title: A direct dynamic dose-response model of propofol for individualized anesthesia care.
abstract: In an effort to open up new opportunities in individualized anesthesia care, this paper presents a dynamic dose-response model of propofol that relates propofol dose (i.e., infusion rate) directly to a clinical effect. The proposed model consists of a first-order equilibration dynamics plus a nonlinear Hill equation model, each representing the transient distribution of propofol dose from the plasma to the effect site and the steady-state dose-effect relationship. Compared to traditional pharmacokinetic-pharmacodynamic (PKPD) models, the proposed model has structural parsimony and comparable predictive capability, making it more attractive than its PKPD counterpart for identifying an individualized dose-response model in real-time. The efficacy of the direct dynamic dose-response model over a traditional PKPD model was assessed using a mixed effects modeling analysis of the electroencephalogram (EEG)-based state entropty (SE) response to intravenous propofol administration in 34 pediatric subjects. An improvement in the mean-squared error and r(2) value of individual prediction, as well as the Akaike's information criterion (AIC) was seen with the direct dynamic dose-response model.
authors: Department of Mechanical Engineering, University of Alberta, Edmonton, AB, T6G2G8 Canada. jinoh.hahn@alum.mit.edu
authors: Jin-Oh
authors: JO
authors: Hahn
authors: Guy A
authors: GA
authors: Dumont
authors: J Mark
authors: JM
authors: Ansermino
mesh_terms: D000293:Adolescent; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002648:Child; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D008954:Models, Biological; D017711:Nonlinear Dynamics; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012815:Signal Processing, Computer-Assisted
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol