Pharmacokinetic concepts for dexmedetomidine target-controlled infusion pumps in children.

Abstract

Pharmacokinetic parameter estimates are used in mathematical equations (pharmacokinetic models) to describe concentration changes with time in a population and are specific to that population. Simulation using these models and their parameter estimates can enrich understanding of drug behavior and serve as a basis for study design. Pharmacokinetic concepts are presented pertaining to future designs of dexmedetomidine target-controlled infusion pumps in children. This manuscript provides the pediatric anesthesiologist with an understanding of the nuances that should be considered when using target-controlled infusion pumps; how the central volume may differ between populations, how clearance changes with age, and the impact of adverse effects on dose. In addition, the ideal loading dose and rate of delivery to achieve target concentration without adverse cardiovascular effects are reviewed, and finally, dose considerations for obese children, based on contact-sensitive half-time, are introduced. An understanding of context-sensitive half-time changes with age enables anesthetic practitioners to better estimate duration of effect after cessation of dexmedetomidine infusion. Use of these known pharmacokinetic parameters and covariate information for the pediatric patient could readily be incorporated into commercial target-controlled infusion pumps to allow effective and safe open-loop administration of dexmedetomidine in children.