Nephrotoxicity of Fluorinated Anaesthetic Agents

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SUMMARY The subject of fluorinated anaesthetic nephrotoxicity can be summarized in two figures. Figure 6 illustrates the time-course of anaesthetic defluorination following administration of methoxyflurane, enflurane and isoflurane. Figure 9 depicts changes in urinary osmolality in response to ADH administration in relationship to peak serum inorganic fluoride levels after anaesthesia. Figure 6 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 of only 90 minutes, peak levels were maintained for three days after administration of methoxyflurane. In contrast, peak inorganic fluoride serum levels after administration of the other two agents were reached shortly after the end of anaesthesia and declined rapidly in the postanaesthetic period. To account for this prolonged elevation of fluoride levels, one has only to realize that methoxyflurane is approximately ten times more lipid soluble than either enflurane or isoflurane and that the great majority of methoxyflurane metabolism occurs in the postoperative period. Peak fluoride levels also are considerably higher after methoxyflurane anaesthesia than after administration of the other two agents. That is because methoxyflurane is biochemically more unstable than either enflurane or isoflurane and is metabolized more per unit time. Consequently, the area under the serum inorganic fluoride curve is much greater for methoxyflurane than it is for enflurane and isoflurane. Figure 9 demonstrates the strong correlation between changes in urinary osmolality after ADH administration and serum inorganic fluoride levels. Patients anaesthetized with halothane, in whom serum inorganic fluoride levels ranged from 1 to 3 /zM, showed a small increase in urinary osmolality. Volunteers anaesthetized with enflurane, in whom fluoride levels were 3 to 5 μM five days after anaesthesia, showed no change in maximum urinary osmolality, whereas an average decrease of approximately 250 mosmol/kg was seen the day after anaesthesia when the mean fluoride level was 33.6 /zM. Following high-dose methoxyflurane anaesthesia, fluoride levels ranged from 80 to 250 μM and the decrement in maximum urinary concentrating ability ranged from 400 to 600 mosmol/kg. It appears that the answers to the questions regarding inorganic fluoride nephrotoxicity are clear. Methoxyflurane is a dose-related nephrotoxin; its use should be reserved for clinical situations where it is specifically indicated, such as when a potent inhalational analgesic agent is required and when total dosage will be low (less than 2 MAC hours). Enflurane would appear to be safe in all patients, including those with mild to moderate renal impairment.