Intrapleural Tissue Plasminogen Activator With or Without Dornase Alfa: A Multicenter Retrospective Cohort Study

Intrapleural tissue plasminogen activator (tPA) and DNase are used when drainage of loculated pleural effusions is inadequate, but the real-world performance of pragmatic once-daily protocols remains uncertain.

We performed a retrospective cohort study across seven hospitals between January 1, 2019, and December 31, 2020. Adults who received intrapleural tPA 20 or 50 mg once daily with optional DNase 5 mg once daily for complicated pleural effusion, empyema, or hemothorax were included. The primary outcome was treatment success, defined as survival to hospital discharge without surgical intervention during the index admission. Secondary outcomes included chest tube drainage change, hospital length of stay, ICU length of stay, mortality, major bleeding, and peri-procedural pain requiring analgesics. A post hoc subgroup analysis compared monotherapy with combination therapy.

Among 120 included patients, treatment success occurred in 102 (85.0%; 95% CI, 77.3%-90.9%). The median paired increase in chest tube drainage was 487.5 mL (IQR, 72.5-979.0; P < .001). Major bleeding occurred in one patient (0.8%), whereas peri-procedural pain requiring additional analgesia occurred in 69 (57.5%). In the exploratory subgroup analysis, treatment success was 83.8% with tPA monotherapy and 87.0% with tPA/DNase combination therapy.

In this multicenter real-world cohort, standardized intrapleural tPA with or without DNase was associated with high observed treatment success, substantial increases in drainage, and rare major bleeding. Comparative findings between combination therapy and monotherapy should be interpreted cautiously because treatment allocation was nonrandomized and exposure groups were imbalanced.