Low-dose morphine may do more harm than good for COPD patients with chronic breathlessness

Treatment with steady-state, low-dose morphine does not appear to improve sleep efficiency, sleep-disordered breathing frequency, or next-day alertness but may rather result in hypoventilation during sleep in chronic obstructive pulmonary disease (COPD) patients with chronic breathlessness, according to the results of a randomized, double-anonymized, crossover trial.

The study included 19 COPD patients experiencing breathlessness. They were randomly assigned to receive sustained-release morphine (20 mg/d for 3 days) (steady-state) or placebo. Sleep efficiency during in-laboratory overnight polysomnography was assessed as the primary outcome.

Other measures such as sleep-disordered breathing (events/h), oxygenation, transcutaneous CO₂ levels, blood and physiology biomarkers, the relationship between sleep and breathlessness, external resistive load responses, and driving simulator performance were delegated as secondary and exploratory outcomes.

Compared with placebo, morphine had no significant effect on sleep efficiency (66 percent vs 67 percent; p=0.89). Furthermore, morphine treatment did not reduce the frequency of sleep-disordered breathing events but instead led to a decrease in breathing frequency.

Morphine was associated with a 2-percent and 5-percent reduction in mean and nadir overnight oxygen saturation (95 percent confidence interval [CI], –2.8 to –1.2 and 95 percent CI, –8 to –1, respectively). Mean transcutaneous CO₂ during sleep with morphine was higher by 3.3 mm Hg (95 percent CI, 1.6–5.1) relative to sleep with placebo.

Nocturnal hypoventilation, as defined by the American Academy of Sleep Medicine criteria, was documented in eight participants (42 percent) with morphine and four (21 percent) with placebo (p=0.02). Morphine did not reduce breathlessness or negatively impact next-day driving simulator performance.

Adverse events occurred more frequently with morphine, the most common being nausea.