What is the preferred corticosteroid, Hydrocortisone (hydrocortisone) or Prednisolone (prednisolone), in acute respiratory distress?

Hydrocortisone vs Prednisolone in Acute Respiratory Distress

Hydrocortisone is the preferred corticosteroid for acute respiratory distress in the context of septic shock, while methylprednisolone (not prednisolone) is preferred for ARDS itself. Neither hydrocortisone nor prednisolone is the optimal choice for ARDS—methylprednisolone demonstrates superior lung tissue penetration and longer residence time, making it the evidence-based selection for this specific indication 1.

Corticosteroid Selection by Clinical Context

For ARDS (Without Septic Shock)

• Methylprednisolone 1 mg/kg/day IV is the recommended agent for early moderate to severe ARDS (PaO₂/FiO₂ <200 within 14 days of onset) 2, 3
• The preference for methylprednisolone over hydrocortisone or prednisolone is based on its greater penetration into lung tissue and longer residence time in pulmonary compartments 1
• Treatment should be initiated early (<72 hours) when fibroproliferation is still in the cellular stage with predominant type III procollagen 2
• Duration should be ≥14 days with gradual tapering rather than abrupt discontinuation 3, 4

For Septic Shock with Respiratory Distress

• Hydrocortisone <400 mg/day (typically 200 mg/day) IV for ≥3 days is recommended when patients have septic shock unresponsive to fluid resuscitation and moderate-to-high dose vasopressors 2, 1, 3
• Administration can be as 50 mg IV bolus every 6 hours or continuous infusion 2
• Consider adding fludrocortisone 50 μg daily for enhanced efficacy in septic shock 5
• Taper gradually over 6-14 days when vasopressors are no longer required to avoid rebound inflammation 1

For Community-Acquired Pneumonia

• Hydrocortisone <400 mg/day or equivalent for 5-7 days is suggested for hospitalized patients with CAP 2, 1
• This reduces mortality, hospital stay, need for mechanical ventilation, and prevents ARDS progression 2

Evidence Quality and Strength

The 2024 American Thoracic Society guidelines provide the most recent high-quality evidence, offering a conditional recommendation with moderate certainty for corticosteroids in ARDS 2. The 2017 SCCM/ESICM guidelines remain the definitive source for agent selection, consistently recommending methylprednisolone for ARDS and hydrocortisone for septic shock 2, 3.

A 2025 meta-analysis of 43 RCTs (n=10,853) demonstrated that corticosteroids reduce short-term mortality in critically ill patients (RR 0.85,95% CI 0.77-0.94), with subgroup analysis confirming that early initiation (≤72 hours), low-dose (<400 mg/day hydrocortisone equivalent), and prolonged therapy (≥7 days) optimize outcomes 6.

Clinical Algorithm

Step 1: Identify the primary pathology

• If septic shock predominates → hydrocortisone
• If ARDS predominates without shock → methylprednisolone
• If community-acquired pneumonia → hydrocortisone

Step 2: Verify timing and severity

• ARDS: Must be within 14 days of onset with PaO₂/FiO₂ <200 2
• Septic shock: Must be unresponsive to fluids and requiring moderate-to-high dose vasopressors (>0.1 μg/kg/min norepinephrine equivalent) 2

Step 3: Initiate appropriate agent and dose

• Methylprednisolone 1 mg/kg/day for ARDS 2, 3
• Hydrocortisone 200 mg/day (divided or continuous) for septic shock 1, 3

Step 4: Plan duration and taper

• ARDS: ≥14 days with gradual taper 3
• Septic shock: ≥3 days at full dose, then taper over 6-14 days when vasopressors discontinued 1, 3

Critical Pitfalls to Avoid

• Do not use prednisolone as first-line for ARDS—it lacks the evidence base and pharmacokinetic advantages of methylprednisolone 1
• Never stop corticosteroids abruptly—this causes rebound inflammation and hemodynamic deterioration 1, 3
• Do not use corticosteroids for sepsis without shock—no mortality benefit exists and potential harm may occur 1, 3
• Avoid late initiation (≥7 days) in ARDS—early treatment (<72 hours) shows superior outcomes with lower required doses 2
• Do not use ACTH stimulation testing to guide treatment decisions—it has no role in determining who should receive corticosteroids 1, 4

Monitoring Requirements

• Monitor blood glucose closely—hyperglycemia occurs more frequently with corticosteroids (RR 1.10-1.12) 6, 7
• Check serum sodium for hypernatremia, particularly during tapering 1
• Surveillance for secondary infections, though rates are not significantly increased (RR 1.01) 6
• Monitor for gastrointestinal bleeding, though risk is not significantly elevated (RR 1.07) 6