Слайд 14JAMA. 2017 Oct 24;318(16):1550-1560. doi: 10.1001/jama.2017.14972.
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 AR1, Shankaran S2, Tyson JE3, Munoz B4, Bell EF5, Goldberg RN6, Parikh NA7, Ambalavanan N8, Pedroza C3, Pappas A2, Das A9, Chaudhary AS10, Ehrenkranz RA11, Hensman AM1, Van Meurs KP12,13, Chalak LF14, Khan AM3, Hamrick SEG15, Sokol GM16, Walsh MC17, Poindexter BB7,16, Faix RG18, Watterberg KL19, Frantz ID 3rd20, Guillet R21, Devaskar U22, Truog WE23,24, Chock VY12,13, Wyckoff MH14, McGowan EC1, Carlton DP15, Harmon HM16, Brumbaugh JE5, Cotten CM6, Sánchez PJ25, Hibbs AM17, Higgins RD26; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.
Author information
Erratum in Author Added to Byline. [JAMA. 2018]
IMPORTANCE: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours.
OBJECTIVE: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy.
DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size.
INTERVENTIONS: Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C).
MAIN OUTCOMES AND MEASURES: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization.
RESULTS: Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively.
CONCLUSIONS AND RELEVANCE: Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.
TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT00614744.
Comment in Bayesian Analysis: Using Prior Information to Interpret the Results of Clinical Trials. [JAMA. 2017]
PMID: 9067428 PMCID: PMC5783566 DOI: 10.1001/jama.2017.14972
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