Efficacy and Safety of Intrapleural Administration of tPA and DNase for Pleural Infections

Introduction: Parapneumonic effusions and empyema cause significant morbidity and mortality. Intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) can improve drainage and avoid surgery, but optimal real-world dosing and the comparative effectiveness of combination versus monotherapy are unclear. We assessed the efficacy and safety of a standardized protocol using intrapleural tPA with or without DNase for complicated pleural infections in a large health system.


Methods: In this multicenter, retrospective cohort study (Jan 2019–Dec 2020), we included adults with complicated parapneumonic effusions, empyema, or hemothorax receiving intrapleural tPA +/- DNase via a standardized protocol. The protocol utilized tPA 20-50 mg once daily with optional DNase 5 mg once daily. The primary outcome was treatment success, defined as avoidance of surgery and survival to discharge. Secondary outcomes included change in chest tube drainage, length of stay, mortality, major bleeding, and peri-procedural pain. A post-hoc analysis compared tPA monotherapy with combination therapy. An artificial intelligence language model was used to edit this abstract for clarity, conciseness, and for consistency with the manuscript. The authors maintained full editorial control over the final version.


Results: Of 172 patients screened, 120 were included (median age 69, 50.8% male). Treatment success was achieved in 102 patients (85.0%). Median chest tube drainage increased by 488 mL (IQR 73, 979). Major bleeding occurred in one patient (0.8%) and peri-procedural pain requiring analgesics in 69 (57.5%). In a subgroup analysis of combination therapy (n=46) vs. monotherapy (n=74), treatment success was 87.0% vs. 83.8% (p=0.636), respectively.


Conclusions: Intrapleural tPA +/- DNase, guided by a standardized protocol, resulted in a high rate of treatment success and increased pleural drainage. Major bleeding was rare, while peri-procedural pain was common. The post-hoc analysis showed no significant benefit for combination therapy over tPA monotherapy, a finding which requires cautious interpretation due to study limitations. These findings support intrapleural fibrinolytics as an effective and relatively safe real-world strategy, though future prospective studies are warranted to optimize use.