title: A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Palliative Medicine, University of Bristol, Bristol Oncology and Haematology Centre, Bristol BS2 8ED, UK. sjk21@doctors.net.uk
authors.forename: S
authors.initials: S
authors.lastname: King
authors.forename: K
authors.initials: K
authors.lastname: Forbes
authors.forename: G W
authors.initials: GW
authors.lastname: Hanks
authors.forename: C J
authors.initials: CJ
authors.lastname: Ferro
authors.forename: E J
authors.initials: EJ
authors.lastname: Chambers
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005060:Europe; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D000701:Analgesics, Opioid