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.

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 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.

Figures

Figure 1

Flow of participants through the trial

Figure 2

Frequency of constipation throughout the treatment periods, by treatment intervention. Data are presented as the percentage of participants indicating each categorical response on each day of the treatment period. Placebo responses are divided between participants who received placebo during the first period (first placebo, then morphine) or the second period (first morphine, then placebo) to show carry over effects