Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation.
Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation.
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DOI：
10.1016/j.brainres.2015.12.034
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发表时间：
2016-06-01
期刊：
影响因子：
2.9
通讯作者：
Bramlett HM
中科院分区：
文献类型：
--
作者：
Dietrich WD;Bramlett HM
治疗性低温（TH）和靶向温度管理（TTM）用于严重创伤性脑损伤（TBI）已在各种临床前和临床情况下进行了测试。早期的临床前研究表明，中度至重度TBI后脑温的轻度降低可改善组织病理学结局并减少神经功能缺损。调查研究还报告了创伤后温度的降低减弱了多种继发性损伤机制，包括兴奋性毒性、自由基产生、凋亡性细胞死亡和炎症。此外，虽然创伤后体温升高加剧了继发性损伤机制，但在受伤患者中成功实施TTM策略以减轻发热负担似乎是有益的。虽然TH已经在一些单一机构的TBI临床研究中成功地进行了测试，但更大规模的随机多中心试验未能证明治疗性低温的益处。TH和TTM用于治疗TBI的使用继续发展，包括患者选择和TH的时间在内的许多因素似乎在成功的试验设计中至关重要。根据现有的数据，很明显，TH和TTM策略治疗严重受伤的患者是一个重要的治疗考虑，需要更多的基础和临床研究。目前的研究涉及替代冷却策略的评估，包括药理学诱导的低温和TH或TTM方法与更具选择性的神经保护或修复治疗的组合。本文总结了临床前和临床文献，强调脑温度在修改继发性损伤机制和改善严重损伤患者创伤结局方面的重要性。
The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induce hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients.