Therapeutic hypothermia was a mainstay of severe traumatic brain injury (TBI) management for half a century. Recent trials have suggested that its effect on long-term functional outcome is neutral or negative, despite apparently promising pre-clinical data. Systematic review and meta-analysis is a useful tool to collate experimental data and investigate the basis of its conclusions. We searched three online databases to identify studies testing systemic hypothermia as monotherapy for treatment of animals subjected to a TBI. Data pertaining to TBI paradigm, animal subjects, and hypothermia management were extracted as well as those relating to risk of bias. We pooled outcome data where sufficient numbers allowed and investigated heterogeneity in neurobehavioral outcomes using multi-variate meta-regression. We identified 90 publications reporting 272 experiments testing hypothermia in animals subject to TBI. The subjects were mostly small animals, with well-established models predominating. Target temperature was comparable to clinical trial data but treatment was initiated very early. Study quality was low and there was some evidence of publication bias. Delay to treatment, comorbidity, and blinded outcome assessment appeared to predict neurobehavioral outcome on multi-variate meta-regression. Therapeutic hypothermia appears to be an efficacious treatment in experimental TBI, which differs from the clinical evidence. The pre-clinical literature showed limitations in quality and design and these both appeared to affect neurobehavioral experiment outcome. These should be acknowledged when designing and interpreting pre-clinical TBI studies in the future.

中文翻译：

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实验性创伤性脑损伤中低温的系统回顾和荟萃分析：为什么有希望的动物研究没有在实用的临床试验中复制？

半个世纪以来，治疗性低温是严重创伤性脑损伤 (TBI) 管理的支柱。最近的试验表明，尽管临床前数据明显有希望，但它对长期功能结果的影响是中性或负面的。系统评价和荟萃分析是整理实验数据和研究其结论基础的有用工具。我们搜索了三个在线数据库，以确定测试全身低温作为治疗 TBI 动物的单一疗法的研究。提取与 TBI 范式、动物受试者和体温过低管理有关的数据以及与偏倚风险相关的数据。我们汇集了足够数量的结果数据，并使用多变量元回归研究了神经行为结果的异质性。我们确定了 90 份出版物，报告了 272 项测试 TBI 动物体温过低的实验。受试者主要是小动物，以完善的模型为主。目标温度与临床试验数据相当，但治疗很早就开始了。研究质量低，有一些发表偏倚的证据。延迟治疗、合并症和盲法结果评估似乎可以预测多变量元回归的神经行为结果。治疗性低温似乎是实验性 TBI 的有效治疗方法，这与临床证据不同。临床前文献显示质量和设计存在局限性，这些似乎都会影响神经行为实验结果。