Uptake and biotransformation of sevoflurane in humans: a comparative study of sevoflurane with halothane, enflurane, and isoflurane

Abstract

Study objective: To compare the volatile anesthetic sevoflurane with halothane, enflurane, and isoflurane on the uptake and biotransformation in humans.

Design: Prospective pharmacokinetic study of sevoflurane administration in human subjects.

Setting: Inpatient surgery clinic at a university medical center.

Patients: Thirty-two Japanese patients, free of systemic diseases, undergoing minor elective surgery with endotracheal general anesthesia.

Interventions: The patients were assigned randomly to one of four groups: halothane, enflurane, isoflurane, or sevoflurane. One of the four volatile anesthetics being investigated [equivalent to 1.1 minimum alveolar concentration (MAC): halothane, 0.85%; enflurane, 1.85%; isoflurane, 1.27%; and sevoflurane, 1.88%; in inspired concentrations throughout the first hour of anesthesia] was administered for 60 minutes.

Measurements and main results: In all patients, serum and urinary fluoride concentrations were measured. The concentrations of all gases were measured separately with a mass spectrometer. The cumulative uptake of each anesthetic agent during a certain period was calculated as an integration of the uptake rate per minute. The results for one-hour inhalation of sevoflurane (1.1 MAC) showed an uptake (corrected for body surface area and MAC) of 490 ml/m2/MAC and estimated degradation rate of 3.3%. For purposes of comparison, similar studies of halothane (uptake, 653 ml/m2/MAC; degradation rate 15.7%), enflurane (1150 ml/m2/MAC; 1.3%), and isoflurane (439 ml/m2/MAC; 0.6%) were also conducted. Sevoflurane had a peak serum inorganic fluoride concentration of 19.3 mumol/L, and no abnormality in hepatic or renal functions was observed in any of the subjects during the two weeks postoperatively.

Conclusions: Accurate determinations of uptake and degradation rate for sevoflurane and three other volatile anesthetics in Japanese patients were obtained. These findings have established that, despite its relatively large MAC (1.71%), sevoflurane has a small uptake due to its low solubility. However, the degradation rate was shown to be as high as 3.3%, resulting in a higher serum fluoride concentration than seen after administration of isoflurane, halothane, and (possibly) enflurane.