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Meta-analysis of targeted temperature management in animal models of cardiac arrest
Intensive Care Medicine Experimental Pub Date : 2020-01-17 , DOI: 10.1186/s40635-019-0291-9
Hilmer Olai 1 , Gustav Thornéus 1 , Hannah Watson 2, 3 , Malcolm Macleod 4 , Jonathan Rhodes 5 , Hans Friberg 6 , Niklas Nielsen 7 , Tobias Cronberg 8 , Tomas Deierborg 1
Affiliation  

Background Targeted temperature management (TTM) of 32 to 34 °C has been the standard treatment for out-of-hospital cardiac arrest since clinical trials in 2002 indicated benefit on survival and neurological outcome. In 2013, a clinical trial showed no difference in outcome between TTM of 33 °C and TTM of 36 °C. In this meta-analysis, we investigate the evidence for TTM in animal models of cardiac arrest. Methods We searched PubMed and EMBASE for adult animal studies using TTM as a treatment in different models of cardiac arrest or global brain ischemia which reported neurobehavioural outcome, brain histology or mortality. We used a random effects model to calculate estimates of efficacy and assessed risk of bias using an adapted eight-item version of the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) quality checklist. We also used a scoring system based on the recommendations of the Stroke Treatment Academic Industry Roundtable (STAIR), to assess the scope of testing in the field. Included studies which investigated a post-ischemic induction of TTM had their treatment regimens characterized with regard to depth, duration and time to treatment and scored against the modified STAIR criteria. Results The initial and updated search generated 17809 studies after duplicate removal. One hundred eighty-one studies met the inclusion criteria, including data from 1,787, 6,495 and 2,945 animals for neurobehavioural, histological and mortality outcomes, respectively. TTM was favoured compared to control for all outcomes. TTM was beneficial using short and prolonged cooling, deep and moderate temperature reduction, and early and delayed time to treatment. Median [IQR] study quality was 4 [3 to 6]. Eighteen studies checked seven or more of the eight CAMARADES quality items. There was no clear correlation between study quality and efficacy for any outcome. STAIR analysis identified 102 studies investigating post-ischemic induction of TTM, comprising 147 different treatment regimens of TTM. Only 2 and 8 out of 147 regimens investigated comorbid and gyrencephalic animals, respectively. Conclusions TTM is beneficial under most experimental conditions in animal models of cardiac arrest or global brain ischemia. However, research on gyrencephalic species and especially comorbid animals is uncommon and a possible translational gap. Also, low study quality suggests risk of bias within studies. Future animal research should focus on mimicking the clinical scenario and employ similar rigour in trial design to that of modern clinical trials.

中文翻译:

心脏骤停动物模型中靶向温度管理的荟萃分析

背景 32 至 34 °C 的目标温度管理 (TTM) 一直是院外心脏骤停的标准治疗方法,因为 2002 年的临床试验表明对生存和神经系统结果有益。2013 年,一项临床试验表明,33 °C 的 TTM 和 36 °C 的 TTM 之间的结果没有差异。在这项荟萃分析中,我们调查了心脏骤停动物模型中 TTM 的证据。方法 我们在 PubMed 和 EMBASE 中搜索了成年动物研究,这些研究使用 TTM 作为报告神经行为结果、脑组织学或死亡率的不同心脏骤停或全脑缺血模型的治疗方法。我们使用随机效应模型来计算疗效估计值并使用经过改编的八项版本的实验研究动物数据元分析和审查协作方法 (CAMARADES) 质量清单评估偏倚风险。我们还使用了基于中风治疗学术行业圆桌会议 (STAIR) 建议的评分系统,以评估该领域的测试范围。纳入的研究缺血后诱导 TTM 的治疗方案在深度、持续时间和治疗时间方面具有特征,并根据修改后的 STAIR 标准进行评分。结果 去除重复项后,最初和更新的搜索产生了 17809 项研究。181 项研究符合纳入标准,包括来自 1,787、6,495 和 2,945 只动物的神经行为、分别为组织学和死亡率结果。与所有结果的对照相比,TTM 更受欢迎。TTM 使用短期和长期冷却、深度和适度降温以及早期和延迟治疗是有益的。中位数 [IQR] 研究质量为 4 [3 至 6]。十八项研究检查了八个 CAMRADES 质量项目中的七个或更多。对于任何结果,研究质量和疗效之间没有明确的相关性。STAIR 分析确定了 102 项研究 TTM 缺血后诱导的研究,包括 147 种不同的 TTM 治疗方案。147 个方案中只有 2 个和 8 个分别调查了共病和回脑动物。结论 TTM 在心脏骤停或全脑缺血动物模型的大多数实验条件下是有益的。然而,对 gyrencephalic 物种,尤其是共病动物的研究并不常见,并且可能存在转化空白。此外,低研究质量表明研究存在偏倚风险。未来的动物研究应侧重于模拟临床场景,并在试验设计中采用与现代临床试验相似的严谨性。
更新日期:2020-01-17
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