What is the role of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNAse) in the treatment of complicated parapneumonic effusions?

Role of tPA and DNAse in Complicated Parapneumonic Effusions

Combination tissue plasminogen activator (tPA) and DNAse should be considered for the treatment of pleural infection when initial chest tube drainage has ceased and leaves a residual pleural collection. 1

Evidence-Based Approach to Parapneumonic Effusions

Initial Assessment and Management

• Small uncomplicated parapneumonic effusions (<10 mm rim of fluid) do not require drainage and can be treated with antibiotics alone
• Moderate to large effusions, especially those associated with respiratory distress or purulent fluid, should be drained
• Initial drainage should be performed using a small-bore chest tube (14F or smaller) 1

When to Consider tPA/DNAse Therapy

Intrapleural fibrinolytic therapy with tPA/DNAse is indicated when:

1. Initial chest tube drainage has ceased but leaves a residual pleural collection
2. The effusion is loculated (compartmentalized)
3. There is ongoing clinical evidence of infection despite drainage

Standard tPA/DNAse Protocol

The British Thoracic Society recommends the following regimen:

• 10 mg tPA twice daily + 5 mg DNAse twice daily for 3 days 1
• Alternative lower-dose regimen: 5 mg tPA twice daily + 5 mg DNAse twice daily for 3 days may be equally effective 1

Efficacy of tPA/DNAse

The combination therapy has been shown to:

• Reduce length of hospital stay
• Reduce likelihood of persistent fevers
• Improve radiographic clearance of pleural opacification
• Potentially reduce the need for surgical intervention 1

Important Clinical Considerations

Single-Agent Therapy Is Not Recommended

• Single agent tPA or DNAse alone should not be used as they do not appear to improve clinical outcomes compared to placebo 1
• The combination of both agents is significantly more effective than either agent alone

Bleeding Risk

• Patient consent should be obtained when using tPA/DNAse due to potential bleeding risk 1
• Consider reduced doses of tPA in patients with higher bleeding risk (e.g., those on therapeutic anticoagulation) 1

Alternative Fibrinolytics

• Streptokinase should not be used for treatment of pleural infection 1
• Urokinase may be an alternative, particularly in pediatric patients, as it has been shown to reduce the need for thoracic surgery and hospital stay 1

Special Situations

1. Sequential courses: In cases with multiple non-communicating loculated collections, sequential courses of tPA/DNAse can be safely administered to different collections 2

2. Very low-dose regimen: In patients with high bleeding risk, very low dose tPA (1 mg) with DNAse (5 mg) has been reported as successful in case reports 3

3. Alternative administration: Some centers use a simplified regimen with coadministration of tPA/DNAse rather than sequential administration, which has shown 85% success rate without surgery 4

Surgical Management

• If there is persistence of moderate to large effusions and ongoing respiratory compromise despite 2-3 days of chest tube management, VATS (video-assisted thoracoscopic surgery) should be considered 1
• VATS is preferred over thoracotomy for surgical management of pleural infection due to:
  • Shorter hospital stay (2.3 days shorter)
  • Less postoperative pain
  • Fewer complications
  • Slightly lower mortality 1

Monitoring and Follow-up

• Chest tube can be removed when pleural fluid drainage is <1 mL/kg/24h (usually calculated over the last 12 hours) and there is no air leak 1
• Monitor for clinical improvement (resolution of fever, decreasing WBC count)
• Follow radiographic resolution of the effusion

Conclusion

The evidence strongly supports the use of combination tPA/DNAse therapy for complicated parapneumonic effusions when initial chest tube drainage is inadequate. This approach has reduced the need for surgical intervention in many patients and should be considered before proceeding to VATS or thoracotomy.