title: Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery.
abstract: BACKGROUND
  Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports.
  
  
  OBJECTIVE
  Multinational observation series to evaluate the pragmatic "real-life" application of tPA/DNase treatment for pleural infection in a large cohort of unselected patients.
  
  
  METHODS
  All patients from eight centers who received intrapleural tPA/DNase for pleural infection between January 2010 and September 2013 were included. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity and inflammatory markers, need for surgery, and adverse events.
  
  
  RESULTS
  Of 107 patients treated, the majority (92.3%) were successfully managed without the need for surgical intervention. No patients died as a result of pleural infection. Most patients (84%) received tPA/DNase more than 24 hours after failing to respond to initial conservative management with antibiotics and thoracostomy. tPA/DNase increased fluid drained from a median of 250 ml (interquartile range [IQR], 100-654) in the 24 hours preceding commencement of intrapleural therapy to 2,475 ml (IQR 1,800-3,585) in the 72 hours following treatment initiation (P < 0.05). We observed a corresponding clearance of pleural opacity on chest radiographs from a median of 35% (IQR 25-31) to 14% (7-28) of the hemithorax (P < 0.001), as well as significant reduction in C-reactive protein (P < 0.05). Pain necessitating escalation of analgesia occurred in 19.6% patients, and nonfatal bleeding occurred in 1.8%.
  
  
  CONCLUSIONS
  This large series of patients who received intrapleural tPA/DNase therapy provides important evidence that the treatment is effective and safe, especially as a "rescue therapy" in patients who do not initially respond to antibiotics and thoracostomy drainage.
authors.affiliation: 1 Department of Medicine, Swan District Hospital, Perth, Australia.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piccolo
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pitman
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhatnagar
authors.forename: Natalia
authors.initials: N
authors.lastname: Popowicz
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Smith
authors.forename: Ben
authors.initials: B
authors.lastname: Brockway
authors.forename: Robert
authors.initials: R
authors.lastname: Nickels
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Burke
authors.forename: Conroy A
authors.initials: CA
authors.lastname: Wong
authors.forename: Ruth
authors.initials: R
authors.lastname: McCartney
authors.forename: Brian
authors.initials: B
authors.lastname: Choo-Kang
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Blyth
authors.forename: Nick A
authors.initials: NA
authors.lastname: Maskell
authors.forename: Y C Gary
authors.initials: YC
authors.lastname: Lee
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D003851:Deoxyribonucleases / Q000627:therapeutic use*; D004322:Drainage; D016724:Empyema, Pleural / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007322:Instillation, Drug; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013902:Radiography, Thoracic; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D002097:C-Reactive Protein; D003851:Deoxyribonucleases; D010959:Tissue Plasminogen Activator
keywords: deoxyribonuclease; empyema; fibrinolytic; infection; pleural; tissue plasminogen activator