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.