Schnider and Eleveld Models for Propofol Target-Controlled Infusion Anesthesia: A Clinical Comparison

Background: Various pharmacokinetic/pharmacodynamic (PK/PD) models have been developed to accurately dose propofol administration during total intravenous anesthesia with target-controlled infusion (TIVA-TCI). We aim to clinically compare the performance of the Schnider model and the new and general-purpose Eleveld PK/PD model during TIVA-TCI.

Methods: We conducted a prospective observational study at a single center, enrolling 78 female patients, including 37 adults (aged < 65 years) and 41 elderly patients (aged ≥ 65 years). These patients underwent breast surgery with propofol-remifentanil TIVA-TCI guided by the bispectral index (BIS) for depth of anesthesia monitoring (target value 40-60) and the surgical plethysmographic index (SPI) for antinociception monitoring (target value 20-50) without neuromuscular blockade. The concentration at the effect site of propofol (CeP) at loss of responsiveness (LoR) during anesthesia maintenance (MA) and at return of responsiveness (RoR), the duration of surgery and anesthesia (min), the time to RoR (min), the propofol total dose (mg), the deepening of anesthesia events (DAEs), burst suppression events (BSEs), light anesthesia events (LAEs) and unwanted spontaneous responsiveness events (USREs) were considered to compare the two PK/PD models.

Results: Patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD model showed a lower CeP at LoR (1.7 (1.36-2.25) vs. 3.60 (3.00-4.18) μg/mL, p < 0.001), higher CePMA (2.80 (2.55-3.40) vs. 2.30 (1.80-2.50) μg/mL, p < 0.001) and at RoR (1.48 (1.08-1.80) vs. 0.64 (0.55-0.81) μg/mL, p < 0.001) than with the Schnider PK/PD model. Anesthetic hysteresis was observed only in the Schnider PK/PD model group (p < 0.001). DAEs (69.2% vs. 30.8%, p = 0.001) and BSEs (28.2% vs. 5.1%, p = 0.013) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the general patient population. DAEs (63.2% vs. 27.3%, p = 0.030) and BSEs (31.6% vs. 4.5%, p = 0.036) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the elderly.

Conclusions: The Schnider and Eleveld PK/PD models impact CePs differently. A greater incidence of DAEs and BSEs in the elderly suggests more attention is necessary in this group of patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD than with the Schnider model.