Malignant Pleural Effusion: Therapeutic Options and Strategies

Tunneled Pleural Catheter

Tunneled pleural catheters (TPCs) are a potentially permanent and minimally invasive therapy which allow intermittent drainage of pleural fluid (Figure 1). The catheter is tunneled under the skin to prevent infection. A polyester cuff attached to the catheter is positioned within the tunnel and induces fibrosis around the catheter, thereby securing the catheter in place. Placement can be performed under local anesthesia at the patient’s bedside or in an outpatient procedure space. Fluid can then be drained via specialized drainage bottles or bags by the patient, a family member, or visiting home nurse. The catheter can also be removed in the event of a complication or the development of spontaneous pleurodesis.

TPCs are an effective palliative management strategy for patients with recurrent effusions and are an efficacious alternative to pleurodesis.^18-20 TPCs may be used in patients with poor prognosis or trapped lung or in those in whom prior pleurodesis has failed.^21-23 Meta-analysis of 19 studies showed symptomatic improvement in 95.6% of patients, with development of spontaneous pleurodesis in 45.6% of patients (range, 11.8% to 76.4%) after an average of 52 days.²⁴ However, most of the studies included in this analysis were retrospective case series. Development of spontaneous pleurodesis from TPC drainage in prospective, controlled trials has been considerably more modest, supporting a range of approximately 20% to 30% with routine drainage strategies.^20,25-27 Spontaneous pleurodesis develops greater rapidity and frequency in patients undergoing daily drainage compared to every-other-day or symptom-directed drainage strategies.^25,26 However, there is no appreciable improvement in quality of life scores with a specific drainage strategy. Small case series also demonstrate that TPC drainage may induce spontaneous pleurodesis in some patients initially presenting with trapped lung physiology.²²

Catheter placement can be performed successfully in the vast majority of patients.²⁸ Increased bleeding risk, significant malignancy-related involvement of the skin and chest wall, and pleural loculations can complicate TPC placement. TPC-related complications are relatively uncommon, but include pneumothorax, catheter malfunction and obstruction, and infections including soft tissue and pleural space infections.²⁴ In a multicenter retrospective series of 1021 patients, only 4.9% developed a TPC-related pleural infection.²⁹ Over 94% were successfully managed with antibiotic therapy, and the TPC was able to be preserved in 54%. Staphylococcus aureus was the most common causative organism and was identified in 48% of cases. Of note, spontaneous pleurodesis occurred in 62% of cases following a pleural space infection, which likely occurred as sequelae of the inflammatory nature of the infection. Retrospective analysis suggests that the risk of TPC-related infections is not substantially higher for patients with higher risks of immunosuppression from chemotherapy or hematologic malignancies.^30,31 Tumor metastasis along the catheter tract is a rare occurrence (< 1%), but is most notable with mesothelioma, which has an incidence as high as 10%.^24,32 In addition, development of pleural loculations can impede fluid drainage and relief of dyspnea. Intrapleural instillation of fibrinolytics can be used to improve drainage and improve symptom palliation.³³

Pleurodesis

Pleurodesis obliterates the potential pleural space by inducing inflammation and fibrosis, resulting in adherence of the visceral and parietal pleura together. This process can be induced through mechanical abrasion of the pleural surface, introduction of chemical sclerosants, or from prolonged use of a chest tube. Chemical sclerosants are the most commonly used method for MPEs and are introduced through a chest tube or under visual guidance such as medical thoracoscopy or video-assisted thoracoscopic surgery (VATS). The pleurodesis process is thought to occur by induction of a systemic inflammatory response with localized deposition of fibrin.³⁴ Activation of fibroblasts and successful pleurodesis have been correlated with higher basic fibroblast growth factor (bFGF) levels in pleural fluid.³⁵ Increased tumor burden is associated with lower bFGF levels, suggesting a possible mechanism for reduced pleurodesis success in these cases. Corticosteroids may reduce the likelihood of pleurodesis due to a reduction of inflammation, as demonstrated in a rabbit model using talc and doxycycline.^36,37 Animal data also suggests that use of nonsteroidal anti-inflammatory drugs may hinder the likelihood of successful pleurodesis, but this has not been observed in humans.^38,39

Patients selected for pleurodesis should have significant symptom relief from large-volume removal of pleural fluid, good functional status, and evidence of full lung re-expansion after thoracentesis. Lack of visceral and parietal pleural apposition will prevent pleural adhesion from developing. As a result, trapped lung is associated with chemical pleurodesis failure and is an absolute contraindication to the procedure.^4,5,12 The pleurodesis process typically requires 5 to 7 days, during which time the patient is hospitalized for chest tube drainage and pain control. When pleural fluid output diminishes, the chest tube is removed and the patient can be discharged. Modified protocols are now emerging which may shorten the required hospitalization associated with pleurodesis procedures.