甲基纳曲酮治疗阿片类药物所致便秘的疗效与安全性：一项随机对照试验的荟萃分析
Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials.
作者信息
Zhang Ying-Ying, Zhou Rong, Gu Wan-Jie
机构信息
Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
出版信息
Pain Ther. 2021 Jun;10(1):165-179. doi: 10.1007/s40122-021-00237-0. Epub 2021 Feb 11.
INTRODUCTION
Opioid-induced constipation (OIC) is a distressing side effect during opioid analgesia and is mainly mediated by gastrointestinal μ-opioid receptors. Methylnaltrexone, a peripheral μ-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may alleviate OIC without reversing analgesia. We performed a meta-analysis to assess the efficacy and safety of methylnaltrexone for the treatment of OIC.
METHODS
This meta-analysis was registered in PROSPERO (CRD42020187290). We searched PubMed, Embase, and Cochrane Library for randomized controlled trials that compared methylnaltrexone with placebo for the treatment of OIC. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model. We used the GRADE approach to assess the certainty of the evidence.
RESULTS
Eight trials with 2034 participants were included. Compared with placebo, methylnaltrexone significantly increased rescue-free bowel movement (RFBM) within 4 h after the first dose (eight trials; 1833 participants; RR 3.74, 95% CI 3.02-4.62; high-certainty evidence), RFBM within 24 h after the first dose (two trials; 614 participants; RR 1.98, 95% CI 1.52-2.58; moderate-certainty evidence), and RFBM ≥ 3 times per week (three trials; 1,396 participants; RR 1.33, 95% CI 1.17-1.52; moderate-certainty evidence) and decreased need to take rescue laxatives (three trials; 807 participants; RR 0.73, 95% CI 0.63-0.85; moderate-certainty evidence). For safety outcomes, there was no difference in any adverse events between the two groups (eight trials; 2034 participants; RR 1.11, 95% CI 0.99-1.23; moderate-certainty evidence), including diarrhea, nausea, vomiting, and flatulence; but for the most commonly reported adverse events, the abdominal pain was higher in methylnaltrexone group than that in placebo group (six trials; 1813 participants; RR 2.30, 95% CI 1.29-4.08; moderate-certainty evidence).
CONCLUSION
Methylnaltrexone is an effective and safe drug for the treatment of OIC, but the safety of abdominal pain should be considered.
引言
阿片类药物引起的便秘（OIC）是阿片类镇痛期间令人苦恼的副作用，主要由胃肠道μ-阿片受体介导。甲基纳曲酮是一种外周μ-阿片受体拮抗剂，穿过血脑屏障的能力有限，可缓解OIC而不逆转镇痛作用。我们进行了一项荟萃分析，以评估甲基纳曲酮治疗OIC的疗效和安全性。
方法
该荟萃分析已在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42020187290）登记。我们检索了PubMed、Embase和Cochrane图书馆，查找比较甲基纳曲酮与安慰剂治疗OIC的随机对照试验。使用随机效应模型汇总相对风险（RR）和95%置信区间（CI）。我们采用GRADE方法评估证据的确定性。
结果
纳入了8项试验，共2034名参与者。与安慰剂相比，甲基纳曲酮显著增加了首剂后4小时内无补救措施的排便次数（RFBM）（8项试验；1833名参与者；RR 3.74，95%CI 3.02 - 4.62；高确定性证据）、首剂后24小时内的RFBM（2项试验；614名参与者；RR 1.98，95%CI 1.52 - 2.58；中等确定性证据）以及每周RFBM≥3次（3项试验；1396名参与者；RR 1.33，95%CI 1.17 - 1.52；中等确定性证据），并减少了使用补救性泻药的需求（3项试验；807名参与者；RR 0.73，95%CI 0.63 - 0.85；中等确定性证据）。对于安全性结局，两组之间在任何不良事件上均无差异（8项试验；2034名参与者；RR 1.11，95%CI 0.99 - 1.23；中等确定性证据），包括腹泻、恶心、呕吐和气胀；但对于最常报告的不良事件，甲基纳曲酮组的腹痛高于安慰剂组（6项试验；1813名参与者；RR 2.30，95%CI 1.29 - 4.08；中等确定性证据）。
结论
甲基纳曲酮是治疗OIC的一种有效且安全的药物，但应考虑腹痛方面的安全性。
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