Loculated Pleural Effusions: Can Intrapleural Streptokinase Help?
abstract & Commentary
Synopsis: Streptokinase appears to improve the resolution of loculated pleural effusions when chest tube drainage fails to achieve symptomatic relief.
Source: Davies CWH, et al. Chest 1999;115:729-733.
Malignant pleural effusion is a frequent complication of some common cancers. It is estimated that symptomatic pleural effusions affect more than 100,000 patients each year.1 Drainage of the pleural fluid by thoracentesis or by chest tube is highly effective at relieving the dyspnea associated with pleural effusions. However, a substantial fraction of patients do not respond completely to the usual treatment measures because the pleural fluid collections are loculated and do not drain to the most dependent portions of the pleural cavity where therapeutic measures are directed. Pathologically, the usual structural basis for the loculations is the formation of fibrin strands that produce localized adhesions in the pleural cavity. These adhesions can be lysed by the blind passage of a rigid tube between the lung and pleural surface (a procedure that can be painful and can produce lung damage and pneumothoraces) or by thoracoscopic procedures that permit direct visualization of the fibrin sheets.
Loculated pleural effusions also occur in some infectious diseases. In the setting of infection, a randomized controlled trial demonstrated that intrapleural administration of streptokinase was able to improve pleural drainage.2 However, streptokinase instillation has not been carefully studied in patients with cancer and at least one editorialist has expressed concerns that the use of the agent in patients with cancer might stimulate widespread fibrinolysis and hemorrhage.3 No data support that fear, but the question has not been carefully studied.
Davies and colleagues treated 10 consecutive patients (aged 39-89 years) with loculated malignant pleural effusions with twice-daily intrapleural injections of streptokinase when a standard chest tube drainage had failed to drain the effusions. The dose of each injection was 250,000 International units. Based on improvements in the chest radiograph, amount of fluid drained, and symptom relief, all 10 patients responded to 500,000 to 1,500,000 International units of intrapleural streptokinase. Before administration of streptokinase, chest tube drainage averaged 843 +/- 690 mL; after streptokinase administration, 2368 +/- 1051 mL of fluid drained (P < 0.001). Treated patients survived from 1- 15+ months after drainage; one patient died from sepsis unrelated to the procedure at one month. One patient had pain with the first instillation of streptokinase, but not with subsequent instillations. No allergic complications or hemorrhages were seen.
When chest tube drainage fails to achieve symptomatic relief in a patient with a pleural effusion and repeat chest radiograph demonstrates persistent fluid not being drained by the chest tube, it is reasonable to dissolve 250,000 International units of streptokinase in 30 mL of normal saline, instill it into the chest tube, clamp the chest tube for two hours, and then open the tube to drainage. When this maneuver is undertaken twice a day, remarkable improvements in chest tube drainage, chest radiograph appearance, and symptoms seem to be the usual outcome. The fear that stimulation of fibrinolysis in the pleural cavity might lead to systemic fibrinolysis and spontaneous hemorrhage was not confirmed in controlled studies of patients with infectious effusions, and did not appear to be any more likely in patients with cancer.
Although this paper reports a small retrospective analysis of a consecutive series of patients rather than a large prospective randomized trial, the results are impressive. Unless efforts to repeat the results in other centers turn up some unexpected toxicities or a poor success rate, controlled trials seem out of place. Streptokinase is an adjunctive therapy that appears to work well and it should be used to relieve symptoms from loculated pleural effusions.
1. Lynch TJ, et al. Chest 1993;103:385S-389S.
2. Davies RJO, et al. Thorax 1997;52:416-421.
3. Anonymous. Drug Ther Bull 1997;35:95.