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 now 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 +/- 6 (mean +/- SD) and median mean blood pressure, esophageal temperature, and end-tidal carbon dioxide levels were 63 mmHg, 36.8 degrees C, and 32 mmHg, respectively. The average serum inorganic fluoride concentration 2 h after anesthesia was 66.2 +/- 14.7 mu M. 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 cu-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.