Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Abstract

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain.

Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival.

Design, setting, and participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021).

Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132).

Main outcomes and measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours).

Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively).

Conclusions and relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference.

Trial registration: ClinicalTrials.gov Identifier: NCT01511666.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Belohlavek reported receiving lecture honoraria from Maquet Company. No other authors reported disclosures.

Figures

Figure 1.. Prehospital Flow of Participants in a Study of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment in Refractory Out-of-Hospital Cardiac Arrest

DSMB indicates data and safety monitoring board; ECLS, extracorporeal life support; CPR, cardiopulmonary resuscitation; ICU, intensive care unit; OHCA, out-of-hospital cardiac arrest; ROSC, return of spontaneous circulation. aRandomization into standard strategy and invasive strategy groups was based on 4 strata (men ≤45 years, men >45 years, women ≤45 years, women >45 years), with block size of 8. bSeven patients were excluded after randomization because consent was refused and information was not available as to how many were randomized to each group for analysis.

Figure 2.. Post Hoc Analysis, Primary Outcome According to Subgroups in a Study of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment in Refractory Out-of-Hospital Cardiac Arrest

ACS indicates acute coronary syndrome; CAD, coronary artery disease; CHF, chronic heart failure; CPR, cardiopulmonary resuscitation; EMS, emergency medical service; OR, odds ratio; ROSC, return of spontaneous circulation. aFor pH and lactate level, the first values after admission are used.