The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial

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Abstract

Purpose

To examine the time to drug administration in patients with a witnessed cardiac arrest enrolled in the Pre-Hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) randomised controlled trial.

Methods

The PARAMEDIC2 trial was undertaken across 5 NHS ambulance services in England and Wales with randomisation between December 2014 and October 2017. Patients with an out-of-hospital cardiac arrest who were unresponsive to initial resuscitation attempts were randomly assigned to 1 mg intravenous adrenaline or matching placebo according to treatment packs that were identical apart from treatment number. Participants and study staff were masked to treatment allocation.

Results

8016 patients were enrolled, 4902 sustained a witnessed cardiac arrest of whom 2437 received placebo and 2465 received adrenaline. The odds of return of spontaneous circulation decreased in both groups over time but at a greater rate in the placebo arm odds ratio (OR) 0.93 (95% CI 0.92–0.95) compared with the adrenaline arm OR 0.96 (95% CI 0.95–0.97); interaction OR: 1.03, 95% CI 1.01–1.05, p = 0.005. By contrast, although the rate of survival and favourable neurological outcome decreased as time to treatment increased, the rates did not differ between the adrenaline and placebo groups.

Conclusion

The rate of return of spontaneous circulation, survival and favourable neurological outcomes decrease over time. As time to drug treatment increases, adrenaline increases the chances of return of spontaneous circulation. Longer term outcomes were not affected by the time to adrenaline administration. (ISRCTN73485024).

Electronic supplementary material

The online version of this article (10.1007/s00134-019-05836-2) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Gavin D. Perkins:

ORCID: http://orcid.org/0000-0003-3027-7548

paramedic@warwick.ac.uk

Journal

Journal ID (nlm-ta): Intensive Care Med

Journal ID (iso-abbrev): Intensive Care Med

Title: Intensive Care Medicine

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0342-4642

ISSN (Electronic): 1432-1238

Publication date (Electronic): 7 January 2020

Publication date PMC-release: 7 January 2020

Publication date (Print): 2020

Volume: 46

Issue: 3

Pages: 426-436

Affiliations

[1 ]GRID grid.7372.1, ISNI 0000 0000 8809 1613, Warwick Clinical Trials Unit, , University of Warwick, ; Coventry, CV4 7AL UK

[2 ]Heartlands Hospital, University Hospitals Birmingham, Birmingham, B9 5SS UK

[3 ]GRID grid.451052.7, ISNI 0000 0004 0581 2008, South Central Ambulance Service NHS Foundation Trust, ; Otterbourne, SO21 2RU UK

[4 ]GRID grid.454385.b, NIHR Southampton Respiratory Biomedical Research Unit, ; Southampton, SO16 6YD UK

[5 ]GRID grid.416091.b, ISNI 0000 0004 0417 0728, Royal United Hospital, ; Bath, BA1 3NG UK

[6 ]GRID grid.83440.3b, ISNI 0000000121901201, Kingston University and St George’s, University of London, ; 6th Floor, Hunter Wing, Cranmer Terrace, London, SW17 0RE UK

[7 ]GRID grid.439800.6, London Ambulance Service NHS Trust, ; 8-20 Pocock Street, London, SE1 0BW UK

[8 ]GRID grid.451052.7, ISNI 0000 0004 0581 2008, West Midlands Ambulance Service University NHS Foundation Trust, ; Brierley Hill, West Midlands, DY5 1LX UK

[9 ]GRID grid.439685.5, Welsh Ambulance Services NHS Trust, ; Swansea, Wales SA2 8PP UK

[10 ]GRID grid.1032.0, ISNI 0000 0004 0375 4078, Curtin University, ; Perth, Australia

[11 ]GRID grid.6572.6, ISNI 0000 0004 1936 7486, Cancer Research UK Clinical Trials Unit, , University of Birmingham, ; Birmingham, B15 2TT UK

Author information

Gavin D. Perkins http://orcid.org/0000-0003-3027-7548

Article

Publisher ID: 5836

DOI: 10.1007/s00134-019-05836-2

PMC ID: 7067734

PubMed ID: 31912202

SO-VID: 11e939b0-1ada-4af6-ba7f-0288c39fd169

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.