Pleural Diseases. Pleural Diseases. Director, Pulmonary Vascular Program Respiratory Institute Cleveland Clinic FACP, FRCP(C), FCCP, FCCM, FAHA

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1 Pleural Diseases Raed A. Dweik, M.D. FACP, FRCP(C), FCCP, FCCM, FAHA Director, Pulmonary Vascular Program Respiratory Institute Cleveland Clinic Cleveland, OH Effusions: Fluid Transudates Exudates Pus Empyema Blood Hemothorax Chyle: Chylothorax Pneumothorax (air) Malignancy (cells) Mesothelioma Secondary Pleural Diseases

2 Does This Patient Have a Pleural Effusion? A 74-year-old man is admitted to the hospital with a 1-week history of dyspnea, fever, and cough. He has no history of respiratory disease but has a 40 pack-year smoking history. You suspect pneumonia, for which there is a 20% to 40% probability of an associated pleural effusion. What would be the most accurate physical examination maneuver(s) for determining if this patient has a pleural effusion or not? A- Absence of reduced tactile vocal fremitus makes a pleural effusion less likely B- Increased intensity of breath sounds makes a pleural effusion more likely C- Dullness to percussion makes a pleural effusion more likely D- A or C E- None of the above, physical examination findings are non-specific Does This Patient Have a Pleural Effusion? A 74-year-old man is admitted to the hospital with a 1-week history of dyspnea, fever, and cough. He has no history of respiratory disease but has a 40 pack-year smoking history. You suspect pneumonia, for which there is a 20% to 40% probability of an associated pleural effusion. What would be the most accurate physical examination maneuver(s) for determining if this patient has a pleural effusion or not? A- Absence of reduced tactile vocal fremitus makes a pleural effusion less likely B- Increased intensity of breath sounds makes a pleural effusion more likely C- Dullness to percussion makes a pleural effusion more likely D- A or C E- None of the above, physical examination findings are non-specific

3 How Much Fluid is There? Blunting of the costophrenic angle: AP: ml of fluid Lateral: ml of fluid 10 mm on lateral decubitus film: amenable to thoracentesis CT: useful in distinguishing i pleural l from parenchymal abnormalities Assessing underlying lung parenchyma Ultrasound: Useful in guiding difficult thoracentesis (loculated, dry tap, body habitus) Superior to CT for distinguishing effusion from masses or thickening

4 Imaging To Tap or Not to Tap? Diagnostic thoracentesis should always be performed whenever a pleural effusion is detected. Exceptions: Less than 1 cm of free fluid on a lateral decubitus X-ray An obvious clinical cause for the effusion (e.g CHF) A bleeding diathesis (usually safe with the INR < 2 and a PTT < 2 X upper limit of normal, plt >25,000) Local skin infection Re-expansion pulmonary edema can occur if volumes >1500 are withdrawn rapidly consider monitoring pleural pressure (keep > -20 cm H 2 O)

5 Pleural Fluid Tests All effusions Additional tests Protein Amylase LDH Creatinine ph Triglycerides-chylomicrons Cell count and differential Hematocrit? Cholesterol? Cholesterol On exudates ANA, RF, complement G stain and culture Adenosine deaminase (ADA) Fungal stain and culture LE cells AFB smear and culture Cytology Exudate vs. Transudate Light s Criteria (1972) Pleural/serum Pleural/serum LDH protein ratio LDH ratio Transudate asudae < < < 200 U/L * Exudate > 0.5 > 0.6 > 200 U/L * *(2/3 upper limit of normal of the serum level) Sensitivity 98% Sensitivity 98% Specificity 92%

6 Protein (g/dl) LDH (IU/L) Match the highlighted pleural effusion with the appropriate patient: A- 70-yr-old male with an indwelling Foley catheter and high grade fever. B- 55-yr-old female experiencing chest pain and fever after an upper endoscopy. C- 33-yr-old female with lymphoma. D- 67-yr-old male with CAD 3 days after hospitalization for CHF. E- 40-yr-old alcoholic li male with pneumonia and persistent t highh fever despite I.V. antibiotics. ph Glucose (mg/dl) Cholesterol (mg/dl) Triglycerides (mg/dl) Protein (g/dl) LDH (IU/L) Match the highlighted pleural effusion with the appropriate patient: A- 70-yr-old male with an indwelling Foley catheter and high grade fever. B- 55-yr-old female experiencing chest pain and fever after an upper endoscopy. C- 33-yr-old female with lymphoma. D- 67-yr-old male with CAD 3 days after hospitalization for CHF. E- 40-yr-old alcoholic li male with pneumonia and persistent t highh fever despite I.V. antibiotics. ph Glucose (mg/dl) Cholesterol (mg/dl) Triglycerides (mg/dl)

7 Exudate vs. Transudate: New Criteria LDH Cholesterol Protein Transudate < 45%* < 45 mg/dl < 2.9 g/dl Exudate >45%* >45mg/dL >29g/dL 2.9 * of serum upper limit of normal Lower threshold for LDH No diagnostic improvement over Light s criteria No need for phlebotomy Cholestrol may be helpful in diuretic-treated CHF (protein 3-4 g/dl) Meta analysis: Heffner, et al. Chest 1997; 111: Mechanisms Leading to Exudates and Transudates Transudates Increased hydrostatic pressure (CHF) Reduced osmotic pressure (nephrotic syndrome) Increased negative intrapleural pressure (acute atelectasis) Exudates Increased capillary permeability (pneumonia) Diseases of the pleural surface (mesothelioma) Increased negative intrapleural pressure (chronic atelectasis, trapped lung) Reduced lymphatic drainage (malignancy)

8 Key Points Transudates are usually due to a systemic problem outside the lung-pleura. Exceptions: early atelectasis, PE Exudates are usually due to direct lungpleural involvement. Exceptions: pancreatitis, subphrenic abscess PE can be associated with a transudate t (atelectasis) or an exudate (infarction). Measurement of pleural l fluid LDH, cholesterol l and protein concentrations can differentiate a transudate from an exudate without phlebotomy. Definitive Diagnoses Based on Pleural Fluid Analysis Diagnosis Criteria Urinothorax ph < 7, transudate, pl/s creat. >1.0 Empyema Pus, positive G stain or culture Malignancy Positive cytology Chylothorax Triglycerides >110 mg/dl, chylomicrons TB, fungal Positive stains, cultures Hemothorax Hct. > 50% of blood Peritoneal dialysis Prot. < 1g/dL, gluc mg/dl Esophageal rupture ph < 7, high amylase (salivary) Lupus pleuritis LE cells, pl/s ANA >1.0

9 Clues From Pleural Fluid Analysis Criteria Lymphocytosis Possible Diagnoses TB, malignancy (>50%) Eosinophilia Air, blood, (BAPE), drug-induced (>10%) Churg-Strauss, parasitic/fungal,?malignancy Glucose < 60 (or < TB, esophageal rupture, malignancy 50% of serum) Glucose < 30 Empyema, rheumatoid arthritis High amylase (pl/s Pancreatitis, pseudocyst, pancreatic >1.0, or higher than cancer (10-30 X s. level, pancreatic) UL in serum) Esophageal rupture (5 X s. level, salivary) Malignancy, ruptured ectopic pregnancy Key Points Pleural fluid ph helpful in diagnosis: ph H<73 <7.3: esophageal rupture, rheumatoid effusion, TB ph <7.0: esophageal rupture, urinothorax Prognosis ph <7.3: in malignancy indicates a large tumor burden, failed pleurodesis, and poor survival Guiding management: Complicated parapneumonic effusion, empyema Beware of urea-splitting organisms (Proteus): empyema with alkaline ph.

10 Match the highlighted g pleural effusion with the appropriate management strategy in a patient t with pneumonia: Glucose (mg/dl) ph LDH U/L Gram Stain Culture negative negative negative negative negative negative positive pending negative positive a. Simple parapneumonic effusion, treat with appropriate antibiotics b. Borderline parapneumonic effusion, needs serial thoracentesist in addition to antibiotics c. Complicated parapneumonic effusion, needs tube thoracostomy in addition to antibiotics d. Empyema, needs tube thoracostomy in addition to antibiotics Match the highlighted g pleural effusion with the appropriate management strategy in a patient t with pneumonia: Glucose (mg/dl) ph LDH U/L Gram Stain Culture negative negative negative negative negative negative positive pending negative positive a. Simple parapneumonic effusion, treat with appropriate antibiotics b. Borderline parapneumonic effusion, needs serial thoracentesist in addition to antibiotics c. Complicated parapneumonic effusion, needs tube thoracostomy in addition to antibiotics d. Empyema, needs tube thoracostomy in addition to antibiotics

11 Parapneumonic Effusions ph Glucose G.Stain/ Management Culture Simple > 7.2 > 40 mg/dl Negative Antibiotics Borderline > 40 mg/dl Negative Serial thoracentesis Complicated < 7 < 40 mg/dl Negative Tube thoracostomy Empyema < 7 < 40 mg/dl Positive Tube thoracostomy Rule of Thumb Indications For Chest Tube Drainage Frank pus Positive pleural fluid gram stain Positive pleural fluid culture Pleural fluid ph < 7.0

12 What About Appearance? Blood-tinged pleural fluid is of little diagnostic value: 10, RBCs/uL: blood tinged fluid (1ml blood in 500) 100,000 RBCs/uL: grossly bloody fluid (1ml in 50) (peripheral blood: 5,000,000 RBCs/uL) Causes of 100,000 RBCs/uL: Trauma (will clot) Malignancy Post-cardiac injury Pulmonary embolism Hemothorax is present when the hematocrit of the pleural fluid is >50% of that of the peripheral blood (tube thoracostomy, exploration). Pleurall Effusions Post-CABG 24% (7/29) CHF 7% (2/29) constrictive pericarditis 3% (1/29)pulmonary embolism 66% (19/29)no discernable cause 42% (8/19) bloody 58% (11/19) nonbloody

13 Pleural Effusions Post-CABG Bloody Likely related to bleeding within the pleural space Maximum size within 1 month after CABG Frequently eosinophilic High levels of LDH Resolve after 1-2 thoracenteses Nonbloody Maximum size more than 1 month after surgery Mostly lymphocytic Low LDH Difficult to manage (recur) Milky-appearing fluid: Clears with centrifugation: consider empyema Does not clear: check triglyceride level.

14 Causes of Chylous and Chyliform Effusions Chylous Trauma (including surgery) Malignancy (usu. lymphoma) Idiopathic Chyliform Chronic RA effusion TB Trapped lung Subclavian vein thrombosis Filariasis Intestinal Lymphangiectasia Superior vena cava obstruction Lymphangioleiomyomatosis (LAM) Chylous vs. Chyliform Effusions Chylous Chyliform Appearance: milky milky Triglycerides: >110 mg/dl < 50 mg/dl Cholesterol: < 200 mg/dl >200 mg/dl (50-200) ( ) Chylomicrons: present absent Cholesterol crystals: absent present

15 Looks like bile Bilious Effusion Pleural /serum bilirubin ratio > 1 Trauma, T-tubes, stents, parasites A35yr 35-yr-old male ex-smoker diagnosed with AIDS 4 years ago receives aerosolized pentamidine for PJP prophylaxis. He is admitted with acute respiratory failure requiring intubation and mechanical ventilation. You are called to the bedside because the patient suddenly developed high airway pressures with a drop in blood pressure and arterial oxygen saturation. When you examine the patient, you notice decreased air entry on the left side with a deviation of the trachea to the right. What should you do next: a. Order a CT scan of the chest. b. Add 10 cm H 2 0 of PEEP. c. Insert a chest tube on the right side. d. Insert a large-bore needle in the second intercostal space on the left. e. Place the patient on his side with the left side down.

16 A35yr 35-yr-old male ex-smoker diagnosed with AIDS 4 years ago receives aerosolized pentamidine for PJP prophylaxis. He is admitted with acute respiratory failure requiring intubation and mechanical ventilation. You are called to the bedside because the patient suddenly developed high airway pressures with a drop in blood pressure and arterial oxygen saturation. When you examine the patient, you notice decreased air entry on the left side with a deviation of the trachea to the right. What should you do next: a. Order a CT scan of the chest. b. Add 10 cm H 2 0 of PEEP. c. Insert a chest tube on the right side. d. Insert a large-bore needle in the second intercostal space on the left. e. Place the patient on his side with the left side down. Tension Pneumothorax The pressure of air in the pleural space exceeds ambient pressure throughout the respiratory cycle. May result in acute respiratory failure hemodynamic compromise, and cardiopulmonary arrest. If tension pneumothorax is suspected, a large-bore needle should be inserted immediately in the affected side to allow immediate relief of the tension until tube thoracostomy can be performed.

17 PNEUMOTHORAX Accumulation of air in the pleural space Primary pneumothorax: without underlying lung disease Secondary pneumothorax: in association with certain lung diseases Iatrogenic

18 Key Points A young woman with a pneumothorax and any patient with parenchymal abnormalities on post drainage CXR should undergo a high-resolution CT to look for underlying lung disease. Primary pneumothorax (no underlying lung disease) can be managed with initial simple aspiration. Secondary pneumothorax (underlying lung disease) requires tube thoracostomy. Consider pleurodesis: recurrent pneumothorax: significantly decreases recurrence rate (13% vs. 36%). occupations in which development of pneumothorax may be dangerous (airplane pilots or deep sea divers). Estimating The Size of a Pneumothorax 2vs. 3 dimensions % ptx= (1-D L3 /D H3 )*100 2 cm difference on CXR = 58% ptx size Lung volume= (6) 3 = 216 cm 3 Hemithorax volume= (8) 3 = 512 cm 3 Lung size=216/512= 42% Pneumothorax size= 58%.

19 Thank You! Good Luck!!

20 Pleural Fluid: What is Normal? um diameter potential space between visceral and parietal pleura Volume: ml/kg Clear liquid Low protein: g/dl WBC: < 1,500/uL 2% PMNs; 10% Lcts; the rest are mesothelial cells and monocytes ph: >7.6 (active transport of HCO3 - )

21 Common Causes of Exudates and Transudates Transudates Congestive heart failure Cirrhosis with ascites Nephrotic syndrome Exudates Pneumonia (parapneumonic effusion) Empyema Hpoproteinemia i Malignancy Peritoneal dialysis Other infections (TB, Viral, Fungal, Parasitic ) Connective tissue disease Other Causes of Exudates and Transudates Transudates Exudates Myxedema Constrictive pericarditis Superior vena cava obstruction Urinothorax Acute atelectasis Pulmonary embolism Sarcoidosis Asbestos pleural effusion Chylothorax Drug reaction Chronic atelectasis Pulmonary embolism Esophageal rupture Post-myocardial infarction Pancreatitis Uremia

22 Categorizing Risk for Poor Outcome in Patients with Parapneumonic Effusion Pleural Fl. Anatomy GS and Cx ph Risk Drainage Minimal (< 10 mm) Free-flowing?? V. low No Small to moderate (>10 mm to <1/2 chest) Negative > 7.2 Low No Free-FlowingFl Large (> 1/2 chest) Loculated Positive Moderate Yes Thickened pleura Pus < 7.0 High Yes Colice, et al. Chest, 2000:118:

23 Effusions of Indeterminate Etiology About half will resolve spontaneously and no disease will be apparent on long-term followup (e.g. BAPE) The other half: carcinoma, mesothelioma, lymphoma, TB, con. tissue dis., PE, druginduced. Many are caused by malignant disease which is either obvious or incurable anyway The most likely treatable or curable diagnosis is TB.

24 Effusions of Indeterminate Etiology Observe the patient (no systemic or constitutional symptoms) Or Proceed with thoracoscopy or thoracotomyt (fever, wt loss, large effusion) Thoracoscopy (medical-vats) Direct visualization of the pleura Sampling Therapy (pleurodesis) Benign Asbestos Pleural Effusion (BAPE) Nonspecific exudate, often bloody Peak incidence is about 10 to 15 years after onset of asbestos exposure (before other pleural complications of asbestos). Persists for a mean of 4 months and then resolves spontaneously in most patients. Does not seem to be an indicator for increased risk of mesothelioma. Diagnosis is by history of asbestos exposure and exclusion of other causes.

25 Pleurodesis Agent and Dose Success Rate Adverse Effects Talc 2.5 to 10 Gm 153/165 (93%) Pain: 9/131 (7%) Fever: 21/131 (16%) Doxycycline 43/60 (72%) Pain: 24/60 (40%) 500 mg Tetracycline (NA) 240/359 (67%) Pain: 51/359 (14%) 500 mg to 20 mg/kg Fever: 36/359 (10%) Bleomycin 108/199 (54%) Pain: 56/199 (28%) 15 to 240 Units Fever: 48/199 (24%) Nausea: 21/199 (11%) Walker-Renard et al. Ann Int Med 1994;120:56.

26 Key Points-Pitfalls CHF effusions after diuresis can appear exudative (prot.>3g/dl), consider cholesterol levels Effusions with malignancy can be transudates: t Early lymphatic obstruction Obstructive atelectasis Concomitant CHF 15-20% of pleural effusions will defy a definitive dx: obscure etiology even after several thoracenteses and closed pleural biopsies. Rule of Thumb Indications For Chest Tube Drainage Frank pus Positive pleural fluid gram stain Positive pleural fluid culture Pleural fluid ph < 7.0

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