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Dyspnoea is a disabling and distressing problem for many patients and carers. Clinicians are often reluctant to prescribe opioids for such patients because of concerns of adverse effects—particularly respiratory depression and sedation—and paucity of evidence of clinical benefit.
Abernethy and colleagues conducted a small (n = 48) double blind, placebo controlled, crossover study. Patients, most of whom had chronic obstructive pulmonary disease (n = 42), were randomised to receive 20 mg/day sustained release morphine or identical placebo. No washout period between the 4 day treatment periods was employed, although the authors acknowledge some carryover effect in patients receiving morphine first in sequence. Patients reported significantly less dyspnoea according to a visual analogue scale and had less sleep disturbance when using active treatment. More patients experienced constipation when receiving morphine, while no differences in other adverse effects, including sedation and depressed respiratory rate, were observed between treatments. The study concluded that sustained release morphine was useful in relieving refractory dyspnoea with reassuring data concerning adverse effects other than troublesome constipation. The authors comment that opioids should be used with caution as the study was not sufficiently powered to detect significant differences in adverse effects.
Although limited by the small number of patients completing the study (n = 38) and uncertain clinical significance of observed effects upon the visual analogue scale, this study provides reassuring evidence of the potential benefits of opioids in relieving intractable dyspnoea. This short trial should pave the way for further large scale studies to investigate the optimum dose of sustained release morphine and to identify which patients benefit most, while also incorporating a rigorous evaluation of adverse effects.