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Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy in Newborn Infants

성인경
대한신생아학회 (THE KOREAN SOCIETY OF NEONATOLOGY)|2017.11|Neonatal medicine|제24권 제4호|pp. 145-156

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키워드

InfantNewbornEncephalopathyHypoxia-ischemia

초록

Neonatal hypoxic-ischemic encephalopathy (HIE) is an ongoing process, which may persist for weeks to years after an acute asphyxial insult, causing delayed programmed cell death. The typical clinical signs and the pathological findings of HIE manifest as the condition evolves in a step-wise manner, beginning with an acute phase, followed by a latent, a secondary energy failure phase, and eventually a tertiary brain injury phase. To date, therapeutic hypothermia (TH) is the only effective treatment strategy known to improve mortality and prevent neurodevelopmental disabilities, as has been proven by the results of several randomized controlled clinical trials. The current protocols describing the use of TH for newborns of gestational age ≥36 weeks with HIE, associated with clinical evidence of asphyxia along with neurological signs of moderate- to-severe encephalopathy, observed at ≤6 hours of age, are close to optimal. Most comorbid conditions observed during TH are related to asphyxia. TH is a safe treatment option—benign sinus bradycardia and thrombocytopenia are frequent hypothermia-related complications. Additional adjuvant agents, which may augment hypothermic neuroprotection are being investigated, and a few of them, such as erythropoietin and melatonin appear to be promising agents for use in this condition. Establishing our own nationwide cooling systems and guidelines for a standard treatment protocol to manage HIE are warranted in the future.

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is an ongoing process, which may persist for weeks to years after an acute asphyxial insult, causing delayed programmed cell death. The typical clinical signs and the pathological findings of HIE manifest as the condition evolves in a step-wise manner, beginning with an acute phase, followed by a latent, a secondary energy failure phase, and eventually a tertiary brain injury phase. To date, therapeutic hypothermia (TH) is the only effective treatment strategy known to improve mortality and prevent neurodevelopmental disabilities, as has been proven by the results of several randomized controlled clinical trials. The current protocols describing the use of TH for newborns of gestational age ≥36 weeks with HIE, associated with clinical evidence of asphyxia along with neurological signs of moderate- to-severe encephalopathy, observed at ≤6 hours of age, are close to optimal. Most comorbid conditions observed during TH are related to asphyxia. TH is a safe treatment option—benign sinus bradycardia and thrombocytopenia are frequent hypothermia-related complications. Additional adjuvant agents, which may augment hypothermic neuroprotection are being investigated, and a few of them, such as erythropoietin and melatonin appear to be promising agents for use in this condition. Establishing our own nationwide cooling systems and guidelines for a standard treatment protocol to manage HIE are warranted in the future.

참고문헌 (71)

  1. Jacobs SE, "Cooling for newborns with hypoxic ischaemic encephalopathy", Cochrane Database Syst Rev, pp.CD003311~ (2013)[DOI]
  2. Edwards AD, "Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data", BMJ, 340, pp.c363~ (2010)
  3. Gluckman PD, "Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicenter randomized trial", Lancet, 365, pp.663~670 (2005)
  4. Shankaran S, "Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy", N Engl J Med, 353, pp.1574~1584 (2005)
  5. Azzopardi DV, "Moderate hypothermia to treat perinatal asphyxial encephalopathy", N Engl J Med, 361, pp.1349~1358 (2009)
  6. Simbruner G, "Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT", Pediatrics, 126, pp.e771~e778 (2010)[DOI]
  7. Jacobs SE, "Whole-body hypothermia for term and nearterm newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial", Arch Pediatr Adolesc Med, 165, pp.692~700 (2011)
  8. Guillet R, "Seven- to eight-year follow-up of the Cool Cap trial of head cooling for neonatal encephalopathy", Pediatr Res, 71, pp.205~209 (2012)
  9. Azzopardi D, "Effects of hypothermia for perinatal asphyxia on childhood outcomes", N Engl J Med, 371, pp.140~149 (2014)
  10. Perlman JM, "Part 11: neonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations", Circulation, 122, pp.S516~S538 (2010)
  11. Wyckoff MH, "Part 13: neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care", Circulation, 132, pp.S543~S560 (2015)
  12. Hassell KJ, "New horizons for newborn brain protection:enhancing endogenous neuroprotection", Arch Dis Child Fetal Neonatal Ed, 100, pp.F541~F552 (2015)
  13. Shah P, "Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy", Arch Dis Child Fetal Neonatal Ed, 89, pp.F152~F155 (2004)
  14. Szydlowska K, "Calcium, ischemia and excitotoxicity", Cell Calcium, 47, pp.122~129 (2010)
  15. Iwata O, "'Therapeutic time window' duration decreases with increasing severity of cerebral hypoxia-ischaemia under normothermia and delayed hypothermia in newborn piglets", Brain Res, 1154, pp.173~180 (2007)
  16. Lorek A, "Delayed ('secondary') cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy", Pediatr Res, 36, pp.699~706 (1994)
  17. Roth SC, "Relation of deranged neonatal cerebral oxidative metabolism with neurodevelopmental outcome and head circumference at 4 years", Dev Med Child Neurol, 39, pp.718~725 (1997)
  18. Fleiss B, "Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?", Lancet Neurol, 11, pp.556~566 (2012)
  19. Drury PP, "Mechanisms of hypothermic neuroprotection", Clin Perinatol, 41, pp.161~175 (2014)
  20. Wassink G, "The mechanisms and treatment of asphyxial encephalopathy", Front Neurosci, 8, pp.40~ (2014)
  21. Mehta S, "Eligibility criteria for therapeutic hypothermia: from trials to clinical practice", J Pediatr Child Health, 53, pp.295~300 (2017)
  22. Thoresen M, "Time is brain: starting therapeutic hypothermia within three hours after birth improves motor outcome in asphyxiated newborns", Neonatology, 104, pp.228~233 (2013)
  23. Youn YA, "The hospital outcomes compared between the early and late hypothermia-treated groups in neonates", J Matern Fetal Neonatal Med, 29, pp.2288~2292 (2016)
  24. Del Río R, "Amplitude integrated electroencephalogram as a prognostic tool in neonates with hypoxic-ischemic encephalopathy: a systematic review", PLoS One, 11, pp.e0165744~ (2016)[DOI]
  25. Rao R, "Safety and short-term outcomes of therapeutic hypothermia in preterm neonates 34-35 weeks gestational age with hypoxicischemic encephalopathy", J Pediatr, 183, pp.37~42 (2017)
  26. "Evaluation of systemic hypothermia initiated after 6 hours of age in infants ≥36 weeks gestation with hypoxic-ischemic encephalopathy: a protocol for the NICHD Neonatal Research Network"[URL]
  27. Stafford TD, "Therapeutic hypothermia during neonatal transport: active cooling helps reach the target", Ther Hypothermia Temp Manag, 7, pp.88~94 (2017)
  28. Kendall GS, "Passive cooling for initiation of therapeutic hypothermia in neonatal encephalopathy", Arch Dis Child Fetal Neonatal Ed, 95, pp.F408~F412 (2010)
  29. Fairchild K, "Therapeutic hypothermia on neonatal transport: 4-year experience in a single NICU", J Perinatol, 30, pp.324~329 (2010)
  30. Osredkar D, "Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic-ischemic brain injury", Resuscitation, 85, pp.567~572 (2014)
  31. Mourvillier B, "Induced hypothermia in severe bacterial meningitis:a randomized clinical trial", JAMA, 310, pp.2174~2183 (2013)
  32. Celik Y, "Comparison of selective head cooling versus whole body cooling", Pediatr Int, 58, pp.27~33 (2016)
  33. Shankaran S, "Effect of depth and duration of cooling on death in the NICU among neonates with hypoxic ischemic encephalopathy:a randomized clinical trial", JAMA, 312, pp.2629~2639 (2014)
  34. Gerrits LC, "Epileptiform activity during rewarming from moderate cerebral hypothermia in the near-term fetal sheep", Pediatr Res, 57, pp.342~346 (2005)
  35. Wang B, "Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxicischemic encephalopathy", J Cereb Blood Flow Metab, 35, pp.781~793 (2015)
  36. Shellhaas RA, "Impact of amplitude-integrated EEG on the clinical care for neonates with seizures", Pediatr Neurol, 46, pp.32~35 (2012)
  37. MastrangeloM, "Acute neonatal encephalopathy and seizures recurrence:a combined aEEG", EEG study, 2013, pp.22, 703~707
  38. Merchant N, "Early predictors of outcome in infants treated with hypothermia for hypoxic-ischemic encephalopathy", Dev Med Child Neurol, 57(Suppl 3), pp.8~16 (2015)
  39. Rollins N, "Predictive value of neonatal MRI showing no or minor degrees of brain injury after hypothermia", Pediatr Neurol, 50, pp.447~451 (2014)
  40. Wintermark P, "Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia", Neuroimage, 85(Pt 1), pp.287~293 (2014)
  41. Azzopardi D, "Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK -analysis of national data", PLoS One, 7, pp.e38504~ (2012)[DOI]
  42. Sarkar S, "Management of neonatal morbidities during hypothermia treatment", Semin Fetal Neonatal Med, 20, pp.97~102 (2015)
  43. Pappas A, "Hypocarbia and adverse outcome in neonatal hypoxic-ischemic encephalopathy", J Pediatr, 158, pp.752~758 (2011)
  44. Armstrong K, "Cardiovascular dysfunction in infants with neonatal encephalopathy", Arch Dis Child, 97, pp.372~375 (2012)
  45. Basu SK, "Hypoglycemia and hyperglycemia are associated with unfavorable outcome in infants with hypoxic ischemic encephalopathy: a post hoc analysis of the CoolCap Study", Arch Dis Child Fetal Neonatal Ed, 101, pp.F149~F155 (2016)
  46. Forman KR, "Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: a retrospective case-control study", BMC Pediatr, 14, pp.277~ (2014)
  47. Murray DM, "Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures", Arch Dis Child Fetal Neonatal Ed, 93, pp.F187~F191 (2008)
  48. Donovan MD, "Pharmacotherapy for neonatal seizures: current knowledge and future perspectives", Drugs, 76, pp.647~661 (2016)
  49. Filippi L, "Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia", Epilepsia, 52, pp.794~801 (2011)
  50. Zhou J, "The effect of therapeutic hypothermia on drug metabolism and response: cellular mechanisms to organ function", Expert Opin Drug Metab Toxicol, 7, pp.803~816 (2011)
  51. van den Broek MP, "Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia", Neonatology, 107, pp.150~156 (2015)
  52. Liu Y, "Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats", Stroke, 35, pp.1460~1465 (2004)
  53. Filippi L, "Oral topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia: a safety study", J Pediatr, 157, pp.361~366 (2010)
  54. "Topiramate as an adjuvant to therapeutic hypothermia for infants with hypoxic ischemic encephalopathy"[URL]
  55. Battin M, "Rebound seizures during rewarming", Pediatrics, 114, pp.1369~ (2004)
  56. Thoresen M, "Supportive care during neuroprotective hypothermia in the term newborn: adverse effects and their prevention", Clin Perinatol, 35, pp.749~763 (2008)
  57. Thoresen M, "Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective", Pediatr Res, 50, pp.405~411 (2001)
  58. Angeles DM, "Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates", Pediatr Res, 61, pp.614~621 (2007)
  59. Roka A, "Elevated morphine concentrations in neonates treated with morphine and prolonged hypothermia for hypoxic ischemic encephalopathy", Pediatrics, 121, pp.844~849 (2008)
  60. Johnston MV, "Treatment advances in neonatal neuroprotection and neurointensive care", Lancet Neurol, 10, pp.372~382 (2011)
  61. Davidson JO, "Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy - where to from here?", Front Neurol, 6, pp.198~ (2015)
  62. Robertson NJ, "Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model", Brain, 136, pp.90~105 (2013)
  63. Dean JM, "Suppression of post-hypoxic-ischemic EEG transients with dizocilpine is associated with partial striatal protection in the preterm fetal sheep", Neuropharmacology, 50, pp.491~503 (2006)
  64. George SA, "Nonadditiveneuroprotection with early glutamate receptor blockade and delayed hypothermia after asphyxia in preterm fetal sheep", Stroke, 43, pp.3114~3117 (2012)
  65. Tan WK, "Suppression of postischemicepileptiform activity with MK-801improves neural outcome in fetal sheep", Ann Neurol, 32, pp.677~682 (1992)
  66. Liu Y, "Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats", Stroke, 35, pp.1460~1465 (2004)
  67. Faulkner SD, "A xenon recirculating ventilator for the newborn piglet: developing clinical applications of xenon for neonates", Eur J Anaesthesiol, 29, pp.577~585 (2012)
  68. Azzopardi D, "Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomized controlled trial", Lancet Neurol, 15, pp.145~153 (2016)
  69. Drobyshevsky A, "Human umbilical cord blood cells ameliorate motor deficits in rabbits in a cerebral palsy model", Dev Neurosci, 37, pp.349~362 (2015)
  70. Bennet L, "Cell therapy for neonatal hypoxia-ischemia and cerebral palsy", Ann Neurol, 71, pp.589~600 (2012)
  71. Galinsky R, "Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies: a systematic review", Dev Neurosci, 36, pp.73~82 (2014)

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