Fluorinated anaesthetic nephrotoxicity: an update.
The potential for fluorinated anaesthetic agents to cause nephrotoxicity can be summarized in two figures: Figure 2 illustrates the time course of anaesthetic defluorination following administration of methoxyflurane, enflurane and isoflurane; Figure 5 depicts changes in urinary osmolality in response to ADH administration versus peak serum fluoride levels after anaesthesia. Figure 2 clearly demonstrates that the shapes of the serum inorganic fluoride curves are different after methoxyflurane, enflurane and isoflurane anaesthesia. Despite the fact that inorganic fluoride has a half life in blood of only 90 minutes, peak levels were maintained for three days after administration of methoxyflurane. By contrast, peak fluoride levels after administration of the other two agents were reached shortly after the end of anaesthesia and they declined rapidly in the postanaesthetic period. To account for the prolonged postanaesthetic elevation of fluoride levels, one only must realize that methoxyflurane is approximately ten times more lipid soluble than either enflurane or isoflurane. Thus, methoxyflurane is present in the body for days after its administration has ended and is available for postoperative metabolism to inorganic fluoride. Peak fluoride levels also are considerably higher after methoxyflurane anaesthesia than after administration of the other two agents. That is because, on a molar basis, methoxyflurane is biochemically more unstable than either enflurane or isoflurane and is metabolized more per unit of time. Consequently, the area under the fluoride curve is much greater after methoxyflurane anaesthesia than after either enflurane or isoflurane. It is the area under the curve which probably best correlates with nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000777:Anesthetics / Q000009:adverse effects*; D000818:Animals; D004737:Enflurane / Q000009:adverse effects; D006221:Halothane / Q000009:adverse effects; D006801:Humans; D007530:Isoflurane / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008733:Methoxyflurane / Q000009:adverse effects; D008738:Methyl Ethers / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344
D000777:Anesthetics; D008738:Methyl Ethers; D008733:Methoxyflurane; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane