Pediatric Pleural Effusion Workup
- Author: Dagnachew (Dagne) Assefa, MD, FAAP, FCCP; Chief Editor: Michael R Bye, MD more...
Tests may need to be ordered to rule out immune dysfunction or other underlying systemic or local pulmonary disorders that cause empyema.
Analysis of the pleural fluid is the single best method to determine the cause of a pleural effusion. Thoracentesis should be performed when sufficient fluid is present to allow a safe procedure, except when the suspected effusion is clearly secondary to a specific underlying disease (for example, congestive heart failure, nephrotic syndrome, ascites, or recent initiation of peritoneal dialysis).
Simple observation of the gross appearance of the fluid may provide a clue as to the cause of the pleural effusion, as follows:
Grossly purulent fluid indicates an empyema
A putrid odor suggests an anaerobic empyema
Clear, pale yellow fluid suggests a transudate
Milky fluid is consistent with a chylothorax
Bloody pleural fluid is seen with trauma, malignancy, tuberculosis, uremia, and empyema due to group A Streptococcus
Aspergillus nigrans infection produces a black pleural fluid
In the appropriate clinical setting, measurement of pleural fluid triglyceride levels (chylous effusion), amylase (pancreatitis, esophageal rupture), and pleural fluid hematocrit (hemothorax) may be useful.
A complete blood count (CBC) with differential, blood cultures, and C-reactive protein (CRP) may help to establish the presence of infection. The white blood cell (WBC) count and CRP may be useful in monitoring treatment progress in infectious effusions. A positive blood culture finding may facilitate the selection of antibiotics in sterile empyema. (Approximately 10-22% of children with complicated parapneumonic effusions have a positive blood culture result.)[37, 46]
Measurement of titers may be helpful if specific organisms, such as Mycoplasma species, Legionella species, or adenovirus, are suspected. However, the use of these tests in early management of parapneumonic effusions is limited due to the need for convalescent titer.
If risk factors for tuberculosis are present, sputum (or gastric aspirates) for acid fast bacilli and a purified protein derivative (PPD) test should be performed.
Serum protein, LDH, amylase, glucose, and hydrogen ion concentration (pH) may be helpful in interpreting results of pleural fluid analysis. If chylous effusion is suspected, serum cholesterol and triglyceride levels should be obtained.
Exudate Versus Transudate
Conventionally, the initial evaluation of pleural fluid is directed at determining whether the effusion is an exudate or a transudate. The classification is based on simple biochemical criteria first proposed by Light et al. However, the Light criteria was developed and tested in adults, and its accuracy in children has been questioned.
According to the Light criteria, the pleural fluid is defined as an exudate if it fulfils at least one of 3 criteria. If none of the criteria are met, then the fluid is considered a transudate. The criteria are as follows:
Pleural fluid–to–serum lactate dehydrogenase (LDH) ratio of more than 0.6
Pleural fluid–to–serum protein ratio of more than 0.5
Pleural fluid LDH level of two thirds the upper limit of the reference range
In general, exudates have protein concentration higher than 2.9 g/dL, with the pleural fluid cholesterol level more than 45 mg/dL.
Biochemical analysis of the pleural fluid provides further information that may be useful in narrowing the differential diagnosis of exudative effusion, as follows:
Low pleural glucose level (< 60 mg/dL) or pleural fluid–to–serum glucose ratio of less than 0.5 - Seen in several conditions, such as parapneumonic effusion, tuberculosis, malignancy, esophageal rupture, and rheumatoid effusions 
Pleural fluid–to–serum LDH ratio of 1 and pleural fluid–to–serum protein ratio less than 0.5 -Suggest effusion due to P jiroveci pneumonia 
Pleural fluid pH below 7.3 (with normal arterial pH) - Seen in parapneumonic effusion, tuberculosis, malignancy, esophageal rupture, systemic acidosis, urinothorax, and rheumatoid effusions;  most exudative effusions have a pH of 7.3-7.45, whereas transudates have a pleural fluid pH ranging from 7.4-7.55  (the pH of normal pleural fluid is about 7.6) 
Pleural fluid cell count, although routinely performed, is not particularly helpful in establishing any of the diagnoses likely to occur in children. However, in certain settings, the predominant cell type may be helpful in determining etiology. Polymorphonuclear cells tend to predominate in recent effusions, and lymphocytes in long-standing ones.
Neutrophilic predominance - Bacterial etiology, pancreatitis (fluid, often hemorrhagic), esophageal rupture (very low pH), and the early stages of pleural tuberculosis 
Lymphocytic predominance (85-95% of total nucleated cells) - Tuberculosis, malignancy, uremia, connective tissue disease, and mycotic infections 
Monocytic effusion - Viral and mycoplasma pneumonia 
Eosinophilic effusion (>10% eosinophils) - Reactive eosinophilic pleuritis (recent pneumothorax or blood in pleural space), drugs (eg, dantrolene and nitrofurantoin), uremia, fungal and parasitic infections [56, 57]
Microbiologic analysis of the pleural fluid should be obtained from patients with undiagnosed exudative pleural effusion. Such analysis includes the following:
Gram, acid-fast bacilli, and fungal (KOH) staining
Culture for bacteria (both aerobic and anaerobic), mycobacteria, and fungi
Direct and enrichment culture for aerobic and anaerobic organisms - In addition send some pleural fluid in anaerobic blood culture bottle 
The yield of microbiologic diagnosis in children may be increased by the use of adjunct techniques to detect bacterial antigens. These include counterimmunoelectrophoresis, latex agglutination, specific (eg, pneumolysin) polymerase chain reaction (PCR) assay, and broad range (eg, 16S rDNA) PCR assay.[7, 8, 59] These tests may be particularly useful in patients who have received antibiotics prior to thoracentesis.
Diagnosis of Tuberculous and Malignant Pleuritis
The pleural fluid adenosine deaminase and interferon-γ levels are elevated in almost all patients with tuberculous pleuritis. Measurement of adenosine deaminase or interferon-γ may be used to establish the diagnosis. However, no universally accepted cutoff point is noted for either of these parameters.
In a meta-analysis, a maximum joint sensitivity and specificity of 93% for adenosine deaminase and 96% for interferon-γ was noted. The specificity of this parameter may be higher when used in conjunction with a lymphocyte-to-neutrophil ratio in pleural fluid of 0.75 or greater.
Molecular techniques, such as PCR assay to detect specific mycobacterial deoxyribonucleic acid (DNA) in pleural fluid, are now available for diagnosis of tuberculous pleuritis. Although PCR assay tests have a great potential for providing a rapid and specific diagnosis of mycobacterial infection, they are limited by low sensitivity.
Cytology can be performed if a malignancy is suspected. However, negative cytology does not rule out malignancy. In a retrospective study, Chaignaud et al found that cytologic examination and immunotyping of cells in pleural fluid were diagnostic in 71% of children with lymphoblastic lymphoma, obviating general anesthesia and open biopsy of the mediastinal masses.
A chest radiograph, while nonspecific, is the simplest and least expensive method of identifying a pleural effusion. A chest radiograph may also reveal underlying pneumonia before pleural fluid starts accumulating. (See the image below.)
Frontal, lateral, and decubitus radiographs may be used to detect a pleural effusion. In general, free-flowing pleural fluid collects in the most dependent part of the pleural space on an upright chest radiograph, usually the posterior costophrenic recess and, less often, the lateral recess. Blunting of the costophrenic recess is the earliest sign of pleural fluid accumulation. (See the images below.)
As effusions increase in size, they produce a characteristic meniscus sign as the fluid tracks superiorly along the pleural surface. Large effusions result in opacification of the hemithorax, with mediastinal shift (see the image below). Absence of shift is suggestive of underlying lobar collapse.
In adults, approximately 50 mL of fluid causes blunting of the posterior costophrenic recess on a lateral chest radiograph. By contrast, at least 200 mL is necessary to blunt the lateral recess on an upright chest radiograph. A lateral decubitus film is the most sensitive view and can detect as little as 5-10 mL of free fluid. A lateral decubitus film obtained with the affected side down provides valuable information about the quantity and quality of effusion.
A fluid layer of more than 1 cm on decubitus film is amenable to thoracentesis. Nonshifting fluid suggests either thick fluid or loculation. A lateral decubitus image obtained with the affected side up may facilitate the evaluation of the underlying lung for atelectasis or infiltrates.
Pleural ultrasonography permits easy characterization of pleural effusion. In experienced hands, it is superior to standard upright chest radiography and supine chest radiography for detecting pleural effusion.
Ultrasonography can easily distinguish between free and loculated pleural effusion (see the images below) and allow pleural fluid to be differentiated from pleural thickening and solid masses. Ultrasonography may also facilitate the identification of the best site for thoracentesis or insertion of a thoracotomy tube.[70, 71] The main limitation of ultrasonography is that its usefulness depends on the examiner’s skill.
Pleural fluid can easily be identified on computed tomography (CT) scans. However, CT scan findings lack the accuracy required for the differentiation of exudates from transudates and chylothorax[72, 73, 74] and for accurately predicting the presence of empyema in patients with parapneumonic effusion. Although CT scanning detects more parenchymal abnormalities than chest radiography does, studies found that the additional information obtained does not seem to alter management decisions or help to predict clinical outcomes. (See the image below.)[76, 77]
CT scanning is increasingly used as the study of choice in empyema; it may provide additional information in complicated cases. In addition, CT scan guidance may also be useful in interventions in which effusions are difficult to access. However, the modality is comparatively expensive, invasive, and time consuming. The omission of routine CT scanning in empyema reduces the exposure of children to unneeded radiation and cuts costs.
Pleural evaluation is greatly aided by the use of intravenous contrast, as the unenhanced pleura cannot normally be visualized.
Thoracentesis, Pleural Biopsy, and Bronchoscopy
Thoracentesis is recommended for most pleural effusions of sufficient size whenever the cause of the effusion is uncertain.
Thoracentesis should not be performed if the diagnosis is thought to be certain and the likelihood of empyema or malignancy is low. Such circumstances include small, bilateral infiltrates in congestive heart failure or nephrosis or a small parapneumonic effusion in an afebrile child recovering from pneumonia.
Thoracentesis should be performed in patients whose respiratory status is compromised by pleural effusion, in patients with empyema or malignancy, or in newborns.
This may be needed in cases of unexplained inflammatory effusion, suspected tuberculosis, or malignancy. The two major complications of pleural biopsy are bleeding and pneumothorax.
Routine flexible bronchoscopy is not indicated in children with pleural effusion. Aspiration of a foreign body in younger children is a possibility and is an indication for bronchoscopy.
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