What is the role of corticosteroids (steroids) in the treatment of Acute Respiratory Distress Syndrome (ARDS)?

Corticosteroids in ARDS

Corticosteroids should be used in patients with early moderate to severe ARDS (PaO₂/FiO₂ <200 within 14 days of onset), as they reduce mortality, shorten mechanical ventilation duration, and improve lung function when initiated early. 1, 2

Patient Selection Criteria

Use corticosteroids when ALL of the following are met:

• PaO₂/FiO₂ ratio <200 (moderate to severe ARDS) 1
• Within 14 days of ARDS onset - this is a critical cutoff, as initiation after 14 days may increase mortality 1, 2, 3
• No active uncontrolled infection - exclude this before starting therapy 4
• Not immunocompromised requiring ongoing immunosuppressive therapy 2

Mortality and Morbidity Benefits

The evidence strongly supports corticosteroid use for improving key outcomes:

• Mortality reduction of approximately 16% (RR 0.84; 95% CI 0.73-0.96) based on pooled analysis of 19 RCTs with 2,790 patients 2
• Reduction in mechanical ventilation duration by 4-7 days 1, 2
• Hospital mortality reduction of 7-11% in patients with mild to severe ARDS 1
• Reduction in hospital length of stay by approximately 8 days 5

These benefits are derived from consistent findings across nine trials investigating prolonged glucocorticoid treatment, which demonstrated significant reductions in inflammatory markers (cytokines, C-reactive protein) and faster disease resolution 1.

Dosing Regimens

Early ARDS (≤7 days from onset):

Methylprednisolone 1 mg/kg/day with slow tapering over 6-14 days 5

Alternative: Dexamethasone 20 mg IV daily for 5 days, then 10 mg IV daily for 5 days 2

Early initiation (<72 hours) when fibroproliferation is still in the cellular stage with predominant type III procollagen shows better response to lower doses and faster disease resolution compared to late initiation 1, 5.

Late Persistent ARDS (days 7-14):

Methylprednisolone 2 mg/kg/day with slow tapering over 13 days 5, 4

Methylprednisolone is preferred over other corticosteroids due to greater penetration into lung tissue and longer residence time 5, 4.

Critical Timing Considerations

The timing of corticosteroid initiation is paramount:

• Optimal window: <72 hours from ARDS onset for maximum benefit 1, 5
• Acceptable window: Up to 14 days from onset 1, 2
• Harmful after 14 days: Starting methylprednisolone >14 days after ARDS onset is associated with significantly increased 60-day and 180-day mortality 3

This timing-dependent effect relates to the pathophysiology of ARDS - early intervention targets the inflammatory phase, while late intervention may interfere with necessary repair processes 1.

Mandatory Monitoring and Management

Hyperglycemia (Most Common Adverse Effect):

• Monitor blood glucose closely, especially within first 36 hours after initiation 2, 5, 4
• Risk increase: RR 1.11 (95% CI 1.01-1.23) 2, 5
• Treat hyperglycemia aggressively with insulin protocols 2
• Hyperglycemia has not been associated with increased morbidity in ARDS trials 1

Infection Surveillance:

• Regular monitoring essential as glucocorticoids blunt febrile response 5
• Prolonged glucocorticoid treatment was not associated with increased risk of nosocomial infection in ARDS trials 1
• Two trials reported significant reduction in risk of developing shock with steroid treatment 1

Neuromuscular Weakness:

• Higher risk when combined with neuromuscular blockers 5
• Monitor for weakness, particularly with prolonged therapy 3

Gastrointestinal Bleeding:

• Consider stress ulcer prophylaxis (H2 receptor inhibitors preferred) 5
• Risk: RR 1.20 (95% CI 0.43-3.34) 5

Critical Pitfalls to Avoid

Do NOT Use High-Dose Pulse Steroids:

High-dose pulse therapy (500-1,000 mg methylprednisolone IV daily for 2-3 days) does NOT improve survival and should be avoided 5. This is distinct from the prolonged low-to-moderate dose regimens that show benefit 1.

Do NOT Abruptly Discontinue:

Abrupt discontinuation may lead to deterioration from reconstituted inflammatory response - always taper slowly 5, 4.

Do NOT Delay Beyond 14 Days:

Starting therapy >14 days after ARDS onset may increase mortality risk 2, 3. If a patient presents late, corticosteroids should generally be avoided unless there is clear evidence of ongoing inflammatory activity 3.

Integration with Other ARDS Therapies

Corticosteroids are an adjunct to, not a replacement for, proven ARDS interventions:

• Continue lung-protective ventilation (tidal volume 6 mL/kg predicted body weight, plateau pressure <30 cmH₂O) throughout treatment 2, 5, 4
• Prone positioning for severe ARDS (PaO₂/FiO₂ <100) 2
• Consider neuromuscular blockade in early severe ARDS as adjunct therapy 2
• Deep vein thrombosis prophylaxis 5
• Semi-recumbent positioning (head of bed elevated 45 degrees) 5
• Sedation protocols with daily interruption/lightening when possible 5

Special Populations Requiring Caution

Exercise heightened surveillance in:

• Immunocompromised patients 2
• Patients with metabolic syndrome 2
• Regions with endemic tuberculosis 2

Evidence Quality and Strength

The recommendation is based on moderate quality evidence from the Society of Critical Care Medicine and European Society of Intensive Care Medicine 2017 guidelines 1, supported by individual patient data analysis of the four largest trials (n=322) confirming improved survival and decreased mechanical ventilation duration 1. The American Thoracic Society provides a conditional recommendation with moderate certainty of evidence 2, 5.