Department of Anesthesiology, E-Da Hospital and I-Shou University, 1 Yida Rd, Yanchao Dist., Kaohsiung, 824, Taiwan.
Institute of Biomedical Sciences, College of Medicine, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Obes Surg. 2023 Apr;33(4):1192-1201. doi: 10.1007/s11695-023-06502-9. Epub 2023 Feb 14.
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 (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.
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.
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.
μ 型阿片受体与不良的胃肠道副作用和呼吸抑制有关。目前尚无长效非 μ 型阿片受体的注射用药物可用于治疗急性和慢性术后疼痛（CPSP）。本双盲临床试验测试了一种长效 κ 型阿片受体激动剂，即丁丙诺啡癸酸酯（SDE，Naldebain®），用于腹腔镜减肥手术后的手术疼痛管理。
患者在手术前>12 小时随机接受 SDE（150mg，n=30）或载体溶液（n=30）的单次肌内注射。所有患者均接受标准围手术期多模式镇痛（MMA）。主要终点是术后 7 天内的疼痛强度。次要终点是术后 7 天内的不良反应发生率和术后 3 个月的 CPSP 发生率。
与安慰剂相比，SDE 组术后 0-48 小时的视觉模拟量表（VAS）曲线下面积显著降低（143.3±65.4 和 105.9±36.3，P=0.025）。SDE 组在术后 48 小时有中度至重度疼痛（VAS≥4）的患者明显较少（16.7% vs 50%；P=0.012）。术后 72 小时和 7 天两组的疼痛强度相似。术后 3 个月的 CPSP 发生率无差异。SDE 并未增加与药物相关的全身不良反应。
除了标准的围手术期 MMA 外，长效 κ 型阿片受体激动剂 SDE 的单次注射可显著改善腹腔镜减肥手术后 48 小时的疼痛管理。长效 κ 型阿片受体激动剂阿片类药物可以改善住院期间的疼痛管理，并促进术后早期出院，而不会增加与药物相关的全身并发症。
