What are the guidelines for hydrocortisone (corticosteroid) trials and dosing?

Guidelines for Hydrocortisone Trials and Dosing

Septic Shock

For septic shock not responsive to fluid and vasopressor therapy, intravenous hydrocortisone should be administered at a dose of 200 mg per day. 1

• Hydrocortisone should only be used when adequate fluid resuscitation and vasopressor therapy are unable to restore hemodynamic stability 1
• The recommended dose is 200 mg per day, which can be administered either as divided doses or as a continuous infusion 1, 2
• Treatment should continue for at least 3 days at full dose, or longer as clinically indicated 1, 2
• Hydrocortisone should be tapered when vasopressors are no longer required rather than stopping abruptly 1
• The adrenocorticotropic hormone (ACTH) stimulation test is not recommended to identify patients who should receive hydrocortisone 1, 2

Acute Respiratory Distress Syndrome (ARDS)

• For early moderate to severe ARDS (PaO₂/FiO₂ < 200 and within 14 days of onset), corticosteroids are suggested 1
• Methylprednisolone at 1 mg/kg/day is preferred due to greater lung tissue penetration 1, 2
• Treatment should be initiated within 14 days of ARDS onset for optimal benefit 1

Community-Acquired Pneumonia (CAP)

• For severe CAP, hydrocortisone at a daily dose less than 400 mg IV for 5-7 days is recommended 2, 3
• Benefits include shortened hospital stay, reduced need for mechanical ventilation, and prevention of ARDS 3
• Corticosteroids are not recommended for pneumonia without shock 2, 3

Inflammatory Bowel Disease - Acute Severe Ulcerative Colitis (ASUC)

• For ASUC, high-dose intravenous corticosteroids are recommended: methylprednisolone 60 mg daily or hydrocortisone 100 mg every 6 hours 1
• Corticosteroid treatment should not be delayed pending results of stool cultures and Clostridium difficile assay 1
• Prophylactic low-molecular weight heparin should be administered concurrently 1

Dosing Considerations

• For oral administration in less severe conditions, hydrocortisone dosing may range from 20 mg to 240 mg per day depending on the disease entity being treated 4
• Weight-adjusted dosing (0.2-0.3 mg/kg/day for lower dose; 0.4-0.6 mg/kg/day for higher dose) reduces variability in cortisol exposure between weight groups 5
• There is significant inter-individual variation in pharmacokinetics, with cortisol exposure (AUC24h) varying more than 10-fold between patients 5

Administration Methods

• For septic shock, continuous infusion is preferred over bolus administration 1, 2
• For ASUC, intravenous administration is recommended during the acute phase 1
• When transitioning from IV to oral therapy, the dose should be tapered gradually rather than stopped abruptly 4

Monitoring and Adverse Effects

• Monitor for potential adverse effects including hyperglycemia, hypernatremia, secondary infections, and gastrointestinal bleeding 2
• Regular blood pressure determinations and serum electrolyte monitoring are recommended 2
• Higher doses of hydrocortisone can increase systolic BP by approximately 5 mm Hg and diastolic BP by 2 mm Hg 6
• Higher doses affect several pathways involved in BP regulation including the renin-angiotensin-aldosterone system 6

Special Considerations

• For COVID-19 requiring respiratory support, corticosteroid therapy has shown benefit, with hydrocortisone 50 mg every 6 hours showing 93% probability of superiority regarding improvement in organ support-free days 7
• Abrupt discontinuation of corticosteroids can lead to deterioration from a reconstituted inflammatory response 2
• In patients with relative adrenal insufficiency during septic shock, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced mortality 8

Common Pitfalls

• Using corticosteroids in sepsis without shock provides no benefit and is not recommended 2, 3
• Extending therapy beyond 7-10 days carries no additional benefit and increases toxicity 1
• Relying solely on clinical symptoms for dose adjustment without considering pharmacokinetic principles may lead to inadequate treatment 9
• Failure to recognize that doubling the hydrocortisone dose in fast metabolizers may not result in proportionally enhanced cortisol exposure 5