Steroid response to ACTH and to ascorbinic acid during infusion of etomidate for general surgery

The characteristics of the steroid response during an etomidate-fentanyl combination was explored in two groups of five patients undergoing major abdominal vascular surgery. Cortisol, androstene-dion, compound-S and ACTH were measured during surgery for three hours. In the fourth hour, an ACTH1-24 stimulation test was performed in one group and the steroid response was assessed. The other group received ascorbinic acid intravenously and the reaction of the adrenals was measured in the same way. The result indicates that etomidate causes a blockade of the adrenal corticosteroid synthesis at the site of the hydroxylation of cholesterol. This blockade is due to the interaction of the imidazole structure with the cytochrome p-450. Ascorbinic acid is able to overcome this blockade, indicating that cytochrome p-450 is involved in the ascorbinic acid metabolism which is obligatory for the hydroxylation of cholesterol.