Nephrotoxicity enflurane

The severity of aminoglycoside nephrotoxicity is additive with that of vancomycin, polymixin, gallium, furosemide, enflurane, cisplatin, and cephalosporins. Aminoglycoside nephrotoxicity is synergistic with that of amphotericin B and cyclosporine. 

The metabolism of enflurane and sevoflurane results in the formation of fluoride ion. However, in contrast to the rarely used volatile anesthetic methoxyflurane, renal fluoride levels do not reach toxic levels under normal circumstances. In addition, sevoflurane is degraded by contact with the carbon dioxide absorbent in anesthesia machines, yielding a vinyl ether called "compound A," which can cause renal damage if high concentrations are absorbed. (See Do We Really Need Another Inhaled Anesthetic ) Seventy percent of the absorbed methoxyflurane is metabolized by the liver, and the released fluoride ions can produce nephrotoxicity. In terms of the extent of hepatic metabolism, the rank order for the inhaled anesthetics is methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide (Table 25-2). Nitrous oxide is not metabolized by human tissues. However, bacteria in the gastrointestinal tract may be able to break down the nitrous oxide molecule. 

Nephrotoxicity leading to renal insufficiency, particularly after prolonged anesthesia, is a potential consequence of general anesthesia with enflurane (22). Several cases of renal insufficiency have been described (SED-11, 209) (23,24), and the mechanism studied. On experimental... 

Mazze RI, Calverley RK, Smith NT. Inorganic fluoride nephrotoxicity prolonged enflurane and halothane anesthesia in volunteers. Anesthesiology 1977 46(4) 265-71. 

Methoxyflurane, enflurane, isoflurane, and sevoflurane all release inorganic fluoride ions as a result of hepatic metabolism. Fluoride is nephrotoxic. 

It has been thought that patients with chronically impaired renal function might be at increased risk of nephrotoxicity due to sevoflurane, because of an increased fluoride load due to reduced excretion. However, this was not confirmed in 41 patients undergoing elective surgery, with a stable increased preoperative serum creatinine concentration, who were randomly allocated to receive sevoflurane (n = 21) or enflurane (n = 20) at a fresh gas inflow rate of 41/minute for... 

Numerous studies have addressed the same issues raised with enflurane regarding fluoride production and nephrotoxic potential including fluoride levels after prolonged exposure [56,57,59], urine concentrating ability [57, 59-61], the effect of obesity [57, 60], and the effect of preexisting renal function impairment [62,63]. The findings demonstrated that sevoflurane has little or no potential for fluoride-induced nephrotoxicity (For further information see section on mechanisms of fluoride toxicity). 

Halothane and sevoflurane are commonly used for inhaled induction of anesthesia in children because they do not have a noxious smell. These drugs and isoflurane or desflurane are then used to maintain anesthesia, according to the preference of the anesthesiologist. Enflurane is rarely used today because it irritates the airway [115]. Therefore, of the inhaled agents currently used in pediatric patients, only sevoflurane has nephrotoxic potential. 

Loehning RW, Mazze Rl. Possible nephrotoxicity from enflurane in a patient with severe renal disease. Anesthesiology... 

Enflurane and sevoflurane are the only volatile anesthetics that have nephrotoxic potential due to their significant release of fluoride ions during metabolism. In sevoflurane s case also due to biodegradation by the currently used CO2 absorbents in anesthesia circuits. 

Isoniazid may increase the metabolism of enflurane, isoflurane or sevoflurane in some patients (probably related to isoniazid acetylator phenotype ) and so increase the release of fluoride ions that may cause nephrotoxicity. However, there do not appear to be any reports of a significant clinical effect on renal function. 

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