Nephrotoxicity Associated with Methoxyflurane Anesthesia

@article{Crandell1966NephrotoxicityAW,
  title={Nephrotoxicity Associated with Methoxyflurane Anesthesia},
  author={Walter B. Crandell and Sam G. Pappas and A Macdonald},
  journal={Anesthesiology},
  year={1966},
  volume={27},
  pages={591–607}
}
Among 94 cases in which methoxyflurane was used, 16 developed a toxic nephropathy characterized by diuresis. A seventeenth case which occurred 2 years previously in an affiliated hospital is also reported. Variations in the severity and duration of water loss modified the clinical features which, in which, well-defined cases, consisted of: urine volume of 2.5 to 4 liters per day with a negative fluid balance and pronounced weight loss for 6 to 10 days; elevation of serum sodium, chloride… 
Methoxyflurane nephrotoxicity. A study of dose response in man.
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The use of methoxyflurane in clinical anesthesia should be restricted to situations where it offers specific advantages and where dosages less than 2.5 MAC hours can be attained.
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Since the renal dysfunction has appeared in the post-anesthetic period, investigation has been focused on this period and the hypothesis that the syndrome results from a renal distal tubular lesion appears well-founded.
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The Fischer 344 rat appears to meet the criteria for being of value in investigations of methoxyflurane-induced nephrotoxicity in man and has the same clinical manifestations of the diseases process.
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Methoxyflurane anesthesia followed by renal failure appears to cause secondary hyperoxaluria, and intrarenal oxalate precipitation may occur when renal function is compromised for any reason during or immediately after surgery.
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Evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction is suggested and a proposed metabolic pathway to support this hypothesis is presented.
Nephropathy associated with methoxyflurane anesthesia. A follow-up report.
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A toxic nephropathy associated with methoxyflurane anesthesia was observed in 17 patients and gradual improvement, over a period of months, was noted on subsequent studies.
RENAL DYSFUNCTION ASSOCIATED WITH METHOXYFLURANE ANESTHESIA, A RANDOMIZED, PROSPECTIVE CLINICAL EVALUATION
TLDR
A syndrome was observed, characterized by polyuria, lack of responsiveness to infusion of vasopressin injection, marked weight loss, and delayed return to preoperative renal concentrating ability, indicating a lesion of the distal nephron.
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