Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia

Background: Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. Methods: One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 μg nalmefene, or 25 μg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation. Results: The need for antiemetic and antipruritic medications during the 24- h study period was significantly lower in the patients receiving nalmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nalmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. Conclusion: Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient- controlled analgesia with morphine.