Bleeding Complications in Neonates Receiving Extracorporeal Membrane Oxygenation and Controlled Hypothermia

Abstract

Objective Safety and efficacy data on controlled hypothermia (CH) for neonates with moderate to severe hypoxic ischemic encephalopathy has been extrapolated to a subgroup of these patients who also require extracorporeal membrane oxygenation for refractory persistent pulmonary hypertension of the newborn (PPHN). However, safety data on the concomitant use of CH and extracorporeal membrane oxygenation (ECMO) are lacking.

Methods This is a single-center retrospective study of neonates ≥35 weeks' gestation with refractory PPHN who required ECMO between January 2010 and December 2020. Study groups were divided into those receiving CH/ECMO versus ECMO only. Baseline characteristics, short-term outcomes, and brain magnetic resonance imaging (MRI) data were compared.

Results A total of 36 neonates who received ECMO for refractory PPHN were included. Of these, 44.4% (n = 16) received CH/ECMO and 55.6% (n = 20) received ECMO only. Bleeding complications were more common in CH/ECMO group 50% (n = 8) versus ECMO only 15% (n = 3, p = 0.023). T1 brain MRI severity scores were higher in CH/ECMO group versus ECMO only group, however, there were no statistical difference in T2 and diffusion-weighted image scores. Functional status and survival to discharge were comparable between groups.

Conclusion In our cohort, neonates who received CH/ECMO had higher bleeding complications than ECMO only group with comparable functional status and survival at discharge.

Key Points

• Safety data on the concomitant use of CH and ECMO are lacking in neonates.

• In our cohort, neonates who received CH/ECMO had higher bleeding complications than ECMO only group.

• Functional status and survival to discharge were no differences between the two groups.

Keywords

controlled hypothermia - extracorporeal membrane oxygenation - Extracorporeal Life Support Organization - hypoxic ischemic encephalopathy - persistent pulmonary hypertension of the newborn - summary score

Note

IRB#4 Saint Christopher's Hospital for Children/The Drexel University Institutional Review Board approved the study ID: 1810006712, with a HIPAA Waiver of Authorization

Authors' Contributions

S.J. conceptualized and designed the study, analyzed the data, drafted the initial manuscript, and reviewed and revised the manuscript. E.P. reviewed MRIs and scored the patients and reviewed the manuscript. V.Q.C. and O.M. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publication History

Received: 09 September 2021

Accepted: 28 February 2022

Accepted Manuscript online:
03 March 2022

Article published online:
17 May 2022

• References

• 1 Cotten CM, Shankaran S. Hypothermia for hypoxic-ischemic encephalopathy. Expert Rev Obstet Gynecol 2010; 5 (02) 227-239
• 2 Shankaran S, Laptook A, Wright LL. et al. Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics 2002; 110 (2 Pt 1): 377-385
• 3 Jacobs SE, Morley CJ, Inder TE. et al; Infant Cooling Evaluation Collaboration. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med 2011; 165 (08) 692-700
• 4 UK Collaborative ECMO Trail Group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet 1996; 348 (9020): 75-82
• 5 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
• 6 Mugford M, Elbourne D, Field D. Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants. Cochrane Database Syst Rev 2008; (03) CD001340
• 7 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
• 8 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
• 9 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
• 10 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
• 11 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
• 12 Wild KT, Rintoul N, Kattan J, Gray B. Extracorporeal Life Support Organization (ELSO): guidelines for neonatal respiratory failure. ASAIO J 2020; 66 (05) 463-470
• 13 Barkovich AJ, Hajnal BL, Vigneron D. et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998; 19 (01) 143-149
• 14 Holland RA, Kirschvink JL, Doak TG, Wikelski M. Bats use magnetite to detect the earth's magnetic field. PLoS One 2008; 3 (02) e1676
• 15 Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med 2009; 37 (03) 1101-1120
• 16 Jacobs S, Hunt R, Tarnow-Mordi W, Inder T, Davis P. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2007; (04) CD003311
• 17 Shankaran S. Therapeutic hypothermia for neonatal encephalopathy. Curr Treat Options Neurol 2012; 14 (06) 608-619
• 18 Wintermark P, Hansen A, Gregas MC. et al. Brain perfusion in asphyxiated newborns treated with therapeutic hypothermia. AJNR Am J Neuroradiol 2011; 32 (11) 2023-2029
• 19 Dalton HJ, Reeder R, Garcia-Filion P. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Factors associated with bleeding and thrombosis in children receiving extracorporeal membrane oxygenation. Am J Respir Crit Care Med 2017; 196 (06) 762-771
• 20 Cashen K, Reeder RW, Shanti C, Dalton HJ, Dean JM, Meert KL. Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN). Is therapeutic hypothermia during neonatal extracorporeal membrane oxygenation associated with intracranial hemorrhage?. Perfusion 2018; 33 (05) 354-362
• 21 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
• 22 Cuevas Guaman M, 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
• 23 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
• 24 Polito A, Barrett CS, Wypij D. et al. Neurologic complications in neonates supported with extracorporeal membrane oxygenation. An analysis of ELSO registry data. Intensive Care Med 2013; 39 (09) 1594-1601
• 25 Cashen K, Meert K, Dalton H. Anticoagulation in neonatal ECMO: an enigma despite a lot of effort!. Front Pediatr 2019; 7: 366