Evaluation of Daily Intrapleural Alteplase and Dornase Alfa for Complicated Parapneumonic Effusions

Introduction: Infected pleural effusions carry significant morbidity and often require surgical intervention. The MIST-2 trial demonstrated that twice-daily sequential intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) improved drainage and reduced surgical need. A paucity of data exists regarding the safety, efficacy, and cost of once-daily intrapleural tPA/DNase.


Methods: This retrospective cohort study included adults (age ≥18) with complicated parapneumonic pleural effusions treated with at least one dose of intrapleural tPA (10 mg) and DNase (5 mg) between January 1st, 2018 and December 31st, 2023. Inclusion required radiographic evidence of pleural fluid necessitating drainage with either purulent, culture-positive, or low-pH fluid. Patients with prior fibrinolytic therapy or a contraindication to either study drug were excluded. The primary endpoint was the need for surgical intervention. Secondary outcomes included total pleural fluid drained, day 7 radiographic improvement, hospital length of stay (LOS), adverse events, and cost. Outcomes of the population were compared to the tPA/DNase arm of the MIST-2 trial.


Results: A total of 206 patients were included. The need for surgical intervention occurred in 8.4% of patients, compared to 4.2% in the tPA/DNase MIST2 group (z = 0.991, p = 0.322). Administration of tPA/Dnase occurred within 24 hours of chest tube placement in the majority of patients (65.2%). Radiographic improvement at day 7 was observed in 80.7% of patients, with 30.1% showing significant (>75%) improvement with a cumulative pleural volume drain average of 1152 milliliters. Median hospital LOS was 10 days. Serious adverse events leading to discontinuation of therapy occurred in 3.4% of patients, compared to 6% in the comparison group (z=0.792; p=0.428). Mean total cost of therapy per patient was $9,234.89.


Conclusions: Once-daily intrapleural tPA and DNase demonstrated comparable rates of surgical intervention to those observed in the MIST-2 trial. Notably, this regimen was associated with fewer significant adverse events and may offer potential cost savings. These findings support the viability of a once-daily dosing strategy in the management of complicated parapneumonic pleural effusions.