Target concentrations of propofol predicted by four different pharmacokinetic/pharmacodynamic models to induce loss of consciousness in neurosurgical patients

Target-controlled infusion (TCI) systems estimate plasma (Cp) and effect-site (Ce) drug concentrations using pharmacokinetic–pharmacodynamic (PK/PD) models rather than direct measurements. Because multiple models are used in clinical practice, predicted concentrations at the same clinical endpoint may differ substantially. Loss of consciousness (LOC) during anesthesia induction provides a clinically relevant reference point for examining these differences. We conducted a retrospective analysis of patients undergoing elective brain or spine surgery under propofol-based anesthesia. The propofol dose required to induce LOC was recorded, and plasma (Cp) and effect-site (Ce) concentrations at LOC were retrospectively estimated using four widely used PK/PD models (Marsh, Modified Marsh, Schnider, and Eleveld) through TCI simulation. Differences in model-derived concentrations were analyzed using mixed two-way ANOVA, with Model as a within-subject factor and Surgical Group (brain vs spine surgery) as a between-subject factor. When significant interactions were observed, post hoc comparisons were performed on log-transformed Ce values. Model-derived concentrations at LOC differed markedly across PK/PD models. Mean Ce values ranged from approximately 1.5 µg/mL with the Marsh and Eleveld models to 4.6 µg/mL with the Schnider model. Mixed ANOVA showed a strong model effect on both Ce and Cp ( p < 0.001). A significant Model × Surgical Group interaction was observed for Ce but not for Cp. Patients undergoing brain surgery received lower propofol doses and reached LOC at lower model-predicted effect-site concentrations than patients undergoing spine surgery. Predicted propofol concentrations at LOC vary considerably across PK/PD models despite identical clinical dosing, highlighting the model-dependent nature of TCI targets. These findings underscore the importance of explicit model specification and adequate user understanding when interpreting TCI-derived concentrations in both clinical practice and research.