By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: For patients with out-of-hospital cardiac arrest that was refractory to initial resuscitation efforts, adding extracorporeal membrane oxygenation to standard CPR did not result in a significant improvement in survival with favorable neurologic outcome.
SOURCE: Suverein MM, Delnoij TSR, Lorusso R, et al. Early extracorporeal CPR for refractory out-of-hospital cardiac arrest. N Engl J Med 2023;388:299-309.
Close to 4 million people worldwide experience out-of-hospital cardiac arrest annually; only about 8% to 12% survive to hospital discharge.1 Adding rapid extracorporeal life support — percutaneous cannulation of the arterial and venous systems, and support of the circulation with extracorporeal membrane oxygenation (ECMO) — has been proposed to improve survival in refractory arrest. By maintaining circulation and allowing treatment of reversible triggers for the arrest, most often by percutaneous coronary intervention, this strategy known as extracorporeal CPR could effectively treat patients who otherwise would not be salvageable. Supporting data are limited.
The Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest (INCEPTION) trial was designed to compare standard CPR with extracorporeal CPR in patients presenting to emergency medical systems in the Netherlands with refractory cardiac arrest and an initial shockable rhythm. Patients were considered refractory if they remained in cardiac arrest after 15 minutes of advanced life support. These patients were enrolled if there was an expectation the cannulation procedure could be started within 60 minutes of the arrest. The 10 cardiac centers involved all were experienced in ECMO, but not necessarily in extracorporeal CPR, before this study.
Between May 2017 and February 2021, 160 patients meeting basic criteria were randomized (70 in the extracorporeal CPR group, 64 in the conventional CPR group, 26 excluded). The average age of enrolled patients was 54 years in the extracorporeal CPR group and 57 years in the CPR only group. The mean time from cardiac arrest to emergency medical system arrival was eight minutes, while the time to arrival in the emergency department was 36 minutes for ECMO patients and 38 minutes for conventional CPR patients.
Only 52 patients in each group received the assigned intervention because 13 patients in the ECMO group and nine in the conventional group experienced return of spontaneous circulation before arriving in the emergency department. Three in the conventional group were cannulated on ECMO despite their treatment assignment. Providers ended treatment before cannulation for two in the ECMO group. Two patients dropped out of the conventional group after initial treatment.
At 30 days, survival with a favorable neurologic outcome was seen in 14 of 70 patients in the extracorporeal CPR group and in 10 of 62 patients in the conventional CPR group (odds ratio, 1.4; 95% confidence interval, 0.5-3.5; P = 0.52). More patients assigned to receive ECMO survived until admission to the ICU. However, survival to hospital discharge was similar in the two groups, as was survival with a favorable neurologic outcome at six months. The authors concluded extracorporeal CPR and conventional CPR produced similar results regarding survival with favorable neurologic outcome among patients with refractory out-of-hospital cardiac arrest.
COMMENTARY
A subset of patients presenting with refractory cardiac arrest, when cared for in a timely fashion within an experienced system, almost certainly stand to benefit from a strategy that includes ECMO support. The results of INCEPTION indicate work remains regarding how providers define the who, the where, and the how.
The authors of prior case series of extracorporeal CPR have reported favorable outcomes. In the first published randomized trial in this space, ARREST, Yannopoulos et al reported a dramatic 36% higher survival rate with ECMO compared with conventional CPR (the data safety monitoring board ended this trial early).2 The contrary conclusion of INCEPTION comes down to important distinctions between these studies.
ARREST was a single-center, open-label study that included only 30 patients before its premature termination. One of 15 patients assigned to conventional treatment in ARREST survived to hospital discharge; none were alive at six months. By contrast, six of 14 patients in the ECMO-facilitated group survived to discharge.
Both the small sample size and the early termination increase the likelihood the results are skewed by chance. In addition, providers at the single center involved in ARREST were experienced in extracorporeal CPR before the trial. There were specific protocols in place for triaging these patients and for instituting extracorporeal CPR.
Contrast this with INCEPTION, where 12 different systems were aware of the trial but did not adopt specific conventions, and no standardized trial protocol was designed for extracorporeal CPR itself. Instead, each hospital used procedures that had been established at that site. Suverein et al dubbed this a “pragmatic design” — no doubt this closely mirrors the situation in centers that hope to adopt extracorporeal CPR. One potential result of this lack of standardization is a loss of efficiency and speed in managing these cases. In comparison with ARREST, centers in INCEPTION recorded significantly longer delays between hospital arrival and cannulation, which may affect downstream survival.
Ultimately, the proof of benefit to extracorporeal CPR may require more studies with larger cohorts, which in turn may help identify the subsets of patients who most likely could benefit. Until then, available data do not yet support the widespread adoption of extracorporeal CPR in out-of-hospital cardiac arrest.
REFERENCES
1. Brooks SC, Clegg GR, Bray J, et al. Optimizing outcomes after out-of-hospital cardiac arrest with innovative approaches to public-access defibrillation: A scientific statement from the International Liaison Committee on Resuscitation. Circulation 2022;145:e776-e801.
2. Yannopoulos D, Bartos J, Raveendran G, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): A phase 2, single centre, open-label, randomised controlled trial. Lancet 2020;396:1807-1816.
For patients with out-of-hospital cardiac arrest that was refractory to initial resuscitation efforts, adding extracorporeal membrane oxygenation to standard CPR did not result in a significant improvement in survival with favorable neurologic outcome.
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