PLEURAL IRRIGATION WITH NORMAL SALINE VERSUS INTRAPLEURAL FIBRINOLYTIC IN PLEURAL INFECTION
Status:
Not yet recruiting
Trial end date:
2025-10-14
Target enrollment:
Participant gender:
Summary
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,
effective drainage of infected fluid and surgical intervention if conservative management
fails. For parapneumonic effusions which require clearance, appropriate therapy is effective
drainage via an intercostal catheter (ICC) with antibiotic therapy. The presence of fibrinous
septae in the pleural space, known as loculations, may result in inadequate drainage of
effusions and therefore non-resolution of infection and systemic sepsis. Without effective
intercostal catheter drainage, surgical intervention (VATS or open) has usually been required
to clear loculations for resolution of infection.
Non-surgical treatment options to reduce the impact of adhesions and locule include (in
addition to appropriate antibiotic therapy) single and multiple thoracocentesis, or single
and multiple intercostal tube thoracostomies, with or without intrapleural fibrinolytic
agents.
Fibrinolytic agents including streptokinase, urokinase, alteplase and recombinant tissue
plasminogen activator (rTPA) have been used safely and effectively intrapleurally for
complicated pleural effusion and empyema.
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 DNase. Dose and duration of intrapleural therapy based
on MIST 2 involve multiple dosing and can be time-consuming for health care providers .
Previous studies showed that complexity of treatment is a factor associated with poor
adherence to a regimen. For this reason, trying to find the minimum effective dose and
simplifying the regimen is essential for minimizing side effects and maximizing adherence.
The review of currently available literature shows concurrent administration of tPA and DNase
to be safe and effective even at lower cumulative dose Other study was carried out in May
2022 in which Modified regimen intrapleural alteplase 16 mg t-PA with 5 mg DNase for total 3
doses that administered sequentially within 24 h had been used. In this study, modified
regimen of t-PA and DNase offer an alternative therapeutic option for patients that are unfit
or refuse surgical intervention but persistent pleural infection. They have demonstrated
similar treatment success comparable to other studies, as evidenced by improvement on pleural
fluid drainage and reduction in pleural opacity on day 7 chest x-ray was approximately 50%
from the baseline using intrapleural 16 mg t-PA with 5 mg DNase. The mechanism of action of
t-PA and DNase in pleural cavity remain unclear. Studies suggested that IPFT may trigger the
monocyte chemoattractant protein 1 (MCP-1) pathway which promote pleural fluid formation and
subsequently causes a therapeutic lavage effect that increases pleural fluid drainage.
Another option for intrapleural therapy may be pleural irrigation with normal saline. The
idea behind is to dilute and remove bacteria, cytokines, inflammatory cells, and
pro-fibrinogenic coagulation factors, which induce pleural fluid organization. Also, the
mechanical process of irrigation increases pleural fluid drainage by reducing stasis and
organization of the intrapleural contents .
A randomised controlled pilot study in which saline pleural irrigation (three times per day
for 3 days) plus best-practice management was compared with best-practice management alone
was performed in patients with pleural infection requiring chest-tube drainage. The primary
outcome was percentage change in computed tomography pleural fluid volume from day 0 to day
3. Patients receiving saline irrigation had a significantly greater reduction in pleural
collection volume on computed tomography compared to those receiving standard care.
Significantly fewer patients in the irrigation group were referred for surgery (30).
However, till date there is no study done on head to head comparison between intrapleural
fibrinolytic with alteplase and DNAse Versus Pleural irrigationwith normal saline.