Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease

Abstract

Background: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. Objectives: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. Methods: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. Results: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. Conclusion: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project

“…Although the rate of intrapleural bleeding in our study was similar to studies of 10mg tPA, there remains a theoretical potential to reduce adverse events with lower doses in stronger powered studies. We have demonstrated similar treatment success, as measured by survival at discharge and avoidance of surgery at 30 days to other pragmatic studies using intrapleural 10mg tPA (with 5mg DNase) (13)(14)(15). Finally, this reduced dosage regimen should reduce total drug costs.…”

“…In the MIST-2, 96% of patients who received intrapleural tPA 10mg/DNase 5mg therapy were successfully treated without needing surgery (9). Similar success rates have been replicated in three open-label series (n=107, 73 and 55) using the same combination doses (13)(14)(15).…”

“…ADAPT-2 is underway to establish the efficacy of tPA 2.5mg/DNase 5mg as a starting regimen. Others have investigated alternatives to the tPA/DNase protocol, eg daily dosing, instilling both drugs simultaneously, use of other fibrinolytics etc (14,15) .…”

“…When used for ischaemic stroke, intravenous administration of tPA (0.9mg/kg, max 90mg) is associated with significant risks of symptomatic intracranial hemorrhage (6.4%, vs 0.6% with placebo) (16,17). Intrapleural administration of tPA (±DNase) at 10mg doses rarely causes systemic hemorrhage but pleural bleeding has been reported at rates between 1.8% and 12% (13)(14)(15)18).…”

Breaking Down the Barriers in Complicated Pleural Sepsis

“…In this issue of Respiration , Mehta et al [7] explore an alternative dosing regimen for intrapleural t-PA/DNase, as the appropriate dose for individual patients is not known, nor has dosing frequency been compared in any of the previous studies. The authors essentially replicated the methodology of MIST-2, but replacing the twice-daily regimen with a once-daily regimen with a similar protocol where t-PA was instilled followed 2 h later by DNase.…”