Pleural Effusion

The pleural cavity is a potential space bordered by the parietal pleura (covering the chest wall, diaphragm, and mediastinum) and the visceral pleura (covering the lung). In humans, an estimated 0.26 mL of serous pleural fluid per kilogram of body weight is contained within the space. The exact amount of fluid is dependent on the balance of hydrostatic and oncotic pressures between the parietal/visceral pleura and the pleural space. However, pleural fluid is continuously produced and reabsorbed, and in disease states, fluid production will exceed clearance and lead to development of an effusion.

(Source: Pleural Disease. N Engl J Med 2018.)

Assessment

History: The majority of cases of pleural effusions result from congestive heart failure, pneumonia, and cancer, although the differential diagnosis is extensive. Therefore, a detailed history should focus on the more common causes. A thoracentesis with diagnostic evaluation of the fluid is needed to limit the differential diagnosis and determine if a pleural effusion is exudative or transudative (see thoracentesis and fluid analysis below).

(Source: Pleural Disease. N Engl J Med 2018.)

Physical examination: The physical exam is critical to the diagnosis of a pleural effusion. The presence of excess fluid in the lung will cause dullness to percussion and the absence of tactile fremitus in the area of the effusion. Furthermore, breath sounds will be diminished or absent because the fluid is external to the lung parenchyma.

The physical exam can also provide hints about etiology. Heart failure often results in pleural effusion, usually (but not exclusively) bilaterally. Therefore, patients should be examined for signs of heart failure (e.g., elevated jugular venous pressure, peripheral edema) to rule it out. Signs of infection (e.g., pneumonia) or metastatic cancer (e.g., lymphadenopathy, hepatosplenomegaly) may help differentiate the etiology of the effusion (exudative vs. transudative).

Investigations

Chest imaging: Pleural effusions can be diagnosed and characterized with chest imaging.

(Source: Case 2-2022: A 70-Year-Old Man with a Recurrent Left Pleural Effusion. N Engl J Med 2022.)

Thoracentesis: The first step in limiting the differential diagnosis is to determine if a pleural effusion is exudative or transudative. To do this, a thoracentesis with diagnostic evaluation of the pleural fluid must be performed (see an instructional video of thoracentesis including indications, contraindications, technique, and fluid analysis).

Analysis of pleural fluid: The most relevant investigation of a new pleural effusion is biochemical, microbiological, and microscopic assessment of the fluid itself. The fluid must be analyzed to determine if it is exudative or transudative. Consequently, all pleural fluid should be tested for pH, lactic dehydrogenase (LDH), protein, Gram stain, microbiological culture, and cytology. Examination of the appearance of the extracted fluid can guide which tests are indicated.

(Source: Pleural Effusion. N Engl J Med 2002.)

Light’s criteria are the most common standards used to discriminate between transudative and exudative effusions. Pleural fluid is exudative if it has one or more of the following three criteria:

• The ratio of pleural fluid protein to serum protein is >0.5.

• The ratio of pleural fluid LDH to serum LDH is >0.6.

• The pleural fluid LDH is >2/3 (0.66%) the upper normal limit for serum LDH.

Other biochemical tests to help differentiate exudative from transudative fluid are listed in the following table:

(Source: Pleural Disease. N Engl J Med 2018.)

After narrowing the diagnosis to an exudative or transudative process, the differential in the first table above can be revisited to determine the most likely etiologies and which further tests are needed.

Treatment

The specific treatment for the effusion depends on its underlying etiology.

Transudative processes are typically systemic manifestations of another disease (e.g., heart failure, cirrhosis, or nephrotic syndrome). Treatment optimization of the underlying disease will often improve or resolve these effusions.

Exudative processes can be more complicated because they often result from inflammation of the pleura itself. The most common exudative pleural effusions in hospitalized patients are due to infection or malignancy.

Broad treatment algorithms for management of pleural effusions due to inflammation and due to malignancy are presented below.

(Source: Pleural Disease. N Engl J Med 2018.)

(Source: Pleural Disease. N Engl J Med 2018.)