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 postoperative requirements for opioid analgesic medication. To determine whether NSAIDs potentiate the respiratory effects of opioids, we studied the effects of ketoprofen (K), an NSAID, on respiratory depression induced by morphine (M) in volunteers. After ethics committee approval, 12 healthy 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, CO2 rebreathing challenges for ventilatory and occlusion pressure responses to CO2 were performed immediately before and 10, 70, 130, 190, and 250 min after drug infusion over 10 min. Venous blood samples for plasma drug concentrations were withdrawn at the same times. Comparisons were made on slopes of ventilatory and occlusion pressure responses to CO2. Venous blood samples confirmed that morphine plasma concentrations were similar when subjects had received morphine alone and when they had received the combination of drugs. Morphine alone induced a respiratory depression with a decrease in both ventilatory and occlusion pressure responses to CO2. Ketoprofen alone did not produce any respiratory effects. The combination of drugs induced a decrease in ventilatory 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, respiratory depression was less marked with the combination of drugs than with morphine alone. Therefore, ketoprofen may reduce the respiratory depression induced by morphine.