Fluoride Metabolites After Prolonged Exposure of Volunteers and Patients to Desflurane

Abstract

We examined the metabolism of desflurane in 13 healthy volunteers given 7.35 +/- 0.81 MAC-hours (mean +/- SD) of desflurane and 26 surgical patients given 3.08 +/- 1.84 MAC-hours (mean +/- SD). Markers of desflurane metabolism included fluoride ion measured via an ion-specific electrode, nonvolatile organic fluoride measured after sodium fusion of urine samples, and trifluoroacetic acid determined by a gas chromatographic-mass spectrometric method. In both volunteer and patient groups, postanesthesia serum fluoride ion concentrations did not differ from background fluoride ion concentrations. Similarly, postanesthesia urinary excretion of fluoride ion and organic fluoride in volunteers was comparable to preanesthesia excretion rates. However, small but significant levels of trifluoroacetic acid were found in both serum and urine from volunteers after exposure to desflurane. A peak serum concentration of 0.38 +/- 0.17 mumol/L of trifluoroacetic acid and a peak urinary excretion rate of 0.169 +/- 0.107 mumol/h were detected in volunteers at 24 h after desflurane exposure. Although these increases in trifluoroacetic acid after exposure to desflurane were statistically significant, they are approximately 10-fold less than levels seen after exposure to isoflurane. Thus, desflurane strongly resists biodegradation, but a small amount is metabolized in humans.

Pharmacology of inhalational anaesthetics in infants and children*

“…In vivo metabolism of inhalational anaesthetics varies as follows: methoxyflurane (50%) > halothane (20%) > sevoflurane (3.3%) > enflurane (2.4%) > isoflurane (0.2%) > desflurane (0.02%) (Wade & Stevens 1981;Shirashi & Ikeda 1990;Sutton et al 1991). The extent of metabolism is probably less in neonates and infants than it is in adults.…”

Designing safer chemicals: predicting the rates of metabolism of halogenated alkanes.

“…Reactions were initiated by injecting the NADPH solution into the vials after a 5-min preincubation at 37°C and were terminated after 30 min by heating the samples at 70°C in a water bath for 5 min followed by cooling in ice for 10 min (18,19). Preliminary experiments were conducted to ensure that all the substrates were present at saturating concentrations and that the reaction progress was linear for at least 30 min, according to the method established by Kharasch and Thummel (20). The samples were transferred to 1.5-ml plastic centrifuge tubes and were centrifuged for 5 min at 3000 rpm on a Sorvall RT6000 bench-top centrifuge to remove precipitated proteins.…”

“…In (25,27,28), and desflurane ([F-] = 0.9 AM) (30). The activation energies were calculated as described above and are shown in Table 2.…”

Perioperative liver protection

“…The production of antibodies should be related to the respective degree of metabolism of each volatile agent (apart from sevoflurane) [49], that is, halothane (15-40%) > enflurane (2.5% [50]) > isoflurane (0.2% [51]) > desflurane (0.02% [52]). Therefore, the formation of autoantibodies should occur proportionately less frequently with isoflurane and desflurane.…”