Journal: Br J Anaesth 101(4):542-548, 2008
Reprint: Department of Anaesthesiology, National Taiwan University Hospital, No. 7, Chung San South Road, Taipei, Taiwan, Republic of China (WZ Sun, MD) SO.05 JA0910/010 ©2009
Faculty Disclosure: Abstracted by S. Ouellette, who has nothing to disclose.
Nalbuphine is a mixed agonist-antagonist opioid. It derives its analgesic and sleep-producing effects through agonism at the kappa-opioid receptor. It also has the potential to attenuate the mu-opioid receptor-related adverse effects. Although morphine is the opioid most commonly used in patient-controlled analgesia (PCA), it may induce adverse events including pruritus, nausea, vomiting, constipation, urinary retention, respiratory depression, and drowsiness. Morphine binds most readily to the mu-opioid receptor and less well to the kappa-opioid receptor. This implies that the most undesirable adverse effects of morphine are from antagonism at the mu-receptor complex. Comparative trials have demonstrated that both morphine and nalbuphine are equally effective on pain relief.
Many drugs have been combined with morphine in PCA to augment analgesic effect or to reduce the adverse events. There is no report of the interaction between morphine and nalbuphine in IV PCA. Potency and clinical effect at the mu-receptor are different between morphine and nalbuphine. The goal of this study was to evaluate the interaction of combining different ratios of morphine and nalbuphine in IV PCA.
This randomized, double-blind controlled study investigated five different combining ratios of morphine and nalbuphine in 311 patients undergoing gynecologic operations. The concentrations (morphine mg/mL/nalbuphine mg/mL) were 1/0 in Group 1; 0.75/0.25 (ratio 3:1) in Group 2; 0.5/0.5 (ratio 1:1) Group 3; 0.25/0.75 (ratio 1:3) in Group 4; and 0/1 in Group 5. PCA requirement, postoperative pain, and adverse events were evaluated throughout the perioperative period.
Twenty-four hour PCA requirements were similar among the five groups. Verbal rating scores for pain were significantly higher in Groups 2 and 4 than in Group 3. The incidences of pruritus were higher in Group 1 (15.6%) than in Group 2 (6.2%), Group 3 (3.4%), Group 4 (1.6%), and Group 5 (0%). The incidence and severity of dizziness, nausea, and vomiting were not statistically significantly different.
The interaction between morphine and nalbuphine in PCA admixture on analgesia is additive. Combinations of morphine and nalbuphine in PCA can decrease the incidence of pruritus, and the antipruritus effect is ratio-dependent. This may provide a novel combination strategy of opioid agonist-antagonist for postoperative pain management after gynecologic surgery. |
