甲基纳曲酮
甲基纳曲酮是甲基化的纳曲酮,是一种非选择性阿片类受体拮抗剂。甲基化形态无法穿过血脑屏障,胃肠道吸收有限。主要经由肾脏排出。[36]Kraft MD. Emerging pharmacologic options for treating postoperative ileus. Am J Health-Syst Pharm. 2007;64:S13-S20.http://www.ncbi.nlm.nih.gov/pubmed/17909271?tool=bestpractice.com它已被证明可以增加阿片类药物相关便秘患者的胃肠动力,而对于术后肠梗阻的疗效还在研究中。一项对术后患者的研究发现甲基纳曲酮可以显著缩短胃排空和首次排便的时间,且无严重不良反应。[73]Viscusi E, Rathmell J, Fischera A, et al. A double-blind, randomized, placebo-controlled trial of methylnaltrexone for postoperative bowel dysfunction in segmental colectomy patients. Anesthesiology. 2005;103:A893.[74]US National Institutes of Health Clinical Trials. Study evaluating IV methylnaltrexone for the treatment of post operative ileus. July 2011. http://www.clinicaltrials.gov (last accessed 26 September 2017).http://clinicaltrials.gov/ct2/show/NCT00387309然而两项随机对照试验显示,使用甲基纳曲酮增强胃肠道功能恢复对预防或缩短术后肠梗阻的持续时间并无任何帮助。[75]Yu CS, Chun HK, Stambler N, et al. Safety and efficacy of methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy: results of two randomized, placebo-controlled phase 3 trials. Dis Colon Rectum. 2011;54:570-578.http://www.ncbi.nlm.nih.gov/pubmed/21471758?tool=bestpractice.com
比沙可啶
通便剂作为辅助疗法加快术后肠道功能恢复的相关研究甚少。一项包含 169 名患者的随机试验显示可加快术后患者 1 天的排便时间。而对于首次排气与耐受固体食物的间并无差异。研究群体中所报道的发病率和死亡率无显著差异。在本胃肠吻合术情况下,评估本疗法的疗效和安全性还需要进行更多的研究。[76]Zingg U, Miskovic D, Pasternak I, et al. Effect of bisacodyl on postoperative bowel motility in elective colorectal surgery: a prospective, randomized trial. Int J Colorectal Dis. 2008;23:1175-1183.http://www.ncbi.nlm.nih.gov/pubmed/18665373?tool=bestpractice.com
葛瑞林激动剂
葛瑞林是一种作用于近端胃肠道生长激素促分泌素受体的分子。此信号通路调节肠道动力、胃排空和迁移传动复合物。葛瑞林激动剂 ulimorelin (TZP-101) 是一种稳定化合物,已被证明在动物模型和胃轻瘫患者中有促进胃肠动力。一项多中心随机双盲安慰剂对照研究表明,相对于安慰剂组,术后使用该复合物的患者肠道功能恢复较快,并且可提早 20 小时出院。[77]Popescu I, Fleshner PR, Pezzullo JC, et al. The Ghrelin agonist TZP-101 for management of postoperative ileus after partial colectomy: a randomized, dose-ranging, placebo-controlled clinical trial. Dis Colon Rectum. 2010;53:126-134.http://www.ncbi.nlm.nih.gov/pubmed/20087086?tool=bestpractice.com然而,一项 meta 分析研究了葛瑞林激动剂(伊帕瑞林、ulimorelin、葛瑞林)的使用,结果发现其对于预防手术后肠梗阻无效。[34]Drake TM, Ward AE. Pharmacological management to prevent ileus in major abdominal surgery: a systematic review and meta-analysis. J Gastrointest Surg. 2016;20:1253-1264.http://www.ncbi.nlm.nih.gov/pubmed/27073081?tool=bestpractice.com