Malignant Pleural Effusion: Therapeutic Options and Strategies

Malignant pleural effusion (MPE) is a common clinical problem in patients with advanced stage cancer. Each year in the United States, more than 150,000 individuals are diagnosed with MPE, and there are approximately 126,000 admissions for MPE.^1-3 Providing effective therapeutic management remains a challenge, and currently available therapeutic interventions are palliative rather than curative. This article, the second in a 2-part review of MPE, focuses on the available management options.

Therapeutic Thoracentesis

Evaluation of pleural fluid cytology is a crucial step in the diagnosis and staging of disease. As a result, large-volume fluid removal is often the first therapeutic intervention for patients who present with symptomatic effusions. A patient’s clinical response to therapeutic thoracentesis dictates which additional therapeutic options are appropriate for palliation. Lack of symptom relief suggests that other comorbid conditions or trapped lung physiology may be the primary cause of the patient’s symptoms and discourages more invasive interventions. Radiographic evidence of lung re-expansion after fluid removal is also an important predictor of success for potential pleurodesis.^4,5

There are no absolute contraindications to thoracentesis. However, caution should be used for patients with risk factors that may predispose to complications of pneumothorax and bleeding, such as coagulopathy, treatment with anticoagulation medications, thrombocytopenia, platelet dysfunction (eg, antiplatelet medications, uremia), positive pressure ventilation, and small effusion size. These factors are only relative contraindications, however, as thoracentesis can still be safely performed by experienced operators using guidance technology such as ultrasonography.

A retrospective review of 1009 ultrasound-guided thoracenteses with risk factors of an international normalized ratio (INR) greater than 1.6, platelet values less than 50,000/μL, or both, reported an overall rate of hemorrhagic complication of 0.4%, with no difference between procedures performed with (n = 303) or without (n = 706) transfusion correction of coagulopathy or thrombocytopenia.⁶ A similar retrospective evaluation of 1076 ultrasound-guided thoracenteses, including 267 patients with an INR greater than 1.5 and 58 patients with a platelet count less than 50,000/μL, reported a 0% complication rate.⁷ Small case series have also demonstrated low hemorrhagic complication rates for thoracentesis in patients treated with clopidogrel^8,9 and with increased bleeding risk from elevated INR (liver disease or warfarin therapy) and renal disease.¹⁰

Complications from pneumothorax can similarly be affected by patient- and operator-dependent risk factors. Meta-analysis of 24 studies including 6605 thoracenteses demonstrated an overall pneumothorax rate of 6.0%, with 34.1% requiring chest tube insertion.¹¹ Lower pneumothorax rates were associated with the use of ultrasound guidance (odds ratio, 0.3; 95% confidence interval, 0.2-0.7). Experienced operators also had fewer pneumothorax complications, though this factor was not significant in the studies directly comparing this variable. Therapeutic thoracentesis and use of a larger-bore needle were also significantly correlated with pneumothorax, while mechanical ventilation had a nonsignificant trend towards increased risk.

Although there is no consensus on the volume of pleural fluid that may be safely removed, it is recommended not to remove more than 1.5 L during a procedure in order to avoid precipitating re-expansion pulmonary edema.^2,12 However, re-expansion pulmonary edema rates remain low even when larger volumes are removed if the patient remains symptom-free during the procedure and pleural manometry pressure does not exceed –20 cm H₂O.¹³ Patient symptoms alone, however, are neither a sensitive nor specific indicator that pleural pressures exceed –20 cm H₂O.¹⁴ Use of excessive negative pressure during drainage, such as from a vacuum bottle, should also be avoided. Comparison of suction generated manually with a syringe versus a vacuum bottle suggests decreased complications with manual drainage, though the sample size in the supporting study was small relative to the infrequency of the complications being evaluated.¹⁵

Given the low morbidity and noninvasive nature of the procedure, serial large-volume thoracentesis remains a viable therapeutic intervention for patients who are unable or unwilling to undergo more invasive interventions, especially for patients with a slow fluid re-accumulation rate or who are anticipated to have limited survival. Unfortunately, many symptomatic effusions will recur within a short interval time span, which necessitates repeat procedures.^16,17 Therefore, factors such as poor symptom control, patient inconvenience, recurrent procedural risk, and utilization of medical resources need to be considered as well.