Establishing the Median Effective Dose of Tegileridine for Immediate Postoperative Analgesia Following Laparoscopic Colorectal Cancer Surgery: A Sequential Dose-Finding Study

Abstract

Background To determine the median effective dose (ED50) of tegileridine for immediate postoperative analgesia following laparoscopic colorectal cancer surgery (LCRS), and to evaluate its safety profile. Methods A modified Dixon’s up-and-down sequential method was employed, starting with an initial tegileridine dose of 15 µg/kg and a dose ratio of 1:1.1. Patients undergoing elective LCRS received a standardized multimodal analgesic background, including a transversus abdominis plane block and intraoperative sufentanil, and received intravenous tegileridine 10 minutes before the end of surgery. A blinded investigator assessed pain using the Numerical Rating Scale (NRS) at 15 and 30 minutes, and 2 hours post-extubation. Effective analgesia was defined as an NRS score ≤ 3 without rescue analgesia within 2 hours. The ED50 was calculated using probit regression analysis. Hemodynamic variables and adverse events were documented, and safety was followed until postoperative day 2. Results Analysis of the 40 patients revealed that the ED50 of tegileridine for LCRS was 7.311 μg/kg (95% confidence interval [CI]: 2.044 to 9.194). Adverse events were mild and no serious adverse events were observed. In the PACU, 5/40 patients (12.5%) experienced adverse events (hypoxaemia, nausea, vomiting, and dizziness). By postoperative day 2, the cumulative incidence was 17.5% (predominantly dizziness and nausea). Conclusion This exploratory study provides a preliminary ED50 estimate for tegileridine in immediate post-LCRS analgesia within a multimodal regimen, with a favorable short-term safety profile. However, the wide CI limits these findings; larger studies are needed to validate dose–response relationships and better define clinically relevant effective doses.