Methoxyflurane nephrotoxicity--a review and a case report.

METr~OX~LtraANE ( 1,1 difluoro, 2,2 diehloro ethyl methyl ether) was first investigated as an anaesthetic in dogs by Van Poznak and Artusio, and, subsequently in 1960, Artusio e t al . ' reported on the clinical use in man. It is estimated that since that time, approximately 15 million methoxyflurane anaesthetics have been administered. The clinical advantages of its u s e have been found in its association with adrenaline, for it does not sensitize the rnyocardlum to eatecholamines, ~ in the management of phaeochromoeytoma, ~ in eye surgery and as an analgesic in obstetrics. The first report of nephrotoxicity appeared in 1964. Paddock et al . 4 mentioned three eases, two of whom died in uraemia with calcium oxalate crystals in the renal tubules. They also reported on a personal communication from Artusio of three patients with increased urinary output, rising blood urea-nitrogen and ereatinine, following methoxyflurane, which resolved in seven to nine days. Their subsequent inveslSgation of 40 healthy males receiving methoxyflurane anaesthesia of not less than one hour duration, failed to detect any changes in renal function as measured by ereatinine clearance, blood urea-nitrogen levels and fluid balance. They therefore exonerated methoxyflurane as a cause of nephrotoxicity in healthy subjects. They also found that 20 out of 200 autopsy specimens of kidneys contained calcium oxalate, none of the patients having received methoxytlurane, but all having had renal disease. In 1966, Crandell, Pappas and MacDonald, ~ writing from White River Junction, Vermont, reported on 94 patients receiving methoxyflurane, of whom 16 ( 17 per cent) developed tox/e nephropathy with urine of low specific gravity, negative fluid balance, clinical dehydration and hypernatraemia, developing in the first postoperative day following methoxyflurane anaesthesia lasting from three to six hours. The syndrome continued for six to ten days. They utilized fluid deprivation, rapid intravenous fluid infusion and antidinretie hormone administration to differentiate between nephropathy and Ann insufficiency but noticed that the patients who recovered early were those who had received high fluid intake early in the postoperative period. The relationship between methoxyflurane and nephrotoxicity was attributed to absence of antidiuresis and inadequate response to ~mH, methoxyflurane being the only common factor in all the eases. A follow-up e reported no further cases at that hospital, since the use of methoxyflurane had been discontinued three years previously. Pezzi e t al . , ~ 1966, found a syndrome in postoperative patients consisting of rising blood urea-nitrogen, increased urinary output, low urinary specific gravity, hypematraernia, dehydration and mental confusion. In 180 methoxyflurane anaes*Departraent of Anaesthesia, University of Toronto and Toronto Gensral Hospital.