Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study

Lung. 2015 Dec;193(6):993-1000. doi: 10.1007/s00408-015-9807-6. Epub 2015 Sep 30.


Background: Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population.

Methods: Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality.

Results: A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events.

Conclusions: If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

Trial registration: NCT01246453.

Keywords: Empyema; Fibrinolytic therapy; Parapneumonic pleural effusion.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chest Tubes
  • Double-Blind Method
  • Empyema, Pleural / drug therapy*
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Pleural Effusion / drug therapy*
  • Thrombolytic Therapy / methods*
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome
  • Urokinase-Type Plasminogen Activator / therapeutic use*


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator

Associated data