Subscribe to RSS
DOI: 10.1055/a-2632-9833
ECMO Use in Neonates with Hypoxic–Ischemic Encephalopathy: A State-of-the-Art Narrative Review of Feasibility, Efficacy, and Safety
Funding None.

Abstract
Extracorporeal membrane oxygenation (ECMO) is an important rescue strategy for neonates with severe cardiorespiratory failure, yet its role in the management of hypoxic–ischemic encephalopathy (HIE) remains subject to debate. Historically, clinicians have been reluctant to offer ECMO to infants with significant neurological injury because of concerns related to poor neurodevelopmental outcomes and elevated risk of complications such as hemorrhage and stroke. Over the past two decades, however, accumulating evidence has suggested that many neonates with HIE not only tolerate ECMO well but may also achieve meaningful survival and functional recovery. In this state-of-the-art narrative review, we surveyed and synthesized observational studies, retrospective cohorts, and case series published since 2000 that evaluated ECMO in neonates with HIE. While randomized controlled trials dedicated exclusively to this population remain scarce, the available data indicate that ECMO can be safely implemented alongside standard therapies—including therapeutic hypothermia—without uniformly prohibitive rates of bleeding or adverse neurodevelopment. Although small sample sizes and single-center experiences limit the strength of these conclusions, survival rates in combined TH-ECMO cohorts are often reported above 80 to 90%, with a substantial proportion of survivors demonstrating acceptable early neurodevelopmental outcomes. Overall, the growing clinical acceptance of ECMO in HIE highlights the need for careful, individualized assessment of benefits and risks, as well as transparent discussions with families. Future multicenter collaborations focusing on robust longitudinal follow-up and evidence-based protocols will be essential to guide best practices and optimize outcomes for this high-risk neonatal population.
Publication History
Received: 23 March 2025
Accepted: 11 June 2025
Accepted Manuscript online:
12 June 2025
Article published online:
07 July 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Aggarwal S, Natarajan G. Biventricular function on early echocardiograms in neonatal hypoxic-ischaemic encephalopathy. Acta Paediatr 2017; 106 (07) 1085-1090
- 2 Lakshminrusimha S, Shankaran S, Laptook A. et al. Pulmonary hypertension associated with hypoxic-ischemic encephalopathy-antecedent characteristics and comorbidities. J Pediatr 2018; 196: 45-51.e3
- 3 Yajamanyam PK, Negrine RJS, Rasiah SV, Plana MN, Zamora J, Ewer AK. Left ventricular dysfunction persists in the first week after re-warming following therapeutic hypothermia for hypoxic-ischaemic encephalopathy. Neonatology 2022; 119 (04) 510-516
- 4 Altit G, Bonifacio SL, Guimaraes CV. et al. Cardiac dysfunction in neonatal HIE is associated with increased mortality and brain injury by MRI. Am J Perinatol 2023; 40 (12) 1336-1344
- 5 Khanduja S, Kim J, Kang JK. et al. Hypoxic-ischemic brain injury in ECMO: pathophysiology, neuromonitoring, and therapeutic opportunities. Cells 2023; 12 (11) 1546
- 6 Shankaran S, Laptook AR, Ehrenkranz RA. et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
- 7 Shankaran S, Pappas A, McDonald SA. et al; Eunice Kennedy Shriver NICHD Neonatal Research Network. Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 2012; 366 (22) 2085-2092
- 8 Chapman RL, Peterec SM, Bizzarro MJ, Mercurio MR. Patient selection for neonatal extracorporeal membrane oxygenation: beyond severity of illness. J Perinatol 2009; 29 (09) 606-611
- 9 Kirsch R, Munson D. Ethical and end of life considerations for neonates requiring ECMO support. Semin Perinatol 2018; 42 (02) 129-137
- 10 Moynihan KM, Basu S, Kirsch R. Discretion over discrimination: toward good decisions for extracorporeal membrane oxygenation use in patients with neurological comorbidities. Pediatr Crit Care Med 2022; 23 (11) 943-946
- 11 Gluckman PD, Wyatt JS, Azzopardi D. et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460) 663-670
- 12 Azzopardi D, Brocklehurst P, Edwards D. et al; TOBY Study Group. The TOBY study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr 2008; 8: 17
- 13 Weems MF, Upadhyay K, Sandhu HS. Survey of ECMO practices for infants with hypoxic ischemic encephalopathy. J Perinatol 2018; 38 (09) 1197-1204
- 14 McNally H, Bennett CC, Elbourne D, Field DJ, Group UKCET. UK Collaborative ECMO Trial Group. United Kingdom collaborative randomized trial of neonatal extracorporeal membrane oxygenation: follow-up to age 7 years. Pediatrics 2006; 117 (05) e845-e854
- 15 Ichiba S, Killer HM, Firmin RK, Kotecha S, Edwards AD, Field D. Pilot investigation of hypothermia in neonates receiving extracorporeal membrane oxygenation. Arch Dis Child Fetal Neonatal Ed 2003; 88 (02) F128-F133
- 16 Horan M, Ichiba S, Firmin RK. et al. A pilot investigation of mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). J Pediatr 2004; 144 (03) 301-308
- 17 Field D, Juszczak E, Linsell L. et al; NEST Study Collaborative Group. Neonatal ECMO study of temperature (NEST): a randomized controlled trial. Pediatrics 2013; 132 (05) e1247-e1256
- 18 Massaro A, Rais-Bahrami K, Chang T, Glass P, Short BL, Baumgart S. Therapeutic hypothermia for neonatal encephalopathy and extracorporeal membrane oxygenation. J Pediatr 2010; 157 (03) 499-501 , 501.e1
- 19 Guaman CM, Lucke AM, Hagan JL, Kaiser JR. Bleeding complications and mortality in neonates receiving therapeutic hypothermia and extracorporeal membrane oxygenation. Am J Perinatol 2018; 35 (03) 271-276
- 20 Okulu E, Erdeve O, Pekcici BB. et al. A successful whole body therapeutic hypothermia for hypoxic ischemic encephalopathy during an ECMO run in a newborn. Front Pediatr 2019; 7: 95
- 21 Agarwal P, Altinok D, Desai J, Shanti C, Natarajan G. In-hospital outcomes of neonates with hypoxic-ischemic encephalopathy receiving extracorporeal membrane oxygenation. J Perinatol 2019; 39 (05) 661-665
- 22 Bhandary P, Daniel JM, Skinner SC. et al. Case series of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy during extracorporeal life support. Perfusion 2020; 35 (07) 700-706
- 23 Basu RC. Risk of Intracranial Hemorrhage or Death during ECMO in Neonates with Hypoxic-ischemic Encephalopathy. 2024 . Accessed June 16, 2025 at: https://2024.pas-meeting.org/fsPopup.asp?PosterID=646990&mode=posterInfo
- 24 Joshi S, Cardona VQ, Poletto E, Menkiti O. Bleeding complications in neonates receiving extracorporeal membrane oxygenation and controlled hypothermia. Am J Perinatol 2024; 41 (08) 1062-1068
- 25 Cicalese E, Seltzer BHS, Fisher JC, Verma S. Outcomes in neonates receiving therapeutic hypothermia and extracorporeal membrane oxygenation versus extracorporeal membrane oxygenation alone. Am J Perinatol 2024
- 26 Agarwal P, Natarajan G, Sullivan K. et al; Children's Hospital Neonatal Consortium (CHNC) ECMO and HIE focus groups. Venovenous versus venoarterial extracorporeal membrane oxygenation among infants with hypoxic-ischemic encephalopathy: is there a difference in outcome?. J Perinatol 2021; 41 (08) 1916-1923
- 27 Peterec SM, Bizzarro MJ, Mercurio MR. Is extracorporeal membrane oxygenation for a neonate ever ethically obligatory?. J Pediatr 2018; 195: 297-301
- 28 Mercurio MR, Cummings CL. Critical decision-making in neonatology and pediatrics: the I-P-O framework. J Perinatol 2021; 41 (01) 173-178
- 29 Di Nardo M, Dalle Ore A, Testa G. et al. Principlism and personalism. comparing two ethical models applied clinically in neonates undergoing extracorporeal membrane oxygenation support. Front Pediatr 2019; 7: 312
- 30 Brodie D, Vercaemst L, Lorusso R. et al. Extracorporeal life support: the ELSO red book. 6th ed. Ann Arbor, Michigan: Extracorporeal Life Support Organization; 2022