THE EFFECTS OF A NONSTEROIDAL ANTIINFLAMMATORY DRUG (KETOPROFEN) ON MORPHINE RESPIRATORY DEPRESSION - A DOUBLE-BLIND, RANDOMIZED STUDY IN VOLUNTEERS

Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the postoperativ e requirements for opioid analgesic medication. To determine whether N SAIDs potentiate the respiratory effects of opioids, we studied the ef fects of ketoprofen (K), an NSAID, on respiratory depression induced b y morphine (M) in volunteers. After ethics committee approval, 12 heal thy male volunteers received infusions of K (1.5 mg/kg), M (0.1 mg/kg) , and KM (1.5 mg/kg + 0.1 mg/kg) in a double-blind, randomized, three- treatment, three-period cross-over trial. During the three sessions, C O2 rebreathing challenges for ventilatory and occlusion pressure respo nses to CO2 were performed immediately before and 10, 70, 130, 190, an d 250 min after drug infusion over 10 min. Venous blood samples for pl asma drug concentrations were withdrawn at the same times. Comparisons were made on slopes of ventilatory and occlusion pressure responses t o CO2. Venous blood samples confirmed that morphine plasma concentrati ons were similar when subjects had received morphine alone and when th ey had received the combination of drugs. Morphine alone induced a res piratory depression with a decrease in both ventilatory and occlusion pressure responses to CO2. Ketoprofen alone did not produce any respir atory effects. The combination of drugs induced a decrease in ventilat ory responses to CO2, but intergroup comparisons showed that this was significantly less marked than the decrease induced by morphine alone, in conclusion, for similar morphine plasma concentrations, respirator y depression was less marked with the combination of drugs than with m orphine alone. Therefore, ketoprofen may reduce the respiratory depres sion induced by morphine.