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 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 in part dependent on 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
Categorization of the effusions is based on laboratory characteristics of the fluid (see table Criteria for Identifying Exudative Pleural Effusions Criteria for Identifying Exudative Pleural Effusions Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more 
). Whether unilateral or bilateral, a transudate can usually be treated without extensive evaluation, whereas the cause of an exudate requires investigation. There are numerous causes (see table Causes of Pleural Effusion Causes of Pleural Effusion* Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more ).
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 failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... 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 (TB) is a chronic, progressive mycobacterial infection, often with a period of latency following initial infection. TB most commonly affects the lungs. Symptoms include productive... read more 
.
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.
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 Criteria for Identifying Exudative Pleural Effusions Criteria for Identifying Exudative Pleural Effusions Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more ).
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 (TB) is a chronic, progressive mycobacterial infection, often with a period of latency following initial infection. TB most commonly affects the lungs. Symptoms include productive... read more , or cancer. Etiology is unknown for about 15% of effusions even after extensive study; many of these effusions are thought to be due to viral infection.
Symptoms and Signs of Pleural Effusion
Some pleural effusions are asymptomatic and are discovered incidentally during physical examination or on chest x-ray. Many 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 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
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 Diagnosis of Pleural Effusion Diagnosis of pleural effusion Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more ).
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. 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 fluid volumes < 10 mL. 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.
CT is not routinely indicated but 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. It may be done for diagnosis and/or therapy. Diagnostic thoracentesis Indicated for almost all patients who have pleural... 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 often are not necessary for pleural effusions that are chronic, have a known cause, and cause no symptoms.
Whenever possible, thoracentesis is done using ultrasonographic guidance, which increases the yield of fluid and decreases risk of complications such as pneumothorax or puncture of an intra-abdominal organ.
Pleural fluid analysis is done to diagnose the cause of pleural effusion. Analysis begins with visual inspection, which can
Fluid should always be sent for total protein, lactate dehydrogenase (LDH), cell count and cell differential, Gram stain, and aerobic and anaerobic bacterial cultures. Other tests (glucose, cytology, tuberculosis fluid markers [adenosine deaminase or interferon-gamma], amylase, mycobacterial and fungal stains and cultures) 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 Criteria for Identifying Exudative Pleural Effusions Criteria for Identifying Exudative Pleural Effusions Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more ), 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 angiography is indicated to look for pulmonary emboli, pulmonary infiltrates, or mediastinal lesions. Findings of pulmonary emboli indicate the need for long-term anticoagulation; parenchymal infiltrates, the need for bronchoscopy; and mediastinal lesions, the need for transthoracic needle aspiration or mediastinoscopy. However, CT angiography requires patients to hold their breath for ≥ 24 seconds, and not all patients can comply. If CT angiography is unrevealing, observation is the best course unless the patient has a history of cancer, weight loss, persistent fever, or other findings suggestive of cancer or tuberculosis, in which case thoracoscopy 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 may be indicated. Needle biopsy of the pleura can be done when thoracoscopy is unavailable. If there is pleural thickening or pleural nodules, CT or ultrasound-guided biopsy is helpful for diagnosis.
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.
Treatment of Pleural Effusion
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.
Thoracentesis How To Do Thoracentesis Thoracentesis is needle aspiration of fluid from a pleural effusion. It may be done for diagnosis and/or therapy. Diagnostic thoracentesis Indicated for almost all patients who have pleural... read more is sufficient treatment 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 usually are classified as transudates or exudates. Detection is by physical examination and... 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 and 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. It may be done for diagnosis and/or therapy. Diagnostic thoracentesis Indicated for almost all patients who have pleural... read more or tube thoracostomy How To Do Surgical Tube 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) drug (eg, a tissue plasminogen activator 10 mg) plus a DNAse (eg, dornase alfa 5 mg) in 100 mL saline solution can be administered intrapleurally twice a day for 3 days. If attempts at drainage are unsuccessful, thoracoscopy should be done to lyse adhesions and remove fibrous tissue coating the lung to allow the lung to expand. If thoracoscopy is unsuccessful, thoracotomy with surgical decortication (eg, removal of scar, clot, or fibrous membrane surrounding the lung) is necessary.
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 catheter drainage is the preferred approach for ambulatory patients because hospitalization is not necessary for catheter insertion and the pleural fluid can be drained intermittently into vacuum bottles. 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 mediastinum has shifted toward the side of the effusion or if the lung does not expand after a chest tube is inserted.
Shunting of pleural fluid to the peritoneum (pleuroperitoneal shunt) is useful for patients with malignant effusion in whom pleurodesis is unsuccessful and in patients who have trapped lung.
Treatment reference
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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
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Transudative effusions are caused by some combination of increased hydrostatic pressure and decreased plasma oncotic pressure.
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Exudative effusions result from increased capillary permeability, leading to leakage of protein, cells, and other serum constituents.
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The most common causes of transudative effusions are heart failure, cirrhosis with ascites, and hypoalbuminemia (usually due to the nephrotic syndrome).
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The most common causes of exudative effusions are pneumonia, cancer, pulmonary embolism, and tuberculosis.
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Evaluation requires imaging (usually chest x-ray) to confirm presence of fluid and pleural fluid analysis to help determine cause.
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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.
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Effusions that are chronic or recurrent and causing symptoms can be treated with pleurodesis or by intermittent drainage with an indwelling catheter.
