Abu-Amara Mahmoud, Gurusamy Kurinchi Selvan, Glantzounis George, Fuller Barry, Davidson Brian R
University Department of Surgery, Royal Free Hospital and University College School of Medicine, 9th Floor, Royal Free Hospital, Pond Street, London, UK, NW3 2QG.
Cochrane Database Syst Rev. 2009 Oct 7;2009(4):CD008154. doi: 10.1002/14651858.CD008154.
Vascular occlusion used during elective liver resection to reduce blood loss results in significant ischaemia reperfusion (IR) injury. This in turn leads to significant postoperative liver dysfunction and morbidity. Various pharmacological drugs have been used in experimental settings to ameliorate the ischaemia reperfusion injury in liver resections.
To assess the relative benefits and harms of using one pharmacological intervention versus another pharmacological intervention to decrease ischaemia reperfusion injury during liver resections where vascular occlusion was performed during the surgery.
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until January 2009.
We included randomised clinical trials, irrespective of language or publication status, comparing one pharmacological agent versus another pharmacological agent during elective liver resections with vascular occlusion.
Two authors independently identified trials for inclusion and independently extracted data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. We planned to calculate the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis or available case analysis. However, all outcomes were only reported on by single trials, and meta-analysis could not be performed. Therefore, we performed Fisher's exact test on dichotomous outcomes.
We identified a total of five randomised trials evaluating nine different pharmacological interventions (amrinone, prostaglandin E1, pentoxifylline, dopexamine, dopamine, ulinastatin, gantaile, sevoflurane, and propofol). All trials had high risk of bias. There was no significant difference between the groups in mortality, liver failure, or perioperative morbidity. The ulinastatin group had significantly lower postoperative enzyme markers of liver injury compared with the gantaile group. None of the other comparisons showed any difference in any of the other outcomes. However, there is a high risk of type I and type II errors because of the few trials included, the small sample size in each trial, and the risk of bias.
AUTHORS' CONCLUSIONS: Ulinastatin may have a protective effect against ischaemia reperfusion injury relative to gantaile in elective liver resections performed under vascular occlusion. The absolute benefit of this drug agent remains unknown. None of the drugs can be recommended for routine clinical practice. Considering that none of the drugs have proven to be useful to decrease ischaemia reperfusion injury, such trials should include a group of patients who do not receive any active intervention whenever possible to determine the pharmacological drug's absolute effects on ischaemia reperfusion injury in liver resections.
择期肝切除术中采用血管阻断以减少失血会导致显著的缺血再灌注（IR）损伤。这进而会导致严重的术后肝功能障碍和发病率增加。在实验环境中，已使用各种药物来减轻肝切除术中的缺血再灌注损伤。
评估在手术中进行血管阻断的肝切除术中，使用一种药物干预与另一种药物干预来减少缺血再灌注损伤的相对益处和危害。
我们检索了Cochrane肝胆组对照试验注册库、Cochrane图书馆中的Cochrane对照试验中央注册库（CENTRAL）、MEDLINE、EMBASE和科学引文索引扩展版，检索截止至2009年1月。
我们纳入了随机临床试验，无论语言或发表状态如何，比较在择期肝切除术中进行血管阻断时一种药物与另一种药物的疗效。
两位作者独立确定纳入的试验并独立提取数据。我们使用RevMan分析软件，采用固定效应模型和随机效应模型对数据进行分析。我们计划根据意向性分析或现有病例分析计算风险比（RR）或均值差（MD）及其95%置信区间（CI）。然而，所有结局仅由单个试验报告，无法进行荟萃分析。因此，我们对二分法结局进行了Fisher精确检验。
我们共识别出五项随机试验，评估了九种不同的药物干预措施（氨力农、前列腺素E1、己酮可可碱、多培沙明、多巴胺、乌司他丁、甘泰莱、七氟烷和丙泊酚）。所有试验均存在高偏倚风险。各治疗组在死亡率、肝衰竭或围手术期发病率方面无显著差异。与甘泰莱组相比，乌司他丁组术后肝损伤酶标志物显著更低。其他任何比较在任何其他结局方面均未显示出差异。然而，由于纳入试验较少、每个试验样本量较小以及存在偏倚风险，存在I型和II型错误的高风险。
在血管阻断下进行的择期肝切除术中，相对于甘泰莱，乌司他丁可能对缺血再灌注损伤具有保护作用。该药物的绝对益处尚不清楚。没有一种药物可推荐用于常规临床实践。鉴于没有一种药物已被证明对减少缺血再灌注损伤有用，此类试验应尽可能纳入一组未接受任何积极干预的患者，以确定该药物对肝切除术中缺血再灌注损伤的绝对影响。
