What are the alternatives to TPA (tissue plasminogen activator) and Dornase (deoxyribonuclease) for pleural drainage?

Alternatives to TPA and Dornase for Pleural Drainage

For patients requiring pleural drainage, urokinase is the recommended alternative to TPA (tissue plasminogen activator) and Dornase (DNase), particularly in children, as it has been studied in randomized controlled trials and shown to shorten hospital stays. 1

Fibrinolytic Alternatives

Urokinase

• Demonstrated efficacy in a randomized controlled trial in children
• Recommended dosing:
  • Adults: 100,000 IU once daily for 3 days 1
  • Children: 40,000 units in 40 ml 0.9% saline twice daily for 3 days (for children ≥1 year); 10,000 units in 10 ml 0.9% saline for children <1 year 1
• Advantages: Non-antigenic (unlike streptokinase), lower risk of immunological reactions
• Limitation: No longer available in North America

Streptokinase

• Traditional option: 250,000 IU twice daily for 3 days 1
• Not recommended by current guidelines due to:
  • Lack of mortality benefit shown in recent trials 1
  • Immunological side effects (fever, allergic reactions)
  • Systemic antibody response that can neutralize later administration
• Patients who receive streptokinase should be given a streptokinase exposure card

Low-dose TPA regimens

• When TPA must be used but bleeding risk is a concern:
  • Consider reduced dose of 5 mg TPA twice daily (instead of standard 10 mg) with 5 mg DNase twice daily for 3 days 1
  • For very high bleeding risk: 2.5 mg TPA with 5 mg DNase has shown effectiveness in recent studies 2

Non-Fibrinolytic Approaches

Saline Irrigation

• Can be considered when intrapleural TPA/DNase or surgery is not suitable 1
• Technique: Flush with 20-50 ml normal saline to ensure chest tube patency 1
• May help maintain drain patency but less effective for breaking down loculations

Surgical Options

• Video-assisted thoracoscopic surgery (VATS) is preferred over thoracotomy 1
• Indications for surgical referral:
  • Persistent sepsis and residual pleural collection after 5-7 days of drainage and antibiotics
  • Organized empyema
  • Multiloculated effusions not responding to tube drainage

Important Clinical Considerations

1. Chest tube management:

   • Use small-bore chest tubes (14F or smaller) for initial drainage 1
   • Ensure tube patency by checking for kinks and flushing with saline if drainage is poor
   • Position tubes under ultrasound guidance for optimal placement

2. Monitoring effectiveness:

   • Assess drainage effectiveness after 5-8 days of treatment
   • Monitor temperature, white blood cell count, clinical symptoms, and radiographic improvement
   • Consider contrast-enhanced CT scanning for patients failing chest tube drainage

3. Contraindications and cautions:

   • Avoid single-agent TPA or DNase therapy (combination is significantly more effective) 1, 3
   • Use reduced doses of fibrinolytics in patients with higher bleeding risk
   • Obtain proper consent when using fibrinolytics due to bleeding risk

4. Special populations:

   • In children: Urokinase has been shown to shorten hospital stay (7.39 vs. 9.49 days) 1
   • In patients with malignant pleural effusions: Modified low-dose protocols (5 mg alteplase/5 mg DNase) may be effective even with pre-existing anemia 4

The choice of alternative should be based on patient factors, local availability of agents, and the nature of the pleural collection. When TPA/DNase cannot be used, urokinase represents the best-studied alternative, particularly in pediatric populations.