Inhibition of Adrenal Steroidogenesis by the Anesthetic Etomidate

The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (±S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8±0.5 μg per deciliter and 0.5±1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450–dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11β-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate Inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used. (N Engl J Med 1984; 310:1415–21.) ETOMIDATE is an intravenous sedative-hypnotic that has been used for the induction and maintenance of anesthesia and for prolonged sedation of critically ill patients. The drug is administered by either bolus injection or continuous infusion 1 and is characterized by a rapid onset of action and recovery, 2 excellent cardiovascular stability, 3 and the absence of histamine release. 4 Although only recently available in the United States, etomidate has gained wide acceptance in Furope as an anesthetic for patients with cardiovascular instability 5 and as a sedative for ventilator-dependent patients. 6 Recently, an intensive-care unit in England reported an increased mortality rate 7 associated with low levels . . .