Serum glutathione S‐transferase concentrations and creatinine clearance after sevoflurane anaesthesia

Abstract

SummaryThe effects of sevoflurane and isoflurane on serum glutathione S-transferase concentrations and creatinine clearance were compared in 50 ASA I-III patients aged over 18 years undergoing body surface surgery of 1-3 h predicted duration. Patients randomly received sevoflurane (n ¼ 24) or isoflurane (n ¼ 26) in nitrous oxide and oxygen (FIO 2 ¼ 0.4) via a nonrebreathing system. Fluids were standardised and patient's lungs ventilated to normocapnia. Expired concentration of anaesthetic agent was adjusted to maintain systolic arterial pressure between 70 and 100% of baseline. Patients received significantly less (p < 0.05) sevoflurane (1.0 MAC-h) than isoflurane (1.5 MAC-h). Using serum glutathione S-transferase concentrations and creatinine clearance as markers of hepatic and renal function respectively, no statistically significant differences were identified between the groups. Although sevoflurane has been administered to over one million patients in Japan and undergone extensive clinical trials in Europe and North America, concerns remain about its potential for organ toxicity [1,2]. A rate of metabolism which is greater than isoflurane or enflurane [3] may increase the risk of hepatotoxicity. Serum glutathione S-transferase (GST) concentration was used in this study as a specific marker of hepatocellular injury owing to its location in centrilobular hepatocytes and a short serum half-life [4,5].Sevoflurane is metabolised to inorganic fluoride which has been associated with nephrotoxicity in patients receiving methoxyflurane [6]. No evidence of impaired renal concentrating ability has been demonstrated with sevoflurane [7], although an increase in urinary N-acetyl-bglucosaminidase (NAG) has been noted in patients undergoing prolonged anaesthesia in conjunction with antibiotic therapy [8]. Other work using NAG has shown a similar effect on renal tubules to that of isoflurane [9]. In this study, serum fluoride concentrations were monitored and serum osmolality and creatinine clearance used as measures of renal function. MethodsWith University Ethics Committee approval and written informed consent, 50 ASA I-III patients were admitted to the study. All were in-patients over 18 years undergoing body surface surgery of 1-3 h predicted duration. Patients with evidence of hepatic or renal dysfunction or a history of heavy alcohol intake (>21 units.week ¹1 for men or >14 units.week ¹1 for women) were excluded. Patients receiving any drugs known to induce hepatic enzymes or who had received general anaesthesia within the previous week were also excluded and all women were tested to exclude pregnancy.Venous blood was drawn for baseline tests of hepatic function including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) activities and serum GST concentration. Serum electrolytes, urea, fluoride, creatinine and osmolality were also measured. A urine sample was obtained for the measurement of urine osmolality and a timed urine collection was started on adm...

The effect of desflurane on liver function markers in infants and children

“…1–3 demonstrate the individual time courses, showing no severe increase but pronounced decreases in children with elevated preanaesthetic values. These decreases seem to be too pronounced to be solely caused by reduced input from nonhepatic sources (22). It may be speculated whether these changes are accidental or whether an improved splanchnic perfusion, as has been demonstrated for desflurane in adults (23), may account for these effects.…”