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A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest
Abstract
Background
In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain.
Methods
We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems in the United Kingdom that involved adults in cardiac arrest for whom vascular access for drug administration was needed. Patients were randomly assigned to receive treatment from paramedics by means of an intraosseous-first or intravenous-first vascular access strategy. The primary outcome was survival at 30 days. Key secondary outcomes included any return of spontaneous circulation and favorable neurologic function at hospital discharge (defined by a score of 3 or less on the modified Rankin scale, on which scores range from 0 to 6, with higher scores indicating greater disability). No adjustment for multiplicity was made.
Results
A total of 6082 patients were assigned to a trial group: 3040 to the intraosseous group and 3042 to the intravenous group. At 30 days, 137 of 3030 patients (4.5%) in the intraosseous group and 155 of 3034 (5.1%) in the intravenous group were alive (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.68 to 1.32; P=0.74). At the time of hospital discharge, a favorable neurologic outcome was observed in 80 of 2994 patients (2.7%) in the intraosseous group and in 85 of 2986 (2.8%) in the intravenous group (adjusted odds ratio, 0.91; 95% CI, 0.57 to 1.47); a return of spontaneous circulation at any time occurred in 1092 of 3031 patients (36.0%) and in 1186 of 3035 patients (39.1%), respectively (adjusted odds ratio, 0.86; 95% CI, 0.76 to 0.97). During the trial, one adverse event, which occurred in the intraosseous group, was reported.
Conclusions
Among adults with out-of-hospital cardiac arrest requiring drug therapy, the use of an intraosseous-first vascular access strategy did not result in higher 30-day survival than an intravenous-first strategy. (Funded by the National Institute for Health and Care Research; PARAMEDIC-3 ISRCTN Registry number, ISRCTN14223494.)
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The views expressed are those of the authors and not necessarily those of the National Institute for Health and Care Research (NIHR) or the Department of Health and Social Care.
This article was published on October 31, 2024, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by a grant (NIHR131105) from the NIHR Health Technology Assessment Programme. Dr. Perkins is supported by the NIHR Applied Research Collaboration West Midlands. The trial received in-kind support from the NIHR Clinical Research Network, Health Care Research Wales, and the Out-of-Hospital Cardiac Arrest Outcomes registry (funded by a grant [HI/Lead/295003] from Resuscitation Council UK and the British Heart Foundation).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the patients and families who participated in the trial; the paramedics, nurses, doctors, and other prehospital clinicians involved in trial recruitment; the ambulance service research teams that led participant follow-up efforts; and the trial steering committee, data monitoring and ethics committee, the trial patient advisory group, and the staff at the hospitals that supported patient follow-up activities.
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New England Journal of Medicine
Copyright
Copyright © 2024 Massachusetts Medical Society. All rights reserved.
For personal use only. Any commercial reuse of NEJM Group content requires permission.
History
Published online: October 31, 2024
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Affiliations
From the Warwick Medical School, Clinical Trials Unit, University of Warwick (K.C., C.J., J.P.N., J.B.L., J.M.M., F.M., C.N., H.N., A.-M.S., M.A.S., K.R.S., S.W., R.L., G.D.P.), and the Critical Care Unit, University Hospital Coventry and Warwickshire NHS Trust (M.A.S.), Coventry, Devon Air Ambulance (N.L., B.T.) and South Western Ambulance Service NHS Foundation Trust (R.O., S.W.), Exeter, East Midlands Ambulance Service NHS Trust, Nottingham (R.E.S.S., G.L.S., G.A.W.), East of England Ambulance Service NHS Trust, Cambridge (S.B., T.F.), Kingston University (T.Q.) and London Ambulance Service NHS Trust (R.T.F., J.K., J.F., A.M.-S.), London, North East Ambulance Service NHS Foundation Trust, Newcastle upon Tyne (K.C., E.B., M.L.), North West Ambulance Service NHS Trust, Bolton (S.B., A. Wright, M.W.), South Central Ambulance Service NHS Foundation Trust, Bicester (C.D.D., M.B., A.C., V.D.), South East Coast Ambulance Service NHS Foundation Trust, Crawley (G.B., J.W.), Welsh Ambulance Services University NHS Trust, Cwmbran (C.M., N.R.), West Midlands Ambulance Service University NHS Foundation Trust, Brierley Hill (A. Walker, C.E., J.M., J.V.W.), the Critical Care Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (G.D.P., K.C.), the Emergency Department, Harrogate and District NHS Foundation Trust, Harrogate (A. Walker), the Department of Anaesthesia, Royal United Hospitals Bath NHS Foundation Trust, Bath (J.P.N.), University Hospital Southampton NHS Foundation Trust, Southampton (C.D.D.), and the University of Bristol, Bristol (J.P.N.) — all in the United Kingdom.
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- The Way to a Patient’s Heart — Vascular Access in Cardiac Arrest, New England Journal of Medicine, 0, 0, (undefined)./doi/full/10.1056/NEJMe2412901
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