The Effects of a Nonsteroidal Antiinflammatory Drug (Ketoprofen) on Morphine Respiratory Depression

Abstract

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 Venous blood samples for plasma drug concentrations were withdrawn at the same times.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.

Cellular Actions Of Opioids And Other Analgesics: Implications For Synergism In Pain Relief

“…This general principle has already been established in postoperative pain, where combined administration of NSAID enhance the analgesic efficacy of opioids 1,2 but, if anything, reduce the severity of respiratory depression. 31 The findings also suggest new avenues for development of medications involving combinations of lowered doses of opioids and specific 5-LOX inhibitors. Such combinations have the potential to reduce the side effects commonly experienced when using powerful opioid analgesics, such as morphine.…”

Continuous spinal anaesthesia/analgesia for the perioperative management of high-risk patients

“…Local anaesthetic agents combined with opioids intrathecally may act synergistically and produce good surgical anaesthesia and excellent postoperative analgesia, thus reducing the total dose of each drug [20][21][22][23]. Similarly, the different sites of analgesic action found with NSAIDs and opioids also suggest additive, or possibly even synergistic effects, and in clinical practice they are often used in combination [24,25]. The opioid-sparing effect of NSAIDs may lead to a reduction in opioid-induced side-effects.…”

Special aspects of cancer pain management in a Chinese general hospital

“…Another survey was carried out in 29 provinces/ municipalities of China, with 933 Chinese health professionals, of whom 819 were physicians. The survey showed that they rated the top two barriers to optimal cancer management as a fear of opioid addiction and the overly restrictive regulations about opioids (Moren et al, 1997).…”