Low-dose morphine ineffective for dyspnoea in COPD patients

Low-dose, extended-release morphine does not relieve severe breathlessness in people with COPD, an Australian study has shown.

A randomised controlled trial conducted at 20 Australian centres and involving 156 people with COPD and severe chronic breathlessness, found that daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after one week of treatment.

The Breathlessness, Exertion, And Morphine Sulfate (BEAMS) trial randomised participants to 8 mg or 16 mg/day of oral extended-release morphine or placebo during week one. At the start of weeks two and three, people were then either uptitrated with a further 8 mg/day of extended-release morphine, added to the prior week’s dose, or received placebo.

According to results published in JAMA (link here) among the 138 patients (88%) who completed treatment at week one, there was no significant change in the primary outcome of  intensity of worst breathlessness between either the 8 mg/day morphine group and the placebo group (mean difference, −0.3 [95% CI, −0.9 to 0.4]) or between the 16 mg/day of morphine group and the placebo group (mean difference, −0.3 [95%, CI, −1.0 to 0.4]).

For the secondary outcome of change in mean daily step count there was no significant difference at week three  between the 8 mg or the 16 mg/day of morphine groups and the placebo group, or between the 32 mg/day of morphine group and the placebo group (mean difference, −1924 [95% CI, −47 699 to 921]).

Similarly there were no differences in other secondary outcomes including symptoms, function, health-related quality of life, and physiological parameters (end-tidal partial pressure of carbon dioxide, oxygen saturation as measured by pulse oximetry, and respiratory rate).

The study investigators, including Dr David Currow from the Australian National Palliative Care Clinical Studies Collaborative, noted that the lack of efficacy was consistent across severities of breathlessness.

“These findings do not support the use of these doses of extended-release morphine to relieve breathlessness,” they wrote.

The study authors said the lack of change observed in step count did not support the hypothesis that the lack of efficacy on breathlessness was due to people increasing their physical activity, thereby masking a true symptom improvement.

They added that  study findings “may not be applicable to people with very advanced COPD and breathlessness who are in palliative care or near the end of life, at which time treatment with opioids may be useful to provide relief of severe dyspnoea.”

An accompanying editorial noted that extended-release opiates are typically reserved for patients with dyspnoea at rest, but most patients with COPD do not experience breathlessness at rest, even those with severe airflow obstruction measured by spirometry.

Since this was not reported in the study participants, ‘the absence of dyspnoea at rest would call into question the premise for use of daily long-acting opiates instead of rapid-onset, short-acting opiates as needed prior to planned exertion. Such a strategy would minimise the adverse events associated with opiate use,” the editorial said.

The author, Dr Richard Schwartzstein of Harvard Medical School, noted that pulmonary rehabilitation has been shown in multiple studies to improve exercise capacity and reduces dyspnoea in patients with COPD even though their lung function is not altered.

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