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
Methodological Preamble and Link to Published Systematic Review
The use of Extracorporeal Cardiopulmonary Resuscitation (ECPR) in cardiac arrest in pediatrics has been included in ILCOR guidelines since 2010 {De Caen, 2010, e-213). The continuous evidence evaluation process to produce the Consensus on Science with Treatment Recommendations (CoSTR) for this topic for pediatrics and for adults started with a systematic review {Holmberg, 2018, 91). In pediatrics, the 2020 & 2021 Pediatric CoSTR {Maconochie, 2020, A120; Maconochie, 2021, 147 Sup 1} is the following: “We suggest that ECPR may be considered as an intervention for selected infants and children (e.g., pediatric cardiac populations) with IHCA refractory to conventional CPR, in settings where resuscitation systems allow ECPR to be well performed and implemented (weak recommendation, very low-quality evidence). There is insufficient evidence in pediatric OHCA to formulate a treatment recommendation for the use of ECPR.” In 2021, an evidence update was conducted by the Pediatric Task Force focused on ECPR. The evidence update in pediatric ECPR conducted from 2018 and 2021 included two systematic reviews {Esangbedo, 2020, e-934; Farhat, 2021, 682} and 15 published studies. These included four retrospective studies using samples of national and international registries;{Brunetti, 2018, 544; Chen, 2018, 1436; Bembea, 2019, e-278; Morell, 2020, 256} one comparative cohort study from an administrative national inpatient hospital data set;{Hamzah, 2021, 2513} six retrospective single center case series;{Beshish, 2018, 665; Khorsandi, 2018, 3; Torres-Andres, 2018, 451; Shakoor, 2019, 582; Anton-Martin, 2020, 607; Melvan, 2020, 265} two retrospective multicenter case series;{De Mul, 2019, 57; De La Llana, 2020, 202} and two secondary analyses of a randomized controlled trial – a comparative cohort study and a case series.{Meert, 2019, 139; Meert, 2019, 393}. The great majority of the studied events were IHCA with two studies included patients with witnessed OHCA. Four reports studied exclusively cardiac populations, one exclusively pulmonary hypertension population, and 10 included a mix of cardiac and non-cardiac populations. Among these 10 studies, cardiac samples represented the majority of analyzed events with a large proportion of ECPR in post-operative cases. In the majority, survival rates were reported on hospital discharge and were reported to be above 40%, ranging from 25% to 65%. Most neurologic outcomes were measured on hospital discharge using the pediatric cerebral performance category (PCPC) scores, dichotomized as PCPC 1-2 vs PCPC 3-4 or 3-5. Only three studies reported neurologic outcomes beyond hospital discharge, at 12 months and at 38 months. Temperature and duration of resuscitation measures before achieving sustained return of circulation were reported in less than half of the studies.
During the same period, an important statement relevant for the field of resuscitation in children with cardiac disease was published by the AHA in 2018 {Marino, 2018, e-691}; it explains why in some physiologic conditions conventional CPR may not provide the most optimal means of providing oxygenated perfusion to the cerebral and systemic circulations. In 2020 AHA Guidelines for CPR and Emergency Cardiovascular Care {Topjian, 2020, S-469} harmonized their nomenclature for ECPR as the application of ECMO “for patients who do not achieve sustained ROSC” to the Extracorporeal Life Support Organization nomenclature {Conrad, 2018, 447}.
Considering the evidence becoming available on this topic both in pediatrics and in adults, the decision was made to update the systematic review {Holmberg 2022 – PROSPERO CRD42022341077}. Evidence was sought and considered by the Advanced Life Support Adult Task Force and Pediatric Task Force groups respectively. The CoSTR for adults is published separately by the Adult Task Force.
Systematic Review
Extracorporeal Cardiopulmonary Resuscitation for Cardiac Arrest: An Updated Systematic Review
Authors: Mathias J. Holmberg, Asger Granfeldt, Anne-Marie Guerguerian, Claudio Sandroni, Cindy H. Hsu, Ryan M. Gardner, Peter C. Lind, Mark A. Eggertsen, Cecilie M. Johannsen, and Lars W. Andersen. Resuscitation (2022), https://doi.org/ 10.1016/j.resuscitation.2022.12.003
PICOST
Population: Adults (≥ 18 years) or pediatric (< 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
The updated systematic review identified 4 observational studies in pediatrics that met inclusion criteria detailed in the publication {Holmberg 2022, page pending}, and 3 randomized controlled trials, 24 observational studies, and 6 cost effectiveness studies in adults. All studies included with pediatric patients evaluated IHCA events. There are no published nor registered randomized clinical trials comparing ECPR to no ECPR in pediatrics. The calendar years of the events included in studies ranged from 2000 to 2017. The number of patient study samples analyzed ranged from 17 to 20,654, the number of exposed patients receiving ECPR ranged from 6 to 1670.
Two studies were secondary analyses using the THAPCA IHCA trial where patients were aged >2 days < 18 years, comatose after IHCA were randomized to one of two temperature targeted therapy regimens {Moler, 2017, 318}. In one study, {Meert, 2018, 96} the clinical characteristics associated with 12-month survival and neurobehavioural function were evaluated. The outcomes were worse among the patients supported with ECMO (N 180) at the time of initiation of targeted therapy compared to the no ECMO group (N 149): the odds of survival at 12-months in the ECMO group compared to no ECMO were 0.52 (0.29, 0.94) and the odds of survival at 12 months with VABS II ≥70 were 0.34 (0.17, 0.67).
Another secondary analysis of the THAPCA IHCA trial intended to compare the cognitive and neurologic scores in 12-month survivors with pre-arrest VABS-II (≥ 70) between three groups: those treated with ECPR (N 57), those who did not receive ECMO (N 56) and those treated with ECMO later in their course (N 14) {Meert, 2019, 299}. The results show that 12-month VABS-II composite scores were normal (≥ 70) for 39 (70.9%) ECPR survivors, 47 (83.9%) survivors treated with no ECMO and 10 (71.4%) in later-ECMO survivors; the odds of having a 12-month VABS-II composite normal score (≥ 70) was calculated to be 0.49 (0.22, 1.12) in ECPR survivors compared to the combined other two groups. Cognitive evaluation composite scores (≥ 70) were achieved for 24 (54.5%) ECPR survivors, 27 (61.4%) survivors treated without ECMO and in 8 (72.7%) later-ECMO survivors. Neurologic examination scores in the none/minimal impairment to mild impairment range were observed for 28 (59.5%) ECPR survivors, 33 (73.3%) survivors treated without ECMO and in 10 (83.3%) later-ECMO survivors. Cognitive and neurologic score distributions were similar between ECPR survivors compared to no-ECMO and later-ECMO groups.
A third study conducted using an administrative in-patient national database in the United States was included evaluating patients coded with ICD-10 codes for cardiac arrest and ECMO procedures on the same day thus assumed to be ECPR {Hamzah, 2021, 2523). These were compared to those not exposed to ECMO. The odds of survival on hospital discharge were 0.98 (0.88, 1.08) for the ECMO and no ECMO groups. Secondary outcomes suggest that the group with cardiac arrest and ECMO had longer length of stay and higher hospitalization costs compared to those with no ECMO.
A fourth study was conducted in a single center evaluating the quality of resuscitation measures with video recordings in 6 ECPR and 11 no ECPR cardiac arrest events {Taeb, 2018, 831). The odds of survival to hospital discharge were calculated to be 0.53 (0.04, 6.66) for the ECPR compared to no ECPR. Similarly, the odds of having a functional status scale score of 1 at hospital discharge {Pollack, 214, 671) were calculated to be 0.53 (0.04, 6.66) for the ECPR compared to no ECPR. The study reports that ECPR events were associated to lower adherence to resuscitation guidelines compared to no ECPR events.
Collectively these 4 pediatric studies favored no ECPR but the confidence intervals when available were broad. The risk of bias was assessed as critical for all studies, primarily due to the risk of confounding and selection bias.
Treatment Recommendations
There is insufficient evidence to change the treatment recommendation from the 2020 & 2021 Pediatric CoSTR {Maconochie, 2020, A120; Maconochie, 2021, 147 Sup 1}.
We suggest that ECPR may be considered as an intervention for selected infants and children (e.g., pediatric cardiac populations) with IHCA refractory to conventional CPR, in settings where resuscitation systems allow ECPR to be well performed and implemented (weak recommendation, very low-quality evidence). There is insufficient evidence in pediatric OHCA to formulate a treatment recommendation for the use of ECPR.
Justification and Evidence to Decision Framework Highlights
In making this weak recommendation, we note that in select pediatric patient populations (i.e., cardiac arrest with cardiac disease) the practice of using ECPR has become widespread across some institutions with systems that support post operative cardiac surgical ecosystems.
We acknowledge that ECPR is a complex system intervention that requires considerable resources and sustained training that may not be universally available.
Knowledge Gaps
The knowledge gaps remain numerous when it comes to comparing the application of ECPR which involves a first period of conventional CPR to conventional CPR alone in pediatrics.
- There are no comparative prospective studies nor randomized trials.
- There are insufficient studies in selected IHCA (e.g., non-cardiac) or in OHCA populations.
- It remains unknown how the transition from conventional CPR to ECPR alters the quality of resuscitation measures.
- It remains unknown how best to provide closed chest CPR and transition to a peripheral or to central ECPR cannulation (with or without a sternotomy) or how to best perform open chest CPR in the context of surgical instrumentation for central ECPR.
- It remains unknown how best to provide immediate and early post cardiac arrest care with ECPR (E-PCAC) (temperature targeted management, oxygenation, decarboxylation, perfusion pressure, transfusion therapies).
- Reporting of studies using ECPR is heterogeneous and not standardized; this domain of resuscitation research would benefit from applying core definitions from the Utstein reporting standards and from incorporating pediatric core outcomes for cardiac arrest (P-COSCA) {Topjian, 2020, e-246}. Moreover, an update in Utstein reporting definitions would serve to enhance the reporting of resuscitation measures applied during this technique (e.g., temperature applied on reperfusion; total duration of cardiac arrest deconstructed with intervals of conventional compressions, open chest compressions, and interruptions…).
Attachments: ECPR Et D 2022
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