Malignant Pleural Effusion: Therapeutic Options and Strategies

Pleurodesis Agents

A variety of chemical sclerosants have been used for pleurodesis, including talc, bleomycin, tetracycline, doxycycline, iodopovidone, and mepacrine. Published data regarding these agents are heterogenous, with significant variability in reported outcomes. However, systematic review and meta-analysis suggests that talc is likely to have higher success rates compared to other agents or chest tube drainage alone for treatment of MPE.^40,41

Additional factors have been shown to be associated with pleurodesis outcomes. Pleurodesis success is negatively associated with low pleural pH, with receiver operating curve thresholds of 7.28 to 7.34.^42,43 Trapped lung, large bulky tumor lining the pleural surfaces, and elevated adenosine deaminase levels are also associated with poor pleurodesis outcomes.^4,5,12,35,43 In contrast, pleural fluid output less than 200 mL per day and the presence of EGFR (epidermal growth factor receptor) mutation treated with targeted tyrosine kinase inhibitors are associated with successful pleurodesis.^44,45

The most common complications associated with chemical pleurodesis are fever and pain. Other potential complications include soft tissue infections at the chest tube site and of the pleural space, arrhythmias, cardiac arrest, myocardial infarction, and hypotension. Doxycycline is commonly associated with greater pleuritic pain than talc. Acute respiratory distress syndrome (ARDS), acute pneumonitis, and respiratory failure have been described with talc pleurodesis. ARDS secondary to talc pleurodesis occurs in 1% to 9% of cases, though this may be related to the use of ungraded talc. A prospective description of 558 patients treated with large particle talc (> 5 μm) reported no occurrences of ARDS, suggesting the safety of graded large particle talc.⁴⁶

Pleurodesis Methods

Chest tube thoracostomy is an inpatient procedure performed under local anesthesia or conscious sedation. It can be used for measured, intermittent drainage of large effusions for immediate symptom relief, as well as to demonstrate complete lung re-expansion prior to instillation of a chemical sclerosant. Pleurodesis using a chest tube is performed by instillation of a slurry created by mixing the sclerosing agent of choice with 50 to 100 mL of sterile saline. This slurry is instilled into the pleural cavity through the chest tube. The chest tube is clamped for 1 to 2 hours before being reconnected to suction. Intermittent rotation of the patient has not been shown to improve distribution of the sclerosant or result in better procedural outcomes.^47,48 Typically, a 24F to 32F chest tube is used because of the concern about obstruction of smaller bore tubes by fibrin plugs. A noninferiority study comparing 12F to 24F chest tubes for talc pleurodesis demonstrated a higher procedure failure rate with the 12F tube (30% versus 24%) and failed to meet noninferiority criteria.³⁹ However, larger caliber tubes are also associated with greater patient discomfort compared to smaller bore tubes.

Medical thoracoscopy and VATS are minimally invasive means to visualize the pleural space, obtain visually guided biopsy of the parietal pleura, perform lysis of adhesions, and introduce chemical sclerosants for pleurodesis (Figure 2). Medical thoracoscopy can be performed under local anesthesia with procedural sedation in an endoscopy suite or procedure room.