, WCC2, Boston, MA 02215 mdonnino{at}
  • Accepted 20 April 2014


Objective To determine if earlier administration of epinephrine (adrenaline) in patients with non-shockable cardiac arrest rhythms is associated with increased return of spontaneous circulation, survival, and neurologically intact survival.

Design Post hoc analysis of prospectively collected data in a large multicenter registry of in-hospital cardiac arrests (Get With The Guidelines-Resuscitation).

Setting We utilized the Get With The Guidelines-Resuscitation database (formerly National Registry of Cardiopulmonary Resuscitation, NRCPR). The database is sponsored by the American Heart Association (AHA) and contains prospective data from 570 American hospitals collected from 1 January 2000 to 19 November 2009.

Participants 119 978 adults from 570 hospitals who had a cardiac arrest in hospital with asystole (55%) or pulseless electrical activity (45%) as the initial rhythm. Of these, 83 490 arrests were excluded because they took place in the emergency department, intensive care unit, or surgical or other specialty unit, 10 775 patients were excluded because of missing or incomplete data, 524 patients were excluded because they had a repeat cardiac arrest, and 85 patients were excluded as they received vasopressin before the first dose of epinephrine. The main study population therefore comprised 25 095 patients. The mean age was 72, and 57% were men.

Main outcome measures The primary outcome was survival to hospital discharge. Secondary outcomes included sustained return of spontaneous circulation, 24 hour survival, and survival with favorable neurologic status at hospital discharge.

Results 25 095 adults had in-hospital cardiac arrest with non-shockable rhythms. Median time to administration of the first dose of epinephrine was 3 minutes (interquartile range 1-5 minutes). There was a stepwise decrease in survival with increasing interval of time to epinephrine (analyzed by three minute intervals): adjusted odds ratio 1.0 for 1-3 minutes (reference group); 0.91 (95% confidence interval 0.82 to 1.00; P=0.055) for 4-6 minutes; 0.74 (0.63 to 0.88; P<0.001) for 7-9 minutes; and 0.63 (0.52 to 0.76; P<0.001) for >9 minutes. A similar stepwise effect was observed across all outcome variables.

Conclusions In patients with non-shockable cardiac arrest in hospital, earlier administration of epinephrine is associated with a higher probability of return of spontaneous circulation, survival in hospital, and neurologically intact survival.


  • We thank Tyler Giberson and Lars Andersen for their final review and editorial assistance and Francesca Montillo for her editorial assistance in preparing the manuscript.

  • Get With The Guidelines-Resuscitation Investigators

  • Besides MWD, members of the Get With The Guidelines-Resuscitation Adult Task Force include: Paul S Chan, Saint Luke’s Mid America Heart Institute; Steven M Bradley, VA Eastern Colorado Healthcare System; Dana P Edelson, University of Chicago; Robert T Faillace, Geisinger Healthcare System; Romergryko Geocadin, Johns Hopkins University School of Medicine; Raina Merchant, University of Pennsylvania School of Medicine; Vincent N Mosesso Jr, University of Pittsburgh School of Medicine; Joseph P Ornato and Mary Ann Peberdy, Virginia Commonwealth University.

  • Contributors: MWD: conception, design, analysis, data interpretation and manuscript writing. SG: analysis. JDS: analysis, data interpretation, manuscript writing. BG: conception, design, interpretation, manuscript writing. MNC: data interpretation, manuscript writing. MDH: analysis, interpretation, extensive editorial review of manuscript. KB: interpretation, manuscript writing. CC: data interpretation, editorial review of manuscript. MWD is guarantor.

  • Funding: The project described was supported, in part, by grant No UL1 RR025758-Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. MWD is supported by NHLBI (1K02HL107447-01A1) and NIH (R21AT005119-01).

  • Competing interest: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required. The database is exempt from institutional review board approval as it is part of a QI registry.

  • Data sharing: No additional data available.

  • Declaration of transparency: The lead author affirms that this manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant) have been explained.

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