Moore R Andrew, McQuay Henry J
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospital, Oxford, UK.
Arthritis Res Ther. 2005;7(5):R1046-51. doi: 10.1186/ar1782. Epub 2005 Jun 28.
Adverse events of opioids may restrict their use in non-cancer pain. Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder. To examine the incidence of common adverse events of opioids in non-cancer pain, a systematic review and meta-analysis of information from randomised trials of all opioids in non-cancer pain was undertaken. Studies used were published randomised trials of oral opioid in non-cancer pain, with placebo or active comparator. Thirty-four trials with 5,546 patients were included with 4,212 patients contributing some information on opioid adverse events. Most opioids used (accounting for 90% of patients) were for treating moderate rather than severe pain. Including trials without a placebo increased the amount of information available by 1.4 times. Because of clinical heterogeneity in condition, opioid, opioid dose, duration, and use of titration, only broad results could be calculated. Use of any oral opioid produced higher rates of adverse events than did placebo. Dry mouth (affecting 25% of patients), nausea (21%), and constipation (15%) were the most common adverse events. A substantial proportion of patients on opioids (22%) withdrew because of adverse events. Because most trials were short, less than four weeks, and because few titrated the dose, these results have limited applicability to longer-term use of opioids in clinical practice. Suggestions for improved studies are made.
阿片类药物的不良事件可能会限制其在非癌性疼痛中的应用。对非癌性疼痛试验中常见不良事件发生率的分析通常仅限于根据世界卫生组织三阶梯止痛法用于治疗重度疼痛的阿片类药物。为了研究阿片类药物在非癌性疼痛中常见不良事件的发生率,我们对所有用于非癌性疼痛的阿片类药物随机试验的信息进行了系统评价和荟萃分析。纳入的研究为已发表的非癌性疼痛中口服阿片类药物的随机试验,有安慰剂或活性对照。纳入了34项试验,共5546例患者,其中4212例患者提供了一些关于阿片类药物不良事件的信息。大多数使用的阿片类药物(占患者的90%)用于治疗中度而非重度疼痛。纳入无安慰剂的试验使可用信息量增加了1.4倍。由于病情、阿片类药物、阿片类药物剂量、疗程和滴定使用方面存在临床异质性,只能计算出大致结果。使用任何口服阿片类药物产生不良事件的发生率均高于安慰剂。口干(影响25%的患者)、恶心(21%)和便秘(15%)是最常见的不良事件。相当一部分服用阿片类药物的患者(22%)因不良事件而退出。由于大多数试验时间较短,不足四周,且很少进行剂量滴定,这些结果在临床实践中对阿片类药物长期使用的适用性有限。文中还提出了改进研究的建议。