Intrapleural Fibrinolysis with Urokinase versus Alteplase in Complicated Pleural Effusions and Empyema: A Prospective Randomized Controlled Trial.

BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. METHODS: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. RESULTS: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean± standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. CONCLUSION: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

Predictive Variables for Failure in Administration of Intrapleural Tissue Plasminogen Activator/Deoxyribonuclease in Patients With Complicated Parapneumonic Effusions/Empyema.

BACKGROUND: Combined intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has been shown to reduce the need for surgical intervention for complicated pleural effusion/empyema (CPE/empyema). For patients in whom tPA/DNase is likely to fail, however, receipt of this therapy may simply delay the inevitable. The goal of this study was to identify risk factors for failure of combined intrapleural therapy. METHODS: We performed a retrospective chart review of patients who received intrapleural tPA/DNase for the treatment of CPE/empyema. Clinical variables included demographic data, radiographic parameters at time of diagnosis, and results from pleural fluid analysis. We used gradient boosted trees-an ensemble machine learning technique, with hyperparameter tuning to mitigate overfitting-to rank the importance of 19 candidate clinical variables with respect to their ability to predict failure of tPA/DNase therapy. RESULTS: We identified 84 patients who received intrapleural tPA/DNase for the treatment of complicated pleural effusions/empyema over a 5-year period. Resolution of CPE/empyema with intrapleural tPA/DNase was achieved in two-thirds of the patients (n = 57). Of the 19 candidate predictors of tPA/DNase failure, the presence of pleural thickening was found to be the most important (48% relative importance), followed by the presence of an abscess or necrotizing pneumonia (24%), the pleural protein level (6%), and the presence of loculated effusion (4%). CONCLUSIONS: Our analysis found that the presence of pleural thickening and the presence of an abscess/necrotizing pneumonia helps to triage patients in whom combined intrapleural therapy is likely to fail. The results warrant further study and validation in a prospective multicenter study.

Safety and Efficacy of Tissue Plasminogen Activator and DNase for Complicated Pleural Effusions Secondary to Abdominal Pathology.

RATIONALE: Exudative pleural effusions may arise secondary to inflammation of intra-abdominal structures. Pleural space loculations can complicate these effusions, preventing adequate chest tube drainage and leading to consideration of surgical intervention. Previous studies have demonstrated that intrapleural administration of tissue plasminogen activator (tPA) combined with human recombinant DNase can improve fluid drainage and reduce surgery for patients with loculated parapneumonic effusions; however, the efficacy of this treatment has not been evaluated for complicated pleural effusions attributed to intra-abdominal inflammation. OBJECTIVES: We assessed the safety and efficacy of tPA/DNase for 17 pleural effusions associated with nonmalignant intra-abdominal pathology that did not drain adequately after placement of one or more chest tubes. METHODS: Efficacy was measured by comparing post- to pretreatment fluid drainage rates, volumetric assessment of pleural fluid on radiographic images before and after treatment, and clinical improvement, including the need for surgical intervention. Symptomatic relief was assessed using the Borg scale for breathlessness. MEASUREMENTS AND MAIN RESULTS: After a median of two doses of tPA/DNase, 23.5% of patients had chest pain and none had pleural bleeding. The volume of pleural fluid drained increased from a median of 325 ml to 890 ml per 24 hours after therapy (P = 0.018). The area of pleural space opacity on chest radiographs decreased from a median of 42.8-17.8% of the hemithorax (P = 0.001). tPA/DNase reduced the pleural fluid volume on chest computed tomographic imaging from a median of 294.4 ml to 116.1 ml. Borg scores improved from a median of 3 (interquartile range = 1-6) to 0 (interquartile range = 0-2) after therapy (P = 0.001). The median duration of chest tube placement and hospital stay were 4 and 11 days, respectively. Two patients required surgical intervention for lung entrapment. Overall, treatment was considered successful for 88.2% of patients. CONCLUSIONS: This retrospective case series suggests that intrapleural tPA/DNase can be safe and effective for patients with complicated pleural effusions attributed to abdominal pathology that do not drain adequately after chest tube placement. Additional studies are needed to determine whether the combination of tPA and DNase is more effective than tPA for this indication.