Pharmacokinetics of desflurane uptake and disposition in piglets.

Introduction: Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Methods: Seven piglets were administered inspiratory 6% desflurane by inhalation over 2 h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. Results: The rates of desflurane body uptake increased considerably in the initial 5 min (79.8 ml.min-1) and then declined slowly until 120 min (27.0 ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2 h, only 21.9% of the desflurane administered had been eliminated from the body. Conclusion: Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Pharmacokinetics of sevoflurane elimination from respiratory gas and blood after coronary artery bypass grafting surgery.

PURPOSE: Sevoflurane, with a relative low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. This study will determine the profiles of four concentration-time curves to characterize the pharmacokinetics of sevoflurane elimination. METHODS: Eight patients (aged 54-76 years) undergoing coronary arterial bypass grafting surgery were enrolled in this study. At the end of surgery, anesthetic gas and blood were sampled 20 min before and after stopping sevoflurane administration, with prior maintenance of a fixed 5% inspired sevoflurane (CIsev) in 6 L/min oxygen flow for 60 min before the cessation of sevoflurane administration for the subsequent 20 min elimination. An infrared analyzer was used to determine both CIsev and end-tidal sevoflurane (CEsev). The sevoflurane concentrations in the internal jugular-bulb (Jsev), arterial (Asev) and pulmonary arterial blood (PAsev) were analyzed by gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: A bi-exponential decay function was the best fit for the CEsev,Jsev, Asev, and PAsev time curves. There were two distinct components, the initial 5-min fast or distribution phase and the subsequent 15-min slow or elimination phase. Before cessation of the sevoflurane supplement, the step-down concentration of sevoflurane was listed in the following order: CIsev > CEsev > Asev ≧ Jsev > PAsev. During the elimination phase, the fastest decay occurred in CEsev, followed by Jsev, Asev and PAsev. Therefore, a reverse step-down pattern was observed (PAsev > Asev ≧ Jsev > CEsev) after 20 min. The ratio of Asev to CEsev was 89% at baseline before stopping sevoflurane administration, but the ratio of Asev to CEsev increased to 128% at the twentieth min of the sevoflurane elimination phase. CONCLUSIONS: During elimination, the initial washout of sevoflurane from the functional residual capacity of the lungs was reflected in the fast component of the CEsev, Jsev, Asev, and PAsev time curves. In contrast, the slow component was dominated by the tangible effects of the physiological membrane barriers, such as the alveoli-pulmonary capillary and blood-brain barriers.

Pharmacokinetics of desflurane elimination from respiratory gas and blood during the 20 minutes after cardiac surgery.

BACKGROUND/PURPOSE: Desflurane, with a low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. Investigation of desflurane elimination from blood and respiratory gas should provide useful information with respect to a patient's recovery from anesthesia. Therefore, this study is designed to characterize the pharmacokinetics of desflurane elimination after cardiac surgery. METHODS: Sixteen patients undergoing coronary artery bypass graft surgery were enrolled. At the end of surgery, multiple gas and blood samples were taken in the 20 minutes before and after stopping desflurane administration, with prior maintenance of a fixed 7% inspired desflurane in 6 L/minute oxygen flow for 60 minutes before the cessation. The blood desflurane concentrations, including internal jugular-bulb blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) were analyzed using gas chromatography. The inspiratory desflurane concentration (CIdes) and end-tidal desflurane (CEdes) were measured with an infrared analyzer, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: Before cessation of desflurane administration, the inspiratory desflurane concentration (CIdes) was relatively higher than end-tidal (CEdes), arterial (Ades), internal jugular-bulb blood (Jdes), and pulmonary (PAdes) concentrations in sequence (CIdes > CEdes > Ades≈ Jdes > PAdes). During the elimination phase, rapid decay occurred in CEdes, followed by Jdes, Ades and PAdes. Twenty minutes after stopping desflurane administration, the desflurane concentrations were: PAdes > Ades≈ Jdes > CEdes. The decay curves of desflurane concentrations demonstrated two distinct elimination components: an initial, fast 5-minute component followed by a slow 15-minute component. CONCLUSION: Desflurane is eliminated fastest from the lungs, as indicated by CEdes, compared to elimination from circulating blood. The initial, rapid 5-minute desflurane washout reflected the diluting effect of functional residual capacity of the lungs.

Pharmacokinetics of isoflurane in human blood.

Investigation of isoflurane washout from the human body and brain provides more precise information about elimination in anesthesia. The elimination pattern of isoflurane remains poorly quantified, and therefore this study tried to clarify the pharmacokinetic pattern of isoflurane elimination. Sixteen patients (aged 48-78 years), undergoing coronary arterial bypass grafting surgery were enrolled in this study. Sixty minutes prior to the end of surgery, we kept a fixed 2% inspired isoflurane in 6,000 ml min(-1) oxygen flow. Isoflurane supplement was then discontinued to study the 20-min isoflurane elimination. An infrared analyzer was used to determine both inspired isoflurane and end-tidal isoflurane. The isoflurane concentration in the internal jugular bulb blood, arterial blood and pulmonary arterial blood were analyzed by gas chromatography. Biexponential decay function was the best fitted for the end-tidal isoflurane- and arterial blood isoflurane-time curves. There were two distinct components, including initial 5-min fast component and the next 15-min slow component. Monoexponential decay function was the best fitted for the pulmonary arterial blood- and jugular bulb blood-time curves. During elimination, the initial washout of isoflurane from functional residual capacity of lungs is reflected in the fast component of the isoflurane concentration time curves. The later slow component is dominated by the tangible manifestation of physiological membrane barriers, including the existence of alveoli-pulmonary capillary, blood-brain barriers.

Pharmacokinetics of isoflurane: uptake in the body.

We investigated the effect of the inspired isoflurane concentration (C(I)iso) on body uptake by comparing the isoflurane concentration in the pulmonary artery blood (PAiso) and that in the arterial blood (Aiso) in 16 patients undergoing coronary artery bypass grafting surgery during the 1st, hour of isoflurane anesthesia. The patients received standardized anesthetics consisting of fentanyl and thiopental and were then allocated to receive either 1% or 2% C(I)iso (n = 8 in each group). C(I)iso and end-tidal isoflurane concentration (C(E)iso) were measured by infrared analysis, and Aiso and PAiso were analyzed by gas chromatography. The cardiac output was measured by thermodilution by use of a pulmonary artery catheter. The body tissue could be represented by the gradient C(I)iso-C(E)iso or Aiso-PAiso over time, respectively. The 2% inspired isoflurane group had twice the gradients (either C(I)iso-C(E)iso or Aiso-PAiso) than the 1% inspired isoflurance group. Additionally, both C(I)iso-C(E)iso and Aiso-PAiso were nearly constant over the hour of the study. The inspired concentration-dependent and near-constant uptake of isoflurane over time has important implications which enable us to apply the uptake pattern of isoflurane to clinical practice.

Pharmacokinetics of isoflurane: uptake in the brain.

We studied the effect of the inspired isoflurane concentration (C(I)iso) on the pharmacokinetics of isoflurane uptake in the brain by comparing the isoflurane concentration in internal jugular-bulb blood (Jiso) with that in arterial blood (Aiso), and analyzed this by gas chromatography. Sixteen patients (aged 43-76 years) undergoing colorectal surgery were enrolled, and anesthesia was maintained with a constant C(I)iso of either 1% (group 1, n = 8) or 2% (group 2, n = 8) during the 1st hour of isoflurane anesthesia. Under constant volume-controlled ventilation, we measured the C(I)iso and the end-tidal isoflurane concentration (C(E)iso) at the mouthpiece by infrared analysis. Our results demonstrate that it takes 40 min for the brain tissue concentration to equal Aiso for 1% C(I)iso, and 50 min for 2% C(I)iso. The Aiso (and/or Jiso) for 2% C(I)iso was approximately double when compared to that for 1% C(I)iso. Except during the initial wash-in period of the functional residual capacity in the first 3 min, the differences between C(I)iso and C(E)iso revealed that the body uptake of isoflurane for 2% C(I)iso was twice that for 1% C(I)iso. These results demonstrate that the pharmacokinetics of isoflurane uptake in the brain is time-dependent for Jiso to equal Aiso, and the midpoint between Aiso and Jiso (likely representing the isoflurane concentration in brain tissue) was dependent on C(I)iso.