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A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest
Open accessAbstract
BACKGROUND: Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients. METHODS: In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]). RESULTS: At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]). CONCLUSIONS: In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024 .).
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“In contrast, a strict requirement for pre-enrolment consent may delay the initiation of an experimental intervention, thereby hampering its potential benefit to the patient. 327”
From European Resuscitation Council Guidelines 2021: Ethics of resuscitation and end of life decisions (2021) · cites this paper as [327]
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Zhang, Q., Pang, Z., Yan, X., Tang, F., Li, S., Shao, X., Zou, W., Xing, T., Guo, S., Xiangjun, M. E. N. G., et al. (2026) · Annals of Medicine · doi:10.1080/07853890.2026.2740275
Melo, R. H., Joelsons, D., Guimarães, H. P., & Passos, R. D. H. (2026) · International Journal of Emergency Medicine · doi:10.1186/s12245-026-01419-3
Blandin, M., Marouk, A., & Lapostolle, F. (2026) · European Journal of Emergency Medicine · doi:10.1097/mej.0000000000001354
The Pharmacologic Management of Cardiac Arrest
Singh, A., Heeney, M. E., & Montgomery, M. E. (2026) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2026.08.006
Bantidos, M. G., Tsintsi, E., Kofos, C., Tasioudis, P., Papadopoulos, A. F., Kommata, C., Kokkinos, A., Nasoufidou, A., Stachteas, P., Apostolopoulou, A., et al. (2026) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2026.2757453
DeVita, M. A. (2026) · Resuscitation · doi:10.1016/j.resuscitation.2026.111376
Metadata
- Authors
- Perkins, G. D., Ji, C., Deakin, C. D., Quinn, T., Nolan, J. P., Scomparin, C., Regan, S., Long, J., Slowther, A., Pocock, H., Black, J. J. M., Moore, F., Fothergill, R. T., Rees, N., O’Shea, L., Docherty, M., Gunson, I., Han, K., Charlton, K., Finn, J., Petrou, S., Stallard, N., Gates, S., & Lall, R.
- Affiliations
- University of Warwick (GB)
- National Institute for Health and Care Research (GB)
- St George's, University of London (GB)
- Royal United Hospital (GB)
- North East Ambulance Service NHS Foundation Trust (GB)
- Curtin University (AU)
- ORCID
- Perkins, Gavin D.
- Ji, Chen
- Deakin, Charles D.
- Quinn, Tom
- Nolan, Jerry P.
- Scomparin, Charlotte
- Regan, Scott
- Long, John
- Slowther, Anne
- Pocock, Helen
- Black, John J.M.
- Moore, Fionna
- Fothergill, Rachael T.
- Rees, Nigel
- O’Shea, Lyndsey
- Docherty, Mark
- Gunson, Imogen
- Han, Kyee
- Charlton, Karl
- Finn, Judith
- Petrou, Stavros
- Stallard, Nigel
- Gates, Simon
- Lall, Ranjit
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-08-23
- Volume
- 379
- Issue
- 8
- Pages
- 711-721
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2883159984
- Cited by
- 794
- References
- 35
- Citations by year
- 2026: 59 · 2025: 88 · 2024: 101 · 2023: 87 · 2022: 74 · 2021: 105 · 2020: 150 · 2019: 102 · 2018: 27
- FWCI
- 117.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- Monash University Research Portal (Monash University) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Research Repository (Kingston University London) (acceptedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion, other-oa)
- eSpace (Curtin University) (submittedVersion)
- amber - ambulance research repository (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Explore Bristol Research (submittedVersion)
- Funders
- Health Technology Assessment Programme (12/127/126)
- Topics
- Health Sciences › Medicine › Emergency Medicine › Cardiac Arrest and Resuscitation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative Care and End-of-Life Issues
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- out-of-hospital cardiac arrest, epinephrine, cardiopulmonary resuscitation, 30-day survival, neurological outcome, modified Rankin Scale, paramedics, ambulance services, United Kingdom National Health Service, resuscitation guidelines
- MeSH terms
- Aged, Combined Modality Therapy, Double-Blind Method, Electric Countershock, Emergency Medical Services, Epinephrine, Female, United Kingdom, Humans, Male, Middle Aged, Nervous System Diseases, Sympathomimetics, Survival Rate, Cardiopulmonary Resuscitation, Hospital Mortality, Out-of-Hospital Cardiac Arrest, Time-to-Treatment
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