Dose-related Sevoflurane Metabolism to Inorganic Fluoride in Rabbits

Serum concentrations and urinary excretion of inorganic fluoride (fluoride ion), a metabolite of sevofluorane, were measured by an ion-chromatographic analyzer after inhalation of three different concentrations of sevoflurane in adult, male Japanese white rabbits weighing 2.6－3.6 kg. Sevoflurane was administered at concentrations of 0% (control), 1%, 2% and 3% (Groups I, II, III and IV, respectively) through a sevoflurane vaporizer for 2 hr under controled ventilation. Blood and urine samples were collected during and after termination of sevoflurane inhalation at scheduled time intervals for 24 hr. The total volume of urine, the urinary pH and the osmolality of serum and urine were not significantly different among any of the groups. Osmolality of the serum and urine was within normal range in all groups of animals. The mean serum peak values of fluoride ion were 0.7±0.5, 22.8±8.7, 31.8±11.0 and 41.5±13.2 μM (mean± SD) in groups I, II, III and IV, respectively. Peak values were recorded within 15 min after the termination of inhalation. The cumulative amounts of fluoride ion excreted in urine in 24 hr were calculated to be 5.0±1.6, 26.1±6.7, 41.4±11.3 and 64.3±18.0 μmol (mean±SD) in groups I, II, III and IV, respectively. Regression analysis revealed significant correlations between the formation and excretion of fluoride ion, and the dose of sevoflurane (r=0.85, p<0.05 and r=0.89, p<0.05, respectively). The authors conclude that the formation and excretion of fluoride ion after sevoflurane anesthesia is dependent on the dose of the drug. This study also concludes that 1－3% of sevoflurane for 2 hr of inhalation is unlikely to produce renal dysfunction.