Laboratory testing distinguishes pleural fluid transudates from exudates. However,
certain types of exudative pleural effusions might be suspected simply by observing the quality of the fluid obtained during thoracentesis.
purulent fluid indicates an empyema.
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
by trauma or surgical procedures.
Grossly bloody fluid indicates the need for a spun hematocrit of the sample. A pleural fluid hematocrit >50% of the peripheral hematocrit defines a hemothorax, which often requires tube thoracostomy.
Although a number of chemical tests have been proposed to distinguish pleural fluid transudates and exudates, the criteria first proposed by Light have become the criterion standard.
The fluid is considered an exudate if the following apply:
Pleural fluid - Serum protein ratio >0.5
Pleural fluid - Serum lactate dehydrogenase (LDH) ratio >0.6
Pleural fluid LDH greater than two thirds of normal serum value
These criteria require simultaneous measurement of pleural fluid and serum protein and LDH. However, a recent meta-analysis suggests that pleural fluid measurement alone might have comparable sensitivity and specificity to Light’s criteria for distinguishing transudates from exudates.
Pleural fluid LDH >0.45 of upper limit of normal serum values
Pleural fluid cholesterol >45 mg/dL
Pleural fluid protein >2.9 g/dL
Determine pleural fluid pH on the initial thoracentesis in most situations.
In parapneumonic effusions, pleural fluid pH <7.1-7.2 indicates the need for urgent drainage of the effusion, and pleural fluid pH >7.3 suggests that the effusion can be managed with systemic antibiotics alone.
In malignant effusions, pleural fluid pH <7.3 is associated with more extensive pleural involvement, higher yield on cytology, decreased success of pleurodesis, and shorter survival times.
Pleural fluid pH is highly correlated with pleural fluid glucose levels, and, for parapneumonic effusions, pleural fluid pH is more predictive of complicated effusions than is pleural fluid glucose.
Handle pleural fluid samples as carefully as arterial samples for pH measurements, with fluid collected in heparinized syringes and transported on ice for measurement within 6 hours.
If an exudate is suspected clinically or confirmed by chemistry tests, send pleural fluid for total and differential cell counts, Gram stain, culture, and cytology.
Suspect malignant effusions in patients with known cancer or with lymphocytic, exudative effusions, especially when bloody.
Direct tumor involvement of the pleura is diagnosed most easily by pleural fluid cytology.
Heparinize samples of 300-500 mL of pleural fluid if bloody and refrigerate if not processed within 1 hour.
Cytological examination of a single pleural fluid specimen has a diagnostic yield of approximately 54-63% for malignancy and increases to 77% when serial specimens are obtained.
Closed needle pleural biopsy is a bedside procedure that can increase the yield for malignancy by an additional 7% over that obtained by cytology alone.
Tumor markers, such as carcinoembryonic antigen, are suggestive of malignant effusions when pleural fluid values are very high but, because of low sensitivity, are not helpful if values are normal or only modestly increased.
Suspect tuberculosis (TB) pleuritis in patients with a history of exposure or a positive purified protein derivative (PPD) and in patients with exudative effusions that are predominantly lymphocytic, especially if <5% mesothelial cells are detected on differential cell counts.
Because most tuberculous pleural effusions probably result from a hypersensitivity reaction to the mycobacterium rather than from microbial invasion of the pleura, acid-fast bacillus stains of pleural fluid rarely are diagnostic (<10% of cases) and pleural fluid cultures grow Mycobacterium tuberculosis in <65% of cases.
In contrast, histology and culture of pleural tissue obtained by closed needle pleural biopsy increase the diagnostic yield to 80-90%.
Adenosine deaminase (ADA) activity >43 U/mL in pleural fluid supports the diagnosis of TB pleuritis.
The test is not 100% sensitive; therefore, pleural ADA values <43 U/mL do not exclude the diagnosis of TB pleuritis.
Additional specialized tests are warranted when specific etiologies are suspected.
Measure pleural fluid amylase if pancreatic origin or ruptured esophagus is suspected or if a unilateral left pleural effusion remains undiagnosed after initial testing. Additional assay of amylase isoenzymes can distinguish a pancreatic source from other etiologies.
Measure triglycerides on milky pleural fluids when chylothorax is suspected.
Consider immunologic studies, including pleural fluid antinuclear antibody and rheumatoid factor, when collagen vascular diseases are suspected.
Despite primary evaluation with serial thoracenteses with cytology and pleural biopsy, approximately 25% of exudative effusions remain undiagnosed. Consider pulmonary embolism in such patients and order radionuclide perfusion lung scanning if reasonable clinical suspicion exists.
Among patients with undiagnosed pleural effusions after primary evaluation, predict a benign course for those who meet all 6 of the following clinical parameters. No further evaluation is necessary. 1. Clinical stability 2. Absence of weight loss 3. Negative PPD and pleural ADA <43 U/mL 4. Absence of fever 5. Pleural fluid differential cell count with <95% lymphocytes 6. Effusion that occupies <50% of the hemithorax
For other patients with undiagnosed exudative effusions, approximately 20% will have a specific etiology determined, including malignancy.
For such patients, weigh the benefits and risks of pursuing a diagnosis using progressively more invasive procedures, given the low likelihood of finding a curable etiology. Consider bronchoscopy only if patient has parenchymal abnormalities or hemoptysis.
For patients in whom TB or malignancy is suspected despite a negative primary evaluation, a second pleural biopsy might yield a diagnosis in 33-50%. Attempt the second biopsy before proceeding to direct surgical exploration of the pleura.
Surgical approaches to the diagnosis of pleural effusions include thoracoscopy (pleuroscopy) and open thoracotomy, which reveal an etiology in 92% of effusions that remain undiagnosed after medical evaluation. However, in the majority of medical centers, surgical exploration by thoracoscopy or thoracotomy entails the risks of general anesthesia and probably is warranted only in patients who are symptomatic and anxious for a diagnosis.
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