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肾功能损害癌症患者中阿片类药物的使用——一项系统评价

The use of opioids in cancer patients with renal impairment-a systematic review.

作者信息

Sande Tonje A, Laird Barry J A, Fallon Marie T

机构信息

Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Edinburgh Cancer Research Centre (CR UK Building), Western General Hospital, Crewe Road, Edinburgh, EH4 2XR, UK.

出版信息

Support Care Cancer. 2017 Feb;25(2):661-675. doi: 10.1007/s00520-016-3447-0. Epub 2016 Oct 15.

Abstract

PURPOSE

Opioids are recommended for moderate to severe cancer pain; however, in patients with cancer, impaired renal function can affect opioid metabolism. The aim of this systematic review was to evaluate the current evidence for the use of opioids in cancer patients with renal impairment.

METHODS

A systematic review was conducted and the following databases were searched: MEDLINE (1966 to 2015), EMBASE (1980 2015) and Cochrane Central Register of Controlled Trials (up to 2015). Eligible studies met the following criteria: patients with cancer pain taking an opioid (defined as per the WHO ladder); >18 years; renal impairment (serum creatinine > normal range (study dependent), creatinine clearance (CrCl) or glomerular filtration rate (GFR) measurements <90 ml/min, or as per the study definition); clinical outcome related to renal impairment. All eligible studies were appraised using the Grading of Recommendation Assessment, Development and Evaluations (GRADE) system.

RESULTS

Eighteen studies (n = 2422) were eligible but heterogeneity meant meta-analysis was not possible. Morphine was examined in eight studies (n = 1418), oxycodone in two studies (n = 325), and fentanyl, alfentanil or sufentanil were discussed in six studies in total (n = 442). No recommendations could be formulated on the preferred opioid in patients with renal impairment.

CONCLUSION

There is lack of consensus within the existing literature on the relationship between morphine, creatinine levels and morphine-related side effects. Based on the current evidence, morphine should be used with caution; however, more evidence is needed. Fentanyl, alfentanil and sufentanil are recommended in patients with renal impairment based on pharmacokinetics and clinical experience. However, the present systematic review found very little clinical evidence for this. Overall, the quality of the existing evidence on opioid treatment in cancer patients with renal impairment is low. There remains a need for high-quality clinical studies examining opioids in patients with renal impairment.

摘要

目的

阿片类药物被推荐用于中度至重度癌痛;然而,癌症患者的肾功能受损会影响阿片类药物的代谢。本系统评价的目的是评估目前关于在肾功能受损的癌症患者中使用阿片类药物的证据。

方法

进行了一项系统评价,并检索了以下数据库:MEDLINE(1966年至2015年)、EMBASE(1980年至2015年)和Cochrane对照试验中心注册库(截至2015年)。符合条件的研究满足以下标准:患有癌痛且正在服用阿片类药物的患者(根据世界卫生组织阶梯定义);年龄>18岁;肾功能损害(血清肌酐>正常范围(取决于研究)、肌酐清除率(CrCl)或肾小球滤过率(GFR)测量值<90 ml/分钟,或根据研究定义);与肾功能损害相关的临床结局。所有符合条件的研究均使用推荐分级评估、制定和评价(GRADE)系统进行评估。

结果

18项研究(n = 2422)符合条件,但异质性意味着无法进行荟萃分析。八项研究(n = 1418)对吗啡进行了研究,两项研究(n = 325)对羟考酮进行了研究,六项研究(总共n = 442)讨论了芬太尼、阿芬太尼或舒芬太尼。对于肾功能受损患者的首选阿片类药物,无法提出建议。

结论

现有文献中关于吗啡、肌酐水平与吗啡相关副作用之间的关系缺乏共识。基于目前的证据,应谨慎使用吗啡;然而,还需要更多证据。基于药代动力学和临床经验,建议肾功能受损患者使用芬太尼、阿芬太尼和舒芬太尼。然而,本系统评价发现这方面的临床证据很少。总体而言,现有关于肾功能受损的癌症患者阿片类药物治疗的证据质量较低。仍然需要高质量的临床研究来研究肾功能受损患者使用阿片类药物的情况。

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