title: [Compound A: toxicology and clinical relevance].
abstract: Sevoflurane, like all currently used volatile anaesthetics, is degraded by carbon dioxide absorbents. The most significant degradant is a haloalkene known trivially as "compound A". Compound A is nephrotoxic in rats and, at higher doses, in nonhuman primates, causing proximal tubular necrosis. There has been much interest in the potential for compound A toxicity in humans. Inhaled compound A concentrations are greatest at low flow rates, high sevoflurance concentrations, warmer absorbent, barium hydroxide vs soda lime, and drier absorbent. Typical inspired compound A concentrations during low-flow and closed-circuit sevoflurane anaesthesia in humans are 8-24 and 20-32 ppm with soda lime and barium hydroxide lime, respectively. Renal effects of compound A production during sevoflurane anesthesia have been examined in surgical patients and volunteers, using standard (creatinine clearance, serum BUN and creatinine) and experimental (urine excretion of protein, glucose, NAG, GST, AAP) markers of renal function. Investigations to date in surgical patients show similar renal effects of low-flow sevoflurane, low-flow isoflurane or high-flow sevoflurane. There have been no case reports of compound A-associated renal injuryin humans. In volunteers, one study found changes in experimental but not conventional renal markers, while other investigations show no significant changes in either standard or experimental markers. The mechanism of compound A nephrotoxicity in rats appears to involve metabolism to glutathione and cysteine conjugates, and their subsequent renal uptake and metabolism by pathways that are different in rats and humans.
authors.affiliation: Department of Anesthesiology, University of Washington, Seattle 98195-6540, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Kharasch
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects / Q000378:metabolism*; D000818:Animals; D004987:Ethers / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008738:Methyl Ethers / Q000009:adverse effects / Q000378:metabolism*; D051381:Rats; 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