Intrapleural Fibrinolysis for Pleural Effusions

Mechanism and Expected Response

The administration of fibrinolytic agents, such as urokinase, results in the lysis of fibrinous septations and clearance of lymphatic pores, allowing for increased pleural fluid drainage in patients with loculated effusions, as recommended by the British Thoracic Society 1, 2
Increased daily drainage volumes are observed in 93-100% of treated patients, indicating successful breakdown of fibrinous strands 3
Substantial increase in pleural fluid output occurs in both loculated and non-loculated effusions after urokinase administration, with 85% showing >40% reduction in pleural opacity versus 35% with placebo 1, 3

In patients with complicated parapneumonic effusions and empyema, fibrinolytic therapy results in significantly increased fluid drainage, leading to shorter hospital stays (mean 6.2 days versus 8.7 days with drainage alone) 3, 4
The British Thoracic Society recommends administering streptokinase 250,000 IU twice daily or urokinase 100,000 IU once daily for 3 days, with reassessment at 5-8 days, for patients with complicated parapneumonic effusions and empyema 4

Evaluate treatment effectiveness at 5-8 days after initiating therapy, with key indicators of successful fibrinolysis including resolution of fever and sepsis, increased daily drainage output, and radiographic improvement with reduction in pleural opacity 4, 5, 2

The increased fluid drainage after fibrinolysis is generally safe, with low bleeding complication rates (2-8.5% of patients) and no clear evidence of increased adverse effects compared to placebo 3
Patients receiving streptokinase must be given a streptokinase exposure card and should receive urokinase or tissue plasminogen activator for any future systemic indications due to antibody formation, as recommended by the British Thoracic Society 4

Alteplase (tPA) regimen: Administer 4 mg (or 0.1 mg/kg for pediatric patients) diluted in 40 mL normal saline once daily. The dose is clamped in the chest tube for a 1‑hour dwell time before unclamping. 6
Chest‑tube clamping after instillation: Immediately clamp the chest tube following delivery of any intrapleural fibrinolytic agent (streptokinase, urokinase, or alteplase) to allow the drug to remain in the pleural space. 7
Post‑dwell suction: After the prescribed dwell period, unclamp the tube and connect it to continuous suction set at –10 to –20 cm H₂O to facilitate drainage. This applies to all fibrinolytic agents. 7
Continuous suction between doses: Maintain the chest tube on continuous suction (–10 to –20 cm H₂O) throughout the treatment course, between each fibrinolytic dose. 6

Removal criteria – air leak: The chest tube may be removed only when no air leak is detected on the drainage system. [8][9]
Removal criteria – drainage volume: The tube can be removed when drainage falls below 1 mL kg⁻¹ 24 h (approximately 25–60 mL total in 24 h for adults). [8][9]
Timing of removal: Successful removal of the chest tube is typically achieved within 48–72 hours after the completion of the fibrinolytic course, provided the above criteria are met. [8][9]