Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil

Abstract

The prevalence of obesity is increasing, resulting in an increase in the number of surgeries performed to treat obesity and diseases induced by obesity. The associated comorbidities as well as the pharmacokinetic and pharmacodynamic changes that occur in obese patients make it difficult to control the appropriate dose of anesthetic agents. Factors that affect pharmacokinetic changes include the increase in adipose tissue, lean body weight, extracellular fluid, and cardiac output associated with obesity. These physiological and body compositional changes cause changes in the pharmacokinetic and pharmacodynamic parameters. The increased central volume of distribution and alterations in the clearance of drugs affect the plasma concentration of propofol and remifentanil in the obese population. Additionally, obesity can affect pharmacodynamic properties, such as the 50% of maximal effective concentration and the effect-site equilibration rate constant (ke0). Conducting a simulation of target-controlled infusions based on pharmacokinetic and pharmacodynamic models that include patients that are obese can help clinicians better understand the pharmacokinetic and pharmacodynamic changes of anesthetic drugs associated with this population.

Keywords

• cardiac output
• computer simulation
• ideal body weight
• metabolic clearance rate
• obesity
• pharmacokinetics