Nephrotoxicity of Halogenated Inhalational Anaesthetics: Fictions and Facts

Inhaled anesthetic agents

“…Nephrotoxicity from inhaled anesthetics has been a concern for nearly 40 years, beginning with the recognition of renal toxicity associated with methoxyflurane (Penthrane [Abbott], which was withdrawn from the market in 2000). 31,32 This effect was thought to be dose related and caused by inorganic fluoride formed secondary to metabolism of the agent. 2,31 Using methoxyflurane as a model, a plasma concentration of inorganic fluoride of >50 μmol/L was thought to result in nephrotoxicity after administration of any inhaled anesthetic.…”

“…31,32 This effect was thought to be dose related and caused by inorganic fluoride formed secondary to metabolism of the agent. 2,31 Using methoxyflurane as a model, a plasma concentration of inorganic fluoride of >50 μmol/L was thought to result in nephrotoxicity after administration of any inhaled anesthetic. 2,33 The production of inorganic fluoride with desflurane, enflurane, halothane, and isoflurane is limited, and these agents are unlikely to cause significant nephrotoxicity in patients with normal renal function.…”

“…2,33 The production of inorganic fluoride with desflurane, enflurane, halothane, and isoflurane is limited, and these agents are unlikely to cause significant nephrotoxicity in patients with normal renal function. 31 However, although plasma concentrations of inorganic fluoride have been reported to exceed 50 μmol/L after prolonged administration of sevoflua MAC = minimum alveolar concentration, NA = not available, CYP = cytochrome P-450. rane, reports of renal dysfunction after sevoflurane administration in patients are no higher than they are with other inhaled anesthetic agents.…”

“…rane, reports of renal dysfunction after sevoflurane administration in patients are no higher than they are with other inhaled anesthetic agents. 8,31,33,34 It is now thought that intrarenal inorganic fluoride, resulting from renal defluorination, may be responsible for the nephrotoxicity seen with methoxyflurane. Sevoflurane undergoes limited metabolism within the kidneys.…”

“…Compound A (fluoromethyl-2,2-difluoro-1-[trifluoromethyl] vinyl ether), 3 a degradation product of sevoflurane resulting from the interaction between sevoflurane and the absorbents used to remove carbon dioxide during administration, has resulted in mild and reversible renal impairment in animal studies. 3,10,31,33 The amount of compound A produced and the theoretical risk of nephrotoxicity may be dose dependent and have a greater potential to occur when sevoflurane is used for prolonged periods or at low flow rates. In clinical trials, administering sevoflurane at a flow rate of 1 L/min resulted in the increased production of compound A as the duration of anesthesia lengthened.…”