Background Propofol dosing guidelines recommend age-based reductions because hypnotic sensitivity increases in older adults. Most real-world evaluations of induction practice, however, have relied on total weight-normalized dose (mg/kg) rather than estimating cerebral exposure using pharmacokinetic models. Because age-related pharmacokinetic changes alter the relationship between administered dose and peak effect-site concentration (Ce,max), mg/kg surrogates may misrepresent true age-dependent exposure during induction.

Methods A retrospective reconstruction of 250,640 adult anesthetic inductions was performed using high-fidelity EHR medication timestamps. Propofol effect-site concentration trajectories were simulated at 1-second resolution using the Eleveld model. Ce,maxwas benchmarked against age-adjusted hypnotic requirements (Ce50) derived from the Eleveld model (standardized to a target Bispectral Index ≈ 47). Age–exposure relationships were estimated using covariate-adjusted natural cubic splines, controlling for BMI, sex, and ASA physical status.

Results From young adulthood (18–24 years) to the oldest cohort (85–89 years), weight-normalized induction doses were reduced by 32% (3.16 to 2.16 mg/kg). However, modeled Ce,max declined by only 17% (3.70 to 3.06 µg/mL), while the estimated physiological requirement declined by 34% (3.37 to 2.21 µg/mL), creating a widening titration offset with age. At age 75, the adjusted probability of exceeding the individual hypnotic requirement was 89.6% (95% CI: 89.3–89.8%). Notably, 54.7% (95% CI: 54.2–55.2%) of 75-year-old patients achieved peak exposures exceeding the aver-age requirement of a healthy 20-year-old, indicating persistent anchoring of exposure to youthful levels. Findings were robust across model specifications and inclusion criteria.

Conclusions In over a quarter-million inductions, real-world age-based dose re-ductions did not produce proportional reductions in peak propofol brain exposure. Achieved concentrations declined far more slowly than modeled geriatric sensitivity increases, consistent with systematic over-exposure in older adults. These findings suggest that weight-based dosing heuristics inadequately capture age-dependent exposure and support a transition toward exposure-informed and neurophysiologically guided induction titration in geriatric anesthesia.

The authors have declared no competing interest.

This study did not receive any funding

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