Effect of morphine on breathlessness and exercise endurance in advanced COPD: a randomised crossover trial

The objective of the present study was to evaluate the effect of morphine on exertional breathlessness and exercise endurance in advanced chronic obstructive pulmonary disease (COPD). In a randomised crossover trial, we compared the acute effect of immediate-release oral morphine versus placebo on physiological and perceptual responses during constant-load cardiopulmonary cycle exercise testing (CPET) in 20 adults with advanced COPD and chronic breathlessness syndrome. Compared with placebo, morphine reduced exertional breathlessness at isotime by 1.2 +/- 0.4 Borg units and increased exercise endurance time by 2.5 +/- 0.9 min (both p <= 0.014). During exercise at isotime, morphine decreased ventilation by 1.3 +/- 0.5 L.min(-1) and breathing frequency by 2.0 +/- 0.9 breaths.min(-1) (both p <= 0.041). Compared with placebo, morphine decreased exertional breathlessness at isotime by >= 1 Borg unit in 11 participants (responders) and by <1 Borg unit in nine participants (non-responders). Baseline participant characteristics, including pulmonary function and cardiorespiratory fitness, were similar between responders and non-responders. A higher percentage of responders versus non-responders stopped incremental CPET due to intolerable breathlessness: 82 versus 33% (p=0.028). Immediate-release oral morphine improved exertional breathlessness and exercise endurance in some, but not all, adults with advanced COPD. The locus of symptom-limitation on laboratory-based CPET may help to identify patients most likely to benefit from morphine.