Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis

Background The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence. Methods A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated. Results Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73–3.32) with a mean absolute risk difference of 8.7% (− 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79–3.71) with a mean absolute risk difference of 10.8% (95%CrI − 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively. Conclusion The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials. Registration INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060). Supplementary Information The online version contains supplementary material available at 10.1186/s13054-024-05008-9.


Information sources
6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies.Specify the date when each source was last searched or consulted.9 Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.9 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

9
Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

9
Data items 10a List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

9,10
10b List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).Describe any assumptions made about any missing or unclear information.

9,10
Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

10
Effect measures 12 Specify for each outcome the effect measure(s) (e.g.risk ratio, mean difference) used in the synthesis or presentation of results.10

Synthesis methods
13a Describe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).
12 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.
12 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.12 13d Describe any methods used to synthesize results and provide a rationale for the choice(s).If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.For more information, visit: http://www.prisma-statement.org/

# Checklist item Location where item is reported RESULTS Study
selection 16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.Present results of all statistical syntheses conducted.If meta-analysis was done, present for each the summary estimate and its precision (e.g.confidence/credible interval) and measures of statistical heterogeneity.If comparing groups, describe the direction of the effect.Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.
1416b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ 2021;372:n71.doi: 10.1136/bmj.n71