Intrapleural urokinase for the treatment of loculated malignant pleural effusions and trapped lungs in medically inoperable cancer patients

Background: Pleural fluid loculations or trapped lungs frequently render patients with symptomatic malignant pleural effusions (MPEs) unsuitable for pleurodesis. Thoracoscopic surgery or thoracotomy with decortication is generally not feasible for patients with a poor performance status. MPEs have augmented procoagulant and depressed fibrinolytic activity that contributes to fibrin deposition within the pleural space. The authors conducted an observational prospective cohort study to investigate the use of intrapleural urokinase (IPUK) for such patients and made a comparison with a historical control group. Methods: Between March of 2000 and August of 2005, 48 consecutive patients with symptomatic MPEs with an average Karnofsky performance scale score of 46.7% were recruited. Dyspnea persisted with the presence of substantial residual loculated MPEs in 36 patients and trapped lungs in 12 patients, when the effectiveness of 8-French intrapleural catheter drainage had decreased despite regular saline flushes. Urokinase was instilled daily through the catheter at a dose of 100,000 IU diluted in 100 ml of normal saline for 3 days. Additional IPUK instillation was required upon partial improvement. The records and chest radiographs of another 52 patients with symptomatic MPEs had met these eligibility criteria between January of 1995 and February of 2000 and received saline flushes only were also reviewed. Results: Immediate lung reexpansion and resolution of dyspnea was achieved in 29 of the 48 patients who underwent IPUK therapy (60.4%). The mean dose of urokinase instillations per patient was 360,000 IU. There were no major complications. A significant association of earlier intervention with the success of IPUK therapy was noted. Responders also had a significantly increased drainage within the 24 hours after the first dose of IPUK. Minocycline pleurodesis was subsequently performed for the 29 IPUK responders. Eighteen patients were followed up until death, with a median survival of 6.5 months. The other remained alive at the time of analysis with a median follow-up of 5 months. Two patients had an immediate failure of pleurodesis at 1 month. Three relapses occurred at 3, 4, and 7 months from pleurodesis, respectively. Twenty-three patients (79.3%) had lifelong pleural symphysis, including 21 having loculated MPEs and two having trapped lungs, respectively. Compared with the historical control group, the IPUK study group had significantly greater improvement on chest radiography and a shorter duration of pleural drainage. Conclusion: These results suggest that IPUK is a safe and useful nonsurgical adjunct therapy for loculated MPEs or trapped lungs in medically inoperable cancer patients.