Intrapleural tissue plasminogen activator and deoxyribonuclease therapy for
pleural infection.
Author(s): Piccolo F(1), Popowicz N(1), Wong D(1), Lee YC(1).
Affiliation(s): Author information:
(1)1 Department of Medicine, Swan District Hospital, Perth, Australia ; 2
Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia ; 3
Respiratory Medicine, Auckland City Hospital, Auckland, New Zealand ; 4 Centre
for Asthma, Allergy & Respiratory Research, School of Medicine & Pharmacology,
University of Western Australia, Perth, Australia.
Publication date & source: 2015, J Thorac Dis. , 7(6):999-1008
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.
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