Extracorporeal cardiopulmonary resuscitation (ECPR) for cardiac arrest – Pediatrics
Pediatric Task Force Authors: Guerguerian AM, de Caen AR, Aickin RP, Tijssen JA, Atkins DL, Bingham R, Couto TB, Meaney PA, Nadkarni VM, Ng KC, Nuthall GA, Ong GYK, Reis AG, Schexnayder SM, Shimizu NS, Van de Voorde P, Morley PT, Rabi Y, Andersen LW, Deakin CD, Maconochie IK. Extracorporeal Cardiopulmonary Resuscitation (ECPR) for Cardiac Arrest – Pediatric Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force, Available from: http://ilcor.org
Methodological Preamble and Link to Published Systematic Review
The continuous evidence process for the production of Consensus on Science with Treatment Recommendations (CoSTR) used the versions published in 2010 (https://www.ahajournals.org/doi/pdf/10.1161/circulationaha.110.971093) (https://www.ncbi.nlm.nih.gov/pubmed/20956224) and in 2015 http://circ.ahajournals.org/content/circulationaha/132/16_suppl_1/S177.full.pdf (https://www.ncbi.nlm.nih.gov/pubmed/26472995) for this topic for pediatric advanced life support and for adult advanced life support, and conducted a systematic review (PROSPERO CRD42018085404).
In 2018, a single PICOST was formulated and the literature published in children and/or adults was screened, selected, reviewed, appraised, and summarized for each population and for each cardiac arrest setting i.e., for the in or the out-of-hospital settings. The systematic review is published as Holmberg et al 2018 and forms the basis of the 2018 CoSTR for adults and for pediatrics. Additional literature published in children was considered to inform the Justification and Evidence to Decision Framework Highlights. When possible, the relative risk, absolute risk reduction, and number per 1000 cases was estimated from the published reports using software (Risk calculator from Scottish Intercollegiate Guidelines Network
https://www.sign.ac.uk/assets/risk.xls) and reported herein.
Holmberg, M. J., G. Geri, S. Wiberg, A. M. Guerguerian, M. W. Donnino, J. P. Nolan, C. D. Deakin, and L. W. Andersen. 2018. Extracorporeal cardiopulmonary resuscitation for cardiac arrest: A systematic review, Resuscitation, 131: 91-100. PMID: 30063963 DOI: 10.1016/j.resuscitation.2018.07.029
The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)
Population: Adults (≥ 18 years) and children (<18 years) with cardiac arrest in any setting (out-of-hospital or in-hospital).
Intervention: ECPR including extracorporeal membrane oxygenation or cardiopulmonary bypass, during cardiac arrest.
Comparator: Manual CPR and or mechanical CPR.
Outcomes: Clinical outcomes, including short-term survival and neurological outcomes (e.g. hospital discharge, 28-days, 30-days, and 1-month), and long-term survival and neurological outcomes (e.g. 3-months, 6-months, and 1-year).
Study design: Randomized trials, non-randomized controlled trials, and observational studies (cohort studies and case-control studies) with a control group were included. Animal studies, ecological studies, case series, case reports, reviews, abstracts, editorials, comments, and letters to the editor were not included.
Time frame: All years and all languages were included as long as there was an English abstract; unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Literature search was conducted on December 19, 2017 and updated to May 22, 2018.
PROSPERO Registration CRD42018085404
 Case series, secondary analyses of trials, registries, health services studies generated from administrative databases were used to inform the Justification and Evidence to Decision Framework Highlights section of the Statement for pediatric populations.
Consensus on Science
In-hospital cardiac arrest
For the critical outcome of favorable longer term neurologic outcome, no pediatric studies were identified.
For the critical outcome of longer term survival, no pediatric studies were identified.
For the critical outcome of favorable neurologic outcome at hospital discharge, we identified very low certainty evidence (downgraded for very serious risk of bias) from one observational study using the Pediatric Cerebral Performance Category score to classify outcomes; this study favored ECPR over conventional CPR (conditional logistic analysis adjusted OR 2.64 [95% CI 1.91 to 3.67] and in propensity analysis adjusted OR 1.78 [95% CI 1.31–2.41] (Lasa 2016 165)). From this study’s unadjusted results, we estimate the relative risk to be 1.5 (95% CI 1.31 – 1.65) in favor of ECPR, with an absolute risk reduction of 9% [95% CI 5-13%], with 0.9 more patients/1000 survived with favorable neurologic outcome with the ECPR intervention [95% CI, 1.3 more patients/1000 to 0.5 more patients/1000 survived with the intervention] compared to conventional CPR.
For the critical outcome of hospital discharge, we identified very low certainty evidence (downgraded for very serious risk of bias and inconsistency) from three studies with pediatric populations. Two studies favored ECPR over conventional CPR (adjusted OR 2.76 [95% CI 2.08-3.66] (Lasa 2016 165); adjusted OR 3.80 [95% CI 1.40-10.32] in medical cardiac and adjusted OR 2.50 [ 95% CI 1.3-4.81] in surgical cardiac (Ortmann 2011 2329)). From the former study’s unadjusted results (Lasa 2016 165), we estimate the relative risk to be 1.48 (CI 95% 1.26 – 1.75) in favor of ECPR, with an absolute risk reduction of 13% [95% CI 9-17%], 1.3 more patients/1000 survived with the ECPR intervention [95% CI, 1.7 more patients/1000 to 0.9 more patients/1000 survived with the intervention] compared to conventional CPR.
One study in cardiac arrests (ECPR n=18) in the catheterization laboratory favored no ECPR (unadjusted OR 0.19 [95% CI 0.06 – 0.66] (Odegard 2014 175)).
Out-of-hospital cardiac arrest:
No studies were identified that addressed this question.
We suggest ECPR may be considered as an intervention for selected children with in-hospital cardiac arrest refractory to conventional CPR in settings where resuscitation systems allow ECPR to be implemented (weak recommendation, very low certainty of evidence).
There is insufficient evidence in pediatric out-of-hospital cardiac arrests to formulate a recommendation for the use of ECPR.
Justification and Evidence to Decision Framework Highlights
In making this weak recommendation for in-hospital pediatric cardiac arrests, we recognize that despite no comparative studies being identified in pediatric populations for in-hospital cardiac arrest, patients with in-hospital cardiac arrest refractory to conventional CPR have a high probability of death.
Guidelines for clinical practice will need to be formulated to serve pediatric populations similar to the studied populations and consider how generalizable the evidence can be to their regional systems of care. Careful consideration should be given to whether the pediatric ECPR studies from which these recommendations are drawn, comprising mostly children with cardiac disease, adequately represents the local population where these guidelines may be implemented.
ECPR has been studied when implemented in selected populations (e.g., cardiac surgical or cardiac medical) and more rarely for pediatric cardiac arrest in general (or across all hospital settings), (Lasa 2016 165) and by organizations with strong institutional-based commitment to sustaining a resuscitation system that includes ECPR and quality improvement systems.(Alsoufi 2007 952, Turek 2013 2140)
Institutions that report using ECPR in very select pediatric populations of in-hospital cardiac arrest have adopted this resuscitation practice following internal audits and iterative evaluation of their performance and outcomes. (Del Nido 1992 II300, Dalton 1993 1020, Duncan 1998 305, Alsoufi 2007 952, Turek 2013 2140) These findings may not be broadly generalizable. (del Nido et al. 1992; Dalton et al. 1993; Duncan et al. 1998; Alsoufi et al. 2007; Turek et al. 2013)
The recommendations provided for adult cardiac arrest in the out-of-hospital setting formulated from studies conducted in adults cannot be applied for pediatric out-of-hospital cardiac arrest given the differences between pediatric and adult populations at the level of the etiology of the event, the techniques applied for ECPR, and the post arrest care interventions.
ECPR is a complex resuscitation intervention compared to conventional CPR that requires added long term commitment to sustain the expertise, resources, training, systems, each to provide support for patients and their families. Delivering this complex intervention involves added upfront investment and costs. (Mahle 2005 1084, Lowry 2013 1422)
The health care utilization and resource allocation necessary to provide quality ECPR is likely to limit its broad adoption. While the cost effectiveness of ECMO has been published in pediatric and in adult conditions, the cost effectiveness of ECPR vs conventional CPR in pediatric cardiac arrest populations is not known.
There are no published randomized trials of ECPR vs conventional CPR in pediatrics. As some organizations have adopted ECPR in selected pediatric populations and may not have equipoise, alternative comparative study designs may be necessary to conduct comparative trials.
- Is the probability of survival between ECPR and conventional CPR in pediatric in-hospital cardiac arrest different?
- Is the probability of favorable neurologic and functional outcome between ECPR and conventional CPR in pediatric in-hospital cardiac arrest different?
The timing and type of cannulation strategy for optimal conventional CPR and ECPR remain to be studied to optimize neuro-cardiopulmonary resuscitation outcomes.
- When should cannulation for ECPR be started during conventional CPR?
- What are the conditions where ECPR should be considered earlier over conventional CPR (e.g., conditions with pulmonary blood flow obstruction)?
- What type and anatomical approach for cannulation for ECPR allows best cerebral-cardiopulmonary resuscitation?
- What other technical aspects of ECPR allows for the best cerebral-cardiopulmonary resuscitation:
- What temperature management strategy should be used?
- What circuit prime solution (reconstituted whole blood or crystalloid)?
- What fraction of device oxygenation should be delivered by the membrane lung?
- What target oxygenation and de-carboxylation should be delivered during ECPR?
- What inotrope or vasoactive medications should be delivered during ECPR?
The post cardiac arrest care strategies following cannulation for ECPR remain to be studied.
- How should post cardiac arrest care therapies be adapted to the context of ECPR?
There is no published comparative study in pediatric out-of-hospital cardiac arrest. Importantly for the field of pediatrics, there is a gap in comparative studies in out-of-hospital cardiac arrest settings in circumstances where a cardiac arrest is associated with submersion/drowning, deep hypothermia/cold environment, a respiratory arrest, or in the context of trauma.
- If ECPR is studied in pediatric out-of-hospital cardiac arrest, what select populations should be considered for initial evaluation?
- If ECPR is studied in pediatric out-of-hospital cardiac arrest, should it be delivered in the in or out-of-hospital settings?
There are no published comparative studies on longer term functional outcomes and in quality of life outcomes in pediatric patients and in their families or caregivers.
- How do longer term functional and quality of life outcomes compare between ECPR and conventional CPR pediatric population and their families and caregivers?
- How do bereavement outcomes compare between families and caregivers of non-survivors of cardiac arrest with ECPR compared to conventional CPR?
Alsoufi, B., O. O. Al-Radi, R. I. Nazer, C. Gruenwald, C. Foreman, W. G. Williams, J. G. Coles, C. A. Caldarone, D. G. Bohn, and G. S. Van Arsdell. 2007. Survival outcomes after rescue extracorporeal cardiopulmonary resuscitation in pediatric patients with refractory cardiac arrest. J Thorac Cardiovasc Surg, 134: 952-59 e2.
Dalton, H. J., R. D. Siewers, B. P. Fuhrman, P. Del Nido, A. E. Thompson, M. G. Shaver, and M. Dowhy. 1993. Extracorporeal membrane oxygenation for cardiac rescue in children with severe myocardial dysfunction. Crit Care Med, 21: 1020-8.
del Nido, P. J., H. J. Dalton, A. E. Thompson, and R. D. Siewers. 1992. Extracorporeal membrane oxygenator rescue in children during cardiac arrest after cardiac surgery. Circulation, 86: II300-4.
Duncan, B. W., A. E. Ibrahim, V. Hraska, P. J. del Nido, P. C. Laussen, D. L. Wessel, J. E. Mayer, Jr., L. K. Bower, and R. A. Jonas. 1998. Use of rapid-deployment extracorporeal membrane oxygenation for the resuscitation of pediatric patients with heart disease after cardiac arrest. J Thorac Cardiovasc Surg, 116: 305-11.
Lasa, J. J., R. S. Rogers, R. Localio, J. Shults, T. Raymond, M. Gaies, R. Thiagarajan, P. C. Laussen, T. Kilbaugh, R. A. Berg, V. Nadkarni, and A. Topjian. 2016. Extracorporeal Cardiopulmonary Resuscitation (E-CPR) During Pediatric In-Hospital Cardiopulmonary Arrest Is Associated With Improved Survival to Discharge: A Report from the American Heart Association's Get With The Guidelines-Resuscitation (GWTG-R) Registry. Circulation, 133: 165-76.
Lowry, A. W., D. L. Morales, D. E. Graves, J. D. Knudson, P. Shamszad, A. R. Mott, A. G. Cabrera, and J. W. Rossano. 2013. Characterization of extracorporeal membrane oxygenation for pediatric cardiac arrest in the United States: analysis of the kids' inpatient database. Pediatr Cardiol, 34: 1422-30.
Mahle, W. T., J. M. Forbess, P. M. Kirshbom, A. R. Cuadrado, J. M. Simsic, and K. R. Kanter. 2005. Cost-utility analysis of salvage cardiac extracorporeal membrane oxygenation in children. J Thorac Cardiovasc Surg, 129: 1084-90.
Odegard, K. C., L. Bergersen, R. Thiagarajan, L. Clark, A. Shukla, D. Wypij, and P. C. Laussen. 2014. The frequency of cardiac arrests in patients with congenital heart disease undergoing cardiac catheterization. Anesth Analg, 118: 175-82.
Ortmann, L., P. Prodhan, J. Gossett, S. Schexnayder, R. Berg, V. Nadkarni, A. Bhutta, and Investigators American Heart Association's Get With the Guidelines-Resuscitation. 2011. Outcomes after in-hospital cardiac arrest in children with cardiac disease: a report from Get With the Guidelines—Resuscitation (GWTG-R). Circulation, 124: 2329-37.
Turek, J. W., N. D. Andersen, D. S. Lawson, D. Bonadonna, R. S. Turley, M. A. Peters, J. Jaggers, and A. J. Lodge. 2013. Outcomes before and after implementation of a pediatric rapid-response extracorporeal membrane oxygenation program. Ann Thorac Surg, 95: 2140-6; discussion 46-7.