BACKGROUND: Tobacco smoke contains various chemicals which may affect drug metabolism. Sevoflurane is metabolized to inorganic fluoride, and elevated serum fluoride concentrations (S-F(-)) may cause deterioration of renal function. Whether smokers develop high S-F(-) and associated disturbances in renal function is not known. METHODS: We investigated sevoflurane metabolism in 25 non-smoking and 25 smoking (> 10 cigarettes/day) generally healthy women, aged 19-68 years, undergoing gynaecological elective surgery under one minimum alveolar concentration-hour (1 MAC-h) standardized sevoflurane anaesthesia. S-F(-) was measured for 24 h. Glomerular and tubular function was assessed by measuring serum and urine tumour-associated trypsin inhibitor (TATI), beta(2)-microglobulin and serum creatinine for 48 h after sevoflurane inhalation. RESULTS: There were no differences between the two study groups with regard to S-F(-). It increased significantly in both groups: in non-smokers, from a baseline between 1.0 and 11 micromol/l (median, 1.6 micromol/l) to a maximum between 8.2 and 40 micromol/l (26 micromol/l) (P < 0.001) and, in smokers, from a baseline between 0.5 and 5.2 micromol/l (1.7 micromol/l) to a maximum between 19 and 71 micromol/l (25 micromol/l) (P < 0.001). In both groups, S-F(-) remained elevated for the entire sampling period (P < 0.001). In all five women (one non-smoker and four smokers) with a maximum S-F(-) of 40 micromol/l or higher and an area under the serum fluoride concentration-time curve (AUC(F0-24)) of 500 micromol/h/l or higher, serum TATI increased above the pathological concentration of 3.0 nmol/l, whereas only six of the 45 patients with S-F(-) below 40 micromol/l had serum TATI above 3.0 nmol/l (P < 0.001). Beta(2)-Microglobulin increased significantly (> 1 mg/l) in two patients with high S-F(-) relative to two of the 45 patients with S-F(-) below 40 micromol/l (P= 0.005). None of the patients developed clinically detectable renal dysfunction. CONCLUSION: Smoking did not affect S-F(-) after sevoflurane anaesthesia. Glomerular dysfunction, seen as increased serum TATI, was noted in five women with S-F(-) above 40 micromol/l. Our results suggest that the renal toxic threshold of S-F(-) seems to be lower than the earlier reported value of 50 micromol/l.
BACKGROUND:Tobacco smoke contains various chemicals which may affect drug metabolism. Sevoflurane is metabolized to inorganic fluoride, and elevated serum fluoride concentrations (S-F(-)) may cause deterioration of renal function. Whether smokers develop high S-F(-) and associated disturbances in renal function is not known. METHODS: We investigated sevoflurane metabolism in 25 non-smoking and 25 smoking (> 10 cigarettes/day) generally healthy women, aged 19-68 years, undergoing gynaecological elective surgery under one minimum alveolar concentration-hour (1 MAC-h) standardized sevoflurane anaesthesia. S-F(-) was measured for 24 h. Glomerular and tubular function was assessed by measuring serum and urine tumour-associated trypsin inhibitor (TATI), beta(2)-microglobulin and serum creatinine for 48 h after sevoflurane inhalation. RESULTS: There were no differences between the two study groups with regard to S-F(-). It increased significantly in both groups: in non-smokers, from a baseline between 1.0 and 11 micromol/l (median, 1.6 micromol/l) to a maximum between 8.2 and 40 micromol/l (26 micromol/l) (P < 0.001) and, in smokers, from a baseline between 0.5 and 5.2 micromol/l (1.7 micromol/l) to a maximum between 19 and 71 micromol/l (25 micromol/l) (P < 0.001). In both groups, S-F(-) remained elevated for the entire sampling period (P < 0.001). In all five women (one non-smoker and four smokers) with a maximum S-F(-) of 40 micromol/l or higher and an area under the serum fluoride concentration-time curve (AUC(F0-24)) of 500 micromol/h/l or higher, serum TATI increased above the pathological concentration of 3.0 nmol/l, whereas only six of the 45 patients with S-F(-) below 40 micromol/l had serum TATI above 3.0 nmol/l (P < 0.001). Beta(2)-Microglobulin increased significantly (> 1 mg/l) in two patients with high S-F(-) relative to two of the 45 patients with S-F(-) below 40 micromol/l (P= 0.005). None of the patients developed clinically detectable renal dysfunction. CONCLUSION: Smoking did not affect S-F(-) after sevoflurane anaesthesia. Glomerular dysfunction, seen as increased serum TATI, was noted in five women with S-F(-) above 40 micromol/l. Our results suggest that the renal toxic threshold of S-F(-) seems to be lower than the earlier reported value of 50 micromol/l.