Mechanisms of Pleurodesis

Pleurodesis aims to obliterate the pleural space by producing extensive adhesion of the visceral and parietal pleura, in order to control relapse of either pleural effusions (mostly malignant) or pneumothorax. A tight and complete apposition between the two pleural layers is a necessary condition to obtain a successful pleurodesis, but – besides this mechanical aspect – there are many biological mechanisms that appear to be common to most of the sclerosing agents currently used. Following intrapleural application of the sclerosing agent, diffuse inflammation, pleural coagulation-fibrinolysis imbalance (favoring the formation of fibrin adhesions), recruitment and subsequent proliferation of fibroblasts, and collagen production are findings in the pleural space. The pleural mesothelial lining is the primary target for the sclerosant and plays a pivotal role in the whole pleurodesis process, including the release of several mediators like interleukin-8, transforming growth factor-β and basic fibroblast growth factor. When the tumor burden is high, normal mesothelial cells are scarce, and consequently the response to the sclerosing agent is decreased, leading to failure of pleurodesis. Also, the type of tumor in the pleural cavity may also affect the outcome of pleurodesis (diffuse malignant mesothelioma and metastatic lung carcinomas have a poorer response). There is general agreement that talc obtains the best results, and there are also preliminary experimental studies suggesting that it can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of the malignant pleural effusion. There is concern about complications (possibly associated with talc but other agents as well) related to systemic inflammation and possible activation of the coagulation cascade. In order to prevent extrapleural talc dissemination, large-particle talc is recommended. Although it could – to some degree – interfere with the mechanisms leading to pleurodesis and a carefully balanced clinical decision has therefore to be made, prophylactic treatment with subcutaneous heparin is recommended during hospitalization (immediately before and after the pleurodesis procedure).