Tissue Plasminogen Activator Combined With Human Recombinant Deoxyribonuclease Is Effective Therapy for Empyema in a Rabbit Model

Abstract

There have been no controlled studies to test the efficacy of tissue plasminogen activator (tPA) or recombinant human deoxyribonuclease (rhDNase) in the treatment of empyema. In vitro studies show that streptokinase without rhDNase does not liquefy empyemic material from rabbits. However, the combination of streptokinase and streptodornase and rhDNase have been shown to liquefy pus in vitro. The aim of this study was to determine if tPA or rhDNase, or a combination of the two, is more effective than saline solution in the treatment of empyema in rabbits. Empyema was induced in rabbits using 10(9) Pasteurella multicoda organisms in infusion agar injected via a surgically placed chest tube. Once empyema was verified, a blinded investigator administered one of four treatments via the chest tube: 3 mL of saline solution; 4 mg of alteplase (recombinant tPA); 1 mg of rhDNase; or 4 mg of alteplase and 1 mg of rhDNase. The rabbits received a treatment every 12 h following the initial for a total of six treatments. The animals were killed at day 10, and the degree of empyema and pleural peel was scored macroscopically on a scale of 0 to 4. The combination group had a significantly lower mean empyema score (1.83 +/- 0.75) than did the saline solution group (3.86 +/- 0.38, p = 0.001), rhDNase group (3.17 +/- 0.75, p = 0.012), and alteplase group (3.71 +/- 0.49, p = 0.02) [+/- SD]. The total volume of pleural fluid was markedly higher in the alteplase and rhDNase combination group (142 +/- 79.1 mL) or the alteplase group (231 +/- 78.0 mL) compared to either the rhDNase group (0.8 +/- 1.6 mL) or the saline solution group (5.8 +/- 14.0 mL). The combination of alteplase and rhDNase is more effective in the treatment of rabbit empyema than either agent alone. The intrapleural injection of alteplase alone or in combination with rhDNase leads to the production of large amounts of pleural fluid.