Pleural Effusion

This is the diagnostic term given to the accumulation of exudative fluid of inflammatory origin within the pleural space. Pleural effusion is characterized by exudative fluid with a protein content of >3gm/dL and a specific gravity (SG) >1.015. Pleural inflammation associated with effusion can be classified into different types:

Dry or Plastic Pleurisy

In this type, inflammation is limited to the visceral pleura, resulting in a small amount of serous (clear yellow) or slightly cloudy fluid. This type of effusion is neutrophilic and occurs due to increased passage of interstitial fluid caused by inflammation. Gram stain or culture of the effusion does not yield any organism.

Serofibrinous or Serosanguineous Pleurisy

This type of pleurisy presents with exudative fluid similar to dry pleurisy, but with a larger volume of effusion.

Empyema (Purulent Pleurisy)

Empyema is associated with visibly purulent thoracocentesis fluid. The fluid has a low pH and a high lactate dehydrogenase (>200IU), indicating a severe infection.

Aetiopathogenesis of Excess Pleural Fluid Accumulation

Pleural effusion or fluid accumulation in the pleural space arises due to an imbalance between filtration and absorption forces, or when lymphatic drainage is compromised. These situations can be categorized as follows:

Increased Filtration in the Presence of Impaired Absorption

In this scenario, there is a heightened filtration of fluid into the pleural space, but the ability to absorb the fluid is impaired.

Normal Filtration in the Presence of Impaired Absorption or Lymphatic Drainage

This situation involves a regular level of fluid filtration, but either the absorption or removal of the fluid through lymphatic channels is hindered.

Types of Pleural Fluid and Associated Clinical Disorders

Type of Fluid (Synonymous Diagnostic Terms)	Associated Clinical Disorders	Pathophysiological Mechanisms
Serofibrinous (Pleural Effusion, Parapneumonic effusion)	Contiguous bacterial pneumonia, Pulmonary tuberculosis, lung infarction, malignancies [primary or metastatic], viral hepatitis, sarcoidosis, pancreatitis, hepatic abscess, and connective tissue diseases (e.g. rheumatoid arthritis and systemic lupus erythematosus)	Increased pleural capillary permeability, or increased oncotic pressure of the interstitial space
Purulent (Empyema thoracis, Pyothorax, or Purulent Pleurisy)	Contiguous pyogenic bacterial pneumonia (especially Staph. aureus & Strept. pneumoniae), Pulmonary tuberculosis, Lung abscess	Increased pleural capillary permeability
Hydropthorax	Hypoproteinaemic states (e.g. nephrotic syndrome, hepatic cirrhosis), peritoneal dialysis, congestive cardiac failure, overhydration and venous obstruction with [venous] hypertension	Increased capillary hydrostatic pressure, decreased plasma oncotic pressure, or inappropriate lymphatic flow (with either inadequate outflow or excessive inflow)
Chylothorax	Congenital chylothorax, hereditary lymphoedema, thoracic duct obstruction, mediastinal lymphadenopathy & fibrosis	Impaired lymphatic flow
Haemothorax	Chest trauma, pulmonary tuberculosis, blood dyscrasias, pulmonary malignancies	Vascular leakage or (neoplastic) erosion

The degree and type of functional pathology associated with pleural effusion depends on:

1. The volume of the fluid,
2. The rapidity of the accumulation,
3. The nature of the fluid.

An increase in the elastic resistance to distension and reduction in lung volume are associated with moderate or massive pleural effusion. Mediastinal displacement may impair contralateral lung expansion, while there is an ipsilateral diaphragmatic displacement. The overall functional pathology includes impaired gaseous exchange and cardiac function.

The general/systemic symptoms and signs of pleural effusion depend on the underlying disease, but the size of the fluid in the pleural space and the thoracic size determine whether or not there are suggestive chest symptoms and findings on clinical examination.

Infective disorders like pneumonia and pulmonary tuberculosis may present with fever and/or weight loss, while anemia is usually associated with post-Staphylococcal pneumonia empyema. Underlying hypoproteinemic states (e.g. nephrosis) may be associated with generalized edema, liver cirrhosis with jaundice and ascites, while prominent joint symptoms may suggest juvenile rheumatoid arthritis.

• Small effusions are generally asymptomatic.
• Large effusions may be associated with mediastinal shift & cardiorespiratory difficulties.
• The triad of cough, breathlessness, and grunting respiration are the commonest symptoms of moderate to severe pleural effusion in children.
• The older child may complain of (pleuritic) chest pain on the affected side or, if the central diaphragm is affected, may have referred shoulder or back pain. Pain may be worsened by straining, coughing, and deep breathing. Occasionally, the child may present with abdominal pain.

Physical Findings of Pleural Effusion

Physical findings of pleural effusion depend on the amount of fluid and the primary morbidity.

At the Stage of Dry Pleurisy:

• A rough friction rub may be heard at inspiration.
• To minimize pleuritic pain, the breathing may be shallow, and the child lies on the affected side at the early stage.
• Grunting respiration.

As Fluid Accumulation Progresses:

• Thoracic excursions may be visibly impaired on the affected side, and occasionally there may be fullness of the intercostal spaces.
• A tracheal/cardiac apex shift to the opposite side.
• Decreased tactile fremitus and vocal resonance, as well as dullness to percussion (which may not necessarily be stony in children due to smaller thoracic dimensions).
• Diminished or absent breath sounds. In neonates and infants, however, the breath sounds may be deceptively loud and clear, or of bronchial quality due to the small thoracic volume. Except in loculated effusions, the above signs may shift with changes in posture.
• Other respiratory features include cyanosis in severe disease, tachypnea, chest wall retractions, and orthopnea.

Course: Except for purulent effusion or empyema (vide infra), tuberculosis and the dyscollagenoses, in all of which a protracted course is expected, the majority of exudative effusions, especially para-pneumonic serous/serofibrinous varieties, are expected to resolve with treatment/resolution of the primary lesion.

The pleura, a double membrane, consists of:

• The inner visceral pleura surrounding each lung
• The outer parietal pleura lining the thoracic cavity

The space between these membranes is the pleural cavity.

The pleural space:

• Is maintained at sub-atmospheric negative pressure
• Contains a thin layer of pleural fluid, acting as a lubricant during breathing
• Healthy pleural fluid volume is about 0.13ml/kg
• Maintained by hydrostatic pressure, oncotic pressure, and lymphatic drainage

The visceral and parietal layers of pleura:

• Lined with flat ciliated mesothelial cells and collagen/elastic fiber layers
• Contain blood and lymphatic vessels
• Prevent pleural fluid accumulation through efficient reabsorption at capillaries
• In health, separated by only 1ml of pleural fluid

Balance between filtration and absorption is governed by Starling forces:

• Convective movement of fluid between vascular and extravascular compartments
• Relationship between Starling forces is illustrated in the table below:

Net liquid re-absorption occurs because the absorptive pressure slightly exceeds the filtration pressure. Comparing the values of filtration and absorptive forces at the parietal and visceral pleurae, fluid is primarily filtered from the parietal end, while absorption mainly occurs at the visceral end.

Abnormalities of the pleural space can involve abnormal accumulation of:

1. Fluid (pleural effusion)
2. Air (pneumothorax)
3. Purulent fluid (empyema)
4. Blood (hemothorax)
5. Lymphatic fluid
6. Mixtures like air and fluid, pus and air

The aims of investigations in pleural effusion include:

• Identifying the presence and nature of the fluid
• Confirming the presence of fluid in the pleural space
• Evaluating co-morbid intrathoracic lesions
• Assessing the microbiological characteristics of the fluid

Radiologic Evaluation: Radiologic methods are crucial for confirming pleural effusion presence, including chest radiography, ultrasonography, and CT scan.

Chest Radiography: Findings depend on fluid nature (free/loculated), size, patient position (supine/upright), and underlying lung pathology.

• Small Effusion: Obliteration of costophrenic or cardiophrenic angles, lateral chest wall fluid extension. Lateral decubitus aids small effusion detection.
• Large Free Pleural Effusion: Dependent homogenous opacity, upward sloping meniscus, diaphragmatic contour obliteration (silhouette sign). Lung collapse and contralateral mediastinal shift may occur.
• Loculated Fluid: Semicircular opacity on lateral chest wall or paravertebral gutter, position remains constant.

Chest Ultrasonography: Useful for confirming effusion in patients with abnormal radiographs, guiding interventions (e.g., thoracocentesis), and characterizing effusions.

• Transudates appear anechoic, while exudative effusions are septated and echoic/anechoic.
• Dependent on user skill for diagnosis.

Chest CT Scan: Detects pleural fluid and parenchymal abnormalities; helpful for confirming loculated effusion. Also aids interventions in challenging cases.

• Free effusion appears as crescent-shaped attenuation in dependent areas.
• Unable to differentiate exudates from transudates, limited by cost and availability.

Limitations: CT scans lack predictive value for clinical outcomes, and their use is restricted in resource-constrained areas.

Identifying the Presence and Nature of Fluid (Thoracocentesis and Pleural Fluid Analysis): Thoracocentesis involves inserting a properly sized needle (connected to a 20ml syringe) into the interspace below the point of maximal dullness, using the inferomedial angle of the scapula on the affected side as a landmark. Insert the needle just above a rib to avoid intercostal vessels, and maintain continuous plunger pull as the needle passes through the parietal pleura. Pleural fluid obtained through thoracocentesis is analyzed based on:

1. Fluid Appearance:
   • Clear Color: Transudative collection (hydrothorax).
   • Straw/Amber Color: Exudative effusion.
   • Purulent Appearance: Empyema thoracis.
   • Bloody or Milky Appearance: Hemothorax or chylothorax, respectively.
   • Putrid Odor: Anaerobic effusion.
   • Black Pleural Effusion: Aspergillus nigrans infection.
2. Biochemistry and Pleural Cell Count:

   Biochemistry aids in differentiating transudates from exudates (Table 1). Elevated pleural adenosine deaminase levels indicate tuberculous pleural effusion. Predominant cell types in pleural fluid suggest aetiology:

   • Neutrophilic Predominance: Bacterial aetiology, early TB, or pancreatitis.
   • Lymphocytic Predominance (>85%): Tuberculosis, connective tissue disorders, malignancies, or uraemia.
   • Eosinophilic Effusion (>10%): Fungal/parasitic infections, ureaemia, nitrofurantoin.
   • Monocytic Effusion: Viral/mycoplasma pneumonia.
   • Malignant Cells: Rare in pediatric pleural fluid, possible in metastatic Wilm's tumor.

Biochemical Differences between Exudates and Transudates:

Pleural Fluid Content	Exudate	Transudate
Pleura Protein Level	>3g/dL	<3g/dL
Pleura Glucose Level	<40mg/dL	>40mg/dL
Pleura Lactate Dehydrogenase (LDH) Level	>250I.U./L	<200 I.U./L
Pleural Fluid Protein to Serum Protein Ratio	>0.5	<0.5
Pleural Fluid Glucose-to-Serum Glucose Ratio	<0.5	>0.5
Pleural Fluid LDH and Serum LDH Ratio	>0.6 or >2/3	<0.6 or <2/3
Pleura Cholesterol	>45mg/dL	<45mg/dL
Pleura pH	<7.2	>7.3
Pleural Specific Gravity	>1.015	<1.015

Microbiological Characteristics of the Fluid:

The initial Gram stain of the fluid may be positive for the causative bacterial agent in exudative fluids of parapneumonic effusions/empyema.

Countercurrent immunoelectrophoresis (CIE) of pleural fluid is invaluable for detecting bacterial antigens like Staph. aureus and H. influenzae. This provides a presumptive basis for the initial choice of antimicrobials.

Zeil-Nielson stain or GeneXpert tests may confirm a tuberculous origin by identifying acid and alcohol fast bacilli.

Culture and sensitivity testing guides subsequent antimicrobial choices if the initial choice fails.

Supportive Tests:

Haematocrit and blood culture confirm anaemia and septicaemia in purulent effusion cases.

Full blood count shows leucocytosis with polymorphonuclear predominance and a high erythrocyte sedimentation rate.

Biopsy of the parietal pleura may be indicated for suspected tuberculous cases (~60% detectable histopathologically) or suspected primary pleural malignancies.

Atelectasis, hypoxemia, and heart failure are usually transient in non-purulent effusion, but iatrogenic complications from diagnostic thoracocentesis and/or chest tube insertion may include:

• Haemothorax
• Pneumothorax
• Other air-leak syndromes

The principles of managing pleural effusion comprise:

• Specific treatment of the underlying disease
• Evacuation of the fluid in moderate to large effusions
• Supportive care including alleviation of pain

Specific treatment of the underlying disease:

• The administration of effective empirical antimicrobials to treat the underlying pneumonia while awaiting microbiological studies for possible subsequent modification.
• Tuberculous effusions will benefit from antituberculous agents chosen according to national guidelines. The use of steroids in protracted tuberculous effusion is considered adjunctive by some authors.
• Anti-inflammatory agents, especially non-steroidal agents, are useful in pleural effusion associated with collagen vascular diseases like rheumatoid arthritis.

Evacuation of the Fluid and Other Surgical Measures:

• In moderate to large effusions: Evacuation via closed thoracostomy tube drainage (CTTD) placed in the fifth intercostal space midway between the middle and anterior axillary line on the affected side.
• Small effusions: Reabsorb with treatment of underlying disease, usually not requiring evacuation (< 10mm on the lateral decubitus).
• Indications for CTTD include:
  • Moderate to large collections
  • Rapidly progressive disease course
  • Severe respiratory distress
  • Purulent appearance of pleural fluid at thoracocentesis
  • Identification of exudative characteristics in pleural fluid
• Rarely, pleural decortication, thoracoplasty, or open flap drainage may be required in empyema with a protracted clinical course and complicating bronchopleural fistula.
• Pericardiocentesis may be necessary in children with a contiguous pericardial collection.

Supportive Care Including Alleviation of Pleuritic Pain:

• Provide analgesics (paracetamol) to alleviate pain from diagnostic thoracocentesis and/or intra-pleural tube placement.
• Offer supplemental oxygen to ameliorate hypoxemia.
• Treat complications (e.g., congestive heart failure).
• Judicious fluid administration, considering the possibility of syndrome of inappropriate ADH secretion (SIADH).
• Provide calorie-dense feeds.