Toxicity Following Methoxyflurane Anesthesia Ii. Fluoride Concentrations in Nephrotoxicity

Taves, Donald R.; Fry, Bill W.; Freeman, Richard B.; Gillies, Alastair J.; Marx, Gertie F.

doi:10.1097/00132586-197106000-00060

Cited by 12 publications

(19 citation statements)

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“…In the present experiment, however, a different pattern of response was observed ( The role of fluoride in the methoxyflurane-mediated depression of water permeability. An elevated concentration of fluoride, a product of the hepatic metabolism of methoxyflurane, has been implicated as the etiology of the vasopressin-resistant polyuria observed in humans and animals receiving methoxyflurane anesthesia (11,12). To determine the role of fluoride in the present study, Ktrans urea and osmotic water flow were measured in bladders treated with 1-5 mM NaF.…”

Section: Inhibition Of Water Flow By General Anestheticsmentioning

confidence: 98%

“…Halothane, despite its effect in toad bladder, does not impair mammalian renal concentrating ability at levels used clinically. Methoxyflurane is well documented as a cause of nephrogenic diabetes insipidus as well as acute renal failure in man and in certain strains of rat (11,12,27,28). These conditions have been attributed to accumulation in the renal parenc.hyma of fluoride and oxalate, respectively, two end products of methoxyflurane metabolism.…”

Section: Inhibition Of Water Flow By General Anesthetics 985mentioning

confidence: 99%

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Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

Levine¹,

Levine²,

Worthington³

et al. 1976

J. Clin. Invest.

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A B S T R A C T Vasopressin increases the permeability of the totad urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or to the lipophilic solute diphenylhydantoin.In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in the toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyfluranetreated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well.We would conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea. INTRODUCTIONThere is evidence in several epithelial tissues that water and small amides such as urea cross the cell membrane via independent pathways. In the toad urinary bladder, for example, vasopressin-stimulated urea transport is blocked by agents such as phloretin, tannic acid, and the oxidizing agents permanganate and chromate, while osmotic water flow is unaltered (1-3). These inhibitory agents appear to act at a luminal membrane site, beyond the generation of cyclic AMP, since cyclic AMPstimulated urea transport is inhibited as effectively as transport stimulated by vasopressin (3).The present study describes the action of three anesthetic agents, the gases methoxyflurane and halothane and the short-acting barbiturate methohexital, which have an effect opposite to that of phloretin and the oxidizing agents; the inhibition of osmotic water flow with no alteration in urea transport. In contrast to the selective inhibitors of urea transport, the anesthetics do not inhibit cyclic AMP-stimulated water movement. This suggests that the independent pathway for xvater movement may involve not only a separate site for penetration at the luminal membrane, but a specific and separate adenylate cyclase-cyclic AMP-mediated control system as well.

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Section: Inhibition Of Water Flow By General Anestheticsmentioning

confidence: 98%

Section: Inhibition Of Water Flow By General Anesthetics 985mentioning

confidence: 99%

Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

Levine¹,

Levine²,

Worthington³

et al. 1976

J. Clin. Invest.

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“…Several investigators have focused upon both inorganic and organic fluorides, known degradation products of MEF, as the possible pathogenetic factors [9,26,28,38], Thus, fluoride content of blood is elevated following MEF use and fluoride levels have been correlated with the degree of renal dysfunction [28], More over, in a strain of rats showing toxicity that was dose-related to MEF ad ministration, similar changes in renal function and histology were produced by fluoride alone [19,26], Observations that fluoride concentrations were greater the day after M EF use may explain the delayed appearance of polyuria.…”

Section: Discussionmentioning

confidence: 99%

Nephrotoxicity Associated with Use of Methoxyflurane

Wong¹,

Rowe²,

Blumenkrantz³

et al. 1974

Nephron

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Two cases of severe renal failure associated with the use of methoxyflurane anesthesia are reported. Both patients had polyuria during the immediate period after anesthesia and 7–10 days later became oliguric. After 26–31 days, a diuresis occurred with very slow recovery of adequate but reduced renal function. One case demonstrated hypernatremia and hyperosmolality. The development of renal failure did not depend upon a prolonged period of anesthesia. In one case, a renal biopsy revealed tubular epithelial cell degeneration, necrosis, and atrophy and crystals resembling calcium oxalate. Multiple mechanisms which may contribute to the development of renal failure associated with methoxyflurane are discussed. Supportive therapy, including dialysis, seems warranted to allow adequate time for return of renal function.

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“…It has been claimed that some fluorinated anesthetics, methoxyfluorane in particular (63)(64)(65)(66)(67)(68)(69)(70)(71), are nephrotoxic. The nephrotoxicity is largely attributed to the accumulation of inorganic fluoride in the renal tubules (67,68,70,72,73)…”

Section: Pathological Effects On the Kidneymentioning

confidence: 99%

“…The nephrotoxicity is largely attributed to the accumulation of inorganic fluoride in the renal tubules (67,68,70,72,73)…”

Section: Pathological Effects On the Kidneymentioning

confidence: 99%

Pathologic changes following chronic exposures to halothane: a review.

Chang¹

1977

Environ Health Perspect

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The toxic effects of halothane on the liver, kidney, and brain are reviewed. Increasing evidence has indicated that hepatic degeneration can be induced in several animal species after exposure to halothane. Recent electron microscopic investigations have also revealed cytological degeneration of the liver cells after chronic exposure to subclinical levels of halothane. Degeneration of the kidney and the nervous system after halothane exposure have also been reported. The pathological effects of halothane on the neonatal (developing) liver, kidney, and brain are also demonstrated by electron nicroscopy. Although the full significance of these observations on experimental animals in relationship to human exposure is still not known, the indication of the toxic potential of halothane on the biological system is strong and deserves further investigation.

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Toxicity Following Methoxyflurane Anesthesia Ii. Fluoride Concentrations in Nephrotoxicity

Cited by 12 publications

References 0 publications

Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

Nephrotoxicity Associated with Use of Methoxyflurane

Pathologic changes following chronic exposures to halothane: a review.

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