title: Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience.
abstract: 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.
  
  
  
  To assess the safety and efficacy of concurrent instillation of intrapleural tPA/DNase guided by radiographic and clinical response in patients with pleural infection.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Adnan
authors.identifier: 0000-0002-6203-5343
authors.initials: A
authors.lastname: Majid
authors.affiliation: 2 Division of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Fayez
authors.initials: F
authors.lastname: Kheir
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Folch
authors.affiliation: 3 Section of Interventional Pulmonology, Clinica Alemana, Universidad Del Desarrollo, Santiago, Chile.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fernandez-Bussy
authors.affiliation: 4 Department of Respiratory Medicine, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
authors.forename: Sumit
authors.initials: S
authors.lastname: Chatterji
authors.affiliation: 5 Division of Pulmonary Diseases and Critical Care, University of Kentucky, Lexington, Kentucky.
authors.forename: Ashish
authors.initials: A
authors.lastname: Maskey
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Meghan
authors.initials: M
authors.lastname: Fashjian
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: George
authors.initials: G
authors.lastname: Cheng
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ochoa
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alape
authors.affiliation: 1 Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Erik
authors.initials: E
authors.lastname: Folch
mesh_terms: D000328:Adult; D000368:Aged; D015505:Chest Tubes / Q000009:adverse effects; D003131:Combined Modality Therapy; D015897:Comorbidity; D003851:Deoxyribonucleases / Q000008:administration & dosage*; D004322:Drainage / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010995:Pleural Diseases / Q000150:complications*; D010996:Pleural Effusion / Q000000981:diagnostic imaging / Q000628:therapy*; D012189:Retrospective Studies; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D014481:United States
chemical_list: D005343:Fibrinolytic Agents; D003851:Deoxyribonucleases; D010959:Tissue Plasminogen Activator
keywords: humanrecombinant DNase; pleural infection; tissue plasminogen activator