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.

PURPOSE

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.

MATERIALS AND METHODS

Patients were randomly assigned to receive a single intramuscular injection of SDE (150 mg, n = 30) or vehicle solution (n = 30) at > 12 h before surgery. All patients received standard perioperative multimodal analgesia (MMA). The primary endpoint was the pain intensity in the beginning 7 days after operation. The secondary endpoints were adverse reactions up to 7 days and incidence of CPSP at 3 months after surgery.

RESULTS

Compared with placebos, the area under curves of visual analog scale (VAS) for 0-48 h 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 48 h. Pain intensities were similar between the two groups at 72 h and 7 days postoperatively. The incidence of CPSP at 3 months was not different. SDE did not increase drug-related systemic adverse events.

CONCLUSION

In addition to the standard perioperative MMA, a single-dose injection of long-acting κ-receptor agonist SDE provides significantly better pain management for 48 h 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.