Department of Palliative Medicine, University of Bristol, Bristol Oncology and Haematology Centre, Bristol BS2 8ED, UK.
Palliat Med. 2011 Jul;25(5):525-52. doi: 10.1177/0269216311406313.
Opioid use in patients with renal impairment can lead to increased adverse effects. Opioids differ in their effect in renal impairment in both efficacy and tolerability. This systematic literature review forms the basis of guidelines for opioid use in renal impairment and cancer pain as part of the European Palliative Care Research Collaborative's opioid guidelines project.
The objective of this study was to identify and assess the quality of evidence for the safe and effective use of opioids for the relief of cancer pain in patients with renal impairment and to produce guidelines.
The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MedLine, EMBASE and CINAHL were systematically searched in addition to hand searching of relevant journals.
Studies were included if they reported a clinical outcome relevant to the use of selected opioids in cancer-related pain and renal impairment. The selected opioids were morphine, diamorphine, codeine, dextropropoxyphene, dihydrocodeine, oxycodone, hydromorphone, buprenorphine, tramadol, alfentanil, fentanyl, sufentanil, remifentanil, pethidine and methadone. No direct comparator was required for inclusion. Studies assessing the long-term efficacy of opioids during dialysis were excluded.
This is a narrative systematic review and no meta-analysis was performed. The Grading of RECOMMENDATIONS Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of the studies and to formulate guidelines.
Fifteen original articles were identified. Eight prospective and seven retrospective clinical studies were identified but no randomized controlled trials. No results were found for diamorphine, codeine, dihydrocodeine, buprenorphine, tramadol, dextropropoxyphene, methadone or remifentanil.
All of the studies identified have a significant risk of bias inherent in the study methodology and there is additional significant risk of publication bias. Overall evidence is of very low quality. The direct clinical evidence in cancer-related pain and renal impairment is insufficient to allow formulation of guidelines but is suggestive of significant differences in risk between opioids.
RECOMMENDATIONS regarding opioid use in renal impairment and cancer pain are made on the basis of pharmacokinetic data, extrapolation from non-cancer pain studies and from clinical experience. The risk of opioid use in renal impairment is stratified according to the activity of opioid metabolites, potential for accumulation and reports of successful or harmful use. Fentanyl, alfentanil and methadone are identified, with caveats, as the least likely to cause harm when used appropriately. Morphine may be associated with toxicity in patients with renal impairment. Unwanted side effects with morphine may be satisfactorily dealt with by either increasing the dosing interval or reducing the 24 hour dose or by switching to an alternative opioid.
在肾功能损害患者中使用阿片类药物会导致不良反应增加。阿片类药物在疗效和耐受性方面对肾功能损害的影响存在差异。本系统文献综述是制定阿片类药物在肾功能损害和癌症疼痛中使用指南的基础，该指南是欧洲姑息治疗研究协作组织阿片类药物指南项目的一部分。
本研究旨在确定和评估安全有效使用阿片类药物缓解肾功能损害相关癌症疼痛的证据质量，并制定指南。
除了手检相关期刊外，还对 Cochrane 系统评价数据库、Cochrane 对照试验中心注册库、MedLine、EMBASE 和 CINAHL 进行了系统检索。
如果研究报告了与选定阿片类药物在癌症相关疼痛和肾功能损害中的使用相关的临床结局，则纳入研究。选定的阿片类药物包括吗啡、海洛因、可待因、右丙氧芬、二氢可待因、羟考酮、氢吗啡酮、丁丙诺啡、曲马多、阿芬太尼、芬太尼、舒芬太尼、瑞芬太尼、哌替啶和美沙酮。纳入研究不要求有直接比较。排除评估阿片类药物在透析期间长期疗效的研究。
这是一篇叙述性系统综述，未进行荟萃分析。采用推荐评估、制定与评价分级（GRADE）方法评估研究质量并制定指南。
确定了 15 篇原始文章。确定了 8 项前瞻性研究和 7 项回顾性临床研究，但没有随机对照试验。未发现海洛因、可待因、二氢可待因、丁丙诺啡、曲马多、右丙氧芬、美沙酮或瑞芬太尼的相关结果。
所有确定的研究都存在固有研究方法学偏倚的显著风险，并且存在额外的发表偏倚显著风险。总体证据质量非常低。在癌症相关疼痛和肾功能损害方面的直接临床证据不足以制定指南，但表明阿片类药物之间存在风险差异。
根据药代动力学数据、非癌症疼痛研究的推断以及临床经验，对肾功能损害和癌症疼痛中的阿片类药物使用提出建议。根据阿片类药物代谢产物的活性、潜在蓄积和成功或有害使用的报告，对肾功能损害中阿片类药物使用的风险进行分层。芬太尼、阿芬太尼和美沙酮被确定为在适当使用时最不可能造成伤害的药物，但有警告。吗啡在肾功能损害患者中可能与毒性有关。吗啡的不良反应如果增加给药间隔、减少 24 小时剂量或改用其他阿片类药物可能会得到满意的处理。
