Adnan Majid1, Fayez Kheir2, Alejandro Folch1, Sebastian Fernandez-Bussy3, Sumit Chatterji4, Ashish Maskey5, Meghan Fashjian1, George Cheng1, Sebastian Ochoa1, Daniel Alape1, Erik Folch1. 1. 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 2. 2 Division of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana. 3. 3 Section of Interventional Pulmonology, Clinica Alemana, Universidad Del Desarrollo, Santiago, Chile. 4. 4 Department of Respiratory Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom. 5. 5 Division of Pulmonary Diseases and Critical Care, University of Kentucky, Lexington, Kentucky.
Abstract
RATIONALE: Treatment of pleural infection with instillation of intrapleural tissue plasminogen activator (tPA) and human recombinant DNase (DNase) has been proven to decrease the length of hospital stay, decrease surgical referral, and improve drainage. The optimal dosage, administration, timing, and frequency of the regimen remain unclear. It is unknown if the two drugs can be administered immediately one after the other (referred to as concurrent) instead of instilling them separately with a 1- to -2-hour interval in between. OBJECTIVES: To assess the safety and efficacy of concurrent instillation of intrapleural tPA/DNase guided by radiographic and clinical response in patients with pleural infection. METHODS: We conducted a retrospective cohort study. Consecutive patients with pleural infection who received concurrent tPA/DNase were included. The initiation and number of doses of tPA/DNase therapy were based on pleural fluid drainage, clinical response, and radiographic findings. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients received concurrent tPA/DNase therapy. Treatment was successful in 90.4% of them; 80.8% were effectively treated with fewer than six doses of therapy (median, 2; interquartile range [IQR], 1-3.5); and 71.2% received their first dose of tPA/DNase within 24 hours after chest tube insertion. The median hospital stay from the first dose of tPA/DNase to discharge was 7 days (IQR, 5-11 d). The volume of pleural fluid drained increased from a median of 295 ml (IQR, 97.5-520 ml) 24 hours before treatment to a median of 1,102 ml (IQR, 627-2,200 ml) 72 hours following therapy (P < 0.001). Nonfatal pleural bleeding occurred in 5.4%, 15.1% had chest pain, and 2.7% died as a result of pleural infection. CONCLUSIONS: This cohort study shows that early administration of concurrent tPA/DNase in patients with pleural infection is relatively safe and effective. Given the high cost of therapy, it is feasible to guide therapy on the basis of clinical and radiographic response.
RATIONALE: Treatment of pleural infection with instillation of intrapleural tissue plasminogen activator (tPA) and human recombinant DNase (DNase) has been proven to decrease the length of hospital stay, decrease surgical referral, and improve drainage. The optimal dosage, administration, timing, and frequency of the regimen remain unclear. It is unknown if the two drugs can be administered immediately one after the other (referred to as concurrent) instead of instilling them separately with a 1- to -2-hour interval in between. OBJECTIVES: To assess the safety and efficacy of concurrent instillation of intrapleural tPA/DNase guided by radiographic and clinical response in patients with pleural infection. METHODS: We conducted a retrospective cohort study. Consecutive patients with pleural infection who received concurrent tPA/DNase were included. The initiation and number of doses of tPA/DNase therapy were based on pleural fluid drainage, clinical response, and radiographic findings. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients received concurrent tPA/DNase therapy. Treatment was successful in 90.4% of them; 80.8% were effectively treated with fewer than six doses of therapy (median, 2; interquartile range [IQR], 1-3.5); and 71.2% received their first dose of tPA/DNase within 24 hours after chest tube insertion. The median hospital stay from the first dose of tPA/DNase to discharge was 7 days (IQR, 5-11 d). The volume of pleural fluid drained increased from a median of 295 ml (IQR, 97.5-520 ml) 24 hours before treatment to a median of 1,102 ml (IQR, 627-2,200 ml) 72 hours following therapy (P < 0.001). Nonfatal pleural bleeding occurred in 5.4%, 15.1% had chest pain, and 2.7% died as a result of pleural infection. CONCLUSIONS: This cohort study shows that early administration of concurrent tPA/DNase in patients with pleural infection is relatively safe and effective. Given the high cost of therapy, it is feasible to guide therapy on the basis of clinical and radiographic response.
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