Intrapleural tPA and DNase in Pleural Infection (MIST2)

Pleural infection (empyema) often requires drainage, but loculations limit catheter drainage. MIST1 showed fibrinolytics alone did not improve outcomes. MIST2 tested the combination of tPA + DNase (which breaks down the fibrin matrix and viscous DNA from neutrophils).

Multicenter RCT (11 UK centers, n=210) with 2×2 factorial design comparing intrapleural tPA + DNase vs. tPA alone, DNase alone, or double placebo in pleural infection.

tPA + DNase significantly reduced pleural opacity on chest X-ray (primary endpoint), reduced surgical referral (2% vs 27%, p<0.001), and reduced hospital stay (12 vs 26 days). Neither agent alone was effective.

Intrapleural tPA (10 mg) + DNase (5 mg) twice daily for 3 days is the standard treatment for complicated parapneumonic effusion/empyema not responding to chest tube drainage. Both agents must be used together — neither works alone. This is now in BTS and IDSA guidelines.

Surrogate primary endpoint (pleural opacity). Excluded patients requiring immediate surgery. Single-center experience may affect generalizability.