Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trials.

Background: Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA.
Methods: The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019-June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013-Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1-2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots.
Findings: The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47-65) and 58 years (IQR 48-66), and the median duration of resuscitation was 58 (IQR 43-69) and 49 (IQR 33-71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6-22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43-0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6-25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7-23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6-29.4; p = 0.01; HR 2.26 [1.23-4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54-10.35); p = 0.005).
Interpretation: In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival.
Funding: None.
Competing Interests: Jan Belohlavek has received research grant from the Internal Grant Agency Ministry of Health, Czech Republic (NT 13225-4/2012) for the PRAGUE OHCA study and is supported by Charles University Research program “Cooperatio – Intensive Care Medicine” and by a research grant from the Ministry of Health, Czech Republic – conceptual development of research organisation, General University Hospital in Prague, MH CZ-DRO-VFN64165. JB also served as a consultant to Abiomed, Getinge, Xenios, and Resuscitec companies. Demetris Yannopoulos has no financial conflicts of interest. Has received NIH funding for the ARREST trial and research in the field of resuscitation. Further has received a grants from Helmsley Charitable Foundation to implement ECPR in the state of MN and deliver 8500 AEDs to first responders. Jason Bartos has no financial conflicts of interest. Has received NIH funding for research in the field of resuscitation. Has received grant funding from the Helmsley Charitable Foundation to implement ECPR in the state of MN and a second grant to distribute AEDs to first responders. Has unpaid positions on the American Heart Association Emergency Care Committee, Science Subcommittee. Served as the President of the Minnesota Mobile Resuscitation Consortium. Fabio Silvio Taccone is a scientific advisor for EUROSETS. Tom P. Aufderheide has no financial conflicts of interest. Has received NIH funding for the ARREST trial and research in the field of resuscitation. He is a consultant for Medtronic, Inc., and has ongoing clinical trials with Cytovale, Inflammatix, Inc., Abbott Laboratories, and ZOLL Medical Corp. All other authors declare no competing interests.
(© 2023 The Authors.)