A pleural effusion is collection of fluid abnormally present in the pleural space, usually resulting from excess fluid production and/or decreased lymphatic absorption.[1] (See the images below.) It is the most common manifestation of pleural disease, and its causes occupy a spectrum ranging from cardiopulmonary disorders with systemic inflammatory conditions to malignancy.
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Large right-side pleural effusion. This effusion was noted to be malignant in nature.
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Left-side pleural effusion.
Pleural effusions are also commonly noted in patients diagnosed with pneumonia (14-44% of patietns admitted for pneumonia), and 40% of these cases may be complicated by parapneumonic effusion or abscess. These may be categorized as uncomplicated, complicated, or empyema thoracis. Management varies, depending on the clinical presentation and the imaging findings, but it often involves drainage with diagnostic, therapeutic, or combined intent. A combined approach that includes antibiotics, intrapleural enzymatic therapy, or surgical intervention is often necessary to achieve improved outcomes.
Of the approximately 1.5 million pleural effusions diagnosed in the United States each year, more than 150,000 are due to new cases of malignant pleural effusion (MPE). Approximately 15% of cancer patients eventually develop MPEs.[2] MPEs are diagnosed on the basis of the presence of tumor cells in pleural fluid cytology or pleural tissue biopsy. They usually signify incurable disease with considerable morbidity and a dismal mean survival (< 1 y).[3]
It is important to differentiate MPEs from paramalignant pleural effusions, which have a different pathophysiology and a different prognosis. Paramalignant effusions are associated with active malignancy, but without any cytologic or pathologic evidence of malignant involvement of the pleural space. These effusions may result from bronchial obstruction, pulmonary embolism, or postobstructive atelectasis with transudative effusion, or they may occur as side effects of cancer treatment.[3]
Heart failure is another common cause of pleural effusion. Such effusions are often bilateral in presentation and are frequently associated with other signs of heart failure, such as bilateral leg swelling. Pulmonary edema and respiratory failure may be noted. Medical management is often the primary modality, with diuretics administered to lower fluid volume and, potentially, vasodilators (eg, nitroglycerin) to reduce afterload. These effusions are likely to recur, with drainage maneuvers serving only as temporizing measures.
In a healthy individual, the pleural space (cavity) is a potential space sandwiched between the parietal and visceral pleurae. The parietal pleura completely lines the inner chest-wall surface of the thoracic cavity, including the bilateral medial mediastinum, the subcostal left and right diaphragmatic leaflets, and the innermost muscle surface of the ribs and associated musculature. The visceral pleura tightly and completely envelops both lungs, folding into the interlobar fissures and meeting the parietal pleura at the hilar root of the lungs. The right and left pleural cavities are separated by the anterior and posterior mediastinum.
In healthy patients, the potential space of the pleural cavity plays a vital role in respiration, joining the natural outward movement of the chest wall to the natural inward movement of the lungs via the following two mechanisms:
First, the potential space's relative vacuum sustains the visceral and parietal pleurae's extreme adherence and is uninterrupted and not disrupted
Second, a diminutive volume of pleural fluid (normally calculated at 0.1-0.2 mL/kg of body weight) serves as a lubricant to facilitate the normal physiologic sliding motion of the two pleural surfaces against each other during inspiration and expiration[4]
This small volume of lubricating pleural fluid, containing a small amount of protein (< 1.5 g/dL), is maintained via a delicate balance between hydrostatic and oncotic pressure. Fluid inflow is from the capillaries lining the parietal pleura, and absorption is facilitated by the visceral capillaries (~90%) and the lymphatic vessels (~10%). Disturbances in any of these mechanisms in the secretion or drainage of pleural fluid can manifest as a pleural effusion.[5, 6]
The normal pleural space contains approximately 10 mL of fluid, representing the balance between (1) hydrostatic and oncotic forces in the visceral and parietal pleural capillaries and (2) persistent sulcal lymphatic drainage. Pleural effusions may result from disruption of this natural balance.
A pleural effusion is rarely a primary disorder; more commonly, it heralds an underlying disease process that may be pulmonary or nonpulmonary in origin and, furthermore, may be acute or chronic.[7, 8] Although the etiologic spectrum of pleural effusion can be extensive, most pleural effusions are caused by congestive heart failure (CHF), pneumonia, malignancy, or pulmonary embolism (PE).
The following mechanisms may play a role in the formation of pleural effusion:
Altered permeability of the pleural membranes (eg, inflammation, malignancy, PE)
Reduction in intravascular oncotic pressure (eg, hypoalbuminemia due to nephrotic syndrome or cirrhosis)
Increased capillary permeability or vascular disruption (eg, trauma, malignancy, inflammation, infection, pulmonary infarction, drug hypersensitivity, uremia, pancreatitis)
Increased capillary hydrostatic pressure in the systemic or pulmonary circulation (eg, CHF, superior vena cava syndrome (SVCS)
Reduction of pressure in the pleural space (eg, from inability of the lung to fully expand during inspiration); this is known as "trapped lung" (eg, extensive atelectasis due to an obstructed bronchus or contraction from fibrosis leading to restrictive pulmonary physiology)
Decreased lymphatic drainage or complete lymphatic vessel blockage, including thoracic duct obstruction or rupture (eg, malignancy, trauma)
Increased peritoneal fluid with microperforated extravasation across the diaphragm via lymphatics or microstructural diaphragmatic defects (eg, hepatic hydrothorax, cirrhosis, peritoneal dialysis)
Movement of fluid from pulmonary edema across the visceral pleura
Persistent increase in pleural fluid oncotic pressure from an existing pleural effusion, causing further fluid accumulation
The net results of effusion formation are flattening or inversion of the diaphragm, mechanical dissociation of the visceral and parietal pleura, and an eventual restrictive ventilatory defect as measured by pulmonary function testing.[9]
Pleural effusions are generally classified as transudates or exudates on the basis of the mechanism of fluid formation and the pleural fluid chemistry. Transudates result from an imbalance between oncotic and hydrostatic pressures, whereas exudates result from inflammatory processes of the pleura, decreased lymphatic drainage, or both. In some cases, pleural fluid may exhibit a mixture of transudative and exudative characteristics.
Transudates result from an imbalance in oncotic and hydrostatic pressures. Transudative effusions are usually ultrafiltrates of plasma squeezed out of the pleura as a result of these unbalanced forces in the chest. However, other mechanisms of injury may include upward movement of fluid from the peritoneal cavity or, in iatrogenic cases, direct infusion into the pleural space from misplaced (or even migrated) central venous catheters or nasogastric feeding tubes.
Causes of transudative effusions make up a relatively small and well-defined group that includes the following:
CHF
Cirrhosis (hepatic hydrothorax)
Atelectasis (may be due to occult malignancy or pulmonary embolism)
Hypoalbuminemia
Nephrotic syndrome
Peritoneal dialysis
Myxedema
Constrictive pericarditis
Urinothorax (usually due to obstructive uropathy)
Cerebrospinal fluid (CSF) leaks to the pleura (in the setting of ventriculopleural shunting or of trauma/surgery to the thoracic spine)
Duropleural fistula (rare, but may be a complication of spinal cord surgery)
Extravascular migration of central venous catheter[10]
Glycinothorax (rare complication of bladder irrigation with 1.5% glycine solution following urologic surgery)
Exudates
Exudative pleural effusions can result from disease in almost any organ and may be triggered by a range of mechanisms. They often require a more extensive evaluation and a more involved treatment strategy than transudative effusions do.
Mechanisms of exudative formation include the following:
Pleural or parenchymal inflammation
Impaired lymphatic drainage of the pleural space
Transdiaphragmatic cephalad movement of inflammatory fluid from the peritoneal space
Altered permeability of pleural membranes
Increased capillary wall permeability or vascular disruption
Pleural membranes are involved in the pathogenesis of the fluid formation. It is worth noting that the permeability of pleural capillaries to proteins is increased in disease states characterized by elevated protein content.
The more common causes of exudates include the following:
Parapneumonic causes[11]
Malignancy (most commonly, lung or breast cancer, lymphoma, and leukemia; less commonly, ovarian carcinoma, stomach cancer, sarcomas, melanoma)[12]
Because pleural effusion is usually the manifestation of an underlying disease process, its precise incidence is difficult to determine. Nevertheless, it is the most common pleural-space disease, with an estimated annual incidence of least 1.5 million cases in the United States.[18] Most of these cases are caused by CHF, bacterial pneumonia, malignancy, and PE. Approximately 150,000 new cases of MPE are diagnosed annually. Lung and breast cancer combined account for more than 60% of MPEs, gastrointestinal (GI) and hematologic cancers account for 11% each, and other malignancies account for the remainder.[3]
In industrialized countries, the estimated prevalence of pleural effusion has been estimated at 320 cases per 100,000 people, with a distribution of etiologies related to the prevalence of underlying diseases.[7]
Age-, sex-, and race-related demographics
Pleural effusions usually occur in adults. However, they appear to be increasing in children, often in the setting of underlying pneumonia.[19] Fetal pleural effusions have also been reported and under certain circumstances may be treated before delivery.[20]
In a 2021 report from the American College of Chest Physicians (ACCP), 60% of the hospitalizations related to pleural infections were found to occur in the 18- to 64-year-old age group, and a male predominance in adult pleural infections was noted.[21] In a 2023 statement from the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS), this age group was found to account for 40% of adult pleural infections in the United Kingdom and Europe.[22] Advancing age leads to an increase in associated comorbidities, including a higher risk of pneumonia and, subsequently, pleural effusions and empyema.
Pleural effusion associated with SLE is specifically more common in women than in men. In the United States, the incidence of pleural effusion in the setting of malignant mesothelioma is higher in men, probably because of their higher occupational exposure to asbestos. Pleural effusions associated with chronic pancreatitis are more common in men, with the majority of male cases having alcohol abuse as the impetus. Rheumatoid effusions also occur more commonly in males than in females.
Given that pleural effusion is usually the manifestation of an underlying disease process, any race-related differences in frequency most likely reflect racial variations in the incidence of the causative disorder.
The prognosis in pleural effusion varies according to the condition’s underlying etiology. Generally, however, the complication rate is substantially lower for patients who seek medical care earlier in the course of their disease and who obtain prompt diagnosis and treatment than for patients who do not.
The morbidity and mortality of pleural effusions are directly related to the cause (and, if applicable, stage) of the underlying disease at the time of presentation, as well as to biochemical findings in the pleural fluid.
Morbidity and mortality are higher in patients with pneumonia and pleural effusions than in those in patients with pneumonia alone. Parapneumonic effusions, when recognized and treated promptly, typically resolve without significant sequelae; however, untreated or inappropriately treated parapneumonic effusions may lead to empyema, constrictive fibrosis, and sepsis.
MPEs are associated with a very poor prognosis (median survival, 4 mo; mean survival, < 1 y).[23, 24] Several studies have shown that patients with an MPE have a higher mortality than patients who have metastatic cancer without MPE. In men, the most common associated malignancy is lung cancer; in women, it is breast cancer. Median survival ranges from 3 to 12 months, depending on the malignancy. Effusions from cancers that are more responsive to chemotherapy (eg, lymphoma or breast cancer) are more likely to be associated with prolonged survival than effusions from lung cancer or mesothelioma.[25, 26]
As noted, cellular and biochemical findings in the fluid may also be indicators of prognosis. For example, a lower pleural fluid pH is often associated with a higher tumor burden and a worse prognosis.[27]
A detailed medical history should be obtained from all patients presenting with a pleural effusion; this may help establish the etiology. Because parapneumonic infections, heart failure, and malignancies are the most common causes of pleural effusion, special emphasis should be placed on these conditions during the course of obtaining a detailed history.
For example, a history of chronic hepatitis or alcoholism with cirrhosis suggests hepatic hydrothorax or alcohol-induced pancreatitis with effusion. A history of recent trauma suggests hemothorax, and surgery to the thoracic spine raises the possibility of a cerebrospinal fluid (CSF) leak. The patient should be asked about a history of cancer, even a remote one, because malignant pleural effusions (MPEs) can develop many years after an initial diagnosis.
An occupational history should also be obtained, including potential asbestos exposure, which could predispose the patient to mesothelioma or benign asbestos-related pleural effusion. The patient should also be asked about any current medications.[7] Inquiring about recent exposure to tuberculosis, previous tuberculosis infection, or travel to endemic areas with tuberculosis is also important.
The clinical manifestations of pleural effusion are variable and often are related to the underlying disease process. The most commonly associated symptoms are progressive dyspnea, cough, and pleuritic chest pain.
Dyspnea
Dyspnea, the symptom most commonly associated with pleural effusion, is related more to distortion of the diaphragm and chest wall during respiration than to hypoxemia. In many patients, drainage of pleural fluid alleviates dyspnea despite limited alterations in gas exchange. Drainage of pleural fluid may also allow the underlying disease to be more easily recognized on repeat chest radiographs. It should be kept in mind that dyspnea may be caused by the condition producing the pleural effusion (eg, underlying intrinsic lung or heart disease or obstructing endobronchial lesions) rather than by the effusion itself.
Cough
Cough in patients with pleural effusion is often mild and nonproductive. More severe cough or the production of purulent or bloody sputum suggests an underlying pneumonia or endobronchial lesion.
Chest pain
The presence of chest pain, which results from pleural irritation, raises the likelihood of an exudative etiology (eg, pleural infection, mesothelioma, or pulmonary infarction).[28] Pain may be mild or severe. It is typically described as sharp or stabbing and is exacerbated with deep inspiration. Pain may be localized to the chest wall, or it may be referred to the ipsilateral shoulder or upper abdomen as a consequence of diaphragmatic irritation. It may diminish in intensity as the effusion grows and the inflamed pleural surfaces are no longer in contact with each other.
Extrapulmonary symptoms
Other symptoms noted in association with pleural effusions may suggest the underlying disease process. Increasing bilateral lower-extremity edema, orthopnea, and paroxysmal nocturnal dyspnea may all occur with congestive heart failure (CHF). Unilateral leg swelling could be indicative of venous thromboembolism (VTE) and pulmonary embolism (PE).
Night sweats, fever, hemoptysis, and weight loss should suggest tuberculosis (TB). Hemoptysis also raises the possibility of malignancy, other endotracheal or endobronchial pathology, or pulmonary infarction. An acute febrile episode, purulent sputum production, and pleuritic chest pain may occur in patients who have an effusion associated with pneumonia.
Physical findings in pleural effusion are variable and depend on the volume of the effusion. Typically, effusions smaller than 300 mL do not give rise to any significant clinical findings. Effusions larger than 300 mL, however, may give rise to the following chest-wall/pulmonary findings:
Dullness to percussion, decreased tactile fremitus, and asymmetrical chest expansion, with diminished or delayed expansion on the side of the effusion - These are the most reliable physical findings of pleural effusion[29, 30]
Mediastinal shift away from the effusion - This finding is observed with effusions larger than 1000 mL
Displacement of the trachea and mediastinum toward the side of the effusion is an important clue to obstruction of a lobar bronchus by an endobronchial lesion, which can be due to malignancy or, less commonly, to a nonmalignant cause, such as a foreign body obstruction
Diminished or inaudible breath sounds
Egophony ("E-to-A" changes) at the most superior aspect of the pleural effusion
Pleural friction rub
Other physical and extrapulmonary findings may suggest the underlying cause of the pleural effusion.
Peripheral edema, distended neck veins, and S3 gallop suggest CHF. Edema may also be a manifestation of nephrotic syndrome, pericardial disease, or, when combined with yellow nailbeds, yellow nail syndrome.
Cutaneous changes and ascites suggest liver disease.
Lymphadenopathy or a palpable mass suggests malignancy.[7]
The easy availability of point-of-care ultrasonography (POCUS) has led to its incorporation into algorithms implemented at the time of emergency assessment in patients with acute respiratory failure. This can lead to a rapid diagnosis and quantification of pleural effusions, in that it is an older application of lung ultrasonography (US).
Incorporation of standardized assessments such as the BLUE (bedside lung ultrasound in emergency) protocol leads to a step-by-step approach for making an accurate diagnosis by surveying a set of standardized thoracic points with the aid of a curvilinear or phased-array probe (5-9 MHz). This application allows for reproductive analysis and has a diverse application for identifying pulmonary pathologies that can cause pleural effusion (eg, pulmonary edema, lung consolidation, and trauma), as well as other thoracic pathologies (eg, pneumothorax).[31]
Pleural effusions are often initially noticed on routine chest imaging (eg, chest radiography or computed tomography [CT]) performed to assess pulmonary pathologies. (See Pleural Effusion Imaging.) The imaging characteristics noted on these modalities are often augmented by the use of ultrasonography (US), which can be more sensitive than CT. US also helps delineate additional characteristics—such as quantity, quality (simple, complex nonseptated, or complex septated), or presence and nature of any subphrenic fluid collection (eg, ascites)—and identify some pleural pathologies.
Thoracocentesis (thoracentesis) should be performed for new and unexplained pleural effusions when sufficient fluid is present to allow a safe procedure. Observation of pleural effusion is reasonable when benign etiologies are likely, as in the setting of overt congestive heart failure (CHF), viral pleurisy, or recent thoracic or abdominal surgery.
Laboratory testing helps distinguish pleural fluid transudates from exudates. However, certain types of exudative pleural effusions might be suspected simply on the basis of the gross appearance.
Guidelines for workup
The American College of Radiology (ACR) found chest radiography or CT with intravenous (IV) contrast to be usually appropriate and equivalent alternatives for the initial imaging of suspected pleural effusion.[32] If CT is performed, imaging should occur 60 seconds after the IV contrast is administered for improved pleura images. The ACR made no recommendation for US in initial imaging, because of insufficient evidence of benefit.
The 2023 British Thoracic Society (BTS) recommendations for the investigation of a unilateral pleural effusion included the following[33] :
Imaging findings should be interpreted in the context of clinical history and knowledge of pleural fluid characteristics
CT follow-up should be considered for patients presenting with pleural infection to exclude occult malignancy if there are ongoing symptoms
Positron-emission tomography (PET)-CT should not be used in the assessment of pleural infection
Thoracocentesis should be imaging-guided to reduce the risk of complications
At least 25 mL, and where possible 50 mL, of pleural fluid should be sent for initial cytologic examination; if this amount is not available, clinicians should be aware of the reduced sensitivity
Pleural fluid samples should be processed by direct smear and cell block preparation
In high prevalence populations, pleural fluid adenosine deaminase (ADA) and/or interferon gamma (IFN-γ) test(s) can be considered for diagnosing tuberculous pleural effusion.
In low prevalence populations, pleural fluid ADA can be considered as an exclusion test for tuberculous pleural effusion
Tissue sampling for culture and sensitivity should be the preferred option for all patients with suspected tuberculous pleural effusion
Pleural fluid antinuclear antibody (ANA) should be considered to support a diagnosis of lupus pleuritis
Serum N-terminal pro B-type natriuretic peptide (NT-proBNP) should be considered to support a diagnosis of heart failure in patients with unilateral pleural effusion suspected of having heart failure
Serum biomarkers should not routinely be used to diagnosis tuberculous pleural effusion but may be considered in high prevalence areas
Serum biomarkers, including NT-proBNP, should not be used in isolation for diagnosing unilateral pleural effusion, because multiple conditions may coexist
Thoracoscopic or image-guided pleural biopsy may be used, depending on the clinical indication and the local availability of techniques; blind (non-image-guided) pleural biopsies should not be conducted
The 2017 American Association for Thoracic Surgery (AATS) guidelines for management of empyema recommended US in addition to chest radiography for diagnosis and for guidance of pleural interventions.[34] The AATS guidelines also recommended CT when pleural infection is suspected.
The 2023 European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS) statement on the management of pleural infection in adults found US to be adequate for initial assessment, clinical decision-making, and guidance of diagnostic sampling.[22] The ERS/ESTS guidelines also recommended contrast CT of the chest if pleural sepsis extends beyond 48 hours.
Effusions larger than about 200 mL are usually apparent as blunting of the costophrenic angle on upright posteroanterior (PA) chest radiographs. On supine chest radiographs, which are commonly used in the intensive care setting, moderate-to-large pleural effusions may appear as a homogenous increase in density spread over the lower lung fields. Apparent elevation of the hemidiaphragm, lateral displacement of the dome of the diaphragm, or increased distance between the apparent left hemidiaphragm and the gastric air bubble suggests subpulmonic effusions. (See the images below.)
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Isolated left-side pleural effusion with visualized loss of left lateral costophrenic sulcus. Posteroanterior upright chest radiograph. Image from All....
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Bilateral pleural effusions with loss of bilateral costophrenic sulci (meniscus sign). Anteroposterior upright chest radiograph. Image from Allen R Th....
Lateral decubitus films more reliably detect smaller pleural effusions (≤ 50 mL). Layering of an effusion on lateral decubitus films defines a freely flowing effusion and, if the layering fluid is 1 cm thick, indicates an effusion larger than 200 mL that is amenable to thoracocentesis. (See the image below.) Failure of an effusion to layer on lateral decubitus films indicates the presence of loculated pleural fluid or some other etiology causing the increased pleural density. It should be noted that decubitus films are almost never obtained in institutions with bedside US capability. (See the image below.)
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Left lateral decubitus film displaying freely layering left-side pleural effusion.
US can provide a quantitative and qualitative assessment of pleural effusion and is shown to be more sensitive and specific for identifying pleural effusion. It is also routinely employed to localize the site for thoracocentesis or chest-tube placement. A phased-array transducer probe (2-5 MHz) is generally preferred because its narrow footprint allows it to fit between the ribs and reduces the shadows generated by the rib cage. Alternatively, some prefer a curvilinear transducer becuase its larger footprint yields a wider field of view.[35]
The examination is usually performed with the patient seated, but it can also be done with the patient in a semirecumbent, supine, or lateral position. The probe is placed in a longitudinal plane on the posterior axillary line at the level of the diaphragm, with the transducer orientation marker pointed cephalad. For correct localization of the effusion as pleural, the following five structures should be identified[36] :
Liver/spleen
Diaphragm
Pleural fluid
Lung
Chest wall
A study by Usta et al found that US-based quantitative assessment using the following formula yielded a strong correlation between calculated and actual volumes drained by thoracocentesis[37] :
Qualitative assessment of pleural effusions on the basis of US features is another vital benefit. The effusions may be characterized as simple or complex as follows:
Simple effusions are anechoic and likely to be transudative in nature
Complex fluid (purulent or viscous) may have more density or shadows within in the pleural fluid collection; they may be homogeneously or heterogeneously echogenic, with or without septations, and are more often exudative; sometimes, fibrinous strands can be seen floating in the pleural fluid
US can effectively distinguish loculated pleural fluid from an infiltrate. The latter may have air bronchograms visible, but the distinction may be difficult if a dense consolidation is present.
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Ultrasonogram shows simple pleural effusion with anechoic fluid collection in subpulmonic space.
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Ultrasonogram of pleural space shows densely septated loculation in pleural space.
US can effectively distinguish loculated pleural fluid from an infiltrate. The latter may have air bronchograms visible, but the distinction may be difficult if a dense consolidation is present.
Additional terms used in diagnostic imaging of pleural effusion include the following:
Plankton sign - Floating debris in the effusion due to punctiform internal echoes swirling with respiration; this often suggests that the effusion is exudative or hemorrhagic in nature[38]
Jellyfish sign - Noted in large pleural effusions, this refers to the collapsed lung moving with respiration; the free movement suggests a transudative effusion, with absence of consolidation or pleural adhesions in the region[38]
US has been reported to outperform CT in the identification of septated pleural effusion. In a study of 285 patients with suspected pleural effusion, US was found to have a sensitivity of 82.6%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0%, and a negative predictive value (NPV) of 92.3% for the diagnosis of septated pleural effusion.[39] For chest CT, the corresponding values were 59.8%, 87.0%, 68.8%, and 82.0%, respectively.
In another study of 397 patients with pleural effusion, where medical thoracoscopy served as the gold standard for confirming the diagnosis of septated pleural effusions, US demonstrated a sensitivity of 82.6% and a specificity of 100.0% for diagnosing septated pleural effusion, whereas enhanced chest CT exhibited a sensitivity of 59.8% and a specificity of 87.0%.[40]
A study involving 41 consecutive patients with hepatic hydrothorax indicated that hepatic hydrothorax virtually always presents with ascites that can be revealed by US or CT.[41] Point-of-care US (POCUS) at the bedside has become the standard of care in many facilities.
Chest CT with contrast should be performed in all patients with an undiagnosed pleural effusion to evaluate underlying complex etiologies and to differentiate empyema from pulmonary abcess. It can help identify parenchymal lesions and thoracic adenopathy, which could be indicative of malignancy. In addition, it may be useful for detection of loculated effusion at atypical locations (superior or anterior), which may facilitate localization of the site for drainage.
Contrast-enhanced CT also helps evaluate pleural pathologies, such as thickened pleura or signs of invasion of underlying or adjacent structures. Split pleura signs show enhancement of the thickened inner visceral and outerparietal pleura, with separation by a collection of pleural fluid often indicating empyema.[42]
CT angiography (CTA) should be ordered if pulmonary embolism (PE) is strongly suggested.
A diagnostic thoracocentesis should be performed if the etiology of the effusion is unclear or if the presumed cause of the effusion does not respond to therapy as expected. Generally, pleural effusion greater than or equal to 10 mm thick on a lateral decubitus chest radiograph is considered safe. Pleural effusions do not require thoracocentesis if they are too small to be safely aspirated or, in clinically stable patients, if their presence can be explained by underlying CHF (especially bilateral effusions) or by recent thoracic or abdominal surgery.
Depending on the clinician’s experience, a pulmonologist or interventional radiologist can be consulted for assistance with high-risk diagnostic thoracocentesis.
Contraindications
An uncooperative patient is an absolute contraindication for this procedure. Relative contraindications include the following:
Small volume of fluid (< 1 cm thickness on a lateral decubitus film)
Severe bleeding diathesis or systemic anticoagulation
Cutaneous disease over the proposed puncture site
Reversal of coagulopathy or thrombocytopenia may not be necessary, as long as the procedure is performed under US guidance by an experienced operator.[43] Mechanical ventilation with positive end-expiratory pressure does not increase the risk of pneumothorax after thoracocentesis, but it increases the likelihood of severe complications (tension pneumothorax or persistent bronchopleural fistula) if the lung is punctured. (See Complications below.)
Procedure
In patients with large, freely flowing effusions and no relative contraindications for the procedure, diagnostic thoracocentesis is usually safe. US, by virtue of its wide availability, has become the standard of care for identifying the puncture site; however, when US capabilities are limited, the site is chosen on the basis of the chest radiograph and located one or two rib interspaces below the level of dullness to percussion on physical examination. US guidance at the bedside significantly increases the likelihood of obtaining pleural fluid and reduces the risk of pneumothorax.[44, 45]
A postprocedure chest film may not be needed, but it is always a good practice to look for US evidence of pneumothorax. The presence of lung sliding would also confirm the absence of a pneumothorax.
The procedure is performed as follows:
After the site is disinfected with chlorhexidine (preferred) or povidone/iodine (no longer recommended) solution and sterile drapes are placed, anesthetize the skin, periosteum, and parietal pleura with 1% lidocaine through a 25-gauge needle; if pleural fluid is not obtained with the shorter 25-gauge needle, continue anesthetizing with a 1.5-inch, 22-gauge needle; for patients with larger amounts of subcutaneous tissue, a 3.5-inch, 22-gauge spinal needle with inner stylet removed can be used to anesthetize the deeper tissues and to aspirate pleural fluid
Confirm the correct location for thoracentesis by aspirating pleural fluid through the 25- or 22-gauge needle before introducing larger-bore thoracocentesis needles or catheters; if pleural fluid is not easily aspirated, stop the procedure, and employ US or chest CT to guide thoracocentesis
Although there is no consensus amount for a diagnostic thoracocentesis, a minimum of 20 mL of fluid should be enough for basic analysis and culture; most of these procedures remove less than 100 mL
When possible, patients should sit upright, they should not lean forward, because this causes pleural fluid to move to the anterior costophrenic space and increases the risk of puncture of the liver or spleen
For debilitated and ventilated patients who cannot sit upright, obtain pleural fluid by puncturing over the eighth rib at the midaxillar to posterior axillary line; to avoid puncturing the liver or spleen, the needle should not be inserted below the ninth rib; in such patients, imaging guidance may be required
Supplemental oxygen is often administered during the procedure to offset hypoxemia produced by changes in ventilation-perfusion relations as fluid is removed and to facilitate reabsorption of pleural air if pneumothorax complicates the procedure
The frequency of complications from thoracocentesis may be lower when the procedure is performed by a practitioner with greater experience and when US guidance is employed.[46] Consequently, in patients who have a higher risk of complications or relative contraindications for thoracocentesis and in patients who cannot sit upright, it is important that the procedure be performed by a skilled and experienced clinician.
Postprocedure expiratory chest radiographs to exclude pneumothorax are not needed in asymptomatic patients after uncomplicated procedures (single needle pass without aspiration of air).[47] However, they are often obtained in routine clinical practice and recommended to establish a new baseline for patients likely to have recurrent symptomatic effusions. US can also be employed for rapid on-site postprocedural evaluation of pneumothorax.
Complications
Complications of diagnostic thoracocentesis include the following:
Pain at the puncture site
Cutaneous or internal bleeding from laceration of an intercostal artery or spleen/liver puncture
Pneumothorax
Empyema
Reexpansion pulmonary edema
Malignant seeding of the thoracocentesis tract
Adverse reactions to anesthetics used in the procedure
Pneumothorax complicates approximately 6% of thoracocenteses but necessitates chest-tube drainage of the pleural space in fewer than 2% of cases.[44] The use of needles larger than 20-gauge increases the risk of a pneumothorax complicating the procedure. In addition, significant chronic obstructive or fibrotic lung disease increases the risk of a symptomatic pneumothorax complicating the thoracentesis.
Normal pleural fluid has the following characteristics:
Clear ultrafiltrate of plasma that originates from the parietal pleura
pH 7.60-7.64
Protein content < 2% (1-2 g/dL)
White blood cell (WBC) count < 1000/μL
Glucose content similar to that of plasma
Lactate dehydrogenase (LDH) < 50% of plasma level
Gross appearance
Laboratory testing helps distinguish pleural fluid transudates from exudates. However, certain types of exudative pleural effusions might be suspected simply by observing the gross characteristics of the fluid obtained during thoracocentesis, as follows:
Frankly purulent fluid indicates an empyema
A putrid odor suggests an anaerobic empyema
A milky, opalescent fluid suggests a chylothorax, resulting most often from lymphatic obstruction by malignancy or thoracic duct injury from trauma or a surgical procedure
Grossly bloody fluid may result from trauma, malignancy, postpericardiotomy syndrome, or asbestos-related effusion and indicates the need for a spun hematocrit test of the sample; a pleural fluid hematocrit level higher than 50% of the peripheral hematocrit level defines a hemothorax, which often necessitates tube thoracostomy
Black pleural fluid suggests a limited number of diseases, including infection with Aspergillus niger or Rizopus oryzae, malignant melanoma, non-small cell lung cancer, ruptured pancreatic pseudocyst, or charcoal-containing empyema[48]
The color and clarity of the effusion can provide some information regarding the underlying etiology, as follows[49] :
A clear effusion without any foam, often described as serous, is more likely to be transudative (eg, CHF)
A cloudier effusion that is still light in color may also be described as serous and could be either transudative or pseudotransudative with higher protein content (eg, chronic transudative effusion, early inflammatory etiologies)
A mildly darker (amber- or red-colored) effusion that is still clear may be described as serosanginous and is often exudative (eg: parapneumonic)
A darker opaque (grossly bloody) effusion, often described as sanginous, occurs as a result of lysis of red blood cells (RBCs) and is exudative (eg, malignancy, pulmonary embolism with infarcts)
Pleural fluid lactate dehydrogenase
Pleural fluid LDH levels higher than 1000 IU/L suggest empyema, malignant effusion, rheumatoid effusion, or pleural paragonimiasis. Pleural fluid LDH levels are also increased in effusions from Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia. The diagnosis is suggested by a pleural fluid–to–serum LDH ratio higher than 1 in conjunction with a pleural fluid–to–serum protein ratio lower than 0.5.
Although pleural fluid LDH is elevated in tuberculosis (TB)-related pleural effusions, levels are generally lower than those seen in empyema. [50]
Pleural fluid protein
Pleural fluid protein levels are important for differentiating transudative from exudative etiologies. Proteinacious effusions are noted in exudative effusions, with a pleural fluid protein level higher than 3.0 g/dL or a pleural fluid–to–serum protein ratio higher than 0.5.
A serum–minus–pleural fluid protein gradient (SPPG) greater than 3.1 g/dL or a serum–minus–pleural fluid albumin gradient (SPAG) greater than 1.2 g/dL can facilitate correct identification of a transudative effusion when there is concern regarding the effect of ongoing diuresis on the protein content of the pleural effusion and possible classification as a pseudoexudate because of a concentrated pleural effusion.
Pleural fluid glucose
A low pleural glucose concentration (30-50 mg/dL) suggests malignant effusion, tuberculous pleuritis, esophageal rupture, or lupus pleuritis. A gulcose concentration lower than 40 mg/dL is also suggestive of complicated pleural effusion or empyema and warrants chest-tube drainage. A very low glucose concentration (< 30 mg/dL) further restricts the diagnostic possibilitie, to rheumatoid pleurisy.
Elevated pleural fluid glucose can also be seen in other settings, such as misplaced central venous catheters or peritoneal dialysis.
Pleural fluid pH
Pleural fluid pH is highly correlated with pleural fluid glucose levels. A pleural fluid pH lower than 7.30 with a normal arterial blood pH is caused by the same diagnoses listed above for low pleural fluid glucose. With parapneumonic effusions, however, a low pleural fluid pH is more predictive of complicated effusions (ie, effusions requiring drainage) than a low pleural fluid glucose level is. In such cases, a pleural fluid pH lower than 7.2 indicates the need for urgent drainage of the effusion, whereas a pH higher than 7.3 suggests that the effusion may be managed with systemic antibiotics alone.
In patients with malignant pleural effusions (MPEs), a pleural fluid pH lower than 7.3 has sometimes been associated with more extensive pleural involvement, higher yield on cytology, decreased success of pleurodesis, and shorter survival times.
For pH measurements, pleural fluid samples must be handled as carefully as arterial samples, with fluid collected in heparinized syringes. Ideally, samples should be transported on ice for measurement within 6 hours. Studies have determined, however, that when pleural fluid is collected in heparinized syringes, its pH does not change significantly even over several hours at room temperature. Consequently, if appropriately collected samples can be processed quickly, pH measurement should not be canceled simply because the sample was not transported on ice. Typically, a pleural fluid pH exceeding the normal upper limit of 7.60 is a result of sampling error.
Pleural fluid cell count and differential
Total nucleated cell (TNC) counts lower than 1000/μL are commonly noted in transudative effusions, whereas TNC counts higher than 1000/μL are more likely to be present in exudative effusions. A polymorphonuclear neutrophil (PMN)-predominant effusion suggests an acute process affecting the pleural surfaces. A TNC count higher than 10,000/μL likely reflects a parapneumonic effusion; however, in frank empyema, the TNC count can be extremely low (< 200/μL) as a consequence of autolysis.
Pleural fluid lymphocytosis, with lymphocytes accounting for more than 85% of TNCs, suggests TB, lymphoma, sarcoidosis, chronic rheumatoid pleurisy, yellow nail syndrome, or chylothorax. Pleural lymphocyte counts in the range of 50-70% of TNCs suggest malignancy.
Pleural fluid eosinophilia (PFE), with eosinophils accounting for more than 10% of TNCs, is seen in approximately 10% of pleural effusions and is not correlated with peripheral blood eosinophilia. PFE is most often caused by air or blood in the pleural space. Blood in the pleural space causing PFE may be the result of PE with infarction or of benign asbestos-related pleural effusion. PFE may also be associated with other nonmalignant diseases, including parasitic disease (especially paragonimiasis) and fungal infection (coccidioidomycosis, cryptococcosis, histoplasmosis), as well as with the use of various medications.
The presence of PFE does not exclude an MPE, especially in patient populations with a high prevalence of malignancy. The presence of PFE doesmake tuberculous pleurisy unlikely and also makes the progression of a parapneumonic effusion to an empyema unlikely.
Mesothelial cells are found in variable numbers in most effusions, but their presence at a level exceeding 5% of TNCs makes a diagnosis of TB less likely. Markedly increased numbers of mesothelial cells, especially in bloody or eosinophilic effusions, suggests PE as the cause of effusion.
A pleural fluid–to–blood hematocrit ratio exceeding 0.5 confirms the diagnosis of hemothorax.
Pleural fluid culture
Cultures of infected pleural fluid yield positive results in approximately 60% of cases, for several reasons: Some organisms are difficult to culture, sterile pockets may exist adjacent to infected pockets in loculated effusions, or samples may have been obtained after initiation of antibiotic therapy. Diagnostic yields, particularly for anaerobic pathogens, may be increased by directly culturing pleural fluid into blood culture bottles.[51] An additional sample in a sterile container should be collected for Gram staining or for inoculation by laboratory personnel if institutional policy does not accept the culture bottles inoculated at the bedside.
Pleural fluid cytology
Malignancy is suspected in patients with known cancer or with lymphocytic exudative effusions, especially when the effusions are bloody. Direct tumor involvement of the pleura is diagnosed most easily by performing pleural fluid cytology. The reported diagnostic yields in cytology range from 60% to 90%, depending on the extent of pleural involvement and the type of primary malignancy. Cytology findings are positive in 58% of effusions related to mesothelioma. The sensitivity may increase by 15% with a second thoracocentesis sample.
The sensitivity of cytology is not strongly related to the volume of pleural fluid tested. Sending more than 50-60 mL of pleural fluid for cytology does not increase the yield of direct cytospin analysis,[52, 53] and a volume of approximately 150 mL is sufficient when both cytospin and cell block preparations are analyzed.[53] Nevertheless, expert recommendations from the College of American Pathologists have stated that when clinicians collect pleural fluid for suspected malignancy, they should submit the maximum feasible volume for cytologic evaluation and ancillary studies.[54]
Tumor markers, such as carcinoembryonic antigen (CEA), Leu-1, and mucin, are suggestive of malignant effusions (especially adenocarcinoma) when pleural fluid values are very high. However, because of low sensitivity, they are not helpful if the pleural fluid values are normal or only modestly increased.
Additional specialized tests are warranted when specific etiologies are suspected, including the following[42] :
Pancreatic origin or ruptured esophagus - The pleural fluid amylase level is checked if a unilateral left-side pleural effusion with high clinical suspicion remains undiagnosed after initial testing (note: increased pleural fluid amylase can also be seen with malignancy); an additional assay of amylase isoenzymes can help distinguish a pancreatic source (diagnosed by elevated pleural fluid pancreatic isoenzymes) from other etiologies
Chylothorax - Pleural fluid triglyceride >110 mg/dL, cholesterol-to-triglyceride ratio < 1; cholesterol and triglyceride levels should be checked in milky pleural fluids when chylothorax or pseudochylothorax is suspected
Hepatic hydrothorax - Pleural fluid–to–serum albumin ratio < 0.6 confirms the diagnosis[55]
Heart failure - Pleural fluid NT-proBNP ≥1500 pg/mL provides very good diagnostic accuracy for heart failure[56]
Tuberculous pleuritis
Tuberculous pleuritis should be suspected in patients with a history of exposure or a positive purified protein derivative (PPD) finding and in patients with lymphocytic exudative effusions, especially if mesothelial cells are less than 5% on differential cell counts. Because most tuberculous pleural effusions probably result from a hypersensitivity reaction to Mycobacterium tuberculosis rather than from microbial invasion of the pleura, acid-fast bacillus stains of pleural fluid are rarely diagnostic (< 10% of cases). Pleural fluid cultures grow M tuberculosis in fewer than 65% of cases. In contrast, the combination of histology and culture of pleural tissue obtained by pleural biopsy increases the diagnostic yield for TB to 90%.
ADA activity exceeding 43 U/mL in pleural fluid supports the diagnosis of tuberculous pleuritis; however, the test has a sensitivity of only 78%. Pleural fluid ADA values lower than 43-50 U/mL do not exclude the diagnosis of tuberculous pleuritis.[57] it is important to keep in mind that ADA testing may yield both false-positive and false-negative results.
IFN-γ concentrations higher than 140 pg/mL in pleural fluid also support the diagnosis of tuberculous pleuritis. Unfortunately, this test is not routinely available.
The key diagnostic distinction between transudative effusions and exudative effusions is based on a set of laboratory biomarkers. A number of chemical tests have been proposed to differentiate pleural fluid transudates from exudates. The tests first proposed by Light et al are still widely considered the criterion standards.[58] The fluid is considered a transudate if all of the following are absent and an exudate if any of the following are found:
Pleural fluid–to–serum protein ratio >0.5
Pleural fluid–to–serum LDH ratio >0.6
Pleural fluid LDH value greater than two thirds of the upper limit of the normal serum value
The utility of these criteria notwithstanding, it is important to recognize that in some cases, distinguishing transudative from exudative effusions can be challenging. In addition, pleural fluid results can sometimes be discordant with clinical findings. Thus, it is vital to interpret pleural fluid results in the light of the overall clinical picture. Several studies have suggested that a combination of pleural fluid measurements might have sensitivity and specificity comparable to those of Light's criteria for distinguishing transudates from exudates.[59] One of the advantages of using this combination of pleural fluid measurements is that it eliminates the need to collect extra blood samples.
With this approach, an effusion may be classified as an exudate when at least one of the following conditions is present:
Pleural fluid LDH value >0.67 × upper limit of normal serum value
Pleural fluid cholesterol level > 55 mg/dL
Pleural fluid protein level >3.0 g/dL
Reported cutoff values have varied, with pleural fluid cholesterol ranging from 45 to 55 mg/dL and pleural fluid LDH from greater than 0.45 to greater than 0.67 times the upper limit of normal.[60, 59] However, the largest single-center study (N = 5299 patients used the cutoff values mentioned in the bulleted list above.[59]
Although both Light's criteria and these alternative criteria identify nearly all exudates correctly, they misclassify 20-25% of transudates as exudates (ie, they are highly sensitive for exudative pleural effusions but only moderately specific), usually in patients on long-term diuretic therapy for CHF (because of the concentrating effect of diuresis on protein and LDH levels within the pleural space).[61] In these patients, exudates can be more correctly identified by using the criterion of an SPPG lower than 3.1 g/dL, rather than a pleural fluid–to–serum ratio higher than 0.5.[62] Although pleural fluid albumin is not typically measured, an SPAG lower than 1.2 g/dL also identifies an exudate in such patients.[63]
In addition, studies have suggested that pleural fluid levels of NT-proBNP are elevated in effusions due to CHF.[64, 61] A study by Porcel et al found that elevated pleural NT-proBNP outperformed pleural fluid BNP as a marker of heart failure–related effusion.[65] Thus, at institutions where this test is available, high pleural levels of NT-proBNP (defined in different studies as >1300-4000 ng/L) may help confirm heart failure as the cause of an otherwise idiopathic chronic effusion.
In a subsequent systematic review, a pleural fluid cholesterol level higher than 55 mg/dL and a pleural LDH level higher than 200 U/L each had better positive and negative likelihood ratios for distinguishing exudates from transudates than Light’s criteria did.[44] Light's criteria may also classify as many as 10% of MPEs as transudates.
Idiopathic exudative effusions
Approximately 20-25% of exudative effusions remain undiagnosed despite having been evaluated with repeated diagnostic thoracocenteses. Diagnostic clues that may have been overlooked in this situation include the following:
Occupational exposure to asbestos 10-20 years earlier, which may suggest benign asbestos effusion
Medication exposure to nitrofurantoin, amiodarone, or medications associated with a drug-induced lupus syndrome
Hepatic hydrothorax that is unrecognized in a patient with minimal or undetectable ascites
Among patients with undiagnosed pleural effusions after the primary evaluation, those who meet all six of the following clinical parameters are predicted to have a benign course, with no need for further evaluation:
The patient is clinically stable
The patient has not lost weight
The results of the PPD test (used in diagnosing tuberculous pleural effusion) are negative, and the pleural fluid ADA value (also used in diagnosing tuberculous pleural effusion) is lower than 43 U/mL
The patient does not have a fever
The percentage of lymphocytes in the pleural fluid differential blood cell count is less than 95%
The effusion occupies less than 50% of the hemithorax
Among other patients with undiagnosed exudative effusions, approximately 20% have a specific etiology determined, including malignancy. For such patients, it is important to assess both the benefits and the risks of pursuing a diagnostic strategy that will involve using progressively more invasive procedures, given the low likelihood of finding a curable cause. Bronchoscopy should be considered if a patient has parenchymal abnormalities or hemoptysis. Pleural biopsy is sometimes indicated if the etiology remains unclear despite extensive evaluation.
Despite extensive diagnostic efforts, the underlying etiology remains unclear for nearly 20-25% of pleural effusions, necessating pleural biopsy for further evaluation. This can be accomplished by means of medical thoracoscopy, video-assisted thoracoscopic surgery (VATS), or image-guided pleural biopsy. With the wider availability of other modalities, closed needle pleural biopsy is being rendered obsolete.
Medical thoracoscopy with the patient under conscious sedation and local anesthesia has emerged as a diagnostic tool for directly visualizing and obtaining a biopsy specimen from the parietal pleura in cases of undiagnosed exudative effusions. It is generally well tolerated and has a high diagnostic yield. It can also play a dual role of being both diagnostic and therapeutic; complete drainage of the effusion and talc sclerosis can be performed at the time of the procedure.
VATS affords additional access to lung tissue and enables operative interventions, including lung biopsy, lobectomy, pericardial window placement, and empyema drainage. VATS is carried out by thoracic surgeons in an operating room with the patient under general anesthesia and receiving single-lung ventilation.[66]
Image-guided (ie, CT- or US-guided) pleural biopsy is a safe and effective method that enables targeted sampling of abnormal pleural tissue, which enhances the diagnostic yield regardless of pleural thickening. This approach remains a viable option for patients who are unable to tolerate thoracoscopy or in whom thoracoscopy has failed.
A key consideration in the management of pleural effusions is whether the effusion is transudative or exudative. Transudative effusions are managed by treating the underlying medical disorder. However, large, refractory pleural effusions that cause severe respiratory symptoms can generally be drained to provide symptomatic relief, regardless of whether they are transudative or exudative.
Management of exudative effusions depends on the underlying etiology of the effusion. Pneumonia, malignancy, and tuberculosis (TB) cause the majority of exudative pleural effusions, with the remainder typically regarded as idiopathic. Complicated parapneumonic effusions and empyemas should be drained to prevent the development of fibrosing pleuritis. Malignant pleural effusions (MPEs) are usually drained to achieve palliation of symptoms; pleurodesis (pleural sclerosis) may be required to prevent recurrence, or insertion of an indwelling pleural catheter may be indicated to facilitate recurrent drainage in a home-based setting.
Medications cause only a small percentage of pleural effusions and are associated with exudative effusions. Early recognition of this iatrogenic cause of pleural effusion avoids unnecessary additional diagnostic procedures and leads to definitive therapy—namely, discontinuance of the offending medication. Implicated drugs include medications that cause drug-induced lupus syndrome (eg, procainamide, hydralazine, and quinidine), nitrofurantoin, dantrolene, methysergide, procarbazine, and methotrexate.
A meta-analysis and systemic review of 19 observational studies determined that pleural effusion drainage in patients on mechanical ventilation is safe and appears to improve oxygenation.[67] No data supported or refuted claims of beneficial effects on clinical outcomes (eg, duration of ventilation and length of stay).
Pharmacologic management of pleural effusion depends on the condition’s etiology. For example, medical management includes diuretics for congestive heart failure (CHF) and pulmonary edema, antibiotics for parapneumonic effusion and empyema, and anticoagulation for pulmonary embolism.
In patients with parapneumonic effusions, empyemas, and effusions associated with esophageal perforation and intra-abdominal abscesses, antibiotics should be administered early when these conditions are suspected.
Antibiotic selection should be based on the suspected causative microorganisms and the overall clinical picture. Considerations include the patient's age, comorbidities, the duration of the illness, the setting (eg, community vs nursing home), and local organism sensitivities. Various effective single agents and combinations of agents exist (see Medications). Antimicrobial coverage should generally include anaerobic organisms. Options may include clindamycin, extended-spectrum penicillins, and imipenem. Aminoglycosides are not recommended for pleural infections, because of their poor pleural penetration and their susceptibility to inactivation in the acidic environment of an empyema.[68]
Intravenous (IV) antibiotics should be given initially (5-7 d), with transition to oral therapy (total, 3 wk) once clinical improvement is observed and adequate pleural fluid drainage has been obtained. Depending on the patient's clinical condition, infectious disease consultation may be appropriate.
Particular attention must be given to potential drug interactions, adverse effects, and preexisting conditions.
Management Approaches for Specific Types of Pleural Effusion
Parapneumonic effusions
Scoring systems, such as RAPID (renal, age, purulence, infection source, and dietary factors), can help identify patients at risk for a poor outcome at presentation.[22, 69] This clinical risk score, derived from the first Multicenter Intrapleural Sepsis Trial (MIST1), stratified patients into low-risk (0-2), medium-risk (3-4), and high-risk (5-7) groups. A RAPID score of 3-4 was associated with an odds ratio (OR) of 24.4 for death at 3 months, whereas a score higher than 4 was associated with an OR of 192.4.
Of the common causes of exudative pleural effusions, parapneumonic effusions have the highest diagnostic priority. Even in the face of antibiotic therapy, infected pleural effusions can rapidly coagulate and organize to form fibrous peels that might require surgical decortication. Prompt recognition of pleural fluid characteristics predictive of a complicated course is therefore essential for identifying parapneumonic effusions that require urgent tube drainage. These are observed more commonly in indolent anaerobic pneumonia than in typical community-acquired pneumonia.
Initiation of antibiotic therapy should not wait for drainage of pleural fluid. As noted, an initial IV course of 5-7 days is commonly administered to dampen the initial systemic inflammatory response. A total course of at least 3 weeks is recommended, depending on clinical, biochemical, and radiologic responses. The choice of antibiotic depends on whether the infection is community- or hospital-acquired.[22]
Patients with parapneumonic effusions who do not meet the criteria for immediate tube drainage should improve clinically within 1 week with appropriate antibiotic treatment. Patients whose clinical condition does not improve or deteriorates should be reassessed with chest computed tomography (CT), ultrasonography (US), or both to evaluate the pleural space and any direct further drainage attempts that may be needed.
Indications for drainage of parapneumonic effusions include the following[70] :
Frankly purulent fluid
Pleural fluid pH < 7.2
Loculated effusions
Bacteria on Gram stain or culture
Small-bore chest tubes are often sufficient and generally better tolerated, provided that their patency is ensured through routine checks and flushing with normal saline. Intrapleural enzymatic therapy (IPET) uses a combination of 10 mg of tissue plasminogen activator (TPA) and 5 mg of deoxyribonuclease (DNase) that is delivered twice daily through the chest tube, left in the pleural cavity for 1 hour, and followed by drainage. IPET is often initiated and managed by a pulmonary specialist or a thoracic surgeon to monitor clinical reponse and potential adverse effects.[22]
Malignant pleural effusions
MPEs are usually a signal of incurable disease, with considerable morbidity and a dismal mean survival (< 1 y). For some patients, drainage of a large MPE relieves dyspnea resulting from the distortion of the diaphragm and chest wall induced by the effusion. Such effusions recur in more than 90% of patients, necessitating repeated thoracocentesis, pleurodesis, or placement of an indwelling tunneled pleural catheter (ITPC).[66] Drainage systems using ITPCs allow patients to drain their effusions as needed at home.
For patients with lung entrapment from MPEs, ITPC drainage systems are the preferred treatment and provide good palliation of symptoms.[71] In patients without lung entrapment, ITPC drainage and pleurodesis are both good options for preventing recurrence of symptomatic effusions. When an ITPC is placed, daily drainage is prefered to improve the likelihood of autopleurodesis, a condition where the visceral and parietal pleurae are regularly apposed to each other and pleurodese with time.
The open-label randomized AMPLE-2 (Aggressive Versus Symptom-Guided Drainage of Malignant Pleural Effusion via Indwelling Pleural Catheters) trial found no differences between aggressive (daily) and symptom-guided drainage regimens for indwelling pleural catheters in providing breathlessness control.[72] However, more patients developed spontaneous pleurodesis in the aggressive group than in the symptom-guided group, both in the first 60 days (16/43 vs 5/44) and at 6 months (19/43 vs 7/44). These data indicated that a daily drainage strategy should be preferred for facilitating autopleurodesis and eventual ITPC removal.
A meta-analysis of five randomized trials comparing ITPC drainage with pleurodesis found no differences in survival or measures of dyspnea in any of the studies.[73] The total length of hospital stay was shorter with ITPC drainage, and repeat pleural interventions were less common; however, the risk of cellulitis was higher with ITPC drainage.
Guidelines for management
The 2023 British Thoracic Society (BTS) guidelines for pleural disease included the following recommendations for the management of MPEs[33] :
Use of talc pleurodesis is preferred to repeated aspiration, especially in those with a better prognosis, but the relative risks and benefits should be discussed with the patient.
Initial treatment options for patients without a known nonexpandable lung are ITPC and pleurodesis. For patients with a radiologically significant (>25%) nonexpandable lung, an ITPC is preferred to talc pleurodesis is preferred; in patients with less than 25% nonexpandable lung, talc slurry pleurodesis may improve quality of life, chest pain, breathlessness and pleurodesis rates.
Patients who elect an ITPC should receive early assessment of the wound site, symptom control, support with ITPC drainage and removal of sutures at discharge.
Talc slurry or talc poudrage may be offered to control fluid and reduce the need for repeated procedures.
Either surgical talc pleurodesis or medical talc slurry can be considered in select patients.
ITPCs are effective at controlling symptoms in nonexpandable lung, but pleural aspiration may be needed first to assess symptomatic response.
To improve breathlessness, intrapleural fibrinolytics can be considered in highly selected symptomatic patients.
The 2018 American Thoracic Society (ATS)/Society of Thoracic Surgeons (STS)/Society of Thoracic Radiology (STR) guidelines on the management of MPEs included the following recommendations[74, 75] :
Use US to guide pleural interventions in known or suspected cases of MPE.
Do not use therapeutic pleural interventions in asymptomatic patients with MPE.
Use either an ITPC or chemical pleurodesis to manage dyspnea in symptomatic patients with MPE and known or suspected expandable lung.
Perform large-volume thoracocentesis to assess lung expansion in cases where it is unclear if symptoms are associated with effusion and/or to see if the lung is expandable.
Use either talc poudrage or talc slurry for patients undergoing talc pleurodesis.
Use an ITPC instead of chemical pleurodesis in patients with nonexpandable lung, failed pleurodesis, or loculated effusion.
Use antibiotics to treat infections associated with the ITPC with the catheter in place; remove the catheter only if the infection persists.
The 2013 American College of Chest Physicians (ACCP) guidelines on diagnosis and management of lung cancer included the following recommendations for the management of MPEs[76] :
In patients with a symptomatic recurrent MPE with a reexpandable lung, ITPC placement or chemical pleurodesis is recommended. Serial thoracocentesis can be considered in patients with a limited life expectancy.
In patients with a symptomatic recurrent MPE with lung trapping, ITPC placement for symptomatic relief and improvement in quality of life is recommended.
In patients with a suspected MPE in whom the diagnosis of stage IV disease is not confirmed, thoracoscopy is recommended over ITPC placement because it provides diagnostic as well as therapeutic benefit.
Graded talc is the pleural sclerosant of choice, owing to its efficacy and safety profile.
Thoracoscopy with talc poudrage is recommended over talc slurry through a bedside chest tube for pleurodesis (if there are no contraindications for thoracoscopy).
Pleural effusions due to heart failure
Patients with symptomatic heart failure–associated pleural effusions refractory to optimal medical therapy should be evaluated for pleural interventions. Thoracocentesis is considered a reasonable low-risk option to relieve symptoms related to pleural effusion in heart failure patients. Talc pleurodesis is another option with a reasonable success rate in refractory pleural effusions necessitating frequent thoracocentesis. [77] A systemic review and meta-analysis conducted by Patil et al showed that ITPCs are also a viable option to treat recurrent benign pleural effusion, including cases related to heart failure.[78] Surgical options are rarely considered for recurrent heart failure–associated effusions.
Tuberculous pleuritis
Tuberculous pleuritis is typically self-limited. However, because 65% of patients with primary tuberculous pleuritis experience disease reactivation within 5 years, empiric anti-TB treatment is usually begun while culture results are pending when sufficient clinical grounds for suspicion (eg, an unexplained exudative or lymphocytic effusion in a patient with a positive PPD finding) are present.
Data on the benefit of corticosteroids in tuberculosis pleuritis are mixed, with several randomized trials showing early resolution of clinical symptoms and signs but no differences in residual lung function and the incidence of residual pleural thickening. Corticosteroids can be considered in patients who have severe symptoms after 2 weeks of antibiotic therapy and therapeutic thoracocentesis.[79]
Chylous effusions
In addition to initial drainage to relieve symptoms, dietary interventions are usually employed for management of chylous effusions. A high-protein, low-fat (< 10 g/day) diet with exlusion of long-chain triglycerols is recommended. Somatostatin analogues also may help reduce the efflux of chyle into the pleural space. If medical management fails, patients may require an interventional approach (eg, percutaneous thoracic duct embolization) or surgical treatment (eg, thoracic duct ligation). These are considered on the basis of local availability and expertise.[80]
Hepatic hydrothorax
Initial management of hepatic hydrothorax includes sodium restriction, diuretics, and abstinence from alcohol. In patients with recurrent effusions despite optimal medical therapy, serial thoracocentesis is the first-line measure for symptom control. If the patient requires frequent thoracocentesis, the following advanced interventions should be considered:
ITPCs are generally avoided in hepatic hydrothorax because of evidence from clinical studies showing higher complication rates and poorer survival outcomes.[55, 81] Pleurodesis attempts often have a high failure rate, attributable to rapid reaccumulation of pleural effusion with subsequent pleural separation.
Therapeutic thoracentesis is used to remove larger amounts of pleural fluid to alleviate dyspnea and to prevent ongoing inflammation and fibrosis in parapneumonic effusions. In addition to the precautions listed previously for diagnostic thoracocentesis, there are three further considerations that should be kept in mind for therapeutic thoracocentesis, as follows:
First, to avoid producing a pneumothorax during the removal of large quantities of fluid, fluid should generally be removed via a catheter, rather than a needle, introduced into the pleural space; various specially designed thoracocentesis trays are commercially available for introducing small catheters into the pleural space; alternatively, newer systems using spring-loaded blunt-tip needles that avoid lung puncture are also available
Second, oxygenation should be closely monitored both during and after thoracocentesis because arterial oxygen tension might worsen after pleural fluid drainage as a consequence of shifts in perfusion and ventilation in the reexpanding lung; empiric use of supplemental oxygen during the procedure may be considered
Third, as suggested in the 2023 BTS guidelines, no more than 1.5 L of pleural fluid should be drained at one time so as to reduce the risk of reexpansion pulmonary edema
Reexpansion pulmonary edema results from excessive negative pressure in the pleural space, surfactant deficiency, and reperfusion injury. Given that multiple studies have found its incidence to be low (0-1%),[82] it is not unreasonable to drain larger volumes to dryness, provided that the patient has no symptoms. For large-volume thoracocentesis, care should be taken to avoid high negative intrapleural pressures (negative-pressure bottle, wall suction). More gradual evacuation may be warranted for higher-risk patients (eg, those with large pneumothoraces, young patients, those whose lung has been down for longer than 7 days, and possibly those who have had more than 3 L of pleural fluid drained.[82]
There are data on beneficial use of pleural manometry during large-volume thoracocentesis, though multiple studies have shown that attention to patient symptoms (eg, chest discomfort) is equally helpful. Accordingly, in clinical practice, the use of pleural manometry is often limited to patients with a suspected nonexpandable lung or those with altered consciousness who are unable to report chest discomfort.[83, 84]
The onset of chest pressure or pain during fluid removal indicates a lung that is not freely expanding, and the procedure should be stopped immediately to avoid reexpansion pulmonary edema.[84] In contrast, cough frequently occurs during fluid removal, but it is not in itself a sufficient reason to stop the procedure unless it is causing the patient discomfort.
Mediastinal position and lung entrapment
The position of the mediastinum on the chest radiograph may predict whether a patient is likely to benefit from the procedure. A mediastinal shift away from the pleural effusion indicates a positive pleural pressure and compression of the underlying lung that can be relieved by thoracocentesis. (See the images below.)
View Image
Massive right-side pleural effusion resulting in mediastinal shift to left.
View Image
Right-side pleural effusion after partial drainage showing improved left mediastinal shift.
In contrast, a mediastinal shift toward the side of the effusion indicates an endobronchial obstruction that prevents reexpansion of the lung when the pleural fluid is removed or the lung is trapped as a result of encasement by chronic pleural thickening. Lung entrapment with MPEs is most common with mesothelioma and primary lung cancer.
Attempts at therapeutic thoracocentesis usually do not improve dyspnea in patients with lung entrapment, because of the inability of the lung to reexpand. In fact, attempts at drainage of fluid in these patients usually results in a hydropneumothorax. (See the image below.)
View Image
Lung entrapment with right hydropneumothorax and pleural drain in place.
Although small, freely flowing parapneumonic effusions can be drained by therapeutic thoracocentesis, complicated parapneumonic effusions or empyemas require drainage by tube thoracostomy.
Traditionally, large-bore (20-36F) chest tubes have been used to drain the thick pleural fluid and to break up loculations in empyemas; however, they are not always well tolerated by patients and are difficult to direct correctly into the pleural space. Small-bore (7-14F) tubes inserted at the bedside or under radiographic guidance have been demonstrated to provide adequate drainage[85] ; in addition, they cause less discomfort than large-bore tubes and are more likely to be placed successfully within a pocket of pleural fluid. Using 20 cm H2O suction and flushing the tube with normal saline every 6-8 hours may prevent occlusion of small-bore catheters.
Insertion of additional pleural catheters, usually under radiographic guidance, or instilling fibrinolytics (eg, streptokinase, urokinase, or alteplase) through the pleural catheter can help with drainage of multiloculated pleural effusions.
A randomized trial of 210 participants with pleural infection documented that instillation of alteplase and DNase, as compared with placebo, produced significantly greater drainage of pleural effusion, less need for surgical referral or surgical intervention, shorter hospital stays, and a decrease in pleural fluid inflammatory markers.[86]
Pleurodesis (pleural sclerosis) involves instilling an irritant into the pleural space to cause inflammatory changes that result in bridging fibrosis between the visceral and parietal pleural surfaces, effectively obliterating the potential pleural space. It is most often used for recurrent MPEs, such as occur in patients with lung cancer or metastatic breast or ovarian cancer. Given the limited life expectancy of these patients, the goal of therapy is to palliate symptoms while minimizing patient discomfort, hospital length of stay, and overall costs.[87, 88]
Patients with poor performance status (Karnofsky score < 70) and a life expectancy shorter than 3 months should not be treated with pleurodesis and can be treated instead with repeated outpatient thoracocentesis as needed to palliate symptoms.[89] Unfortunately, pleural effusions can reaccumulate rapidly, and the risk of complications increases with repeated drainage.
Patients with lung entrapment from MPEs are not good candidates for repeated thoracocentesis, because the procedure may not relieve their dyspnea; they are also not good candidates for pleurodesis, because the visceral and parietal pleural surfaces cannot stay apposed to allow the bridging fibrosis. The best treatment for effusions in such patients may be the insertion of an ITPC, which allows removal of pleural fluid as needed at home.[90]
A 2006 systematic review found that in pleurodesis for MPE, rotating the patient through different positions did not appear necessary to ensure distribution of soluble sclerosing agents throughout the pleural space.[91] In addition, neither protracted drainage after instillation of sclerotics nor the use of larger-bore chest tubes increased the effectiveness of pleurodesis.
Pleurodesis is likely to be successful only if the pleural space is drained completely before pleurodesis and if the lung is fully reexpanded to appose the visceral and parietal pleura after sclerosis. Data from animal studies have suggested that systemic corticosteroids can reduce inflammation during sclerosis and can cause pleurodesis failures.
Sclerosing agents
Various agents (eg, talc, doxycycline, bleomycin sulfate, zinc sulfate, and quinacrine hydrochloride) can be employed to sclerose the pleural space and effectively prevent recurrence of an MPE.
Talc is the most effective commercially available sclerosing agent. It can be administered as slurry through chest tubes or pleural catheters. Although a systematic review suggested that direct insufflation of talc via thoracoscopy was more effective than talc slurry, the two methods were equally effective in a 2005 prospective trial focusing on MPEs.[92] Because talc particles tend to occlude the small drainage holes in small pleural catheters, any pleural catheters intended for use in talc pleurodesis should be at least 10-12 French.
Doxycycline and bleomycin are also effective in most patients and can be administered more easily through small-bore catheters; however, they are somewhat less effective than talc and substantially more expensive.
All sclerosing agents can produce fever, chest pain, and nausea. Talc rarely causes more serious adverse effects, such as empyema and acute lung injury. The latter appears to be related to the particle size and the amount of talc injected for pleurodesis.
Injection of 50 mL of 1% lidocaine hydrochloride before instillation of the sclerosing agent has been advocated to help alleviate pain,[26, 66] but it is not universally used. Additional analgesia might be required in some cases. Chest tubes should be clamped for approximately 2 hours after instillation of the sclerosing agent.
Tunneled pleural catheters were approved by the US Food and Drug Administration (FDA) in 1997 and are a valid alternative for pleurodesis in MPEs and some benign effusions.[93] An ITPC can be inserted as an outpatient procedure and can be intermittently drained at home, minimizing the amount of time spent in the hospital for patients with short prognoses. Unlike pleurodesis, ITPCs can be used for patients with effusions and trapped lungs.[90]
Both talc pleurodesis and ITPCs improve dyspnea when used for MPEs, but talc pleurodesis requires significantly more days spent in the hospital and more pleural procedures.[94, 95] Consequently, ITPC placement is the most cost-effective approach for patients with MPEs who have an expected survival longer than 3 months.[96] The combination of thoracoscopic talc poudrage with simultaneous ITPC placement for rapid pleurodesis has been reported to have a 92% success rate and a median hospital stay of 1.79 days after the procedure.[97]
ITPC placement has also been shown to palliate refractory symptoms from recurrent effusions due to class III or IV heart failure, with effectiveness similar to that of thoracoscopic talc pleurodesis while being associated with a significantly shorter hospital stay, less operative morbidity, and a lower readmission rate.[98]
Complications reported from ITPC use include catheter malfunction (9.1%), clogging (3.7%), and pain (5.6%).[93] Less common but serious complications associated with ITPC use include infection (2.8%) and (in the setting of an MPE) tumor invasion of the catheter track (< 1%). Notably, systemic chemotherapy does not increase the risk of pleural infection and can be used in these patients.[89]
It is essential to record the amount and quality of fluid drained and to monitor for air leakage (bubbling through the water seal) at each shift. Large air leaks (steady streams of air throughout the respiratory cycle) may be indications of loose connectors or of a catheter drainage port that has migrated out to the skin. Consequently, dressings should be taken down and the position of the catheter inspected at the puncture site. Alternatively, such leaks may indicate large bronchopleural fistulae. Briefly clamping the catheter at the skin helps determine whether the air leak originates from within the pleural cavity (in which case it stops when the tube is clamped) or from outside the chest (in which case it persists).
When drainage decreases to less than 100 mL/day, the chest radiographs should be repeated to evaluate whether the effusion has been fully drained. If a large effusion persists radiographically, the position of the chest catheter should be reevaluated with chest CT to ensure that the drainage ports are still positioned within the pleural collection. If the catheter is positioned appropriately, injection of thrombolytics through the chest tube to break up clots that may be obstructing drainage may be considered. Alternatively, chest CT may reveal lung entrapment (trapped lung), which is unlikely to respond to further drainage.
Surgical intervention is most often required for parapneumonic effusions that cannot be drained adequately via a needle or a small-bore catheter. Surgery may also be required to establish a diagnosis and for pleural sclerosis therapy of exudative effusions. Insufflating talc directly onto the pleural surface by means of VATS is an alternative to using talc slurries for pleurodesis.
Decortication is considered for trapped lungs to remove the thick, inelastic pleural peel that restricts ventilation and produces progressive or refractory dyspnea. In patients with chronic, organizing parapneumonic pleural effusions, technically demanding operations may be required to drain loculated pleural fluid and to obliterate the pleural space.
Surgically implanted pleuroperitoneal shunts are another treatment option for recurrent, symptomatic effusions, most often in the setting of malignancy, but they are also used for management of chylous effusions. However, the shunts are prone to malfunction over time, can require surgical revision, and are poorly tolerated by patients. In unusual cases, surgery might be required to close diaphragmatic defects (thereby preventing recurrent accumulation of pleural effusions in patients with ascites) and to ligate the thoracic duct to prevent reaccumulation of chylous effusions.
Restriction of fat intake may help in the treatment of chylous effusions, though management remains controversial. Ongoing drainage of these effusions can rapidly deplete patients of fat and protein stores and lymphocytes. Limiting oral fat intake may slow the accumulation of chylous effusions in some patients. Hyperalimentation or total parenteral nutrition (TPN) can preserve nutritional stores and limit accumulation of the chylous effusion but probably should be restricted to patients in whom definitive therapy for the underlying cause of the chylous effusion is possible.
Drainage of complicated effusions usually requires consultation with a pulmonologist, an interventional radiologist, or a thoracic surgeon, depending on the location of the effusion and the clinical situation.
The following organizations have released guidelines for the workup and management of pleural effusions, including parapneumonic pleural effusions and empyema as well as malignant effusions. Key diagnostic and treatment recommendations have been reviewed and integrated throughout the article.
American College of Radiology (ACR): Workup of pleural effusion or pleural disease (2024)[32]
British Thoracic Society (BTS): Guideline for pleural disease (2023)[33]
European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS): Management of pleural infection in adults (2023)[22]
American Thoracic Society (ATS)/Society of Thoracic Surgeons (STS)/Society of Thoracic Radiology (STR): Management of malignant pleural effusions (2018)[74, 75]
American Association for Thoracic Surgery (AATS): Consensus guidelines for the management of empyema (2017)[34]
American College of Chest Physicians (ACCP): Symptom management in patients with lung cancer (2013)[76]
What is a pleural effusion (fluid on the lungs)?What is the anatomy of the pleural space?What is the role of the pleural space in respiration?What causes the formation of a pleural effusion (fluid on the lungs)?What are the physiological effects of pleural effusion (fluid on the lungs)?How are pleural effusions (fluid on the lungs) classified?What is the incidence of pleural effusions (fluid on the lungs) in the US?What is the worldwide prevalence of pleural effusions (fluid on the lungs)?Are pleural effusions (fluid on the lungs) more common in men or women?Are there racial differences in the prevalence of pleural effusions (fluid on the lungs)?Does the risk for development of pleural effusions (fluid on the lungs) vary by age?What is the effect of early treatment on the prognosis of pleural effusions (fluid on the lungs)?What factors affect the morbidity and mortality rates associated with pleural effusions (fluid on the lungs)?What is the prognosis of malignant pleural effusion?What is the role of pleural fluid analysis in determining the prognosis of malignant pleural effusion?What causes transudates in pleural effusions (fluid on the lungs)?How do exudative effusions develop in pleural effusions (fluid on the lungs)?What causes exudates in pleural effusions (fluid on the lungs)?Why is a detailed medical history required from patients presenting with pleural effusion (fluid on the lungs)?What are the signs and symptoms of a pleural effusion (fluid on the lungs)?What are the physical findings of pleural effusion (fluid on the lungs)?What should be considered in the differential diagnoses of transudative pleural effusion?Which conditions should be considered in the differential diagnoses of exudative pleural effusion (fluid on the lungs)?When is thoracentesis indicated in the evaluation of pleural effusion (fluid on the lungs)?What is the role of lab testing in the evaluation of pleural effusion (fluid on the lungs)?What are the characteristics of normal pleural fluid?Which findings on chest radiography suggest pleural effusions (fluid on the lungs)?Which type of chest radiography is more reliable in the detection of small pleural effusions?When are specialized lab tests considered in the workup for pleural effusion (fluid on the lungs)?What is the role of medical thoracoscopy in the workup for pleural effusion (fluid on the lungs)?When should CT scan–guided cutting-needle pleural biopsy (CT-CNPB) be considered in the workup of pleural effusion (fluid on the lungs)?How is pleural fluid used to differentiate transudates from exudates in the evaluation of pleural effusion (fluid on the lungs)?Which factors may lead to misclassification of transudates and exudates in the evaluation of pleural effusion (fluid on the lungs)?Can pleural fluid levels of N-terminal pro-brain natriuretic peptide (NT-proBP) be used as a marker for heart failure–related pleural effusions?Can pleural fluid cholesterol levels be used to differentiate exudates from transudates in the evaluation of pleural effusion (fluid on the lungs)?What is the role of pleural fluid LDH levels in the workup for pleural effusion (fluid on the lungs)?What is the role of pleural fluid glucose and pH levels in the evaluation pleural effusion (fluid on the lungs)?How are pleural fluid samples collected and handled during the evaluation of pleural effusion (fluid on the lungs)?What should be done if an exudate is suspected in the pleural fluid during the workup for pleural effusion (fluid on the lungs)?What is the role of pleural fluid lymphocytosis in the evaluation of pleural effusion (fluid on the lungs)?What is the role of pleural fluid eosinophilia in the workup for pleural effusion (fluid on the lungs)?What is the relevance of mesothelial cells found during the workup for pleural effusions (fluid on the lungs)?How often do cultures of pleural fluid yield positive results in the workup for pleural effusion (fluid on the lungs)?When should malignancy be suspected in the evaluation of pleural effusion (fluid on the lungs)?How much pleural fluid is recommended for cytology testing in the workup for pleural effusion (fluid on the lungs)?When are tumor markers suggestive of malignant pleural effusions?When should tuberculous pleuritis be suspected in the workup for pleural effusion (fluid on the lungs)?Are acid-fast bacillus stains of pleural fluid useful in the diagnosis of tuberculous pleural effusions?How are pleural fluid levels of adenosine deaminase (ADA) and interferon-gamma used in the diagnosis of tuberculous pleuritis?How is ultrasonography used in the workup for pleural effusion (fluid on the lungs)?What is the role of chest CT scanning in the diagnosis of suspected pleural effusion (fluid on the lungs)?When is diagnostic thoracentesis indicated in the workup for pleural effusion (fluid on the lungs)?When is a specialist needed for assistance in performing diagnostic thoracentesis in the workup for pleural effusion (fluid on the lungs)?What are the contraindications to diagnostic thoracentesis the workup for pleural effusion (fluid on the lungs)?What are the possible complications of diagnostic thoracentesis in the workup for pleural effusion (fluid on the lungs)?Which devices are used as guidance in a diagnostic thoracentesis the workup for pleural effusions (fluid on the lungs)?How is the diagnostic thoracentesis performed in the workup for pleural effusion (fluid on the lungs)?How much fluid is typically removed during a diagnostic thoracentesis procedure in the workup for pleural effusion (fluid on the lungs)?How should patients be positioned during a diagnostic thoracentesis procedure in the workup for pleural effusion (fluid on the lungs)?Should supplemental oxygen be administered during diagnostic thoracentesis in the workup for pleural effusion (fluid on the lungs)?How can complications from diagnostic thoracentesis be reduced during workup for pleural effusion (fluid on the lungs)?Is chest radiography recommended following diagnostic thoracentesis in the workup for pleural effusion (fluid on the lungs)?Which risk factors are often overlooked in undiagnosed exudative pleural effusions?After the primary evaluation of undiagnosed pleural effusions (fluid on the lungs), which clinical conditions must be met before discontinuing further evaluation?When are further invasive procedures considered in the evaluation of undiagnosed exudative pleural effusions?What are the treatment considerations in transudative pleural effusion?What are the treatment considerations in exudative pleural effusion?What is the role of medications in the development of pleural effusion (fluid on the lungs)?Is pleural effusion drainage safe in patients on mechanical ventilation?Why is the identification of parapneumonic effusions the highest diagnostic priority for patients with pleural effusion (fluid on the lungs)?What are the indications for urgent drainage of parapneumonic effusions?When is drainage of malignant pleural effusions indicated?What is the preferred treatment for lung entrapment due to malignant pleural effusions?What is the treatment for tuberculous pleuritis?How are chylous effusions managed?When is surgery indicated for pleural effusion (fluid on the lungs)?Which surgical procedures are used in the treatment of pleural effusion (fluid on the lungs)?When are consultations advisable for pleural effusion (fluid on the lungs)?When is drainage via tube thoracostomy indicated in the treatment of pleural effusion (fluid on the lungs)?Are alteplase and deoxyribonuclease (DNase) effective treatments for pleural effusion (fluid on the lungs)?How is pleurodesis (pleural sclerosis) used in the treatment of pleural effusions (fluid on the lungs)?When is pleurodesis (pleural sclerosis) indicated in the treatment of pleural effusion (fluid on the lungs)?Is pleurodesis (pleural sclerosis) an effective treatment in pleural effusion (fluid on the lungs)?Which sclerosing agents may prevent the recurrence of malignant pleural effusions?What are the adverse effects of sclerosing agents used to prevent the recurrence of malignant pleural effusions?How can pain from the use of sclerosing agents be reduced in patients with pleural effusion (fluid on the lungs)?What are the alternative treatments to pleurodesis (pleural sclerosis) for malignant pleural effusion?What are the possible complications of tunneled pleural catheters (TPC) used to treat malignant pleural effusions?How should the pleural fluid drainage be monitored in pleural effusion (fluid on the lungs)?Are chest radiographs useful in the monitoring of pleural fluid drainage in pleural effusions?Are diet restrictions recommended in the treatment of pleural effusion (fluid on the lungs)?What should be considered during a therapeutic thoracentesis in pleural effusion (fluid on the lungs)?Which symptoms indicate that a therapeutic thoracentesis should be stopped immediately in patients with pleural effusion (fluid on the lungs)?Which findings on chest radiography help identify candidates for therapeutic thoracentesis among patients with pleural effusions (fluid on the lungs)?What treatment guidelines have been released for malignant pleural effusions?What are the British Thoracic Society (BTS) guidelines for the investigation of a unilateral pleural effusion?What are the British Thoracic Society (BTS) treatment guidelines for malignant pleural effusions?When are antibiotics indicated in the management of pleural effusion (fluid on the lungs)?How are antibiotics selected in the management of pleural effusion (fluid on the lungs)?Which medications in the drug class Antibiotics, Lincosamide are used in the treatment of Pleural Effusion?Which medications in the drug class Antibiotics, Other are used in the treatment of Pleural Effusion?Which medications in the drug class Anticoagulants, Hematologic are used in the treatment of Pleural Effusion?Which medications in the drug class Carbapenems are used in the treatment of Pleural Effusion?
Enambir Singh Josan, MD, FCCP, Clinical Assistant Professor of Medicine, Departments of Interventional Pulmonology, Pulmonary Disease, and Critical Care Medicine, Graduate School of Medicine, The University of Tennessee Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Ahmad Othman, MBBS, Fellow, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Tennessee Graduate School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Guy W Soo Hoo, MD, MPH, Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Medical Intensive Care Unit, Chief, Pulmonary, Critical Care and Sleep Section, West Los Angeles VA Healthcare Center, Veteran Affairs Greater Los Angeles Healthcare System
Disclosure: Nothing to disclose.
Additional Contributors
Jeffrey Rubins, MD, Professor of Medicine, University of Minnesota Medical School; Director, Palliative Medicine, Hennepin County Medical Center
Disclosure: Nothing to disclose.
Acknowledgements
Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School
Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.
Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine
Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi
Disclosure: See below for list of all activities None None
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Gunn S, Taylor D. Diseases of the pleura. Ali J, Summer WR, Levitzky MG, eds. Pulmonary Pathophysiology. 3rd ed. New York: Lange Medical Books/McGraw-Hill; 2010. 189-208.
Large right-side pleural effusion. This effusion was noted to be malignant in nature.
Left-side pleural effusion.
Isolated left-side pleural effusion with visualized loss of left lateral costophrenic sulcus. Posteroanterior upright chest radiograph. Image from Allen R Thomas, MD.
Bilateral pleural effusions with loss of bilateral costophrenic sulci (meniscus sign). Anteroposterior upright chest radiograph. Image from Allen R Thomas, MD.
Left lateral decubitus film displaying freely layering left-side pleural effusion.
Ultrasonogram shows simple pleural effusion with anechoic fluid collection in subpulmonic space.
Ultrasonogram of pleural space shows densely septated loculation in pleural space.
Massive right-side pleural effusion resulting in mediastinal shift to left.
Right-side pleural effusion after partial drainage showing improved left mediastinal shift.
Lung entrapment with right hydropneumothorax and pleural drain in place.
Large right-side pleural effusion. This effusion was noted to be malignant in nature.
Left-side pleural effusion.
Left lateral decubitus film displaying freely layering left-side pleural effusion.
Lung entrapment with right hydropneumothorax and pleural drain in place.
Massive right-side pleural effusion resulting in mediastinal shift to left.
Right-side pleural effusion after partial drainage showing improved left mediastinal shift.
Bilateral pleural effusions with loss of bilateral costophrenic sulci (meniscus sign). Anteroposterior upright chest radiograph. Image from Allen R Thomas, MD.
Isolated left-side pleural effusion with visualized loss of left lateral costophrenic sulcus. Posteroanterior upright chest radiograph. Image from Allen R Thomas, MD.
Ultrasonogram shows large simple effusion with anechoic fluid collection. Additionally, thoracentesis needle can be seen, showing additional utility for needle placement or preprocedural site marking.
Ultrasonogram of pleural space shows densely septated loculation in pleural space.
Ultrasonogram shows simple pleural effusion with anechoic fluid collection in subpulmonic space.
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