【评论】直肠切除术前机械肠道准备加口服抗生素术后吻合口漏和总体并发症的发生率(MOBILE2试验):一项随机对照试验

[Comment]Morbidity after mechanical bowel preparation and oral antibiotics prior to rectal resection:the MOBILE2 randomized clinical trial

背景手术部位感染,尤其是吻合口漏,是直肠切除术后发病率和死亡率的主要影响因素。机械肠道准备加口服抗生素在预防直肠切除术后并发症的作用目前存在争议。目的评估与机械肠道准备加安慰剂相比,机械肠道准备加口服抗生素是否使择期直肠切除术后的吻合口漏和总体并发症的发生率降低。方法这是一项多中心、双盲、安慰剂对照的随机对照临床试验,于2020年3月18日至2022年10月10日进行。参与者包括来自芬兰3所大学医院的因直肠肿瘤(MRI提示肿瘤距离肛缘15 cm以下)而计划行择期直肠前切除术合并一期吻合(包括结肠—直肠吻合以及结肠—肛门吻合)的患者,分为机械肠道准备加口服抗生素组(机械肠道准备+口服抗生素)和机械肠道准备组(机械肠道准备+口服安慰剂),并根据肿瘤的距离和是否接受新辅助治疗划分亚组。机械肠道准备包含嘱患者服用2 L聚乙二醇和至少1 L的清流质饮食,可在术前2天的下午3点开始实施,于术前1天下午3点完成。完成机械肠道准备后,机械肠道准备加口服抗生素组患者被指导在术前1天下午3点和晚上11点口服1 g新霉素和1 g甲硝唑。机械肠道准备组患者在同一时间服用安慰剂。所有患者围手术期预防性静脉使用抗生素(头孢呋辛1.5 g,甲硝唑500 mg;3例因过敏使用其他抗生素)。主要终点是术后30天内综合并发症指数。次要终点是术后30天内手术部位感染和吻合口漏的数量和分类。结果565例患者最终分别纳入机械肠道准备组【n=288;中位年龄69(62,74)岁;男性190例(66.0%)和女性98例(34.0%)】和机械肠道准备加口服抗生素组【n=277;中位年龄70(62,75)岁;男性158例(57.0%)和女性119例(43.0%)】。与机械肠道准备组相比,机械肠道准备加口服抗生素组患者的综合并发症指数更小【0(0,8.66)vs.8.66(0,20.92),P<0.001】,手术部位感染发生率更低(8.3%vs.16.7%,OR=0.45,95%CI为0.27~0.77),吻合口漏发生率更低(5.8%vs.13.5%,OR=0.39,95%CI为0.21~0.72)。结论在接受择期直肠切除术的患者中,采用机械肠道准备加口服抗生素术后总体并发症、手术部位感染和吻合口漏发生率更低。机械肠道准备加口服抗生素应被视为择期直肠切除术患者的标准护理方案。

Importance Surgical site infections(SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection.The role of mechanical and oral antibiotics bowel preparation(MOABP)in preventing complications of rectal resection is currently disputed.Objective To assess whether MOABP reduces overall complications and SSIs after elective rectal resection compared with mechanical bowel preparation(MBP)plus placebo.Design,setting,and participants This multicenter,double-blind,placebo-controlled randomized clinical trial was conducted at 3 university hospitals in Finland between March 18,2020,and October 10,2022.Patients aged 18 years and older undergoing elective resection with primary anastomosis of a rectal tumor 15 cm or less from the anal verge on magnetic resonance imaging were eligible for inclusion.Outcomes were analyzed using a modified intention-to-treat principle,which included all patients who were randomly allocated to and underwent elective rectal resection with an anastomosis.Interventions Patients were stratified according to tumor distance from the anal verge and neoadjuvant treatment given and randomized in a 1:1 ratio to receive MOABP with an oral regimen of neomycin and metronidazole(n=277)or MBP plus matching placebo tablets(n=288).All study medications were taken the day before surgery,and all patients received intravenous antibiotics approximately 30 minutes before surgery.Main outcomes and measures The primary outcome was overall cumulative postoperative complications measured using the Comprehensive Complication Index.Key secondary outcomes were SSI and anastomotic dehiscence within 30 days after surgery.Results In all,565 patients were included in the analysis,with 288 in the MBP plus placebo group(IQR age,62-74 years;190 males[66.0%])and 277 in the MOABP group(IQR age,62-75 years;158 males[57.0%]).Patients in the MOABP group experienced fewer overall postoperative complications(IQR Comprehensive Complication Index,[0-8.66]vs.[0-20.92];Wilcoxon effect size,0.146;P<0.001),fewer SSIs(23 patients[8.3%]vs.48 patients[16.7%];odds ratio,0.45[95%CI,0.27-0.77]),and fewer anastomotic dehiscences(16 patients[5.8%]vs.39 patients[13.5%];odds ratio,0.39[95%CI,0.21-0.72])compared with patients in the MBP plus placebo group.Conclusions and relevance Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences in patients undergoing elective rectal resection compared with MBP plus placebo.Based on these findings,MOABP should be considered as standard treatment in patients undergoing elective rectal resection.