What is the recommended dosage of hydrocortisone (cortisol) for the management of septic shock?

Hydrocortisone Dosage in Septic Shock

For septic shock that remains unresponsive to adequate fluid resuscitation and moderate-to-high dose vasopressors, administer intravenous hydrocortisone 200 mg per day for at least 3 days at full dose, given either as a continuous infusion or divided doses (50 mg every 6 hours). 1, 2

When to Initiate Hydrocortisone

• Only use hydrocortisone in septic shock patients who remain hypotensive despite adequate fluid resuscitation AND vasopressor therapy (typically requiring >0.1 μg/kg/min of norepinephrine or equivalent). 1
• Do NOT use corticosteroids in sepsis without shock—this provides no benefit and may cause harm. 1, 2
• The hemodynamic instability must persist after appropriate fluid loading and vasopressor initiation before considering hydrocortisone. 3

Dosing Regimen

Standard Adult Dose

• 200 mg/day of hydrocortisone is the recommended dose. 1, 2, 4
• This can be administered as:
  • Continuous infusion (preferred method per guidelines) 1, 3
  • Divided doses: 50 mg IV every 6 hours 4, 5

Duration

• Minimum 3 days at full dose before considering any dose reduction. 1, 2
• Continue until vasopressors are no longer required. 1, 2
• Typical total duration is 5-7 days. 1

Tapering Protocol

• Taper gradually over 6-14 days when vasopressors are discontinued—never stop abruptly. 1, 2
• Abrupt discontinuation can cause rebound inflammation and hemodynamic deterioration. 2

Dosing Considerations: Higher vs. Lower Doses

While the standard recommendation is 200 mg/day, the evidence shows nuanced findings:

• Doses <400 mg/day for ≥3 days are associated with better outcomes than high-dose, short-course regimens. 1, 2
• A pilot study comparing 200 mg/day versus 300 mg/day found no mortality difference, but the 300 mg group had more shock relapses requiring hydrocortisone resumption. 6
• One trial suggested 100 mg/day may reduce hyperglycemia (63.9% vs 86.5%) with shorter time to shock reversal compared to 200 mg/day, without increasing mortality. 7
• However, the established guideline dose remains 200 mg/day based on the preponderance of evidence from multiple trials. 1, 2

Pediatric Dosing

For children with septic shock at risk of adrenal insufficiency who remain in shock despite epinephrine or norepinephrine:

• Dosage range: 1-2 mg/kg/day for stress coverage up to 50 mg/kg/day titrated to reversal of shock. 1
• Can be administered as intermittent or continuous infusion. 1

What NOT to Do

• Do not use the ACTH stimulation test to decide who should receive hydrocortisone—it has no role in guiding treatment decisions. 1, 2, 3
• Avoid etomidate for intubation in septic shock patients, as it suppresses the hypothalamic-pituitary-adrenal axis and may worsen outcomes when used before steroid administration. 2, 3, 6
• Do not use high-dose corticosteroids (>400 mg/day)—these are associated with increased harm without benefit. 1, 5
• Do not use short-course therapy (<3 days)—prolonged low-dose therapy is superior. 1

Monitoring During Treatment

• Monitor serum sodium for hypernatremia, especially if treatment extends beyond 48-72 hours. 2, 4
• Monitor glucose closely—hyperglycemia is the most common adverse effect. 1, 2
• Watch for signs of superinfection, though the risk is not significantly increased with low-dose therapy. 1, 5
• Consider switching to methylprednisolone if hypernatremia develops with prolonged high-dose therapy. 4

Preparation and Administration

Per FDA labeling, for the 100 mg vial: 4

• Reconstitute with ≤2 mL of Bacteriostatic Water for Injection
• For continuous infusion, add reconstituted solution to 100-1000 mL of 5% dextrose in water or normal saline
• Solutions are stable for at least 4 hours after reconstitution

Clinical Context

The benefit of hydrocortisone in septic shock centers on improved shock reversal and reduced vasopressor requirements, though mortality benefit remains controversial across studies. 1, 5 The mechanism involves addressing relative adrenal insufficiency and peripheral cortisol resistance that occurs in severe septic shock. 8 Patients with more severe shock (higher vasopressor requirements, greater fluid needs) appear to derive the most benefit. 8, 9