Pharmacokinetics of Isoflurane in Human Blood

Abstract

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.

Awakening arterial blood and end-tidal concentrations of isoflurane in female surgical patients

“…Based on the awakening arterial concentration as 0.20% in this study, the estimated awakening time among the previous cardiac patients could be 35.6 minutes by using the extrapolated slopes of arterial concentrations from 0.57% at 15 minutes to 0.48% at 20 minutes. [10] Beyond expectation, the awakening time among patients in the present study was not significantly correlated with anesthesia duration. The relatively shorter duration of anesthesia (mean of 108 minutes) and limited BMI ranges (95% confidence interval, 22.1–24.3) may have diminished the ranges of total body uptake.…”

“…[21] In this study, the awakening time was 18.5 minutes after discontinuing 1.29 MAC isoflurane, which was longer than 15.5 minutes in pediatric neurosurgical patients receiving maintained 0.9 to 1.0 MAC isoflurane. [5] Furthermore, the actual arterial blood concentration of isoflurane was 1.18% at the end of mean 330-minute cardiac surgery in our previous 20-minute pharmacokinetic study, [10] which was higher than 0.84% in this mean 108-minute study. Based on the awakening arterial concentration as 0.20% in this study, the estimated awakening time among the previous cardiac patients could be 35.6 minutes by using the extrapolated slopes of arterial concentrations from 0.57% at 15 minutes to 0.48% at 20 minutes.…”

“…Slow alveolar washout was conducted by decreasing anesthetic concentrations in predetermined steps of 15 minutes to allow equilibration between the brain, arterial, and alveolar partial pressures, while fast washout was obtained after directly discontinuing inhaled anesthetics. [22] By examining the arterial concentrations before and after discontinuation in our previous studies, [10–12] we could clarify the actual arterial-to-end-tidal differences during elimination. The rapid reduction of the end-tidal, but not arterial concentrations in the initial 5 minutes, reflects fast washout of anesthetics from functional residual capacity of lungs, while the later 15-minute slow component is dominated by the tangible manifestation of physiological membrane barriers, including the existence of alveoli-pulmonary capillary and blood–brain barriers.…”

“…[8] As a result, a certain time period is needed after initiation of isoflurane anesthesia to: cross the alveolar membrane, enter into the blood and brain, and achieve the minimal alveolar concentration (MAC), as 1.15% for isoflurane, [9] to prevent movement in 50% patients in response to surgical stimulus. Similarly, elimination of isoflurane, [10] sevoflurane, [11] and desflurane [12] from circulation blood into the lungs is known to be time-dependent.…”

Isoflurane compared with fentanyl-midazolam-based anesthesia in patients undergoing heart transplantation

“…After tracheal intubation, an inspired concentration of 2% isoflurane in 6 L/min oxygen flow was administered to wash in functional residual capacity for 5 minutes, and then fresh gas flow was reduced to 0.3 L/min for the maintenance of minimal low flow anesthesia with inspired 2% to 5% isoflurane, [12] according to the hemodynamic status and surgical stimuli. During cardiopulmonary bypass, the perfusionist administered 1.5% to 2.5% isoflurane into the bypass circuit to maintain mean arterial blood pressure 50 to 80 mm Hg.…”