Pharmacokinetics of Isoflurane: Uptake in the Body

Abstract

We investigated the effect of the inspired isoflurane concentration (C_Iiso) 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_Iiso (n = 8 in each group). C_Iiso and end-tidal isoflurane concentration (C_Eiso) 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_Iiso–C_Eiso or Aiso–PAiso over time, respectively. The 2% inspired isoflurane group had twice the gradients (either C_Iiso–C_Eiso or Aiso-PAiso) than the 1% inspired isoflurance group. Additionally, both C_Iiso–C_Eiso 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 in Human Blood

“…Isoflurane is inhaled and absorbed into the body via alveoli, as described previously in isoflurane uptake [5,6] . After cessation of isoflurane, the washout commences from the brain and body via circulating blood, delivering Table 4.…”

“…A 2% inspired concentration of isoflurane in 6,000 ml min -1 oxygen flow was administered to wash in functional residual capacity for 5 min, and then the oxygen flow rate was reduced to 300 ml min -1 for the maintenance of minimal-low-flow anesthesia [9,10] , which provided 1.5-2.5% inspired isoflurane concentration according to the dynamic status and the surgical stimuli. After intubation, a single-lumen central venous catheter and a pulmonary arterial catheter were inserted into the right internal jugular bulb and pulmonary artery, respectively, for blood sampling [5,6,11,12] . The cardiopulmonary bypass (CPB) set up was uniform for all patients, namely with a crystalloid prime, a Medtronic membrane oxygenator, moderate hypothermia (28 ° C), hemodilution to a hematocrit of 20-25%, and alpha stat pH management.…”

“…Arterial, jugular bulb and pulmonary artery blood samples were each taken up into 1-ml heparinized syringes. Blood samples were immediately placed in tightly sealed 10-ml glass vials, stored at 4 ° C and measured within 24 h. All of them were analyzed for isoflurane concentration via gas chromatography and the method used in our previous studies [5,6] . All of patients were interviewed 24 h after surgery to determine their awareness during the isoflurane elimination phase.…”

“…It is generally accepted that isoflurane washout from the well-perfused brain is more rapid compared to the rest of the body during the elimination phase. Determination of blood isoflurane concentration (partial pressure) using gas chromatography has made in vivo pharmacokinetic study possible [5,6] . Isoflurane elimination from the brain reflects the isoflurane decaying in the jugular bulb venous blood (Jiso).…”

“…Previous published research on isoflurane uptake demonstrated that end-tidal isoflurane (CEiso) is not similar to isoflurane concentration in arterial blood (Aiso) at a constant 2% inspired isoflurane concentration (CIiso) [5][6][7] . To our knowledge, there is still little investigation of isoflurane elimination in humans, and the elimination pattern of isoflurane remains poorly quantified [3,8] .…”