Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea.
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.
Abernethy
Amy P
AP
Department of Palliative and Supportive Services, Division of Medicine, Flinders University of South Australia, Bedford Park, South Australia 5042, Australia.
Currow
David C
DC
Frith
Peter
P
Fazekas
Belinda S
BS
McHugh
Annie
A
Bui
Chuong
C
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*
D003692:Delayed-Action Preparations; D009294:Narcotics; D009020:Morphine