A Dose-Response Relationship Study of Prophylactic Nalbuphine to Reduce Pain During the Awakening Period in Patients Undergoing Laparoscopic Total Hysterectomy: A Randomized, Controlled, Double-Blind Clinical Study

PURPOSE: Prophylactic intravenous nalbuphine was administered to observe its median effective dose (ED(50)) in reducing pain after undergoing laparoscopic total hysterectomy. To investigate the effect of different doses of nalbuphine on postoperative analgesia and adverse reactions in patients. PATIENTS AND METHODS: The 120 patients undergoing laparoscopic total hysterectomy were divided into 6 groups: group C (control) and group P (5 different doses of nalbuphine) with 20 patients per group. The doses of nalbuphine in group P were in an equally proportional series (groups P1, P2, P3, P4, and P5 received doses of 0.280, 0.200, 0.140, 0.100, and 0.070 mg/kg, respectively), diluted to 20 mL with saline and administered 5 min before the induction of anesthesia. A similar volume (20 mL) of saline was administered to group C 5 min before the induction of anesthesia. The numeric rating scale (NRS) of patients during awakening and after surgery, the number of postoperative salvage analgesia, and the occurrence of postoperative adverse effects were recorded. RESULTS: The ED(50) (95% confidence interval (CI)) of nalbuphine in preventing pain during the awakening period in patients calculated using the point-slope method was 0.125 (0.108, 0.145) mg/kg. NRS scores differed among the 6 groups at 30 min and 1 h after extubation (P < 0.001; P < 0.001). Pairwise comparisons between groups revealed that, at 30 min after extubation, compared with group P1, the NRS scores of groups P4, P5, and C were higher (P = 0.001, P < 0.001, P < 0.001); compared with group P2, groups P5 and C had higher NRS scores (P = 0.011, P = 0.001). At 1 h after extubation, the NRS scores of groups P1 and P2 were lower than that of group P4 (P = 0.046, P = 0.036). Compared with the control, only the group P1 had a lower cough score (P = 0.009) and there were no differences in the other groups. There were no differences in sedation score at 10 min after extubation, the incidence of adverse events at 24 h postoperatively, or the number of remedial analgesics at 24 h postoperatively (P > 0.05). CONCLUSION: The ED(50) (95% CI) of nalbuphine as a prophylactic in reducing pain during recovery was 0.125 (0.108, 0.145) mg/kg. Compared with the control, nalbuphine at doses of 0.140, 0.200, and 0.280 mg/kg prevented pain during the awakening period. Among these doses, 0.280 mg/kg was determined to be the best, the occurrence of cough was less during extubation and the postoperative analgesic effect was good. However, it is necessary to pay attention to the occurrence of adverse reactions.