Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest

Kirstie L Haywood; Chen Ji; Tom Quinn; Jerry P Nolan; Charles D Deakin; Charlotte Scomparin; Ranjit Lall; Simon Gates; John Long; Scott Regan; Rachael T Fothergill; Helen Pocock; Nigel Rees; Lyndsey O'Shea; Gavin D Perkins

doi:10.1016/j.resuscitation.2021.01.019

Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest

Resuscitation. 2021 Mar:160:84-93. doi: 10.1016/j.resuscitation.2021.01.019. Epub 2021 Jan 30.

Authors

Affiliations

¹ Warwick Research in Nursing, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
² Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
³ Kingston University and St George's, University of London, London SW17 0RE, UK.
⁴ Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; Royal United Hospital, Bath BA1 3NG, UK.
⁵ South Central Ambulance Service NHS Foundation Trust, Otterbourne SO21 2RU, UK; NIHR Southampton Respiratory Biomedical Research Unit, Southampton SO16 6YD, UK.
⁶ Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK.
⁷ Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; Kingston University and St George's, University of London, London SW17 0RE, UK; London Ambulance Service NHS Trust, London SE1 8SD, UK.
⁸ Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; South Central Ambulance Service NHS Foundation Trust, Otterbourne SO21 2RU, UK.
⁹ Welsh Ambulance Service NHS Trust, Institute of Life Sciences, Swansea University, Swansea, Wales SA2 8PP, UK.
¹⁰ Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham B91 2JL, UK. Electronic address: g.d.perkins@warwick.ac.uk.

PMID: 33524488
DOI: 10.1016/j.resuscitation.2021.01.019

Abstract

Aims: We recently reported early outcomes in patients enrolled in a randomised trial of adrenaline in out-of-hospital cardiac arrest: the PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) trial. The purpose of the present paper is to report long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months.

Methods: PARAMEDIC2 was a pragmatic, individually randomised, double blind, controlled trial with an economic evaluation. Patients were randomised to either adrenaline or placebo. This paper reports results on the modified Rankin Scale scores at 6-months, survival at 6 and 12-months, as well as other cognitive, functional and quality of life outcomes collected at 3 and 6 months (Two Simple Questions, the Mini Mental State Examination, the Informant Questionnaire on Cognitive Decline Evaluation for Cardiac Arrest, Hospital Anxiety and Depression Scale, the Post Traumatic Stress Disorder Checklist - Civilian Version, Short-Form 12-item Health Survey and the EuroQoL EQ-5D-5L).

Results: 8014 patients were randomised with confirmed trial drug administration. At 6-months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93, 1.97]). 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05, 1.96], reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00, 1.92]). Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups.

Conclusion: Adrenaline improved survival through to 12-months follow-up. The study did not find evidence of improvements in favourable neurological outcomes. (ISCRTN 73485024).

Keywords: Adrenaline; Cardiac arrest; Cognitive; Drugs; Functional; Health related quality of life; Long term.

Publication types

Pragmatic Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Cost-Benefit Analysis
Double-Blind Method
Epinephrine
Humans
Out-of-Hospital Cardiac Arrest* / drug therapy
Quality of Life
Surveys and Questionnaires

Substances

Epinephrine

Grants and funding

12/127/126/DH_/Department of Health/United Kingdom