Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis.

Background: In Europe, approximately 291,000 cardiac arrests occur annually. Despite critical care therapy, hospital mortality remains high. This systematic review assessed whether, in comatose survivors of cardiac arrest, any drug therapy, compared to placebo or usual care, improves outcomes.
Methods: We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and The International Clinical Trials Registry Platform for randomized controlled trials of drug therapy in comatose survivors of cardiac arrest (last searched 20th October 2024). The primary outcome was mortality at 30 days/hospital discharge. Other outcomes reflected those of the Core Outcome Set for Cardiac Arrest. Risk of bias was assessed using Cochrane Risk-Of-Bias Version 1. Studies of steroids, coenzyme Q10 and thiamine were meta-analysed.
Results: From 2562 records, 207 full texts were screened and 45 studies (5800 patients) investigating 30 therapies were included. Studies were grouped thematically as supportive drug therapies (n = 10), neuroprotective agents (n = 19), and anti-inflammatory/antioxidants (n = 16). Four studies reported reduced mortality at 30 days/hospital discharge: one of the anticholinergic penehyclidine hydrochloride, two of intra-arrest vasopressin and methylprednisolone plus hydrocortisone for post resuscitation shock, and one of the traditional Chinese medicine, shenfu. Studies of steroids, coenzyme Q10 and thiamine were meta-analysed. We could not detect an effect on mortality with steroids (n = 739, risk ratio (RR), 0.93; 95 % CI 0.83-1.04, p = 0.21; I ²  = 60 %, low certainty), coenzyme Q10 (n = 107, RR, 0.91; 95 % CI 0.61-1.37, p = 0.65; I ²  = 0 %, low certainty), or thiamine (n = 149, RR, 1.11; 95 % CI 0.88-1.40, p = 0.39; I ²  = 0 %, very low certainty).
Conclusion: In comatose survivors of cardiac arrest, the majority of trials of drug therapy reported no effect on mortality. Meta-analyses of steroids, coenzyme Q10 and thiamine demonstrated no evidence of an effect on mortality. However, the low certainty of evidence warrants further research.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LMCH reports receiving support from the Health Research Board Ireland, Clinical Trial Network Award CTN 2021-010. LMCH’s work also includes the investigator initiated TAME and STEPCARE trials in Ireland. ADN reports receiving support from the Health Research Board Ireland, Clinical Trial Network Award CTN 2021-010. ADN was the Principal Investigator for the completed and published investigator-initiated TAME trial and National Investigator for the STEPCARE trial. MBS reports receiving lecture fees from Bard Medical (Ireland) in 2021 and 2022. DFMA reports receiving grants from NIHR, Innovate UK, MRC, Novavax, Northern Ireland HSC R&D division, Randox, Wellcome Trust. DFM, through Queen’s University Belfast, holds a patent for novel treatment for inflammatory disease (USB962032). DFM reports receiving consulting fees from Bayer, Aptarion, Direct Biologics, Aviceda, GlaxoSmithKline, Boehringer Ingelhelm, Novartis, Eli Lilly and SOBI. DFM reports receiving honoraria from GlaxoSmithKline. DFM reports participation on a Data Safety Monitoring Board for Vir Biotechnology, Inc and Faron Pharmaceuticals. DFM holds leadership roles with Intensive Care Society, MRC/NIHR and NIHR. DFM’s spouse has received consultancy fees from Insmed and payment for participation in a grant review panel for California Inst For Regenerative Medicine. The remaining authors declare that they have no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)