title: Absence of renal and hepatic toxicity after four hours of 1.25 minimum alveolar anesthetic concentration sevoflurane anesthesia in volunteers.
abstract: Sevoflurane is degraded by CO2 absorbents to Compound A. The delivery of sevoflurane with a low fresh gas flow increases the generation of Compound A. The administration of Compound A to rats can produce injury to renal tubules that is dependent on both the dose and duration of exposure to Compound A. The present study evaluated renal and hepatic function in eight volunteers after a 1-L/min delivery of 3% (1.25 minimum alveolar anesthetic concentration) sevoflurane for 4 h. Volunteers gave their informed consent and provided 24-h urine collections before and for 3 days after sevoflurane anesthesia. Urine samples were analyzed for glucose, protein, albumin, and alpha- and pi-glutathione-S-transferase. Daily blood samples were analyzed for markers of renal and liver injury or dysfunction. Circuit Compound A and plasma fluoride concentrations were determined. During anesthesia, the average maximal inspired Compound A concentration was 39 +/- 6 (mean +/- SD). The median mean arterial pressure, esophageal temperature, and end-tidal CO2 were 62 +/- 6 mmHg, 36.5 +/- 0.3 degrees C, and 30.5 +/- 0.5 mm Hg, respectively. Two hours after anesthesia, the plasma fluoride concentration was 50 +/- 9 micromol/L. All markers of hepatic and renal function were unchanged after anesthesia (repeated-measures analysis of variance P > 0.05). Low-flow sevoflurane was not associated with renal or hepatic injury in humans based on unchanged biochemical markers of renal and liver function.
  
  
  CONCLUSIONS
  Sevoflurane delivered in a 3% concentration with a fresh gas flow of 1 L/min for 4 h generated an average maximal Compound A concentration of 39 ppm but did not result in any significant increase in sensitive markers of renal function or injury, including urinary protein, albumin, glucose, and alpha- and pi-glutathione-S-transferase.
authors.affiliation: Department of Anesthesiology and Physiology, The Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee 53295, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Ebert
authors.forename: L D
authors.initials: LD
authors.lastname: Messana
authors.forename: T D
authors.initials: TD
authors.lastname: Uhrich
authors.forename: T S
authors.initials: TS
authors.lastname: Staacke
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D001831:Body Temperature / Q000187:drug effects; D004987:Ethers / Q000378:metabolism*; D005982:Glutathione Transferase / Q000652:urine; D006029:Glycosuria / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008738:Methyl Ethers / Q000008:administration & dosage*; D011507:Proteinuria; D000077149:Sevoflurane; D013997:Time Factors
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