Uptake and biotransformation of sevoflurane in humans: a comparative study of sevoflurane with halothane, enflurane, and isoflurane.
OBJECTIVE
To compare the volatile anesthetic sevoflurane with halothane, enflurane, and isoflurane on the uptake and biotransformation in humans.


METHODS
Prospective pharmacokinetic study of sevoflurane administration in human subjects.


METHODS
Inpatient surgery clinic at a university medical center.


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


METHODS
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.


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.
Shiraishi
Y
Y
Department of Anesthesiology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Ikeda
K
K
D000328:Adult; D000770:Anesthesia, Endotracheal; D000769:Anesthesia, Inhalation; D000777:Anesthetics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D001784:Blood Gas Analysis; D004737:Enflurane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004987:Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005459:Fluorides / Q000097:blood / Q000652:urine; D006221:Halothane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007530:Isoflurane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D008738:Methyl Ethers; D008875:Middle Aged; D011446:Prospective Studies; D012119:Respiration; D000077149:Sevoflurane
D000777:Anesthetics; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D004737:Enflurane; D007530:Isoflurane; D005459:Fluorides; D006221:Halothane