What are the considerations for hydrocortisone (cortisol) administration?

Hydrocortisone Administration: Key Considerations

Hydrocortisone dosing must be tailored to the clinical context, with stress-dose requirements (100-200 mg/day) dramatically exceeding physiologic replacement (15-25 mg/day), and continuous intravenous infusion being superior to bolus dosing during major physiologic stress. 1, 2

Perioperative Stress Dosing

Adults with Adrenal Insufficiency

For major surgery, administer hydrocortisone 100 mg IV at induction, followed immediately by continuous infusion of 200 mg over 24 hours. 1

• Postoperatively, continue 200 mg/24h IV infusion while nil by mouth or if vomiting occurs 1
• Alternative: hydrocortisone 50 mg IM/IV every 6 hours if continuous infusion unavailable 1
• Once oral intake resumes, double the usual oral hydrocortisone dose for 48 hours after uncomplicated surgery, or up to one week following major surgery 1

Adults on Chronic Glucocorticoid Therapy

For patients receiving prednisolone ≥5 mg daily (or equivalent) for ≥4 weeks:

• Major surgery: Same protocol as adrenal insufficiency—100 mg IV at induction, then 200 mg/24h continuous infusion 1
• Intermediate surgery: 100 mg IV at induction, then 200 mg/24h infusion 1
• Alternative option for major surgery: dexamethasone 6-8 mg IV provides adequate coverage for 24 hours 1

Pediatric Dosing

Children with adrenal insufficiency require 2 mg/kg IV hydrocortisone at induction for any surgery under general anesthesia. 1

• Postoperatively after major surgery: 2 mg/kg every 4 hours IV/IM, or continuous infusion if unstable 1
• No child with adrenal insufficiency should be fasted >6 hours 1
• Monitor blood glucose hourly if fasting exceeds 4 hours and until enteral intake resumes 1
• Once eating, double normal hydrocortisone dose for 48 hours, then return to standard dosing 1

Obstetric Considerations

At onset of active labor (contractions every 5 minutes for 1 hour OR cervical dilation >4 cm), give hydrocortisone 100 mg IV, followed by continuous infusion of 200 mg/24h. 1

• Alternative: hydrocortisone 50 mg IM every 6 hours 1
• Rapid taper over 1-3 days to regular replacement dose after uncomplicated delivery 1
• Consider increasing maintenance dose by 20-40% in late pregnancy, as physiologic cortisol increases during this period 1

Septic Shock Management

In septic shock, use hydrocortisone 200 mg/day ONLY if adequate fluid resuscitation and vasopressors fail to restore hemodynamic stability. 1

• Administer as continuous infusion rather than bolus dosing 1
• Do NOT use ACTH stimulation test to determine who should receive hydrocortisone 1
• Taper hydrocortisone when vasopressors are no longer required 1
• Do NOT administer corticosteroids for sepsis without shock 1

The evidence strongly supports continuous infusion over bolus administration during major stress, as it is the only delivery mode that persistently achieves median cortisol concentrations in the physiologic stress range 2. Linear pharmacokinetic modeling confirms that continuous IV infusion of 200 mg over 24 hours, preceded by an initial bolus of 50-100 mg, best maintains appropriate cortisol concentrations 2.

Acute Adrenal Crisis Treatment

Immediately administer hydrocortisone 100 mg IV bolus, followed by 100-300 mg/day as continuous infusion or 50 mg IV/IM every 6 hours. 1

• Simultaneously give rapid IV infusion of 0.9% saline (1 L over first hour) 1
• Do NOT delay treatment for diagnostic testing—draw blood for cortisol/ACTH, then treat immediately 1
• Continue IV saline at slower rate for 24-48 hours 1
• Taper parenteral glucocorticoids over 1-3 days to oral replacement once stable 1
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 1

Pharmacokinetic Principles

Hydrocortisone has a short half-life (mean 76.5 minutes, range 40-225 minutes) with highly variable absorption characteristics between individuals. 3

• Following IV injection, demonstrable effects occur within 1 hour and persist variably 4
• Excretion is nearly complete within 12 hours 4
• For constantly high blood levels, injections should be given every 4-6 hours if continuous infusion unavailable 4
• During "low-dose" therapy (100 mg bolus + 10 mg/h infusion), plasma cortisol levels initially reach 3,587 nmol/L (median) on day 1, then decline to 1,310 nmol/L by day 7 despite constant dosing 5

Critical Special Populations

Patients with concurrent diabetes insipidus and adrenal insufficiency require strict fluid balance monitoring, as cortisol is necessary to excrete water loads. 1

• These patients (typically with hypothalamic/pituitary disease) are at high risk for water intoxication if inadequate hydrocortisone is given perioperatively 1
• Mandatory strict fluid balance with adequate cortisol replacement to avoid hyponatremia and associated morbidity 1

Dose Equivalency Reference

The standard conversion ratio is 4:1 (hydrocortisone:prednisone):

• 20 mg hydrocortisone = 5 mg prednisone 6
• 200 mg hydrocortisone = 50 mg prednisone 6
• However, prednisolone has approximately 25 times less mineralocorticoid activity than hydrocortisone, which may be clinically relevant in certain contexts 6

Common Pitfalls to Avoid

• Never use bolus dosing alone during major stress—continuous infusion is superior for maintaining therapeutic cortisol levels 2
• Do not underdose in septic shock—200 mg/day is required, not lower "physiologic" doses 1, 7
• Avoid high-dose corticosteroids (methylprednisolone ≥30 mg/kg/day equivalent) in critical illness—they provide no benefit and may cause harm 7
• Do not forget to restart fludrocortisone—when hydrocortisone doses exceed 50 mg/day, the mineralocorticoid effect is adequate, but fludrocortisone must be restarted during taper 1