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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

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Abstract

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.

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Data Availability

Data and associated documentation will be available to users from the corresponding authors on reasonable request.

Abbreviations

ASA PS:

American Society for Anesthesiologist physical statuses

AUC:

Area under the curve

BMI:

Body mass index

CPSP:

Chronic postsurgical pain

ERAS:

Enhanced recovery after surgery

IBW:

Ideal body weight

MMA:

Multimodal analgesia

MME:

Morphine milligram equivalent

NRS:

Numeric rating scale

NSAID:

Non-steroidal anti-inflammatory drugs

PACU:

Post-anesthesia care unit

PONV:

Postoperative nausea and vomiting

QoL:

Quality of life

SDE:

Sebacoyl dinalbuphine ester

SF-12:

12-Item short form

VAS:

Visual analog scale

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Funding

This study was funded in part by the Ministry of Science and Technology of Taiwan (grant number MOST 109–2314-B-650–007-MY2) and institutional grants from E-Da Hospital, located in Taiwan (EDPJ109034 and EDPJ109064 to CFL).

Author information

Author notes

  1. Tien-Chou Soong and Chen-Fuh Lam contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, E-Da Hospital and I-Shou University, 1 Yida Rd, Yanchao Dist., Kaohsiung, 824, Taiwan

    Ying-En Lee, Shao-Ye Wang & Chen-Fuh Lam

  2. Institute of Biomedical Sciences, College of Medicine, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Ying-En Lee & Yow-Ling Shiue

  3. Division of General Surgery, Department of Surgery, E-Da Hospital and I-Shou University, 1 Yida Rd, Yanchao Dist., Kaohsiung, 824, Taiwan

    Jian-Han Chen & Chung-Yen Chen

  4. Bariatric and Metabolism International Surgery Center, E-Da Hospital and I-Shou University, 1 Yida Rd, Yanchao Dist., Kaohsiung, 824, Taiwan

    Jian-Han Chen & Chung-Yen Chen

  5. School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan, 8 Yida Rd, Yanchao Dist., Kaohsiung, 824, Taiwan

    Jian-Han Chen, Chung-Yen Chen & Chen-Fuh Lam

  6. Institute of Precision Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Yow-Ling Shiue

  7. Department of Weight Loss and Health Management Center, E-DA Dachang Hospital and I-Shou University, 305 Dachang 1St Rd., Sanmin Dist., Kaohsiung, 807, Taiwan

    Tien-Chou Soong

  8. Department of Asia Obesity Medical Research Center, E-DA Cancer Hospital and I-Shou University, 21 Yida Rd, Yanchao Dist., 824, Kaohsiung, Taiwan

    Tien-Chou Soong

  9. Department of Anesthesiology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 2 Min-Sheng Rd, Dalin Town, 622, Chia-Yi, Taiwan

    Chen-Fuh Lam

Authors
  1. Ying-En Lee
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Contributions

Ying-En Lee, MD, helped with conceptualization of the study and study design, study drug administration, data collection, patient follow-up, statistical analysis, interpretation of data, and drafting the manuscript. The author approved the final version of manuscript.

Shao-Ye Wang, RN, helped with patient administration, assistance in drug administration, clinical data collection, and patient follow-up. The author approved the final version of manuscript.

Jian-Han Chen, MD, helped with conceptualization of the study and study design and performed surgery, patient follow-up, statistical analysis, and drafting of the manuscript. The author approved the final version of manuscript.

Chung-Yen Chen, MD., helped with study design, performed surgery, patient follow-up, and drafting of the manuscript. The author approved the final version of manuscript.

Yow-Ling Shiue, PhD., helped with conceptualization of the study and study design and interpretation of data. The author approved the final version of manuscript.

Tien-Chou Soong, MD., helped with study design; performed surgery, patient follow-up, supervision of study progress, statistical analysis, and interpretation of data; and critically revised the manuscript. The author approved the final version of manuscript.

Chen-Fuh Lam, MD, PhD., helped with the study design, supervision of study progress, statistical analysis, and interpretation of data, obtained research funds, critically revised the manuscript, and is responsible for the submission of the manuscript. The author approved the final version of manuscript.

Corresponding author

Correspondence to Chen-Fuh Lam.

Ethics declarations

Ethical Approval

All procedures involving human participants in this study were conducted in accordance with the institutional ethical standards and with the 1964 Helsinki declaration and its later amendments.

Conflict of Interest

This was a PI-initiated clinical research project, and the authors declare that they have no competing interests.

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Key Points

• Long-acting non-μ-receptor opioids were previously not available for postsurgical pain management.

• Injection of a long-acting κ-receptor agonist sebacoyl dinalbuphine ester (SDE) significantly improves surgical pain intensity up to 48 h following laparoscopic bariatric surgery.

• SDE does not increase systemic adverse events but may induce focal reactions in patients with obesity.

Supplementary Information

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Supplementary file1 (DOCX 15 KB)

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Lee, YE., Wang, SY., Chen, JH. et al. 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. OBES SURG 33, 1192–1201 (2023). https://doi.org/10.1007/s11695-023-06502-9

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