Pleural Fluid Analysis

It is about interpretation of information delivered as results of pleural fluid exams, including physical characteristics, differentiation between transudates and exudates, cell counts, culture and cytology.

1. Pleural fluid analysis by W alaa Elfar MBBS, MSc (Critical Care Medicine) Registrar Intensivist Security Forces Hospital Program, Riyadh, KSA

2. Thoracentesis (pleural tapping) should be performed for new and unexplained pleural effusions .

3. Cont. physical characteristics Certain types of pleural effusions can be suspected simply by observing the physical characteristics of the fluid obtained: A purulent fluid (pus) indicates an empyema A bad (putrid) odor suggests an anaerobic empyema A milky white fluid suggests a chylothorax (an accumulation of lymphatic fluid in the pleural space)

4. Cont. physical characteristics A bloody fluid suggests either hemorrhagic effusion ( hemothorax ) or traumatic pleural taps . Differentiation is possible by observing serial samples of pleural tap which clear up in the case of a traumatic pleural tap . Moreover , A hematocrit performed on the pleural fluid can assist diagnosis. Bloody pleural fluid with a hematocrit of ≥ 50 % of the peripheral blood hematocrit is termed a hemothorax . CONT

5. Cont. physical characteristics A Black pleural fluid can be seen with some diseases including: Aspergillus niger infection, malignant melanoma , non-small cell lung cancer , ruptured pancreatic pseudocyst , charcoal-containing empyema CONT.

6. Normal Pleural Fluid Characteristics Normal pleural fluid is a Clear ultrafiltrate of plasma that originates from the parietal pleura: pH of 7.60-7.64 Protein content of less than 2% (1-2 g/ dL ) Fewer than 1000 white blood cells (WBCs) per cubic millimeter Glucose content similar to that of plasma Lactate dehydrogenase (LDH) less than 50% of plasma

7. Transudates vs Exudates Light’s criteria are the standard way to differentiate. Light’s criteria for exudative pleural effusion: Pleural fluid protein divided by serum protein > 0.5 Pleural fluid LDH divided by serum LDH > 0.6 Pleural fluid LDH more than two-thirds the upper limit of normal serum LDH

8. CONT. Transudates vs Exudates The fluid is considered an exudate if any of the three criteria (Light’s criteria) is found. The fluid is considered a transudate if all of the three criteria are absent. Light’s criteria require simultaneous measurement of pleural fluid and serum protein and LDH. Clinical judgment is required when pleural fluid test results fall near the cutoff points.

9. CONT. Transudates vs Exudates Light’s criteria identify nearly all exudates correctly, but they misclassify approximately 20-25% of transudates as exudates, usually in patients with HF-associated effusions and those with liver cirrhosis-associated effusions because of the concentrating effect of long-term diuretic therapy on protein and LDH levels within the pleural space).

10. CONT. Transudates vs Exudates To solve such a problem it is recommended to use one of the following If the clinical picture is consistent with HF-associated effusion or liver cirrhosis-associated effusion but the pleural fluid meets Light's exudative criteria: - serum-effusion protein gradient (serum protein minus pleural protein concentration ). If >3.1 g/ dL , it indicates transudate effusion.(5) - serum-effusion albumin gradient (serum albumin minus pleural effusion albumin level). If it is > 1.2 g/ dL , it indicates transudate. (this criterion is preferable If the clinical picture is consistent with HF but the pleural fluid meets Light's exudative criteria ). (5) - effusion-to-serum albumin ratio (pleural fluid albumin divided by serum albumin). If <0.6, it indicates transudate. this criterion is preferable In the context of cirrhosis. (5)

11. CONT. Transudates vs Exudates In a more recent systematic review, pleural fluid cholesterol greater than 55 mg/ dL and pleural fluid LDH greater than 200 U/L each had better positive and negative likelihood ratio for distinguishing exudates from transudates than did Light’s criteria. [ 4 ]

12. Pleural Fluid LDH, Glucose, and pH Pleural fluid LDH Pleural fluid LDH levels › 1000 IU/L suggest: empyema , malignant effusion, rheumatoid effusion. Pleural fluid LDH levels are also increased in effusions from Pneumocystis jiroveci (formerly, Pneumocystis carinii ) pneumonia. The diagnosis of Pneumocystis jiroveci pneumonia is suggested by: - a pleural fluid/serum LDH ratio of › 1, with - a pleural fluid/serum protein ratio of ‹ 0.5.

13. cont. Pleural Fluid LDH, Glucose, and pH Pleural fluid glucose A low pleural glucose concentration (30-50 mg/ dL ) suggests malignant effusion, tuberculous pleuritis , esophageal rupture, or lupus pleuritis . A very low pleural glucose concentration ( ie , < 30 mg/ dL ) further restricts diagnostic possibilities, to rheumatoid pleurisy or empyema.

14. cont. Pleural Fluid LDH, Glucose, and pH Pleural fluid pH Pleural fluid pH is highly correlated with pleural fluid glucose levels . A pleural fluid pH of less than 7.30 with a normal arterial blood pH level is caused by the same diagnoses listed for low pleural fluid glucose.

15. cont. Pleural Fluid LDH, Glucose, and pH Pleural fluid pH For parapneumonic effusions , a low pleural fluid pH level is predictive of complicated effusions (that require drainage) . In such cases, a pleural fluid pH of less than 7.1-7.2 indicates the need for urgent drainage of the effusion, while a pleural fluid pH of more than 7.3 suggests that the effusion may be managed with systemic antibiotics alone.

16. Next steps If an exudate is suspected clinically or is confirmed by chemistry test results, send the pleural fluid for : total and differential cell counts, Gram stain and culture , cytology .

17. Pleural Fluid Cell Count Pleural fluid lymphocytosis, with lymphocyte values greater than 85% of the total nucleated cells, suggests: TB, lymphoma , Chylothorax , sarcoidosis , chronic rheumatoid pleurisy, yellow nail syndrome . Pleural lymphocyte values of 50-70% of the nucleated cells suggest malignancy.

18. Pleural Fluid Culture Cultures of infected pleural fluids yield positive results in approximately 60% of cases. This occurs even less often for anaerobic organisms. Diagnostic yields, particularly for anaerobic pathogens, may be increased by directly culturing pleural fluid into blood culture bottles .

19. Pleural Fluid Cytology Malignancy is suspected in patients with lymphocytic exudative effusions, especially when bloody. Direct tumor involvement of the pleura is diagnosed most easily by performing pleural fluid cytology. The reported diagnostic yields in cytology vary from 60-90%, depending on the extent of pleural involvement and the type of primary malignancy.

20. Tuberculous pleuritis Suspect tuberculous pleuritis in patients with lymphocytic exudative effusions, especially if less than 5% mesothelial cells are detected on differential cell counts.

21. cont. Tuberculous pleuritis Most tuberculous pleural effusions probably result from a hypersensitivity reaction to the Mycobacterium rather than from microbial invasion of the pleura. So that, acid-fast bacillus stains of pleural fluid are rarely diagnostic ( < 10% of cases ), and Pleural fluid cultures grow M tuberculosis in < 65% of cases.

22. cont. Tuberculous pleuritis pleural biopsy : The combination of histology and culture of pleural tissue obtained by pleural biopsy increases the diagnostic yield for TB to 90%.

23. cont. Tuberculous pleuritis Adenosine deaminase (ADA) activity of greater than 50 U/mL in pleural fluid supports the diagnosis of tuberculous pleuritis . However , pleural ADA values of less than 50 U/mL do not exclude the diagnosis of TB pleuritis .

24. pleural fluid criteria in case of: TB Exudate, lymphocytic predominance , positive acid-fast bacillus smear or cultures , ADA > 50 U/L

25. pleural fluid criteria in case of : empyema Exudative with PMN predominance/pus, positive Gram stains or cultures , LDH > 1000 , glucose < 40 mg %, pH < 7.2 PMNs = polymorph nuclear leukocytes, which are a special family of white blood cells that ncludes neutrophils , eosinophils, and basophils.

26. P leural fluid criteria in case of: Fungal infection Black-colored, fungal smear, culture positive

27. P leural fluid criteria in case of: malignancy Exudate , lymphocytic predominance, positive cytology

28. P leural fluid criteria in case of: Hemothorax Hemorrhagic , hematocrit > 50% of blood

29. P leural fluid criteria in case of: C hylothorax Triglycerides > 110 mg/ dL , chylomicrons, cholesterol/triglyceride ratio < 1

30. P leural fluid criteria in case of: Rheumatoid pleurisy Exudate, lymphocytic predominance, rheumatoid factor positive > 1:320 , low glucose < 40 mg %, ADA > 50 U/L

31. P leural fluid criteria in case of: Lupus pleuritis Exudate with PMN predominance , LE cells positive, ANA positive > 1:160

32. P leural fluid criteria in case of: Esophageal rupture pH < 7, high salivary amylase

33. References: https ://emedicine.medscape.com/article/299959-workup https://www.pulmonologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/hemorrhagic-pleural-effusions-and-hemothorax/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753987/ Wilcox ME, Chong CA, Stanbrook MB, Tricco AC, Wong C, Straus SE. Does this patient have an exudative pleural effusion? The Rational Clinical Examination systematic review. JAMA. 2014 Jun 18. 311(23):2422-31. [Medline]. https://www.ncbi.nlm.nih.gov/pubmed/22372660

34. T hank you