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Intrapleural Fibrinolytic Therapy for Treatment of Adult Parapneumonic Effusions and Empyemas
Study Question: What is the role of fibrinolytic therapy in the management of parapneumonic effusions and empyemas?
Study Description: This systematic review and meta-analysis utilized multiple databases to identify randomized controlled trials comparing fibrinolytic therapy to placebo in the treatment of parapneumonic effusions and empyemas. Only studies involving adults (> 19 years of age) were included. Data included: study publication year, country of origin, study design, number of patients in each arm, chest tube size, type, dose, and duration of fibrinolytic given, need for thoracic surgery, death, and treatment failure.
Results: A total of 682 citations were identified. Based on title and abstract alone, 669 were excluded and 13 were retrieved for full review. One study was then excluded based on lack of a placebo arm and five because the study population was made up of mainly tuberculous pleural effusions. Seven studies were included in the final analysis yielding a total of 801 patients (384 in fibrolytic group; 417 in placebo group). The overall quality of the studies was determined to be good using the Jadad Scale and Cochrane allocation approach. Doses of fibrinolytics utilized in the studies include: streptokinase 250,000 IU daily or BID x 3 or 7 days, urokinase 100,000 IU daily x 3 days, and alteplase 10 mg BID x 3 days +/- DNase 5mg BID x 3 days. Fibrinolytic therapy was found to be beneficial for the outcome of treatment failure (need for surgical intervention or death) (RR 0.50; 95% CI 0.28-0.87) as well as to decrease the need for surgical intervention alone (RR 0.61; 95% CI 0.45-0.82). There was no difference in mean duration of hospital stay with fibrinolytic therapy compared to placebo (standard mean difference 0.69; 95% CI -1.54-0.16) or a reduction in death (RR 1.14; 95% CI 0.74-1.74). A subgroup analysis of loculated pleural effusions showed a statistically significant decrease in surgical interventions with fibrinolytics (RR 0.41; 95% CI 0.26-0.65) but did not decrease overall treatment failure (RR 0.55; 95% CI 0.30-1.01). A sensitivity analysis was performed, which did not change the statistical outcomes.
Conclusion(s): Fibrinolytic therapy may be beneficial in the management of parapneumonic effusions and empyemas in the adult population, but evidence is insufficient to support routine use. There may be a role for fibrinolytics in patients with loculated pleural effusions to decrease surgical interventions.
Perspective: Despite no definitive recommendations regarding treatment, fibrinolytics have been utilized in the setting of pleural infection since the 1950s. This meta-analysis attempts to identify their place in therapy, but ultimately bases its conclusions on only 7 trials. Of note, the two most recent trials (MIST1 and MIST2) showed no benefit in terms of surgical intervention, mortality, duration of hospitalization, or radiographic improvement with fibrinolytic therapy. However, the adverse effect profile of fibrinolytics in this setting has been shown to be favorable and the subgroup analysis demonstrating benefit in the setting of loculated pleural effusions suggests they may be an option in elderly patients or non-surgical candidates. Unfortunately, further studies are still required to definitively address the impact of fibrinolytic therapy on clinical outcomes as well as the role of DNase in this setting.