Extracorporeal Cardiopulmonary Resuscitation for Cardiac Arrest

In the United States, both in-hospital cardiac arrests (IHCA) and out-of-hospital cardiac arrests (OHCA) are common, with estimated incidences of 200,000 and 350,000 per year, respectively. Survival rates for these patients are low, with survival from IHCA ranging from 6% to 26% and survival from OHCA less than 10%.¹ At discharge, survivors have limited neurologic and functional recovery. As part of a global endeavor to enhance patient outcomes, medical centers worldwide have adopted extracorporeal techniques to restore oxygenation and circulation for patients having both IHCA and OHCA.

The use of extracorporeal cardiopulmonary resuscitation (eCPR) has become a subject of considerable debate in recent years, with reported success varying across studies. Suverein et al attempted to address this controversy by conducting the multicenter, randomized controlled trial INCEPTION in the Netherlands.² The study’s primary aim was to assess whether eCPR, used for OHCA secondary to ventricular arrhythmia, surpassed conventional CPR in achieving survival with a favorable neurologic outcome at 30 days.³

While high-quality chest compressions have been a cornerstone of basic life support and advanced cardiac life support education—especially following significant changes in American Heart Association guidelines in 2010—the importance of exploring alternative methodologies becomes evident when these fundamental measures prove inadequate. In instances where cardiac arrest becomes refractory to standard medical management and conventional CPR, patient survival rapidly diminishes over time.⁴ In such critical scenarios, eCPR emerges as a potential intervention capable of mitigating cerebral hypoxic injury. Moreover, it provides healthcare professionals with valuable time to stabilize the patient and identify the underlying cause of cardiac arrest.

The INCEPTION study was a multicenter, randomized, controlled trial in which patients with OHCA were randomly assigned to receive either eCPR or conventional CPR (standard advanced cardiac life support). Eligible patients were aged 18 to 70, had received bystander CPR, had an initial ventricular arrhythmia, and did not achieve spontaneous circulation within 15 minutes of CPR initiation. The primary outcome was survival with a favorable neurologic outcome at 30 days, defined by a Cerebral Performance Category score of 1 or 2. Of the 160 patients randomized, 70 received extracorporeal CPR, and 64 received conventional CPR. At 30 days, 20% in the eCPR group and 16% in the conventional CPR group had a favorable neurologic outcome. The odds ratio was 1.4 (95% CI, 0.5 to 3.5, P = 0.52). The number of serious adverse events per patient was comparable between the two groups.²

The study’s pragmatic design mirrored real-world conditions, increasing the applicability of the findings across diverse clinical settings. The use of permuted block randomization, stratified by center, bolstered the credibility of the randomization process, ensuring a robust methodology. The incorporation of a smartphone application for randomization minimized selection bias, while the blinding of the steering committee during the interim analysis further augmented methodologic rigor. Ethical considerations were addressed through the use of deferred consent, aligning with Dutch legislation and acknowledging the challenges posed by OHCA. This practical approach reflects a nuanced perspective on obtaining consent in emergency situations. The study’s clinical relevance is underscored by its focus on a significant issue—the management of refractory OHCA resulting from ventricular arrhythmias, a major contributor to mortality.

The study faced several methodologic challenges that could impact the reliability of its findings. The lack of standardization in eCPR protocols across participating centers introduced variability, potentially influencing outcomes and limiting the generalizability of the findings. The unfeasibility of blinding in the treatment assignment due to the nature of the intervention introduced the risk of performance bias, potentially influencing clinicians’ decision-making process. Crossovers from conventional CPR to eCPR and exclusions post-randomization due to the return of spontaneous circulation further introduced biases that may complicate the interpretation of results. Although the trial was powered to detect a substantial increase in survival with a favorable neurologic outcome, the small sample size and wide confidence intervals pose limitations on the precision of effect estimates.

Despite potential advantages, the efficacy of eCPR for OHCA, particularly concerning neurologic outcomes and overall survival, remains unproven by existing observational studies or randomized controlled trials.⁵ The data from the Extracorporeal Life Support Organization Registry reveals a substantial rise in annual eCPR, from fewer than 100 in 2009 to more than 1500 in 2019. This evidence not only highlights a significant increase in the utilization of eCPR during the past decade but also sheds light on the growing prominence of extracorporeal techniques as sought-after modalities in the cardiac arrest population.

Although enhanced outcomes are more consistently documented in patients with IHCA, future studies comparing them to OHCA eCPR cohorts must consider factors such as the prompt identification of suitable candidates, the recognition of shockable rhythms, and the swift initiation of extracorporeal membrane oxygenation on hospital arrival.⁶ As medical professionals continue to grapple with the complexities of resuscitative measures, ongoing research is crucial to delineate the role of eCPR and ascertain its place in optimizing outcomes for patients with OHCA.

References

1. Virani SS, Alonso A, Benjamin EJ, et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics: 2020 update: a report From the American Heart Association. Circulation. 2020 Mar 3;141(9):e139-e596.
2. Suverein MM, Delnoij TSR, Lorusso R, et al. Early extracorporeal CPR for refractory out-of-hospital cardiac arrest. N Engl J Med. 2023 Jan 26;388(4):299-309. doi:10.1056/NEJMoa2204511
3. Peris A, Bulletti F, Lazzeri C, Bonizzoli M. Out of hospital extracorporeal cardiopulmonary resuscitation: the physiopathological rationale. Eur J Emerg Med. 2023 Oct 1;30(5):309-310.
4. Grand J, Hassager C. State of the art post-cardiac arrest care: evolution and future of post cardiac arrest care. Eur Heart J Acute Cardiovasc Care. 2023 Aug 24;12(8):559-570.
5. Abrams D, MacLaren G, Lorusso R, et al. Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications. Intensive Care Med. 2022 Jan;48(1):1-15.
6. Bartos JA, Grunau B, Carlson C, et al. Improved survival with extracorporeal cardiopulmonary resuscitation despite progressive metabolic derangement associated with prolonged resuscitation. Circulation. 2020 Mar 17;141(11):877-886.