When is hydrocortisone (cortisol) used in the treatment of infections?

Hydrocortisone in Infection: When and How to Use It

Hydrocortisone should be reserved exclusively for patients with septic shock who remain hypotensive despite adequate fluid resuscitation and moderate-to-high dose vasopressor therapy (typically >0.1 μg/kg/min norepinephrine equivalent); it has no role in sepsis without shock. 1, 2, 3

Clinical Indications

Use Hydrocortisone ONLY in Vasopressor-Unresponsive Septic Shock

• Administer hydrocortisone 200 mg/day intravenously when patients with septic shock fail to achieve hemodynamic stability after adequate fluid resuscitation AND require moderate-to-high dose vasopressors 1, 2, 3
• The 2018 BMJ guideline makes a weak recommendation for corticosteroids in septic shock, acknowledging that both using and not using steroids are reasonable options depending on patient values 4
• Do NOT use hydrocortisone in patients with severe sepsis who are not in shock—the HYPRESS trial definitively showed no difference in progression to septic shock or mortality (21.2% vs 22.9% shock development, p=0.70) 2, 5

Specific Dosing Protocol

• Dose: 200 mg/day of hydrocortisone (NOT exceeding 400 mg/day) 1, 2, 3
• Route: Continuous intravenous infusion is preferred over divided doses 1, 3
• Duration: Continue for at least 3-5 days at full dose before considering tapering 1, 2, 3
• Tapering: When vasopressors are discontinued, taper hydrocortisone gradually over 6-14 days rather than stopping abruptly to avoid rebound inflammation and hemodynamic deterioration 2, 3

Pediatric Considerations

The evidence in children differs substantially from adults:

• In pediatric septic shock, hydrocortisone is recommended ONLY for patients with suspected or proven absolute adrenal insufficiency (peak cortisol <18 μg/dL after ACTH stimulation) 4
• Stress-dose hydrocortisone (50 mg/m²/24h) may be considered in children with fluid-refractory, catecholamine-resistant shock, though evidence is insufficient for routine use 4
• The 2010 pediatric consensus found no survival benefit with low-dose hydrocortisone in children with septic shock, unlike adult data 4

Diagnostic Testing: What NOT to Do

Do not use the ACTH stimulation test to decide who receives hydrocortisone—this is a critical pitfall 1, 2, 3. The test does not predict shock reversal or mortality benefit and should not guide therapy decisions 3. Random cortisol levels may identify absolute adrenal insufficiency but have no role in determining relative adrenal insufficiency in septic shock 1.

Mechanism and Expected Benefits

Hydrocortisone works through multiple pathways in septic shock:

• Anti-inflammatory effects: Reduces pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-6) 6
• Hemodynamic stabilization: Increases systemic vascular resistance and reduces vasopressor requirements 6, 7, 8
• Shock reversal: Meta-analyses confirm improved shock reversal time, though mortality benefit remains controversial 4, 1, 9

The Surviving Sepsis Campaign guidelines note that while hydrocortisone may reduce shock duration, the overall mortality benefit is uncertain with low-quality evidence 2.

Critical Risks and Monitoring

Common Adverse Effects

• Hyperglycemia: Most common adverse effect requiring blood glucose monitoring (target <150 mg/dL) 4, 2, 3
• Hypernatremia: Monitor serum sodium levels regularly 2, 3
• Superinfection: Increased risk of secondary infections including new sepsis episodes 4, 1, 3

Serious Risks

• High-dose corticosteroids (>400 mg/day) increase mortality and secondary infections—never use high-dose regimens 4, 3
• Abrupt discontinuation causes hemodynamic deterioration and rebound inflammation 2, 3

Common Pitfalls to Avoid

1. Using hydrocortisone in sepsis without shock: This provides no benefit and may cause harm 2, 3, 5

2. Etomidate for intubation: Avoid etomidate in patients who may require hydrocortisone, as it suppresses the hypothalamic-pituitary-adrenal axis and worsens outcomes 4, 1, 2

3. High-dose, short-course steroids: These are ineffective or harmful—always use low-dose (200 mg/day), long-duration therapy 4, 3

4. Relying on ACTH stimulation testing: This has no role in septic shock management decisions 1, 2, 3

5. Abrupt cessation: Always taper when discontinuing to prevent rebound effects 2, 3

Special Populations

Neutropenic Patients

• Do NOT use substitutive doses of hydrocortisone in neutropenic patients with sepsis—the CORTICUS trial showed no mortality benefit and increased secondary infections 4
• Continue corticosteroids only if already prescribed for other conditions (e.g., graft-versus-host disease) 4

Contraindications

• Do not use in cerebral malaria (no evidence of benefit) 2
• Avoid in influenza (increased mortality risk: OR 3.06,95% CI 1.58-5.92) 2
• Not recommended for traumatic brain injury (increased mortality) 10

Patient Selection Algorithm

Step 1: Confirm septic shock diagnosis (sepsis + vasopressor requirement to maintain MAP ≥65 mmHg + lactate >2 mmol/L despite adequate fluid resuscitation) 4

Step 2: Ensure adequate fluid resuscitation completed 1, 3

Step 3: Assess vasopressor dose—if requiring >0.1 μg/kg/min norepinephrine equivalent, consider hydrocortisone 2, 3

Step 4: Initiate hydrocortisone 200 mg/day continuous infusion 1, 2, 3

Step 5: Monitor for hyperglycemia, hypernatremia, and superinfection 2, 3

Step 6: When vasopressors discontinued, taper hydrocortisone over 6-14 days 2, 3

Patients who place higher value on avoiding death over quality of life concerns are more likely to choose hydrocortisone therapy, while those prioritizing functional status may reasonably decline 4.