Absence of Biochemical Evidence for Renal and Hepatic Dysfunction after 8 Hours of 1.25 Minimum Alveolar Concentration Sevoflurane Anesthesia in Volunteers

Background Sevoflurane is degraded by carbon dioxide absorbents to a difluorovinyl ether (compound A) that can cause renal and hepatic injury in rats. The present study applied sensitive markers of renal and hepatic function to determine the safety of prolonged (8 h), high concentration (3% end‐tidal) sevoflurane anesthesia in human volunteers. Methods Thirteen healthy male volunteers provided informed consent to undergo 8 h of 1.25 minimum alveolar concentration sevoflurane anesthesia delivered with a fresh gas flow of 2 l/min. Glucose, protein, albumin, N‐acetyl‐beta‐D‐glucosaminidase (NAG), and alpha‐ and pi‐glutathione‐S‐transferase (GST) levels were analyzed in urine collected at 24 h before and for 3 days after sevoflurane anesthesia. Daily blood samples were analyzed for creatinine, blood urea nitrogen (BUN), alanine aminotransferase, alkaline phosphatase, and bilirubin concentrations. Circuit compound A and plasma fluoride concentrations were measured. Results During anesthesia, average and maximum inspired compound A concentrations were 27 +/‐ 7 and 34 +/‐ 7 6 (mean +/‐ SD) and median mean blood pressure, esophageal temperature, and end‐tidal carbon dioxide levels were 63 mmHg, 36.8 [degree sign] Celsius, and 32 mmHg, respectively. The average serum inorganic fluoride concentration 2 h after anesthesia was 66.2 +/‐ 14.7 micro Meter. Results of tests of hepatic function and renal function (BUN, creatinine concentration) were unchanged after anesthesia. Glucose, protein, albumin, and NAG excretion were not significantly increased after anesthesia. Urine concentrations of alpha‐GST and pi‐GST were increased on day 1 after anesthesia and alpha‐GST was increased on day 2 after anesthesia but returned to normal afterward. Conclusions Prolonged (8 h), high concentration (3%) sevoflurane anesthesia administered to volunteers in a fresh gas flow of 2 l/min does not result in clinically significant changes in biochemical markers of renal or hepatic dysfunction.

[1]  K. Ikeda,et al.  Effects of low-flow sevoflurane anesthesia on renal function: comparison with high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia. , 1997 .

[2]  A. Artru,et al.  Assessment of Low‐flow Sevoflurane and Isoflurane Effects on Renal Function Using Sensitive Markers of Tubular Toxicity , 1997, Anesthesiology.

[3]  R. Weiskopf,et al.  Nephrotoxicity of Sevoflurane Versus Desflurane Anesthesia in Volunteers , 1997, Anesthesia and analgesia.

[4]  E. Kharasch,et al.  Role of Renal Cysteine Conjugate beta‐Lyase in the Mechanism of Compound A Nephrotoxicity in Rats , 1997, Anesthesiology.

[5]  J. G. Kenna,et al.  Sevoflurane degradation by soda lime in a circle breathing system , 1996, Anaesthesia.

[6]  E. Eger,et al.  Factors Affecting Production of Compound A from the Interaction of Sevoflurane with Baralyme Registered Trademark and Soda Lime , 1996, Anesthesia and analgesia.

[7]  E. Eger,et al.  The safety of sevoflurane has not been adequately established. , 1996, Anesthesia and analgesia.

[8]  J. Lerman,et al.  Plasma Inorganic Fluoride Concentrations after Sevoflurane Anesthesia in Children , 1996, Anesthesiology.

[9]  K. Ikeda,et al.  Renal and Hepatic Function in Surgical Patients After Low-Flow Sevoflurane or Isoflurane Anesthesia , 1996, Anesthesia and analgesia.

[10]  P. Prokocimer,et al.  Inhalation Toxicity Study of a Haloalkene Degradant of Sevoflurane, Compound A (PIFE), in Sprague‐Dawley Rats , 1995, Anesthesiology.

[11]  K. Peter,et al.  Renal Function and Serum Fluoride Concentrations in Patients with Stable Renal Insufficiency After Anesthesia with Sevoflurane or Enflurane , 1995, Anesthesia and analgesia.

[12]  Ronald M. Jones,et al.  Serum Fluoride Concentration and Urine Osmolality After Enflurane and Sevoflurane Anesthesia in Male Volunteers , 1995, Anesthesia and analgesia.

[13]  T. Baillie,et al.  Nephrotoxicity of sevoflurane compound A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether] in rats: evidence for glutathione and cysteine conjugate formation and the role of renal cysteine conjugate beta-lyase. , 1995, Biochemical and biophysical research communications.

[14]  E. Kharasch,et al.  Human Kidney Methoxyflurane and Sevoflurane Metabolism: Intrarenal Fluoride Production as a Possible Mechanism of Methoxyflurane Nephrotoxicity , 1994, Anesthesiology.

[15]  E. Bellorín-Font,et al.  Role of protein kinase C on the acute desensitization of renal cortical adenylate cyclase to parathyroid hormone. , 1995, Kidney international.

[16]  Y. Numata,et al.  Varied value of urinary N-acetyl-beta-D-glucosaminidase isoenzyme B in males of reproductive age. , 1994, Kidney international. Supplement.

[17]  K. Ikeda,et al.  Long‐duration, Low‐flow Sevoflurane Anesthesia Using Two Carbon Dioxide Absorbents: Quantification of Degradation Products in the Circuit , 1994, Anesthesiology.

[18]  S. Morgan,et al.  Renal Concentrating Function with Prolonged Sevoflurane or Enflurane Anesthesia in Volunteers , 1994, Anesthesiology.

[19]  E. Eger,et al.  Toxicity of Compound A in Rats: Effect of Increasing Duration of Administration , 1994, Anesthesiology.

[20]  K. Ikeda,et al.  Closed‐circuit Anesthesia with Sevoflurane in Humans Effects on Renal and Hepatic Function and Concentrations of Breakdown Products with Soda Lime in the Circuit , 1994, Anesthesiology.

[21]  M. Malcomson,et al.  Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients. , 1992, Anesthesiology.

[22]  A. J. Gandolfi,et al.  Plasma inorganic fluoride with sevoflurane anesthesia: correlation with indices of hepatic and renal function. , 1992 .

[23]  C. Mogensen,et al.  Graded exercise and protein excretion in diabetic man and the effect of insulin treatment. , 1982, Kidney international.

[24]  R. G. Price.  Urinary enzymes, nephrotoxicity and renal disease. , 1982, Toxicology.

[25]  R. R. Robinson.  Isolated proteinuria in asymptomatic patients. , 1980, Kidney international.

[26]  N. T. Smith,et al.  Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers. , 1977, Anesthesiology.

[27]  M. Cousins,et al.  Methoxyflurane nephrotoxicity. A study of dose response in man. , 1973, JAMA.

[28]  J. I. Levitt.  The prognostic significance of proteinuria in young college students. , 1967, Annals of internal medicine.