Rethinking the Doses of Tissue Plasminogen Activator and Deoxyribonuclease Administrated Concurrently for Intrapleural Therapy for Complicated Pleural Effusion and Empyema

Background Complicated parapneumonic effusions empyema (CPEE) is fairly common and associated with increased morbidity and mortality. The Multicenter Intrapleural Sepsis Trial 2 (MIST 2) established the combination of intrapleural deoxyribonuclease (DNase) and tissue plasminogen activator (tPA) as an effective treatment for CPEE, thereby avoiding surgery and decreasing the length of hospitalization. MIST 2, however, used a labor-intensive protocol with some risk of bleeding. We hypothesize the simpler regimen of concurrent administration of intrapleural tPA and DNase (lower dose of tPA and a higher DNAse dose) to be equally effective with a decreased risk of bleeding. Methods Retrospective analysis of the concurrent administration of intrapleural tPA and DNase for CPEE during November 2014 to February 2016 was done at a tertiary care center. The inclusion criteria included 1) pleural fluid with any of the following: (a) exudative and loculated effusion in a patient with pneumonia, (b) gram stain/culture positive, (c) macroscopically purulent 2) chest tube placement during current hospitalization 3) concurrent administration of intrapleural tPA and DNase (4mg and 10mg per instillation respectively). The exclusion criteria was 1) chest tube placement prior to current hospitalization and 2) age < eighteen. Results Seventeen patients received concurrent tPA and DNase therapy for CPEE in the study period. Two had chest tubes placed prior to current hospitalization and were excluded. Twelve patients (80%) were successfully discharged with clinical resolution of CPEE with medical therapy. One (7%) patient required surgery. No mortality due to pleural sepsis was noted. The median number of concurrent tPA and DNase treatment was two. Median cumulative tPA dose was 8 mg (mean: 14.1±17 mg) and median cumulative DNase dose was 20mg (mean: 19.7 ± 12.2 mg). The median dwell time for the chest tubes was 8.5 days. Our regimen had similar success when compared to MIST 2 and allowed for lesser treatments and cumulative doses. No complication of intrapleural therapy with hemorrhagic conversion of CPEE, or worsening pain leading to discontinuation of therapy was noted. Conclusion The concurrent administration of intrapleural therapy at lower doses than the current standard MIST 2 protocol is practical, efficient and effective. We suggest a higher DNase dose with a lower tPA dose which may further decrease hemorrhagic complications. Further randomized trials are required to establish the optimal dose of intrapleural therapy for CPEE.