title: A systematic review of the use of opioids in the management of dyspnoea.
abstract: BACKGROUND
  Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this.
  
  
  METHODS
  The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using meta-regression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented.
  
  
  RESULTS
  Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis.
  
  
  CONCLUSIONS
  This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.
authors.affiliation: Department of Palliative Medicine, The North London Hospice and Barnet and Chase Farm Hospitals NHS Trust, London N12 8TF, UK. cbaxter@northlondonhospice.co.uk
authors.forename: A-L
authors.initials: AL
authors.lastname: Jennings
authors.forename: A N
authors.initials: AN
authors.lastname: Davies
authors.forename: J P T
authors.initials: JP
authors.lastname: Higgins
authors.forename: J S R
authors.initials: JS
authors.lastname: Gibbs
authors.forename: K E
authors.initials: KE
authors.lastname: Broadley
mesh_terms: D000284:Administration, Oral; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D006801:Humans; D007263:Infusions, Parenteral; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis
chemical_list: D009294:Narcotics