Oliceridine to prevent postoperative nausea and vomiting in high-risk patients undergoing general anaesthesia: a study protocol for a double-blind, randomised, controlled trial

Background: Postoperative nausea and vomiting (PONV) are distressing symptoms that considerably diminish postoperative satisfaction. We are conducting a double-blind, randomised, controlled trial to evaluate the efficacy of a novel G-protein-biased µ-opioid receptor agonist, oliceridine, in preventing PONV after general anaesthesia in high-risk patients. The study also seeks to determine whether traditional opioids, such as fentanyl, can be replaced during tracheal intubation and for postoperative analgesia. The objectives of this trial include assessing the impact of oliceridine on PONV. Methods: In this study, 280 adult female patients (aged 18–65 years) undergoing elective laparoscopic gynaecological under general surgery who meet the inclusion criteria will be randomly assigned to an experimental group (oliceridine) and a control group (fentanyl) in a 1:1 ratio. The primary outcome indicator is the incidence of nausea and vomiting within 48 hours after surgery. The secondary outcome indicators are the analgesic effect in the perioperative period (anaesthesia induction period, intraoperative period, and 48 hours post-surgery), the overall incidence of severe complications post-surgery, length of hospital stay, and time of food and drink intake. Conclusions: This trial demonstrates that oliceridine provides comparable analgesia to fentanyl in high-risk surgical patients, positioning it as a promising alternative with a superior PONV profile. Clinical Trial Registration: ChiCTR2400089121.

Oliceridine fumarate injection; Postoperative nausea and vomiting; General anaesthesia; Fentanyl

[1] Knoth S, Weber B, Lotz H, Vojnar B, Eberhart LHJ. Update PO(N)V—what is new in the prophylaxis and treatment of postoperative nausea and vomiting? Die Anaesthesiologie. 2025; 74: 171–186. (In German)

[2] Sizemore DC, Singh A, Dua A, Singh K, Grose BW. Postoperative nausea. StatPearls Publishing: Treasure Island (FL). 2022.

[3] Andrew BY, Holmes R, Taicher BM, Habib AS. The association of guideline-directed prophylaxis with postoperative nausea and vomiting in adult patients: a single-center, retrospective cohort study. Anesthesia & Analgesia. 2024; 139: 1006–1016.

[4] Apfel CC, Kranke P, Eberhart LH. Comparison of surgical site and patient’s history with a simplified risk score for the prediction of postoperative nausea and vomiting. Anaesthesia. 2004; 59: 1078–1082.

[5] Zimmerman A, Laitman A. Safe management of adverse effects associated with prescription opioids in the palliative care population: a narrative review. Journal of Clinical Medicine. 2024; 13: 2746.

[6] Mark EB, Okdahl T, Kahlke DG, Hansen LEM, Krogh K, Frøkjær JB, et al. Effects of opium tincture on gastrointestinal function and motility in healthy volunteers: a magnetic resonance imaging study. Neurogastroenterology & Motility. 2024; 36: e14941.

[7] Bock A, Bermudez M. Allosteric coupling and biased agonism in G protein-coupled receptors. The FEBS Journal. 2021; 288: 2513–2528.

[8] Ni Y, Huang R, Yang S, Yang XY, Zeng S, Yao A, et al. Pharmacokinetics and safety of oliceridine fumarate injection in Chinese Patients with chronic non-cancer pain: a phase I, single-ascending-dose, open-label clinical trial. Drug Design, Development and Therapy. 2024; 18: 2729–2743.

[9] French AR, van Rijn RM. An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects. Pharmacological Research. 2022; 177: 106091.

[10] Goudra B. Oliceridine—opioid of the 21st century. Saudi Journal of Anaesthesia. 2022; 16: 69–75.

[11] Biskupiak J, Oderda G, Brixner D, Wandstrat TL. Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods. Journal of Comparative Effectiveness Research. 2024; 13: e230041.

[12] Kienbaum P, Schaefer MS, Weibel S, Schlesinger T, Meybohm P, Eberhart LH, et al. Update on PONV—what is new in prophylaxis and treatment of postoperative nausea and vomiting?: Summary of recent consensus recommendations and Cochrane reviews on prophylaxis and treatment of postoperative nausea and vomiting. Anaesthesist. 2022; 71: 123–128. (In German)

[13] Yurkonis AV, Tollinche L, Alter J, Pope SE, Traxler P, Hill HE, et al. Standardizing the dosage and timing of dexamethasone for postoperative nausea and vomiting prophylaxis at a safety-net hospital system. Joint Commission Journal on Quality and Patient Safety. 2024; 50: 601–605.

[14] Zufferey PJ, Chaux R, Lachaud PA, Capdevila X, Lanoiselée J, Ollier E. Dose-response relationships of intravenous and perineural dexamethasone as adjuvants to peripheral nerve blocks: a systematic review and model-based network meta-analysis. British Journal of Anaesthesia. 2024; 132: 1122–1132.

[15] Ding X, Zhu X, Zhao C, Chen D, Wang Y, Liang H, et al. Use of sugammadex is associated with reduced incidence and severity of postoperative nausea and vomiting in adult patients with obesity undergoing laparoscopic bariatric surgery: a post-hoc analysis. BMC Anesthesiology. 2023; 23: 163.

[16] Sim J, Chen Q. Enhanced recovery after surgery in breast reconstruction patients reduces post operative nausea and vomiting rates (PONV). Clinical Nutrition ESPEN. 2023; 57: 790.

[17] Wang J, Zhang Z. Gastric negative pressure suction method reduces the incidence of PONV after orthognathic surgery. Frontiers in Surgery. 2022; 9: 882726.

[18] Gan TJ, Belani KG, Bergese S, Chung F, Diemunsch P, Habib AS, et al. Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesthesia & Analgesia. 2020; 131: 411–448.