亚低温辅助治疗重型颅脑损伤临床效果的Meta分析

Meta-analysis of the effect of therapeutic hypothermia on severe brain injury

目的总结国内、外亚低温辅助治疗重型颅脑损伤的研究结果,采用Meta分析方法综合评价亚低温辅助治疗重型颅脑损伤的临床效果,探讨应用亚低温治疗重型颅脑损伤的可行性。方法制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Ovid、Springer和中国期刊全文数据库等,获得亚低温辅助治疗重型颅脑损伤的临床文献。使用国际Cochrane中心推荐的方法进行文献质量评价后,采用Review Manager4.22软件对满足纳入标准的有关亚低温治疗重型颅脑损伤效果的RCT研究进行Meta分析。选取颅内压(ICP)和预后作为观察指标,得出合并后ICP的加权均数差(WMD)、疗效的优势比(OR)及两者95%置信区间(CI)进行定性、定量综合评估。结果共检索出1028篇文献,符合纳入标准的11篇RCT研究进入Meta分析,纳入研究均未采用盲法,漏斗图检验未发现发表偏倚。Meta分析结果显示,治疗后24h亚低温组(n=741)ICP显著低于对照组(n=743),7项RCT研究,ICP21.32mmHgvs25.60mmHg,WMD=-4.57,95%CI:-4.96^-4.18,P<0.00001(1mmHg=0.133kPa);治疗后72h亚低温组(n=677)ICP显著低于对照组(n=671),6项RCT研究,ICP18.51mmHgvs24.24mmHg,WMD=-5.04,95%CI:-5.36^-4.72,P<0.00001;治疗后7d亚低温组(n=677)ICP显著低于对照组(n=671),6项RCT研究,ICP14.16mmHgvs21.05mmHg,WMD=-6.99,95%CI:-7.32^-6.67,P<0.00001;有11项研究报道了亚低温组(n=903)和对照组(n=908)患者的预后情况,8项研究随访3个月至6年,Meta分析结果显示,亚低温治疗后患者的预后优于对照组(58.1%vs37.7%,OR=2.40,95%CI:1.97~2.92,P<0.00001),剔除没有明确随访时间的RCT研究,进行敏感度分析,发现结果不变(53.9%vs35.4%,OR=2.18,95%CI:1.75~2.71,P<0.00001)。结论在重型颅脑损伤常规治疗的基础上,采用亚低温辅助治疗可减轻患者颅内高压,改善患者预后。

Objective Hypothermia has been used to treat severe brain injury. However, there is controversy about its therapeutic effect. In this article, we summarized the studies of mild hypothermia in the management of severe brain injury. Using meta-analysis method, we assessed the effect of hypothermia on severe brain injury. Methods PubMed, EMBASE, Ovid, Springer and CNKI database were searched by using the terms Hypothermia and Severe Brain Injury for human clinical trials, including unpublished documents from scientific meetings and theses, and the similar documents listed in the reference of above documents were also included. All of the randomized controlled trials were included, which compared hypothermia with routine therapy for the treatment of patients with severe brain injury. Two reviewers independently performed data extraction and appraised using Juni instrument. Disagreements were resolved by consensus. Double data were input and analyzed by software of Review Manager 4.22, recommended by Cochrane Collaboration. Intracranial pressure （ICP） and outcome of patients were selected to evaluate the combined WMD and OR value and 95% confidence interval （CI） of them. Results Eleven randomized controlled, but non-blind trials were included, involving 1 811 patients. Publication bias was not found through funnel plot analysis. There were 7 publications that reported the change of ICP, including 741 patients in the hypothermia group and 743 in the routine therapy group. Compared to the routine therapy, hypothermia could significantly degrade the ICP of patients after treatment 24 h （WMD = -4.57,95%CI： -4.96～ -4. 18, P〈0.00001 ）,72h（WMD= -5.04,95%CI： -5.36～ -4.72,P〈0.00001） and7d（ WMD = - 6.99, 95 % CI ： - 7.32～ - 6.67, P 〈 0. 000 01 ）, respectively. There are 11 publications reported the prognosis of patients who were treated with hypothermia therapy （ n = 903 ） or routine therapy （ n = 908 ）. The duration of follow-up was from 3 months to 6 years. Compared to the patients with routine therapy, the prognosis of patients with hypothermia therapy was significantly improved. （OR=2.40, 95%CI： 1.97 -2.92, P〈0.000 01）. Conclusions The therapy with hypothermia can degrade the ICP of patients with severe brain injury and improve the prognosis of these patients.