Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) Study-2: Use of 2.5mg alteplase as a starting intrapleural dose.

Abstract

Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) therapy is increasingly used in pleural infection. Bleeding risks and costs associated with tPA remain the clinical concerns. Our dose de-escalation series aims to establish the lowest effective dosing regimen for tPA/DNase. This study assesses the intrapleural use of 2.5mg tPA/5mg DNase for pleural infection. Consecutive patients with pleural infection treated with a starting regime of 2.5mg tPA/5mg DNase were included from two centres in Australia and UK. Escalation of tPA dose was permitted if clinical response was inadequate. Sixty-nine patients (mean age 61.0 years) received intrapleural 2.5mg tPA/5mg DNase. Most (88.4%) were treated successfully and discharged from hospital without surgery by 90 days. Patients received a median of 5 [interquartile range [IQR]=3-6] doses of tPA/DNase. Total amount of tPA used per patient was 12.5mg [median, IQR=7.5-15.0]. Seventeen patients required dose escalation of tPA; most (n= 12) for attempted drainage of distant non-communicating locule(s). Treatment success was corroborated by clearance of pleural opacities on radiographs (from median 27.0% [IQR=17.1-44.5] to 11.0% [IQR=6.4-23.3] of hemithorax, p< 0.0001), increased pleural fluid drainage (1.98 L [median, IQR=1.38-2.68] over 72 h following commencement of tPA/DNase) and reduction of serum C-reactive protein level (by 45.0% [IQR=39.3-77.0] from baseline at day 5, p< 0.0001). Two patients required surgery. Six patients with significant comorbidities (e.g., advanced cancer) had ongoing infection when palliated and died. Two patients experienced self-limiting pleural bleeding and received blood transfusion. A starting intrapleural regime of 2.5mg tPA/5mg DNase, with up-titration if needed, can be effective and deserves further exploration.