Effect of Low Dose Nebulised Morphine on Exercise Endurance in Patients with Chronic Lung Disease

Low dose nebulised morphine may relieve dyspnoea through a direct effect on lung afferent nerves. To study this further 11 adult patients with advanced chronic lung disease (FEV1 range 0.4-1.41), whose exercise endurance was limited by dyspnoea, were entered into a double blind, randomised, crossover study in which low dose morphine or a placebo was inhaled. The effects were assessed by an endurance exercise test at 80% of maximum work load. One hour after a control endurance test patients inhaled 5 ml of morphine 1 mg/ml or isotonic saline for 12 minutes from a jet nebuliser. An endurance exercise test was repeated 15 minutes later and change in endurance time recorded. The two endurance tests were repeated on a separate day, before and after inhalation of the alternative solution. In all tests 100% oxygen was inhaled from a demand valve. The mean (SD) increase in endurance time was significantly greater after the subjects had inhaled morphine (64.6 (115) s, 35%) than after placebo (8.9 (55) s, 0.8%; p less than 0.01). The mean dose of morphine nebulised was 1.7 (0.66) mg, giving a mean inhaled dose of about 0.6 mg, on the assumption of 30% retention of the nebulised dose by each patient. No side effects were reported. Possibly small amounts of morphine delivered to the lungs act directly on lung afferent nerves to reduce dyspnoea.