title: Dose-related biochemical markers of renal injury after sevoflurane versus desflurane anesthesia in volunteers.
abstract: Sevoflurane (CH2F-O-CH[CF3]2) reacts with carbon dioxide absorbents to produce Compound A (CH2F-O-C[=CF2][CF3]). Because of concern about the potential nephrotoxicity of Compound A, the United States package label (but not that of several other countries) for sevoflurane recommends the use of fresh gas flow rates of 2 L/min or more. We previously demonstrated in humans that a 2-L/min flow rate delivery of 1.25 minimum alveolar anesthetic concentration (MAC) sevoflurane for 8 h can injure glomeruli (i.e., produce albuminuria) and proximal tubules (i.e., produce glucosuria and urinary excretion of alpha-glutathione-S-transferase [alpha-GST]). The present report extends this investigation to fasting volunteers given 4 h (n = 9) or 2 h (n = 7) of 1.25 MAC sevoflurane versus desflurane at 2 L/min via a standard circle absorber anesthetic system (all subjects given both anesthetics). Markers of renal injury (urinary creatinine, albumin, glucose, alpha-GST, and blood urea nitrogen) did not reveal significant injury after anesthesia with desflurane. Sevoflurane degradation with a 2-L/min fresh gas inflow rate produced average inspired concentrations of Compound A of 40 +/- 4 ppm (mean +/- SD, 8-h exposure [data from previous study]), 42 +/- 2 ppm (4 h), and 40 +/- 5 ppm (2 h). Relative to desflurane, sevoflurane given for 4 h caused statistically significant transient injury to glomeruli (slightly increased urinary albumin and serum creatinine) and to proximal tubules (increased urinary alpha-GST). Other measures of injury did not differ significantly between anesthetics. Neither anesthetic given for 2 h at 1.25 MAC produced injury. We conclude that 1.25 MAC sevoflurane plus Compound A produces dose-related glomerular and tubular injury with a threshold between 80 and 168 ppm/h of exposure to Compound A. This threshold for renal injury in normal humans approximates that found previously in normal rats.
  
  
  CONCLUSIONS
  Human (and rat) kidneys are injured by a reactive compound (Compound A) produced by degradation of the clinical inhaled anesthetic, sevoflurane. Injury increases with increasing duration of exposure to a given concentration of Compound A. The response to Compound A has several implications, as discussed in the article.
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
authors.initials: D
authors.lastname: Gong
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: R B
authors.initials: RB
authors.lastname: Weiskopf
mesh_terms: D000328:Adult; D000768:Anesthesia, General / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D015415:Biomarkers / Q000097:blood / Q000652:urine; D056486:Chemical and Drug Induced Liver Injury; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D005459:Fluorides / Q000097:blood; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects / Q000493:pharmacokinetics; D007530:Isoflurane / Q000009:adverse effects / Q000031:analogs & derivatives*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers; D000077149:Sevoflurane; D013696:Temperature; D013990:Tidal Volume
chemical_list: D018685:Anesthetics, Inhalation; D015415:Biomarkers; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D000077335:Desflurane; D007530:Isoflurane; D005459:Fluorides