Effect of cimetidine premedication on morphine-induced ventilatory depression

The potential respiratory interaction between morphine and cimetidine was studied by determining resting ventilation, PETCO2 and ventilatory response to added carbon dioxide in eight healthy volunteers on three separate occasions following administration of : (1) cimetidine 600 mg p.o., (2) morphine 10 mg IM, (3) morphine 10 mg IM preceded by cimetidine 600 mg p.o. Individual entry into the study was randomized and separated by at least one week. All measurements were determined at time 0, 30, 60, 120, 180, 240, 360, 480, 600, 720 minutes and at the end of 24 hours. In addition, serum morphine levels were measured in six subjects during the first six hours following morphine administration. Cimetidine alone had negligible respiratory effects. Morphine alone reduced resting ventilation, elevated PETCO2 and reduced the ventilatory response to added CO2, while the morphine-cimetidine combination caused a more profound depression of the CO2 response and delay in its recovery. No significant difference between resting ventilation and PETCO2 was observed. We conclude that cimetidine premedication interacts with morphine to prolong the respiratory depression but the magnitude of this interaction is small and clinically insignificant in healthy subjects. Caution, however, should be exercised in susceptible patients.