title: Intrapleural use of tissue plasminogen activator and DNase in pleural infection.
abstract: BACKGROUND
  More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial.
  
  
  METHODS
  We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events.
  
  
  RESULTS
  The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P=0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P=0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P=0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P=0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups.
  
  
  CONCLUSIONS
  Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.).
authors.affiliation: UKCRC Oxford Respiratory Trials Unit, Oxford Centre for Respiratory Medicine, Nuffield Department of Medicine, University of Oxford, Churchill Hospital Site, Headington, Oxford OX3 7LJ, United Kingdom. najib.rahman@ndm.ox.ac.uk
authors.forename: Najib M
authors.initials: NM
authors.lastname: Rahman
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Maskell
authors.forename: Alex
authors.initials: A
authors.lastname: West
authors.forename: Richard
authors.initials: R
authors.lastname: Teoh
authors.forename: Anthony
authors.initials: A
authors.lastname: Arnold
authors.forename: Carolyn
authors.initials: C
authors.lastname: Mackinlay
authors.forename: Daniel
authors.initials: D
authors.lastname: Peckham
authors.forename: Chris W H
authors.initials: CW
authors.lastname: Davies
authors.forename: Nabeel
authors.initials: N
authors.lastname: Ali
authors.forename: William
authors.initials: W
authors.lastname: Kinnear
authors.forename: Andrew
authors.initials: A
authors.lastname: Bentley
authors.forename: Brennan C
authors.initials: BC
authors.lastname: Kahan
authors.forename: John M
authors.initials: JM
authors.lastname: Wrightson
authors.forename: Helen E
authors.initials: HE
authors.lastname: Davies
authors.forename: Clare E
authors.initials: CE
authors.lastname: Hooper
authors.forename: Y C Gary
authors.initials: YC
authors.lastname: Lee
authors.forename: Emma L
authors.initials: EL
authors.lastname: Hedley
authors.forename: Nicky
authors.initials: N
authors.lastname: Crosthwaite
authors.forename: Louise
authors.initials: L
authors.lastname: Choo
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Helm
authors.forename: Fergus V
authors.initials: FV
authors.lastname: Gleeson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nunn
authors.forename: Robert J O
authors.initials: RJ
authors.lastname: Davies
mesh_terms: D000328:Adult; D000368:Aged; D003851:Deoxyribonucleases / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007322:Instillation, Drug; D057194:Intention to Treat Analysis; D016014:Linear Models; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010995:Pleural Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D010996:Pleural Effusion / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011859:Radiography; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D003851:Deoxyribonucleases; D010959:Tissue Plasminogen Activator