Canadian Journal of Anesthesia, Vol 31, 36-43, Copyright © 1984 by Canadian Anesthesiologists' Society

Effect of Cimetidine Premedication on Morphine-Induced Ventilatory Depression

¹ Department of Anaesthesia, University Hospital and University of Western Ontario, London

Address correspondence to: A.M. Lam MD, Department of Anaesthesia, University Hospital, P.O. Box 5339, Postal Stn. A., London, Canada N6A 5A5.

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.

Key Words: ANALGESICS: morphine • PREMEDICATION: cimetidine • VENTILATION: carbon dioxide response • INTERACTIONS (DRUGS): morphine, cimetidine