title: Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea.
abstract: OBJECTIVE
  To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated.
  
  
  METHODS
  Randomised, double blind, placebo controlled crossover study.
  
  
  METHODS
  Four outpatient clinics at a hospital in South Australia.
  
  
  METHODS
  48 participants who had not previously been treated with opioids (mean age 76, SD 5) with predominantly chronic obstructive pulmonary disease (42, 88%) were randomised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo, or vice versa. Laxatives were provided as needed.
  
  
  METHODS
  Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale, quality of sleep, wellbeing, performance on physical exertion, and side effects as measured at the end of the four day treatment period.
  
  
  RESULTS
  38 participants completed the study; three withdrew because of definite and two because of possible side effects of morphine (nausea, vomiting, and sedation). Participants reported significantly different dyspnoea scores when treated with morphine: an improvement of 6.6 mm (95% confidence interval 1.6 mm to 11.6 mm) in the morning and of 9.5 mm (3.0 mm to 16.1 mm) in the evening (P = 0.011 and P = 0.006, respectively). During the period in which they were taking morphine participants also reported better sleep (P = 0.039). More participants reported distressing constipation while taking morphine (9 v 1, P = 0.021) in spite of using laxatives. All other side effects were not significantly worse with morphine, although the study was not powered to address side effects.
  
  
  CONCLUSIONS
  Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting.
authors.affiliation: Department of Palliative and Supportive Services, Division of Medicine, Flinders University of South Australia, Bedford Park, South Australia 5042, Australia.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Abernethy
authors.forename: David C
authors.initials: DC
authors.lastname: Currow
authors.forename: Peter
authors.initials: P
authors.lastname: Frith
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Fazekas
authors.forename: Annie
authors.initials: A
authors.lastname: McHugh
authors.forename: Chuong
authors.initials: C
authors.lastname: Bui
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002908:Chronic Disease; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*
chemical_list: D003692:Delayed-Action Preparations; D009294:Narcotics; D009020:Morphine