Choice of intrapleural fibrinolytic agents in the treatment of adult complicated parapneumonic effusion and empyema: Network meta-analysis

Background The appropriate use of intrapleural fibrinolytic agents in patients with complicated parapneumonic effusion and empyema remains unclear, especially regarding the choice of fibrinolytic agents. We conducted a network meta-analysis comparing outcomes of intrapleural fibrinolytic agents in patients with complicated parapneumonic effusion and empyema. Methods MEDLINE and EMBASE were searched through April 2022 to identify randomized controlled trials (RCTs) that investigated outcomes in patients with complicated parapneumonic effusion or empyema who were treated with intrapleural fibrinolytic agents. The outcomes of interest were surgical requirements, bleeding, length of hospital stay, and all-cause mortality. Results Our analysis included 10 RCTs that enrolled 1085 patients treated with intrapleural tissue plasminogen activator (TPA) ( n = 138), TPA + deoxyribonuclease (DNase) ( n = 52), streptokinase ( n = 311), urokinase ( n = 75), DNase ( n = 51), or placebo ( n = 458). The rates of surgical requirement were significantly lower with TPA and TPA + DNase than with placebo (risk ratio [RR]; 95% confidence interval [CI] = 0.36 [0.14–0.97], p = 0.038, RR [95% CI] = 0.25 [0.08–0.78], p = 0.017, respectively). The risk of bleeding was higher with TPA + DNase than with placebo (RR [95% CI] = 10.91 [1.53–77.99], p = 0.017), as well as TPA and TPA + DNase than with urokinase (RR [95% CI] = 17.90 [1.07–299.44], p = 0.044, RR [95% CI] = 89.3 [2.88–2772.49], p = 0.010, respectively). All-cause mortality was similar among the groups. Conclusion TPA and TPA + DNase reduced the rates of surgical requirement compared with placebo. However, TPA + DNase increased the risk of bleeding compared with placebo. Intrapleural agents for complicated parapneumonic effusion and empyema should be selected with an individual risk assessment.