Abstract
OBJECTIVE: This study aimed to investigate the effective dose of oliceridine for suppressing hemodynamic responses to tracheal intubation during general anesthesia induction and to evaluate the influence of age on dosing requirements, thereby providing evidence for clinical medication protocols. METHODS: A prospective single-center sequential dosing trial was conducted using a modified Dixon's up-and-down method. Patients scheduled for elective surgery under general anesthesia with tracheal intubation were enrolled and divided into a young group (18-65 years) and an elderly group (≥65 years). The initial doses were 45 μg/kg for the young group and 39 μg/kg for the elderly, with 3 μg/kg adjustments based on intubation response until seven crossovers occurred. A positive cardiovascular response was defined as an increase in mean arterial pressure or heart rate exceeding 20% from baseline within 3 minutes after intubation initiation. ED50 and ED95 values were estimated using Probit regression. Secondary outcomes included the incidence of injection-related cough, sedation success rate (MOAA/S score ≤2), peri-intubation hemodynamic changes, and adverse events. RESULTS: Fifty-eight patients were enrolled (28 young, 30 elderly). The ED50 of oliceridine was 46.5 μg/kg (95% CI 42.0-51.19) and ED95 was 55.4 μg/kg (95% CI 43.58-86.56) in the young group. In the elderly group, ED50 was 39.73 μg/kg (95% CI 34.17-44.76) and ED95 was 50.11 μg/kg (95% CI 37.31-77.87). Probit models demonstrated good fit in both groups. No injection-related cough reactions were observed, and the sedation success rate was 100%. Heart rate and blood pressure decreased during induction and normalized after intubation, with no significant intergroup differences. Adverse event incidence was comparable between groups. CONCLUSION: Under standardized general anesthesia induction, the ED95 of oliceridine for suppressing tracheal intubation-induced hemodynamic elevation shows age-related differences, being approximately 55 μg/kg in younger patients and 50 μg/kg in the elderly. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT07134660.