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#081-#085 - Therapeutic Hypothermia for HIE

Hello friends 👋

This week we are talking about therapeutic hypothermia for neonatal encephalopathy. As usual, we started by reviewing the history of this intervention which dates back further than you might imagine. We reviewed the major trials assessing the effects of hypothermia on HIE and Daphna walked us through the pathophysiology of HIE and how cooling can reduce the degree of brain injury. We had the pleasure and the honor to welcome Dr. Michael Weiss who answered a few burning questions on the topic of cooling (pun intended). We reviewed a few studies that looked at alternative use of hypothermia and concluded our week as we usually do with an episode focused on board review questions.

We wanted to thank you again for your continued support.

Please find resources below👇

Link to download the PowerPoint and notes from these episodes 👇

The articles covered on this series of episodes can be found here 👇

Caveats of Cooling: Available Evidence and Ongoing Investigations of Therapeutic Hypothermia.

Parga-Belinkie J, Foglia EE, Flibotte J.Neoreviews. 2019 Sep;20(9):e513-e519. doi: 10.1542/neo.20-9-e513.PMID: 31477599 Review.

Hypothermia treatment and the newborn.

Wyatt JS, Thoresen M.Pediatrics. 1997 Dec;100(6):1028-30. doi: 10.1542/peds.100.6.1028.PMID: 9374575 No abstract available.

Factors in Neonatal Resistance to Anoxia. I. Temperature and Survival of Newborn Guinea Pigs Under Anoxia.

Miller JA.Science. 1949 Jul 29;110(2848):113-4. doi: 10.1126/science.110.2848.113.PMID: 17780238 No abstract available.


MILLER JA Jr, MILLER FS, WESTIN B.Biol Neonat. 1964;6:148-63. doi: 10.1159/000239893.PMID: 14136494 No abstract available.

School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term.

Robertson CM, Finer NN, Grace MG.J Pediatr. 1989 May;114(5):753-60. doi: 10.1016/s0022-3476(89)80132-5.PMID: 2469789

Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants.

Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R.Early Hum Dev. 1991 May;25(2):135-48. doi: 10.1016/0378-3782(91)90191-5.PMID: 1713544

Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia.

Coimbra C, Wieloch T.Acta Neuropathol. 1994;87(4):325-31. doi: 10.1007/BF00313599.PMID: 8017166

Keeping a cool head, post-hypoxic hypothermia--an old idea revisited.

Thoresen M, Wyatt J.Acta Paediatr. 1997 Oct;86(10):1029-33. doi: 10.1111/j.1651-2227.1997.tb14799.x.PMID: 9350876 Review.

Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep.

Gunn AJ, Gunn TR, Gunning MI, Williams CE, Gluckman PD.Pediatrics. 1998 Nov;102(5):1098-106. doi: 10.1542/peds.102.5.1098.PMID: 9794940

Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants.

Shankaran S, Laptook A, Wright LL, Ehrenkranz RA, Donovan EF, Fanaroff AA, Stark AR, Tyson JE, Poole K, Carlo WA, Lemons JA, Oh W, Stoll BJ, Papile LA, Bauer CR, Stevenson DK, Korones SB, McDonald S.Pediatrics. 2002 Aug;110(2 Pt 1):377-85. doi: 10.1542/peds.110.2.377.PMID: 12165594 Clinical Trial.

Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.

Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH; National Institute of Child Health and Human Development Neonatal Research Network.N Engl J Med. 2005 Oct 13;353(15):1574-84. doi: 10.1056/NEJMcps050929.PMID: 16221780 Free article. Clinical Trial.

Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial.

Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ.Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.PMID: 15721471 Clinical Trial.

Moderate hypothermia to treat perinatal asphyxial encephalopathy.

Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group.N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854.PMID: 19797281 Free article. Clinical Trial.

Hypothermia: a systematic review and meta-analysis of clinical trials.

Shah PS.Semin Fetal Neonatal Med. 2010 Oct;15(5):238-46. doi: 10.1016/j.siny.2010.02.003. Epub 2010 Mar 7.PMID: 20211588 Review.

Cooling neonates who do not fulfil the standard cooling criteria - short- and long-term outcomes.

Smit E, Liu X, Jary S, Cowan F, Thoresen M.Acta Paediatr. 2015 Feb;104(2):138-45. doi: 10.1111/apa.12784. Epub 2014 Sep 29.PMID: 25164710

Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial.

Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Grisby C, Huitema CM, Garg M, Ehrenkranz RA, Shepherd EG, Chalak LF, Hamrick SE, Khan AM, Reynolds AM, Laughon MM, Truog WE, Dysart KC, Carlo WA, Walsh MC, Watterberg KL, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.JAMA. 2014 Dec 24-31;312(24):2629-39. doi: 10.1001/jama.2014.16058.PMID: 25536254 Free PMC article. Clinical Trial.

Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial.

Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Huitema CMP, Grisby C, Devaskar U, Ehrenkranz RA, Harmon HM, Chalak LF, DeMauro SB, Garg M, Hartley-McAndrew ME, Khan AM, Walsh MC, Ambalavanan N, Brumbaugh JE, Watterberg KL, Shepherd EG, Hamrick SEG, Barks J, Cotten CM, Kilbride HW, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.JAMA. 2017 Jul 4;318(1):57-67. doi: 10.1001/jama.2017.7218.PMID: 28672318 Free PMC article. Clinical Trial.

Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial.

Laptook AR, Shankaran S, Tyson JE, Munoz B, Bell EF, Goldberg RN, Parikh NA, Ambalavanan N, Pedroza C, Pappas A, Das A, Chaudhary AS, Ehrenkranz RA, Hensman AM, Van Meurs KP, Chalak LF, Khan AM, Hamrick SEG, Sokol GM, Walsh MC, Poindexter BB, Faix RG, Watterberg KL, Frantz ID 3rd, Guillet R, Devaskar U, Truog WE, Chock VY, Wyckoff MH, McGowan EC, Carlton DP, Harmon HM, Brumbaugh JE, Cotten CM, Sánchez PJ, Hibbs AM, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.JAMA. 2017 Oct 24;318(16):1550-1560. doi: 10.1001/jama.2017.14972.PMID: 29067428 Free PMC article. Clinical Trial.

Cooling infants with mild hypoxic ischaemic encephalopathy- Do we have the evidence?

Buchiboyina A, Yip CSA, Mehta S.J Matern Fetal Neonatal Med. 2022 Dec;35(25):8511-8513. doi: 10.1080/14767058.2021.1986481. Epub 2021 Oct 6.PMID: 34612151 No abstract available.

Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis.

Kariholu U, Montaldo P, Markati T, Lally PJ, Pryce R, Teiserskas J, Liow N, Oliveira V, Soe A, Shankaran S, Thayyil S.Arch Dis Child Fetal Neonatal Ed. 2020 Mar;105(2):225-228. doi: 10.1136/archdischild-2018-315711. Epub 2018 Dec 19.PMID: 30567775 Free article.

Treating Hypoxic Ischemic Encephalopathy With Hypothermia Jose M. R. Perez, MD; Alexander Feldman, DO; Gad Alpan, MD, MBA. Neoreviews (2015) 16 (7): e413–e419.

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