Combination of opioid agonist and agonist-antagonist: patient-controlled analgesia requirement and adverse events among different-ratio morphine and nalbuphine admixtures for postoperative pain.

BACKGROUND: Nalbuphine, a mixed agonist-antagonist opioid, has a potential to attenuate the mu-opioid effects and to enhance the kappa-opioid effects. However, when morphine and nalbuphine are mixed together, the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown.

METHODS: This randomized, double-blind controlled study investigated five different combining ratios of morphine and nalbuphine in 311 patients undergoing gynaecologic operations. The concentrations [morphine (mg ml(-1))]/[nalbuphine (mg ml(-1))] were 1/0 in Group 1, 0.75/0.25 (ratio 1:3) in Group 2, 0.5/0.5 (ratio 1:1) in Group 3, 0.25/0.75 (ratio 3:1) in Group 4, and 0/1 in Group 5. Patient-controlled analgesia (PCA) requirement, postoperative pain, and adverse events were evaluated throughout the postoperative 24 h period.

RESULTS: Twenty-four hour PCA requirements were similar among the five groups. Verbal rating scores for pain were statistically 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 incidences and severity of dizziness, nausea, and vomiting were not significantly different.

CONCLUSIONS: 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 and agonist-antagonist for postoperative pain management after gynaecologic surgery.