Serumfluoridkonzentrationen und exokrine Nierenfunktion bei Anwendung von Sevofluran und Enfluran Eine offene, randomisierte, vergleichende Phase III – Studie an nierengesunden Patienten

Zusammenfassung

In einer offenen, randomisierten, prospektiven und vergleichenden Studie zwischen Sevofluran und Enfluran wurden bei 30 nierengesunden Patienten die Serumfluoridkonzentrationen und die exokrine Nierenfunktion bis zum 3. postoperativen Tag untersucht. Die applizierte Dosis betrug in beiden Gruppen ca. 1,65 MAC-Stunden. Die maximale Serumfluoridkonzentration war mit 34,5 μmol/l nach Sevofluran fast doppelt so hoch wie nach Enfluran (19,4 μmol/l). 24 h nach Anästhesieende war die Serumfluoridkonzentration in der Sevoflurangruppe auf ca. 25% des Maximalwerts abgefallen, in der Enflurangruppe auf ca. 40% des Maximalwerts. Ab diesem Zeitpunkt war kein Unterschied mehr zwischen den beiden Gruppen nachweisbar. Die Fluoridbelastung (Area under the curve, AUC) war nach Sevofluran (688 μmol/l·h) etwas größer als nach Enfluran (591 μmol/l·h). Die Korrelation von MAC-Stunden (applizierte Dosis) und AUC war in beiden Gruppen besser als die von MAC-Stunden und maximaler Serumfluoridkonzentration. Veränderungen von Laborvariablen (Natrium, Osmolalität, Kreatinin, Harnstoff und Harnsäure i.S., spez. Gewicht, Osmolalität und pH-Wert i.U.), die auf eine Nierenschädigung hinweisen würden, wurden nicht nachgewiesen.

Abstract

Sevoflurane is a “new” volatile inhaled anaesthetic. Owing to its lower blood-gas solubility coefficient, emergence from anaesthesia is faster with sevoflurane than with isoflurane, enflurane, or halothane. Sevoflurane undergoes metabolic biodegradation, releasing inorganic fluoride ions that could produce nephrotoxicity. In this study, we compared serum inorganic fluoride concentrations (IFCs) in patients receiving either sevoflurane or enflurane. Furthermore, indices of renal function were evaluated until the 3rd postoperative day.

Methods. Thirty patients with no history of renal or hepatic disease and with an anticipated duration of anaesthesia of at least 3 h were studied in an open, prospective, randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone, and vecuronium for facilitating endotracheal intubation. Anaesthesia was maintained with sevoflurane or enflurane, 60% nitrous oxide in oxygen, and additional doses of fentanyl. Blood samples for serum IFCs were obtained preoperatively and 2 and, if possible, 4 and 6 h after starting sevoflurane or enflurane, at the end of anaesthesia, and 1, 2, 4, 8, 12, 24, 48 and 72 h post-anaesthesia. Fluoride analysis was performed using an ion-selective electrode. Indices of renal function (serum sodium, osmolality, creatinine, urea, and uric acid, urine specific gravity, osmolality, and pH) were evaluated preoperatively, at the end of anaesthesia, and 24, 48, and 72 h post-anaesthesia.

Results. The duration of anaesthetic exposure was approximately 1.65 MAC-h for both inhaled anaesthetics. Peak serum IFCs were higher with sevoflurane (34.5 μmol/l) than with enflurane (19.4 μmol/l). Fluoride levels decreased more rapidly with sevoflurane: 24 h post-anaesthesia there was no difference between sevoflurane and enflurane (Fig. 1). The area under the curve (AUC) was greater with sevoflurane (688 μmol/l·h) than with enflurane (591 μmol/l·h). For both groups correlation coefficients were higher for MAC-h and AUC than for MAC-h and peak serum IFC (Figs. 2 and 3). Indices of renal function did not change in either group.

Discussion. In our study 1.69 MAC-h sevoflurane produced peak serum IFCs of 34.5 μmol/l. This is in accordance with the investigation of Frink et al. [4], who reported approximately 30 μmol/l after 1.4 MAC-h sevoflurane. Peak serum IFCs with sevoflurane were twice those with enflurane. Within the first 24 h post-anaesthesia, fluoride levels decreased more rapidly after sevoflurane. AUC may be more important than peak serum IFC in evaluating patients who are at risk for renal concentrating defects. In our study there was no evidence of renal dysfunction in either group.