纳洛酮治疗前阿片类药物治疗持续时间是腹泻的显著独立危险因素：一项回顾性队列研究。

Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study.

作者信息

Okamoto Akiharu, Ikemura Kenji, Mizutani Eri, Iwamoto Takuya, Okuda Masahiro

机构信息

Department of Pharmacy, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Department of Clinical Pharmaceutics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

出版信息

J Pharm Health Care Sci. 2021 Feb 1;7(1):3. doi: 10.1186/s40780-020-00187-3.

DOI:10.1186/s40780-020-00187-3

PMID:33517900

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7849155/

Abstract

BACKGROUND

The most common adverse event (AE) associated with opioid analgesics is opioid-induced constipation (OIC). Naldemedine (NAL) is widely used for the treatment of OIC. However, diarrhea has been reported as the most common treatment-emergent AE of NAL, and little is known about the risk factors associated with the development of diarrhea during NAL administration. This study examined the risk factors for NAL-induced diarrhea via a retrospective chart review of hospitalized patients.

METHODS

The data of 101 hospitalized adult patients who received NAL for the first time for the treatment of OIC at Mie University Hospital between June 2017 and December 2018 were extracted from electronic medical records. According to the inclusion and exclusion criteria, 70 of the 101 patients were enrolled in this study. Diarrhea was defined as "diarrhea" on the medical record within 2 weeks of NAL administration. Univariate and multivariate analyses were performed to identify risk factors for the development of diarrhea in patients receiving NAL.

RESULTS

Twenty-two of the 70 patients enrolled (31%) developed diarrhea within 2 weeks of NAL administration. The median duration (range) of NAL treatment before diarrhea onset was 3 (1-12) days. Patients with diarrhea had a significantly longer duration of opioid therapy before NAL administration than patients without diarrhea (P=0.002). Multivariate logistic regression analysis indicated that the independent risk factors for the development of NAL-induced diarrhea were NAL administration after more than 17 days of opioid therapy (odds ratio [OR]=7.539; P=0.016) and pancreatic cancer (OR=6.217; P=0.025). In fact, the incidence of diarrhea in patients who were administered NAL within a day of opioid therapy was significantly lower than that in patients who were administered NAL after more than 17 days of opioid therapy (13% vs. 54%, P=0.030).

CONCLUSIONS

These results suggested that a prolonged duration of opioid therapy prior to NAL initiation is associated with increased incidence of diarrhea.

摘要

背景

与阿片类镇痛药相关的最常见不良事件（AE）是阿片类药物引起的便秘（OIC）。纳洛酮（NAL）被广泛用于治疗OIC。然而，腹泻已被报道为NAL最常见的治疗中出现的AE，关于NAL给药期间腹泻发生的相关危险因素知之甚少。本研究通过对住院患者的回顾性病历审查来研究NAL引起腹泻的危险因素。

方法

从电子病历中提取2017年6月至2018年12月在三重大学医院首次接受NAL治疗OIC的101例住院成年患者的数据。根据纳入和排除标准，101例患者中的70例纳入本研究。腹泻定义为在NAL给药后2周内病历上记录为“腹泻”。进行单因素和多因素分析以确定接受NAL治疗的患者发生腹泻的危险因素。

结果

纳入的70例患者中有22例（31%）在NAL给药后2周内出现腹泻。腹泻发作前NAL治疗的中位持续时间（范围）为3（1 - 12）天。腹泻患者在NAL给药前的阿片类药物治疗持续时间明显长于无腹泻患者（P = 0.002）。多因素逻辑回归分析表明，NAL引起腹泻的独立危险因素是阿片类药物治疗超过17天后给予NAL（比值比[OR] = 7.539；P = 0.016）和胰腺癌（OR = 6.217；P = 0.025）。事实上，在阿片类药物治疗1天内给予NAL的患者腹泻发生率明显低于在阿片类药物治疗超过17天后给予NAL的患者（13%对54%，P = 0.030）。