远隔缺血预处理对肝切除术患...果的系统评价与Meta分析_田春.pdf

版权归中国普通外科杂志所有http:/2023 年 1 月中国普通外科杂志Vol.32 No.1第 32 卷 第 1 期China Journal of General SurgeryJan.2023远隔缺血预处理对肝切除术患者干预效果的系统评价与Meta分析田春1，王爱华2，高苑淞1，邓小红2（1.重庆医科大学附属永川医院 麻醉科，重庆 402160；2.重庆市永川区人民医院 重症医学科，重庆 402160）摘 要 背景与目的：尽管大量的动物实验已证实远隔缺血预处理（RIPC）可显著改善肝切除术后残余肝早期的组织灌注和氧合作用，减少肝缺血-再灌注损伤（HIRI），改善手术预后，提高生存率。然而，在临床研究中关于RIPC减少HIRI的作用仍存在争议。因此，本研究通过Meta 分析评价RIPC在肝切除术中的有效性和安全性，为临床提供循证参考。方法：检索多个国内外文献数据库，收集评估RIPC策略有效性和安全性的随机对照试验（RCT），检索时间段为建库至 2022 年 5 月。对纳入的 RCT 进行质量评价，采用 Revman 5.3 统计软件进行分析。主要评价指标为术后肝功能指标、手术时间、术中出血量、住院时间、主要手术并发症。结果：共纳入 11 项 RCT，包含 851 例患者，其中 RIPC 组 422 例，对照组 429 例。Meta 分析结果显示，两组术前各项肝功能指标差异均无统计学意义（均P0.05）；术后第1天，RIPC组的丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）水平明显低于对照组（WMD=-74.92，95%CI=-126.18-23.67，P=0.004；WMD=-66.37，95%CI=-106.47-26.27，P=0.001），但各研究间有明显异质性（I2=98%，I2=95%），两组术后第 3、7 天 ALT 与 AST 水平差异均无统计学意义（均 P0.05），两组术后第 1、3、7 天的总胆红素、白蛋白水平差异均无统计学意义（均P0.05）；两组间其余评价指标差异均无统计学意义（均P0.05）。结论：RIPC应用于肝切除术中的临床获益有限，并不能减轻肝切除术后HIRI引起的肝损伤。但以上结论仍需要纳入更多高质量的多中心RCT研究加以验证。此外，目前所有临床研究都是在异丙酚麻醉或异丙酚复合吸入性麻醉下进行的，这也是一个争论的热点话题。关键词 肝切除术；再灌注损伤；缺血预处理；Meta分析中图分类号：R657.3A systematic review and Meta-analysis of the intervention effect of remote ischemic preconditioning on patients undergoing hepatectomyTIAN Chun1,WANG Aihua2,GAO Yuansong1,DENG Xiaohong2(1.Department of Anesthesiology,Yongchuan Hospital of Chongqing Medical University,Chongqing 402160,China;2.Department of Critical Care Medicine,Chongqing Yongchuan District Peoples Hospital,Chongqing 402160,China)专题研究 doi:10.7659/j.issn.1005-6947.2023.01.004China Journal of General Surgery,2023,32(1):48-63.http:/dx.doi.org/10.7659/j.issn.1005-6947.2023.01.004基金项目：重庆市永川区自然科学基金资助项目（Ycstc，2020nb0229）；重庆市科卫联合医学科研基金资助项目（2020FYYX033）。收稿日期：2022-05-24；修订日期：2022-07-20。作者简介：田春，重庆医科大学附属永川医院主治医师，主要从事临床麻醉与器官保护方面的研究。通信作者：邓小红，Email:48第 1 期田春，等：远隔缺血预处理对肝切除术患者干预效果的系统评价与Meta分析 版权归中国普通外科杂志所有http:/Abstract Background and Aims:Although many animal experiments have confirmed that remote ischemic preconditioning(RIPC)can significantly improve the early tissue perfusion and oxygenation of the residual liver after hepatectomy,reduce the hepatic ischemia-reperfusion injury(HIRI),accelerate the surgical prognosis,and improve the survival rate.However,there is still controversy over the role of RIPC in relieving HIRI in clinical studies.Therefore,this study was conducted to evaluate the efficacy and safety of RIPC in hepatectomy through Meta-analysis to provide evidence-based information for clinical decision-making.Methods:Randomized controlled trials(RCTs)evaluating the efficacy and safety of RIPC strategy were collected by searching several national and international literature databases.The search spanned the period from the inception of each database to May 2022.After data extraction and quality evaluation of the included studies,Meta-analysis was performed using RevMan 5.3 software.The main evaluation indicators were postoperative liver function parameters,operative time,intraoperative blood loss,length of postoperative hospital stay,and the major postoperative complications.Results:A total of 11 RCTs were included,involving 851 patients,with 422 cases in the RIPC group and 429 cases in the control group.The results of Meta-analysis showed that there was no significant difference in each liver function parameter before operation between the two groups(all P0.05);the levels of alanine transaminase(ALT)and aspartate transaminase(AST)on postoperative day(POD)1 were significantly lower in RIPC group than those in control group(WMD=-74.92,95%CI=-126.18-23.67,P=0.004;WMD=-66.37,95%CI=-106.47-26.27,P=0.001),but significant heterogeneity existed among the studies(I2=98%;I2=95%),there were no significant differences in ALT and AST levels on POD 3 and 7 between the two groups(all P0.05),and there were no significant differences in levels of total bilirubin and albumin on POD 1,3 and 7 between the two groups(all P0.05);no statistical differences were noted in other evaluation indicators between the two groups(all P0.05).Conclusion:The application of RIPC in hepatectomy offers limited clinical benefit and cannot alleviate liver injury caused by HIRI after hepatectomy.However,more high-quality multicenter RCT studies still need to verify the above conclusions.In addition,all current clinical studies are performed under propofol anesthesia or propofol combined with inhalation anesthesia,which is also a hot topic of debate.Key words Hepatectomy;Reperfusion Injury;Ischemic Preconditioning;Meta-AnalysisCLCCLC numbenumber r:R657.32020 年全球癌症监测数据1显示，肝癌发病率居全球恶性肿瘤第 5 位（发病率为 9.5/10 万），病死率却居所有恶性肿瘤第 3 位（病死率为 8.7/10 万）。目前，肝切除术仍是治疗原发性和继发性肝癌最基础有效的治疗方法，特别是对于早、中期局限性肝癌患者，可以将肿瘤完全切除而明显改善预后2-3。随着现代医学的发展，精准肝切除术日益成熟，但对麻醉和围术期管理也提出了更高要求4。在肝切除术中，外科医师和麻醉医师常分别借助入肝血流阻断（Pringle 手法）和限制性液体输入策略来实现控制性低中心静脉压（control low central venous pressure，CLCVP）状态，最终达到提供清晰手术视野和有效减少术中出血量的目的5。但上述策略往往会显著降低患者肝实质离断之前肝组织的灌注及氧合，引起残余肝脏的肝缺血-再灌 注 损 伤（hepatic ischemia-reperfusion injury，HIRI）6。HIRI 是肝切除术的主要并发症，也是导致术后肝功能衰竭的主要原因之一7。HIRI 主要通过激活肝 Kupffer 细胞、肝窦内皮细胞、肝星状细胞等释放大量炎症介质引发一系列炎症级联反应，进而导致肝细