Role of Dexamethasone in ARDS
The American Thoracic Society conditionally recommends using corticosteroids, including dexamethasone, for patients with ARDS (PaO2/FiO2 <300), as they probably reduce mortality and duration of mechanical ventilation. 1, 2
Evidence for Mortality Benefit
Pooled analysis of 19 randomized controlled trials including 2,790 patients demonstrated that corticosteroids probably decrease mortality (RR 0.84; 95% CI 0.73-0.96; moderate certainty of evidence). 2
The landmark DEXA-ARDS trial showed that dexamethasone reduced 60-day mortality from 36% to 21% (absolute difference -15.3%; p=0.0047) in patients with established moderate-to-severe ARDS. 3
In COVID-19-related ARDS specifically, the CoDEX trial demonstrated that dexamethasone increased ventilator-free days (6.6 vs 4.0 days; p=0.04) and reduced organ dysfunction scores. 4
Optimal Dosing Regimen
Use dexamethasone 20 mg IV daily for 5 days, followed by 10 mg IV daily for 5 days. 2, 3, 4
This regimen was validated in the DEXA-ARDS trial and resulted in a mean increase of 4.8 ventilator-free days (95% CI 2.57-7.03; p<0.0001). 3
Alternative regimens using methylprednisolone (2 mg/kg/day with slow tapering) may be considered for late persistent ARDS after day 6, though the optimal agent remains unclear due to trial heterogeneity. 2
Animal studies suggest that higher doses (1 mg/kg) may have faster onset and more effective suppression of inflammatory markers compared to lower doses (0.5 mg/kg). 5
Critical Timing Considerations
Initiate corticosteroids within the first 14 days of mechanical ventilation; starting after 2 weeks may cause harm. 1, 2
The DEXA-ARDS trial enrolled patients with persistent ARDS at 24 hours after onset, demonstrating that early administration is both safe and effective. 3, 6
Chinese guidelines during COVID-19 recommended methylprednisolone for 3-5 days in severe cases to prevent progression to cytokine storm, emphasizing early intervention. 1
Patient Selection Criteria
Apply corticosteroids to patients meeting these criteria: 1, 2
- PaO2/FiO2 ratio ≤200 mmHg on PEEP ≥10 cmH2O and FiO2 ≥0.5
- Within 14 days of mechanical ventilation initiation
- No contraindications (active uncontrolled infection, immunosuppression requiring ongoing therapy)
Monitoring and Safety
Monitor blood glucose closely, especially within the first 36 hours, as hyperglycemia occurs in approximately 76% of patients. 2, 3
The most common adverse event in DEXA-ARDS was hyperglycemia (105/139 patients [76%] in dexamethasone group vs 97/138 [70%] in control group). 3
New infections occurred at similar rates between dexamethasone and control groups (24% vs 25%), suggesting no increased infection risk with this regimen. 3
Exercise heightened surveillance in immunocompromised patients, those with metabolic syndrome, or patients in regions with endemic tuberculosis or fungal infections. 1, 2
Assess for gastrointestinal bleeding, neuromuscular weakness, and barotrauma during therapy. 2, 3
Integration with Other ARDS Therapies
Continue lung-protective ventilation (tidal volume 4-8 mL/kg predicted body weight, plateau pressure <30 cmH2O) throughout corticosteroid treatment. 1, 2
Corticosteroids should be used alongside, not instead of, proven ARDS interventions including prone positioning for severe ARDS (PaO2/FiO2 <100). 1
Consider neuromuscular blockade in early severe ARDS as an adjunct to corticosteroid therapy. 1
Special Populations
In COVID-19-related ARDS, patients with cardiovascular disease have increased risk of death or requiring invasive mechanical ventilation (RR 7.64; 95% CI 1.24-47.06), warranting closer monitoring. 7