Extracorporeal Cardiopulmonary Resuscitation (ECPR) for Cardiac Arrest: ALS SR

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: (none applicable)

The following Task Force members and other authors declared an intellectual conflict of interest, and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: (none applicable)

CoSTR Citation

Insert citation for ILCOR.org posting of CoSTR when published

Methodological Preamble and Link to Published Systematic Review

The continuous evidence evaluation process to produce the Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review (Holmberg 2018 91) and an updated systematic review (Holmberg 2023 109665) with involvement of clinical content experts. Considering new evidence becoming available on this topic, the decision was made to update the systematic review. Evidence for adult and pediatric literature was sought and considered by the Advanced Life Support Adult Task Force and Pediatric Task Force groups respectively. The CoSTR for children will be published separately by the Pediatric Task Force.

Systematic Review

Webmaster to insert the Systematic Review citation and link to Pubmed using this format when it is available if published

PICOST

Population: Adult (≥ 18 years) patients with cardiac arrest in any setting (out-of-hospital or in-hospital)

Intervention: Extracorporeal cardiopulmonary resuscitation (ECPR) including extracorporeal membrane oxygenation or cardiopulmonary bypass during cardiac arrest

Comparators: Manual or mechanical cardiopulmonary resuscitation (CPR)

Outcomes: Any clinical outcome

Study Designs: This was an update of the previous ILCOR systematic review addressing ECPR for cardiac arrest (Holmberg 2023 109665). New randomized controlled trials (RCTs) were included. Observational studies, animal studies, ecological studies, case series, case reports, reviews, abstracts, editorials, comments, letters to the editor, and unpublished studies were not included. Studies assessing cost-effectiveness were included for a descriptive overview. Studies exclusively assessing the use of extracorporeal life support for cardiac and/or respiratory failure after sustained ROSC were not included. Studies assessing extracorporeal circulation for deep hypothermia (or other conditions) were only included if cardiac arrest was documented.

Timeframe: June 21, 2022 – May 10, 2023. All languages were included if there was an English abstract or an English full-text article.

PROSPERO Registration CRD42022341077

Consensus on Science for Adult Cardiac Arrests

The updated systematic review identified 2 studies in adult patients, including 1 randomized controlled trial and 1 cost-effectiveness study. These studies add to the previous systematic reviews (Holmberg 2018 91; Holmberg 2023 109665) that identified 3 randomized controlled trials, 45 observational studies, and 6 cost-effectiveness studies in adult patients.

Given that evidence was available from 4 randomized trials and because the observational studies identified in the previous systematic reviews were limited by a critical risk of bias, only randomized trials were considered for the updated consensus on science. A summary of the observational studies is provided in the published systematic reviews. [Holmberg 2018 91; Holmberg 2023 109665]

For the outcomes of survival to hospital discharge or 30 days, long-term survival, favorable neurological outcome at hospital discharge or 30 days, or long-term favorable neurological outcome we identified four randomized trials (Yannopoulos 2020 1807; Hsu 2021 92; Belohlavek 2022 737; Severein 2023 299). The overall certanity of evidence was rated as low (downgraded for serious inconsistency and serious imprecision) for out-of-hospital cardiac arrest and as very low (downgraded for serious inconsistency, serious indirectness, and serious imprecision) for in-hospital cardiac arrest for all outcomes. The individual studies were all at a moderate risk of bias due to potential deviations from the intended interventions (lack of blinding). Because of a high degree of heterogeneity between the randomized trials, no meta-analyses were performed.

The trial by Yannopoulos et al, enrolling 30 adult out-of-hospital cardiac arrests, showed a benefit from an ECPR strategy when compared with standard care for survival to hospital discharge (absolute risk difference [ARD], 36%; 95%CI, 7.4% to 65%), survival to 6 months (ARD, 43%; 95%CI, 17% to 69%), favorable neurological outcome at hospital discharge (ARD, 21%; 95%CI, 0% to 43%), and favorable neurological outcome at 6 months (ARD, 43%; 95%CI, 17% to 69%). The trial was terminated early due to superiority.

The trial by Hsu et al, enrolling 15 adult out-of-hospital cardiac arrests, showed no benefit from an ECPR strategy when compared with standard care for survival to hospital discharge (ARD, -33%, 95%CI, -87% to 20%), survival to 3 months (ARD, -33%, 95%CI, -87% to 20%), favorable neurological outcome at hospital discharge (ARD, 0%, 95%CI, 0% to 0%), and favorable neurological outcome at 3 months (ARD, 0%, 95%CI, 0% to 0%). The trial was terminated early due to a low enrollment rate.

The trial by Belohlavek et al, enrolling 264 adult out-of-hospital cardiac arrests, showed no benefit from an ECPR strategy when compared with standard care for survival to 30 days (ARD, 9.4%; 95%CI, -2.4% to 21%), survival to 180 days (ARD, 8.1%; 95%CI, -3.0% to 19%) and favorable neurological outcome at 180 days (ARD, 10%; 95%CI, -1.3% to 20%), but showed a benefit from an ECPR strategy when compared with standard care for favorable neurological outcome at 30 days (ARD, 13%; 95%CI, 2.0% to 23%). The trial was terminated early due to futility in the primary outcome although there was an overall signal towards benefit.

The trial by Suverein et al, enrolling 134 adult out-of-hospital cardiac arrests, showed no benefit from an ECPR strategy when compared with standard care for survival to hospital discharge (ARD, -0.3%; 95%CI, -14% to 13%), for favorable neurological outcome at 30 days (ARD, 3.9%; 95%CI, -9.2% to 17%), and for favorable neurological outcome at 6 months (ARD, 4.1%; 95%CI, -8.9% to 17%).

Treatment Recommendations

We suggest extracorporeal cardiopulmonary resuscitation (ECPR) may be considered as a rescue therapy for selected adults with out-of-hospital cardiac arrest when conventional cardiopulmonary resuscitation is failing to restore spontaneous circulation, in settings where this can be implemented (weak recommendation, low certainty of evidence).

We suggest extracorporeal cardiopulmonary resuscitation (ECPR) may be considered as a rescue therapy for selected adults with in-hospital cardiac arrest when conventional cardiopulmonary resuscitation is failing to restore spontaneous circulation, in settings where this can be implemented (weak recommendation, very low certainty of evidence).

Justification and Evidence to Decision Framework Highlights

• This topic was prioritized by the Advanced Life Support Task Force based on one new randomized trial of ECPR vs standard care for cardiac arrest (Severein 2023 299) since our previous systematic review (Holmberg 2023 109665).
• In making this weak recommendation, we note that this patient population (i.e., cardiac arrest where conventional CPR is failing) has an extremely high mortality rate, particularly when refractory to standard ACLS. Therefore, the potential for benefit and value of this intervention remains despite the overall low certainty in the evidence.
• The published randomized trials use highly selected patients for ECPR and not the general population of all cardiac arrest cases. The trial by Yannopoulos et al. enrolled out-of-hospital cardiac arrests with an initial shockable rhythm and randomized patients upon hospital arrival, whereas the trials by Hsu et al. and Belohlavek et al. enrolled out-of-hospital cardiac arrests with any initial rhythm and randomized patients in the prehospital setting. The trial by Suverein et al. enrolled out-of-hospital cardiac arrests with an initial shockable rhythm and randomized the majority of patients in the prehospital setting (63% in the ECPR group and 66% in the conventional CPR group). The ECPR strategy in the trials by Yannopoulos et al. and Belohlavek et al. included immediate access to a catetherization laboratory. Guidelines for clinical practice should ideally apply to similar populations, although randomized trials have not been performed to define the optimal population. For this reason, the findings of individual trials should be interpreted cautiously in the context of the trial setting and population.
• We acknowledge that ECPR is a complex intervention that requires considerable resources and training that are not universally available, but also acknowledge the value of an intervention that may be successful in individuals where usual CPR techniques have failed. In addition, ECPR can sustain perfusion while another intervention such as coronary angiography and percutaneous coronary intervention can be performed.

Knowledge Gaps

• There are few, and no large, randomized trials of ECPR vs standard care
• The optimal patient population who may benefit from ECPR
• The optimal time to initiate ECPR in cases of refractory cardiac arrest
• Whether ECPR for out-of-hospital cardiac arrest should be initiated in the pre-hospital or in-hospital setting
• The optimal techniques for providing safe and timely ECPR
• The optimal post-cardiac arrest care strategy for patients resuscitated using ECPR
• Whether there are population-specific differences in performing ECPR for in-hospital cardiac arrest and out-of-hospital cardiac arrest
• Whether there are differences in quality of life between survivors of ECPR and standard CPR
• The cost-effectiveness of ECPR

Note to Webmaster: CoSTR posting should be linked to ETD summary table

Attachment: ALS Et D ECPR

References

Holmberg MJ, Geri G, Wiberg S, Guerguerian AM, Donnino MW, Nolan JP, Deakin CD, Andersen LW; International Liaison Committee on Resuscitation’s (ILCOR) Advanced Life Support and Pediatric Task Forces. Extracorporeal cardiopulmonary resuscitation for cardiac arrest: A systematic review. Resuscitation. 2018 Oct;131:91-100. doi: 10.1016/j.resuscitation.2018.07.029

Holmberg MJ, Granfeldt A, Guerguerian AM, Sandroni C, Hsu CH, Gardner RM, Lind PC, Eggertsen MA, Johannsen CM, Andersen LW. Extracorporeal cardopulmonary resuscitation for cardiac arrest: An updated systematic review. Resuscitation. 2023 Jan; 182:109665. doi: 10.1016/j.resuscitation.2022.12.003

Yannopoulos D, Bartos J, Raveendran G, Walser E, Connett J, Murray TA, Collins G, Zhang L, Kalra R, Kosmopoulos M, John R, Shaffer A, Frascone RJ, Wesley K, Conterato M, Biros M, Tolar J, Aufderheide TP. 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 Dec 5;396(10265):1807-1816. doi: 10.1016/S0140-6736(20)32338-2

Hsu CH, Meurer WJ, Domeier R, Fowler J, Whitmore SP, Bassin BS, Gunnerson KJ, Haft JW, Lynch WR, Nallamothu BK, Havey RA, Kidwell KM, Stacey WC, Silbergleit R, Bartlett RH, Neumar RW. Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport. Ann Emerg Med. 2021 Jul;78(1):92-101. doi: 10.1016/j.annemergmed.2020.11.011

Belohlavek J, Smalcova J, Rob D, Franek O, Smid O, Pokorna M, Horák J, Mrazek V, Kovarnik T, Zemanek D, Kral A, Havranek S, Kavalkova P, Kompelentova L, Tomková H, Mejstrik A, Valasek J, Peran D, Pekara J, Rulisek J, Balik M, Huptych M, Jarkovsky J, Malik J, Valerianova A, Mlejnsky F, Kolouch P, Havrankova P, Romportl D, Komarek A, Linhart A; Prague OHCA Study Group. 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. JAMA. 2022 Feb 22;327(8):737-747. doi: 10.1001/jama.2022.1025

Suverein MM, Delnoij TSR, Lorusso R, Bruinsma GJBB, Otterspoor L, Kraemer CVE, Vlaar APJ, Heijden JJ, Scholten E, Uil C, Jansen T, Bogaard B, Kuijpers M, Lam KY, Cabezas JMM, Driessen AHG, Rittersma SZH, Heijnen BG, Miranda DDR, Bleeker G, Metz J, Hermanides RS, Matta JL, Eberl S, Donker DW, Thiel RJ, Akin S, Meer O, Henriques J, Bokhoven KC, Mandigers L, Bunge JJH, Bol MR, Winkens B, Esser B, Weerwind PW, Maessen JG, Poll MCG. Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest. NEJM. 2023 Jan 26;388(4):299-309. doi: 10.1056/NEJMoa2204511