A comparison of the effects of oliceridine and sufentanil on the quality of recovery after hysteroscopic surgery: a prospective double-blind randomized controlled trial

Purpose Oliceridine is a G protein-biased μ-opioid receptor agonist that selectively activates G protein signaling while significantly reducing β-arrestin pathway recruitment. Clinical data indicate that this unique signaling bias may help mitigate common adverse effects associated with traditional opioids. The objective of this study was to compare the effects of oliceridine and sufentanil on postoperative recovery quality in patients undergoing hysteroscopic surgery.

In this prospective, double-blind, randomized controlled trial, 108 patients undergoing hysteroscopic surgery were enrolled and randomly assigned to either the oliceridine group (Group O) or the sufentanil group (Group S). The primary outcome was the 15-item Quality of Recovery Scale (QoR-15) score assessed at 24 h post-operatively.

One hundred one patients were included in the analysis (Group O: n = 51; Group S: n = 50). At 24 h post-operatively, Group O had significantly higher total QoR-15 scores than Group S did (123 [IQR 120–125] vs. 116.5 [IQR 114–118]; difference = 6.5, P < 0.001). Group O also scored higher on specific QoR-15 domains: enjoyment of food, general well-being, and nausea or vomiting. Adverse events were less common in Group O, which had significantly lower rates of respiratory depression and nausea/vomiting. Intraoperative monitoring revealed less pronounced effects on heart and respiratory rates in Group O vs. Group S. No statistically significant differences were observed in sedation onset time, total propofol dose, or emergence time.

When compared with sufentanil, oliceridine significantly enhanced early postoperative recovery quality in patients undergoing hysteroscopic surgery while reducing the incidence of respiratory depression and nausea/vomiting. Similar content being viewed by others Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request.

Vilos GA, Abu-Rafea B. New developments in ambulatory hysteroscopic surgery. Best Pract Res Clin Obstet Gynaecol. 2005;19(5):727–42. Soysal C, Ince O, Taşçı Y. The effect of cervical length on procedure time and VAS pain score in office hysteroscopy. Sci Rep. 2025;15(1):1975. Paulo AAS, Solheiro MHR, Paulo COS, Afreixo VMA. What proportion of women refers moderate to severe pain during office hysteroscopy with a mini-hysteroscope? A systematic review and meta-analysis. Arch Gynecol Obstet. 2016;293(1):37–46. Levytska K, Yu Z, Wally M, Odum S, Hsu JR, Seymour R, Brown J, Crane EK, Tait DL, Puechl AM, Lees B, Naumann RW, Beuhler M, Bosse MJ, Gibbs M, Griggs C, Gulati A, Jarrett S, Leas D, Odum S, Roomian T, Runyon M, Saha A, Sullivan DM, Watling B. Enhanced recovery after surgery (ERAS) protocol is associated with lower post-operative opioid use and a reduced office burden after minimally invasive surgery. Gynecol Oncol. 2022;166(3):471–5. Bougie O, Blom J, Zhou G, Murji A, Thurston J. Use and misuse of opioid after gynecologic surgery. Best Pract Res Clin Obstet Gynaecol. 2022;85:23–34. Ventriglia E, Rizzo A, Gomez JL, Friedman J, Lam S, Solís O, Rais R, Bonaventura J, Michaelides M. Essential role of P-glycoprotein in the mechanism of action of oliceridine. Neuropsychopharmacology. 2023;48(5):831–42. Zhang M, Chen T, Lu X, Lan X, Chen Z, Lu S. G protein-coupled receptors (GPCRs): advances in structures, mechanisms and drug discovery. Signal Transduct Target Ther. 2024;9(1):88. Wolf A, Unterberg M, Witowski A, Adamzik M, Wolf A. Efficacy, safety, and side effects of oliceridine in acute postoperative pain, a protocol for a systematic review and meta-analysis. PLoS ONE. 2024;19(2):e0299320. Azzam AAH, Lambert DG. Preclinical discovery and development of oliceridine (Olinvyk®) for the treatment of post-operative pain. Expert Opin Drug Discov. 2022;17(3):215–23. Daksla N, Wang A, Jin Z, Gupta A, Bergese SD. Oliceridine for the management of moderate to severe acute postoperative pain: a narrative review. Drug Des Devel Ther. 2023. https://doi.org/10.2147/DDDT.S372612. Myles PS, Shulman MA, Reilly J, Kasza J, Romero L. Measurement of quality of recovery after surgery using the 15-item quality of recovery scale: a systematic review and meta-analysis. Br J Anaesth. 2022;128(6):1029–39. Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013;118(6):1332–40. Myles PS, Myles DB. An updated minimal clinically important difference for the QoR-15 scale. Anesthesiology. 2021;135(5):934–5. Che T, Roth BL. Molecular basis of opioid receptor signaling. Cell. 2023;186(24):5203–19. Wang Y, Zhuang Y, DiBerto JF, Zhou XE, Schmitz GP, Yuan Q, Jain MK, Liu W, Melcher K, Jiang Y. Structures of the entire human opioid receptor family. Cell. 2023;186(2):413–27.e17. Zhang Z, Li C, Xu L, Sun X, Lin X, Wei P, Li J. Effect of opioid-free anesthesia on postoperative nausea and vomiting after gynecological surgery: a systematic review and meta-analysis. Front Pharmacol. 2024;14:1330250. Kahokehr A, Sammour T, Zargar-Shoshtari K, Thompson L, Hill AG. Implementation of ERAS and how to overcome the barriers. Int J Surg. 2009;7(1):16–9. Joshi GP, Kehlet H. Postoperative pain management in the era of ERAS: an overview. Best Pract Res Clin Anaesthesiol. 2019;33(3):259–67. Wang H, Li H, Cheng J. Oliceridine (TRV130): a biased agonist of the μ opioid receptor as a novel analgesic. In: Yu B, Zhan P, editors. Drug discovery stories. Elsevier; 2025. p. 551-69. DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C. Ag protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther. 2013;344(3):708–17. Ma B, Li Y, Leng C, Ji A, Zhang N, Tao X, Cao Q, Wang S. A comparative evaluation of the safety and efficacy of oliceridine and sufentanil in gastrointestinal endoscopy: a single-center, randomized controlled trial. Drug Des Dev Ther. 2025;19:5111–21. Simpson KN, Fossler MJ, Wase L, Demitrack MA. Cost-effectiveness and cost-benefit analysis of oliceridine in the treatment of acute pain. J Comp Eff Res. 2021;10(15):1107–19. Wessels E, Perrie H, Scribante J, Jooma Z. Quality of recovery in the perioperative setting: a narrative review. J Clin Anesth. 2022;78:110685. Léger M, Campfort M, Cayla C, Parot-Schinkel E, Lasocki S, Rineau E. Validation of an alternative French version of the quality of Recovery-15 score: the FQoR-15. Br J Anaesth. 2020;125(4):e345–7. Myles P, Burke J. Development and psychometric evaluation of a postoperative quality of recovery score. Anesthesiology. 2013;118:1332–40. Baldo BA, Rose MA. Mechanisms of opioid-induced respiratory depression. Arch Toxicol. 2022;96(8):2247–60. Bateman JT, Saunders SE, Levitt ES. Understanding and countering opioid-induced respiratory depression. Br J Pharmacol. 2023;180(7):813–28. Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994–6004. Weingarten TN, Deljou A, Sprung J. Research and clinical implications of emerging evidence regarding patterns of postoperative opioid-induced respiratory depression. Biomol Biomed. 2025;25(2):327. Bergese S, Berkowitz R, Rider P, Ladouceur M, Griffith S, Segura Vasi A, Cochrane K, Wase L, Demitrack MA, Habib AS. Low incidence of postoperative respiratory depression with oliceridine compared to morphine: a retrospective chart analysis. Pain Res Manag. 2020;2020(1):7492865. Jin Z, Gan TJ, Bergese SD. Prevention and treatment of postoperative nausea and vomiting (PONV): a review of current recommendations and emerging therapies. Ther Clin Risk Manag. 2020. https://doi.org/10.2147/TCRM.S256234. Wu S, Gan C, Huang X, Jiang D, Xu Y, Liao Y, Ma F, Hong Y, Duan H, Lin P. Incidence and risk factors of postoperative nausea and vomiting in lung cancer patients following lobectomy and application of analgesic pumps. J Int Med Res. 2022;50(6):03000605221105343. Elvir-Lazo OL, White PF, Yumul R, Eng HC. Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review. F1000Research. 2020;9:F1000 Faculty Rev-983. Feng C-d, Xu Y, Chen S, Song N, Meng X-w, Liu H, Ji F-h, Peng K. Opioid-free anaesthesia reduces postoperative nausea and vomiting after thoracoscopic lung resection: a randomised controlled trial. Br J Anaesth. 2024;132(2):267–76. Beard TL, Michalsky C, Candiotti KA, Rider P, Wase L, Habib AS, Demitrack MA, Fossler MJ, Viscusi ER. Oliceridine is associated with reduced risk of vomiting and need for rescue antiemetics compared to morphine: exploratory analysis from two phase 3 randomized placebo and active controlled trials. Pain Ther. 2021;10(1):401–13. Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER. Apollo-2: a randomized, placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the μ-opioid receptor, for management of moderate to severe acute pain following abdominoplasty. Pain Pract. 2019;19(7):715–31. Patel PA, Tilley DG, Rockman HA. Beta-arrestin-mediated signaling in the heart. Circ J. 2008;72(11):1725–9. Ma L, Pei G. Beta-arrestin signaling and regulation of transcription. J Cell Sci. 2007;120(Pt 2):213–8. Funding This work was supported by a grant from the Guangdong Medical Association, China (GDMA2024098013). Author information Authors and Affiliations Contributions Zongxing Ke: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing—original draft, Writing—review and editing, Project administration, and Funding acquisition. Ying He: Conceptualization, Methodology, Validation, Writing—review and editing. Qinqing Hu: Methodology, Validation, Formal analysis, Investigation, Writing—review and editing. Dehao Zheng: Methodology, Validation, Writing—review and editing. Zanmin Yao: Methodology, Validation, Writing—review and editing. Wuzhao Zhou: Methodology, Validation, Writing—review and editing. Corresponding author Ethics declarations Conflict of interest The authors have no conflicts of interest to declare. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. About this article Cite this article Ke, Z., He, Y., Hu, Q. et al. A comparison of the effects of oliceridine and sufentanil on the quality of recovery after hysteroscopic surgery: a prospective double-blind randomized controlled trial. J Anesth 40, 235–244 (2026). https://doi.org/10.1007/s00540-025-03578-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00540-025-03578-8