‘Renal Function and Serum Fluoride Concentrations in Patients with Stable Renal Insufficiency After Anesthesia with Sevoflurane or Enflurane Peter F. Conzen, MD*, Manfred Nuscheler, MD*, Anne Melotte, MDt, Marleen Verhaegen, MDt, Thorsten Leupolt, MD, Hugo Van Aken, MDt, and Klaus Peter, MD* Institutes of Anesthesiology, *Ludwig-Maximilians-University, Munich, Germany, and tcatholic University of Leuven, Leuven, Belgium Sevoflurane is metabolized to hexa-fluoro-isopropanol and inorganic fluoride by the human liver. Its use as an anesthetic may lead to peak plasma fluoride concentra- tions exceeding those seen after enflurane. Although there is no nephrotoxicity after sevoflurane anesthesia in humans with normal kidneys, those with chronically impaired renal function might be at increased risk be- cause of increased fluoride load due to prolonged elim- ination half-life. In this study, measures of renal func- tion after sevoflurane anesthesia were compared to those after enflurane in patients with chronically im- paired renal function. Forty-one elective surgical pa- tients with a stable preoperative serum creatinine con- centration 2 1.5 mg/dL were randomly allocated to receive sevoflurane (n = 21) or enflurane (n = 20) at a fresh gas inflow rate of 4 L/min for maintenance of an- esthesia. Serum fluoride concentrations were meas- ured by ion-selective electrode. Renal function (cre- atinine, urea, sodium, osmolality) was assessed in serum and urine preoperatively and for up to 7 days postoperatively. Peak serum inorganic fluoride concen- trations were significantly higher after sevoflurane than after enflurane anesthesia (25.0 + 2.2 vs 13.3 ? 1.1 PM; mean 2 SEM). Laboratory measures of renal func- tion remained stable throughout the postoperative pe- riod in both groups. No patient suffered a permanent deterioration of preexisting renal insufficiency and none required dialysis. Thus, neither sevoflurane nor enflurane deteriorated postoperative renal function in these patients with preexisting renal insufficiency. There is no evidence that fluoride released by metabo- lism of sevoflurane metabolism worsened renal func- tion in these patients with stable, permanent serum cre- atinine concentrations more than 1.5 mg/dL. Our data also suggest that the peak fluoride concentrations meas- ured in peripheral blood may not be a good predictor of nephrotoxic potential after sevoflurane anesthesia in these patients. (Anesth Analg 1995;81:569-75) S evoflurane is partly metabolized to hexa-fluoro- isopropanol and inorganic fluoride ions by the human hepatic cytochrome P450 2El (1). It is claimed that increased plasma levels of inorganic flu- oride are nephrotoxic as they were regularly associ- ated with a vasopressin-resistant polyuric renal failure after methoxyflurane anesthesia (2,3). An assumption is that the fluoride nephrotoxicity is dose-dependent and that both the peak plasma concentration and the duration of its increase contribute to the development of renal failure (4). The study was supported by a grant from Abbott Company. Accepted for publication May 11, 1995. Address correspondence and reprint requests to Peter F. Conzen, MD, Institute of Anesthesiology, Ludwig-Maximilians-Universitzt, KIinikum Grosshadern, Marchioninistr. 15, 81377, Miinchen, Germany. Increased serum inorganic fluoride concentrations also occur after enflurane anesthesia, although there is no published evidence that this is of significant risk for individuals with normal or impaired renal function (5). Prolonged enflurane anesthesia in healthy volun- teers produced only transient increases in serum cre- atinine, decreases in creatinine clearance, and impair- ment of renal concentrating ability as assessed by vasopressin (6). Measurements of serum inorganic flu- oride concentrations after sevoflurane anesthesia in human volunteers and in surgical patients regularly yield peak concentrations exceeding those seen after enflurane (6-9). However, the low blood solubility and rapid elimination of sevoflurane limit its metab- olism so that fluoride concentrations decrease rapidly after the completion of anesthesia, and differences between sevoflurane- and enflurane-treated subjects 01995 by the International Anesthesia Research Society 0003-2999/95/$5.00 Anesth Analg 1995;81:569-75 569