Different-doses Nalmefene Combined with Hydromorphone Hydrochloride for Postoperative Analgesia After Colorectal Surgery: A Randomized Controlled Study

Abstract

Abstract Background Hydromorphone hydrochloride has a satisfactory postoperative analgesic effect for patients with colorectal cancer but isaccompanied by a relatively high incidence of adverse events. Low-dose naloxone combined with opioids for patient-controlled analgesia (PCA) can reduce the incidence of drug-related adverse events. Nalmefene is a more selective opioid receptor antagonist than naloxone. We hypothesized that low-dose nalmefene combined with hydromorphone hydrochloride for PCA could enhance the analgesic effect and reduce the incidence of adverse events of hydromorphone hydrochloride. Methods The 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 was hydromorphone hydrochloride (0.15 mg/kg) added to 100 ml of normal saline for all groups, to which 2 μg/kg nalmefene was added in Group N1 and 0.5 μg/kg nalmefene was added in Group N2, Group C received hydromorphone hydrochloride only. The PCA was connected to the patient after the operation. The following data were recorded: the degree of pain (NRS score) at 1, 6, 12, 24 and 48 h after surgery; the occurrence of nausea, vomiting and pruritus; the total analgesic consumption of the PCA pump; the time to postoperative exhaust; the time to drainage tube extubation; and the overall length of hospital stay. Results The NRS scores of Group N1 (2 μg/kg) were significantly lower than those of Group C (P = 0.25). Among the three groups, the NRS scores of Group N1 (2 μg/kg) were significantly lower than those of Group C at 12 h (P = 0.01) and 48 h (P = 0.01) post-operatively. Compared with 12 hours post-operatively, the NRS scores were lower at 24 hours post-operatively in Group N1 and Group C (P < 0.05), and significantly lower at 48 hours post-operatively in all three groups (P < 0.001). There was a significant difference in the incidence of pruritus among the three groups (P = 0.036). Conclusions Nalmefene at a dosage of 2 μg/kg enhances the postoperative analgesic effect of hydromorphone hydrochloride and reduces the occurrence of postoperative pruritus. Trial Registration: The trial was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2000033520, date: 03/06/2020).