Pleural
infection remains a global health burden associated with significant morbidity. Drainage of the infected pleural fluid is important but can often be hindered by septations and loculations. Intrapleural
fibrinolytic therapy alone, to break pleural adhesions, has shown no convincing advantages over placebo in improving clinical outcome. Deoxyribonucleoprotein from degradation of leukocytes contributes significantly to high viscosity of infected pleural fluid. Recombinant
deoxyribonuclease (
DNase) is effective in reducing pleural fluid viscosity in pre-clinical studies. The combination of
tissue plasminogen activator (tPA) and
DNase was effective in animal model experiments of
empyema. The benefits were established in a randomized clinical trial: those (n=48) treated with tPA/
DNase had significantly improved radiological outcomes and reduced need of surgery and duration of
hospital stay. A longitudinal observational series of 107 patients further confirmed the effectiveness and safety of tPA/
DNase therapy, including its use as 'rescue
therapy' when patients failed to respond to
antibiotics and
chest tube drainage. Overall, a short course of intrapleural tPA (10 mg) and
DNase (5 mg)
therapy provides a cure in over 90% of patients without requiring surgery. The treatment stimulates pleural fluid formation, enhances radiographic clearance and resolution of systemic
inflammation. Serious complications are uncommon; pleural
bleeding requiring transfusion occurred in ~2% of cases.
Pain can occur, especially with the first dose. Treatment is contraindicated in those with significant
bleeding diathesis or a bronchopleural
fistula. Future research is required to optimize dosing regimens and in refining patient selection.