Pleural effusion diagnostic study of choice
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Because the treatment of pleural effusion varies based on the cause it is important to have a good differential diagnosis. This would drive the diagnostic approach and ultimately the diagnostic study of choice based on the presentation. After determining whether the effusion is unilateral or bilateral through chest x-ray, the likely cause should be considered. If the diagnosis is clearly pointing towards nephrotic syndrome or congestive heart failure, then these patients do not necessarily need to have a thoracentesis performed and should be treated. However, a thoracentesis becomes the diagnostic study of choice in the following circumstances:
- an unclear cause
- patient experiencing pleuritic chest pain
- patient experiencing symptoms out of proportion to the size of the effusion
- no response to treatment
Diagnostic Study of Choice
Study of choice
The diagnostic study of choice is a thoracentesis that should be performed with a current chest x-ray and under ultrasound guidance. The procedure uses a 21 gauge needle with a 50 mL syringe. After the fluid is removed, it is analyzed. Macroscopically, the fluid can point to differentials. If milky, consider a chylothorax, pus can point to empyema and blood can indicate malignancy. LDH and protein are also measured to determine if the fluid is an exudate or transudate as per Light's Criteria. 
- Pleural fluid protein/serum protein >0.5 or
- Pleural fluid LDH/serum LDH >0.6, or
- Pleural fluid LDH > 2/3 the upper limit of normal.
Exudates are caused by inflammation or impaired lymphatic drainage whereas transudates are caused by changes in the hydrostatic or oncotic pressures.  The initial goal of the thoracentesis is to differentiate between these two and so Light's Criteria remains the guideline of choice for this diagnostic study. 
The fluid is further analyzed for pH levels, glucose, amylase, triglycerides, biomarkers and cytology. It is recommended to check pH levels if the cause may be infectious. If the pH levels are less than 7.2, it is advised to drain the fluid immediately to decrease the risk of parapneumonic pleural effusion. Low glucose in the fluid can indicate empyema, tuberculosis, rheumatoid arthritis and malignancy.  High amylase content can indicate acute pancreatitis, chronic pancreatitis or esophageal rupture.  Elevated levels of triglycerides (greater than 110 mg/dL) would indicate chylothorax. 
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