A Primer on the Management of Pleural Effusions

Diagnosis

Classification of Pleural Effusions

Accurate classification of pleural effusions using a combination of imaging and laboratory findings is essential, guiding management of both the effusion and the causative agent. Pleural effusions form when the rate of pleural fluid formation exceeds the ability of the lymphatics in the parietal pleura to reabsorb the fluid. Under normal physiologic conditions, fluid enters the pleural space via capillaries in the parietal pleura; however, it can also originate from interstitial spaces in the lung, visceral pleura, or tiny holes in the diaphragm under pathologic conditions. The rate of reabsorption in humans has been estimated at 0.36 mL/kg/h per hemithorax, or in more practical terms, 470 mL per hemithorax per day in a 70-kg patient.[1] On a standard chest X-ray, effusions of as little as 50 mL can be detected on lateral films and 200 mL on standard PA view ([Fig. 1]).

Fig. 1 Lateral chest radiograph demonstrates a small pleural effusion collecting in the posterior sulcus (arrow).

Traditionally, the first step in the diagnosis of pleural effusions has been to determine whether it is transudative or exudative. A transudative effusion occurs due to alteration of systemic factors which influence the formation and absorption of pleural fluid and an exudative effusion occurs when local factors are altered. Application of lights criteria serves as a good initial step, identifying the transudative effusions which can be managed by treating the systemic factors. Further characterization of the more common exudative effusions is described later.

Parapneumonic Effusions

Parapneumonic effusions occur as a result of bacterial pneumonia, lung abscess, or bronchiectasis. In the initial exudative stage (0–2 weeks), interstitial fluid accumulates around the infection site and crosses the visceral pleura into the pleural space. This fluid is typically sterile and will have a normal pH and glucose with a high protein content. In the subsequent fibropurulent stage (2–4 weeks), bacterial invasion of the pleural space accelerates the immune response causing further migration of neutrophils and activation of the coagulation cascade, often with formation of fibrin barriers which result in loculated pockets. In the final organizing stage (4–6 weeks), fibroblastic response results in creation of a thick pleural peel which resists respiratory motion and negates the efficacy of percutaneous drainage.[2]

In 2000, the American College of Chest Physicians (ACCP) developed a categorization system for parapneumonic pleural effusions based on imaging findings and pleural fluid analysis.[3]

Category 1—Any minimal free-flowing effusion with an unknown pleural fluid analysis. A minimal effusion is defined as less than 10 mm on lateral decubitus radiograph. With the increased reliance on CT imaging and infrequent use of lateral decubitus radiographs, fluid separating the lung from the chest wall by less than 10 mm can also serve to define a category 1 effusion. The risk of poor outcome in these scenarios is described as very low and no drainage is indicated.[4] Of note, if a thoracentesis was performed in this case and positive cultures/Gram stain or glucose less than 60 was found on pleural fluid analysis, findings are likely to be false positive. Consideration should then be given for repeat thoracentesis should the effusion enlarge or if the patient's clinical condition deteriorates.

Category 2—A small to moderate free-flowing effusion with negative culture/Gram stain and pH greater than or equal to 7.2, regardless of prior antibiotic use. Small to moderate is defined as pleural fluid separating the lung from the chest wall by greater than 10 mm but occupying less than one-half of the hemithorax. The risk of poor outcome is low and drainage is not considered necessary. However, should the patient's condition deteriorate, consideration should be given to repeat thoracentesis and drainage.

Category 3—Any large free-flowing effusion occupying more than one-half of the hemithorax, any effusion with loculations or thickened parietal pleura, and a small or larger (>10 mm of fluid separating the chest wall) effusion with thickened parietal pleura. Risk of poor outcome is considered moderate. Of note, larger pleural effusions are more difficult to drain, probably due to the increased likelihood of loculations.[5] And although perhaps intuitive, the presence of loculations portends a worse prognosis.[6] Category 3 effusions warrant drainage.

Category 4—Empyema. The term “empyema” is reserved for frank purulent effusions. Empyema is associated with a high risk of poor outcome and drainage is indicated. When assessing imaging of patients with parapneumonic effusions, it is important to note that thickening of the parietal pleura on contrast-enhanced CT is suggesting of empyema.[7]

Malignant Pleural Effusions

A malignant pleural effusion results from direct invasion of the pleura by cancer cells of primary or secondary tumors. Tumor-induced angiogenesis subsequently increases vascular permeability and vascular leakage of fluid resulting in pleural effusion. On CT, the most reliable features for distinguishing benign versus malignant pleural disease are the presence of a pleural rind (defined as circumferential involvement of the hemithorax, including the mediastinum), nodular pleural thickening, pleural thickening greater than 1 cm, and mediastinal pleural involvement, with pleural calcifications indicating a benign process.[8] FDG-PET/CT has also shown promise in distinguishing benign from malignant pleural disease. In a study of 79 patients with exudative pleurisy, SUV values were significantly higher in all malignant pleural diseases, with a cutoff value of 2.2 SUVbw (SUV normalized for body weight) resulting in an accuracy of 82.3% for the diagnosis of malignant pleural effusion.[9]

Ultimately, pleural fluid analysis is required to confirm the diagnosis of malignant pleural effusion. Chemical analysis (total protein, glucose, albumin, lactate dehydrogenase, pH) can be helpful in identifying if the fluid is an exudate, as almost all malignant pleural effusions are exudates; however, several other entities manifest with exudative effusions including bacterial pneumonia, viral process, and pancreatitis, to name a few. Fluid cytology yields a cytopathologic diagnosis conclusive for cancer in 90.5% of cases with the additional advantage of distinguishing the carcinomatous type.[10] If cytology is negative and there is continued high clinical suspicion for malignant pleural effusion, a pleural biopsy can be obtained. Image-guided percutaneous approaches have an overall sensitivity of 87.5% (95% when pleural thickening is > 1 cm) and thoracoscopic biopsies have a sensitivity of 94.1%.[11]

Hemothorax

Hemothorax is the presence of blood in the pleural space and is defined as pleural fluid hematocrit of at least 50% of the peripheral blood hematocrit. Often seen in the setting of trauma, hemothorax can also occur following thoracic interventional procedures such as lung tumor ablation.[12] Iatrogenic hemothorax is typically the result of damage to an intercostal or chest wall artery.

Chylothorax

Chylothorax is the presence of intestinal lymph (chyle) within the pleural space and results from leakage of the lymphatic vessels, most commonly the thoracic duct.[1] The etiology of chylothorax generally divided into traumatic and nontraumatic etiologies with iatrogenic injury accounting for 80% of traumatic causes. Nontraumatic etiologies include malignancy, infection, systemic diseases such as lupus erythematosus, and congenital disorders of the lymphatic system.[13]

The thoracic duct transports chyle from the intestinal system and flow rate ranges from 10 to 100 mL/kg of body weight per day, or on average 2.5 L per day.[14] The thoracic duct transports 70 to 80% of ingested fat in addition to fat-soluble vitamins and proteins. Unsurprisingly, the clinical findings of thoracic duct rupture include metabolic, nutritional, and immunologic deficiencies such as malnutrition and muscle wasting.

Aspirate of a chylothorax has traditionally been described as milky and odorless; however, not all effusions with these characteristics are necessarily chylous, and other etiologies such as empyema and pseudochylothorax need to be excluded with laboratory analysis. Pseudochylothorax is also known as cholesterol pleural effusion and can occur in longstanding pleural effusions, thought to result from the destruction of inflammatory cells.[14] Diagnosis of pseudochylothorax can be confirmed by the presence of cholesterol crystals in the aspirate.

The most widely used criteria for assessing the presence of chyle were initially published by Staats et al[15] where the diagnosis of chylothorax can be confirmed with fluid triglyceride levels greater than 110 mg/dL and triglyceride levels less than 50 mg/dL unlikely for chyle. The use of lipoprotein electrophoresis has been described in the diagnosis of chylothorax; however, it remains too costly and labor intensive for routine use and should only be considered in cases where triglyceride levels are equivocal (between 50 and 110 mg/dL) or where clinical suspicion of chylothorax is high.[16]

• References

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