[Fluoride-induced nephrotoxicity: factor fiction?].
In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. Based upon the clinical experience with methoxyflurane, serum fluoride concentrations exceeding 50 mumol/l were considered to be nephrotoxic. Without further reevaluation, this 50 mumol/l threshold was subsequently applied to other fluorinated anaesthetics as well. Enflurane and even isoflurane may, when used during prolonged operations, also yield anorganic fluoride levels in excess of 50 mumol/l. Nevertheless, no cases of renal dysfunction attributable to prolonged use of these anesthetics have been reported. About 4% of the new inhalational anaesthetic sevoflurane is metabolized, and fluoride concentrations exceeding those after enflurane are frequently measured. Numerous studies have examined the nephrotoxic potential of sevoflurane degradation products. However, fluoride-related toxicity has been observed neither in animal nor in clinical studies, including prolonged administration and patients with pre-existing renal disease. New insights into the intrarenal metabolisation of volatile anaesthetics may well explain the absence of nephrotoxicity after sevoflurane. The threshold for fluoride nephrotoxicity of 50 mumol/l, still given in many medical text-books, can no longer be applied as an indicator of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore, the elevated serum fluoride concentrations consistently recorded following anaesthesia with sevoflurane are devoid of clinical significance.
Nuscheler
M
M
Institut für Anästhesiologie, Ludwig-Maximilians-Universität München.
Conzen
P
P
Schwender
D
D
Peter
K
K
D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D005459:Fluorides / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008738:Methyl Ethers; D000077149:Sevoflurane; D013329:Structure-Activity Relationship
D018685:Anesthetics, Inhalation; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D005459:Fluorides
Fluoridinduzierte Nephrotoxizität: Fakt oder Fiktion?