Objectives:Intrapleural thrombolytics have been trialed for facilitating pleural fluid drainage
in patients with complicated parapneumonic effusion. The present study is a network metaanalysis
of randomized clinical trials (RCTs) that have evaluated these thrombolytics.Methods:Electronic databases (Medline, Cochrane CENTRAL, and Google Scholar) were searched
for appropriate RCTs evaluating the therapeutic effect of thrombolytics in patients with complicated
parapneumonic effusion. Mortality, the proportion of patients referred for surgical intervention, and
serious adverse events were the outcome measures. Random-effects model was used for generating
direct and mixed treatment comparison pooled estimates. Grading of the evidence for key comparisons
was carried out. Odds ratio with 95% confidence intervals was used to represent the pooled estimates.Results:Seventy-six studies were retrieved with the search strategy, of which 16 were included. No
significant differences were observed in mortality. Compared to normal saline, significantly less proportion
of patients was referred for surgical intervention with streptokinase (0.4, 0.2 to 0.8), urokinase
(0.4, 0.2 to 0.8), alteplase (0.3, 0.1 to 0.7), and alteplase + DNase (0.2, 0.1 to 0.7). DNase alone increased
the risk of referral to surgical intervention (3.4, 1.5 to 7.6). Only streptokinase was observed
with an increased risk of serious adverse events compared to normal saline (2.8, 1.1 to 7.1) and alteplase
(6.7, 1.1 to 39.9). Moderate quality of evidence was observed for streptokinase with normal saline
for the proportion of patients referred for surgical intervention, while either low or very low quality
strength was observed for all other comparisons.Conclusion:Streptokinase, urokinase, alteplase, and alteplase + DNase were observed in patients referred
for surgical interventions when used intrapleural in patients with parapneumonic effusion. Alteplase
+ DNase is likely to outperform others as it was observed with the least risk of patients referred
for surgical interventions. Until additional data emerges that changes the pooled estimates,
thrombolytics other than streptokinase are preferred due to the increased risk of serious adverse
events.