Intrapleural Fibrinolysis: tPA-Based Regimens
For intrapleural fibrinolysis in pleural infection, use tPA 10 mg combined with DNase 5 mg twice daily for 3 days, as this combination is significantly more effective than either agent alone and represents the current standard of care. 1
Standard Dosing Protocol
The recommended regimen is tPA 10 mg + DNase 5 mg administered twice daily for 3 days (6 total doses). 1 This protocol has demonstrated:
- Significant reduction in hospital length of stay compared to placebo 1
- Decreased likelihood of persistent fevers 1
- Increased radiographic improvement with better clearance of pleural opacification 1
- Increased fluid drainage volume 1
Administration Technique
- Administer through an existing chest tube after initial drainage has slowed 1
- Clamp the chest tube for 1 hour after tPA/DNase instillation to allow adequate dwell time 1
- Obtain patient consent due to potential bleeding risk 1
Dose De-escalation Options
A reduced-dose regimen of tPA 5 mg + DNase 5 mg twice daily may be equally effective and should be considered, particularly in patients with higher bleeding risk. 1, 2
The ADAPT study demonstrated that this lower dose achieved:
- 93.4% treatment success without surgery 2
- Significant clearance of pleural opacities (from 42% to 16% of hemithorax) 2
- Increased pleural fluid drainage from 175 ml to 2,025 ml over 72 hours 2
- Only 4.9% required blood transfusions for gradual pleural blood loss 2
Consider dose escalation to tPA 10 mg if clinical response is inadequate after initial lower-dose therapy. 2
Alternative Single-Agent Regimens (When DNase Unavailable)
If DNase is not available, alternative tPA-only regimens include:
Higher-Dose tPA Protocol
- tPA 4 mg daily with 12-hour dwell time has shown effectiveness comparable to standard tPA/DNase regimens 3
- Median of 2 doses per effusion (84% required ≤3 doses) 3
- 78% achieved complete drainage 3
- No significant bleeding complications 3
- Logistically simpler than twice-daily dosing 3
Pediatric Dosing
- Alteplase 0.1 mg/kg twice daily for children with parapneumonic effusions 4
- Safely increases pleural drainage and decreases pleural fluid volume compared to saline 4
- Benefit persists for up to 72 hours with repeated dosing 4
- No bleeding complications reported 4
Critical Caveat: Do NOT Use Single Agents
tPA and DNase should NOT be used as single agents in standard practice, as they do not improve clinical outcomes when used individually. 1 The synergistic effect of the combination is essential for optimal efficacy.
Comparison with Other Fibrinolytics
Streptokinase
Streptokinase should NOT be used for pleural infection treatment. 1 The BTS/MRC trial demonstrated:
- No beneficial effect in adult empyema 5, 6
- Increased post-treatment complications 1
- Highly antigenic with systemic antibody responses 6
- Higher risk/benefit ratio compared to other fibrinolytics 6
Urokinase
While urokinase (100,000 IU once daily for 3 days) was previously recommended 5, it has significant limitations:
- No longer available in North America 6
- Non-antigenic but rare hypersensitivity reactions possible 6
- In direct comparison with alteplase, showed inferior efficacy (33% vs 41% reduction in pleural opacity, p=0.014) 7
Alteplase demonstrated greater efficacy than urokinase with a similar adverse effect profile. 7
Special Considerations for Retained Hemothorax
For traumatic retained hemothorax specifically, higher doses of tPA are recommended:
- Dosing ranges from 6 to 100 mg per dose 8
- Volume of 50 to 120 mL normal saline 8
- Greater than 80% success rate with less than 7% bleeding rate 8
- Higher doses and volumes are needed compared to empyema treatment 8
Safety Profile
Pain is the most common adverse effect (40-60% of patients), followed by fever. 7
Bleeding complications:
- Rare but reported, particularly with traumatic drain insertion 6
- Consider reduced tPA doses in patients on therapeutic anticoagulation 1
- Minor side effects include transient blood staining of drainage fluid 6
When to Escalate to Surgery
If medical management with tPA/DNase fails, surgical intervention should be considered, with VATS preferred over thoracotomy. 1 Failure is defined by persistent sepsis with residual pleural collection despite adequate fibrinolytic therapy and antibiotics.