Pleural Effusion: Causes and Treatment

Last Updated on December 11, 2019

A pleural effusion is an abnormal collection of fluid in the pleural space resulting from excess fluid production or decreased absorption or bot

The estimated prevalence of pleural effusion is 320 cases per 100,000 people. There is no gender predilection, though it may be seen depending on the causative disease.

For example, pleural effusion associated with systemic lupus erythematosus is also more common in women than in men and pleural effusions associated with chronic pancreatitis are more common in males.

Pleural effusions usually occur in adults. However, they appear to be increasing in children, often in the setting of underlying pneumonia.

Pathophysiology and Causes of Pleural Effusion

The normal pleural space contains approximately 10 mL of fluid, representing the balance between

• Hydrostatic and oncotic forces in the visceral and parietal pleural vessels
• Extensive lymphatic drainage.

Pleural effusions result from disruption of this balance.

The following mechanisms play a role in the formation of pleural effusion:

• Altered permeability of the pleural membranes as in inflammation
• Decrease in intravascular oncotic pressure  as in  hypoalbuminemia
• Increased capillary permeability or vascular disruption as in trauma, malignancy, inflammation etc
• Increased capillary hydrostatic pressure in the systemic and/or pulmonary circulation as in congestive heart failure
• Reduction of pressure in the pleural space, due to the inability of the lung to fully expand during inspiration [trapped lung] as in extensive atelectasis due to obstructed bronchus or contraction from fibrosis
• Decreased lymphatic drainage or complete blockage, including thoracic duct obstruction or rupture in  malignancy or trauma
• Increased peritoneal fluid, with migration across the diaphragm via the lymphatics or structural defect (cirrhosis, peritoneal dialysis)

Types of Pleural effusion

Pleural effusions are generally classified as transudates or exudates, based on the mechanism of fluid formation and chemistry of pleural fluid.

Transudates result from an imbalance in oncotic and hydrostatic pressures, whereas exudates are the result of inflammation of the pleura or decreased lymphatic drainage.

More on transudates and exudates

Transudates

Transudates are usually ultrafiltrates of plasma in the pleura due to an imbalance in hydrostatic and oncotic forces in the chest. However, they can also be caused by the movement of fluid from peritoneal spaces or by iatrogenic infusion into the pleural space.

Causes of Tranusdative Pleural Effusion

• Cirrhosis
• Atelectasis [Malignancy or pulmonary embolism]
• Hypoalbuminemia
• Nephrotic syndrome
• Peritoneal dialysis
• Myxedema
• Constrictive pericarditis
• Cerebrospinal fluid (CSF) leaks to the pleura
  • Ventriculopleural shunting
  • Trauma
  • Surgery of  the thoracic spine
• Extravascular migration of the central venous catheter
• Glycinothorax – A rare complication of bladder irrigation with 1.5% glycine solution following urologic surgery

Exudates

Exudates are the result of inflammation of the pleura or decreased lymphatic drainage

Exudates arise from

• Pleural or lung inflammation
• Impaired lymphatic drainage of the pleural space
• Transdiaphragmatic movement of inflammatory fluid from the peritoneal space
• Altered permeability of pleural membranes
• Increased capillary wall permeability

The more common causes of exudates include the following:

• Parapneumonic causes
• Malignancy
  • Lung cancer
  • Breast cancer
  • Lymphoma
  • Leukemia
  • Ovarian carcinoma
  • Stomach cancer
  • Sarcomas
• Pulmonary embolism
• Collagen-vascular conditions
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
• Tuberculosis
• Pancreatitis
• Trauma
• Postcardiac injury syndrome
• Esophageal perforation
• Radiation pleuritis
• Sarcoidosis
• Fungal infection
• Pancreatic pseudocyst
• Intra-abdominal abscess
• Meigs syndrome  – Benign pelvic neoplasm with ascites and pleural effusion
• Ovarian hyperstimulation syndrome
• Drug-induced
• Asbestos-related pleural disease
• Yellow nail syndrome (yellow nails, lymphedema, pleural effusions)
• Uremia
• Localized pleural scarring
• Chylothorax

Clinical Presentation of Pleural Effusion

The symptoms of pleural effusion vary and often are related to the underlying disease. Dyspnea [most common], cough, and pleuritic chest pain are the usual symptoms.

Dyspnea is due to distortion of the diaphragm and chest wall during respiration. Dyspnea may be caused by the underlying condition causing the pleural effusion [intrinsic lung or heart disease etc.]

A cough in patients with pleural effusion is often mild and nonproductive.

Pain may be mild or severe, localized to the chest wall or referred to the ipsilateral shoulder or upper abdomen. The referred pain occurs because of diaphragmatic irritation. The pain is felt as sharp or stabbing and is exacerbated with deep inspiration.

Pain may decrease in intensity as the pleural effusion increases in size and the inflamed pleural surfaces are no longer in contact with each other.

There may be present associated symptoms which suggest the underlying disease process.

• Lower extremity edema, orthopnea, and paroxysmal nocturnal – congestive heart failure.
• Night sweats, fever, hemoptysis, and weight loss – Tuberculosis
• Hemoptysis –  Malignancy, endotracheal or endobronchial pathology, or pulmonary infarction.
• Acute fever, purulent sputum, and pleuritic chest – pneumonia.
• History of chronic hepatitis or alcoholism with cirrhosis – hepatic, hydrothorax or alcohol-induced pancreatitis
• Recent trauma or spine surgery – CSF leak.

Generally, there are no physical findings for effusions smaller than 300 mL. With effusions larger than 300 mL, findings may include the following:

• Dullness to percussion
• Decreased tactile fremitus
• Asymmetrical chest expansion [diminished or delayed expansion on the side]
• Mediastinal shift away from the effusion. [ in effusions > 1000 mL]. Trachea and mediastinum shift toward the side of the effusion indicates obstruction of a lobar bronchus.
• Diminished or inaudible breath sounds
• Egophony
• Pleural friction rub

Other physical findings suggesting the underlying cause of the pleural effusion:

• Peripheral edema, distended neck veins suggest congestive heart failure.
• Edema – nephrotic syndrome, pericardial disease, or the yellow nail syndrome.
• Cutaneous changes and ascites  – Liver disease.
• Lymphadenopathy or a palpable mass suggests malignancy.

Differential Diagnoses

• Congestive heart failure
• Diaphragmatic injuries
• Esophageal rupture and tears

Lab Studies

Laboratory testing helps to distinguish pleural fluid transudates from exudates.

Thoracentesis should be performed if sufficient fluid is present. It may not be performed when benign etiologies are likely such as overt congestive heart failure, viral pleurisy, or recent thoracic or abdominal surgery. In such cases, observation of the fluid is sufficient.

After thoracocentesis, it needs to be established if the fluid is transudate or exudate.

Normal pleural fluid

[Pleural fluid analysis]

The normal pleural fluid has the following characteristics:

• A pH of 7.60-7.64
• Protein content of less than 2% (1-2 g/dL)
• < 1000 white blood cells
• Glucose similar to that of plasma
• Lactate dehydrogenase less than 50% of plasma

Certain types of exudative pleural effusions might be suspected by observing the gross characteristics of the fluid

Frankly purulent fluid indicates an empyema

• A putrid odor –  anaerobic empyema
• A milky, opalescent fluid – chylothorax
• Grossly bloody fluid – trauma, malignancy, postpericardiotomy syndrome, or asbestos-related effusion
• Black pleural fluid Aspergillus niger infection or Rizopus oryzae, malignant melanoma, non-small cell lung cancer or ruptured pancreatic pseudocyst, or charcoal-containing empyema

Additional Laboratory Tests

These tests are warranted to look for specific etiologies.

Pleural fluid amylase levels if pleural effusion is

• Of pancreatic origin
• Ruptured esophagus is suspected
• Unilateral, left-sided pleural effusion remains undiagnosed after initial testing.
• Pleural fluid amylase can also be seen with malignancy.

Triglyceride and cholesterol levels in milky pleural fluids when chylothorax or pseudochylothorax is suspected.

Consider immunologic studies, including pleural fluid antinuclear antibody and rheumatoid factor, when collagen-vascular diseases are suspected.

Biopsy

Pleural biopsy should be considered, only if TB or malignancy is suggested. Medical thoracoscopy with the patient under conscious sedation and local anesthesia.

Imaging

Chest Radiography

Blunting of the costophrenic angle on upright posteroanterior chest radiographs seen when pleural effusion more than 175 ml.

Lateral decubitus films more reliably detect smaller pleural effusions.

Supine x-rays show pleural effusions as a homogeneous increase in density spread over the lower lung fields.

A mediastinal shift away from the pleural effusion indicates a positive pleural pressure and compression of the underlying lung

A mediastinal shift towards the side of the effusion indicates an endobronchial obstruction.

CT

• Should be performed in all patients with an undiagnosed pleural effusion
• Can detect thickened pleura or signs of invasion of underlying or adjacent structures.
• CT angiography in pulmonary embolism

Idiopathic Exudative Effusions

In spite of this work up, about 20% of exudative effusions remain undiagnosed.

Look for

• Occupational exposure to asbestos 10-20 years earlier
• Drug exposure to nitrofurantoin, amiodarone, or medications associated with a drug-induced lupus syndrome
• Hepatic hydrothorax unrecognized in a patient with minimal or undetectable ascites.

No further evaluation is necessary if the patient has all of the following

• Patients are clinically stable
• Patients do not have weight loss
• Negative purified protein derivative (PPD) test and pleural adenosine deaminase < 43 U/mL
• No fever
• < 95% lymphocytes in pleural fluid
• The effusion occupies less than 50% of the hemithorax

For other patients, the following tests should be done

• Bronchoscopy – If a patient has parenchymal abnormalities or hemoptysis
• Pleuroscopy and thoracoscopy for direct visualization and biopsy

Treatment of Pleural Effusion

Transudative effusions are managed by treating the underlying medical disorder.

The management of exudative effusions depends on the underlying etiology of the effusion.

• Complicated parapneumonic effusions and empyemas should be drained
• Malignant effusions are usually drained to palliate symptoms and may require pleurodesis to prevent recurrence.
• Stopping the medications

Regardless of whether transudative or exudative, large, refractory pleural effusions causing severe respiratory symptoms can be drained to provide symptomatic relief.

Parapneumonic effusions

Indications for urgent drainage of parapneumonic effusions include

• Frankly purulent fluid
• Pleural fluid pH of less than 7.0-7.1
• Loculated effusions
• Bacteria on Gram stain or culture.

Otherwise, patients should improve clinically within one week with appropriate antibiotic treatment.

Malignant pleural effusions

It signifies incurable disease and mean survival of less than one year. Drainage of large, malignant effusions for relieving dyspnea may be done though they tend to recur.

Tuberculous pleuritis

Tuberculous pleuritis is typically self-limited. Empirical anti-TB treatment is usually begun pending culture results when sufficient clinical suspicion is present.

Chylous effusions

Chylous effusions are usually managed by dietary and surgical modalities. somatostatin analogs also may help.

So does the restriction of fat intake.

Drugs

Drugs used in pleural effusion depends on the condition’s etiology.

For example

• Nitrates and diuretics for congestive heart failure and pulmonary edema
• Antibiotics for parapneumonic effusion and empyema, esophageal perforation
• Anticoagulation for pulmonary embolism.

Surgical treatment

Therapeutic Thoracentesis

Therapeutic thoracentesis is used to remove larger amounts of pleural fluid to alleviate dyspnea and to prevent ongoing inflammation and fibrosis in parapneumonic effusions.

More on thoracocentesis

Tube Thoracostomy

Complicated parapneumonic effusions or empyemas require drainage by tube thoracostomy.

Traditionally, large-bore chest tubes have been used to drain the thick pleural fluid and to break up loculations in empyemas.

More on tube thoracostomy

Pleurodesis

Pleurodesis or pleural sclerosis involves instilling an irritant into the pleural space to cause inflammatory changes that result in bridging fibrosis between the visceral and parietal pleural surfaces. It effectively obliterates the potential pleural space.

Pleurodesis is most often used for recurrent malignant effusions and expected life expectancy > 3 months. The goal of therapy is to palliate symptoms while minimizing patient discomfort.

A patient with a life expectancy of fewer than 3 months should be treated with repeated outpatient thoracentesis as needed to palliate symptoms

Sclerosing agents used are talc, doxycycline, bleomycin sulfate (Blenoxane), zinc sulfate, and quinacrine hydrochloride.

Talc is the most effective sclerosing commercially available agent.

Indwelling Tunneled Pleural Catheters

Tunneled pleural catheters can be inserted and intermittently drained at home.

It is used to relieve refractory symptoms from recurrent effusions due to class III or IV heart failure.

Surgically implanted pleuroperitoneal shunts are another treatment option.

Decortication

Decortication is usually removal of the thick, inelastic pleural peel that restricts ventilation and produces progressive or refractory dyspnea.

Other surgeries

Closure of diaphragmatic defects prevents recurrent accumulation of pleural effusions in patients with ascites. Ligation of the thoracic duct is done to prevent reaccumulation of chylous effusions.

Prognosis

The prognosis in pleural effusion varies in accordance with the condition’s underlying etiology. However, patients who seek medical care earlier have a substantially lower rate of complications than do patients who do not.

Morbidity and mortality of pleural effusions are directly related to cause and stage of the underlying disease at the time of presentation, and biochemical findings in the pleural fluid.