ECPR in Pediatric Cardiac Patients with Single Ventricle Physiology: PLS 4030.09 and 4030.10 TF 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

Raymond TT, Guerguerian AM, Lasa J, Dhillon G, Moga MA, Atkins, DL - on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. ECPR in Pediatric Cardiac Patients with Single Ventricle Physiology Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Pediatric Life Support Task Force, 2025 January XX. Available from: http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review (Raymond, 2024, PROSPERO CRD42023479671) conducted by the members of the PLS TF with involvement of clinical content experts. Evidence for pediatric literature was updated and considered by the Pediatric Life Support Task Force with assistance from Jessie Cunningham, Information Specialist at The Hospital for Sick Children, Toronto, Canada. Evidence was sought and considered by members of the Pediatric Life Support Task Force group when formulating the Treatment Recommendations.

This is a new PICOST (4030.09, 4030.10). In the pediatric cardiac population and particularly those with single ventricle physiology who are at highest risk of cardiac arrest, conventional CPR may not provide the most optimal means of providing oxygenated perfusion to the cerebral and systemic circulations. Current ILCOR treatment recommendations⁷ suggest that ECPR may be considered as an intervention for select 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 currently no specific recommendation for ECPR that delineates pediatric cardiac patients with single ventricle physiology versus biventricular physiology with IHCA refractory to conventional CPR.

Systematic Review

Raymond T, Guerguerian AM, Lasa J, Dhillon G, Moga MA, Atkins, DL. Extracorporeal Cardiopulmonary Resuscitation for Pediatric Cardiac Patients with Single Ventricle Physiology (in preparation)

PICOST

PROSPERO Registration CRD42017080475

Consensus on Science

Sixteen studies were included in the systematic review.1-6,8-17 None of these provided clinical trial data. All of the identified studies were observational studies and provided very low certainty evidence for the comparisons with the important and critical outcomes described. There were no pediatric studies identified that compared pediatric cardiac patients with single ventricle physiology who received extracorporeal cardiopulmonary resuscitation (ECPR) vs conventional or manual cardiopulmonary resuscitation without ECPR.

There were 5 studies identified that compared pediatric cardiac patients with single ventricle physiology who received ECPR vs extracorporeal membrane oxygenation (ECMO) without ECPR (ECMO non-ECPR).3,4,13,14,16 ECPR was defined as placement on cardiopulmonary bypass or ECMO during active chest compressions for cardiac arrest. ECMO non-ECPR was defined as placement electively onto cardiopulmonary bypass or ECMO without active chest compressions for cardiac arrest.

Three of the five studies were single-center retrospective studies able to be included in a meta-analysis for the outcome of survival to hospital discharge^3,4,16, and two studies were retrospective registry-based cohort studies

that had overlapping years of patient inclusion and were thus analyzed separately from the meta-analysis for the outcome survival to hospital discharge.^13,14

An additional 11 studies were identified that described ECPR in single ventricle patients, but none of the studies had any comparator group to the single ventricle ECPR group.^{1,2,5,6,8-12,15,17} Of these, 8 studies were single center observational cohorts with a total of 318 single ventricle ECPR patients with a survival to hospital discharge rate ranging from 32-62%.^{1,6,9-12,15,17} The remaining 3 studies were registry cohorts from the Extracorporeal Life Support Organization with a total of 805 single ventricle ECPR patients with a survival to hospital discharge rate ranging from 32-34%.^2,5,8

All results are presented as a relative effect with OR and absolute effect with assessment of statistical significance based on a 95% confidence interval (CI 95%).

Studies comparing ECPR vs Conventional or manual CPR without ECPR:

There were no pediatric studies identified that compared pediatric cardiac patients with single ventricle physiology who ECPR vs conventional or manual cardiopulmonary resuscitation without ECPR.

Studies comparing ECPR vs ECMO non-ECPR:

Survival to Hospital Discharge

For the critical outcome of survival to hospital discharge we identified 3 observational studies^3,4,16 with 91 pediatric single ventricle patients (pooled OR=0.445 [95%CI 0.193 -1.024]) and 2 registry studies^13,14 (OR=1.09 [0 .71-1.71] and OR=0.665 [0.26- 1.72]) with very low certainty of evidence (downgraded for risk of bias and imprecision). Collectively these studies found no significant difference in survival to hospital discharge in ECPR compared to ECMO without ECPR in pediatric single ventricle patients.

Decannulation from ECMO

For the important clinical outcome decannulation from ECMO, we identified 1 observational study of 40 pediatric single ventricle patients (OR=1.75 [95%CI 0.50-6.09]) with very low certainty of evidence (downgraded for risk of bias and imprecision) that decannulation from ECMO is not significantly different in ECPR compared to ECMO non-ECPR.

Survival to Hospital Discharge with Good Neurologic Outcome

We identified no pediatric studies that evaluated the important clinical outcome of survival to hospital discharge with good neurological outcome.

Subgroup Analysis

Single ventricle patient’s s/p Stage I (Norwood/Hybrid) palliation

For the critical outcome of survival to hospital discharge we identified 2 observational studies^4,14 with pediatric single ventricle patients status post Stage I Norwood palliation (OR=1.09 [95%CI 0.71 -1.71] and OR=0.52 [95%CI 0.10-2.54]) with very low certainty of evidence (downgraded for risk of bias and imprecision) that survival to hospital discharge is not statistically different in ECPR compared to ECMO without ECPR in pediatric single ventricle patients.

Single ventricle patient’s s/p Stage II (Hemi-Fontan/Bidirectional Glenn) or Stage III (Fontan) palliation

For the critical outcome of survival to hospital discharge we identified 1 observational study with pediatric single ventricle patients status post Stage III Fontan palliation (OR=0.66 [95%CI 0.26 -1.72] with very low certainty of evidence (downgraded for risk of bias and imprecision) that survival to hospital discharge is not statistically different in ECPR compared to ECMO without ECPR in pediatric single ventricle patients.¹³ There were no studies identified in single ventricle patients status post Stage II Hemi-Fontan/Bidirectional Glenn palliation comparing ECPR to ECMO without ECPR.

Treatment Recommendations

There is insufficient evidence to make a treatment recommendation for or against the use of ECPR during cardiac arrest in patients with single ventricle physiology.

There is insufficient evidence to make a treatment recommendation for or against the use of ECPR compared to ECMO non-ECPR in patients with single ventricle physiology.

Justification and Evidence to Decision Framework Highlights

The risk of cardiac arrest in a child with single ventricle physiology is elevated. Conventional CPR may not provide adequate reperfusion in this physiology and low likelihood of ROSC.¹⁸

There is no published evidence in pediatrics that allows us to compare ECPR with conventional CPR. The available evidence suggests that when comparing ECPR to ECMO non-ECPR in a child with single ventricle physiology the risk of survival to hospital discharge is not statistically different in ECPR compared to ECMO non-ECPR.

Each of these studies were conducted in an era where there remained significant hesitation in using ECMO in patients with single ventricle physiology which may have altered the timing of the decision making and been associated with delays in therapeutic interventions.

ETD summary table: Deferred

Knowledge Gaps

• There are no comparative prospective studies or randomized trials of ECPR vs conventional or manual CPR.
• There is limited data on survival with neurologic outcome following cardiac arrest with ECPR.
• There is limited data on subgroups of single ventricle patients before Stage I, and after Stage I, II and III single ventricle palliation who undergo ECPR.
• 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 sternal opening for ECPR cannulation or how to perform open chest CPR in the context of cannulating to central ECPR.
• In cardiac patients who have cyanotic heart disease it remains unknown if their oxygenation targets in conventional CPR and at the transition to ECPR should be aligned with their baseline pre-arrest saturations.
• It is not known if there is a circuit prime and transfusion management at the time of ECPR that is optimal.
• It remains unknown how best to provide early post cardiac arrest care with ECPR (oxygenation, decarboxylation, perfusion pressure).
• It is not known if temperature targeted management should be delivered with ECPR.

References

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