How obesity affects the disposition of intravenous anesthetics.

Abstract

Understanding the changes in drug disposition of intravenous anesthetics in patients with obesity and administering appropriate doses are critical to avoid intraoperative awareness with recall because of underdosing and over-sedation and delayed emergence due to overdosing. Pharmacokinetic simulation or target-controlled infusion (TCI) using models that have been adapted to patients with obesity are necessary to select appropriate dosing regimens. This review aimed to describe the pharmacokinetic concepts underpinning the use of intravenous anesthetics, including propofol, remifentanil, and remimazolam, in patients with obesity. In the last 5 years, a series of pharmacokinetic models for propofol, remifentanil, and remimazolam that were estimated from populations that included obese patients have been published. These new pharmacokinetic models can be considered 'second generation' compared with earlier models in that they expand the range of covariate effects (e.g. the extremes of body weight and age) accounted for by the models. The predictive performances of each pharmacokinetic model have been shown in the literature to be within clinically acceptable limits. Among them, the propofol model by Eleveld et al. has been externally validated and has shown reasonable predictive accuracy. Pharmacokinetic simulations or TCI using pharmacokinetic models that account for the influence of obesity on a drug's disposition are essential to predict plasma/effect-site concentrations of intravenous anesthetics and understand the temporal profile of drug concentrations and effect in patients with obesity, particularly severe obesity.