What is the role of dexamethasone (Dexa) in the management of Acute Respiratory Distress Syndrome (ARDS)?

Dexamethasone in ARDS: Evidence-Based Recommendations

Primary Recommendation

Corticosteroids, including dexamethasone, should be used in patients with established moderate-to-severe ARDS, as they reduce mortality and duration of mechanical ventilation. 1, 2

Mortality and Ventilation Benefits

• Dexamethasone reduces 60-day mortality by approximately 15% (absolute risk reduction) in moderate-to-severe ARDS. 3 The landmark DEXA-ARDS trial demonstrated 21% mortality in the dexamethasone group versus 36% in controls (p=0.0047). 3

• Pooled analysis of 19 RCTs (2,790 patients) confirms corticosteroids probably decrease mortality (RR 0.84; 95% CI 0.73-0.96; moderate certainty). 1, 2

• Dexamethasone increases ventilator-free days by approximately 4.8 days (95% CI 2.57-7.03; p<0.0001) in established ARDS. 3

• Duration of mechanical ventilation is reduced by a mean of 4 days (95% CI -5.5 to -2.5; low certainty). 1, 2

Specific Dosing Protocol

Use dexamethasone 20 mg IV daily for 5 days, then 10 mg IV daily for 5 days (total 10-day course). 2, 3, 4 This regimen was validated in the DEXA-ARDS trial and represents the most rigorously studied protocol. 3

• Alternative: Methylprednisolone 1-2 mg/kg/day with slow tapering may be considered, particularly for late persistent ARDS (after day 6). 2

Critical Timing Considerations

Initiate dexamethasone within 24 hours of meeting ARDS criteria (PaO2/FiO2 ≤200 mmHg on PEEP ≥10 cm H2O and FiO2 ≥0.5) but before 14 days of ARDS onset. 2, 3

• Do NOT initiate corticosteroids >2 weeks after ARDS onset—this may cause harm. 2, 5

• The DEXA-ARDS trial specifically enrolled patients with persistent ARDS at 24 hours, demonstrating this is the optimal window. 3

Patient Selection Criteria

Treat patients with moderate-to-severe ARDS defined as:

• PaO2/FiO2 ratio ≤200 mmHg 3
• PEEP ≥10 cm H2O 3
• FiO2 ≥0.5 3
• Assessed at 24 hours after ARDS onset 3

Exclude patients with:

• Brain death 3
• Terminal-stage disease 3
• Already receiving immunosuppressive drugs 3
• Influenza-associated ARDS (corticosteroids contraindicated per IDSA guidelines) 6
• Onset >14 days prior 2, 5

Safety Profile and Monitoring

Hyperglycemia is the most common adverse effect, occurring in approximately 76% of patients. 3

• Corticosteroids increase risk of serious hyperglycemia (RR 1.11; 95% CI 1.01-1.23; moderate certainty). 1, 2

• Monitor blood glucose closely, especially within 36 hours of initiation, and treat hyperglycemia aggressively. 2

• Gastrointestinal bleeding risk may increase (RR 1.20; 95% CI 0.43-3.34; low certainty), though evidence is less certain. 1

• New infections occurred in 24% of dexamethasone-treated patients versus 25% of controls in DEXA-ARDS (no significant difference). 3

• Enhanced surveillance is essential in immunocompromised patients, those with metabolic syndrome, or in regions with endemic tuberculosis. 2, 5

Concurrent Supportive Care Requirements

Continue lung-protective ventilation throughout corticosteroid therapy:

• Tidal volume 4-8 mL/kg predicted body weight 1, 2
• Plateau pressure <30 cm H2O 1
• All patients in DEXA-ARDS received lung-protective ventilation as standard care. 3

Consider prone positioning for >12 hours daily in severe ARDS (PaO2/FiO2 <100 mmHg), as this remains a strong recommendation independent of corticosteroid use. 1

Evidence Quality and Strength

The American Thoracic Society 2024 guidelines provide a conditional recommendation with moderate certainty of evidence for corticosteroid use in ARDS. 1 This conditional designation reflects:

• Moderate certainty for mortality benefit 1
• Low certainty for ventilation duration and hospital length of stay 1
• Variability in corticosteroid agents, doses, and durations across trials 2

However, the DEXA-ARDS trial (2020) represents the highest quality single study with clear mortality benefit, making dexamethasone the preferred agent when corticosteroids are indicated. 3

Special Populations

COVID-19-associated ARDS: The CoDEX trial confirmed dexamethasone efficacy in COVID-19 ARDS, showing increased ventilator-free days (6.6 vs 4.0 days; p=0.04) and improved SOFA scores. 4

Influenza-associated ARDS: Do NOT use corticosteroids—IDSA recommends against adjunctive corticosteroid therapy for influenza-associated ARDS unless another clinical indication exists. 6