title: Target controlled infusion for kids: trials and simulations.
abstract: Target controlled infusion (TCI) for Kids is a computer controlled system designed to administer propofol for general anesthesia. A controller establishes infusion rates required to achieve a specified concentration at the drug's effect site (C(e)) by implementing a continuously updated pharmacokinetic-pharmacodymanic model. This manuscript provides an overview of the system's design, preclinical tests, and a clinical pilot study. In pre-clinical tests, predicted infusion rates for 20 simulated procedures displayed complete convergent validity between two software implementations, Labview and Matlab, at computational intervals of 5, 10, and 15s, but diverged with 20s intervals due to system rounding errors. The volume of drug delivered by the TCI system also displayed convergent validity with Tivatrainer, a widely used TCI simulation software. Further tests, were conducted for 50 random procedures to evaluate discrepancies between volumes reported and those actually delivered by the system. Accuracies were within clinically acceptable ranges and normally distributed with a mean of 0.08 +/- 0.01 ml. In the clinical study, propofol pharmacokinetics were simulated for 30 surgical procedures involving children aged 3 months to 9 years. Predicted C(e) values during standard clinical practice, the accuracy of wake-up times predicted by the system, and potential correlations between patient wake-up times, C(e), and state entropy (SE) were assessed. Neither Ce nor SE was a reliable predictor of wake-up time in children, but the small sample size of this study does not fully accommodate the noted variation in children's response to propofol. A C(e) value of 1.9 mug/ml was found to best predict emergence from anesthesia in children.
authors.affiliation: Dept. of Anesthesiology, Pharmacology&Therapeutics, The Univ. of British Columbia, Vancouver, CANADA.
authors.forename: Disha
authors.initials: D
authors.lastname: Mehta
authors.forename: Jon
authors.initials: J
authors.lastname: McCormack
authors.forename: Parry
authors.initials: P
authors.lastname: Fung
authors.forename: Guy
authors.initials: G
authors.lastname: Dumont
authors.forename: J
authors.initials: J
authors.lastname: Ansermino
mesh_terms: D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics; D007262:Infusions, Intravenous / Q000379:methods; D008954:Models, Biological; D015742:Propofol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol