Efficacy and Safety of Parenteral Injection of an Extended Release κ-receptor Opioid Sebacoyl Dinalbuphine Ester for Acute and Chronic Pain After Laparoscopic Bariatric Surgery: a Randomized, Placebo-Controlled, Double-Blind Trial.

Abstract

μ-receptor opioids are associated with unwanted gastrointestinal side effects and respiratory depression. A long-acting non-μ-receptor parenteral opioid is not currently available for management of acute and chronic postsurgical pain (CPSP). This double-blind clinical trial tested an extended-release κ-receptor agonist, sebacoyl dinalbuphine ester (SDE, Naldebain®) for management of surgical pain after laparoscopic bariatric surgery. Patients were randomly assigned to receive a single intramuscular injection of SDE (150mg, n = 30) or vehicle solution (n = 30) at > 12h before surgery. All patients received standard perioperative multimodal analgesia (MMA). The primary endpoint was the pain intensity in the beginning 7days after operation. The secondary endpoints were adverse reactions up to 7days and incidence of CPSP at 3months after surgery. Compared with placebos, the area under curves of visual analog scale (VAS) for 0-48h after operation were significantly reduced in SDE group (143.3 ± 65.4 and 105.9 ± 36.3, P = 0.025). There were significantly fewer patients in the SDE group who had moderate-to-severe pain (VAS ≥ 4) (16.7% vs 50%; P = 0.012) at postoperative 48h. Pain intensities were similar between the two groups at 72h and 7days postoperatively. The incidence of CPSP at 3months was not different. SDE did not increase drug-related systemic adverse events. In addition to the standard perioperative MMA, a single-dose injection of long-acting κ-receptor agonist SDE provides significantly better pain management for 48h following laparoscopic bariatric surgery. A long-acting κ-receptor agonist opioid could improve in-hospital pain management and potentiate early discharge after operation without increasing drug-related systemic complications.