Pump-Predicted Ciprofol Ce50 for Suppressing the Cardiovascular Response to Tracheal Intubation During Fixed Sufentanil–Esketamine Induction: An Age-Stratified Dixon Up-and-Down Study

Abstract

Purpose: To estimate the ciprofol pump-predicted effect-site target concentration associated with a 50% probability of suppressing the cardiovascular response to tracheal intubation (Ce50) during fixed sufentanil-esketamine induction in two age cohorts. Patients and Methods: In this single-center, prospective, age-stratified Dixon up-and-down study, 53 adults undergoing elective surgery received sufentanil 0.3 μg/kg, esketamine 0.3 mg/kg, and ciprofol effect-site target-controlled infusion (TCI). Independent cohorts aged 45– 64 and 65– 79 years started at a pump-predicted target concentration (Ce) of 1.10 μg/mL, adjusted in 0.05 μg/mL steps. Ce50 was estimated by reversal-pair midpoints and Probit analysis. The trial was registered on March 31, 2026 (ChiCTR2600121464). Results: Thirty-two middle-aged and 21 older adults were analyzed. Midpoint Ce50 was 0.975 μg/mL (approximate 95% confidence interval [CI], 0.910– 1.040) and 1.096 μg/mL (1.072– 1.121), respectively. Probit Ce50 was 0.991 μg/mL (95% CI, 0.773– 1.103) and 1.112 μg/mL (1.078– 1.152). At target Ce, mean arterial pressure fell by 19.2% ± 11.0% and 22.5% ± 12.5% from baseline. Hypotension occurred in 20/32 (62.5%) and 13/21 (61.9%) participants. Conclusion: These exploratory Ce50 estimates are specific to the CONCERT-III pump model and the studied co-induction and rescue protocol in small, nonrandomized cohorts at a single center. Frequent hypotension and norepinephrine use accompanied induction. The estimates do not establish an independent age effect or individual dosing targets and require external validation. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2600121464; prospectively registered March 31, 2026. Keywords: ciprofol, target-controlled infusion, effect-site concentration, tracheal intubation, esketamine, hypotension

The authors' abstract, as published at the source. Drug Design Development and Therapy, 2026 · DOI ↗