tPA Dosing for Pleural Adhesions via Chest Tube
For pleural infection with loculated effusions, administer 10 mg tPA twice daily combined with 5 mg DNase twice daily for 3 days, with each dose dwelling for 1 hour before drainage. 1
Standard Dosing Regimen
The British Thoracic Society 2023 guideline establishes the evidence-based protocol for intrapleural fibrinolytic therapy:
- Primary 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 based on retrospective data and can be used when deemed necessary 1
- Dwell time: Standard protocol uses 1-hour dwell time per the randomized controlled trial data 1
When to Initiate Treatment
Combination tPA and DNase should be considered when initial chest tube drainage has ceased and leaves a residual pleural collection. 1
- Treatment is indicated for pleural infection that fails to drain adequately with chest tube alone 1
- Small bore chest tubes (14F or smaller) are recommended for initial drainage 1
Important Safety Considerations
Bleeding Risk Management
- Patient consent is mandatory due to potential bleeding risk 1
- Reduced tPA doses should be considered in patients with higher bleeding risk, particularly those on therapeutic anticoagulation that cannot be temporarily stopped 1
- Therapeutic anticoagulation significantly increases bleeding risk (33% hemorrhage rate vs 0% without therapeutic anticoagulation), while prophylactic anticoagulation does not increase risk 2
What NOT to Use
- Single agent tPA or DNase alone should NOT be used for pleural infection 1
- Streptokinase should NOT be used for pleural infection 1
Alternative Approaches When Standard Therapy Unavailable
If combination tPA/DNase or surgery is not suitable, saline irrigation can be considered as an alternative 1. However, this is a conditional recommendation and represents a second-line approach.
Clinical Pearls
- The combination therapy regimen is based on the MIST2 trial, which demonstrated superior outcomes compared to single-agent therapy 1
- Most patients respond within 3 doses when using alternative protocols, though the standard 3-day protocol (6 total doses) remains the guideline-recommended approach 3, 4
- Early administration (within 24 hours of chest tube insertion) may improve outcomes 4
- Video-assisted thoracoscopic surgery (VATS) should be considered if medical drainage fails, not as initial treatment 1