Intrapleural tissue plasminogen activator and deoxyribonuclease administered concurrently and once daily for complex parapneumonic pleural effusion and empyema

Abstract

BackgroundPleural infection is life‐threatening and increasingly prevalent. In addition to usual care, twice‐daily, separate administration of tissue plasminogen activator and deoxyribonuclease (tPA‐DNase) reduces radiological pleural opacity with lower surgical referral rates.AimsThis retrospective cohort study examines the use of once‐daily, concurrent administration of tPA‐DNase for complex parapneumonic pleural effusion and empyema.MethodsPatients with pleural infection who received intrapleural tPA‐DNase between October 2014 and July 2020 at Logan Hospital, where it is given concurrently and once‐daily as salvage therapy, were retrospectively identified. Radiographic opacification, inflammatory markers, clinical response and complications were examined.ResultsThirty‐one patients were identified. Mean age was 48.8 years (standard deviation [SD], 17.2). Median tPA‐DNase administration was 3 (interquartile range [IQR], 2–3). Chest x‐ray pleural opacity decreased significantly (P = 0.047) from a median of 39.6% (IQR, 28.8–65.7%) to 9.7% (IQR, 2.5–23.2%), a median relative reduction of 75.5% (IQR, 47.7–93.9%). White cell count and C‐reactive protein improved significantly (P = 0.002 and P = 0.032, respectively) from a median of 16.3 × 109/L (IQR, 11.8–20.6 × 109/L) to 9.9 × 109/L (IQR, 8.0–12.3 × 109/L) and 311.0 mg/L (IQR, 218.8–374.0 mg/L) to 69.0 mg/L (IQR, 36.0–118.0 mg/L), respectively. No patients experienced significant bleeding or died. Five patients (16.1%) were referred for surgery.ConclusionThis is pilot evidence that a practical regimen of concurrent, once‐daily intrapleural tPA‐DNase improved pleural opacification and inflammatory markers without bleeding or mortality. The surgical referral rate was higher than in studies assessing twice‐daily administration, though the validity of this outcome as a measure of treatment success is limited, and further studies are needed to assess the optimal dose and frequency of intrapleural therapy and indications for surgical referral.

Infective Pleural Effusions—A Comprehensive Narrative Review Article

“…The daily dosing of IET has been retrospectively studied with the results suggesting the safety and practicality of once-a-day dosing. However, the findings also suggested a higher surgical referral rate to what has been previously reported in the literature [ 56 , 57 ]. Furthermore, a study by Cheong et al revealed that a modified regimen of 16 mg of tPA and 5 mg of DNase can be safe and effective.…”