The role of ascorbic acid in etomidate toxicity

Etomidate, a short-acting hypnotic used in anaesthesia, has been shown to block steroidogenesis in man. The free imidazole radical in etomidate binds to cytochrome P450. Serious side-effects of etomidate have only been observed in guinea-pigs and in man, both species relying for restoration of ascorbic acid pools upon resynthesis and upon the daily dietary intake of vitamin C. It has been shown that ascorbic acid and not ACTH can increase serum cortisol concentration during etomidate infusion. Ascorbic acid even restores the ACTH/cortisol ratio to pre-operative values. It is therefore suggested that etomidate blocks ascorbic acid metabolism. Resynthesis of ascorbic acid cannot occur because of the blockade of cytochrome P450. Depletion of the ascorbic acid pool would then cause inhibition of steroidogenesis. This is the case in man and probably also in the guinea-pig. All other species can synthesize their own ascorbic acid from alpha ketogluconic acid.