The consensus is that the use of<unk>  should be restricted only to healthy individuals, in situations where it offers specific advantages and even then, only at dosages less than 2.5 MAC hours. The National Institute for Occupational Safety and Health maintains a recommended exposure limit for<unk>  as waste anesthetic gas of 2 ppm (13.5 mg/m3) over 60 minutes. Kidney The first report of nephrotoxicity appeared in 1964, when Paddock and colleagues reported three cases of acute kidney injury, two of whom were found to have calcium oxalate crystals in the renal tubules at autopsy. In 1966, Crandell and colleagues reported a series in which 17/95 (18%) of patients developed an unusual type of nephropathy after operations in which<unk>  was used as a general anesthetic. This particular type of chronic kidney disease was characterized by vasopressin-resistant high-output kidney failure (production of large volumes of poorly concentrated urine) with a negative fluid balance, pronounced weight loss, elevation of serum sodium, chloride, osmolality and blood urea nitrogen. The urine of these patients was of a relatively fixed specific gravity and an osmolality very similar to that of the serum. Furthermore, the high urine output persisted a challenge test of fluid deprivation. Most cases resolved within 2–3 weeks, but evidence of renal dysfunction persisted for more than one year in 3 of these 17 cases (18%), and more than two years in one case (6%). Compared with halothane,<unk>  produces dose-dependent abnormalities in kidney function. The authors showed that subclinical nephrotoxicity occurred following<unk>  at minimum alveolar concentration (MAC) for 2.5 to 3 hours (2.5 to 3 MAC hours), while overt toxicity was present in all patients at dosages greater than five MAC hours. This study provided a model that would be used for the assessment of the nephrotoxicity of volatile anesthetics for the next two decades. Furthermore, the concurrent use of tetracyclines and<unk>  has been reported to result in fatal renal toxicity. Liver Reports of severe and even fatal hepatotoxicity related to the use of<unk>  began to appear in 1966. Mechanism The biodegradation of<unk>  begins immediately. The kidney and liver toxicity observed after anesthetic doses is attributable to one or more metabolites produced by O-demethylation of<unk> . Products of this catabolic process include methoxyfluoroacetic acid (MFAA), dichloroacetic acid (DCAA), and inorganic fluoride.<unk>  nephrotoxicity is dose dependent and irreversible, resulting from O-demethylation of<unk>  to fluoride and DCAA. It is not entirely clear whether the fluoride itself is toxic—it may simply be a surrogate measure for some other toxic metabolite. The concurrent formation of inorganic fluoride and DCAA is unique to<unk>  biotransformation compared with other volatile anesthetics, and this combination is more toxic than fluoride alone. This may explain why fluoride formation from<unk>  is associated with nephrotoxicity, while fluoride formation from other volatile anesthetics (such as enflurane and sevoflurane) is not.
Methoxyflurane
Isoflurane
Desflurane
Halothane
Sevoflurane
Etomidate
Methitural
Methacholine