PLEURAL EFFUSION
Etiology and Diagnostic Approach
Pleural effusion is defined as excess fluid accumulation in the pleural space. It can result from increased pleural fluid formation in the lung interstitium, parietal pleura, or peritoneal cavity, or from decreased pleural fluid removal by the parietal pleural lymphatics. The two major classes of pleural effusions are transudates, which are caused by systemic influences on pleural fluid formation or resorption, and exudates, which are caused by local influences on pleural fluid formation and resorption. Common causes of transudative effusions are left ventricular heart failure, cirrhosis, and nephrotic syndrome. Common causes of exudative effusions are bacterial pneumonia, malignancy, viral infection, and pulmonary embolism. A more comprehensive list of the etiologies of transudative and exudative pleural effusions is provided in . Additional diagnostic procedures are indicated with exudative effusions to define the cause of the local disease. Exudates fulfill at least one of the following three criteria: high pleural fluid/serum protein ratio (>0.5), pleural fluid lactate dehydrogenase (LDH) greater than two-thirds of the laboratory normal upper limit for serum LDH, or pleural/serum LDH ratio >0.6. Transudative effusions typically do not meet any of these criteria. However, these criteria misidentify about 25% of transudates as exudates. For exudative effusions, pleural fluid should also be tested for pH, glucose, white blood cell count with differential, microbiologic studies, cytology, and amylase. An algorithm for determining the etiology of a pleural effusion is presented in Fig. A subset of the most common types of pleural effusions is described in the following sections.
Transudative Pleural Effusions
Transudative pleural effusions related to left ventricular failure are often bilateral; if unilateral, right-sided effusions are more common than left-sided effusions. Thoracentesis is not always required to confirm the transudative nature of the pleural effusions if congestive heart failure is present; however, if the effusions are not comparable in size, if the pt is febrile, or if pleuritic chest pain is present, thoracentesis should be strongly considered. A pleural fluid N-terminal pro-brain natriuretic peptide (NT-proBNP) >1500 pg/mL is highly suggestive of an effusion related to congestive heart failure.
Parapneumonic Effusion/Empyema
Parapneumonic effusions are exudates that are associated with contiguous bacterial lung infections, including pneumonia and lung abscess. In the setting of pulmonary infections, the presence of free pleural fluid can be demonstrated with a lateral decubitus x-ray, chest CT scan, or ultrasound. If the pleural fluid is grossly purulent, it is referred to as an empyema. Tube thoracostomy (i.e., chest tube) for management of parapneumonic effusions is likely indicated if any of the following applies (in descending order of importance): (1) gross pus is present, (2) Gram’s stain or culture of pleural fluid is positive, (3) pleural fluid glucose is <3.3 mmol/L (<60 mg/dL), (4) pleural fluid pH is <7.20, or (5) there is loculated pleural fluid. If chest tube drainage does not result in complete removal of pleural fluid, a fibrinolytic agent (e.g., tissue plasminogen activator 10 mg) can be instilled through the tube, or thoracoscopy can be performed to lyse adhesions. If these approaches are not effective, surgical decortication may be required.
Malignant Pleural Effusions
Metastatic cancer is a common cause of exudative pleural effusions. Tumors that frequently cause malignant effusions include lung cancer, breast cancer, and lymphoma. The pleural fluid glucose level may be markedly reduced. Cytologic examination of the pleural fluid is usually diagnostic. If cytologic examination of thoracentesis fluid is negative, thoracoscopy should be considered. Symptomatic relief of dyspnea can be provided by therapeutic thoracentesis. If the pleural fluid recurs, pleural sclerosis can be performed with pleural abrasion via thoracoscopy or with instillation of a sclerosing agent, such as doxycycline, through a chest tube; alternatively, a small indwelling catheter can be placed.
Effusions Related to Pulmonary Thromboembolism
Pleural effusions in pulmonary thromboembolism are usually exudative but can be transudative. The presence of a pleural effusion does not alter the standard treatment for pulmonary embolism . If the effusion increases in size during anticoagulation treatment, possible explanations include recurrent embolism, hemothorax, or empyema.
Tuberculous Pleuritis
Usually associated with primary tuberculosis (Tb) infection, tuberculous pleural effusions are exudative with predominant lymphocytosis. High levels of Tb markers in the pleural fluid, such as adenosine deaminase and interferon γ, are present. Mycobacterial cultures obtained from pleural fluid (low positive culture rate) or pleural biopsy (high positive culture rate with needle biopsy or thoracoscopy) can definitively confirm the diagnosis. Although tuberculous pleuritis often resolves without treatment, active tuberculosis can develop years later if antimycobacterial treatment is not given.
Effusion Secondary to Viral Infection
No diagnosis is established for approximately 20% of exudative effusions, and viral infections likely account for many of these cases. Pleural effusions related to viral infection resolve spontaneously.
Rheumatoid Arthritis (RA)
RA can cause pleural effusions that are exudative. Effusions may precede particular symptoms. Pleural fluid shows very low glucose and pH. Rheumatoid pleural effusions are usually seen in males.
Chylothorax
Chylothorax is an exudative pleural effusion with milky fluid and an elevated triglyceride level (>1.2 mmol/L or >110 mg/dL). The most common etiologies are trauma to the thoracic duct and mediastinal tumors. Chest tube placement is often required, and octreotide administration may be beneficial. Prolonged chest tube drainage can lead to malnutrition.
Hemothorax
Hemothorax commonly results from trauma; blood vessel rupture and tumor are other potential etiologies. When frankly bloody pleural fluid is noted at thoracentesis, the hematocrit should be tested. If the hematocrit of the pleural fluid is >50% of the bloodstream hematocrit, a hemothorax is present. Chest tube placement is typically required. If pleural blood loss is >200 mL/h, thoracic surgical intervention should be pursued.
PNEUMOTHORAX
Pneumothorax (Ptx) is defined as gas in the pleural space. Spontaneous Ptx occurs without trauma to the thorax. Primary spontaneous Ptx occurs in the absence of underlying lung disease and typically results from apical pleural blebs. Simple aspiration may be adequate treatment for an initial primary spontaneous Ptx, but recurrence typically requires thoracoscopic intervention. Secondary spontaneous Ptx occurs in the setting of underlying lung disease, most commonly chronic obstructive pulmonary disease. Chest tube placement is typically required for secondary spontaneous Ptx; thoracoscopy and/or pleurodesis (with pleural abrasion or a sclerosing agent) should also be considered. Traumatic Ptx, resulting from either penetrating or nonpenetrating chest trauma, usually requires chest tube placement. Iatrogenic Ptx can occur from transthoracic needle biopsy, thoracentesis, placement of a central venous catheter, or transbronchial biopsy. Treatment with O2 or aspiration is often adequate for iatrogenic Ptx, but chest tube placement may be required. Tension Ptx can result from trauma or mechanical ventilation. Positive pleural pressure in mechanical ventilation can rapidly lead to a tension Ptx with reduced cardiac output. Urgent treatment is required, either with a chest tube or, if not immediately available, with a large-bore needle inserted into the pleural space through the second anterior intercostal space.
MEDIASTINAL DISEASE
Mediastinitis
Mediastinitis can be an acute or chronic process. Acute mediastinitis can result from esophageal perforation or after cardiac surgery with median sternotomy. Esophageal perforation can occur spontaneously or iatrogenically; surgical exploration of the mediastinum, repair of the esophageal perforation, and drainage of the pleural space and mediastinum are required. Mediastinitis after median sternotomy typically presents with wound drainage and is diagnosed by mediastinal needle aspiration. Treatment requires immediate drainage, debridement, and IV antibiotics. Chronic mediastinitis can cause a spectrum of disease ranging from granulomatous inflammation of lymph nodes to fibrosing mediastinitis. Chronic mediastinitis is commonly caused by Tb and histoplasmosis; other etiologies are also possible, including sarcoidosis and silicosis. Granulomatous mediastinal inflammation is usually asymptomatic. Fibrosing mediastinitis causes symptoms related to compression of mediastinal structures, such as the superior vena cava, esophagus, or large airways. Fibrosing mediastinitis is very difficult to treat.
Mediastinal Masses
Different types of mediastinal masses are found in the anterior, middle, and posterior mediastinal compartments. The most common mass lesions in the anterior mediastinum are thymomas, lymphomas, teratomas, and thyroid lesions. In the middle mediastinum, vascular masses, enlarged lymph nodes (e.g., metastatic cancer or granulomatous disease), and bronchogenic or pleuropericardial cysts are found. Posterior mediastinal masses include neurogenic tumors, gastroenteric cysts, and esophageal diverticula. CT scans are invaluable for evaluating mediastinal masses. Barium swallow studies can assist in evaluating posterior mediastinal masses. Biopsy procedures are typically required to diagnose mediastinal masses; needle biopsy procedures (e.g., percutaneous or bronchoscopy), mediastinoscopy, and thoracoscopy are potential options.
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