When to administer stress dose steroids (corticosteroids)?

From the Guidelines

Stress dose steroids should be administered to patients with adrenal insufficiency undergoing surgical procedures, with a recommended dose of hydrocortisone 100 mg intravenously at the start of surgery, followed by an infusion of 200 mg/24 h. This is based on the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK, as reported in the study by Woodcock et al. 1. The study highlights the importance of stress dose steroids in preventing adrenal crisis in patients with adrenal insufficiency, particularly during the peri-operative period.

The guidelines recommend that patients with primary or secondary adrenal insufficiency should receive stress doses of hydrocortisone during the peri-operative period, with the dose and duration of treatment depending on the severity of the stress and the individual patient's needs. For example, for minor stress, such as minor illness or procedures under local anesthesia, a dose of hydrocortisone 25-50 mg or equivalent may be sufficient, while for major stress, such as critical illness or major surgery, a dose of hydrocortisone 100-150 mg/day or equivalent in divided doses may be required.

It is also important to note that patients who have been on prednisone ≥5 mg daily (or equivalent) for more than 2-3 weeks within the past year are at risk for adrenal insufficiency and should receive stress dosing, as chronic exogenous steroid use suppresses the hypothalamic-pituitary-adrenal axis, preventing the natural cortisol surge that occurs during stress 1. The duration of stress dosing typically ranges from 1-3 days, tapering back to maintenance dose as the stressor resolves.

Some key points to consider when administering stress dose steroids include:

• The dose and duration of treatment should be individualized based on the patient's needs and the severity of the stress.
• Hydrocortisone is the preferred steroid for stress dosing, due to its rapid onset of action and short half-life.
• The route of administration may be intravenous or intramuscular, depending on the patient's condition and the availability of intravenous access.
• Patients with primary adrenal insufficiency may require additional mineralocorticoid replacement, as hydrocortisone has minimal mineralocorticoid activity.

Overall, the administration of stress dose steroids is a critical aspect of the management of patients with adrenal insufficiency, and should be guided by the individual patient's needs and the severity of the stress.

From the FDA Drug Label

Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy who are subjected to any unusual stress before, during, and after the stressful situation To avoid drug-induced adrenal insufficiency, supportive dosage may be required in times of stress (such as trauma, surgery, or severe illness) both during treatment with fludrocortisone acetate and for a year afterwards Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted

Stress dose steroids should be given to patients on corticosteroid therapy who are subjected to any unusual stress, such as:

• Trauma
• Surgery
• Severe illness before, during, and after the stressful situation, to avoid drug-induced adrenal insufficiency 2, 3, 4.

From the Research

Indications for Stress Dose Steroids

• Adrenal insufficiency (AI) is a life-threatening condition that requires life-long glucocorticoid substitution therapy and stress adaptation to prevent adrenal crises 5
• Relative adrenal insufficiency is the most common cause of low cortisol levels and failed adrenocorticotropic hormone (ACTH) challenge in ill patients, and corticosteroid therapy can result in immediate hemodynamic benefits 6
• Patients with adrenal insufficiency have a higher mortality than the general population, possibly due to excess glucocorticoid exposure at inappropriate times 7, 8

Timing and Dosage of Stress Dose Steroids

• The Endocrine Society Guidelines recommend a daily glucocorticoid replacement dose of 15 to 25 mg with a midpoint of 20 mg of hydrocortisone in divided doses in otherwise healthy individuals with AI 9
• A daily glucocorticoid replacement dose of 4.3 to 26 mg/d hydrocortisone with a midpoint of 15 mg/d is predicted from current measurements of daily cortisol production rates and oral hydrocortisone bioavailability 9
• Low-dose prednisolone of 2-4 mg is safe and effective in most patients with AI, and doses can be titrated with either 4-, 6-, or 8-h single time point drug levels 7

Special Considerations

• Hydrocortisone should be the choice of steroid for most relative AI patients, and fludrocortisone can be added on a case-by-case basis in refractory shock 6
• Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due to its longer duration of action and lower cost, but mortality rates with prednisolone versus hydrocortisone are similar 8