H. Pleural Effusion

Introduction

Normally, very small amounts of pleural fluid are present in the pleural spaces, and fluid is not detectable by routine methods. When certain disorders occur, excessive pleural fluid may accumulate and cause pulmonary signs and symptoms. Simply put, pleural effusions occur when the rate of fluid formation exceeds that of fluid absorption. Once a symptomatic, unexplained pleural effusion occurs, a diagnosis needs to be established.

Signs and Symptoms

Pleuritic chest pain, chest pressure, dyspnea, and cough are the most common symptoms of pleural effusion. Pain may occur with little fluid formation as the symptom is related to the intense inflammation of the pleural surfaces. Chest pressure usually does not occur until the effusion is in the moderate (500-1500 ml) to large (>1500 ml) category. Dyspnea rarely occurs with small effusions unless significant pleurisy is present and often the patient will not complain of dyspnea until the effusion is massive with contralateral mediastinal shift on the chest x-ray. Cough is usually related to the associated atelectasis, which to some degree accompanies all pleural effusions. Classic physical findings associated with pleural effusions may occur when the volume begins to exceed 500 ml and include diminished breath sounds, dullness to percussion, reduced tactile and vocal fremitus, and occasionally a pleural friction rub. In contrast to pneumonia and atelectasis, crackles are not heard with an isolated pleural effusion.

Noninvasive Diagnostic Techniques

When the presence of a pleural effusion is suspected by physical examination, confirmation with a chest x-ray is necessary. With some pleural effusions, especially when subpulmonic in location (layering below the lung but above the hemidiaphragm), a lateral decubitus film usually confirms the presence of fluid. Pleural space ultrasound is extremely helpful to locate small amounts or isolated loculated pockets of fluid. Thoracentesis can be performed simultaneously using ultrasound guidance. Chest CT is most helpful to distinguish between parenchymal and pleural disease and may demonstrate pleural thickening, pleural calcification, a pleural based mass, or loculated collections of fluid.

Thoracentesis and Pleural Fluid Analysis

To establish the etiology, a thoracentesis usually needs to be performed. Fifty to 100 ml of fluid are usually removed and sent for analysis (See Table 14). Not every effusion needs to be tapped, but when the patient has no obvious clinical cause for the effusion, is febrile, or has pulmonary compromise, fluid should be removed. The first step is to determine if the fluid is a transudate or an exudate. Transudative effusions occur when systemic factors that influence the formation and absorption of pleural fluid are altered (e.g., low serum proteins and increased pulmonary venous pressure). Exudative effusions occur when local factors that influence the formation and absorption of fluid are altered (e.g., infection and malignancy). The lactate dehydrogenase (LDH), protein levels or specific gravity of the fluid can distinguish these two. Most agree that exudates must meet one or more of the following criteria, whereas transudates meet none:

Pleural fluid/serum protein > 0.5 or absolute value > 3 g/dl.
Pleural fluid/serum LDH > 0.6 or absolute value > 0.45 upper normal serum limit
Pleural fluid specific gravity > 1.018

Once an effusion is categorized as transudative or exudative, etiologic considerations narrow. Additional pleural fluid studies that help to establish a diagnosis include glucose, amylase, white blood cell counts with differential, and cytologic and microbiologic examination.

Etiology of Pleural Effusions

Transudates: The causes of transudative pleural effusions are listed in Table 15.

Congestive Heart Failure:
This is the most common cause of pleural effusion. Frequently the effusions are bilateral (approximately 75% of the time) but may occur alone on either side with the right side being more common. Fluid is usually straw colored, with low white blood cell counts (<500 cells/mm3) and a mononuclear cell predominance. With severe congestive heart failure, fluid may persist in spite of vigorous diuresis.

Cirrhosis, Nephrotic Syndrome, and Hepatic Hydrothorax:
In disorders associated with low serum proteins and ascites, bilateral effusions are common. Cell counts are low and lymphocytes predominate. Glucose remains normal (>60 mg/dl). Hepatic hydrothorax occurs in about 5% of patients with ascites and cirrhosis. The effusion occurs (usually on the right side) because of direct movement of peritoneal fluid through communications in the hemidiaphragm.

Exudates: The causes of exudative pleural effusions are listed in Table 16. The most common causes of exudative pleural effusions are parapneumonic (associated with pneumonia), malignancy, pulmonary embolism, trauma (including hemothorax and esophageal perforation), collagen vascular disease (especially rheumatoid arthritis), post-cardiac injury (including surgery), tuberculosis, trapped lung, and atelectasis. The characteristics of pleural fluids are listed in Table 17.

Parapneumonic Effusion:
Bacterial pneumonias are frequently associated with pleural effusions (as often as 50 % of the time) and when they become complicated, require drainage. Complicated parapneumonic effusions include empyema (the finding of gross pus in the pleural space), those with positive pleural fluid cultures or Gram stains, and those in which the microbiology is negative but the patient continues to show signs of infection with fever, severe pleuritic pain and leukocytosis. In this last category the pleural fluid usually shows high white blood cell counts with polymorphonuclear predominance, glucose <30 mg/dl, and high LDH (>500 units/dl). Complicated parapneumonic effusions require drainage by tube thoracoscopy. The patient who has pneumonia with a small amount of pleural fluid present and is clinically responding to antibiotic therapy (now afebrile, no pleuritic pain, normal white blood cell count) does not require thoracentesis. By contrast, rapid accumulation of pleural fluid in a patient with pneumonia is an indication for immediate thoracentesis.

Malignant Effusions: Malignancy is the second most common cause of exudative pleural effusions with lung (36%), breast (25%) and lymphoma (10%) being the most frequent causes. Typical pleural fluid characteristics include a mononuclear predominant exudate (average 2500 cells/mm3), with an average red blood cell count of 40,000 cells/mm3, normal glucose (>60mg/dl) and positive cytology. At the time of diagnosis one-third of patients have a low pleural fluid glucose (<60mg/dl), which is associated with more extensive disease and a poorer prognosis.

Effusion Secondary to Pulmonary Embolism: These exudative effusions are usually bloody, and associated with pleurisy and dyspnea. The effusion may increase in size the first 24-48 hours after initial anticoagulation. Unless there is significant pulmonary compromise, or the effusion continues to increase, these effusions can be observed. There are reports of transudative effusions associated with pulmonary embolism, but atelectasis secondary to splinting from pleurisy is a more likely cause.

Tuberculous Effusion: Typically, this predominantly lymphocytic exudate is devoid of mesothelial cells and may occur without any obvious parenchymal involvement. The glucose may be low (<60 mg/dl) and adenosine deaminase levels are usually elevated (>70 IU/l). Historically, in the non-immunocompromised host, pleural fluid smears are rarely positive but pleural fluid cultures are positive in 25%. In contrast, thoracoscopic pleural biopsy and culture is positive more than 80% of the time. Initially the tuberculin skin test (TST) may be negative but after a 6 to 8 week observation time usually converts to positive. Although tuberculous pleurisy that develops in the course of primary infection is a self-limited disease that clears without treatment, in as many as 65% of these patients pulmonary tuberculosis or disease elsewhere will develop within 5 years. If all tests, including the TST, are negative but tuberculous pleurisy is suspected, a repeat TST should be done and if positive the patient requires 6 months of multidrug therapy.

Effusions Secondary to Collagen Vascular Disease: Effusions secondary to rheumatoid arthritis are predominantly mononuclear cell exudates, typically with very low glucose levels (<10mg/dl), high titers of rheumatoid factor (>640) and a cloudy appearance (pseudochylous or cholesterol effusions). They are usually moderate in size and unilateral. In systemic lupus erythematosus effusions are usually small, bilateral and are polymorphonuclear exudates. The finding of an ANA titer that exceeds that of serum is diagnostic. Severe pleurisy is frequent.

Miscellaneous: Atelectasis is a common cause of small to moderate effusions. Frequently they are seen postoperatively or with prolonged bed rest and inactivity. There are no unique diagnostic features and these effusions usually fit exudative criteria, have normal glucose levels, and WBC counts of 1000 to 2000 cells/mm3 with mononuclear cell predominance. Transudates may occur with atelectasis. Since this is a diagnosis of exclusion, other causes of pleural effusions must be eliminated. Esophageal rupture and pancreatitis produce polymorphonuclear-predominant exudative effusions, with high amylase and normal or low glucose (< 30 mg/dl) values. Chylothorax occurs when the thoracic duct is disrupted and is characterized by the presence of chylomicrons and triglyceride values of >110 mg/dl in the pleural fluid. Lymphoma, trauma, and thoracic surgery are the most common causes of chylothorax. Dressler’s syndrome may occur as a complication of myocardial infarction or open-heart surgery; the resulting pleural fluid demonstrates a polymorphonuclear-predominant exudate without specific findings. With a trapped lung (one that cannot fully expand secondary to a visceral pleural peel), exudative pleural fluid fills the pleural space and the characteristics of the fluid depend on the etiology (e.g., malignancy, post-parapneumonic, trauma).

Diagnostic Thoracoscopy and Pleural Biopsy

Thoracoscopy is an excellent technique to determine the etiology of an undiagnosed exudative pleural effusion. The procedure is superior to the old closed pleural biopsy techniques because of its higher diagnostic yield. A rigid thoracoscope with a cold light source is used and second point of entry is necessary to provide biopsy forceps access to the pleural space. This technique continues to be most helpful in diagnosing malignant effusions (including mesothelioma), tuberculosis, and trapped lung.

When to Refer

Depending on local medical practice, referral to determine if thoracentesis is necessary and to perform the thoracentesis may be most appropriate. Because some imaging techniques including ultrasound and chest CT may be necessary to coordinate thoracentesis and chest tube placement, referral to combine these efforts is indicated. In patients with persistent and undiagnosed pleural effusions, or effusions in severely ill patients with pneumonia, referral to facilitate prompt diagnostic and therapeutic measures is recommended. This includes evaluation for thoracoscopy, chest tube placement and pleurodesis.

Medicolegal Concerns

Most medicolegal issues involving pleural disease are usually related to complications that occur in the following situations: 1) lack of appropriate follow-up (e.g., complicated parapneumonic effusion resulting in fibrothorax), 2) system failure where physicians do not receive critical data (e.g., a positive TB culture at 8 weeks), and 3) missed diagnosis of a potentially life threatening event such as a pulmonary embolism. ALWAYS, always follow up on pleural fluid cultures and cytologies.

Summary

Pleural effusions are associated with many systemic disorders. Thoracentesis to determine if the pleural fluid is a transudate or an exudate coupled with other appropriate diagnostic studies provides a diagnosis most of the time. Because pleural fluid findings are often nonspecific (except for positive cytology and bacteriology), clinical correlation and response to therapy are critical. Not every pleural fluid study needs to be ordered on every pleural effusion. Clinical judgement remains the key.

References

Heffner JE. Evaluating diagnostic tests in the pleural space. Clin Chest Med 1998;19.2:277-293. Excellent somewhat sophisticated article which looks at the most commonly used pleural fluid studies to determine between transudates and exudates.

Light RL. Disorders of the Pleura. Harrison’s Principles of Internal Medicine 1998; chapter 262, 13472-1475. A classic review of etiology and features of pleural effusions, which is well summarized.

Sahn SA. Malignancy metastatic to the pleura. Clin Chest Med 1998;19.2:351-361. Well organized and well written article that covers pathogenesis, clinical presentation, pleural fluid characteristics, diagnosis, prognosis and treatment of malignant effusions. An excellent reference list is provided.

Roper WH. Primary serofibrinous pleural effusion in military personnel. Am Rev Tuberc 1955;71:616-634. A classic article hat drives home the point that an untreated tuberculous effusion will usually spontaneously resolve; however, there is up to a 65% chance of the patient developing active pulmonary or extrapulmonary tuberculosis within five years.

Kinasewitz GT. Pleuritis and Pleural Effusion. Pulmonary and Critical Care Medicine on CD-ROM 1997; Chapter One. The absolute best detailed current review covering all aspects of pleural disease. Excellent tables, well referenced.

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