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 anesthesia is associated with an increased urinary excretion of biochemical markers, 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 examine 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 sevoflurane (LS), high-flow sevoflurane plus probenecid (HSP), and high-flow sevoflurane (HS). Probenecid (2.0 g) was administered orally 2 h before the induction 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 groups. All patients underwent prolonged low-flow (1 l/min) or high-flow (6 l/min) sevoflurane anesthesia. Urinary excretion of protein, albumin, beta(2)-microglobulin, glucose, and N-acetyl-beta-d-glucosaminidase was measured for up to 7 days postoperatively.


RESULTS
Sevoflurane doses were similar in all four groups. There were no differences in blood urea nitrogen, creatinine, or creatinine clearance among the four groups after anesthesia. Average values for urinary excretion of protein, beta(2)-microglobulin, and N-acetyl-beta-d-glucosaminidase in the 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-flow sevoflurane groups (HSP, HS).


CONCLUSIONS
Low-flow sevoflurane, which produces a sevenfold higher compound A exposure than high-flow sevoflurane, resulted in significant increases of several biochemical markers in half of the patients. Probenecid appears to provide protection against these renal effects.
Higuchi
H
H
Department of Anesthesia, Self Defense Force Central Hospital, Tokyo, Japan. higu-chi@ka2.so-net.or.jp
Wada
H
H
Usui
Y
Y
Goto
K
K
Kanno
M
M
Satoh
T
T
D000328:Adult; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004987:Ethers / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000009:adverse effects*; D011184:Postoperative Period; D011339:Probenecid / Q000494:pharmacology*; D000077149:Sevoflurane; D014528:Uricosuric Agents / Q000494:pharmacology*; D001613:beta 2-Microglobulin / Q000652:urine
D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D014528:Uricosuric Agents; D001613:beta 2-Microglobulin; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D003404:Creatinine; D005947:Glucose; D011339:Probenecid