Enhanced Postoperative Analgesic Effect of Hydromorphone Hydrochloride and Decreased Incidence of Pruritus via Continuous Low-dose Pumping of Nalmefene: A Randomized Controlled Study

Background: Hydromorphone hydrochloride has a satisfactory effect on postoperative analgesia for patients with colorectal cancer, yet accompanied by a relatively incidence of adverse events. Low-dose naloxone combined with opioids for Patient Controlled Analgesia (PCA) can reduce the incidence of drug-related adverse events. Meanwhile, Nalmefene is a more selective opioid receptor antagonist than naloxone. This study hypothesized that low-dose nalmefene combined with hydromorphone hydrochloride for PCA could enhance the analgesic effect of the drug and reduce the incidence of adverse events. Methods: The present research was designed as a randomized, double-blind, controlled study. Ninety-nine patients undergoing selective radical resection of colorectal cancer were enrolled and randomly divided into three groups. The postoperative analgesia plan of the three groups was Hydromorphone hydrochloride (0.15mg/kg) added to 100 ml of normal saline, among which 2μg/kg of Nalmefene was added to group N1, 0.5μg/kg Nalmefene to group N2, and normal saline only in group C. The induction and maintenance plan of general anesthesia were the same in the three groups, and PCA was connected after operation. Furthermore, the following data were recorded, including the degree of pain (NRS score) at 1, 6, 12, 24 and 48h after surgery, the occurrence of nausea, vomiting and pruritus, the frequency of PCA, the time of postoperative exhaust, the time of drainage tube extubation, and the overall length of hospital stay. Results: After being approved by the Ethics Committee of our hospital, our study included ninety-three patients with written informed consent provided. Compared with group C, the NRS scores were significantly lower in group N1 at 12 and 48 hours after operation (P<0.05), but there was no significant difference in group N2. Compared with 12 hours after operation, the NRS scores of the three groups decreased at 48h after operation (P<0.05). There was no significant difference in the incidence of nausea and vomiting, but a difference was observed in the incidence of pruritus among three groups(P<0.05). Conclusion: Nalmefene at the dosage of 2μg/kg enhances the postoperative analgesic effect of hydromorphone hydrochloride and reduces the occurrence of postoperative pruritus. Trial Registration: The trial was registered on the Chinese Clinical Trial Registry (Registration number: ChiCTR2000033520, date: 03/06/2020).