Anrikefon-based Patient-controlled Intravenous Analgesia After Laparoscopic Surgery
Summary
Visceral pain following laparoscopic surgery is frequently underestimated, yet it is associated with a range of adverse outcomes. Effective visceral pain management should constitute an essential component of postoperative analgesic strategies following laparoscopic procedures. However, conventional analgesic agents, including μ-opioid receptor agonists, lack specificity for visceral pain. Anrikefon, a novel selective peripheral κ-opioid receptor agonist, demonstrates unique efficacy in alleviating visceral pain with a favorable safety profile. Preliminary studies showed that a single intravenous dose of anrikefon effectively alleviates postoperative pain after abdominal surgery with a low risk of adverse effects. The investigators hypothesize that an appropriate dosing regimen of anrikefon administered via patient-controlled intravenous analgesia (PCIA) pump, as part of a multimodal analgesic strategy, can specifically target and alleviate visceral pain after laparoscopic surgery, thereby achieving comprehensive postoperative analgesia.
Timeline
- Start
- 2025-12-25
- Primary completion
- 2026-02-11
- Completion
- 2026-03-11
Publications
- Background Liu Y, Xiao S, Yang H, Lv X, Hou A, Ma Y, Jiang Y, Duan C, Mi W; CAPOPS Group. Postoperative pain-related outcomes and perioperative pain management in China: a population-based study. Lancet Reg Health West Pac. 2023 Jun 10;39:100822. doi: 10.1016/j.lanwpc.2023.100822. eCollection 2023 Oct.
- Background Armstrong RA, Fayaz A, Manning GLP, Moonesinghe SR; Peri-operative Quality Improvement Programme (PQIP) delivery team; Oliver CM; PQIP collaborative. Predicting severe pain after major surgery: a secondary analysis of the Peri-operative Quality Improvement Programme (PQIP) dataset. Anaesthesia. 2023 Jul;78(7):840-852. doi: 10.1111/anae.15984. Epub 2023 Mar 2.
- Background Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery. Lancet. 2019 Apr 13;393(10180):1537-1546. doi: 10.1016/S0140-6736(19)30352-6.
- Background Wildbrett P, Oh A, Naundorf D, Volk T, Jacobi CA. Impact of laparoscopic gases on peritoneal microenvironment and essential parameters of cell function. Surg Endosc. 2003 Jan;17(1):78-82. doi: 10.1007/s00464-002-9015-3. Epub 2002 Sep 30.
- Background Papparella A, Noviello C, Romano M, Parmeggiani P, Paciello O, Papparella S. Local and systemic impact of pneumoperitoneum on prepuberal rats. Pediatr Surg Int. 2007 May;23(5):453-7. doi: 10.1007/s00383-006-1860-z.
- Background Hatipoglu S, Akbulut S, Hatipoglu F, Abdullayev R. Effect of laparoscopic abdominal surgery on splanchnic circulation: historical developments. World J Gastroenterol. 2014 Dec 28;20(48):18165-76. doi: 10.3748/wjg.v20.i48.18165.
- Background de Lacy FB, Taura P, Arroyave MC, Trepanier JS, Rios J, Bravo R, Ibarzabal A, Pena R, Deulofeu R, Lacy AM. Impact of pneumoperitoneum on intra-abdominal microcirculation blood flow: an experimental randomized controlled study of two insufflator models during transanal total mesorectal excision : An experimental randomized multi-arm trial with parallel treatment design. Surg Endosc. 2020 Oct;34(10):4494-4503. doi: 10.1007/s00464-019-07236-5. Epub 2019 Nov 7.
- Background Cheong JY, Keshava A, Witting P, Young CJ. Effects of Intraoperative Insufflation With Warmed, Humidified CO2 during Abdominal Surgery: A Review. Ann Coloproctol. 2018 Jun;34(3):125-137. doi: 10.3393/ac.2017.09.26. Epub 2018 Jun 30.
- Background Sikandar S, Dickenson AH. Visceral pain: the ins and outs, the ups and downs. Curr Opin Support Palliat Care. 2012 Mar;6(1):17-26. doi: 10.1097/SPC.0b013e32834f6ec9.
- Background Kendall GP. Visceral pain. Br J Surg. 1985 Sep;72 Suppl:S4-5. doi: 10.1002/bjs.1800721304. No abstract available.
- Background Golzari SE, Nader ND, Mahmoodpoor A. Underlying Mechanisms of Postoperative Pain After Laparoscopic Surgery. JAMA Surg. 2016 Mar;151(3):295-6. doi: 10.1001/jamasurg.2015.3934. No abstract available.
- Background Choi JB, Kang K, Song MK, Seok S, Kim YH, Kim JE. Pain Characteristics after Total Laparoscopic Hysterectomy. Int J Med Sci. 2016 Jul 5;13(8):562-8. doi: 10.7150/ijms.15875. eCollection 2016.
- Background Blichfeldt-Eckhardt MR, Ording H, Andersen C, Licht PB, Toft P. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy. Pain. 2014 Nov;155(11):2400-7. doi: 10.1016/j.pain.2014.09.019. Epub 2014 Sep 22.
- Background Ruiz-Tovar J, Garcia A, Ferrigni C, Duran M. Application of Vitamin E Acetate on Staple Lines and Anastomoses of Roux-en-Y Gastric Bypass: Impact on Postoperative Pain and Acute Phase Reactants. Obes Surg. 2020 Aug;30(8):2988-2993. doi: 10.1007/s11695-020-04635-9.
- Background Koh JC, Kong HJ, Kim MH, Hong JH, Seong H, Kim NY, Bai SJ. Comparison of Analgesic and Adverse Effects of Oxycodone- and Fentanyl-Based Patient-Controlled Analgesia in Patients Undergoing Robot-Assisted Laparoscopic Gastrectomy Using a 55:1 Potency Ratio of Oxycodone to Fentanyl: A Retrospective Study. J Pain Res. 2020 Sep 4;13:2197-2204. doi: 10.2147/JPR.S264764. eCollection 2020.
- Background Jiang Z, Zhou G, Song Q, Bao C, Wang H, Chen Z. Effect of Intravenous Oxycodone in Combination With Different Doses of Dexmedetomdine on Sleep Quality and Visceral Pain in Patients After Abdominal Surgery: A Randomized Study. Clin J Pain. 2018 Dec;34(12):1126-1132. doi: 10.1097/AJP.0000000000000645.
- Background Ehrlich AT, Kieffer BL, Darcq E. Current strategies toward safer mu opioid receptor drugs for pain management. Expert Opin Ther Targets. 2019 Apr;23(4):315-326. doi: 10.1080/14728222.2019.1586882. Epub 2019 Mar 15.
- Background Waldhoer M, Bartlett SE, Whistler JL. Opioid receptors. Annu Rev Biochem. 2004;73:953-90. doi: 10.1146/annurev.biochem.73.011303.073940.
- Background Beck TC, Hapstack MA, Beck KR, Dix TA. Therapeutic Potential of Kappa Opioid Agonists. Pharmaceuticals (Basel). 2019 Jun 20;12(2):95. doi: 10.3390/ph12020095.
- Background Wang X, Gou X, Yu X, Bai D, Tan B, Cao P, Qian M, Zheng X, Wang H, Tang P, Zhang C, Ye F, Ni J. Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch. Front Pharmacol. 2021 Nov 16;12:773204. doi: 10.3389/fphar.2021.773204. eCollection 2021.
- Background Zhong Y, Xu Y, Lei Q, Yang M, Wang S, Hu X, Xie H, Li Y, Qin Z, Gu Z, Zhang J, Wang Y, Wu J, Wang H, Ming Y, Xia Z, Zhai H, Jiang K, Zhang P, Wang Z, Wang L, Li L, Cheng Z, Jiang H, Wang G, Chen J, Zhao Z, Chen X, Yan M. HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials. Nat Commun. 2025 May 24;16(1):4830. doi: 10.1038/s41467-025-60013-y.
- Background Shao R, Wang HY, Ruan ZR, Jiang B, Yang DD, Hu Y, Xu YC, Yang JT, Gao W, Zhao WY, Yan M, Lou H. Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers. Basic Clin Pharmacol Toxicol. 2024 Dec;135(6):743-754. doi: 10.1111/bcpt.14094. Epub 2024 Oct 13.
- Background Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Anrikefon | Unknown | 5 ug/ml | Intravenous |
| Subject | Anrikefon | Unknown | 7.5 ug/ml | Intravenous |
| Subject | Anrikefon | Unknown | 10 ug/ml | Intravenous |
| Comparator | Morphine | Other / unclassified | 0.5 mg/ml | Intravenous |
Indications
No indication recorded.