The Effect of Age on the Delivery of Intravenous Anesthesia: a Physiologically-based Modeling Approach to Pediatric Patients

Selection of optimal dosing in anesthesia is a complex task because of the inter-individual variability in patients’ response. In this context, computer-aided modelling can be a powerful tool to assess the impact of anatomical and physiological differences among patients and simulate different administration protocols. In silico simulations via pharmacokinetic (PK) and pharmacodynamic (PD) models allow investigating the concentration profiles and the resulting effects of drugs in patients. A physiologically-based (PB) approach to pharmacokinetic modeling is thus required to account for the influence of both anatomical and physiological features. We focus on the administration of propofol to patients from 1 to 19 years old and propose new correlations for the estimation of volumes of organs and tissues in these patients. The adapted PBPK model is then combined with a specific PD model, to predict the hypnotic effects of propofol in pediatric patients. The proposed model can thus be used for simulation, training, and control applications.