What is the recommended treatment with hydrocortisone (cortisol) for a patient with sepsis and suspected adrenal insufficiency (AI)?

Hydrocortisone Treatment for Sepsis with Suspected Adrenal Insufficiency

For patients with septic shock and suspected adrenal insufficiency who remain hypotensive despite adequate fluid resuscitation and vasopressor therapy, administer hydrocortisone 200 mg/day intravenously (50 mg every 6 hours or continuous infusion) for at least 7 days or until ICU discharge. 1, 2

Patient Selection Criteria

Reserve hydrocortisone exclusively for vasopressor-unresponsive septic shock after completing adequate fluid resuscitation. 2, 3 The specific indications include:

• Patients requiring moderate-to-high dose vasopressors (≥0.1 μg/kg/min norepinephrine equivalent) despite adequate fluid resuscitation 2
• Refractory shock requiring high-dose vasopressors based on the ADRENAL and APROCCHSS trials, which demonstrated earlier shock reversal and potential mortality benefit 1
• Do not administer hydrocortisone in sepsis without shock, as it provides no benefit and may cause harm 2, 3

Absolute Indications for Hydrocortisone

Certain clinical scenarios warrant immediate hydrocortisone regardless of testing:

• Absolute adrenal insufficiency (peak cortisol after ACTH stimulation <18 μg/dL) with catecholamine-resistant shock 2, 4
• Purpura fulminans or Waterhouse-Friderichsen syndrome 2
• Prior chronic steroid therapy or known pituitary/adrenal abnormalities 2
• Patients with cirrhosis and relative adrenal insufficiency (cortisol increase <9 μg/dL after Synacthen), which occurs in 49% of decompensated cirrhosis patients and is associated with significantly higher 90-day mortality (26% vs. 10%) 1

Dosing and Administration

Adult Dosing

Administer hydrocortisone 200 mg/day intravenously using one of two methods: 1, 2

• 50 mg IV every 6 hours (intermittent bolus), OR
• 200 mg continuous IV infusion over 24 hours 1

The 2024 AASLD guidelines specifically recommend either 50 mg IV q6h or 200-mg infusion for 7 days or until ICU discharge. 1 Some guidelines suggest doses up to 300 mg/day for severe cases. 1, 5

Duration: Continue at full dose for at least 3-7 days, then taper gradually when vasopressors are no longer required. 2, 3, 6 Do not stop abruptly, as this may precipitate adrenal crisis. 6

Pediatric Dosing

For children with septic shock and suspected adrenal insufficiency:

• Initial stress dose: 50 mg/m²/24 hours (approximately 5-6 mg/kg/day) 2, 7
• Alternative dosing: 1 mg/kg every 6 hours 1
• For refractory shock: May titrate up to 50 mg/kg/day if needed to reverse shock 7
• Approximately 25% of children with septic shock have absolute adrenal insufficiency, and death can occur within 8 hours of presentation 2, 7, 4

Diagnostic Considerations

Do not delay treatment while awaiting cortisol test results in critically ill patients with suspected adrenal insufficiency. 3, 7 However, if time permits:

• Draw baseline cortisol before initiating hydrocortisone 7
• Adrenal insufficiency can be diagnosed by: 6
  • Delta cortisol <9 μg/dL after ACTH (250 μg) stimulation, OR
  • Random total cortisol <10 μg/dL
• The ACTH stimulation test should NOT be used to determine which septic shock patients receive glucocorticoids 6

Timing of Initiation

Initiate hydrocortisone as early as possible once criteria are met. A 2023 study demonstrated that early initiation (≤3 hours) versus late (>3 hours) reduced time to vasopressor discontinuation (25 vs. 37 hours, p=0.009), though ICU mortality and length of stay were similar. 8 The speed of treatment initiation influences prognosis. 1

Monitoring Parameters

Monitor the following during hydrocortisone therapy:

• Hyperglycemia (most common adverse effect requiring monitoring) 2
• Blood pressure and hemodynamic parameters for shock reversal 2, 7
• Signs of new infection or superinfection, including new sepsis and septic shock 2, 7
• Serum sodium (risk of hypernatremia with prolonged high-dose therapy beyond 48-72 hours) 9
• Serum electrolytes, particularly potassium 7

Critical Pitfalls to Avoid

• Avoid etomidate for intubation in septic shock patients, as it suppresses the hypothalamic-pituitary-adrenal axis and may increase mortality 2
• Do not use dexamethasone instead of hydrocortisone for critical illness-related corticosteroid insufficiency, as hydrocortisone has better mineralocorticoid activity 7, 6
• Do not use high-dose short courses (≥400 mg/day); use low-dose, long-duration therapy 2, 6
• Do not abruptly discontinue hydrocortisone; taper gradually to avoid precipitating adrenal crisis 2, 6
• Do not delay treatment while waiting for cortisol test results in critically ill patients 3, 7

Pharmacokinetic Considerations

A 2020 study demonstrated that continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg, was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. 10 This supports the use of continuous infusion over intermittent bolus administration when feasible. 10