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Systematic review
Use of opioids in patients with cancer with hepatic impairment—a systematic review
  1. Lewis Thomas Hughes1,
  2. David Raftery2,
  3. Paul Coulter3,
  4. Barry Laird1 and
  5. Marie Fallon1
  1. 1 Edinburgh Palliative and Supportive Care Team, The University of Edinburgh MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK
  2. 2 School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK
  3. 3 Ardgowan Hospice, Greenock, Inverclyde, UK
  1. Correspondence to Dr Lewis Thomas Hughes, Edinburgh Palliative and Supportive Care Team, The University of Edinburgh MRC Institute of Genetics and Molecular Medicine, Edinburgh EH8 9YL, UK; lewis.hughes5{at}nhs.scot

Abstract

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

Methods A systematic review was conducted and the following databases searched: AMED (−2021), MEDLINE (−2021), EMBASECLASSIC + EMBASE (−2021) and Cochrane Central Register of Controlled Trials (−2021). Eligible studies met the following criteria: patients with cancer-related pain, taking an opioid (as defined by the WHO Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents); >18 years of age; patients with hepatic impairment defined using recognised or study-defined definitions; clinical outcome hepatic impairment related; and primary studies. All eligible studies were appraised using the Grading of Recommendations Assessment, Development and Evaluation system.

Results Three studies (n=95) were eligible but heterogeneity meant meta-analysis was not possible. Each individual study focused on only one each of oxycodone±hydrocotarnine, oxycodone/naloxone and morphine. No recommendations could be formulated on the preferred opioid in patients with hepatic impairment.

Conclusions Morphine is the preferred opioid in hepatic impairment owing to clinical experience and pharmacokinetics. This review, however, found little clinical evidence to support this. Dose adjustments of morphine and the oxycodone formulations reviewed remain necessary in the absence of quality evidence. Overall, the quality of existing evidence on opioid treatments in cancer pain and hepatic impairment is low and there remains a need for high-quality clinical studies examining this.

  • cancer
  • pain
  • pharmacology
  • clinical decisions
  • chronic conditions

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/bmjspcare-2021-003065

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Twitter @lewyhughey

    • Contributors Professor MF was responsible for the conception of the subject of this paper. Planning was led by Professor MF, Dr BL and Dr LTH. Dr LTH formulated the search strategy with Mr DR and specific search strings with guidance from Dr BL. Dr LTH and Mr DR conducted independent reviews of all papers returned and agreed on final inclusion with all authors. Dr LTH led the manuscript writing with Mr DR, with overall support by Dr BL. All authors, including Dr PC, contributed to the manuscript writing and approved the final document. Dr LTH is responsible for the overall content.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.