Lack of effect of high doses of inhaled morphine on exercise endurance in chronic obstructive pulmonary disease

Systemic opiates may relieve dyspnoea and improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Small doses of inhaled opiates may have similar effects; however, recent studies have shown no benefit. We studied higher doses of inhaled morphine and measured systemic absorption to determine whether any beneficial actions are local or systemic. Twenty and 40 mg doses and 0.9% saline were nebulized in a randomized, double-blind study of 16 patients with stable COPD. Patients performed 6 min walk tests immediately after the nebulized test solution (Walk 1) and again 60 min later (Walk 2). Arterial oxygen saturation (Sa,O2), modified Borg dyspnoea score and cardiac frequency were recorded during each walk. There was no difference between placebo and either dose of nebulized morphine on these measurements. The higher dose of nebulized morphine achieved a higher plasma concentration. The highest plasma concentration was measured immediately after nebulization, and this decreased steadily in the hour thereafter (p<0.002). There was no correlation between the change in walk distance and the change in plasma morphine concentration after either dose of nebulized morphine. We conclude that higher doses of nebulized morphine do not improve exercise endurance or relieve dyspnoea in patients with chronic obstructive pulmonary disease, and that morphine is rapidly absorbed systemically after inhalation.