title: Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers.
abstract: Present package labeling for sevoflurane recommends the use of fresh gas flow rates of 2 L/min or more when delivering anesthesia with sevoflurane. This recommendation resulted from a concern about the potential nephrotoxicity of a degradation product of sevoflurane, "Compound A," produced by the action of carbon dioxide absorbents on sevoflurane. To assess the adequacy of this recommendation, we compared the nephrotoxicity of 8 h of 1.25 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 10) versus desflurane (n = 9) in fluid-restricted (i.e., nothing by mouth overnight) volunteers when the anesthetic was given in a standard circle absorber anesthetic system at 2 L/min. Subjects were tested for markers of renal injury (urinary albumin, glucose, alpha-glutathione-S-transferase [GST], and pi-GST; and serum creatinine and blood urea nitrogen [BUN]) before and 1, 2, 3, and/or 5-7 days after anesthesia. Desflurane did not produce renal injury. Rebreathing of sevoflurane produced average inspired concentrations of Compound A of 41 +/- 3 ppm (mean +/- SD). Sevoflurane was associated with transient injury to: 1) the glomerulus, as revealed by postanesthetic albuminuria; 2) the proximal tubule, as revealed by postanesthetic glucosuria and increased urinary alpha-GST; and 3) the distal tubule, as revealed by postanesthetic increased urinary pi-GST. These effects varied greatly (e.g., on postanesthesia Day 3, the 24-h albumin excretion was < 0.03 g (normal) for one volunteer; 0.03-1 g for five others; 1-2 g for two others; 2.1 g for one volunteer; and 4.4 g for another volunteer). Neither anesthetic affected serum creatinine or BUN, nor changed the ability of the kidney to concentrate urine in response to vasopressin, 5 U/70 kg subcutaneously (i.e., these measures failed to reveal the injury produced). In addition, sevoflurane, but not desflurane, caused small postanesthetic increases in serum alanine aminotransferase (ALT), suggesting mild, transient hepatic injury.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0464, USA.
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: D D
authors.initials: DD
authors.lastname: Koblin
authors.forename: T
authors.initials: T
authors.lastname: Bowland
authors.forename: P
authors.initials: P
authors.lastname: Ionescu
authors.forename: M J
authors.initials: MJ
authors.lastname: Laster
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.forename: D
authors.initials: D
authors.lastname: Gong
authors.forename: J
authors.initials: J
authors.lastname: Sonner
authors.forename: R B
authors.initials: RB
authors.lastname: Weiskopf
mesh_terms: D000328:Adult; D000419:Albuminuria; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D000077335:Desflurane; D004987:Ethers / Q000009:adverse effects*; D005459:Fluorides / Q000097:blood; D005982:Glutathione Transferase / Q000652:urine; D006029:Glycosuria; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects; D007530:Isoflurane / Q000009:adverse effects / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D003404:Creatinine; D000077335:Desflurane; D007530:Isoflurane; D005982:Glutathione Transferase; D005459:Fluorides