Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy A Randomized 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
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DOI：
10.1001/jama.2017.14972
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发表时间：
2017-10-24
影响因子：
120.7
通讯作者：
Higgins, Rosemary D.
中科院分区：
文献类型：
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作者：
Laptook, Abbot R.;Shankaran, Seetha;Higgins, Rosemary D.
重要性出生后6小时内开始的低温可减少妊娠36周或更晚的缺氧缺血性脑病婴儿的死亡或残疾。据我们所知，低温试验尚未在婴儿出生后6小时内进行。目的：评估在出生后6至24小时内进行低温治疗可降低缺氧缺血性脑病婴儿18个月时死亡或残疾风险的可能性。和参与者2008年4月至2016年6月期间，在妊娠36周或更晚患有中度或重度缺氧的婴儿中进行了一项随机临床试验-缺血性脑病在出生后6至24小时入组。21个美国新生儿研究网络中心参与了研究。鉴于预期的样本量有限，预先指定了贝叶斯分析。干预对168名婴儿使用了目标食道温度。83名体温过低的婴儿在33.5摄氏度（可接受的范围，33摄氏度-34摄氏度）下保持96小时，然后复温。85名未冷却的婴儿维持在37.0摄氏度（可接受的范围，36.5摄氏度至37.3摄氏度）。在18至22个月时，根据脑病水平和随机化时的年龄进行调整。（平均值[SD]，分别为39 [2]和39 [1]周妊娠），83例患者中分别有47例（57%）和85例患者中分别有55例（65%）为男性。两组在出生时都是酸血症，主要是转移到治疗中心的中度脑病，并在平均（SD）16（5）和15（5）小时分别随机分为低温组和非冷却组。主要结局发生在78例低体温婴儿中的19例（24.4%）和79例未冷却婴儿中的22例（27.9%）（绝对差异，3.5%; 95%CI，-1%至17%）。使用中性先验的贝叶斯分析表明，相对于非冷却组，低温导致死亡或残疾的后验概率降低了76%（调整后验风险比为0.86; 95%可信区间为0.58-1.29）。冷却婴儿死亡或残疾的概率至少比非冷却婴儿低1%、2%或3%，分别为71%、64%和56%.CONCLUSIONS AND RELEVANCE在患有缺氧缺血性脑病的足月婴儿中，出生后6 ~ 24小时开始的低温与非冷却婴儿相比，导致死亡或残疾减少的概率为76%，在18到22个月时，死亡或残疾至少减少2%的概率为64%。出生后6至24小时开始的低温可能有益，但其有效性尚不确定。
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 hypothermiainitiated 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 degrees C (acceptable range, 33 degrees C-34 degrees C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0 degrees C (acceptable range, 36.5 degrees C-37.3 degrees 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.