Establishing the Median Effective Dose of Tegileridine for Immediate Postoperative Analgesia Following Laparoscopic Colorectal Cancer Surgery: A Sequential Dose-Finding Study
Background: To determine the median effective dose (ED 50 ) 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 ED 50 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 ED 50 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 ED 50 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.