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Pre-incision versus pre-closure intravenous tegileridine for analgesia after laparoscopic cholecystectomy: a randomized, double-blind, three-arm trial

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Laparoscopic cholecystectomy is frequently associated with clinically relevant early postoperative pain, including incisional pain, visceral pain, and post-laparoscopic shoulder pain, which may impair postoperative recovery. Tegileridine is a novel G protein-biased µ-opioid receptor agonist with analgesic potential. This trial evaluated whether the timing of intravenous tegileridine administration influences postoperative analgesia and early recovery after elective laparoscopic cholecystectomy. In this prospective, randomized, double-blind, placebo-controlled, single-centre trial, adults aged 18 ~ 65 years with American Society of Anesthesiologists physical status I or II undergoing elective laparoscopic cholecystectomy were randomly assigned in a 1:1:1 ratio to receive intravenous tegileridine 1 mg before skin incision, intravenous tegileridine 1 mg before skin closure, or placebo at both time points. All patients received standardised general anesthesia and postoperative patient-controlled intravenous analgesia with sufentanil and ondansetron. The primary outcome was postoperative visual analogue scale measurements across multiple time points for longitudinal analysis, assessed using a 0 ~ 10 visual analogue scale. Secondary outcomes included rescue analgesia, effective patient-controlled intravenous analgesia demands within 48 h, 15-item Quality of Recovery questionnaire scores, hemodynamic variables, and adverse events. Of 174 screened patients, 144 were randomized and 126 were included in the final analysis, with 42 patients per group. Baseline characteristics were comparable among groups. Postoperative VAS scores showed significant effects of group, time, and the group-by-time interaction (all P < 0.001). Groups T 1 and T 2 had lower VAS scores than group C at all assessed time points (all adjusted P < 0.001). Group T 1 had a lower VAS score than group T 2 at 4 h (adjusted P < 0.001), but no differences were observed between the two tegileridine groups at the other time points. Effective PCIA use, rescue analgesia requirement, and postoperative nausea and vomiting were lower in groups T 1 and T 2 than in group C. Rescue analgesia was required in 16.7%, 14.3%, and 50.0% of patients, and PONV occurred in 11.9%, 7.1%, and 40.5% of patients in groups T 1 , T 2 , and C, respectively (both overall P < 0.001). QoR-15 scores on postoperative days 1 and 2 were higher in both tegileridine groups than in group C (all adjusted P < 0.001). Extubation time was longer in group T 1 than in group T 2 , while adjusted hemodynamic outcomes did not differ among groups. In patients undergoing laparoscopic cholecystectomy, both pre-incision and pre-closure administration of intravenous tegileridine were associated with lower postoperative pain scores, reduced postoperative opioid requirements, and improved early quality of recovery compared with placebo. Pre-incision administration appeared to provide a more consistent early analgesic benefit, although it was associated with a modest prolongation of extubation time. No major safety signals were observed within the limited sample size and 48-h follow-up period; however, the study was not powered to detect uncommon adverse events. Larger multicenter studies are warranted to further evaluate the safety of tegileridine. Trial registration: ClinicalTrials.gov NCT07277153 registered on 27 November 2025.

Source: Scientific Reports

DOI: 10.1038/s41598-026-63473-4