Normally, 10 to 20 mL of pleural fluid, similar in composition to plasma but lower in protein (< 1.5 g/dL [< 15 g/L]), is spread thinly over the visceral and parietal pleurae, facilitating movement between the lungs and chest wall. The fluid enters the pleural space from systemic capillaries in the parietal pleurae and exits via parietal pleural stomas and lymphatics. The fluid ultimately drains into the right atrium, so clearance is dependent on capillary and, in part, right-sided pressures. Pleural fluid accumulates when too much fluid enters or too little exits the pleural space.
Etiology of Pleural Effusion
Pleural effusions are usually categorized as
Transudates
Exudates
Categorization of the effusions is based on laboratory characteristics of the fluid (see table ). Whether unilateral or bilateral, a transudate can usually be treated without extensive evaluation, whereas the cause of an exudate requires investigation. There are numerous (> 50) causes (see table ).
Transudative effusions are caused by some combination of increased hydrostatic pressure and decreased plasma oncotic pressure. Heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more 
is the most common cause, followed by cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more with ascites and by hypoalbuminemia, usually due to the nephrotic syndrome Overview of Nephrotic Syndrome Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more .
Exudative effusions are caused by local processes that lead to increased capillary permeability, resulting in exudation of fluid, protein, cells, and other serum constituents. Causes are numerous; the most common are pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , cancer, pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more 
, viral infection, and tuberculosis Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more 
(TB).
Yellow nail syndrome is a rare disorder causing chronic exudative pleural effusions, lymphedema, and dystrophic yellow nails—all thought to be the result of impaired lymphatic drainage.
Chylous effusion (chylothorax) is a milky white effusion high in triglycerides caused by traumatic or neoplastic (most often lymphomatous) damage to the thoracic duct. Chylous effusion also occurs with the superior vena cava syndrome.
Chyliform (cholesterol or pseudochylous) effusions resemble chylous effusions but are low in triglycerides and high in cholesterol. Chyliform effusions are thought to be due to release of cholesterol from lysed red blood cells and neutrophils in long-standing effusions when absorption is blocked by the thickened pleura. The most common causes are rheumatoid pleuritis and chronic TB.
Hemothorax is bloody fluid (pleural fluid hematocrit > 50% peripheral hematocrit) in the pleural space due to trauma or, rarely, as a result of coagulopathy or after rupture of a major blood vessel, such as the aorta or pulmonary artery.
Empyema is pus in the pleural space. It can occur as a complication of pneumonia, thoracotomy, abscesses (lung, hepatic, or subdiaphragmatic), or penetrating trauma with secondary infection. Empyema necessitatis is soft-tissue extension of empyema leading to chest wall infection and external drainage.
Trapped lung is a lung encased by a fibrous peel caused by empyema or tumor. Because the lung cannot expand, the pleural pressure becomes more negative than normal, increasing transudation of fluid from parietal pleural capillaries. The fluid characteristically is borderline between a transudate and an exudate; ie, the biochemical values are within 15% of the cutoff levels for Light’s criteria (see table ).
Iatrogenic effusions can be caused by migration or misplacement of a feeding tube into the trachea or perforation of the superior vena cava by a central venous catheter, leading to infusion of tube feedings or IV solution into the pleural space.
Effusions with no obvious cause are often due to occult pulmonary emboli Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more , tuberculosis Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more , or cancer (1 Etiology reference Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and are usually classified as transudates or exudates. Detection is by physical examination,... read more 
). Etiology is unknown for some effusions even after extensive study (also referred to as non-specific pleuritis); many of these effusions are thought to be due to viral infection.
Etiology reference
1. Roberts ME, Rahman NM, Maskell NA, et al. British Thoracic Society Guideline for pleural disease. Thorax 2023;78(Suppl 3):s1-s42. doi:10.1136/thorax-2022-219784
Symptoms and Signs of Pleural Effusion
Some pleural effusions are asymptomatic and are discovered incidentally during physical examination or on chest x-ray.
Many effusions cause dyspnea, pleuritic chest pain, or both. Pleuritic chest pain, a vague discomfort or sharp pain that worsens during inspiration, indicates inflammation of the parietal pleura. Pain is usually felt over the inflamed site, but referred pain is possible. The posterior and peripheral portions of the diaphragmatic pleura are supplied by the lower 6 intercostal nerves, and irritation there may cause pain in the lower chest wall or abdomen that may simulate intra-abdominal disease. Irritation of the central portion of the diaphragmatic pleura, innervated by the phrenic nerves, causes pain that is referred to the neck and shoulder.
Physical examination reveals absent tactile fremitus, dullness to percussion, and decreased breath sounds on the side of the effusion. These findings can also be caused by pleural thickening. With large-volume effusions, respiration is usually rapid and shallow.
A pleural friction rub, although infrequent, is the classic physical sign. The friction rub varies from a few intermittent sounds that may simulate crackles to a fully developed harsh grating, creaking, or leathery sound synchronous with respiration, heard during inspiration and expiration. Friction sounds adjacent to the heart (pleuropericardial rub) may vary with the heartbeat and may be confused with the friction rub of pericarditis. Pericardial rub is best heard over the left border of the sternum in the 3rd and 4th intercostal spaces, is characteristically a to-and-fro sound synchronous with the heartbeat, and is not influenced significantly by respiration. Sensitivity and specificity of the physical examination for detecting effusion are probably low.
Diagnosis of Pleural Effusion
Chest x-ray
Thoracic ultrasonography
Pleural fluid analysis
Sometimes CT with venous contrast, CT angiography, or other tests
Pleural effusion is suspected in patients with pleuritic pain, unexplained dyspnea, or suggestive signs. Diagnostic tests are indicated to document the presence of pleural fluid and to determine its cause (see figure ).
Presence of effusion
Chest x-ray is the first test done to confirm the presence of pleural fluid. The lateral upright chest x-ray should be examined when a pleural effusion is suspected. In an upright x-ray, 75 mL of fluid blunts the posterior costophrenic angle. Blunting of the lateral costophrenic angle usually requires about 175 mL but may take as much as 500 mL. Larger pleural effusions opacify portions of the hemithorax and may cause mediastinal shift; effusions > 4 L may cause complete opacification of the hemithorax and mediastinal shift to the contralateral side.
Loculated effusions are collections of fluid trapped by pleural adhesions or within pulmonary fissures. Further imaging (lateral decubitus x-rays, chest CT, or ultrasonography) should be done if it is unclear whether an x-ray density represents fluid or parenchymal infiltrates or whether suspected fluid is loculated or free-flowing; these tests are more sensitive than upright x-rays and can detect small fluid volumes. Loculated effusions, particularly those in the horizontal or oblique fissure, can be confused with a solid pulmonary mass (pseudotumor). They may change shape and size with changes in the patient’s position and amount of pleural fluid.
Thoracic ultrasonography is considered standard of care for diagnosis of pleural effusion and is done at the bedside by pulmonologists, or sometimes emergency physicians, avoiding the need for radiologist review. It is highly accurate for the detection of small volumes of pleural fluid and provides additional diagnostic information (eg, the presence of septation, pleural thickening).
CT with venous contrast is a valuable next investigation that provides information on pleural enhancement and potential pleural nodularity. CT with venous contrast is valuable for evaluating the underlying lung parenchyma for infiltrates or masses when the lung is obscured by the effusion or when the detail on chest x-rays is insufficient for distinguishing loculated fluid from a solid mass.
Cause of effusion
Thoracentesis How To Do Thoracentesis Thoracentesis is needle aspiration of fluid from a pleural effusion. Thoracentesis may be done for diagnosis and/or therapy. Diagnostic thoracentesis Indicated for almost all patients who have... read more 
should be done in almost all patients who have pleural fluid that is ≥ 10 mm in thickness on CT, ultrasonography, or lateral decubitus x-ray and that is new or of uncertain etiology. In general, the only patients who do not require thoracentesis are those who have heart failure with symmetric pleural effusions and no chest pain or fever; in these patients, diuresis can be tried, and thoracentesis avoided unless effusions persist for ≥ 3 days. Thoracentesis and subsequent pleural fluid analysis are also often unnecessary for pleural effusions that are chronic, have a known cause, and cause no symptoms.
Thoracentesis should be done using ultrasonographic guidance in all cases because it increases procedure accuracy and prevents complications.
Pleural fluid analysis is done to diagnose the cause of pleural effusion. Analysis begins with visual inspection, which can
Distinguish bloody and chylous (or chyliform) from other effusions
Identify purulent effusions strongly suggestive of empyema
Identify viscous fluid, which is characteristic of some mesotheliomas
Fluid should always be sent for total protein, glucose, lactate dehydrogenase (LDH), cell count and cell differential, and Gram stain. Other tests such as pleural fluid pH, aerobic and anaerobic bacterial cultures, cytology, tuberculosis fluid markers [adenosine deaminase or interferon-gamma], amylase, mycobacterial and fungal stains and cultures, triglycerides, and cholesterol are used in appropriate clinical settings.
Fluid analysis helps distinguish transudates from exudates; multiple criteria exist, but not one perfectly discriminates between the 2 types. When Light’s criteria are used (see table ), serum LDH and total protein levels should be measured as close as possible to the time of thoracentesis for comparison with those in pleural fluid. Light’s criteria correctly identify almost all exudates but misidentify about 20% of transudates as exudates. If transudative effusion is suspected (eg, due to heart failure or cirrhosis) and none of the biochemical measurements are < 15% above the cutoff levels for Light’s criteria, the difference between serum and the pleural fluid protein is measured. If the difference is > 3.1 g/dL (> 31 g/L), the patient probably has a transudative effusion.
Imaging may also help. If the diagnosis remains unclear after pleural fluid analysis, CT with venous contrast enhancement is indicated to assess for pleural enhancement, pleural nodularity, pulmonary infiltrates, or mediastinal lesions. CT pulmonary angiography is indicated to rule out suspected pulmonary embolus. Findings of pulmonary emboli indicate the need for long-term anticoagulation. Pleural nodularity and thickening indicate the need for pleural biopsy (thoracoscopic or image guided). The presence of lung infiltrates or lesions, depending on suspected causes, may indicate the need for bronchoscopy or image-guided lung biopsy.
When tuberculous pleuritis is suspected, the level of adenosine deaminase in the pleural fluid is measured. A level > 40 U/L (667 nkat/L) has a 95% sensitivity and specificity for the diagnosis of tuberculous pleuritis (1 Diagnosis reference Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and are usually classified as transudates or exudates. Detection is by physical examination,... read more ); however, the adenosine deaminase level can also be positive in patients with cancer.
Diagnosis of Pleural Effusion
 * Based on presence of fever, weight loss, history of cancer, or other suggestive symptoms. TB = tuberculosis. |
Diagnosis reference
1. Roberts ME, Rahman NM, Maskell NA, et al. British Thoracic Society Guideline for pleural disease. Thorax 2023;78(Suppl 3):s1-s42. doi:10.1136/thorax-2022-219784
Treatment of Pleural Effusion
Treatment of symptoms and underlying disorder
Drainage of some symptomatic effusions
Other treatments for parapneumonic and malignant effusions
The effusion itself generally does not require treatment if it is asymptomatic because many effusions resorb spontaneously when the underlying disorder is treated, especially effusions due to uncomplicated pneumonias, pulmonary embolism, or surgery. Pleuritic pain can usually be managed with nonsteroidal anti-inflammatory drugs (NSAIDs) or other oral analgesics. At times, a short course of oral opioids is required.
Therapeutic thoracentesis How To Do Thoracentesis Thoracentesis is needle aspiration of fluid from a pleural effusion. Thoracentesis may be done for diagnosis and/or therapy. Diagnostic thoracentesis Indicated for almost all patients who have... read more (usually around 1 to 1.5 L in a single treatment) is sufficient for many symptomatic effusions and can be repeated for effusions that reaccumulate. There are no arbitrary limits on the amount of fluid that can be removed (1 Treatment reference Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and are usually classified as transudates or exudates. Detection is by physical examination,... read more ). Removal of fluid can be continued until the effusion is drained or the patient develops chest tightness, chest pain, or severe coughing.
Effusions that are chronic, recurrent, and causing symptoms can be treated with pleurodesis or by intermittent drainage with an indwelling catheter. Effusions caused by pneumonia or cancer may require additional specific measures.
Parapneumonic effusion and empyema
In patients with adverse prognostic factors (pH < 7.20, glucose < 60 mg/dL [< 3.33 mmol/L], positive Gram stain or culture, loculations), the effusion should be completely drained via thoracentesis How To Do Thoracentesis Thoracentesis is needle aspiration of fluid from a pleural effusion. Thoracentesis may be done for diagnosis and/or therapy. Diagnostic thoracentesis Indicated for almost all patients who have... read more or tube thoracostomy How To Do Tube and Catheter Thoracostomy Surgical tube thoracostomy is insertion of a surgical tube into the pleural space to drain air or fluid from the chest. Pneumothorax that is recurrent, persistent, traumatic, large, under tension... read more . If complete drainage is impossible, a thrombolytic (fibrinolytic) medication (eg, alteplase) plus a DNAse (eg, dornase alfa) can be administered intrapleurally. If intrapleural treatment is unsuccessful, thoracic surgical intervention is indicated. Video-assisted thoracoscopic surgery Thoracoscopy and Video-Assisted Thoracoscopic Surgery Thoracoscopy is a procedure in which an endoscope is introduced to visualize the pleural space. Thoracoscopy can be used for visualization (pleuroscopy) or for surgical procedures. Surgical... read more (VATS) is usually tried first, although thoracotomy may be required.
Malignant pleural effusion
If dyspnea caused by malignant pleural effusion is relieved by thoracentesis but fluid and dyspnea redevelop, chronic (intermittent) drainage or pleurodesis is indicated. Asymptomatic effusions and effusions causing dyspnea unrelieved by thoracentesis do not require additional procedures.
Indwelling pleural catheters and pleurodesis are equally effective for treating malignant pleural effusion. Choice depends on patient preference. Both decrease dyspnea and improve quality of life effectively. Talc pleurodesis requires hospital admission but long-term complications are more frequent with indwelling catheters.
Pleurodesis is done by instilling a sclerosing agent into the pleural space to fuse the visceral and parietal pleura and eliminate the space. The most effective and commonly used sclerosing agents are talc, doxycycline, and bleomycin delivered via chest tube or thoracoscopy. Pleurodesis is contraindicated if the lung does not expand after full drainage with a chest tube (entrapped lung), in which case indwelling pleural catheter is indicated.
Shunting of pleural fluid to the peritoneum (pleuroperitoneal shunt) is rarely done but is an option in patients who have trapped lung.
Surgical treatment (pleurectomy or decortication) should be considered in patients with trapped lung who have good performance status and a good prognosis.
Treatment reference
1. Feller-Kopman D, Berkowitz D, Boiselle P, et al: Large-volume thoracentesis and the risk of reexpansion pulmonary edema. Ann Thoracic Surg 84:1656–1662, 2007.
Key Points
Transudative effusions are caused by some combination of increased hydrostatic pressure and decreased plasma oncotic pressure.
Exudative effusions result from increased capillary permeability, leading to leakage of protein, cells, and other serum constituents.
The most common causes of transudative effusions are heart failure, cirrhosis with ascites, and hypoalbuminemia (usually due to the nephrotic syndrome).
The most common causes of exudative effusions are pneumonia, cancer, pulmonary embolism, and tuberculosis.
Evaluation requires imaging (usually chest x-ray and thoracic ultrasonography) to confirm presence of fluid and pleural fluid analysis to help determine cause.
Lateral decubitus x-rays, chest CT, or ultrasonography should be done if it is unclear whether an x-ray density represents fluid or parenchymal infiltrates or whether suspected fluid is loculated or free-flowing.
Effusions that are chronic or recurrent and causing symptoms can be treated with pleurodesis or by intermittent drainage with an indwelling catheter.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
talc |
Sclerosol, STERITALC |
alteplase |
Activase, Cathflo Activase |
dornase alfa |
Pulmozyme |
doxycycline |
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs |
bleomycin |
Blenoxane |
