Within a very short period of time after their discovery, corticosteroids were being used for a variety of medical conditions with outstanding results. Unfortunately, within an equally short period of time—just a few years—the adverse effects associated with the use of exogenous corticosteroid administration were recognized, attenuating the initial enthusiasm for these drugs. In the early 1950s, reports began to appear in the medical literature of patients who had been chronically receiving corticosteroids who developed refractory circulatory shock when undergoing major surgical procedures. Clinicians quickly recognized that exogenous corticosteroids suppressed the hypothalamic-pituitary-adrenal (HPA) axis. During any major insult to homeostasis, individuals with a suppressed HPA axis do not release adrenocorticotropic hormone (ACTH, or corticotropin) in sufficient quantities, and, therefore, the adrenal glands do not release an adequate amount of endogenous corticosteroids to handle the stress.

In the past, the solution to suppression of the HPA axis was to administer corticosteroids in sufficient quantities to match what the adrenal glands would have released when maximally stimulated. Because even 2 weeks of corticosteroid use within the previous 3 months has been found to inhibit the HPA axis, recommendations were developed that such patients should receive exogenous corticosteroids when they were undergoing major operations. For these criteria to have been met, the dose of corticosteroids that the patient should have taken would have had to have been high enough to suppress the HPA axis—20 mg of prednisone or its equivalent (Table 234-1). However, because the dose and duration of the use of corticosteroids varied so much, it was not always clear which patients should receive perioperative corticosteroids. Some patients using topical, ophthalmic, or inhaled corticosteroids were found to have suppressed HPA axes.

An ACTH stimulation test in which cosyntropin is administered can test the viability of the HPA axis. In the low-dose version of this test, serum cortisol levels are measured immediately before and 30 min after intravenous injection of a 1-μg/1.73 m² or 0.5-μg/1.73 m² dose of cosyntropin. In the high-dose version, serum cortisol levels are measured immediately before and 30 and 60 min after intravenous injection of 250 μg of cosyntropin. A serum cortisol concentration of less than 18 μg/dL at 30 min denotes impaired adrenocortical reserve, and the patient may not release sufficient ACTH from the adrenal gland to mount an adequate response to a major stressor. However, cosyntropin stimulation tests are expensive and time consuming to perform. An easier, less expensive alternative has been advocated and adopted for perioperative steroid replacement therapy. Typically, a 100-mg dose of hydrocortisone or its equivalent is administered the day of surgery, with the first dose of steroids administered the morning of surgery.