PLEURAL EFFUSION Patariya Malaisri, MD.

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1 PLEURAL EFFUSION Patariya Malaisri, MD

2 INTRODUCTION Pleural effusions are a common medical problem with more than 50 recognised causes including disease local to the pleura or underlying lung, systemic conditions, organ dysfunction and drugs.

3 Physiology of pleural space
Pleural effusions are generally generated from microvessels in both parietal and visceral pleurae. (parietal > visceral) Effusions exit the pleural space by bulk flow via lymphatic vessels in parietal pleural stroma. The entry rate of pleural liquid is approximately 0.5 ml/hr or 12 ml/day in an adult human. The half life of pleural liquid is about 6-8 hr. The exit rate is about 0.2 ml/kg/hr, which 20-3o times greater than the entry rate. Light RW. Disorder of the pleura. In: Murray & Nadel’s Textbook of Respiratory Medicine 5th edition 2010:

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5 Physiology of pleural space
Pleural effusions could be generated from: Excess fluid in pulmonary interstitium Other intrathoracic blood vessels, or lymphatic vessels Intraabdominal fluid; ascites Pleural-to-plasma protein ratio is usually about 0.15.

6 Pathophysiology of ‘becoming pleural effusion’
BOTH the entry rate must increase and the exit rate must decrease. If only the entry rate increase: It would required a sustained rate of entrance more than 30 times normal (to exceed the lymphatic removal capacity). If only the exit rate decrease: It would take more than a month to produce effusion detected by chest radiograph.

7 Pleural effusion : Definition
Abnormal accumulation of fluid in the pleural space due to a disruption of the equilibrium across pleural membranes Normal pleural fluid clear ultrafiltrate of plasma pH Protein content <2%, WBC <1000 LDH <50% of plasma LDH 2 types : Transudate and Exudate Light RW, MacGregor MI, Luchsinger PC. Ann Intern Med 1972;77:

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10 CLINICAL ASSESSMENT AND HISTORY
The history and physical examination of a patient with a pleural effusion may guide the clinician as to whether the effusion is a transudate or an exudate. Approximately 75% of patients with pleural effusion have a history of pleuritic pain. The patient’s drug history and occupational history are also important.

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14 Approach to patient with pleural effusion
การตรวจวิเคราะห์ น้ำในช่องเยื่อหุ้มปอด สามารถให้การวินิจฉัยโรคได้ 75% แนวทางการซักประวัติ มีอาการหรือไม่ : เหนื่อยและเจ็บหน้าอก ลักษณะอาการเจ็บหน้าอก : เจ็บแปลบๆ เป็นมากขึ้นเวลาหายใจเข้าลึกๆ ไอหรือ จาม เป็นบริเวณชายโครง อาจร้าวไปยังหัวไหล่ และคอข้างเดียวกัน (refer pain ควรนึกถึงพยาธิสภาพบริเวณกระบังลม) อาการร่วมอื่นๆ : ช่วยวินิจฉัยสาเหตุ

15 Approach to patient with pleural effusion
Physical findings: Dullness to percussion** Decreased breath sounds Egophony Decreased tactile fremitus** Asymmetrical expansion* Bulging of intercostal spaces* **the most useful findings (JAMA 2009;301: ) *could be found if large effusion

16 Approach to patient with pleural effusion
Pleural effusion should be suspicious if chest radiograph showed: Blunted posterior costophrenic angle Invisible posterior part of the diaphragm in lateral veiw Light RW. Disorder of the pleura. In: Murray & Nadel’s Textbook of Respiratory Medicine 5th edition 2010:

17 INITIAL DIAGNOSTIC IMAGING
Plain radiography Bedside Ultrasound

18 Approach to patient with pleural effusion
A diagnostic thoracocentesis should be performed on nearly every patients with free pleural fluid measured more than 10 mm on the decubitus radiograph. If CHF is obvious, thoracocentesis can be postponed. General differentiations are depended on characters of effusions as ‘exudates’ or ‘transudates’

19 Differentiating between a pleural fluid Exudate and Transudate : Light’s criteria
Pleural fluid is an exudate if one or more of the following criteria are met : Pleural fluid protein divided by serum protein is >0.5 Pleural fluid lactate dehydrogenase (LDH) divided by serum LDH is >0.6 Pleural fluid LDH >2/3 the upper limits of laboratory normal value for serum LDH. Thorax 2010;65(Suppl 2):ii4eii17. doi: /thx.2010.

20 Transudate vs exudate However, 10-25% of patients with CHF and cirrhosis, especially who received the diuretics, could be found ‘false’ exudative effusions. In these cases, transudative effusions should be diagnosed if: Serum-pleural fluid protein gradient > 3.1 g/dl OR Serum-pleural fluid albumin gradient > 1.2 g/dl Romero-Candeira S, et al. Am J Med 2001;110:81-6. Burgess LJ, Meritz FJ, Taljaard JJ. Chest 1995;107:

21 Indication for diagnostic thoracocenthesis
New pleural fluid except viral pleurisy or uncomplicated heart failure. Consider pleural aspiration for CHF in Unilateral pleural effusion esp. left side Unequal bilateral pleural effusion Pleurisy symptom Febrile Normal heart size on CXR Widened A-a difference out of proportion to symptom (caution : atelectasis or mass)

22 PLEURAL ASPIRATION A diagnostic pleural fluid sample should be aspirated with a fine-bore (21G) needle and a 50 ml syringe. Ultrasound increases the chances of successful aspiration and minimises the need for repeated attempts.

23 APPEARANCE

24 Causes of pleural exudates
Common causes Malignancy Parapneumonic effusions Tuberculosis Less common causes Pulmonary embolism Rheumatoid arthritis and other autoimmune pleuritis Benign asbestos effusion Pancreatitis Post-myocardial infarction Post-coronary artery bypass graft Thorax 2010;65(Suppl 2):ii4eii17.

25 Causes of pleural transudates
Common causes Left ventricular failure Liver cirrhosis Less common causes Hypoalbuminaemia Peritoneal dialysis Hypothyroidism Nephrotic syndrome Mitral stenosis Thorax 2010;65(Suppl 2):ii4eii17.

26 Transudates versus Exudates
Congestive Heart Failure Cirrhosis Hepatic hydrothorax Nephrotic Syndrome Peritoneal Dialysis Myxedema Constrictive Pericarditis Atelectasis Etc. Parapneumonic effusions Empyema Malignancy (3-10% due to lymphatic obstruction) CA lung Lymphoma Mesothilioma Pulmonary Embolism TB Pleura Asbestos-related pleural effusion Acute pancreatitis Trauma Dressler's Syndrome post-heart injury syndrome Esophageal perforation Drug-induced reaction Chylothorax Etc.

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28 การแยก PA / AP CXR PA Clavicle : slope จะเข้ากลางและลงล่าง (medial end ต่ำกว่า lateral end) เห็น air fluid level ใน stomach C-spine process : จะชี้ขึ้น Scapular : อยู่นอก lung parenchyma AP Clavicle : slope จะเข้ากลางและขึ้นบน (medial end สูงกว่า lateral end) ไม่เห็น air fluid level ใน stomach C-spine process : จะชี้ตรงๆ, ชี้ลง Scapular : อยู่ซ้อนใน lung parenchyma

29 Exposure quality Intervertebral space ควรจะเห็นจางๆ เมื่อ มองผ่านเงาของหัวใจ T5-6 spinous process ควรเห็นชัดเจน Vertebral body ที่อยู่ต่ำกว่า diaphragm ควรจะจางจนแทบมองไม่เห็น ควรเห็นเงาของ Rib หลังหัวใจได้ชัดเจน

30 Underpenetrated Overpenetrated CXR ที่ได้ adequate inspiration คือ dome ของ diaphragm ควรจะอยู่ในระดับ posterior rib ที่ 9-11 หรือ anterior rib ที่ 4-6

31 the concave menisci blunting both posterior costophrenic angles
~200 ml of fluid  detect in the frontal film ~75ml of fluid  detect in the lateral film

32 Small effusion : Blunting ของ CP angle : fluid ~ 300 cc.
Moderate : meniscus sign เป็น pleural fluid (ซึ่งมักเป็น free form, non loculated) ที่มีจํานวน มากขึ้น และเห็นเป็นเงาทึบที่ชายปอด มี ขอบบน เป็น concave ปลายยอดจะอยู่ทาง lateral แต่ในท่า supine position จะไม่พบ meniscus sign แต่จะพบว่า opacity เพิ่มขึ้น โดยที่ pulmonary vessel ยงัเห็นเป็นปกติอยู่ (filter effect sign)

33 Pleural fluid (arrows) layers out on this left lateral decubitis film.

34 Meniscus sign เป็น pleural fluid (ซึ่งมักเป็น free form, non loculated) ที่มี จำนวนมากขึ้น และเห็นเป็นเงาทึบที่ชายปอด มีขอบบน เป็น concave ปลายยอดจะอยู่ทาง lateral แต่ในท่า supine position จะไม่พบ meniscus sign แต่จะพบว่า opacity เพิ่มขึ้น โดยที่ pulmonary vessel ยังเห็นเป็นปกติอยู่

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39 Interlobular effusion : มักจะเป็น fusiform homogenous shadow ที่มี ขอบเขตชัดเจน อยู่ในบริเวณของ interlobular fissure (เห็นได้ชัดเจนขึ้น ในท่า lateral CXR) และเมื่อได้รับการรักษาที่ ถูกต้อง ก้อนนี้จะหายไป = pseudo tumor หรือ vanishing tumor Loculated effusion จะแยกออกจาก chest wall, mediasternum หรือ parenchyma ยาก บ่งถึง inflammatory process ที่มี fibrin หรือ cell มาก และ ความหนืดสูง

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41 Fusiform homogeneous shadow in major fissure

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43 The posteroanterior (PA) chest x-ray is abnormal in the presence of about 200 ml of pleural fluid.
Subpulmonic effusions occur when pleural fluid accumulates between the diaphragmatic surface of lung and diaphragm. Pleural effusion ในท่า erect หรือ upright ก็จะพบ blunting ของ costophrenic angle หรือ meniscus sign แต่ในท่า นอนราบ effusion จะฉาบอยู่ด้านหลังของปอด ทำให้มีลักษณะฝ้าเหมือน ground-glass โดยที่ยงัเห็นเงา ของ pulmonary vessels ชัดเจนอยู่ ( filter effect ) และไม่พบ air bronchogram

44 A large pleural effusion has wrapped around the lateral and apical lung surfaces.
How much fluid must accumulate before you expect to see changes in the supine patient's chest x-ray? …… >500 ml

45 Massive effusion : ปอดข้างนั้นจะทึบ(apex อาจ spared) ร่วมกับ tracheal และ mediasternum ที่ shift ไปด้านตรงข้าม ถ้าหากไม่ shift ให้นึกถึง fixed mediasternum หรือ effusion ร่วมกับ process ของ volume loss อื่น ๆ ในปอด ด้านนั้น Subpneumonic effusion เป็น effusion ที่อยู่ระหว่าง inferior surface ของ ปอดและ superior surface ของ diaphragm ทำให้ดูเหมือนว่ามี elevation ของ diaphragm ปกติ Dome ของ diaphragm จะอยู่บริเวณ medial 1/3 ถ้าหาก dome อยู่ออกไปทาง lateral ให้ suggest ถึงภาวะนี้ การทํา lateral decubitus CXR จะช่วยให้ เห็น effusion ได้ชัดเจนขึ้น

46 ตำแหน่งที่เป็นจุดสูงสุดของกระบังลมเลื่อนออกไปทางด้านข้างมากขึ้น
Pseudo-diaphragmatic elevation ในสภาวะปกติ right diaphragm จะสูงกว่า left side แต่ไม่เกิน 2 ซม. ตำแหน่งที่เป็นจุดสูงสุดของกระบังลมเลื่อนออกไปทางด้านข้างมากขึ้น

47 กรณีมีพยาธิสภาพข้างซ้าย ระยะห่างระหว่าง gastric air bubble และ ขอบของ diaphragm ห่างกันเกิน 2 ซม.

48 Elevation, laterally position of hemidiaphragm

49 Hydropneumothorax

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52 Ultrasound Bedside ultrasound guidance significantly increases the likelihood of successful pleural fluid aspiration and reduces the risk of organ puncture. Ultrasound detects pleural fluid septations with greater sensitivity than CT.

53 Pleural fluid differential cell counts
Pleural malignancy, cardiac failure and tuberculosis are common specific causes lymphocyte-predominant effusions. Neutrophil-predominant pleural effusions are associated with acute processes. They occur in parapneumonic effusions, pulmonary embolism, acute TB and benign asbestos pleural effusions.

54 pH Pleural fluid acidosis (pH <7.30) occurs in malignant effusions, complicated pleural infection, connective tissue diseases (particularly rheumatoid arthritis), tuberculous pleural effusions and oesophageal rupture In a parapneumonic effusion, a pH of <7.2 indicates the need for tube drainage.

55 Glucose A low pleural fluid glucose level (<3.4 mmol/l) may be found in complicated parapneumonic effusions, empyema, rheumatoid pleuritis and pleural effusions associated with TB, malignancy and oesophageal rupture. The most common causes of a very low pleural fluid glucose level (<1.6 mmol/l) are rheumatoid arthritis and empyema.

56 CYTOLOGY Malignant effusions can be diagnosed by pleural fluid cytology in about 60% of cases.

57 OTHER MARKERS : ADA A positive serum or pleural fluid mesothelin level is highly suggestive of pleural malignancy and might be used to expedite a tissue diagnosis, but a negative result cannot be considered reassuring.

58 FURTHER DIAGNOSTIC IMAGING
Computed tomography (CT) Magnetic resonance imaging (MRI) PET-CT imaging

59 INVASIVE INVESTIGATIONS
Percutaneous pleural biopsy undiagnosed effusion where malignancy is suspected and areas of pleural nodularity are shown on contrast-enhanced CT. Thoracoscopy Thoracoscopy is the investigation of choice in exudative pleural effusions where a diagnostic pleural aspiration is inconclusive and malignancy is suspected. Bronchoscopy

60 SPECIFIC CONDITIONS AND TESTS
Tuberculous pleurisy When pleural biopsies are taken, they should be sent for both histological examination and culture to improve the diagnostic sensitivity for TB. Surrogate markers of pleural TB are useful ‘rule out’ tests in low incidence countries. Adenosine deaminase is the most thoroughly validated to date.

61 Chylothorax and pseudochylothorax
If the pleural fluid appears milky, chylothorax and pseudochylothorax must be considered

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63 PARAPNEUMONIC EFFUSIONS

64 Parapneumonic Effusions : Definitions
Any pleural effusion associated with bacterial pneumonia, lung abscess or bronchiectasis Most common cause of exudative pleural effusions 40-60% of bacterial pneumonias result in pleural effusions Three types Uncomplicated parapneumonic effusion Complicated parapneumonic effusion Empyema

65 ‘Exudative’ effusions, which PMN predominated
20-40% of in-hospital patients who had bacterial pneumonia were found PPE. Especially among pneumococcal pneumonia (up to 60%) Patients with CAP and PPE increased mortality rate about 3 times than patients without PPE. Hasley PB, et al. Arch Intern Med 1996;156:

66 Clinical Manifestations
History Acute febrile episode Dyspnea Cough - w/ purulent sputum Pleuritic chest pain Physical exam Dullness to percussion Diminished breath sounds in affected hemithorax Decreased tactile fremitus Egophony

67 Uncomplicated Effusions
Parenchymal infection leads to increased interstitial fluid that causes accumulation of sterile pleural effusion Pleural fluid is often small (<10mm) sterile w/ small amount of PMNs glucose and pH Resolve with resolution of pneumonia and treatment w/ antibiotics

68 Complicated Effusions
Persistent bacterial infection of previously sterile pleural fluid Pleural fluid Many PMNs, bacteria and cell debris Acidosis - pH and glucose decrease LDH increases Possible deposition of fibrin on pleura - formation of multiple locules

69 Empyema Characterized by bacteria seen on gram stain or aspiration of pus 60% from complicated parapneumonic effusions 20% after thoracic surgery

70 Analysis of Pleural Fluid : Characteristics of Pleural Fluid
Simple parapneumonic effusion Complicated parapneumonic effusion Empyema Appearance May be slightly turbid Cloudy Pus Biochemical markers pH >7.30 pH <7.20 n/a LDH maybe slightly elevated LDH >1000 IU/L Glucose >60 mg/dL or pleural/serum ratio >0.5 Glucose <35 mg/dL Nucleated cell count Neutrophils usually <10,000 cells/μL Neutrophils + + (usually >10,000 cells/μL) Microbiology: Gram stain Negative May be positive Microbiology: culture

71 CT CHEST Pleural enhancement can be seen in patients with active inflammation “split pleura sign” Distinguish pleural from parenchymal abnormalities Determine the precise location and extent Detect loculations Find airway and parenchymal abnormalities that may be relevant to the etiology of the pleural infection.

72 split pleura sign

73 Classification of Parapneumonic pleural effusion according to line of Therapy

74 Bacteriological etiology
Examination of pleural fluids Positive result of G/S 58% Positive result of C/S Aerobes 35% Anaerobes 7% Polymicrobial 12% 40% of patients with negative result of G/S and C/S could be positive result for PCR Maskell N, et al. Am J Crit Care Med 2006;174:

75 Bacteriological etiology
Aerobic bacterial infection Acute or abrupt onset High grade fever Productive cough and pleuritic chest pain If clinical deterioration was after 48 hours of antibiotics, the effusion could be complicated PPE or empyema. Anaerobic bacterial infection Subacute onset (> 7-10 days) Fatigue (70%), weight loss (60%), fever (50%), anemia Risks of aspiration pneumonia

76 Further investigations
Chest Radiography Ultrasonography Computed tomography of thorax

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78 Treatment of parapneumonic effusion and empyema
Antibiotics administration Drainage of effusions

79 Treatment : Antibiotics
Decisions for antibiotics in PPE and empyema are similar to those in bacterial pneumonia. Almost groups of ATB could be passed to pleural space , except aminoglycoside which be less effective especially in more acidic circumstance. Duration of ATB administration Depended on multi-factors Pathogens, antibiotics susceptibility Severity of disease Efficacy of pleural effusion drainage Immune status Generally give patient ATB until clinical will be improved (but pleural thickening could be found for 4-6 months), approximately 2-4 weeks.

80 Mandell LA, et al. Clin Infect Dis 2007;44(Suppl2):S27-72.

81 Treatment: Effusion drainage
Complicated PPE Empyema Frank Pus Positive pleural fluid Gram stain Pleural fluid glucose < 60 mg/dl Pleural fluid pH < 7.20 Positive pleural fluid culture Pleural fluid LDH > 3 times to UNL in serum Loculated pleural effusion

82 Indication for drainage
Prolonged pneumonia symptoms, co morbid disease Failure to respond to antibiotic therapy Presence of anaerobic organisms Chest radiograph : Effusion involving >50% of the hemothorax Loculation or an air-fluid level

83 Indication for drainage
Aspiration of pus, a putrid odor associated with an anaerobic infection, a positive Gram stain or culture result, pH <7.20, a glucose level <40 mg/dL, and an LDH level >1000 IU/L USG-Stranding or septation CT-marked pleural enhancement, pleural thickening, and the split pleura sign

84 Treatment: Effusion drainage
Therapeutic thoracocentesis Tube thoracostomy Intrapleural thrombolytic agents Video-assisted thoracoscopic surgery Decortication / thoracotomy Open drainage (Eloesser flap)

85 Therapeutic Thoracocentesis
Drainage in the first time of diagnostic thoracocentesis In less complicated PPE, if clinical improved, other draining methods may be not necessary. If thoracocentesis was done more than 3 times, other draining methods should be considered. Light RW, Rodriguez RM. Clin Chest Med 1998;19:

86 Tube Thoracostomy Delayed ICD in complicated PPE could generate loculation and increase mortality up to 16%. Size of ICD is not corresponding to efficacy of treatment. Large size (32-38F) Small size (28F or less) Influent factors for ICD success Ultrasonography-guided or CT-guided Combined multiple loculated and nonloculated effusions Shankar S, et al. Eur Radiol 2000;10:495-9. Ashbaugh DG. Chest 1991;99:

87 Tube Thoracostomy Clinical and CXR should be improved in hr after ICD. If not improved!!! Inappropriate placement of ICD Occlusion of ICD ICD cannot access loculated PPE Marked thickening viseral pleura > lung cannot full expand Reevaluation by ultrasound or CT Choose other modalities of treatment More ICD Fibrinolytic agent Surgery

88 Tube Thoracostomy

89 Intrapleural Fibrinolytic Agents
In purpose to lysis fibrin membranes of loculated effusions which are difficult to drain. Intrapleural fibrinolytic agents is recommened in early stage of complicated PPE (fibropurulent stage), and contraindicated in patients with coagulopathy or receiving anticoagulant.

90 Most effective in the early fibrinolytic stage : streptokinase, streptodornase, urokinase, and rt-PA
Indications occluded small-bore catheter multiloculated pleural space as a trial before committing the patient to surgery

91 Video-Assisted Thoracoscopic Surgery (VATS)
Choice of therapeutic modality in patients with Loculated effusions irresponsible to ICD Multiloculated empyema About 80% of patients underwent VATS were not required surgery. VATS reduced length of hospital stay and duration of treatment by ICD, compared to surgery, without difference in mortality and morbidity. Chan DT, et al. Ann Thorac Surg 2007;84: Luh SP, Chou MC, Wang LS, Chen JY, Tsai TP. Chest 2005;127: Cassina PC, et al. J Thorac Cardiovasc Surg 1999;117:234-8.

92 VATS

93 Decortication By opened thoracotomy
Extend capacity of drainage and fibrin lysis Significantly reduced thickness of visceral pleura Reduced pleural sepsis Greater lung expansion Early decortication in period of sepsis Delayed decortication in patients with controlled infection but restrictively thickened visceral pleura (after 4-6 month) Molnar T. Eur J Cardiothorac Surg 2007;32:

94 Open drainage by Eloesser flap

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