Efficacy and safety of urokinase in the treatment of loculated pleural effusions caused by various etiologies: a systematic review and meta-analysis.

Background: Loculated pleural effusion caused by fibrinous septation often leads to incomplete drainage and prolonged hospitalization. Urokinase facilitates fibrin degradation; however, its overall efficacy and safety across different etiologies remain uncertain. This meta-analysis evaluated the clinical effectiveness and safety of intrapleural urokinase for loculated pleural effusions of various causes. Methods: A comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Database (CBM) was performed up to December 2024. Randomized controlled trials (RCTs) comparing urokinase plus standard drainage with drainage alone or with saline were included. Eligible studies enrolled patients with radiologically confirmed loculated or multiloculated pleural effusions and reported at least one quantitative efficacy or safety outcome. Trials using other fibrinolytics or steroids were excluded. The primary outcome was treatment success rate. Secondary outcomes included total drainage volume (mL), hospital stay (days), and adverse events. Data were synthesized using RevMan 5.4. Subgroup analyses were performed based on etiology and control group intervention (thoracentesis Results: Twenty-five RCTs involving 1,990 patients (1,018 urokinase; 972 controls) met the inclusion criteria. Urokinase significantly improved treatment success rate [odds ratio (OR) =5.28, 95% confidence interval (CI): 3.98-7.01; P<0.001] and increased total drainage volume [mean difference (MD) =622.32 mL, 95% CI: 377.22-867.43; P<0.001]. It shortened pleural effusion absorption time (MD =-7.31 days), hospital stay (MD =-6.94 days), and reduced residual pleural thickness (MD =-0.93 mm; all P<0.05). Subgroup analysis based on control group intervention (thoracentesis Conclusions: Intrapleural urokinase appears to be a safe and effective adjunctive therapy for loculated pleural effusions of diverse etiologies, consistently improving drainage and clinical outcomes. Nevertheless, the certainty of evidence is limited by moderate study quality, dosing heterogeneity, and potential publication bias. Further high-quality randomized trials are warranted. This review was registered in PROSPERO (CRD42024581473).