Pleural Fluid

Aka: Pleural Fluid, Pleural Fluid Analysis, Pleural Fluid Examination, Thoracentesis Interpretation, Transudate Pleural Effusion Findings, Exudate Pleural Effusion Findings, Empyema Pleural Effusion Findings, Bloody Pleural Effusion Findings

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II. Indications

  1. Evaluation of Pleural Effusion

III. Technique

  1. Fluid for analysis is obtained during Thoracentesis

IV. Labs: Recommended Pleural Fluid Panel

  1. Pleural Fluid Gram Stain
  2. Pleural Fluid Cell Count with Differential
  3. Pleural Fluid culture
  4. Pleural Fluid cytology
  5. Pleural Fluid Protein (and Serum Protein)
  6. Pleural Fluid LDH (and serum LDH)

V. Labs: Initial - Differentiate transudate from exudate

  1. See exudate interpretation below
  2. Light Criteria for Exudate (Adult Patients only, positive if any 1 of 3 criteria positive)
    1. Pleural Fluid Protein to Serum Protein ratio >0.5 OR
    2. Pleural Fluid LDH to serum LDH ratio >0.6 OR
    3. Pleural Fluid LDH > 0.67 x serum LDH upper limit of normal
    4. Test Sensitivity 95.5% and Test Specificity 85%
    5. False Positives (mis-identifies transudate as exudate up to 25% of time, esp after Diuretics)
      1. False Positive Light Criteria typically have borderline positive criteria
      2. Transudates typically have serum to pleural Protein gradient >3.1 g/dl
      3. Transudates typically have serum to pleural albumin gradient >1.2 g/dl
  3. Three Test Rule for Exudate
    1. Pleural Cholesterol >45 mg/dl OR
    2. Pleural LDH >0.45 fold higher than serum LDH upper limit OR
    3. Pleural Fluid Protein >2.9 g/dl
    4. Test Sensitivity 98.4% and Test Specificity 85%
  4. Pleural Lactate Dehydrogenase (LDH, compared with serum LDH)
    1. Correlates with level of inflammation within pleural space, and distinguishes exudate from transudate
    2. Pleural LDH >300 IU/L
      1. Exudative Pleural Effusion ( Test Sensitivity: 70%, Test Specificity: 98%)
    3. Pleural LDH >1000 IU/L
      1. Empyema
      2. Parapneumonic Effusion
      3. Cholesterol effusion
      4. Rheumatoid pleuritis
      5. Lymphoma
  5. Pleural Protein (compared with Serum Protein)
    1. Pleural Protein <1 g/dl
      1. MIgration of Ventriculoperitoneal Shunt
      2. Migration of central venous catheter
      3. Peritoneal Dialysis
      4. Urinothorax
    2. Pleural Protein >3 g/dl
      1. Exudative Pleural Effusion ( Test Sensitivity: 88%, Test Specificity: 86%)
    3. Pleural Protein >4 g/dl
      1. Tuberculosis
      2. Cholesterol effusion
    4. Pleural Protein >7-8 g/dl
      1. Paraproteinemia (e.g. Multiple Myeloma, waldenstrom Macroglobulinemia)

VI. Labs: Initial - Identify cause (especially exudate)

  1. In addition to pleural LDH and pleural Protein as above)
  2. Pleural cell count with differential
    1. WBC <300 to 1000/ul
      1. Transudate
    2. WBC >500 to 1000/ul
      1. Exudate
    3. WBC >10000/ul
      1. Parapneumonic Effusion
      2. Acute Pancreatitis
      3. Pulmonary Infarction
      4. Lupus pleuritis
      5. Rheumatoid Pleuritis
      6. Pericardial Injury Syndrome
    4. WBC>50000/ul
      1. Pancreaticopleural fistula
    5. Neutrophil predominance
      1. Acute Parapneumonic Effusion (half of cases)
      2. Pulmonary Embolism
      3. Acute Pancreatitis
      4. Uncommonly due to malignancy or Tuberculosis (typically Lymphocyte predominance)
    6. Lymphocyte predominance
      1. Malignancy
      2. Tuberculosis
      3. Post-CABG
      4. Chylothorax
      5. Sarcoidosis
      6. Rheumatoid Pleuritis
    7. Eosinophil predominance (esp. Eosinophil percentage >10%)
      1. Drug-Induced Pleural Effusion
      2. Malignancy (not typically responsible for very high Eosinophil Counts)
      3. Hemothorax
      4. Pneumothorax
      5. Asbestosis
      6. Lung Fungal Infection
      7. Lung Parasitic Infection
      8. Pulmonary Embolism with Pulmonary Hemorrhage
  3. Pleural Gram Stain and culture
    1. Indicated in suspected infection or exudative effusion without identified cause
    2. Cultures identify organism in 70% of empyema, but only 22% of other complicated Parapneumonic Effusions
    3. Obtain Blood Cultures at same time to increase overall sensitivity
    4. Culture does not identify Tuberculosis
  4. Pleural Fluid cytology (Test Sensitivity: 60%)
    1. Test Sensitivity in malignancy is only 50% (but increases to 60% on repeat sampling)
    2. Highest Test Sensitivity for adenocarcinoma
    3. False Negatives in Mesothelioma, Sarcoma, Lymphoma and Squamous Cell Carcinoma
    4. Immunocytochemistry may identify specific tumor types
      1. Tumor Markers include epithelial membrane Antigen, CEA, calretinin, CA-125, AFP and many others
      2. Tumor Markers may also be used for monitoring known cancer
  5. Pleural Cholesterol
    1. See exudate findings below
    2. Pleural Cholesterol <52 mg/dl
      1. Transudate
    3. Pleural Cholesterol >55 to 60 mg/dl (or Pleural to serum Cholesterol >0.3)
      1. Exudate
    4. Pleural Cholesterol >250 mg/dl (Cholesterol Effusion)
      1. Tuberculosis
      2. Rheumatoid Pleuritis
  6. Pleural Triglycerides
    1. Pleural Triglyceride >110 mg/dl
      1. Chylothorax (Trauma, cancer)
    2. Pleural Triglyceride 50 to 110 mg/dl
      1. Chylothorax (Trauma, cancer) if Chylomicrons present
    3. Pleural Triglyceride <50 mg/dl
      1. Pseudochylothorax (Tuberculosis and other chronic disease)
  7. Pleural Hematocrit
    1. Calculation
      1. Pleural Hematocrit may be estimated from pleural RBC Count / 100,000
      2. Examples
        1. Pleural RBC Count = 1,000,000, the pleural Hematocrit = 10%
        2. Pleural RBC Count = 2,000,000, the pleural Hematocrit = 20%
        3. Pleural RBC Count = 3,000,000, the pleural Hematocrit = 30%
    2. Pleural Hematocrit >1%
      1. Pneumonia
      2. Pulmonary Embolism
      3. Cancer
      4. Trauma
    3. Pleural Hematocrit > (Blood Hematocrit x 0.5)
      1. Hemothorax
  8. Pleural Amylase
    1. Pleural amylase 100 IU/L to 139 IU/L (or pleural to Serum Amylase level >1)
      1. Malignancy
      2. Esophageal Rupture
      3. Pancreatic Disease
    2. Pleural amylase >100,000 IU/L
      1. Pancreaticopleural fistula
  9. Pleural pH
    1. Pleural pH < 7.20
      1. Parapneumonic Effusion or empyema
      2. Esophageal Perforation
    2. Pleural pH <7.30
      1. Malignant effusion
      2. Connective Tissue Disease (e.g. Rheumatoid Pleuritis, Rheumatoid Pleuritis)
    3. Pleural pH 7.45 to 7.55
      1. Transudate
    4. Pleural pH 7.30 to 7.44
      1. Exudate
      2. Pancreatic effusion
  10. Pleural Glucose
    1. Glucose = 0 mg/dl
      1. Rheumatoid Pleuritis
      2. Empyema
    2. Glucose <60 mg/dl
      1. Parapneumonic Effusion or empyema
      2. Hemothorax
      3. Churg-Strauss Syndome
      4. Esophageal Rupture
      5. Lupus Pleuritis
    3. Glucose same in pleural as plasma (normal)
      1. Most transudates
      2. Many exudates
    4. Glucose greater in pleura than plasma
      1. Esophageal Rupture with continued intake
      2. Migration of central venous catheter infusing dextrose
      3. Peritoneal Dialysis
  11. Pleural NT-BNP
    1. Similar levels in both serum and pleura
    2. Pleural NT-BNP >1500 pg/ml suggests Congestive Heart Failure
  12. Adenosine deaminase (ADA)
    1. Adenosine deaminase >35 to 40 U/L
      1. Tuberculosis (Test Sensitivity 93%, Test Specificity 90%)
    2. Adenosine deaminase >250 U/L (extremely high)
      1. Empyema
      2. Lymphoma

VII. Labs: Initial - Pleural Fluid gross exam

  1. Transudate
    1. Textbooks describe transudate as watery, clear, pale yellow color
    2. However, this textbook appearance is only present in 15% of cases
  2. Bilious fluid (green fluid)
    1. Cholothorax from biliary fistula
    2. Rheumatoid Pleuritis (green yellow fluid)
  3. Bloody fluid
    1. Malignancy (bloody in 40% of cancer-related Pleural Effusion)
    2. Trauma
    3. Pulmonary Embolism (bloody in 60% of PE-related Pleural Effusion)
    4. Postcardiac injury syndrome
    5. Asbestosis
    6. Traumatic Thoracentesis (vessel injury on entry)
  4. Black fluid
    1. Aspergillus infection
  5. Brown fluid
    1. Ruptured amoebic abscess
  6. Food particulate matter
    1. Esophageal Rupture or perforation
  7. Milky fluid
    1. Pustular fluid (empyema)
      1. Supernatant is clear when centrifuged
    2. Lipids and cholesterol Pleural Effusions (supernatant remains white when centrifuged)
      1. Chylothorax due to lymph
        1. Increased Triglyceride >110 mg/dl,
        2. Chylomicrons
        3. Pleural to serum Cholesterol ratio <1
      2. Pseudochylothorax
        1. Decreased Triglyceride <50 mg/dl (poor Test Sensitivity but excludes Chylothorax)
        2. Cholesterol crystals
      3. Cholesterol effusion
      4. Migrated Central Venous Catheter infusing Total Parenteral Nutrition
  8. Pustular Fluid (Empyema)
    1. Pus is yellow-white opaque, viscous fluid
    2. Pus from Empyema is the only fluid accurately defined on gross fluid exam
  9. Foul odor
    1. Anaerobic empyema (50% are putrid)
  10. Urine (ammonia or urine smell)
    1. Urinothorax
  11. Clear fluid with water-like viscosity
    1. Cerebrospinal Fluid Leakage (displaced Ventriculoperitoneal Shunt)
  12. Viscous Fluid
    1. Empyema (pus)
    2. Malignant Mesothioma

VIII. Labs: Inital - Other labs (as indicated)

  1. Urine Protein (Nephrotic Syndrome)
  2. Thyroid Stimulating Hormone or TSH (Hypothyroidism)

IX. Labs: Other - Infection suspected

  1. PCR for Streptococcus Pneumoniae
  2. Infection suspected despite non-purulent fluid
    1. Pleural Fluid pH
  3. Tuberculosis suspected
    1. Adenosine deaminase (see above)
      1. Sensitive and specific for Tuberculosis at >90%
      2. Extremely elevated levels in Lymphoma and empyema
    2. Interferon (alternative to Adenosine deaminase)
    3. PCR for Mycobacterium tuberculosis
    4. Culture for Mycobacterium tuberculosis
    5. Acid Fast Bacillus (AFB) smears are rarely positive

X. Labs: Other - Cancer suspected

  1. Tumor Markers
    1. Carcinoembryonic Antigen
    2. Cancer Antigen 125
    3. Cancer Antigen 15-3
    4. Cytokeratin 19 fragment
    5. Mesothelin
  2. Pleural amylase (Cancer, Pancreatitis, Esophageal Perforation, Tuberculosis)
  3. Triglycerides (Lymphoma, Trauma)

XI. Findings: Transudate

  1. See Transudate Pleural Effusion Causes
  2. Clear fluid
  3. Protein < 3 g/dl
  4. Lactate Dehydrogenase (LDH) <200 IU/L
  5. Glucose >60 mg/dl
  6. White Blood Cell Count <300-1000/ml

XII. Findings: Exudate

  1. See Exudate Pleural Effusion Causes
  2. False Positive in CHF after Diuretics
    1. Correction for Diuretics: Serum Protein - Pleural Protein >3.1 g/dl
    2. Correction for Diuretics: Serum Albumin - pleural albumin >1.2 g/dl
  3. Clear, cloudy or bloody fluid
  4. Protein
    1. Pleural Protein > 3 g/dl
    2. Pleural Protein to Serum Protein ratio >0.5
  5. Lactate Dehydrogenase
    1. Pleural LDH > 200 IU/L
    2. Pleural LDH > 2/3 serum LDH upper normal limit
    3. Pleural LDH to serum LDH ratio >0.6
  6. Glucose < 60 mg/dl
  7. White Blood Cell Count >500-1000/ml
  8. Pleural Cholesterol
    1. Pleural Cholesterol >55 mg/dl
    2. Pleural Cholesterol to serum Cholesterol ratio > 0.3

XIII. Findings: Empyema

  1. See Empyema Pleural Effusion Causes
  2. White Blood Cell Count > 10,000 cells/cu mm
  3. Gram Stain
  4. Pleural Fluid culture positive
  5. Glucose > 40 mg/dl
  6. pH < 7.2
  7. Additional tests to consider when infection suspected
    1. Consider PCR for Streptococcus Pneumoniae
    2. Tuberculosis Testing is described above

XIV. Findings: Uniformly bloody effusion

  1. See Bloody Pleural Effusion Causes
  2. Causes include cancer, PE, Trauma, Asbestosis, Traumatic Thoracentesis
  3. Fluid Hematocrit >1% (Hemothorax if >50% Hematocrit)
  4. Red Blood Cell Count >100,000 per mm3

XV. References

  1. Natesan (2020) Crit Dec Emerg Med 34(7): 29-41
  2. Hooper (2010) Thorax 65(suppl 2): ii4-17 [PubMed]
  3. Light (2002) N Engl J Med 346:1971-7 [PubMed]
  4. Medford (2005) Postgrad Med J 81 (961):702-10 [PubMed]
  5. Porcel (2006) Am Fam Physician 73:1211-20 [PubMed]
  6. Rabman (2005) Br Med Bull 72:31-47 [PubMed]
  7. Saguil (2014) Am Fam Physician 90(2): 99-104 [PubMed]

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