REVIEW

Permissive Hypothermia as a Reducing Measure for Neurosurgical Intervention in Hypoxic-Ischemic Encephalopathy in Neonates: a robust metanalysis in pediatric neurosurgery

Hipotermia Permissiva como Medida Redutora de Intervenção Neurocirúrgica na Encefalopatia Hipóxico-Isquêmica em Neonatos: uma robusta metanálise em neurocirurgia pediátrica

  • Bianca Frigo Pires    Bianca Frigo Pires
  • Felipe Kenji Ito    Felipe Kenji Ito
  • Danielle Simha Ghiberti    Danielle Simha Ghiberti
  • Alana Camera Bloise Pieroni    Alana Camera Bloise Pieroni
  • Tainan Lima Borges    Tainan Lima Borges
  • Hugo Belavenuta Pinto    Hugo Belavenuta Pinto
  PDF  English version
  Views: 284
  Downloads: 18

Resumo

Introdução: a encefalopatia hipóxico-isquêmica (EHI) é um subtipo de encefalopatia neonatal cuja causa é uma limitação do oxigênio e do fluxo sanguíneo próximo ao momento do nascimento, sendo uma das principais causas de morte neonatal com comprometimento neurológico de longo prazo. Objetivo: fornecer uma referência para o diagnóstico e tratamento da encefalopatia hipóxico-isquêmica com o objetivo de reduzir a necessidade de intervenção neurocirúrgica ou de melhorar o prognóstico. Métodos: Busca com base no método PRISMA, artigos relacionados a “hipotermia permissiva; lesão cerebral hipóxica; neonatos com hipotermia” publicados nos últimos 5 anos. Resultados: o prognóstico dos pacientes foi óbito em 466 (13%) dos casos e 2066 (48,71%) com lesão cerebral, dentre os quais 76,29% não foram tratados com hipotermia em momento oportuno. Discussão: A EHI tem natureza dinâmica, sendo sua evolução um desafio para a tomada de decisão clínica precoce e pragmática. Por outro lado, estudos recentes têm demonstrado que a cautela excessiva em não utilizar hipotermia permissiva aumentou a progressão das encefalopatias para níveis mais graves. Conclusão: Esta revisão sistemática e meta-análise confirmam que a hipotermia permissiva é uma intervenção eficaz na redução da necessidade de intervenções neurocirúrgicas em neonatos com encefalopatia hipóxico-isquêmica. Além disso, o tratamento reduz a mortalidade e a gravidade da lesão cerebral, levando a melhores resultados de neurodesenvolvimento.

Palavras-chave

Hipotermia permissiva; Lesão cerebral hipóxica; Hipotermia, neonatos

Abstract

Introduction: hypoxic ischemic encephalopathy (HIE) is a subtype of neonatal encephalopathy whose cause is a limitation of oxygen and blood flow close to the moment of birth, being one of the main causes of neonatal death with long-term neurological impairment. Objective: to provide a reference for the diagnosis and treatment of hypoxic-ischemic encephalopathy aiming to reduce the need for neurosurgical intervention or improve prognosis. Methods: Search based on the PRISMA method, articles related to “permissive hypothermia; hypoxic brain injury; neonates with hypothermia” published in the last 5 years were identified. Results: the patients’ prognosis was death in 466 (13%) of cases and brain injury for 2066 (48.71%), among which 76.29% were not treated with HT at an opportune time. Discussion: HIE has a dynamic nature, its evolution being a challenge for early and pragmatic clinical decision-making. On the other hand, recent studies have demonstrated that excessive caution in not using permissive hypothermia increased the progression of encephalopathies to more severe levels. Conclusion: This systematic review and meta-analysis confirm that permissive hypothermia is an effective intervention in reducing the need for neurosurgical interventions in neonates with hypoxic-ischemic encephalopathy. In addition, the treatment reduces mortality and severity of brain injury, leading to improved neurodevelopmental outcomes.

Keywords

Permissive hypothermia; Hypoxic brain injury; Hypothermia neonates

References

1. Wachtel EV, Verma S, Mally PV. Update on the current management of newborns with neonatal encephalopathy. Curr Probl Pediatr Adolesc Health Care. 2019;49(7):100636. http://doi.org/10.1016/j. cppeds.2019.07.001. PMid:31371100.
2. Sabsabi B, Huet C, Rampakakis E, et al. Asphyxiated neonates treated with hypothermia: birth place matters. Am J Perinatol. 2022;39(3):298- 306. http://doi.org/10.1055/s-0040-1715823. PMid:32854133.
3. Grass B, El Shahed A, Ly LG, et al. Therapeutic hypothermia for hypoxic-ischemic encephalopathy after perinatal sentinel events: less brain injury on MRI and improved neurodevelopmental outcome at 18-36 months. J Perinatol. 2020;40(4):633-9. http://doi.org/10.1038/ s41372-020-0602-8. PMid:32051541.
4. Lopez Laporte MA, Wang H, Sanon PN, et al. Association between hypocapnia and ventilation during the first days of life and brain injury in asphyxiated newborns treated with hypothermia. J Matern Fetal Neonatal Med. 2019;32(8):1312-20. http://doi.org/10.1080/14767058 .2017.1404980. PMid:29129133.
5. Szakmar E, Smith J, Yang E, Volpe JJ, Inder T, El-Dib M. Association between cerebral oxygen saturation and brain injury in neonates receiving therapeutic hypothermia for neonatal encephalopathy. J Perinatol. 2021;41(2):269-77. http://doi.org/10.1038/s41372-020-00910-w. PMid:33462339.
6. Xu EH, Claveau M, Yoon EW, et al. Neonates with hypoxic-ischemic encephalopathy treated with hypothermia: observations in a large Canadian population and determinants of death and/or brain injury. J Neonatal Perinatal Med. 2020;13(4):449-58. http://doi.org/10.3233/ NPM-190368. PMid:32310192.
7. Rao R, Mietzsch U, DiGeronimo R, et al. Utilization of therapeutic hypothermia and neurological injury in neonates with mild hypoxic-ischemic encephalopathy: a report from children’s hospital neonatal consortium. Am J Perinatol. 2022;39(3):319-28. http://doi. org/10.1055/s-0040-1716341. PMid:32892328.
8. McGowan MM, O’Kane AC, Vezina G, et al. Serial plasma biomarkers of brain injury in infants with neonatal encephalopathy treated with therapeutic hypothermia. Pediatr Res. 2021;90(6):1228-34. http://doi. org/10.1038/s41390-021-01405-w. PMid:33654280.
9. Wang Z, Zhang D, Zhang P, et al. Safety and efficacy of therapeutic hypothermia in neonates with mild hypoxic-ischemic encephalopathy. BMC Pediatr. 2023;23(1):530. http://doi.org/10.1186/s12887-023- 04365-8. PMid:37884911.
10. Joanna RGV, Lopriore E, Te Pas AB, et al. Persistent pulmonary hypertension in neonates with perinatal asphyxia and therapeutic hypothermia: a frequent and perilous combination. J Matern Fetal Neonatal Med. 2022;35(25):4969-75. http://doi.org/10.1080/1476705 8.2021.1873941. PMid:33615985.
11. Thiim KR, Garvey AA, Singh E, Walsh B, Inder TE, El-Dib M. Brain injury in infants evaluated for, but not treated with, therapeutic hypothermia. J Pediatr. 2023;253:304-9. http://doi.org/10.1016/j. jpeds.2022.09.027. PMid:36179889.
12. Thayyil S, Montaldo P, Krishnan V, et al. Whole-body hypothermia, cerebral magnetic resonance biomarkers, and outcomes in neonates with moderate or severe hypoxic-ischemic encephalopathy born at tertiary care centers vs other facilities: a nested study within a randomized clinical trial. JAMA Netw Open. 2023;6(5):e2312152. http://doi.org/10.1001/ jamanetworkopen.2023.12152. PMid:37155168.
13. Goswami I, Guillot M, Tam EWY. Predictors of long-term neurodevelopmental outcome of hypoxic-ischemic encephalopathy treated with therapeutic hypothermia. Semin Neurol. 2020;40(3):322- 34. http://doi.org/10.1055/s-0040-1702939. PMid:32079030.
14. Rao R, Trivedi S, Distler A, et al. Neurodevelopmental outcomes in neonates with mild hypoxic ischemic encephalopathy treated with therapeutic hypothermia. Am J Perinatol. 2019;36(13):1337-43. http:// doi.org/10.1055/s-0038-1676973. PMid:30609430.
15. Nour I, Elmaghraby R, Shehata R, et al. Selective head cooling and acute kidney injury in neonates with hypoxic ischemic encephalopathy. J Neonatal Perinatal Med. 2020;13(1):21-30. http://doi.org/10.3233/ NPM-180200. PMid:31561395.
16. Wu TW, L Wisnowski J, Geisler RF, et al. An in vivo assessment of regional brain temperature during whole-body cooling for neonatal encephalopathy. J Pediatr. 2020;220:73-79.e3. http://doi.org/10.1016/j. jpeds.2020.01.019. PMid:32089332.
17. Montaldo P, Lally PJ, Oliveira V, et al. Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study. Arch Dis Child Fetal Neonatal Ed. 2019;104(5):F515-20. http://doi.org/10.1136/archdischild-2018-316040. PMid:30425113.
18. Spencer APC, Lee-Kelland R, Brooks JCW, et al. Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy. Dev Med Child Neurol. 2023;65(3):367-75. http://doi.org/10.1111/dmcn.15369. PMid:35907252.
19. Gilmore MM, Tekes A, Perin J, et al. Later cooling within 6 h and temperatures outside 33-34 °C are not associated with dysfunctional autoregulation during hypothermia for neonatal encephalopathy. Pediatr Res. 2021;89(1):223-30. http://doi.org/10.1038/s41390-020-0876-8. PMid:32268341.
20. Mietzsch U, Radhakrishnan R, Boyle FA, Juul S, Wood TR. Active cooling temperature required to achieve therapeutic hypothermia correlates with short-term outcome in neonatal hypoxic-ischaemic encephalopathy. J Physiol. 2020;598(2):415-24. http://doi.org/10.1113/ JP278790. PMid:31777079.
21. Bach AM, Fang AY, Bonifacio S, et al. Early magnetic resonance imaging predicts 30-month outcomes after therapeutic hypothermia for neonatal encephalopathy. J Pediatr. 2021;238:94-101.e1. http://doi. org/10.1016/j.jpeds.2021.07.003. PMid:34237346.
22. Montaldo P, Puzone S, Caredda E, et al. Magnetic resonance biomarkers and neurological outcome of infant with mild hypoxic-ischaemic encephalopathy who progress to moderate hypoxic-ischaemic encephalopathy. Neonatology. 2023;120(1):153-60. http:// doi.org/10.1159/000527871. PMid:36549280.
23. Harbert MJA, Sey R, Arnell K, Rasmussen M. Identifying ways to fix outcome disparities among outborns needing therapeutic hypothermia. Am J Perinatol. 2021;38(S01):e21-5. http://doi. org/10.1055/s-0040-1702990 PMid:32120421.
24. Im SA, Tomita E, Oh MY, Kim SY, Kang HM, Youn YA. Volumetric changes in brain MRI of infants with hypoxic-ischemic encephalopathy and abnormal neurodevelopment who underwent therapeutic hypothermia. Brain Res. 2024;1825:148703. PMid:38101694.
25. Aker K, Støen R, Eikenes L, et al. Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2020;105(4):405-11. http://doi.org/10.1136/archdischild-2019-317311. PMid:31662328.
26. León-Lozano MZ, Arnaez J, Valls A, et al. Cerebrospinal fluid levels of neuron-specific enolase predict the severity of brain damage in newborns with neonatal hypoxic-ischemic encephalopathy treated with hypothermia. PLoS One. 2020;15(6):e0234082. http://doi.org/10.1371/ journal.pone.0234082. PMid:32479533.
27. Goenka A, Yozawitz E, Gomes WA, Nafday SM. Selective head versus whole body cooling treatment of hypoxic-ischemic encephalopathy: comparison of electroencephalogram and magnetic resonance imaging findings. Am J Perinatol. 2020;37(12):1264-70. http://doi. org/10.1055/s-0039-1693466. PMid:31344712.
28. Basti C, Maranella E, Cimini N, et al. Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: a single center observational study. Seizure. 2020;83:154-9. http://doi.org/10.1016/j. seizure.2020.10.021. PMid:33160202.
29. Li J, Zhang G, Wang X, et al. Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia. BMC Pediatr. 2023;23(1):609. http://doi.org/10.1186/ s12887-023-04421-3. PMid:38037071.
30. Sarkar SS, Gupta S, Bapuraj JR, Dechert RE, Sarkar S. Brainstem hypoxic- ischemic lesions on MRI in infants treated with therapeutic cooling: effects on the length of stay and mortality. J Perinatol. 2021;41(3):512-8. http://doi.org/10.1038/s41372-020-00873-y. PMid:33223525.
31. Goswami IR, Whyte H, Wintermark P, et al. Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia. J Perinatol. 2020;40(2):275-83. http://doi. org/10.1038/s41372-019-0551-2. PMid:31723237.

1Faculdade de Medicina de Marília, Marília, SP, Brazil.

2Pediatric Intensive Care Medicine, Faculdade de Medicina de Marília, Marília, SP, Brazil.

 

Received Oct 8, 2024

Accepted Dec 2, 2024

  Voltar

JBNC  Brazilian Journal of Neurosurgery

JBNC
  •   ISSN (print version): 0103-5118
  •   e-ISSN (online version): 2446-6786
iThenticate
Open Access

Contact

Social Media

   

ABNc  Academia Brasileira de Neurocirurgia

  •   Rua da Quitanda 159 – 10º andar - Centro - CEP 20091-005 - Rio de Janeiro - RJ
  •   +55 21 2233.0323
  •    abnc@abnc.org.br

Sponsor

  • Brain4Care
  • Hospital INC
  • Strattner
  • Zeiss