What is acute respiratory distress syndrome (ARDS) and how is it managed?

Acute Respiratory Distress Syndrome (ARDS): Pathophysiology and Management

ARDS is a devastating critical illness characterized by severe hypoxemia, bilateral pulmonary infiltrates, and non-cardiogenic pulmonary edema with mortality rates of 30-40%, requiring lung-protective ventilation strategies and potentially adjunctive therapies based on severity. 1

Definition and Diagnosis

ARDS is defined by the Berlin criteria as:

• Acute onset within 1 week of known clinical insult
• Bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload
• Respiratory failure not explained by cardiac failure
• Impaired oxygenation with PaO₂/FiO₂ ratio ≤300 mmHg with at least 5 cmH₂O PEEP
• Severity classification:
  • Mild: 200 < PaO₂/FiO₂ ≤ 300 mmHg
  • Moderate: 100 < PaO₂/FiO₂ ≤ 200 mmHg
  • Severe: PaO₂/FiO₂ ≤ 100 mmHg 1

Pathophysiology

ARDS develops through a complex cascade of events:

1. Initiating Insult: Various triggers can cause ARDS, including:

   • Direct lung injury: pneumonia, aspiration, inhalation injury
   • Indirect lung injury: sepsis, trauma, pancreatitis, transfusion-related injury 1, 2

2. Inflammatory Response:

   • Leukocyte infiltration and immune activation
   • Release of pro-inflammatory cytokines
   • Alveolar epithelial and endothelial injury 1

3. Increased Vascular Permeability:

   • Damage to alveolar-capillary barrier
   • Pulmonary edema formation
   • Surfactant dysfunction 1

4. Pathological Changes:

   • Loss of aerated lung tissue
   • Decreased lung compliance
   • Ventilation-perfusion mismatch
   • Impaired gas exchange leading to hypoxemia 1

Management Strategies

Ventilation Strategies

Lung-Protective Ventilation (cornerstone of management):

• Tidal volume: 4-8 mL/kg predicted body weight
• Plateau pressure ≤30 cmH₂O
• Driving pressure (Pplat-PEEP) ≤15 cmH₂O 1, 3

PEEP Management:

• Initial PEEP: 5-8 cmH₂O as starting point
• Higher PEEP (>10 cmH₂O) for moderate to severe ARDS
• Titrate based on oxygenation, compliance, and hemodynamic effects 1, 3
• We recommend against using prolonged lung recruitment maneuvers in moderate to severe ARDS 1

Adjunctive Therapies

For Severe ARDS (PaO₂/FiO₂ ≤100 mmHg):

• Prone positioning for >12 hours/day (strong recommendation) 1, 3
• Neuromuscular blockers in early severe ARDS (conditional recommendation) 1, 3
• Venovenous ECMO in selected patients (conditional recommendation) 1
• Corticosteroids may be considered (conditional recommendation) 1, 3

Hemodynamic Management

• Ensure adequate intravascular volume while avoiding fluid overload
• Monitor for right ventricular dysfunction and acute cor pulmonale (occurs in 20-25% of cases)
• Consider norepinephrine for shock unresponsive to fluids
• Implement RV-protective ventilation strategies when needed 1

Additional Supportive Care

• Conservative fluid management strategy once hemodynamically stable
• DVT prophylaxis
• Stress ulcer prophylaxis
• Minimize sedation when appropriate
• Elevate head of bed 30-45° to prevent aspiration
• Enteral nutrition when appropriate 3

Monitoring

• Regular assessment of oxygenation (target SpO₂ 92-97% for most patients)
• Monitor plateau pressure, driving pressure, and patient-ventilator synchrony
• Echocardiography to assess for right ventricular dysfunction
• Daily assessment for readiness to wean from mechanical ventilation 1, 3

Heterogeneity and Precision Medicine

ARDS demonstrates significant heterogeneity on three levels:

1. Aetiological (diverse triggering factors)
2. Physiological (variable respiratory mechanics)
3. Biological (different inflammatory patterns)

This heterogeneity suggests that a precision medicine approach may be beneficial, with treatments tailored to specific ARDS phenotypes rather than a one-size-fits-all approach 1.

Prognosis

Despite advances in supportive care, ARDS continues to have high mortality rates:

• Overall in-hospital mortality: 30-40%
• Mortality increases with severity of hypoxemia
• Significant long-term morbidity among survivors, including cognitive impairment, muscle weakness, and reduced quality of life 1

Early recognition and implementation of lung-protective ventilation strategies remain crucial for improving outcomes in patients with ARDS.