title: Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers.
abstract: BACKGROUND
  Sevoflurane is degraded by carbon dioxide absorbents to a difluorovinyl ether (compound A) that can cause renal and hepatic injury in rats. The present study applied sensitive markers of renal and hepatic function to determine the safety of prolonged (8 h), high concentration (3% end-tidal) sevoflurane anesthesia in human volunteers.
  
  
  METHODS
  Thirteen healthy male volunteers provided informed consent to undergo 8 h of 1.25 minimum alveolar concentration sevoflurane anesthesia delivered with a fresh gas flow of 2 l/min. Glucose, protein, albumin, N-acetyl-beta-D-glucosaminidase (NAG), and alpha- and pi-glutathione-S-transferase (GST) levels were analyzed in urine collected at 24 h before and for 3 days after sevoflurane anesthesia. Daily blood samples were analyzed for creatinine, blood urea nitrogen (BUN), alanine aminotransferase, alkaline phosphatase, and bilirubin concentrations. Circuit compound A and plasma fluoride concentrations were measured.
  
  
  RESULTS
  During anesthesia, average and maximum inspired compound A concentrations were 27 +/- 7 and 34 +/- 6 (mean +/- SD) and median mean blood pressure, esophageal temperature, and end-tidal carbon dioxide levels were 63 mmHg, 36.8 degrees C, and 32 mmHg, respectively. The average serum inorganic fluoride concentration 2 h after anesthesia was 66.2 +/- 14.7 microM. Results of tests of hepatic function and renal function (BUN, creatinine concentration) were unchanged after anesthesia. Glucose, protein, albumin, and NAG excretion were not significantly increased after anesthesia. Urine concentrations of alpha-GST and pi-GST were increased on day 1 after anesthesia and alpha-GST was increased on day 2 after anesthesia but returned to normal afterward.
  
  
  CONCLUSIONS
  Prolonged (8 h), high concentration (3%) sevoflurane anesthesia administered to volunteers in a fresh gas flow of 2 l/min does not result in clinically significant changes in biochemical markers of renal or hepatic dysfunction.
authors.affiliation: Department of Anesthesiology, VA Medical Center, Milwaukee, Wisconsin 53295, USA. tjebert@mcw.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Ebert
authors.forename: E J
authors.initials: EJ
authors.lastname: Frink
authors.forename: E D
authors.initials: ED
authors.lastname: Kharasch
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000097:blood; D005982:Glutathione Transferase / Q000097:blood; D006029:Glycosuria; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced; D008099:Liver / Q000187:drug effects*; D008738:Methyl Ethers / Q000633:toxicity*; D011507:Proteinuria; D000077149:Sevoflurane; D014838:Volunteers
chemical_list: D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D005982:Glutathione Transferase; D000410:Alanine Transaminase