What is the role of Flolan (epoprostenol) in severe Acute Respiratory Distress Syndrome (ARDS)?

Role of Flolan (Epoprostenol) in Severe ARDS

Inhaled epoprostenol (Flolan) should be considered as a rescue therapy in severe ARDS cases with refractory hypoxemia when conventional treatments have failed, but it is not recommended as a first-line therapy.

Conventional Management of Severe ARDS

Before considering epoprostenol, the following evidence-based interventions should be implemented:

1. Lung-protective ventilation strategies:

   • Low tidal volumes (4-8 ml/kg predicted body weight)
   • Plateau pressure ≤30 cmH₂O
   • Driving pressure <15 cmH₂O
   • Appropriate PEEP strategy based on severity 1

2. First-line adjunctive therapies for severe ARDS (PaO₂/FiO₂ ≤100 mmHg):

   • Prone positioning for >12 hours/day (strong recommendation) 2, 1
   • Neuromuscular blockade in early stages 2, 1
   • Consideration of corticosteroids 1

Role of Epoprostenol in Severe ARDS

Epoprostenol may be considered when:

• Severe hypoxemia persists despite optimized conventional therapies
• Patient is non-responsive to other pulmonary vasodilators like inhaled nitric oxide
• Rapid improvement in oxygenation is needed as a bridge to other therapies

Evidence for Epoprostenol Use:

• Inhaled epoprostenol has been shown to improve oxygenation in severely hypoxemic patients, with studies showing a median increase of 44.5% in PaO₂/FiO₂ ratio within the first 4 hours of administration 3
• Earlier intervention (within 7 days of intubation) appears more efficacious at improving oxygenation 4
• Comparative effectiveness analyses have found no significant differences in outcomes between inhaled nitric oxide and epoprostenol in severe acute respiratory failure 5

Practical Considerations:

• Starting dose: Typically 30 ng/kg/min (mean starting dose from studies) 3
• Monitoring: Close monitoring for hypotension (observed in 18.8% of patients) 3
• Administration concerns: Medication errors have been observed in up to 25% of patients, requiring careful protocol implementation 3

Veno-Venous ECMO Consideration

If epoprostenol and other rescue therapies fail to improve oxygenation, VV-ECMO should be considered:

• The American Thoracic Society suggests VV-ECMO in selected patients with severe ARDS (conditional recommendation, low certainty of evidence) 2
• VV-ECMO should be reserved for patients with:
  • Very severe hypoxemia (PaO₂/FiO₂ ratio < 80 mm Hg)
  • Hypercapnia (pH < 7.25 with PaCO₂ > 60 mm Hg)
  • Early ARDS course (<7 days)
  • Reversible etiology of respiratory failure 2

Algorithm for Epoprostenol Use in Severe ARDS

1. Confirm severe ARDS (PaO₂/FiO₂ ≤100 mmHg)
2. Implement conventional therapies:
   • Lung-protective ventilation
   • Prone positioning
   • Neuromuscular blockade
   • Consider corticosteroids
3. Assess response after 12-24 hours
4. If persistent severe hypoxemia:
   • Consider inhaled epoprostenol at 30 ng/kg/min
   • Monitor for improvement in oxygenation within 4 hours
   • Watch for hypotension and other adverse effects
5. If no response to epoprostenol:
   • Consider VV-ECMO if patient meets criteria
   • Transfer to an ECMO-capable center if necessary

Pitfalls and Caveats

• Medication errors are common with epoprostenol administration, requiring standardized protocols and trained staff 3
• Hypotension is the most common adverse effect and requires close hemodynamic monitoring 3
• The impact of epoprostenol on mortality in ARDS remains unknown, as most studies focus on oxygenation improvement 3
• Epoprostenol should not delay consideration of ECMO in appropriate candidates 2
• Epoprostenol should be used as part of a comprehensive approach to ARDS management, not as a standalone therapy

While epoprostenol shows promise in improving oxygenation in severe ARDS, its effects on mortality remain uncertain, and it should be considered as part of a sequential approach to managing refractory hypoxemia in severe ARDS.