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. Design Randomised, double blind, placebo controlled crossover study. Setting Four Outpatient clinics at a hospital in South Australia. Participants 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. Main outcome measures Dyspnoea in the morning and evening as shown on a 100 turn 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 upsilon 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.