An international survey on the use of intrapleural tissue plasminogen activator/DNase therapy for pleural infection

Abstract

IntroductionIntrapleural tissue plasminogen activator (tPA) combined with human recombinant DNase (DNase) could be an effective alternative to surgery in managing pleural infection as demonstrated in the Multi-centre Intrapleural Sepsis Trial (MIST)-2. However, the optimal delivery regime is still unknown. The aim of this survey is to identify the current practice of tPA/DNase use by physicians with published interests in pleural infection, and their opinions on dose de-escalation of tPA/DNase therapy.MethodsPotential participants were identified using four search strategies. Only practicing physicians who are managing patients with pleural infections and are either actively involved in pleural research and publications, or members of relevant pleural disease guideline panels at the time of survey were included.ResultsAn invitation email with the questionnaire was sent to 102 participants of which 49 (48%) responded. Most respondents (90%, n=44) have used tPA/DNase to manage pleural infection but the dosing and delivery regimens employed varied. Many (86%, n=38/44) respondents have used 10 mg tPA, while 73% (n=32), 16%, (n=7) and 9% (n=4) have used 5 mg, 2.5 mg and 1 mg doses respectively. Most respondents instilled tPA/DNase concurrently (61%, n=27) and routinely administered 6 doses of tPA/DNase (52%, n=23) twice daily (82%, n=36). Respondents would consider using a lower starting dose of tPA (with the possibility of escalation if clinically needed) if 80% [IQR 50–80] of patients could be successfully treated at that dose.ConclusionThis survey observed a large variation in the current treatment protocol of intrapleural tPA/DNase therapy worldwide and the need for more data on this subject.

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

“…The success rates (using the same definitions) were similar to our published data using 10 and 5 mg of tPA 4,14 . Our recent international survey of opinion leaders in the field suggests a general acceptance of starting at a low dose of tPA with a proviso of escalating doses if clinical responses are inadequate 9 . We have published case reports of the successful use of 1 mg tPA (with 5 mg DNase) in patients with high bleeding risks 16 .…”

“…4,14 Our recent international survey of opinion leaders in the field suggests a general acceptance of starting at a low dose of tPA with a proviso of escalating doses if clinical responses are inadequate. 9 We have published case reports of the successful use of 1 mg tPA (with 5 mg DNase) in patients with high bleeding risks. 16 Our high response rate with 2.5 mg tPA supports further dose de-escalation and ADAPT-3 (using 1 mg tPA) is underway.…”

“…This may potentially be confounding but it reflects real-life practice in many centres as shown in our recently published survey. 9 Nevertheless, a cohort study by Majid et al showed that the administration of concurrent (differing from MIST-2) tPA/DNase in patients with pleural infection is effective. 5 No studies to date have compared the instillation methods or showed differences in their efficacies.…”

“…The current established dose of 10 mg tPA was arbitrarily chosen, therefore dose optimization is important. A recent consensus statement 8 and survey of international experts 9 highlighted clinicians' concerns of bleeding risks and costs associated with tPA use. Pleural bleeding requiring blood transfusion occurs in ~5% of individuals treated with 10 mg of tPA, and in 28% of patients given 20 mg of tPA, 10 mirroring the dose‐dependent bleeding risk observed with intravenous tPA for stroke management 11 .…”

Ubi pus, ibi evacua: Optimizing intrapleural fibrinolytic therapy in pleural infections

“…2 In daily practice, a physician's decision to use fibrinolytic therapy is influenced by patient's clinical response, the complexity of the infection, risk of bleeding and other side effects, staffing issues and costs. 3 Especially, concerns about costs and bleeding risks may contribute to some reluctance towards the use of fibrinolytics in pleural infections. A sentiment echoed by the European Association of Cardio-Thoracic Surgery.…”