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Diagnostic value of pleural effusion


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Pleural Effusion evaluation and differential diagnosis

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Diagnostic value of pleural effusion

  1. 1. Pleural Effusion S. A. Saleemi
  2. 2. PLEURAL EFFUSION •Fluid production exceeds absorption. •Fluid is formed in the parietal pleura and absorbed in parietal pleural lymphatics. •Lymphatics have the capacity to absorb 20 times more than what is Produced. •Fluid can also enter the pleural cavity from interstitial spaces of lung through visceral pleura. •Peritoneal fluid can enter the pleural cavity via diaphragm pores.
  3. 3. Mechanism of Pleural effusions increased hydrostatic pressure(LVF) decreased oncotic pressure in microcirculation (hypoalbuminemia) decrease in pleural pressure (atelectasis) increased permeability of microcirculation ( pneumonia) impaired lymphatic drainage from pleural space (malignancy) movement of fluid from abdomen to pleural space ( cirrhosis)
  4. 4. In health, the volume of pleural fluid in humans is small (<1 ml), forming a film about 10 micro thick between the visceral and parietal pleural surfaces.
  5. 5. Normal composition of pleural fluid Volume Cells/mm³ %mesothelial cells %monocytes %lymphocytes %granulocytes % eosinophils Protein %albumin Glucose LDH 0.1-0.2 ml/kg 1000-5000 3-70% 30-70% 2-30% ~ 10% 0% 1-2 gm/dl 50-70% ~plasma level <50% plasma level
  6. 6. Differentiation between transudate and exudate parameter transudate exudate Total protein <30 g/l >30 g/l Pleural-serum protein ratio <0.5 >0.5 LDH <200 u/l >200 u/l Pleural-serum LDH ratio <0.6 >0.6 cholestrol <45mg/dl >45 mg/dl Bilirubin pleural- <0.6 serum ration >0.6
  7. 7. Light Criteria 1- Pleural fluid protein-to-serum protein ratio more than 0.5 2- Pleural fluid LDH-to-serum LDH ratio more than 0.6 3-Pleural fluid LDH level greater than two third the upper limit of normal serum level
  8. 8. Modified 1997 (NO SERUM LEVELS) (by Haffner) 1-Pl. fluid protein more than 2.9g/dl(29g/L 2- Pl. fluid LDH more than 66% of upper limit of normal serum reference range 3- Pl. fluid cholestrol more than 45 mg/dl
  9. 9. Serum-effusion albumin gradient (SAG) In general Light’s criteria occasionally misidentify a transudative effusion as an exudative effusion as in cardiac failure with diuretic therapy Clinically if a patient should have a transudative effusion, but meets Light’s criteria for an exudative effusion, measure serum - pleural fluid albumin gradient Serum- effusion albumin gradient of more than 1.2 g/dl is used to diagnose presence of transudate effusion.
  10. 10. Causes of transudative pleural effusions Very common causes – Left ventricular failure – Liver cirrhosis – Hypoalbuminaemia – Peritoneal dialysis Less common causes – Hypothyroidism – Nephrotic syndrome – Mitral stenosis – Pulmonary embolism Rare causes – Constrictive percarditis – Urinothorax – Superior vena cava obstruction – Ovarian hyperstimulation – Meigs’ syndrome
  11. 11. Causes of exudative pleural effusions Common causes – Malignancy – Parapneumonic effusions Less common causes – Pulmonary infarction – Rheumatoid arthritis – Autoimmune diseases – Benign asbestos effusion – Pancreatitis – Post-myocardial infarction syndrome Rare causes – Yellow nail symdrome – Drug (see box1 ) – Fungal infections
  12. 12. Drugs known to cause pleural effusions Over 100 reported cases globally – Amiodarone – Nitrofurantoin – Phenytoin – Methotrexate 20-100 reported cases globally – Carbamazepine – Procainamide – Propylthiorucil – Penicillamine – GCSF – Cyclophosphamide – Bromocriptine * (2001)
  13. 13. Approximate annual incidence of various types of pleural effusions in the USA Etiology Congestive heart failure Other causes Pneumonia Malignant disease Pulmonary embolism Cirrhosis with ascites Gastrointestinal disease Collagen vascular disease Tuberculosis Asbestos pleuritis Mesothelioma TOTAL Number 500,000 Percentage Percentage of noncardiac effusions 37.5 63.6 400,000 200,000 150,000 50,000 25,000 6,000 2,500 2,000 1,500 100.0 48.0 24.0 18.0 6.0 3.0 0.7 0.3 0.25 0.2 100.0
  14. 14. Frequency distribution of noncardiac effusions Authors Number Neoplastic % Infectious % Various % Idiopathic % Storey et al. 115 56 6 16 22 Hirsch et al. 295 39 31 9 21 194 46 33.5 12 20 646 34.5 26.5 15 12.5 250 34 39 18 9 42 29 14 15 Lamy et al. Engel, Loddenkemper, 1500 TOTAL
  15. 15. Useful Tests in the Evaluation of Pleural Effusions Test Abnormal Values Frequently Associated Condition Red blood cells, per mm3 >100.000 Malignancy, trauma, pulmonary embolism White blood cells, per mm3 >10.000 Pyogenic infection neutorphils, % >50 Acute pleuritis lymphocytes, % >90 Tuberculosis, malignancy, lymphoma eosinophilia, % >10 Asbestos effusion, hydro-pneumothorax, resolving infection mesothelial cells absent Tuberculosis
  16. 16. Cont:Glucose, mg/dl <40 Empyema, TB, malignancy, rheumatoid arthritis pH <7.20 Esophageal rupture, empyema, TB, malignancy, rheumatoid arthritis Amylase, PF/S >1 Pancreatitis, esophageal rupture Bacteriologic Positive Etiology of effusion Cytology Positive Diagnostic of malignancy
  17. 17. Pleural fluid eosinophilia (>10%) Usually due to air or blood in the pleural space Consider drug reactions – Dantrolene, bromocriptine, nitrofurantoin Frequent with asbestos pleural effusion Rarely paragonimiasis or Churg-Strauss syndrome – also low glucose and pH Frequently no diagnosis obtained
  18. 18. Appearance of pleural fluid Fluid Suspected disease Putrid odour Anaerobic empyema Food particles Oesophageal rupture Bile stained Cholothorax (biliary fistula) Milky Chylothorax/pseudoch ylo- thorax “Anchovy sauce” like fluid Ruptured amoebic abscess
  19. 19. Pleural infections
  20. 20. Pleural infection was first described by Hippocrates in 500BC. Open thoracic drainage was the only treatment for this disorder until the 19th century when closed chest tube drainage was first described. open surgical drainage was associated with a mortality rate of up to 70%.
  21. 21. Characteristics of parapneumonic pleural effusions Stages Macroscopic appearance Pleural fluid characteristics Comments Simple parapneumonic Clear fluid pH >7.2 LDH <1000 IU/l Glucose >2.2 mmol/L No organism on culture or Gram stain Will usually resolve with antibiotics alone Perform chest tube drainage for symptom relief if required Complicated parapneumonic Clear fluid or cloudy/turbid pH <7.2 LDH >1000 IU/l Glucose <2.2 mmol/l May be positive Gram stain/culture Requires chest tube drainage Empyema Frank pus May be positive Gram stain/culture Requires chest tube drainage No additional biochemical tests necessary on pleural fluid (do not measure pH)
  22. 22. Classification of and Therapies for Parapneumonic Effusion and Empyema Appearance and Studies Class Type 1 Insignificant pleural effusion (<10 mm thick) on decubitus radiograph) Thoracentesis not indicated 2 Typical parapneumonicpH >7.2 pleural effusion (>10 mm thick) Glucose >40 mg/dL Radiologic Appearance Gram stain and culture negative Treatment Antibiotics alone
  23. 23. Classification of and Therapies for Parapneumonic Effusion and Empyema (cont.) Appearance and Studies Radiologic Appearance Class Type Treatment 3 Bordeline complicated pleural effusion ph 7.0-7.2 and/or No loculations LDH >1000IU/L and Glucose >40 mg/dL Gram stain and culture negative Antibiotics and repetition 4 Simple complicated pleural effusion ph<7.0 and/or Not loculated, Glucose <40 mg/dL nonpurulent and/or Gram stain culture positive Tube thoracostomy and antibiotics or serial thoracentesis
  24. 24. Classification of and Therapies for Parapneumonic Effusion and Empyema (cont;) Appearance and Radiologic Class Type Studies Appearance Treatment 5 Complex complicated pH<7.0 and/or Multiloculated Tube thoracostomy a pleural effusion Glucose <40 mg/dL nonpurulent & thrombolytic agent and/or In rare instances Gram stain or culture surgical intervention positive 6 Simple empyema Frank pus 7 Complex empyema Frank pus Single loculation or Tube thoracostomy with or without decortication Multiple locules Tube thoracostomy & thrombolytic agents Often thoracoscopy or decortication
  25. 25. Septation Loculation
  26. 26. Resolution of pleural effusion Disease Incidence% Therapy Resolution time Parapneumonic 9-66 Antibiotics 2-8 weeks Tubeculosis 3-23 No therapy 2-4 months Anti-TB treatment 1-2 months Post CABG 40-90 Self limiting 8 weeks(6w-20m) RA 4-7 NSAID, Prednisone 3-4m(1m-5y) SLE 16-37 Steroids 1-6w PE 10-50 Heparin 3-7d PCIS 40-68 NSAID, Steroids 1w-4m Sarcoidosis 0-7.5 Self limiting,steroids 1-3m Chest 119(5), 2001
  27. 27. Resolution of pleural effusion by time interval <2 months 2-6 months 6m-1year Benign persistent Parapneumonic CHF Acute pancreatitis PCIS Post CABG PE SLE Sarcoidosis Traumatic chylothorax Uremic effusion TB PCIS Post CABG RA sarcoidosis RA Benign asbestosis Trapped lung Lymphangiectasia Noonan’s syndrome LAM Yellow nail syndrome Chest 119(5), 2001
  28. 28. Resolution of parapneumonic pleural effusion organism Incidence% Therapy Resolution time (Range) S pneumoniae 30-60 B-lactams, macrolides 4-8 weeks M pneumoniae 4-20 Macrolide, tetracyclines 2-3 weeks L pneumoniae 12-35 Macrolides 3-4 weeks Adenovirus 2-18 Self limiting 2-3 weeks Chest 119(5), 2001
  29. 29. Tuberculous pleural effusion AFB stain positive in only 10-20% AFB culture positive 25-50% Diagnostic yield increases to 90% with addition of pleural biopsy histology and biopsy cultures for AFB
  30. 30. Pleural fluid markers for tuberculosis Adenosine Deaminase (ADA) Gamma interferon PCR for DNA of M. tuberculosis
  31. 31. Pleural fluid ADA T-lymphocyte enzyme Patients with TB have levels above 45 IU/L unless they are immunologically suppressed High levels also seen with empyema and rheumatoid pleuritis Specificity increased if combined with PF lymph/poly ratio greater than 3 Pleural fluid ADA helpful in areas of high TB prevelance Fluid ADA levels not useful in HIV patients with TB
  32. 32. Pleural fluid gamma interferon Produced by lymphocytes Lymphocytes specifically sensitized to PPD produce gamma interferon when incubated with PPD PF levels above 140pg/ml are very suggestive of TB Elevated whether or not the patient is immunosuppressed Is more expensive than ADA
  33. 33. PCR for the diagnosis of tuberculous pleuritis With PCR one can identify the presence of DNA from M. tuberculosis in the pleural fluid Study from spain on 107 pleural fluids – PCR positive in 17/21 with TB – PCR positive in only two others and they probably had TB – PCR was not superior to an ADA level >45 Querol JM et al. Am J Respir Crit Care Med 1995;152:1977
  34. 34. Diagnosis of tuberculous pleuritis If pleural fluid ADA >70 units - diagnostic If pleural fluid gamma interferon is high diagnostic Granulomas on pleural biopsy - diagnostic If lymphocytic effusion and positive PPD, treat for TB pleuritis if pleural fluid ADA is above 40
  35. 35. Pleural effusions in HIV infection A pleural effusion is seen in 7–27% of hospitalised patients with HIV Leading causes are Kaposi sarcoma parapneumonic effusion Tuberculosis Lymphoma pneumocystic carinii pneumonia
  36. 36. Chylothorax and Psudochylothorax
  37. 37. Fluid Triglyceride >110 mg /dl - Diagnostic Presence of Chylomicron - Diagnostic Fluid Triglyceride 50-110 mg/dl – probable Fluid Triglyceride <50 mg/dl – Not chylothorax
  38. 38. Laboratory differentiation of chylothorax and pseudothorax Pseudochylothorax Chylothorax <0.56 mol/l (50mg/dl) >1.24 mmol/l (110 mg/dl) Cholesterol >5.18 mmol/l (200 mg/dl) >5.18 mmol/l (200 mg/dl) Cholesterol crystals Often present Absent Absent Present Feature Triglycerides Chylomicrons
  39. 39. Causes of chylothorax and pseudochylothorax Chylothorax – – – Neoplasm: lymphoma, metastatic carcinoma Trauma: operative, penetrating injuries Miscelaneous: tuberculosis, sarcoidosis, lymphangioleiomyomatosis, cirrhosis, obstruction of central veins, amyloidosis Pseudochylothorax – – – Tuberculosis Rheumatoid arthritis Poorly treated empyema
  40. 40. Malignant pleural effusion
  41. 41. Malignant pleural effusion
  42. 42. Pleural fluid cytology Very useful test 1st specimen positive in 60% and if three specimens submitted, may be positive in >80% Very effective with adenocarcinoma Less effective with lymphoma, squamous cell carcinoma, mesothelioma or Hodgkin’s disease cytology much better than needle biopsy in most series looking at malignant effusions – in one series of patients with malignancy, pleural biopsy positive in only 20/118 (17%) with negative cytology – rarely is needle biopsy indicated
  43. 43. Sensitivity of pleural fluid cytology in malignant pleural effusion Reference No.of patients No. caused by malignancy % diagnosed by cytology Salyer et al10 271 95 72.6 Prakash et al12 414 162 57.6 Nance et al11 385 109 71.0 Hirsch39 300 117 53.8 Total: 1370 371 61.6
  44. 44. Malignant pleural effusion Observation Observation is recommended if the patient is asymptomatic or there is no recurrence of symptoms after initial thoracentesis. [C] Therapeutic pleural aspiration Repeat pleural aspiration is recommended for the palliation of breathlessness in patients with a very short life expectancy. [C] Caution should be taken if removing more than 1.5 L on a single occasion. [C] The recurrence rate at 1 month after pleural aspiration alone is close to 100%. [B] Intercostal tube drainage without pleurodesis is not recommended because of a high recurrence rate. [B]
  45. 45. Success rates of commonly used pleurodesis agents Chemical agent Talc Total Successful patients (n) (%) 165 dose 93 2.5-10g Doxycycline 60 72 500mg tetracycline 359 67 500mg Bleomycin 199 54 15-250 units
  46. 46. Rheumatoid arthritis associated pleural effusions
  47. 47. • Suspected cases should have a pleural fluid pH, glucose and complement measured. • Rheumatoid arthritis is unlikely to be the cause of an effusion if the glucose level in the fluid is above 1.6 mmol/l (29 mg/dl).
  48. 48. Frequency of low glucose values in pleural effusions Entity Frequency (%) Rheumatoid Arthritis Empyema 85 Malignant effusion 30 Tuberculous 20 Lupus 20 80
  49. 49. SLE associated pleural effusion
  50. 50. The presence of LE cells in pleural fluid is diagnostic of SLE. The pleural fluid ANA level should not be measured as it mirrors serum levels and is therefore unhelpful.
  51. 51. Hepatic hydrothorax
  52. 52. Pleural effusion associated with liver cirrhosis Mostly associated with ascites Can occur without ascites Diagnostic tap of both pleural effusion and ascites Difficult to treat Pleurodesis usually unsuccessful
  53. 53. MANAGEMENT OF PERSISTENT UNDIAGNOSED PLEURAL EFFUSION • In persistently undiagnosed effusions the possibility of pulmonary embolism and tuberculosis should be reconsidered since these disorders are amenable to specific treatment. • Undiagnosed pleural malignancy proves to be the cause of many “undiagnosed” effusions with sustained observation.
  54. 54. Pleural Effusion Pearls Presence of transudate effusion indicates the existence of systemic disease. Exudative effusion is caused by a local pleural process. Spontaneous bacterial empyema can complicate hepatic hydrothorax. TB and malignancy are the two commonest causes of unexplained exudative effusion. TB effusion is caused with equal frequency by primary & reactivated TB Hemothorax if HCT > 20%
  55. 55. Pleural Effusion Pearls Massive pleural effusions are most commonly due to malignancy. [B] The majority of malignant effusions are symptomatic. [C] Very low glucose in the absence of infection is highly suggestive of RA
  56. 56. Thank you