title: Renal safety and extrahepatic defluorination of sevoflurane in hepatic transplantations.
abstract: BACKGROUND
  The main metabolic pathway for defluorination of sevoflurane in the liver produces inorganic fluoride (Fl). The metabolism and effect of sevoflurane on the kidney is not clear during anhepatic phase in liver transplantation. The goal of the present study was to investigate the metabolism and renal effect of sevoflurane by measuring plasma and urine inorganic fluoride, urinary N-acetyl-glucosaminidase (NAG), and plasma creatinine levels in patients undergoing liver transplantations.
  
  
  METHODS
  After institutional approval and informed consent, we studied nine cases of orthotopic liver transplantation after anesthesia was induced with 5 mg . kg(-1) thiopental, 1 mug . kg(-1) fentanyl intravenously, the trachea was intubated after vecuronium bromide 0.1 mg . kg(-1). Anesthesia was maintained with sevoflurane (2%), O(2), and N(2)O at a total gas flow of 6 L . min(-1) using a semiclosed circle system with a sodalime canister. Blood and urine samples were obtained to measure plasma and urine fluoride concentrations and urinary NAG excretions before induction (P0), hourly during resection (P1, P2, P3), every 15 minutes during anhepatic phase (A1, A2, A3), hourly after reperfusion (neohepatic phase) (N1, N2, N3), and postoperative first hour (Po1). Preoperative (T0) and postoperative day 1 (T1), 3 (T3), 7 (T7) plasma blood urea nitrogen (BUN) and creatinine (Cr) levels were also recorded.
  
  
  RESULTS
  Mean duration of surgery was 9:06 +/- 0:09 hours. Mean inorganic fluoride concentrations in plasma were in the range of 0.71 +/- 0.30 to 28.73 +/- 3.31 mumole . L(-1). In P3, N1, N2, N3, increases in plasma inorganic fluoride concentrations were significant (P < .05) and reached a peak value at Po1. The mean urine inorganic fluoride concentrations were 12.49 +/- 2.04 to 256.7 +/- 49.62 mumole . L(-1). In A2, A3, N1, N2, and N3, mean urine inorganic fluoride concentrations were significantly increased (P < .05) and the peak value was observed at Po1. Mean NAG concentrations in urine varied (5.6 +/- 1.6 IU . L(-1) to 12.5 +/- 1.14 IU . L(-1)) and peak level was observed at 30 minutes of the anhepatic phase (A2), which did not exceed the normal values for urine NAG levels (1.5 to 6.1 U . L(-1)). No impairment was observed in serum BUN and creatinine levels at any time. While there was only a slight increase in NAG during anhepatic phase, there was no change in plasma F1.
  
  
  CONCLUSIONS
  Sevoflurane seemed to have minimal effect on kidney functions of BUN and Cr levels during liver transplantation. Although urine F1 and NAG levels increased during the anhepatic phase plasma F1, BUN, and Cr levels did not, suggesting that renal F1 production may occur in the absence of hepatic function. The renal effect of sevoflurane in chronic liver disease is controversial and must be investigated in further studies.
authors.affiliation: Department of Anesthesiology and Reanimation, Hacettepe University Faculty of Medicine, Sihhiye, Ankara 06100, Turkey. mkanbak@hacettepe.edu.tr
authors.forename: M
authors.initials: M
authors.lastname: Kanbak
authors.forename: A H
authors.initials: AH
authors.lastname: Karagoz
authors.forename: N
authors.initials: N
authors.lastname: Erdem
authors.forename: B
authors.initials: B
authors.lastname: Oc
authors.forename: F
authors.initials: F
authors.lastname: Saricaoglu
authors.forename: N
authors.initials: N
authors.lastname: Ertas
authors.forename: A
authors.initials: A
authors.lastname: Berkkan
authors.forename: O
authors.initials: O
authors.lastname: Abbasoglu
authors.forename: U
authors.initials: U
authors.lastname: Aypar
mesh_terms: D000117:Acetylglucosamine / Q000652:urine; D000293:Adolescent; D000328:Adult; D000758:Anesthesia / Q000379:methods; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D001711:Biotransformation; D002648:Child; D005459:Fluorides / Q000097:blood / Q000652:urine; D006801:Humans; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D008738:Methyl Ethers / Q000627:therapeutic use*; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012449:Safety; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D010975:Platelet Aggregation Inhibitors; D000077149:Sevoflurane; D005459:Fluorides; D000117:Acetylglucosamine