What are the therapeutic options for severe Acute Respiratory Distress Syndrome (ARDS)?

Therapeutic Management of Severe ARDS

For severe ARDS (PaO₂/FiO₂ <100 mmHg), immediately implement lung-protective ventilation with tidal volumes of 4-8 mL/kg predicted body weight and plateau pressure ≤30 cmH₂O, combined with prone positioning for >12 hours daily—these are the only interventions with strong evidence for mortality reduction. 1, 2

Foundational Ventilatory Strategy

Lung-Protective Ventilation (Mandatory)

• Set tidal volume at 4-8 mL/kg predicted body weight (not actual body weight) and maintain plateau pressure ≤30 cmH₂O—this is a strong recommendation with moderate confidence in mortality benefit 1, 3
• Target SpO₂ no higher than 96% to avoid oxygen toxicity 2, 4
• Use higher PEEP strategy (>12 cmH₂O) in severe ARDS, though this is a conditional recommendation with moderate confidence 1, 2, 5

Recruitment Maneuvers (Use Cautiously)

• Consider brief recruitment maneuvers in severe ARDS, but avoid prolonged recruitment maneuvers as they carry risk without clear benefit 2, 3
• This is a conditional recommendation with low confidence in effect estimates 1

What NOT to Do

• Do not use high-frequency oscillatory ventilation—this is strongly recommended against based on high-quality evidence showing potential harm in moderate-to-severe ARDS 1, 3, 5

Prone Positioning (Critical for Severe ARDS)

Implement prone positioning for 12-16 hours daily in all patients with severe ARDS (PaO₂/FiO₂ <100 mmHg)—this is a strong recommendation with demonstrated mortality reduction 1, 2, 4

• Begin prone positioning early (≤48 hours after onset of severe ARDS) and repeat in 16-hour sessions 6
• Apply deep sedation and analgesia during prone positioning 4
• This intervention has moderate confidence in effect estimates for mortality benefit 1

Neuromuscular Blockade

Consider cisatracurium infusion for 48 hours in early severe ARDS to improve ventilator synchrony, reduce oxygen consumption, and potentially improve outcomes 2, 4, 5

• This is particularly beneficial when ventilator-patient dyssynchrony persists despite adequate sedation 4, 7
• Use in patients with PaO₂/FiO₂ ≤20 kPa (approximately ≤150 mmHg) 5, 6
• This is a conditional recommendation with low certainty of evidence 2

Fluid Management

Implement a conservative fluid management strategy to minimize pulmonary edema while maintaining adequate organ perfusion 2, 3, 4

• Avoid fluid overload, which worsens oxygenation, promotes right ventricular failure, and increases mortality 4
• Monitor fluid balance carefully and consider hemofiltration for specific indications 6
• This strategy is suggested for all ARDS patients 5

Corticosteroids

Administer systemic corticosteroids in severe ARDS—this is a conditional recommendation with moderate certainty of evidence 2

• Corticosteroids may be particularly beneficial in patients with fibroproliferation 3
• COVID-19 ARDS has shown specific mortality benefit with corticosteroids 2

Rescue Therapies for Refractory Hypoxemia

Inhaled Pulmonary Vasodilators

• Consider a trial of inhaled pulmonary vasodilators (such as inhaled nitric oxide) as rescue therapy for severe hypoxemia despite optimized ventilation 2, 4
• Discontinue if no rapid improvement in oxygenation occurs 2
• Do not use inhaled nitric oxide routinely—the evidence does not support routine use 2, 5

Extracorporeal Membrane Oxygenation (ECMO)

Consider venovenous ECMO in selected patients with severe ARDS (PaO₂/FiO₂ <100 mmHg) who fail conventional management—this is a conditional recommendation with low certainty of evidence 2, 4

• ECMO should only be implemented at centers with ECMO expertise 4, 5
• Reserve for patients with reversible disease and very severe ARDS 4, 7
• Blood is pumped from the femoral vein and returns to the right atrium through the internal jugular vein after membrane oxygenation 4
• Additional evidence is necessary to make a definitive recommendation for or against ECMO 1

Monitoring Requirements

Continuously monitor the following parameters to guide therapy and detect complications:

• Oxygen saturation, respiratory mechanics (driving pressure, plateau pressure, dynamic compliance), and hemodynamics 3, 4
• Use echocardiography to assess right ventricular function and detect acute cor pulmonale, as inappropriate ventilator settings can cause right ventricular dysfunction 2, 3
• Assess for ventilator-patient dyssynchrony 4
• Monitor for barotrauma, especially when using higher PEEP strategies (PEEP >10 cmH₂O) 2

Algorithmic Approach to Refractory Hypoxemia

When severe hypoxemia persists despite lung-protective ventilation:

1. First-line interventions: Optimize PEEP (>12 cmH₂O), perform brief recruitment maneuvers, initiate prone positioning (12-16 hours daily), and administer neuromuscular blockade (cisatracurium for 48 hours) 7, 6

2. Second-line interventions: Trial inhaled pulmonary vasodilators (discontinue if no rapid response), ensure conservative fluid management, consider corticosteroids 2, 7

3. Last resort: Transfer to ECMO-capable center for venovenous ECMO in selected patients with reversible disease 2, 4, 7

Common Pitfalls

• Excessive fluid administration worsens oxygenation and outcomes—careful monitoring of fluid balance is essential 3, 4
• Using actual body weight instead of predicted body weight for tidal volume calculations leads to ventilator-induced lung injury 1, 3
• Delaying prone positioning beyond 48 hours reduces its mortality benefit 6
• Continuing inhaled pulmonary vasodilators without rapid improvement in oxygenation wastes resources without benefit 2