Effect of Combining Ultralow-dose Naloxone with Morphine in Intravenous Patient-controlled Analgesia: The Cut-off Ratio of Naloxone to Morphine for Antiemesis After Gynecologic Surgery

Abstract

Admixing an ultralow dose of naloxone with intravenous morphine patient-controlled analgesia (PCA) has been shown to decrease postoperative nausea. However, the cut-off ratio of the naloxone-morphine admixture for antiemetic effects has not been investigated. The purpose of this study was to investigate the cut-off ratio of naloxone-morphine admixture in PCA for antiemesis after gynecologic surgery. This double-blind study enrolled 120 female patients who were scheduled for gynecologic surgery under general anesthesia. Patients were randomly allocated to one of three groups (n = 40 for each group). The concentration of naloxone and morphine respectively was 0 microg/mL and 1 mg/mL in group 1, 0.1 microg/mL and 1 mg/mL in group 2 (1:10,000), and 1 microg/mL and 1 mg/mL in group 3 (1:1000). Morphine consumption, verbal rating score of wound pain at rest and with exertion, and morphine-related side effects were investigated at 1, 2, 4 and 24 hours postoperatively. A total of 112 patients completed the study (37 in group 1, 36 in group 2, 39 in group 3). The incidence of nausea during the postoperative 4-24 hours was significantly lower in group 3 than in group 1 (23.1% vs. 56.8%, p < 0.05). Furthermore, the overall incidence of severe nausea was significantly lower in group 3 than in group 1 (2.6% vs. 24.3%, p < 0.05) as was the rescue antiemetic requirements (5.1% vs. 24.3%, p < 0.05). However, there were no significant differences between groups 2 and 1. The pain scores (at rest and with exertion) and 24-hour morphine consumption were not significantly different among the three groups. The antiemetic efficacy of ultralow-dose naloxone combined with PCA morphine is limited by a cut-off ratio of naloxone to morphine of 1:10,000.