Effects of probenecid on renal function in surgical patients anesthetized with low-flow sevoflurane

Background: Dehydrofluorination of sevoflurane by carbon dioxide absorbents in anesthesia machines produces compound A, which is nephrotoxic in rats. Several clinical studies indicate that prolonged low-flow sevoflurane anest hesia is associated with an increased urinary excretion of biochemical mark ers, such as protein. Probenecid, a competitive inhibitor of organic anion transport, diminishes compound A nephrotoxicity in rats. The purpose of the present study was to examine the effects of low and high-flow sevoflurane anesthesia on urinary excretion of biochemical markers in humans and to exa mine the effects of probenecid on urinary excretion of these markers. Methods: Elective surgical patients (n = 64) were assigned to four groups ( n = 16 each): low-flow sevoflurane plus probenecid (LSP), low-flow sevoflur ane (LS), high-flow sevoflurane plus probenecid (HSP), and high-flow sevofl urane (HS), Probenecid (2.0 g) was administered orally 2 h before the induc tion of anesthesia in both the LSP and HSP groups. Nothing was administered orally 2 h before the induction of anesthesia in either the LS or HS group s. All patients underwent prolonged low-flow (1 l/min) or high-flow (G l/mi n) sevoflurane anesthesia. Urinary excretion of protein, albumin, beta (2)- microglobulin, glucose, and N-acetyl-beta -D-glucosaminidase was measured f or up to 7 days postoperatively. Results: Sevoflurane doses were similar in all four groups. There were no d ifferences in blood urea nitrogen, creatinine, or creatinine clearance amon g the four groups after anesthesia. Average values for urinary excretion of protein, beta (2)-microglobulin, and N-acetyl-beta -D-glucosaminidase in t he LS group were significantly higher than those in the other groups (LSP, HSP, HS; P < 0.05). There was no significant difference between the LS and LSP groups in average values for urinary excretion of albumin and glucose, although there were significant differences between the LS and both high-fl ow sevoflurane groups (HSP, HS). Conclusions: Low-flow sevoflurane, which produces a seven-fold higher compo und A exposure than high-flow sevoflurane, resulted in significant increase s of several biochemical markers in half of the patients. Probenecid appear s to provide protection against these renal effects.