eMedicine Specialties > Emergency Medicine > Pulmonary

Pleural Effusion: Differential Diagnoses & Workup

Author: C Crawford Mechem, MD, MS, FACEP, Associate Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; Emergency Medical Services Medical Director, Philadelphia Fire Department
Contributor Information and Disclosures

Updated: Nov 13, 2009

Differential Diagnoses

Other Problems to Be Considered

Transudative pleural effusion 

Congestive heart failure (most common)
Cirrhosis with hepatic hydrothorax
Nephrotic syndrome
Peritoneal dialysis/continuous ambulatory peritoneal dialysis
Hypoproteinemia
Glomerulonephritis
Superior vena cava obstruction
Fontan procedure
Urinothorax
Cerebrospinal fluid leak to the pleural space

Exudative pleural effusion 

Malignancy
Pneumonia
Tuberculosis
Pulmonary embolism
Fungal infection
Pancreatic pseudocyst
Intra-abdominal abscess
After coronary artery bypass graft surgery
Postcardiac injury syndrome
Pericardial disease
Meigs syndrome
Ovarian hyperstimulation syndrome
Rheumatoid pleuritis
Lupus erythematosus
Drug-induced pleural disease
Asbestos pleural effusion
Yellow nail syndrome
Uremia
Trapped lung
Chylothorax
Pseudochylothorax

Workup

Laboratory Studies

• Laboratory evaluation of patients with a pleural effusion is directed at first determining if the effusion is an exudate or a transudate. As a consequence, with few exceptions, patients who present with a new pleural effusion should undergo a diagnostic thoracentesis. Subsequent testing is aimed at further identifying the underlying etiology or grading the severity of disease. Depending on the clinical setting, this evaluation may be completed in the emergency department or initiated in the emergency department and completed in an inpatient service.
• The distinction between transudate and exudate is generally made by measurement of serum and pleural fluid lactate dehydrogenase (LDH) and protein concentrations.
  • Exudates have a higher protein concentration due to increased capillary permeability or decreased lymphatic drainage. As a result, the pleural effusion generally is an exudate if the pleural fluid – to – serum total protein ratio is greater than 0.50, the pleural fluid LDH is greater than 0.67 of the upper limits of normal serum LDH, or if the pleural fluid–to–serum LDH ratio greater than 0.6 (Light's criteria). Pleural fluid cholesterol also tends to be higher in exudates than in transudates.
  • The pleural effusion is generally a transudate if both the pleural fluid – to – serum total protein ratio and the pleural fluid – to – serum LDH ratios are less than or equal to 0.50 and less than 0.67, respectively.
  • These criteria may not accurately identify transudates caused by congestive heart failure or renal failure, especially in patients taking diuretics.¹²
• Exudative effusions require further laboratory investigation. The pleural fluid should be
  analyzed for the following:
  • Cell count with differential
  • Glucose level
  • Amylase level
  • pH: Pleural fluid acidosis, defined as a pH less than 7.30, is seen in a limited number of conditions including empyema; rheumatoid, tuberculous, or lupus pleuritis; malignancy; urinothorax; or esophageal rupture.⁵
  • Cytologic analysis (especially if malignancy or Pneumocystis carinii is suspected)
  • In the appropriate clinical setting, Gram staining, acid-fast bacilli staining, fungal (KOH) staining, and culture and sensitivity for aerobic and anaerobic organisms and fungi
  • Additional studies should be requested on the basis of the gross appearance of the pleural fluid or when a specific condition is suspected.

Imaging Studies

• After the initial stabilization of the patient, clinical suspicion for pleural effusion should be confirmed with appropriate radiographic evaluation. The most frequently ordered studies are chest radiography, ultrasonography, and CT.
• Chest radiography is the primary diagnostic tool because of its availability, accuracy, and low cost. It may both confirm the presence of effusion and suggest the underlying etiology.
  • Pleural fluid typically collects in the most dependent portion of the pleural space on an upright chest radiograph, primarily the posterior costophrenic recess, followed by the lateral recess. As little as 50 mL of fluid will cause blunting of the posterior costophrenic recess on a lateral upright film, whereas 200 mL are required to cause blunting of the lateral recess on a posteroanterior (PA) film. A lateral decubitus chest radiograph may detect as little as 5 mL of fluid.²⁰ Additional findings suggestive of pleural effusion include homogenous opacification or diffuse haziness with a ground-glass appearance, visibility of pulmonary vessels through the haziness, and an absence of air bronchograms.
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    Anteroposterior upright chest radiograph shows bilateral pleural effusions and loss of bilateral costophrenic angles (meniscus sign). Image courtesy of Allen R. Thomas, MD.

    [ CLOSE WINDOW ]

    

    Anteroposterior upright chest radiograph shows bilateral pleural effusions and loss of bilateral costophrenic angles (meniscus sign). Image courtesy of Allen R. Thomas, MD.

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    Chest radiograph, lateral view shows loss of bilateral posterior costophrenic angles. Image courtesy of Allen R. Thomas, MD.

    [ CLOSE WINDOW ]

    

    Chest radiograph, lateral view shows loss of bilateral posterior costophrenic angles. Image courtesy of Allen R. Thomas, MD.

  • A massive effusion is often attributable to an underlying malignancy. Other conditions that must be considered include congestive heart failure, tuberculosis (TB), cirrhosis with ascites, transdiaphragmatic rupture of a liver abscess into the pleural space (>90% right-sided), paragonimiasis (usually unilateral), peritoneal dialysis (90% right sided), cryptococcosis, pancreatic pseudocyst, chronic pancreatitis, Meigs syndrome, uremic pleuritis, yellow nail syndrome, and effects of medications.
  • Massive effusions usually have an accompanying mediastinal shift to the contralateral side. However, in the absence of mediastinal shift, the differential diagnosis is narrowed to carcinoma of the ipsilateral mainstem bronchus with or without ipsilateral lung atelectasis, fixed mediastinum caused by fibrosis or tumor infiltration of mediastinal lymph nodes, tumor infiltration of the ipsilateral lung, malignant mesothelioma, or complete atelectasis of the ipsilateral lung.
  • Bilateral effusions with an enlarged cardiac silhouette are most likely due to congestive heart failure. In the absence of cardiomegaly, malignancy (either lymphoma or carcinoma, with the exception of breast and lung cancer) is the most common cause. Other possible etiologies include lupus pleuritis, rheumatoid pleurisy, nephrotic syndrome, cirrhosis with ascites, pulmonary embolism, TB, esophageal rupture, benign asbestos pleural effusion, Meigs syndrome, uremic pleuritis, yellow nail syndrome, and medication-associated effusion.
  • The location of the pleural effusion can help in differential diagnosis.
  • Isolated right-sided pleural effusions commonly occur with cirrhosis, peritoneal dialysis, subphrenic or intrahepatic abscess, amebic liver abscess, echinococcal infection, liver transplantation, Meigs syndrome, or catamenial hemothorax (thoracic endometriosis).
  • Isolated left-sided effusions occur with esophageal rupture, pancreatic disease, subphrenic or splenic abscess, splenic infarction, diaphragmatic hernia, pericardial disease, or following coronary artery bypass graft surgery.
  • Chest radiography may yield other findings, such a pleural thickening or plaques, pulmonary parenchymal changes, or mediastinal enlargement, of value in determining the underlying disease process.¹² When an air-fluid level is present in the pleural space, the following must be considered: bronchopleural fistula, pneumothorax, trauma, presence of gas-forming organisms, diaphragmatic hernia, fluid-filled bullae or lung cysts, and rupture of the esophagus into the pleural space. Diaphragmatic hernias can be excluded or confirmed with the administration of GI contrast material.
• Ultrasonography of the chest may be rapidly performed by emergency physicians at the bedside to evaluate patients with suspected pleural effusion.²¹
  • Ultrasonography detects as little as 5-50 mL of pleural fluid and has a 100% sensitivity for effusions greater than 100 mL.
  • It can identify loculated fluid collections.
  • It may detect pleura- or chest wall-based tumors.
  • Ultrasonography can be used to guide needle insertion for thoracentesis or chest tube placement^12,22
• A spiral chest CT should be obtained for most patients with pleural effusion whose etiology is not readily determined. Scanning permits imaging of the entire pleural space, pulmonary parenchyma and vasculature, mediastinum, and pericardium. Abdominal slices may also be obtained if an intra-abdominal etiology for the effusion is suspected.
  • Chest CT can help in distinguishing benign from malignant pleural involvement. One or more of the following suggests malignancy: circumferential pleural thickening, nodular pleural thickening, parietal pleural thickening (>1 cm), and mediastinal pleural involvement.
  • CT scans are highly sensitive for discrete pleural plaques, but they are rarely helpful in differentiating transudates, exudates, and chylous pleural effusions.
• MRI may be used in evaluating patients with pleural effusion. However, its use is rarely part of the ED workup. MRI may be helpful in distinguishing benign from malignant pleural disease. In addition, it complements CT in evaluating patients with mesothelioma.²³
• Echocardiography may be performed to further assess patients with pleural effusion related to congestive heart failure or if pericardial effusion is suspected.

Other Tests

• Additional diagnostic testing is guided by the suspected etiology of the effusion and the patient's clinical status.
  • Contrast material–enhanced study of the esophagus
    • Esophageal perforation is a medical emergency that requires rapid diagnosis and treatment. When this condition is suspected, contrast-enhanced studies of the esophagus should be performed.
    • If esophageal perforation is suspected, surgical consultation should be obtained early in the patient's evaluation.
  • Ventilation-perfusion scanning: In many EDs, helical chest CT has replaced ventilation-perfusion scanning in the evaluation of patients with suspected pulmonary embolism. However, V-Q scans still have a role in some settings and when the patient is not a candidate for a CT scan.

Procedures

• After the presence of a pleural effusion is established, the cause should be identified. Thoracentesis is the first-line invasive diagnostic procedure and can be safely performed in most patients, including those undergoing mechanical ventilation. Thoracentesis can also be used as a therapeutic modality. Other diagnostic procedures include percutaneous pleural biopsy, bronchoscopy, thoracoscopy, and open pleural biopsy. However, thoracentesis and chest tube placement usually suffice for evaluation or treatment of in the ED.
• Thoracentesis
  • Most patients with a new pleural effusion should undergo diagnostic thoracentesis, which involves the removal of 50-100 mL for laboratory analysis. An exception would be in clinically stable, afebrile patients when the diagnosis is clear, such as congestive heart failure (CHF), recent thoracic surgery, or known renal or hepatic disease. In these cases, treatment of the underlying etiology may be appropriate. If the effusion does not improve, delayed thoracentesis can then be performed.
  • The most common complications of thoracentesis are pneumothorax, cough, and infection. Less common complications include hemothorax, splenic rupture, intra-abdominal hemorrhage, unilateral pulmonary edema, air embolism, and shearing off of a catheter fragment within the pleural space.
  • A chest radiograph is frequently obtained following thoracentesis to assess for pneumothorax. However, this may not be necessary when the procedure only involved a single pass and the patient has no risk of pleural adhesions and remains asymptomatic.²⁴
  • For massive effusions with a midline mediastinum or ipsilateral mediastinal shift, consultation with a pulmonologist is indicated prior to any intervention. In such patients, bronchoscopy, rather than thoracentesis, is generally the initial diagnostic procedure of choice.
• Tube thoracostomy
  • Tube thoracostomy is indicated for initial management of empyema, diagnosed by the presence of pus on thoracentesis, a positive Gram stain, fluid glucose less than 60 mg/dL, a pH less than 7.20, or elevated LDH.²⁵
  • Placement of a chest tube in the setting of a malignant tumor that obstructs a mainstem or lobar bronchus is contraindicated because the obstruction prevents expansion of the lung underlying the effusion.

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