Effects of cigarette smoking on serum fluoride concentrations and renal function integrity after 1 MAC‐h sevoflurane anaesthesia

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), β 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 μmol/l (median, 1.6 μmol/l) to a maximum between 8.2 and 40 μmol/l (26 μmol/l) ( P < 0.001) and, in smokers, from a baseline between 0.5 and 5.2 μmol/l (1.7 μmol/l) to a maximum between 19 and 71 μmol/l (25 μmol/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 μmol/l or higher and an area under the serum fluoride concentration–time curve ( AUC F0–24 ) of 500 μmol/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 μmol/l had serum TATI above 3.0 nmol/l ( P < 0.001). β 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 μmol/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 μmol/l. Our results suggest that the renal toxic threshold of S‐F − seems to be lower than the earlier reported value of 50 μmol/l.