[Volatile anesthetics and low-flow anesthesia].
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Anesthesia, Inhalation↗
Biomedical subjects
M Nuscheler
Publications and source records attributed to M Nuscheler.
[Sevoflurane: metabolism and toxicity].
The new inhalational anesthetic sevoflurane is biotransformed by approximately 5%. Serum fluoride concentrations resulting from transformation mainly depend on rate of hepatic defluorination, total amount of anesthetic given and the solubility of the volatile anesthetic, as expressed by its blood gas partition coefficient. Enflurane is metabolized by 5-11%. However subsequent peak fluoride levels are lower than after sevoflurane which is a consequence of its lower rate of hepatic defluorination. To date numerous studies have examined the nephrotoxic potential of the sevoflurane degradation product fluoride. However, fluoride-related toxicity was not observed, neither in clinical or in animal studies, nor after prolonged administration or in patients with preexisting renal disease. New insights into intrarenal metabolisation of volatile anesthetics may well explain absence of nephrotoxicity after sevoflurane. The threshold of fluoride nephrotoxicity of 50 mumol/l, which has been empirically found after methoxyflurane, and which is still listed in many medical textbooks, can not be assumed a marker of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore also, the elevated serum fluoride concentrations, as regularly obtained after anesthesia with sevoflurane are devoid of clinical significance. In addition, exposure to sevoflurane or its metabolites is not associated with hepatic toxicity.
Anesthetics, Inhalation↗
[New inhalation anesthetics].
Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease.
Anesthesia, Inhalation↗
[Fluoride-induced nephrotoxicity: factor fiction?].
In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. Based upon the clinical experience with methoxyflurane, serum fluoride concentrations exceeding 50 mumol/l were considered to be nephrotoxic. Without further reevaluation, this 50 mumol/l threshold was subsequently applied to other fluorinated anaesthetics as well. Enflurane and even isoflurane may, when used during prolonged operations, also yield anorganic fluoride levels in excess of 50 mumol/l. Nevertheless, no cases of renal dysfunction attributable to prolonged use of these anesthetics have been reported. About 4% of the new inhalational anaesthetic sevoflurane is metabolized, and fluoride concentrations exceeding those after enflurane are frequently measured. Numerous studies have examined the nephrotoxic potential of sevoflurane degradation products. However, fluoride-related toxicity has been observed neither in animal nor in clinical studies, including prolonged administration and patients with pre-existing renal disease. New insights into the intrarenal metabolisation of volatile anaesthetics may well explain the absence of nephrotoxicity after sevoflurane. The threshold for fluoride nephrotoxicity of 50 mumol/l, still given in many medical text-books, can no longer be applied as an indicator of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore, the elevated serum fluoride concentrations consistently recorded following anaesthesia with sevoflurane are devoid of clinical significance.
Anesthetics, Inhalation↗
Renal function and serum fluoride concentrations in patients with stable renal insufficiency after anesthesia with sevoflurane or enflurane.
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 concentrations 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 because of increased fluoride load due to prolonged elimination half-life. In this study, measures of renal function after sevoflurane anesthesia were compared to those after enflurane in patients with chronically impaired renal function. Forty-one elective surgical patients with a stable preoperative serum creatinine concentration > or = 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 anesthesia. Serum fluoride concentrations were measured by ion-selective electrode. Renal function (creatinine, urea, sodium, osmolality) was assessed in serum and urine preoperatively and for up to 7 days postoperatively. Peak serum inorganic fluoride concentrations were significantly higher after sevoflurane than after enflurane anesthesia (25.0 +/- 2.2 vs 13.3 +/- 1.1 microM; mean +/- SEM). Laboratory measures of renal function Laboratory measures of renal function remained stable throughout the postoperative period 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 metabolism of sevoflurane metabolism worsened renal function in these patients with stable, permanent serum creatinine concentrations more than 1.5 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)
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