Does late therapeutic hypothermia reduce risk of death or disability?
Does late therapeutic hypothermia reduce risk of death or disability?
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晚期低温治疗是否会降低死亡或残疾的风险？
DOI：
10.1111/apa.14334
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Dietz,RobertM
中科院分区：
文献类型：
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作者：
Bourque,StephanieL;Dietz,RobertM
缺氧缺血性脑病（HIE），也称为新生儿脑病，每1000例活产婴儿中估计有1-3例足月婴儿受到影响，并导致显著的长期发病率和死亡率（1）。几项临床试验评估了使用治疗性低温（TH），在出生后6小时内开始将核心体温冷却至33-34 ℃持续72小时，已经证明了在18-22个月时减少中度至重度残疾或死亡的益处（2）。因此，TH已成为HIE婴儿的标准护理。虽然动物研究已经证明了6小时之前开始的早期冷却的上级治疗效果（3），但并非所有符合条件的婴儿都在这个理想的时间范围内开始TH。Laptook及其同事的这项随机临床试验招募了符合TH临床或实验室标准的婴儿，但在随机化时年龄在6至24小时之间（4）。婴儿接受全身冷却至目标核心温度33.5 ℃（范围33-34 ℃），持续96小时。与标准的72小时相比，选择更长的冷却时间是因为之前的数据表明，更长的低温对于神经保护是必要的，尽管最近这一点被反驳了（5）。这项研究的结果表明，在> 6小时的年龄开始低温的益处远小于更早开始低温的益处，这得到了临床前数据的支持。然而，尽管大多数患者在随机分组时年龄> 12小时，但贝叶斯分析表明，尽管随机分组时TH组的癫痫发作负担增加，但TH仍有小幅获益。加之缺乏增加院内严重不良反应的治疗
Hypoxic-ischemic encephalopathy (HIE), also known as neonatal encephalopathy, affects an estimated 1-3 term infants per 1000 live births and leads to significant long-term morbidity and mortality (1). Several clinical trials evaluating the use of therapeutic hypothermia (TH), cooling the core body temperature to 33-34 C for 72 hours, initiated within 6 hours of birth, have demonstrated benefit with decreased moderate-severe disability or death at 18-22 months (2). As such, TH for infants with HIE has become standard of care. While animal studies have demonstrated superior treatment effect with early cooling initiated prior to 6 hours of age (3), not all eligible infants undergo initiation of TH within this ideal timeframe.This randomized clinical trial by Laptook and colleagues enrolled infants who met clinical or laboratory criteria for TH, but who were between 6 and 24 hours of age at time of randomization (4). Infants underwent whole body cooling to a goal core temperature of 33.5 C (range 33-34 C) for 96 hours. This longer cooling time, compared to the standard 72 hours, was chosen due to previous data suggesting that longer hypothermia was necessary for neuroprotection, although this has been recently refuted (5). The results of this study suggest that the benefit of beginning hypothermia> 6 hours of age is much less than starting it earlier which is supported by preclinical data. However, despite most of the patients being> 12 hours of age at randomization, there was still a small benefit to TH, indicated by Bayesian analysis, despite an increased seizure burden in the TH group at randomization. Combined with the lack of increased serious in-hospital adverse effects in the treatment