title: Effects of cigarette smoking on serum fluoride concentrations and renal function integrity after 1 MAC-h sevoflurane anaesthesia.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland. merja.laisalmi@kuh.fi
authors.forename: M
authors.initials: M
authors.lastname: Laisalmi
authors.forename: H
authors.initials: H
authors.lastname: Kokki
authors.forename: A
authors.initials: A
authors.lastname: Soikkeli
authors.forename: H
authors.initials: H
authors.lastname: Markkanen
authors.forename: A
authors.initials: A
authors.lastname: Yli-Hankala
authors.forename: P
authors.initials: P
authors.lastname: Rosenberg
authors.forename: L
authors.initials: L
authors.lastname: Lindgren
mesh_terms: D000328:Adult; D000368:Aged; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000378:metabolism*; D005260:Female; D005459:Fluorides / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008738:Methyl Ethers / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D000077149:Sevoflurane; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000097:blood; D014554:Urination
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D014359:Trypsin Inhibitor, Kazal Pancreatic; D005459:Fluorides