What is the recommended treatment for critical illness related to corticosteroid (CS) insufficiency?

Treatment of Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

For patients with septic shock unresponsive to fluid resuscitation and moderate-to-high dose vasopressors (>0.1 μg/kg/min norepinephrine equivalent), use IV hydrocortisone 200 mg/day administered as either continuous infusion or divided doses (50 mg every 6 hours) for at least 3 days at full dose. 1, 2

When to Initiate Corticosteroids

• Start hydrocortisone only when shock remains refractory despite adequate fluid resuscitation AND moderate-to-high dose vasopressors (>0.1 μg/kg/min norepinephrine or equivalent) 2
• Do NOT use corticosteroids in sepsis without shock—no mortality benefit has been demonstrated and potential harm exists 1, 2, 3
• Clinical indicators suggesting CIRCI include hypotension refractory to fluids, decreased catecholamine sensitivity, fever, confusion, persistent hypoxia, hypoglycemia, hyponatremia, hyperkalemia, and metabolic acidosis 1

Specific Dosing Protocol

• Hydrocortisone 200 mg/day is the recommended dose, administered preferably as continuous IV infusion over 24 hours 2, 3, 4
• Alternative regimen: hydrocortisone 50 mg IV bolus every 6 hours if continuous infusion is unavailable 2, 5
• Critical principle: Use doses <400 mg/day for ≥3 days at full dose—this is where mortality benefit has been demonstrated 1, 2
• High-dose, short-course regimens (>400 mg/day for <3 days) do NOT improve outcomes and may cause harm 2, 5
• Continue treatment until vasopressors are no longer required 2, 3

Why Hydrocortisone Over Other Steroids

• Hydrocortisone is preferred because it provides mineralocorticoid activity at physiologic doses, which other synthetic corticosteroids lack 2
• Network meta-analysis showed hydrocortisone boluses/infusions were more effective than methylprednisolone for shock reversal 2
• Steroid equivalencies: hydrocortisone 20 mg = prednisone 5 mg = dexamethasone 0.75 mg 2

Diagnostic Testing Considerations

• Do NOT use the ACTH stimulation test to identify which patients with septic shock should receive hydrocortisone—it has no role in treatment decisions 1, 2, 6
• If diagnostic testing is desired for other reasons, a delta cortisol <9 μg/dL after cosyntropin (250 μg) or random total cortisol <10 μg/dL may indicate adrenal insufficiency 1, 4, 6
• Plasma total cortisol is preferred over plasma free cortisol or salivary cortisol 1, 6

Tapering Protocol

• Begin tapering when vasopressors are no longer required, NOT abruptly 1, 2, 4
• Taper gradually over 6-14 days to avoid rebound inflammation and hemodynamic deterioration 1, 2
• Maintain full-dose hydrocortisone for at least 3-5 days before initiating taper 1, 2
• Abrupt discontinuation can lead to deterioration from reconstituted inflammatory response 1, 2

Monitoring Requirements

• Hyperglycemia is the most common adverse effect (90.9% vs 81.5% in placebo) and requires regular blood glucose monitoring 1, 2
• Monitor serum sodium for hypernatremia 1, 2
• Regular blood pressure determinations and serum electrolyte monitoring are essential 1, 7
• No increased risk of secondary infections (RR 1.02,95% CI 0.87-1.20) or gastrointestinal bleeding has been demonstrated 2

Condition-Specific Variations

Severe Community-Acquired Pneumonia (CAP)

• Use hydrocortisone <400 mg/day for 5-7 days in hospitalized patients with severe CAP 1, 3
• Benefits include shortened hospital stay, reduced need for mechanical ventilation, and prevention of ARDS 1, 3

Early Moderate-to-Severe ARDS

• Use IV methylprednisolone 1 mg/kg/day for ≥14 days in patients with PaO2/FiO2 <200 within 14 days of onset 1, 6
• Methylprednisolone is preferred for ARDS due to greater lung tissue penetration and longer residence time 1

Major Trauma

• Do NOT use corticosteroids in patients with major trauma—analysis of 19 trials showed no mortality benefit (RR 1.00,95% CI 0.89-1.13) 1, 6

Influenza Pneumonia

• Do NOT use corticosteroids in adults with influenza—increased risk of death (OR 3.06,95% CI 1.58-5.92) and superinfection 1, 3

Critical Pitfalls to Avoid

• Never delay treatment in suspected adrenal crisis while awaiting diagnostic confirmation 2
• Avoid starting other hormone replacements (thyroid, testosterone, estrogen) before corticosteroids—these accelerate cortisol clearance and can precipitate adrenal crisis 2
• Do not use dexamethasone to treat CIRCI—it lacks mineralocorticoid activity 4
• Etomidate use prior to hydrocortisone initiation may worsen outcomes 1
• Avoid vaccination (especially smallpox) and other immunization procedures during high-dose corticosteroid therapy due to neurological complications risk and lack of antibody response 7

Special Precautions

• Corticosteroids may mask signs of infection, and new infections may appear with decreased resistance 7
• Monitor for psychiatric effects ranging from euphoria and insomnia to severe depression and frank psychotic manifestations 8
• Use cautiously in patients with ocular herpes simplex due to possible corneal perforation 8
• Patients on immunosuppressant doses should avoid exposure to chicken pox and measles—if exposed, prophylaxis with VZIG or IG may be indicated 7