Laboratory Studies
No specific laboratory studies of the serum suggest the presence of a parapneumonic effusion or empyema. However, the possibility of a parapneumonic effusion and empyema should be a consideration for every patient with pneumonia. The presence of pleural fluid may be suggested based on physical examination findings; however, small pleural effusions may not be detected during the physical examination. In this case, any significant effusion can be visualized using 2-view (ie, posteroanterior, lateral) chest radiography.
Sputum should be submitted for culture, especially if purulent (see Sputum Culture). The infecting organism may be suggested based on Gram stain results. Mixed florae are often seen in anaerobic infections.
As with any infection, leukocytosis may be present (>12,000/µL) (see Leukocyte Count); however, it should decrease with adequate antibiotic therapy. Persistent fever and leukocytosis despite adequate antibiotic therapy may signal a persistent focus of infection, such as a complicated parapneumonic effusion or empyema, with subsequent evaluation as outlined in the following sections. Diagnosing a complicated parapneumonic effusion and/or empyema is crucial for optimal management because a delay in drainage of the pleural fluid substantially increases morbidity.
A retrospective study from a single center determined that pleural cytology does not add any additional value over traditional markers for distinguishing a complicated parapneumonic effusion from an uncomplicated parapneumonic effusion. [9]
A small study determined that combining semiquantitative polymerase chain reaction with next-generation sequencing of pleural fluids can help diagnose parapneumonic effusions and empyema and identify the causal bacteria. [10]
Imaging Studies
Chest radiography
Lateral chest radiography usually demonstrates the presence of a significant amount of pleural fluid, as shown in the image below.
If either of the diaphragms is not visible throughout its entire length, the posterior costophrenic angles are blunted, or a lateral meniscus is visible, then bilateral decubitus chest radiographs should be obtained.
Free pleural fluid is seen as a dense linear shadow layering between the chest wall and the lung parenchyma.
Unchanging pleural-based linear densities, pleural-based mass-liked densities, or collections with obtuse angles suggest the presence of loculated fluid, especially if the differences in the fluid or the appearance between upright and lateral views are minimal.
If the pleural fluid distance measures more than 10 mm from the chest wall, sufficient free-flowing fluid is present to perform a diagnostic thoracentesis.
Ultrasonography
Ultrasonography can be used to localize fluid for a thoracentesis. Fluid appears dark or black on ultrasound images, and most bedside ultrasonography devices permit measurement of the depth of location from the chest wall.
Complex fluid (purulent or viscous) may have more density or shadows within in the pleural fluid collection. Sometimes, fibrinous strands can be seen floating in the pleural fluid.
Other structures such as the diaphragm or lung parenchyma can provide landmarks to assist in needle placement for thoracentesis.
Loculated pleural effusions may be difficult to localize during physical examination, but they can usually be identified with ultrasonography.
Ultrasonography 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. If a loculated pleural effusion is suspected, an ultrasonographic examination is recommended for diagnosis and marking the area for thoracentesis.
CT scanning of the thorax
CT scanning of the chest with contrast, as shown in the image below, enhances the pleural surface and assists in delineating the pleural fluid loculations.
CT scan of thorax shows loculated pleural effusion on left and contrast enhancement of visceral pleura, indicating the etiology is likely an empyema.
Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, showing a thickened contrast-enhanced pleural rind, high-density pleural effusion, loculation, and septation. Thoracentesis yielded foul-smelling pus.
Pleural enhancement can be seen in patients with active inflammation and severe pleuropulmonary infections, which provides another sign of the possibility of a complicated pleural effusion or empyema. The split pleura sign on contrast-enhanced chest CT, often seen in empyema, is enhancement of both pleural surfaces separated by a fluid collection, as shown in the panel below.
Chest CT scan with intravenous contrast (axial, coronal, and sagittal views) of an alcoholic male patient with an anaerobic empyema demonstrating the split pleura sign.
CT scanning of the chest may also help detect airway or parenchymal abnormalities such as endobronchial obstruction or the presence of lung abscesses.
Other Tests
While no diagnostic serum laboratory tests are available for a parapneumonic effusion, serum total protein and lactic dehydrogenase (LDH) levels should be obtained to help characterize whether the pleural fluid is an exudate or transudate. The ratio of pleural fluid/serum protein and LDH is used to distinguish between these two entities.
Procedures
Thoracentesis is recommended when the suspected parapneumonic pleural effusion is greater than or equal to 10 mm thick on a lateral decubitus chest radiograph. [11] See the image below.
A right lateral decubitus chest radiograph shows a free-flowing pleural effusion, which should be sampled with thoracentesis for pH determination, Gram stain, and culture.
Pleural fluid appearance may vary from a clear yellow liquid to an opaque turbid fluid to grossly purulent thick, viscous, foul-smelling pus. Foul-smelling fluid indicates an anaerobic infection.
Pleural fluid studies
Blood cell count (WBC count) and differential: Results generally are not diagnostic, but most transudates are associated with a WBC counts of less than 1000 cells/µL and empyemas are exudates, with WBC counts generally greater than 50,000 cells/µL.
Pleural fluid total protein, LDH, and glucose (corresponding serum protein and LDH): Exudates are defined by pleural/serum total protein ratio of greater than 0.5 and a pleural/serum LDH ratio of greater than 0.6 or a pleural fluid LDH value greater than two thirds the upper limit of normal. One criterion is sufficient to classify fluid as an exudate.
Pleural fluid pH (iced blood gas syringe): Values of less than 7.20 are suggestive of a complicated pleural effusion.
Other laboratories suggestive of complicated pleural effusion or empyema: These include (1) an LDH value of greater than 1000 U/L, (2) a pH of less than 7.00, and (3) a glucose level of less than 40 mg/dL.
Microbiology (Gram stain, bacterial culture)
Acid-fast bacilli and fungal infections may cause pleural effusions or empyema, but these organisms are more difficult to culture from pleural fluid.
Biomarkers
Several pleural fluid and serum biomarkers have been evaluated to help distinguish parapneumonic pleural effusions from other causes of exudative effusions or distinguish complicated parapneumonic pleural effusions from uncomplicated parapneumonic pleural effusions in nonpurulent effusions. Among those, the most promising and practically applicable biomarkers are both pleural fluid and serum C-reactive protein (CRP). Pleural fluid CRP greater than 100 mg/L or serum CRP greater than 200 mg/L were shown to increase the chance of complicated parapneumonic pleural effusion and predicting the need for a drainage procedure. [12, 13, 14] Less consistent data were for pleural fluid procalcitonin, which was not very sensitive based on a systematic review and meta-analysis, [14, 15] although it is widely available in many laboratories. Other biomarkers, for example, are pleural fluid tumor necrosis factor-α, [16] pleural fluid defensins, [17] pleural fluid neutrophil gelatinase–associated lipocalin (NGAL), [18] serum and pleural fluid matrix metalloproteinases (MMP-2, MMP-8, MMP-9), [19] pleural fluid myeloperoxidase, [20] and pleural fluid pentraxin-3 (PTX3). [21, 22] Most studies were limited by small sample sizes, lack of confirmatory findings, no proven superiority to traditional pleural biochemistries, and the biomarker test not being routinely available.
Histologic Findings
Multiple granulocytes are typically identified on histologic examination. Necrotic debris may be present. Bacteria are seen in the pleural fluid in severe infections.
Staging
The classification and treatment scheme below has been used to characterize parapneumonic effusions and empyema.
Category 1 (parapneumonic effusion) is as follows:
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Minimal free-flowing fluid, smaller than 10 mm on decubitus films
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Culture, Gram stain, and pH unknown
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No thoracentesis needed; treatment with antibiotics alone
Category 2 (uncomplicated parapneumonic effusion) is as follows:
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Larger than 10 mm fluid and less than half the hemithorax on decubitus films
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Gram stain and culture negative
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pH higher than 7.20
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Treatment with antibiotics alone
Category 3 (complicated parapneumonic effusion) is as follows:
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Large free-flowing effusion, more than half the hemithorax
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pH lower than 7.20, LDH level greater than 1000 U/L and glucose level greater than 40 mg/dL
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Gram stain or culture positive
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Treatment with tube thoracostomy and antibiotics
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Multiloculated effusions may require multiple tubes
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Thrombolytics may help resolution
Category 4 (empyema) is as follows:
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Large free-flowing effusion, greater than equal to half the hemithorax
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Loculated effusion or effusion with thickened pleura
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Gross pus on aspiration
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Treatment with tube thoracostomy
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Thrombolytics may help resolution
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May require decortication
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Left pleural effusion developed 4 days after antibiotic treatment for pneumococcal pneumonia. Patient developed fever, left-sided chest pain, and increasing dyspnea. During thoracentesis, purulent pleural fluid was removed, and the Gram stain showed gram-positive diplococci. The culture confirmed this to be Streptococcus pneumoniae.
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Left lateral chest radiograph shows a large, left pleural effusion.
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A right lateral decubitus chest radiograph shows a free-flowing pleural effusion, which should be sampled with thoracentesis for pH determination, Gram stain, and culture.
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CT scan of thorax shows loculated pleural effusion on left and contrast enhancement of visceral pleura, indicating the etiology is likely an empyema.
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Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, showing a thickened contrast-enhanced pleural rind, high-density pleural effusion, loculation, and septation. Thoracentesis yielded foul-smelling pus.
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Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, 3 days following thoracostomy and intrapleural fibrinolysis (Reteplase).
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Chest CT scan with intravenous contrast (axial, coronal, and sagittal views) of an alcoholic male patient with an anaerobic empyema demonstrating the split pleura sign.
