What is the stress dose for adrenal insufficiency (cortisol deficiency)?

From the Guidelines

For patients with cortisol deficiency experiencing stress, the recommended stress dose of hydrocortisone is 100 mg by intravenous injection at induction of anaesthesia, followed by a continuous infusion of hydrocortisone at 200 mg/24 h, until the patient can take double their usual oral glucocorticoid dose by mouth, as stated in the most recent guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.

Key Considerations

• The stress dose of hydrocortisone should be administered intravenously, with a bolus dose of 100 mg at induction of anaesthesia, followed by a continuous infusion of 200 mg/24 h 1.
• Patients should be educated on "Sick Day Rules", which refer to doubling the dose of steroids during periods of physiological stress, and injecting hydrocortisone intramuscularly or intravenously in situations of major stress or surgery 1.
• The patient's endocrinologist should be involved in planning scheduled surgery and caring for postoperative cases, especially for patients with multiple risk factors (age, comorbidities) 1.
• All patients with adrenal insufficiency should carry an emergency kit containing injectable hydrocortisone (100 mg), syringes, and wear medical alert identification 1.

Tapering and Maintenance

• The continuous infusion of hydrocortisone should be tapered back to the patient's maintenance dose as the stressor resolves, typically over 1-3 days, but may take up to a week for major or complicated surgery 1.
• Patients should be educated to increase their steroid dose during illness and seek medical attention if unable to tolerate oral medication 1.

Importance of Stress Dosing

• Stress dosing is necessary because the normal adrenal gland increases cortisol production significantly during stress, and patients with adrenal insufficiency cannot mount this response, putting them at risk for adrenal crisis which can be life-threatening without appropriate glucocorticoid coverage 1.

From the FDA Drug Label

In certain overwhelming, acute, life-threatening situations, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages. The initial dose of SOLU-CORTEF Sterile Powder is 100 mg to 500 mg, depending on the specific disease entity being treated In this latter situation, it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient's condition.

The stress dose for adrenal insufficiency (cortisol deficiency) is 100 mg to 500 mg of hydrocortisone, depending on the specific situation and clinical condition of the patient. The dose may be repeated at intervals of 2,4, or 6 hours as indicated by the patient's response and clinical condition 2.

From the Research

Stress Dose for Adrenal Insufficiency

The stress dose for adrenal insufficiency, also known as cortisol deficiency, is a crucial aspect of managing patients with this condition. According to the studies, the following points can be noted:

• A stress dose of hydrocortisone above 50 mg 6-hourly would rarely be necessary in managing acute illness 3.
• Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress 4.
• Linear pharmacokinetic modeling identified continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range 4.
• The usefulness of time-point serum cortisol and ACTH measurements for the adjustment of glucocorticoid replacement in adrenal insufficiency has been evaluated, and single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients 5.

Key Findings

Some key findings from the studies include:

• An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance 3.
• Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis 4.
• A baseline cortisol concentration of <25 microg/dL in patients with septic shock was a better discriminator of adrenal insufficiency than the standard and low-dose corticotropin stimulation tests 6.
• Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile 5.

Cortisol Replacement Therapy

Cortisol replacement therapy is essential in patients with primary and secondary adrenal insufficiency. The studies suggest that:

• Conventional twice daily hydrocortisone administration may not mimic physiological cortisol secretion in patients with adrenal insufficiency 7.
• The aim of mimicking the physiological nyctohemeral secretion of cortisol is difficult to achieve in practice and raises a number of important considerations unique to steroid substitution therapy in children and adolescents 7.
• Hydrocortisone replacement therapy in children and adolescents with hypopituitarism should be carefully monitored to avoid the risks of hypoglycaemia and adrenal crisis associated with undertreatment, and to avoid growth suppression and reduced final height potential associated with steroid excess 7.