Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment

Area of Science:

• Anesthesiology
• Pharmacokinetics
• Pharmacodynamics

Background:

• Obesity presents unique challenges for anesthetic drug management.
• Accurate pharmacokinetic-pharmacodynamic (PKPD) modeling is crucial for safe and effective propofol administration.

Purpose of the Study:

• To develop and validate a propofol PKPD model for effect-site target-controlled infusion (TCI) specifically in obese patients.
• To compare the performance of the derived model against existing PK models.

Main Methods:

• A three-compartment PK model linked to a sigmoidal Emax pharmacodynamic model was utilized.
• Population modeling was performed using nonlinear mixed-effects regression (NONMEM) with pooled data from obese adults.
• Predictive performance was assessed using an independent dataset, evaluating median predictive errors (MDPE) and median absolute predictive errors (MDAPE).

Main Results:

• Total body weight was identified as the optimal covariate for volumes and clearances in the PK model.
• A lag time parameter significantly improved the model fit for Bispectral Index (BIS) response.
• The derived model demonstrated acceptable predictive performance for both PK and PD parameters in obese patients.

Conclusions:

• A propofol PKPD model was successfully derived and validated for TCI in obese patients.
• The model, developed using obese patient data, is not recommended for lean individuals due to potential underdosing.
• Further validation and refinement of propofol TCI models for diverse patient populations are warranted.