Empyema remains a significant clinical challenge globally, particularly in stages II–III where fibrinous loculations and thick pleural rind complicate lung expansion. This literature review aims to compare clinical outcomes between VATS and open decortication in stage II–III empyema and evaluate the role of intrapleural fibrinolytic therapy (IPFT) in influencing surgical decision-making and outcomes. A systematic literature search was conducted on PubMed, Scopus, ScienceDirect, and Google Scholar for studies published between 2022–2026, yielding 15 articles that met inclusion criteria. Data were synthesized narratively due to heterogeneity across study designs. Findings indicate that VATS offers advantages in perioperative outcomes including reduced morbidity, shorter hospital stay, and faster recovery compared to open decortication in stage II empyema, while open decortication remains a crucial salvage option for complex stage III cases. IPFT, particularly tPA-DNase regimen, serves as an effective adjuvant therapy to improve drainage and reduce loculation complexity, yet bleeding risk remains a significant concern. The evidence supports a multimodal approach integrating IPFT, VATS, and open decortication based on individual patient characteristics and disease stage. However, high-quality evidence from large-scale randomized controlled trials is still needed to establish definitive recommendations. This review provides practical guidance for clinicians in selecting optimal treatment strategies for stage II–III empyema.
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