Intrapleural Alteplase-Tyloxapol vs Intrapleural Alteplase-DNase in Pleural Infection

Overview

Pneumonia, thought to be the chief aetiological process in the development of pleural space infection, is defined as an infection of the lung parenchyma with an estimated annual incidence rate of 5-11 cases per 1000 population, with around 50,000 hospital admissions in the U.K. per year. Parapneumonic effusions caused by an infection of the pleural membranes occur in 40-57% of cases of pneumonia. A variable percentage (10-20%) of parapneumonic effusions progresses to empyema (pus) and/or abscess formation (encapsulation). Pleural infection is associated with significant morbidity and mortality, which may be as high as 20-35% in immunocompromised patients. Standard treatment of these collections in adults involves antibiotic therapy, adequate drainage of infected fluid, and surgical intervention if conservative management fails. Appropriate treatment is adequate drainage via an intercostal catheter (ICC) with antibiotic therapy for parapneumonic effusions requiring clearance. Frequently, simple ICC drainage is ineffective due to the presence of loculations, formed predominantly by fibrinous material deposited in the fibrinopurulent phase of empyema, preventing free drainage of infected pleural fluid. The presence of fibrinous septae in the pleural space, known as loculations, may result in inadequate drainage of effusions and, therefore, nonresolution of infection and systemic sepsis. Surgical intervention (VATS or open) is usually required to clear loculations and resolve infection without adequate intercostal catheter drainage. Although the success rate of surgical intervention remains high, the morbidity and mortality of both VATS and open thoracotomy are of concern, particularly in a cohort of patients who may be older and with significant comorbidity. Less invasive therapies, which promote pleural space drainage and effective resolution of pleural infection, are therefore likely to be of considerable clinical utility. The MIST 2 trial has established intrapleural therapy as the mainstay of CPEE treatment, hence avoiding surgery and decreasing the length of hospitalization; however, little is known about the correct dosage needed for tPA and Dornase Alfa/Deoxyribonuclease (DNase). Dose and duration of intrapleural therapy based on MIST 2 involve multiple dosing and can be time-consuming for health care providers. Nevertheless, treatment of pleural infection with fibrinolytic therapy has been incorporated in the British Thoracic Society guideline 2023. Another study in 2022 by Cheong et al. used a modified regimen of intrapleural alteplase 16 mg t-PA with 5 mg DNase for three doses administered sequentially within 24 h. In this study, a modified regimen of t-PA and DNase offers an alternative therapeutic option for patients who are unfit or refuse surgical intervention but have persistent pleural infection. They have demonstrated similar treatment success comparable to other studies, as evidenced by improved pleural fluid drainage and reduced pleural opacity on day 7 chest x-ray, approximately 50% from the baseline. The mechanism of action of t-PA and DNase in the pleural cavity remains unclear. Studies suggested that IPFT may trigger the monocyte chemoattractant protein 1 (MCP-1) pathway, which promotes pleural fluid formation and subsequently causes a therapeutic lavage effect that increases pleural fluid drainage.