A Monitor-Decoupled Pharmacodynamic Model of Propofol in Children Using State Entropy as Clinical Endpoint

Abstract

This paper presents a new monitor-decoupled model of propofol pharmacodynamics (PD) using the state entropy (SE) as the clinical endpoint of interest. In our model, the dynamics of the entropy monitor are separated from the PD response of the patient by explicitly accounting for the model of the entropy monitor in the PD identification process. The monitor model was then excluded from the identified PD model for the patient. The PD model, thus, obtained is distinct from its traditional counterpart in that it reflects the PD response of a patient with the dynamic effects of the monitor included as a specific entity. System identification trials using SE data of 31 pediatric subjects show that the PD models derived from the proposed approach are an improvement on the traditional approach. For the Paedfusor pharmacokinetic (PK) model, population-averaged effect site equilibration rate constant k(e0) was 5.4 and 3.0 for the proposed and traditional PD models ( p < 0.001), respectively. For the Kataria PK model, population-averaged k(e0) was 2.3 and 1.4 (p < 0.01). This significant difference suggests that the effects of the monitor must be considered when searching for the intrinsic PD of a patient that is free from the bias induced by the monitor characteristics.