Pleural effusion

Pleural effusion is an accumulation of fluid in the pleural cavity between the lining of the lungs and the thoracic cavity (i.e., the visceral and parietal pleurae). The pleural fluid is called a transudate if it permeates (transudes) into the pleural cavity through the walls of intact pulmonary vessels. It is called an exudate if it escapes (exudes) into the pleural cavity through lesions in blood and lymph vessels, e.g., as caused by inflammation and tumors. The accumulation of transudate is typically due to increased hydrostatic pressure (e.g., in congestive heart failure) and/or decreased oncotic pressure (e.g., in cirrhosis or nephrotic syndrome). Since transudate is a filtrate, it is typically a clear fluid with a low protein and cell content. By contrast, the lesions responsible for the outflow of exudate allow larger molecules and even solid matter to pass into the pleural cavity. For this reason, exudate is a cloudy fluid with a high protein and cell content. The effusion follows gravity and, unless the patient is bedridden, collects in the lower margins of the pleural cavity. Percussion over the area of effusion generates a dull tone, and breath sounds are diminished or completely absent on auscultation. Chest x-ray and ultrasound are usually performed as first-line tests to diagnose pleural effusion, but chest CT is sometimes required (e.g., for very small effusions). Thoracentesis with pleural fluid analysis is required to establish the underlying diagnosis in most pleural effusions and can also serve a therapeutic role. Treatment should focus on correcting the underlying condition.

• Definition: an excessive amount of fluid between pleural layers that impairs the expansion of the lungs

Symptoms ^[3]

• Patients with a small pleural effusion (< 300 mL) are often asymptomatic.
• Characteristic symptoms
  • Dyspnea
  • Pleuritic chest pain (sharp retrosternal pain)
  • Dry, nonproductive cough
  • Symptoms of the underlying disease (e.g., fever in empyema, cachexia in cases of malignancy, symptoms of left-sided heart failure)

Physical exam findings

• Inspection and palpation
  • Asymmetric expansion and unilateral lagging on the affected side
  • Reduced tactile fremitus due to fluid in the pleural space
• Auscultation
  • Faint or absent breath sounds over the area of effusion
  • Pleural friction rub (squeaking sound of inflamed pleural layers rubbing together during inspiration and expiration)
• Percussion: dullness over the area of effusion

Imaging ^[3][4]

Chest x-ray ^[4][5]

• Indications
  • Standard initial imaging modality for detecting pleural effusion.
  • Lateral decubitus view (most sensitive): allows for detection of fluid collections as small as 5 mL ^[6]
• Supportive findings
  • Typically unilateral blunting of the costophrenic angle
  • Homogeneous density with a meniscus-shaped margin (meniscus sign)
  • Large effusion
    • Complete opacification of the lung
    • Mediastinal shift
    • Tracheal deviation away from the effusion (space-occupying lesion)
  • Disease-specific signs: See “Pleural empyema”, “Lung cancer”, “Active primary tuberculosis”, "Pneumonia diagnostics”, and “Pneumothorax.”

Ultrasound ^[4][7]

• Indications
  • Quick bedside assessment
  • Thoracentesis planning
• Procedure: The imaging sequence is similar to the FAST protocol commonly used for trauma assessment.
• Supportive findings: hypoechoic/anechoic structures in the lower margins of the pleural cavity (costodiaphragmatic recess)
  • Very sensitive: can detect fluid amounts as low as 20 mL
  • Hemothorax and empyema may appear heterogeneous.
  • Pleural fluid septations may be present.
  • Allows for detection of pleural thickening and pleural nodules

Chest CT ^[4][7]

• Indications: gold standard but use is limited due to radiation and contrast exposure
  • Guiding placement of indwelling pleural catheters
  • Directed thoracentesis of a loculated effusion
  • Suspected parenchymal or pleural pathology
  • Better quantification of the amount of fluid (compared to CXR) is desired
• Procedure: chest CT without IV contrast is usually sufficient
  • With IV contrast: allows for the detection of underlying malignancy (e.g., metastases and/or primary tumor)
  • CT angiogram: helps to identify vascular pathology (e.g., dissection or AVM)
• Supportive findings
  • Can detect > 3–5 mL of fluid
  • Fluid density measurement can help differentiate pleural effusion from empyema and hemothorax ^[8]
  • Disease-specific signs: See “Pleural empyema.”

Diagnostic thoracentesis ^[3][9]

Analysis of the pleural fluid (via thoracentesis) is usually required to definitively establish the underlying etiology but may not be necessary if there is already a clear diagnosis of an underlying condition (e.g., known CHF or connective tissue disease).

• Description
  • Aspiration of fluid from the pleural space for diagnostic (e.g., transudate vs. exudate) purposes
  • Check serum protein, lipid panel, and LDH as well for calculation of Light criteria.
• Indications ^[3][9]
  • Any new unilateral effusion > 1 cm on x-ray in an undiagnosed patient
  • History of malignant tumor with effusion > 1 cm on x-ray
  • Pneumonia with parapneumonic effusion > 5 cm on x-ray
  • Heart failure in conjunction with atypical findings (e.g., pleuritic chest pain, fever, unilateral effusion)
  • Suspected transudative bilateral effusions with atypical features (e.g., fever, pleuritic chest pain, effusions of disparate size)
• Contraindications to thoracentesis
  • There are no absolute contraindications.
  • Relative contraindications
    • Infection over the puncture site (e.g., cellulitis, herpes zoster)
    • Coagulopathy (e.g., INR > 1.6, platelets < 50 cells/mm³)

Complications

• See “Therapeutic thoracentesis” below.

Pleural fluid analysis ^[3][7][10]

Differentiating transudates from exudates (incl. Light criteria) ^[6][11]

Narrowing the differential diagnosis of exudative effusions

Transudate is usually clear, has a decreased cell count, and has low levels of protein, albumin, and LDH. Exudate typically appears cloudy, has an increased cell count, and has high levels of protein, albumin, and LDH.

MEAT has low glucose: Malignancy, Empyema, Arthritis (rheumatoid pleurisy), and Tuberculosis are causes of pulmonary effusion associated with low glucose levels.

Pleural fluid with a bloody appearance suggests a malignant etiology or hemothorax!

Approach ^[6][9][12]

• Stabilize patients with respiratory distress.
  • Provide supplemental oxygen (see “Basic oxygen delivery systems”, “NIPPV”, and “Mechanical ventilation”).
  • Consider urgent therapeutic thoracentesis for patients with:
    • Signs of increased work of breathing
    • Hypoxemic respiratory failure
    • Hypercapnic respiratory failure
    • Hemodynamic compromise secondary to the effusion
• Identify and treat the underlying condition.
• Consider elective therapeutic thoracentesis based on individual risk-benefit ratios.
• Consider specialized procedures and/or surgical therapy after specialty consultation.

Treat the underlying cause ^[6]

• Acute congestive heart failure: loop diuretics (see “Treatment of heart failure”)
• Collagen vascular diseases: steroids (see “Systemic lupus erythematosus” and “Rheumatoid arthritis”)
• Pancreatitis: See “Acute pancreatitis” for general treatment measures.
• Pancreaticopleural fistula: Endoscopic or surgical intervention is recommended. ^[13][14][15]
• Meigs syndrome: Removal of ovarian tumor is recommended.
• Other malignancy: targeted cancer immunotherapy, chemotherapy, radiotherapy, or surgical resection

Therapeutic thoracentesis ^[9]

The goal of a therapeutic thoracentesis is to remove fluid (especially in exudate because of increased risk of infection). Removal of 400–500 mL of fluid is usually sufficient to relieve symptoms (e.g., dyspnea).

Indications

• Large effusion with dyspnea and/or cardiac decompensation
• Complicated parapneumonic effusions

Contraindications

• See “Contraindications to thoracentesis.”

Complications

• Vascular injury and hemothorax
• Pneumothorax
• Infection (e.g., pleuritis, empyema)
• Re-expansion pulmonary edema ^[16][17]
  • Definition: self-limiting noncardiogenic pulmonary edema that develops within 24 hours following rapid re-expansion of lung tissue that has collapsed as a result of air, pleural fluid, or mucus plugging
  • Risk factors
    • Age 20–40 years
    • Diabetes
    • Lung collapse > 3–7 days
    • Fluid removal > 3 L
    • Large associated pneumothorax
  • Clinical features
    • Dyspnea, increased work of breathing
    • Cough, frothy sputum
    • Tachycardia, tachypnea, hypoxemia
  • Diagnosis: confirmed by CXR or bedside ultrasound
  • Treatment
    • Supplemental oxygen
    • Severe cases: NIPPV or invasive mechanical ventilation
  • Prevention ^[18]
    • Limit pleural fluid removal to < 1.2–1.8 L at a time.
    • Avoid pleural pressures < -20 cm H₂O.

Therapeutic thoracentesis should be halted if patients develop chest discomfort, cough, or hypoxia, which could represent re-expansion pulmonary edema.

Indwelling pleural catheter ^{[19][20][21][22]}

• Goal: recurrent pleural fluid removal without repeated puncture
• Indication: rapidly reaccumulating pleural effusions (e.g., malignant effusions ) ^[21][22]
• Contraindications: See “Contraindications to thoracentesis.”
• Procedure ^[23]
  • A pleural catheter is inserted under the guidance of interventional radiology.
  • Similar to thoracentesis, except that the catheter is tunneled into the skin and can remain in situ for months.
• Complications ^[23][24]
  • Pain
  • Mechanical: dislodgement, blockage, leak, tube fracture
  • Infection: cellulitis, tunnel infection, empyema
  • Fibrosis and loculation within the pleural cavity
  • Catheter tract metastasis (i.e., deposition of malignant tissue at insertion site)

Surgical procedures ^[6]

• Consultation with a thoracic surgeon and/or chest physician is recommended.

Tube thoracostomy

• Indications
  • Pleural effusion in combination with significant cardiac and/or respiratory decompensation ^[25]
  • For recurrent pleural effusion or urgent drainage of infected and/or loculated effusions ^[26][27]
  • Drainage of high-viscosity fluid that is likely to clog ^[28][29]
    • Empyema ^[27][30][31]
    • Hemothorax ^[32][33][34]
• Procedure: See “Tube thoracostomy.”

Video-assisted thoracoscopic surgery (VATS)

• Definition: a minimally invasive surgical method used for diagnosis and treatment of various thoracic pathologies
• Indications
  • Collection of histological samples in malignant effusions
  • Pleural biopsy
  • Drainage of parapneumonic effusions that cannot be sufficiently controlled by tube thoracostomy
  • Drainage of pleural empyema and debridement of fibrin deposits, adhesions, and scar tissue

Pleurodesis ^[20][21]

• Definition: chemical or surgical obliteration of the pleural space
• Indication
  • Recurrent malignant effusions ^[22]
  • Effusions that do not respond to drugs (e.g., diuretics, antibiotics)
• Contraindications ^[19]
  • Predicted survival < 3 months
  • Trapped lung
• Procedure
  • After draining the pleural effusion, a substance (e.g., talc) is introduced into the pleural cavity.
  • This induces an inflammatory reaction that causes the pleural layers to bind together.
  • Alternatively, thoracoscopic pleurodesis with partial resection of the pleural layers may be performed.
• Complication: fibrothorax

A chest x-ray should be performed after each of these procedures to rule out iatrogenic pneumothorax.

• Supplemental oxygen as needed
• Check serum protein and LDH.
• Perform diagnostic thoracentesis with pleural fluid analysis.
• Repeat CXR after thoracentesis.
• Identify and treat the underlying cause (see pleural fluid analysis and common causes of pleural effusion).
• Consider pleural biopsy for further investigation (e.g., suspected tuberculosis, malignant disease).
• Consider indwelling pleural catheter placement or pleurodesis for malignant or recurrent effusion.
• Administer empiric IV antibiotics if there is a concern for empyema (see antimicrobial therapy for pleural infection).

Pleural fluid analysis is necessary in almost all cases to distinguish between the various subtypes of pleural effusion. Treatment depends on the underlying cause. Subtypes of pleural effusion include the following:

• Parapneumonic effusion
• Pleural empyema
• Nontraumatic hemothorax
• Malignant pleural effusion
• Chylothorax
• Pseudochylothorax

Definition ^[3][35]

• Accumulation of exudative fluid in the pleural cavity in response to pneumonia
  • Uncomplicated: without direct bacterial invasion
  • Complicated: extension of bacterial infection into the pleural space

Distinguishing features ^{[4][9][12][35]}

• Clinical features
  • Fever, chills
  • Cough
  • Chest discomfort
• Diagnostics
  • Imaging: associated pneumonia
  • Pleural fluid analysis
    • Exudative effusion
    • Cloudy or purulent appearance
    • WBC count > 10,000 cells/μL
    • Positive Gram stain/culture for complicated parapneumonic effusion
  • Pleural fluid criteria for complicated parapneumonic effusion
    • pH < 7.2
    • ↑ LDH
    • Glucose < 60 mg/dL (< 3.3 mmol/L)

Treatment ^{[9][27][36][37][38]}

• All patients: systemic antibiotic treatment
  • Early antibiotic treatment can prevent progression to complicated effusion and empyema.
  • See “Pneumonia treatment” for empiric antibiotic regimens.
• Patients with complicated parapneumonic effusions: therapeutic thoracentesis

Definition ^[35]

• Accumulation of pus in the pleural cavity

Etiology ^[12][35]

• Most common: pneumonia
• Less common
  • Infected hemothorax
  • Ruptured lung abscess
  • Esophageal tear
  • Thoracic trauma

Classification ^[39][40]

• Stage I (exudative): accumulation of fluid and pus
• Stage II (fibrinopurulent): aggregation of fibrin deposits that form septations and pockets
• Stage III (organizing): formation of thick fibrous peel on pleural surface that restricts lung movement

Distinguishing features ^[35]

• Clinical features
  • Fever, chills
  • Cough
  • Chest discomfort
• Diagnostics
  • CXR: will typically show opacity with one or more of the following characteristics ^[41]
    • Meniscus sign
    • Lenticular shape
    • Diffuse consolidation of adjacent lung
  • Ultrasound: heterogeneous fluid collection
  • Chest CT ^[8]
    • Distinctive appearance of empyema fluid
    • Split pleura sign: thickening of visceral and parietal pleura caused by fibrin that adheres to the surfaces, resulting in vascular proliferation
    • Septations
    • Displacement and compression of the adjacent lung
  • Pleural fluid analysis
    • Exudative effusion
    • Grossly purulent appearance
    • Positive Gram stain and bacterial culture
    • pH < 7.2
    • Low glucose (< 30–60 mg/dL)

Treatment of pleural empyema

Empiric antibiotic therapy for pleural infection ^{[27][36][37][38]}

All patients should receive empiric antibiotics adjusted to their needs, local resistance patterns, and institutional guidelines.

• Community-acquired pleural empyema ^[39]
  • Combination therapy with a parenteral second- or third-generation cephalosporin (e.g., ceftriaxone ) PLUS one of the following for anaerobic coverage:
    • Metronidazole
    • Clindamycin
  • Or single-agent therapy with a parenteral aminopenicillin and β-lactamase inhibitor (e.g., ampicillin-sulbactam )
• Hospital-acquired pleural empyema: Add MRSA and pseudomonal coverage to the above. ^[39]
  • Vancomycin PLUS one of the following:
    • Cefepime and metronidazole
    • Piperacillin-tazobactam
    • Meropenem (if extended-spectrum β-lactamase-producing organisms are suspected)
• Additional considerations ^[39]
  • Aminoglycoside antibiotics are not recommended because of poor pleural bioavailability.
  • Use empyema fluid culture to guide therapy.
  • Intrapleural antibiotics are not recommended.
  • Drainage should be arranged as quickly as possible for source control.
  • Duration of therapy depends on the identified organism, source control, and clinical response.
  • See tuberculosis therapy for the treatment of suspected tuberculous effusion.

Definitive treatment ^[39]

• Stage I
  • Chest tube (thoracostomy) to remove empyema fluid
  • Consider intrapleural administration of fibrinolytic agents.
• Stage II or mixed stage II/III
  • First-line: chest tube drainage
  • Second-line: VATS debridement if chest-tube drainage is ineffective
• Stage III
  • VATS debridement
  • Pleurectomy and lung decortication via open thoracotomy

Definition ^[33][42]

• Spontaneous or nontraumatic accumulation of blood in the pleural cavity

Etiology ^[33]

• Most common: spontaneous pneumothorax
• Less common
  • Vascular disease
  • Malignancy
  • Coagulation disorders
  • Necrotizing pneumonia ^[43]
  • Endometriosis
  • Bony exostoses
• See ”Penetrating trauma” for traumatic causes.

Distinguishing features

• Clinical
  • Symptoms of underlying disorder
  • If there is significant blood loss: hypotension, tachycardia
• Diagnostics
  • CXR: can show associated pneumothorax or malignancy
  • Ultrasound: heterogeneous fluid collection
  • Chest CT: hyperattenuating fluid collection; can reveal an underlying malignancy
  • Chest CTA: allows for the identification of the source of hemorrhage (e.g., vascular abnormalities)
  • Pleural fluid analysis
    • Bloody appearance
    • RBC count > 5,000 cells/μL
    • Hematocrit > 0.5 × peripheral hematocrit
  • Laboratory studies: ↓ hemoglobin

Treatment of nontraumatic hemothorax ^[33][42]

• Stabilize the patient.
  • Fluid resuscitation and blood transfusions as needed
  • Anticoagulant reversal (if applicable)
  • Chest tube (thoracostomy) with blood evacuation
  • Urgent surgical exploration and repair (i.e., open thoracotomy) in the case of:
    • Massive hemothorax (> 1500 mL)
    • Continuous bleeding (> 200 mL/hour for ≥ 4 hours)
    • Sustained hemodynamic instability requiring repeated transfusions
• Identify and treat the underlying cause.
• Consult surgery or interventional radiology for bleeding from tumors or vascular pathology.

A hemothorax, however small, must always be drained because blood in the pleural cavity will clot if not evacuated, resulting in a trapped lung or an empyema.

Description ^[44]

• Definition: accumulation of exudative fluid and malignant cells in the pleural cavity
• Pathophysiology: cancer-related barrier dysfunction of the capillary walls → increased permeation of plasma protein, blood cells, and tumor cells

Etiology ^[44]

• Caused by either direct invasion of the pleural space or distant metastases
  • Most common: lung cancer, breast cancer
  • Less common: mesothelioma, lymphoma, and pleural metastases

Distinguishing features ^[44]

• Clinical: symptoms of underlying malignancy (e.g., constitutional symptoms, cachexia, hemoptysis)
• Diagnostics
  • Imaging: associated underlying malignancy
  • Pleural fluid analysis
    • Cell-rich exudative effusion
    • Cloudy or straw-colored appearance
    • Abnormal cytology
      • Pronounced nucleoli
      • Cells with multiple nuclei
      • Numerous figures of mitosis
    • pH < 7.2
    • Glucose < 60 mg/dL
    • Amylase > 200 mcg/dL
    • LDH usually high (> 0.45 x normal serum LDH)
    • If hemorrhagic: bloody appearance, RBC count > 5,000 cells/μL
  • Laboratory studies: positive tumor markers

Treatment ^[45]

• Asymptomatic: supportive care
• Symptomatic
  • Therapeutic thoracentesis
  • Indwelling pleural catheter
  • Chemical pleurodesis
• Treatment of underlying malignancy as needed

Definition ^[7]

• Accumulation of lymphatic fluid from the thoracic duct (chyle) in the pleural cavity

Etiology ^[7]

• Trauma (including iatrogenic)
• Malignancy (e.g., lymphoma, bronchogenic carcinoma)
• Congenital lymphatic anomalies (e.g., lymphangiectasis)

Distinguishing features ^[7]

• Clinical: Chest pain is rare.
• Diagnostics ^[2]
  • Chest CT: underlying malignancy or thoracic injury
  • Lymphangiography: source of chyle leak or obstruction
  • Pleural fluid analysis
    • Cloudy, milky fluid with high concentrations of lipids (triglycerides, cholesterol, chylomicrons, and fat-soluble vitamins)
    • Exudative effusion
    • Total cholesterol usually < 200 mg/dL
    • Triglyceride concentration > 110 mg/dL
    • LDH usually low
    • Glucose level similar to the plasma glucose level
    • Lymphocyte predominance

Treatment of chylothorax ^[46]

• First-line conservative treatment of chylothorax
  • Total parenteral nutrition and special diet
  • Adjunctive medication: somatostatin and octreotide
  • Therapeutic thoracentesis as needed based on symptoms and the patient's functional needs
  • Treatment of underlying disorder
• Surgical treatment: via thoracotomy, thoracoscopy, or VATS
  • Indications
    • Unsuccessful conservative treatment
    • Clinical deterioration (e.g., nutritional or metabolic)
    • Chyle drainage
      • > 1,000–1,500 mL/day
      • Up to 1,000 mL/day for ≥ 5 days
      • Unchanged over 1–2 weeks
    • Persistent chyle leak: > 100 mL/day for > 2 weeks
  • Procedures
    • Thoracic duct: leak repair or ligation
    • Pleura: defect repair, pleurodesis, or pleurectomy
    • Diversion of chyle into a vein, the peritoneum, or externally
• Interventional radiology
  • Indications: an alternative for patients who cannot tolerate operative procedures and for whom the treatment is anatomically feasible
  • Procedures
    • TIPS procedure (for hepatic chylothorax)
    • Embolization or disruption of the lymph ducts
    • Percutaneous repair of the thoracic ducts

Definition ^[7][47]

• Accumulation of cholesterol-rich fluid due to chronic inflammation in the pleural cavity

Etiology ^[7][47]

• Chronic pleural inflammation (e.g., due to underlying rheumatoid arthritis, pulmonary tuberculosis)

Distinguishing features ^[7][47]

• Clinical
  • Chronic symptoms of underlying disorder
  • Dyspnea and chest pain in ∼ 75% of patients ^[47]
• Diagnostics
  • Imaging: signs of underlying disorder
  • Pleural fluid analysis
    • Cloudy, milky appearance
    • Exudative effusion
    • Total cholesterol usually > 200 mg/dL
    • Triglyceride concentration < 110 mg/dL
    • Presence of cholesterol crystals

In contrast to chylothorax, a pseudochylothorax is characterized by high cholesterol and low triglyceride levels in the pleural fluid. The presence of cholesterol crystals may also help to differentiate a pseudochylothorax from a chylothorax.

Treatment

• Identical to first-line conservative treatment of chylothorax ^[47]

Etiology ^[48][49]

• Viral infections
  • Most common cause
  • Adenovirus, coxsackieviruses, CMV, EBV, influenza virus, parainfluenza virus, RSV
• Bacterial infections
  • Pneumonia (parapneumonic pleuritis)
  • Tuberculosis (TB pleuritis)
• Inflammatory conditions
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Sjoegren syndrome
• Pulmonary conditions
  • Pneumothorax
  • Asbestosis
  • Malignancy e.g., mesothelioma
  • Pulmonary embolism
• Cardiac conditions
  • Myocardial infarction
  • Aortic dissection
  • Cardiac surgery
• Drugs
  • Amiodarone, bleomycin, methotrexate
  • Isoniazid, procainamide, hydralazine

Clinical features

• Pleuritic chest pain
• Pleural friction rub
• Further symptoms depend on the underlying disease, e.g.:
  • Dry cough
  • Dyspnea
  • Shortness of breath
  • Constitutional symptoms

Diagnosis ^[50]

• History and physical examination
• Chest x-ray: signs of underlying pulmonary pathology e.g., pneumonia, pleural effusion
• Further investigation to rule out differential diagnoses; e.g., ECG to assess for signs of MI or pericarditis

Differential diagnosis of pleuritic chest pain ^[50]

• Myocardial infarction
• Pulmonary embolism
• Pneumothorax
• Pericarditis
• Bornholm disease

Treatment ^[48]

• Analgesia: NSAIDs (first-line) can be used for relief of symptoms
• Treat underlying cause accordingly.

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