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: not 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: not applicable
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) with involvement of clinical content experts. Considering new evidence becoming available on this topic, the decision was made to update the systematic review (Holmberg 2022 – PROSPERO CRD42022341077). 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.
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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 ILCOR systematic review addressing ECPR for cardiac arrest in 2018. New randomized controlled trials (RCTs), non-randomized controlled trials, and observational studies (cohort studies and case-control studies) with a control group (patients not receiving ECPR) were included. Ecological studies, case series, case reports, reviews, abstracts, editorials, comments, letters to the editor, and unpublished studies were not included.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: New studies published between January 1, 2018, and June 21, 2022. 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 31 studies in adult patients, including 3 randomized trials, 23 observational studies, and 6 cost-effectiveness studies (1 was an observational study). These studies add to the systematic review from 2018 that identified 22 observational studies in adult patients. The search for registered ongoing or unpublished randomized trials identified 4 randomized trials.
Given that new evidence was available from 3 randomized trials and because the 45 adult observational studies identified in the previous and present 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 are provided in the systematic reviews. [Holmberg 2018 91; Holmberg 2022, submitted]
For the outcomes of survival to hospital discharge or 30 days, long-term survival, favorable neurological outcome at hospital discharge or 30 days, and long-term favorable neurological outcome we identified three randomized trials (Yannopoulos 2020 1807; Hsu 2021 92; Belohlavek 2022 737).
The trial by Yannopoulos et al, enrolling 30 adult out-of-hospital cardiac arrests, showed a benefit of 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 of 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 of 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 of 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 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 an intermediate 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 could be performed.
We suggest extracorporeal cardiopulmonary resuscitation (ECPR) may be considered as a rescue therapy for selected patients 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 patients 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 three new randomized trials of ECPR vs standard care for cardiac arrest since our previous systematic review in 2018 (Holmberg 2018 91) and CoSTR in 2019 (Soar 2019 e826, Soar 2019 95).
- 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 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
- There are few, and no large, randomized trials of ECPR vs standard care
- What is the optimal patient population who may benefit from ECPR?
- Are there differential benefits of ECPR in subgroups of patients such as cardiac arrests related to pregnancies or pulmonary embolism?
- What is the optimal time to initiate ECPR in cases of refractory cardiac arrest?
- Should ECPR be initiated in the pre-hospital or in-hospital setting?
- What are the optimal techniques for providing safe and timely ECPR?
- What is the optimal post-cardiac arrest care strategy for patients resuscitated using ECPR?
- What are the population-specific differences in performing ECPR for in-hospital cardiac arrest and out-of-hospital cardiac arrest?
- What are the differences in quality of life between survivors of ECPR and standard CPR?
- There are no robust studies on the cost-effectiveness of ECPR
Attachment: ECPR Et D
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