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阿片类药物引起的肠道功能障碍的定义、诊断和治疗策略——北欧工作组的建议

Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction-Recommendations of the Nordic Working Group.

作者信息

Drewes Asbjørn M, Munkholm Pia, Simrén Magnus, Breivik Harald, Kongsgaard Ulf E, Hatlebakk Jan G, Agreus Lars, Friedrichsen Maria, Christrup Lona L

机构信息

Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark.

NOH (Nordsjællands Hospital) Gastroenterology, Denmark.

出版信息

Scand J Pain. 2016 Apr;11:111-122. doi: 10.1016/j.sjpain.2015.12.005. Epub 2016 Feb 4.

Abstract

BACKGROUND AND AIMS

Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth, gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications and treatment of OIBD.

METHODS

The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements.

RESULTS

The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered in this context. There are no available tools to assess OIBD, but many rating scales have been developed to assess constipation, and a few specifically address OIC. A clinical treatment strategy for OIBD/OIC was proposed and presented in a flowchart. First-line treatment of OIC is conventional laxatives, lifestyle changes, tapering the opioid dosage and alternative analgesics. Whilst opioid rotation may also improve symptoms, these remain unalleviated in a substantial proportion of patients. Should conventional treatment fail, mechanism-based treatment with opioid antagonists should be considered, and they show advantages over laxatives. It should not be overlooked that many reasons for constipation other than OIBD exist, which should be taken into consideration in the individual patient.

CONCLUSION AND IMPLICATIONS

It is the belief of this Nordic Working Group that increased awareness of adverse effects and OIBD, particularly OIC, will lead to better pain treatment in patients on opioid therapy. Subsequently, optimised therapy will improve quality of life and, from a socio-economic perspective, may also reduce costs associated with hospitalisation, sick leave and early retirement in these patients.

摘要

背景与目的

由于阿片类药物在全球范围内广泛用于止痛,阿片类药物引起的肠道功能障碍(OIBD)问题日益严重。它表现为多种不同症状,如口干、胃食管反流、呕吐、腹胀、腹痛、厌食、大便干结、便秘及排便不尽。阿片类药物引起的便秘(OIC)是其众多症状之一,可能也是最常见的症状。本综述阐述了OIBD的病理生理学、临床意义及治疗方法。

方法

成立了北欧工作组,为斯堪的纳维亚地区多个相关领域的专家提供参考意见。确定了七个主要主题及相关陈述。工作计划为系统评价提供了结构化格式,并包括了根据GRADE指南评估证据水平的说明。支持不同陈述的证据质量被评为高、中或低。在第二次会议上,小组对各部分进行了讨论并投票,并对陈述提出了(弱和强)建议。

结果

文献综述支持阿片受体在整个胃肠道均有表达这一事实。当被外源性阿片类药物阻断时,会出现运动、液体分泌与吸收以及括约肌功能的变化,这些变化反映在临床症状中。该小组支持最近关于OIC的共识声明,该声明考虑了至少一周的排便习惯改变,而不是关注排便频率。许多疼痛患者接受阿片类药物治疗,随之而来的便秘与发病率增加及医疗资源利用增多相关。急性术后疼痛的阿片类药物治疗会延长术后肠梗阻时间,在这种情况下也应予以考虑。目前尚无评估OIBD的可用工具,但已开发出许多评估便秘的量表,有一些专门针对OIC。提出了OIBD/OIC的临床治疗策略并以流程图形式呈现。OIC的一线治疗是使用传统泻药、改变生活方式、逐渐减少阿片类药物剂量及使用替代镇痛药。虽然阿片类药物轮换也可能改善症状,但仍有相当一部分患者症状未得到缓解。如果传统治疗失败,应考虑使用阿片类拮抗剂进行基于机制的治疗,与泻药相比,其具有优势。不应忽视的是,除了OIBD外,还有许多导致便秘的原因,在个体患者中应予以考虑。

结论与启示

该北欧工作组认为,提高对不良反应及OIBD(尤其是OIC)的认识,将使接受阿片类药物治疗的患者获得更好的疼痛治疗。随后,优化治疗将改善生活质量,从社会经济角度来看,还可能降低这些患者的住院、病假及提前退休相关成本。

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