The pleural space lies between the lung and the chest wall and normally contains a very thin layer of fluid, which serves as a coupling system. A pleural effusion is present when there is an excess quantity of fluid in the pleural space.
Pleural fluid accumulates when pleural fluid formation exceeds pleural fluid absorption. Normally, fluid enters the pleural space from the capillaries in the parietal pleura and is removed via the lymphatics in the parietal pleura. Fluid also can enter the pleural space from the interstitial spaces of the lung via the visceral pleura or from the peritoneal cavity via small holes in the diaphragm. The lymphatics have the capacity to absorb 20 times more fluid than is formed normally. Accordingly, a pleural effusion may develop when there is excess pleural fluid formation (from the interstitial spaces of the lung, the parietal pleura, or the peritoneal cavity) or when there is decreased fluid removal by the lymphatics.
When a patient is found to have a pleural effusion, an effort should be made to determine the cause (Fig. 263-1). The first step is to determine whether the effusion is a transudate or an exudate. A transudative pleural effusion occurs when systemic factors that influence the formation and absorption of pleural fluid are altered. The leading causes of transudative pleural effusions in the United States are left-ventricular failure and cirrhosis. An exudative pleural effusion occurs when local factors that influence the formation and absorption of pleural fluid are altered. The leading causes of exudative pleural effusions are bacterial pneumonia, malignancy, viral infection, and pulmonary embolism. The primary reason for making this differentiation is that additional diagnostic procedures are indicated with exudative effusions to define the cause of the local disease.
Approach to the diagnosis of pleural effusions. CHF, congestive heart failure; CT, computed tomography; LDH, lactate dehydrogenase; PE, pulmonary embolism; TB, tuberculosis; PF, pleural fluid.
Transudative and exudative pleural effusions are distinguished by measuring the lactate dehydrogenase (LDH) and protein levels in the pleural fluid. Exudative pleural effusions meet at least one of the following criteria, whereas transudative pleural effusions meet none:
Pleural fluid protein/serum protein >0.5
Pleural fluid LDH/serum LDH >0.6
Pleural fluid LDH more than two-thirds normal upper limit for serum
These criteria misidentify ~25% of transudates as exudates. If one or more of the exudative criteria are met and the patient is clinically thought to have a condition producing a transudative effusion, the difference between the protein levels in the serum and the pleural fluid should be measured. If this gradient is >31 g/L (3.1 g/dL), the exudative categorization by these criteria can be ignored because almost all such patients have a transudative pleural effusion.
If a patient has an exudative pleural effusion, the following tests on the pleural fluid should be obtained: description of the appearance of the fluid, glucose level, differential cell count, microbiologic studies, and cytology.
Effusion Due to Heart Failure
The most common cause of pleural effusion is left-ventricular failure. The effusion occurs because the increased amounts of fluid in the lung interstitial spaces exit in part across the visceral pleura; this overwhelms the capacity of the lymphatics in the parietal pleura to remove fluid. In patients with heart failure, a diagnostic thoracentesis should be performed if the effusions are not bilateral and comparable in size, if the patient is febrile, or if the patient has pleuritic chest pain to verify that the patient has a transudative effusion. Otherwise the patient's heart failure is treated. If the effusion persists despite therapy, a diagnostic thoracentesis should be performed. A pleural fluid N-terminal pro-brain natriuretic peptide (NT-proBNP) >1500 pg/mL is virtually diagnostic of an effusion secondary to congestive heart failure.
Pleural effusions occur in ~5% of patients with cirrhosis and ascites. The predominant mechanism is the direct movement of peritoneal fluid through small openings in the diaphragm into the pleural space. The effusion is usually right-sided and frequently is large enough to produce severe dyspnea.
Parapneumonic effusions are associated with bacterial pneumonia, lung abscess, or bronchiectasis and are probably the most common cause of exudative pleural effusion in the United States. Empyema refers to a grossly purulent effusion.
Patients with aerobic bacterial pneumonia and pleural effusion present with an acute febrile illness consisting of chest pain, sputum production, and leukocytosis. Patients with anaerobic infections present with a subacute illness with weight loss, a brisk leukocytosis, mild anemia, and a history of some factor that predisposes them to aspiration.
The possibility of a parapneumonic effusion should be considered whenever a patient with bacterial pneumonia is initially evaluated. The presence of free pleural fluid can be demonstrated with a lateral decubitus radiograph, computed tomography (CT) of the chest, or ultrasound. If the free fluid separates the lung from the chest wall by >10 mm, a therapeutic thoracentesis should be performed. Factors indicating the likely need for a procedure more invasive than a thoracentesis (in increasing order of importance) include the following:
Loculated pleural fluid
Pleural fluid pH <7.20
Pleural fluid glucose <3.3 mmol/L (<60 mg/dL)
Positive Gram stain or culture of the pleural fluid
Presence of gross pus in the pleural space
If the fluid recurs after the initial therapeutic thoracentesis and if any of these characteristics are present, a repeat thoracentesis should be performed. If the fluid cannot be completely removed with the therapeutic thoracentesis, consideration should be given to inserting a chest tube and instilling a fibrinolytic agent (e.g., tissue plasminogen activator, 10 mg) or performing a thoracoscopy with the breakdown of adhesions. Decortication should be considered when these measures are ineffective.
Effusion Secondary to Malignancy
Malignant pleural effusions secondary to metastatic disease are the second most common type of exudative pleural effusion. The three tumors that cause ~75% of all malignant pleural effusions are lung carcinoma, breast carcinoma, and lymphoma. Most patients complain of dyspnea, which is frequently out of proportion to the size of the effusion. The pleural fluid is an exudate, and its glucose level may be reduced if the tumor burden in the pleural space is high.
The diagnosis usually is made via cytology of the pleural fluid. If the initial cytologic examination is negative, thoracoscopy is the best next procedure if malignancy is strongly suspected. At the time of thoracoscopy, a procedure such as pleural abrasion should be performed to effect a pleurodesis. An alternative to thoracoscopy is CT- or ultrasound-guided needle biopsy of pleural thickening or nodules. Patients with a malignant pleural effusion are treated symptomatically for the most part, since the presence of the effusion indicates disseminated disease and most malignancies associated with pleural effusion are not curable with chemotherapy. The only symptom that can be attributed to the effusion itself is dyspnea. If the patient's lifestyle is compromised by dyspnea and if the dyspnea is relieved with a therapeutic thoracentesis, one of the following procedures should be considered: (1) insertion of a small indwelling catheter or (2) tube thoracostomy with the instillation of a sclerosing agent such as doxycycline, 500 mg.
Malignant mesotheliomas are primary tumors that arise from the mesothelial cells that line the pleural cavities; most are related to asbestos exposure. Patients with mesothelioma present with chest pain and shortness of breath. The chest radiograph reveals a pleural effusion, generalized pleural thickening, and a shrunken hemithorax. Thoracoscopy or open pleural biopsy is usually necessary to establish the diagnosis. Chest pain should be treated with opiates, and shortness of breath with oxygen and/or opiates.
Effusion Secondary to Pulmonary Embolization
The diagnosis most commonly overlooked in the differential diagnosis of a patient with an undiagnosed pleural effusion is pulmonary embolism. Dyspnea is the most common symptom. The pleural fluid is almost always an exudate. The diagnosis is established by spiral CT scan or pulmonary arteriography (Chap. 262). Treatment of a patient with a pleural effusion secondary to pulmonary embolism is the same as it is for any patient with pulmonary emboli. If the pleural effusion increases in size after anticoagulation, the patient probably has recurrent emboli or another complication, such as a hemothorax or a pleural infection.
(See also Chap. 165) In many parts of the world, the most common cause of an exudative pleural effusion is tuberculosis (TB), but tuberculous effusions are relatively uncommon in the United States. Tuberculous pleural effusions usually are associated with primary TB and are thought to be due primarily to a hypersensitivity reaction to tuberculous protein in the pleural space. Patients with tuberculous pleuritis present with fever, weight loss, dyspnea, and/or pleuritic chest pain. The pleural fluid is an exudate with predominantly small lymphocytes. The diagnosis is established by demonstrating high levels of TB markers in the pleural fluid (adenosine deaminase >40 IU/L or interferon γ >140 pg/mL). Alternatively, the diagnosis can be established by culture of the pleural fluid, needle biopsy of the pleura, or thoracoscopy. The recommended treatments of pleural and pulmonary TB are identical (Chap. 165).
Effusion Secondary to Viral Infection
Viral infections are probably responsible for a sizable percentage of undiagnosed exudative pleural effusions. In many series, no diagnosis is established for ~20% of exudative effusions, and these effusions resolve spontaneously with no long-term residua. The importance of these effusions is that one should not be too aggressive in trying to establish a diagnosis for the undiagnosed effusion, particularly if the patient is improving clinically.
A chylothorax occurs when the thoracic duct is disrupted and chyle accumulates in the pleural space. The most common cause of chylothorax is trauma (most frequently thoracic surgery), but it also may result from tumors in the mediastinum. Patients with chylothorax present with dyspnea, and a large pleural effusion is present on the chest radiograph. Thoracentesis reveals milky fluid, and biochemical analysis reveals a triglyceride level that exceeds 1.2 mmol/L (110 mg/dL). Patients with chylothorax and no obvious trauma should have a lymphangiogram and a mediastinal CT scan to assess the mediastinum for lymph nodes. The treatment of choice for most chylothoraxes is insertion of a chest tube plus the administration of octreotide. If these modalities fail, a pleuroperitoneal shunt should be placed unless the patient has chylous ascites. An alternative treatment is ligation of the thoracic duct. Patients with chylothoraxes should not undergo prolonged tube thoracostomy with chest tube drainage because this will lead to malnutrition and immunologic incompetence.
When a diagnostic thoracentesis reveals bloody pleural fluid, a hematocrit should be obtained on the pleural fluid. If the hematocrit is more than one-half of that in the peripheral blood, the patient is considered to have a hemothorax. Most hemothoraxes are the result of trauma; other causes include rupture of a blood vessel or tumor. Most patients with hemothorax should be treated with tube thoracostomy, which allows continuous quantification of bleeding. If the bleeding emanates from a laceration of the pleura, apposition of the two pleural surfaces is likely to stop the bleeding. If the pleural hemorrhage exceeds 200 mL/h, consideration should be given to thoracoscopy or thoracotomy.
Miscellaneous Causes of Pleural Effusion
There are many other causes of pleural effusion (Table 263-1). Key features of some of these conditions are as follows: If the pleural fluid amylase level is elevated, the diagnosis of esophageal rupture or pancreatic disease is likely. If the patient is febrile, has predominantly polymorphonuclear cells in the pleural fluid, and has no pulmonary parenchymal abnormalities, an intraabdominal abscess should be considered.
Table 263-1 Differential Diagnoses of Pleural Effusions |Favorite Table|Download (.pdf)
Table 263-1 Differential Diagnoses of Pleural Effusions
|Transudative Pleural Effusions|
1. Congestive heart failure
3. Pulmonary embolization
4. Nephrotic syndrome
5. Peritoneal dialysis
6. Superior vena cava obstruction
|Exudative Pleural Effusions|
1. Neoplastic diseases
a. Metastatic disease
2. Infectious diseases
a. Bacterial infections
c. Fungal infections
d. Viral infections
e. Parasitic infections
3. Pulmonary embolization
4. Gastrointestinal disease
a. Esophageal perforation
b. Pancreatic disease
c. Intraabdominal abscesses
d. Diaphragmatic hernia
e. After abdominal surgery
f. Endoscopic variceal sclerotherapy
g. After liver transplant
5. Collagen vascular diseases
a. Rheumatoid pleuritis
b. Systemic lupus erythematosus
c. Drug-induced lupus
d. Immunoblastic lymphadenopathy
e. Sjögren's syndrome
f. Granulomatosis with polyangiitis (Wegener's)
g. Churg-Strauss syndrome
6. Post-coronary artery bypass surgery
7. Asbestos exposure
10. Meigs' syndrome
11. Yellow nail syndrome
12. Drug-induced pleural disease
13. Trapped lung
14. Radiation therapy
15. Post-cardiac injury syndrome
17. Iatrogenic injury
18. Ovarian hyperstimulation syndrome
19. Pericardial disease
The diagnosis of an asbestos pleural effusion is one of exclusion. Benign ovarian tumors can produce ascites and a pleural effusion (Meigs' syndrome), as can the ovarian hyperstimulation syndrome. Several drugs can cause pleural effusion; the associated fluid is usually eosinophilic. Pleural effusions commonly occur after coronary artery bypass surgery. Effusions occurring within the first weeks are typically left-sided and bloody, with large numbers of eosinophils, and respond to one or two therapeutic thoracenteses. Effusions occurring after the first few weeks are typically left-sided and clear yellow, with predominantly small lymphocytes, and tend to recur. Other medical manipulations that induce pleural effusions include abdominal surgery; radiation therapy; liver, lung, or heart transplantation; and the intravascular insertion of central lines.
Pneumothorax is the presence of gas in the pleural space. A spontaneous pneumothorax is one that occurs without antecedent trauma to the thorax. A primary spontaneous pneumothorax occurs in the absence of underlying lung disease, whereas a secondary pneumothorax occurs in its presence. A traumatic pneumothorax results from penetrating or nonpenetrating chest injuries. A tension pneumothorax is a pneumothorax in which the pressure in the pleural space is positive throughout the respiratory cycle.
Primary Spontaneous Pneumothorax
Primary spontaneous pneumothoraxes are usually due to rupture of apical pleural blebs, small cystic spaces that lie within or immediately under the visceral pleura. Primary spontaneous pneumothoraxes occur almost exclusively in smokers; this suggests that these patients have subclinical lung disease. Approximately one-half of patients with an initial primary spontaneous pneumothorax will have a recurrence. The initial recommended treatment for primary spontaneous pneumothorax is simple aspiration. If the lung does not expand with aspiration or if the patient has a recurrent pneumothorax, thoracoscopy with stapling of blebs and pleural abrasion is indicated. Thoracoscopy or thoracotomy with pleural abrasion is almost 100% successful in preventing recurrences.
Most secondary pneumothoraxes are due to chronic obstructive pulmonary disease, but pneumothoraxes have been reported with virtually every lung disease. Pneumothorax in patients with lung disease is more life-threatening than it is in normal individuals because of the lack of pulmonary reserve in these patients. Nearly all patients with secondary pneumothorax should be treated with tube thoracostomy. Most should also be treated with thoracoscopy or thoracotomy with the stapling of blebs and pleural abrasion. If the patient is not a good operative candidate or refuses surgery, pleurodesis should be attempted by the intrapleural injection of a sclerosing agent such as doxycycline.
Traumatic pneumothoraxes can result from both penetrating and nonpenetrating chest trauma. Traumatic pneumothoraxes should be treated with tube thoracostomy unless they are very small. If a hemopneumothorax is present, one chest tube should be placed in the superior part of the hemithorax to evacuate the air and another should be placed in the inferior part of the hemithorax to remove the blood. Iatrogenic pneumothorax is a type of traumatic pneumothorax that is becoming more common. The leading causes are transthoracic needle aspiration, thoracentesis, and the insertion of central intravenous catheters. Most can be managed with supplemental oxygen or aspiration, but if these measures are unsuccessful, a tube thoracostomy should be performed.
This condition usually occurs during mechanical ventilation or resuscitative efforts. The positive pleural pressure is life-threatening both because ventilation is severely compromised and because the positive pressure is transmitted to the mediastinum, resulting in decreased venous return to the heart and reduced cardiac output.
Difficulty in ventilation during resuscitation or high peak inspiratory pressures during mechanical ventilation strongly suggest the diagnosis. The diagnosis is made by physical examination showing an enlarged hemithorax with no breath sounds, hyperresonance to percussion, and shift of the mediastinum to the contralateral side. Tension pneumothorax must be treated as a medical emergency. If the tension in the pleural space is not relieved, the patient is likely to die from inadequate cardiac output or marked hypoxemia. A large-bore needle should be inserted into the pleural space through the second anterior intercostal space. If large amounts of gas escape from the needle after insertion, the diagnosis is confirmed. The needle should be left in place until a thoracostomy tube can be inserted.