Toxicity following methoxyflurane anaesthesia

Abstract

SINCE THE PUBLICATION Of the initial reports from this institution, 1-:* the pathophysiology and aetiology of the nephrotoxicity following the administration of methoxyflurane have been explored rather completely. Various studies have established that the defect in the concentrating ability of the kidney is related to the effect of fuoride ion resulting from the biotransformation of methoxyfluraue. 4-r' As expected, a correlation between methoxyflurane dose and serum fluoride ion has been demonstrated, but there have been rather large individual differences in every study. 5,~uo,u,l:~,~4 Presumably these variations are related to differences in either uptake and distribution of the anaesthetic or the rates of biotransformation. Although a logical scheme for the metabolic pathways involved has been proposed, 4'5 the appropriate labelling studies have not been done to confirm these hypothetical pathways in man. In particular, the role of the organic fluorinated metabolites in providing a source of continuing fluoride ion has not been elucidated. In view of the very high lipid solubility of methoxyflurane, obese patients might be expected to take up more of the administered drug and hence have a larger store available for metabolism. In a previous publication we saw such an effect in one patient, but were unable to draw any meaningful conclusionsY ~ The present study was designed to compare the effects of a standard exposure to methoxyfturane in normal and obese patients under as rigorous controls as possible in a clinical setting. A group of patients receiving another anaesthetic technique was also included as a control. In addition to the usual measures of renal function and fluoride ion concentration, the organic metabolite and renal clearances were also studied in an attempt to understand the puzzling differences in individual susceptibility to the nephrotoxicity of methoxyflurane. METHODSTwenty patients scheduled for elective operations outside the body cavities were studied. (Table I) All patients were hospitalized for at least 24 hours before operation. None had a history of prior renal or hepatic disease, significant cardiopulmonary dysfunction, or long-term drug therapy. The design of tile stud), and the procedures were described to the patients and informed consent was obtained l)epartments

Trace Elements in Patients with Chronic Kidney Disease

“…85 Fluoride exposure from anesthetic gases including methoxyfluorane has been reported to reduce renal urate excretion. 86 In some parts of the world fluoride is added to domestic water to reduce dental caries. Patients with CKD are more likely to retain fluoride 87 and be at risk of fluorosis.…”