Elimination pharmacokinetics of sevoflurane and desflurane during the recovery phase of anesthesia

ABSTRACT

BACKGROUND: Sevoflurane and desflurane are widely used anesthetics and can be simulated in pharmacokinetic models. These models are related to steady state pharmacokinetics, As anesthetic elimination is a non-steady state process, we evaluated the elimination data of volatile anesthetics using a two-compartment model (bi-exponential function). 50, 80, and 90% context-sensitive decrement times were evaluated with this function. These times are related to awakening and cognitive function recovery. METHODS: Forty-eight healthy patients were enrolled for minimal surgery under general anesthesia. They were randomly anesthetized with either sevoflurane or desflurane. At the end of surgery, when the administration of the volatile anesthetics was discontinued, end-tidal concentrations (PE) were recorded for 15 minutes. We calculated and analyzed the fraction of anesthetic concentrations (PE/PE0) using a bi-exponential function (PE0 the last end-tidal concentration of anesthetics during anesthesia). RESULTS: A bi-exponential function was fit to the elimination data using non-linear mixed-effect modeling. It showed that the anesthetic duration had effects on the coefficients of early and late components and not on the log rate constants. The coefficient of late components increased and the coefficient of early components decreased with prolonged anesthetic duration. Irrespective to the type of anesthetics, prolonged anesthesia did not affect the context-sensitive half-life; however, a prolonged period of time was required to reach 80 and 90% decrement after prolonged anesthesia. CONCLUSIONS: Prolonged anesthetic duration slowed down the elimination of volatile anesthetics. It delayed awakeness and a return to normal cognitive function after anesthesia.