FLUORIDE - INDUCED NEPHROTOXICITY - FACT OR FICTION

In the 1960s, the widespread use of the inhalational anaesthetic metho xyflurane was associated with a significant occurrence of postoperativ e renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions in to the circulation. Based upon the clinical experience with methoxyflu rane, serum fluoride concentrations exceeding 50 mu mol/1 were conside red to be nephrotoxic. Without further reevaluation, this 50 mu mol/1 threshold was subsequently applied to other fluorinated anaesthetics a s well. Enflurane and even isoflurane may, when used during prolonged operations, also yield anorganic fluoride levels in excess of 50 mu mo l/1. Nevertheless, no cases of renal dysfunction attributable to prolo nged use of these anesthetics have been reported. About 4% of the new inhalational anaesthetic sevoflurane is metabolized, and fluoride conc entrations exceeding those after enflurane are frequently measured. Nu merous studies have examined the nephrotoxic potential of sevoflurane degradation products. However, fluoride-related toxicity has been obse rved neither in animal nor in clinical studies, including prolonged ad ministration and patients with preexisting 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 mu mol/1, still given in many medic al textbooks, can no longer be applied as an indicator of nephrotoxici ty after isoflurane, enflurane or sevoflurane. Therefore, the elevated serum fluoride concentrations consistently recorded following anaesth esia with sevoflurane are devoid of clinical significance.