Effusions from parapneumonic infections and empyema 行政院衛生署 桃園醫院 胸腔內科 李世偉醫師

AGENDA The clinical importance of infection in the pleural space Historical perspective The epidemiology of pleural infection The pathophysiology of pleural infection Bacteriology The diagnosis and clinical asessment of pleural infection Differential diagnosis Predictors of clinical outcome in pleural infection Radiology Antibiotics Chest catheter drainage Intrapleural fibrinolytics Future directions NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

The clinical importance of infection in the pleural space Frank purulent pleural empyema has an overall mortality up to 20%, which rise further to about 35% in the immunocompromised host. The actual mortality rise from empyema is substantially influenced by the presence of co-morbid disease. In addition to this mortality, up to 40% of patients will fail treatment which chest tube drainage and antibiotics alone and still require surgical drainage of their pleural collection. Simple parapneumonic effusions arise in up to 57% of cases of pneumonia. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

The clinical importance of infection in the pleural space Parapneumonic effusion occurred in 20 to 40% of patients who are hospitalized with pneumonia. The mortality in patients with parapneumonic effusion is higher than that in patients with pneumonia without a parapneumonic effusion. Some of the excess mortality is due to mismanagement of the parapneumonic effusion. Light RW. Pleural diseases, 4th ed. Baltimore: Lippincott, Williams and Wilkins; 2001.

Definition Parapneumonic effusion is any pleural effusion secondary to pneumonia ( bacterial or viral ) or lung abscess. Empyema is , by definition, pus in the pleural space. A complicated parapneumonic effusion is a parapneumonic pleural effusion for which an invasive procedure is necessary for its resolution, or a parapneumonic effusion on which the bacterial cultures are positive. Light RW. Pleural diseases, 4th ed. Baltimore: Lippincott, Williams and Wilkins; 2001.

Historical perspective 500BC. Hippocrates: open thoracic drainage. 1876-1891: chest tube and under water seal. 1919 First World War: open early surgical drainage, mortality as high as 70%. Hewitt and Bulau: adequate pus drainage with a closed chest tube, avoidance of early open drainage, obliteration of the pleural space, proper nutritional support. Reduced the mortality to 4.3%. 1940s: Penicillin 1940s Tillett: intrapleural fibrinolytic therapy; frequent antigenic side effects 1897 Estlander and 1890 Schede: thoracoplasty 19th Century end Fowler and Beck: decortication of the pleura Video assisted thoracoscopic surgery ( VATS) NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

The epidemiology of pleural infection More common in the elderly and childhood. Men are affected twice as often as women. Higher in those with diabetes, alcoholism and substance abuse, rheumatoid arthritis and chronic lung disease. Poor dentition and risk factors for aspiration are associated with an increase prevalence of anaerobic infection. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Parapneumonic effusion 70% post bacterial pneumonia hospital acquired pneumonia Primary empyema 4% Post operative 12% Traumatic 3% blunt trauma penetrating trauma Iatrogenic e.g. post chest tube insertion Abdominal infection 2% e.g. subphrenic abscess Miscellaneous esophageal perforation bacteremia rupture of lung abscess into pleural cavity intravenous drug abuse ( contaminated needles ) NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

The pathophysiology of pleural infection Development of the initial pleural effusion: the exudative phase The evolution of infection: the fibropurulent phase Natural healing: the organizing stage Andrews NC, Parker EF, Shaw RR, Wilson NJ, Webb WR. Management of nontuberculous empyema. Am Rev Respir Dis 1962;85:935–936.

Development of the initial pleural effusion: the exudative phase There is rapid outpouring of fluid into the pleural space. Most of the fluid is due to increased pulmonary interstitial fluid traversing the pleura to enter the pleural space but some of this is due to increased permeability of the capillaries in the pleural space. The pleural fluid in this stage is characterized by negative bacterial studies, a glucose level above 60 mg/dl, a pH above 7.20, and a lactic acid dehydrogenase (LDH) level of less than three times the upper normal limit of serum. If the patient does not see a physician or receives the wrong antibiotic, the effusion may proceed to the second stage, which is the fibropurulent stage. The Proceedings of the American Thoracic Society 3:75-80 (2006)

The evolution of infection: the fibropurulent phase The pleural fluid in this stage is characterized by positive bacterial studies, a glucose level below 60 mg/dl, a pH below 7.20, and a pleural fluid LDH more than three times the upper normal limit for serum. In this stage, the pleural fluid becomes infected and progressively loculated. The pleural fluid needs to be drained in this stage and drainage becomes progressively difficult as more loculations form. If a stage 2 effusion is not drained, the effusion may progress to the third stage. The Proceedings of the American Thoracic Society 3:75-80 (2006)

Natural healing: the organizing stage Fibroblasts grow into the pleural fluid from both the visceral and parietal pleurae, producing a thick pleural peel. The peel over the visceral pleura prevents the lung from expanding. Because the pleural space must be eradicated if a pleural infection is going to be eliminated, this peel must be removed if the infection is going to be cured. The Proceedings of the American Thoracic Society 3:75-80 (2006)

Light’s classification of parapneumonia effusions and empyema Class1-Non significant Small<10mm thick on decubitus No thoracentesis needed Class2-Typical parapneumonic >10mm thick Glucose>40, pH>7.2, Gram stain and culture negative Class3-Borderline complicated pH 7.0-7.2 or LDH>1000 Gram stain and culture negative Class4-Simple complicated pH<7.0 , Gram stain and culture positive, no loculated or frank pus Class5-Complex complicated pH<7.0, Gram stain and culture positive, multiple loculation Class 6-Simple empyema Frank pus, single locule or free Class 7-Complex empyema Frank pus, multiple loculations

Aerobic and gram positive (180) Viridan streptococcus 46 48% S milleri group 44 Staphylococcus group 39 S pneumonia 31 Other streptococcus spp. 14 Enterococcus spp. 6 Aerobic gram-negative (101) Klebsiella pneumonia 43 27% Pseudomonas spp. 15 Escherichia coli Haemophilus spp. 10 Enterobacter spp. 8 Proteus mirabilis 5 E. Corrodens 4 Salmonella spp. 2 Anaerobes (86 ) Peptostreptococcus spp. 24 23% Bacteroides spp. 23 Fusobacterium spp. 18 Prevotella spp. 7 Veillonella spp. Porphyromonas spp. 3 ‘anaerobes’ mixed Actinomycetes spp Miscellaneous/ Others (8 ) 2%

Bacteriology Aerobic organisms are the most frequent organisms identified from infected pleural fluid. These are most commonly Gram-positive organisms from Streptococcal species, followed by Staphylococcus aureus. Gram-negative empyema is more frequent in patients with underlying diseases, especially those with diabetes and alcoholism. Staphylococcus aureus and Gram-negative enteric bacteria such as Klebsiella pneumonia have a particular propensity to cause pleural infection. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

The diagnosis and clinical asessment of pleural infection History, examination and CXR Measure pleural fluid pH Request fluid Gram’s stain and culture Pleural effusion and evidence for infection Yes Gram’s stain positive Or culture positive Or pH<7.2 No Start antibiotics Perform diagnostic pleural aspiration With image guidance if required No Frank purulent pleural fluid? Pleural infection unlikely Treat with antibiotics provided Clinical progress is good Yes Yes Pleural infection likely Proceed to chest drainage Flow diagram describing a diagnostic pathway for patients with possible pleural infection

Differential diagnosis Pleural involvement occurs in up to 5% of patients with rheumatoid arthritis. Pleural malignancy Chylothorax and pseudochylous effusion Pulmonary embolism Esophageal rupture NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Predictors of clinical outcome in pleural infection Pleural infection has a high mortality and morbidity and presents a clinical challenge in the timing of surgical intervention. Frankly purulent pleural fluid, co-morbid diabetes, delayed referral and pleural drainage, the presence of fluid loculation and a low pleural fluid white count may predict a poor outcome. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Radiology The presence of fever, pulmonary infiltrates and fluid should always alert clinician to the possibility of a parapneumonic collection. Ultrasound is good visualizing septations within loculations that are not usually seen on CT images, but may not identify some separate fluid loculations in inaccessible areas of the thorax. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Five basic ultrasound patterns of pleural effusions Figure 1. Five basic ultrasound patterns of pleural effusions. Top left, I = anechoic pattern: no echogenic density within the effusion; Top right, IIB = complex nonseptated and relatively nonhyperechoic pattern: some visible bright spots as echogenic density within the effusion, and the echogenic shape changed with respiration; Center left, IIA = complex nonseptated and relatively hyperechoic pattern: predominant hyperechoic spots visible within the effusion, and the echogenic shape not changed with respiration; Center right, III = complex septated pattern: prominent fibrinous septation visible within the effusion; Bottom, IV = homogenously echogenic pattern: echogenic spots density evenly distributed within the effusion. Arrowheads indicate a homogenously echogenic pleural effusion (D = diaphragm). Tu, C.-Y. et al. Chest 2004;126:1274-1280

Five basic ultrasound patterns of pleural effusions Top left, I = anechoic pattern: no echogenic density within the effusion Top right, IIB = complex nonseptated and relatively nonhyperechoic pattern: some visible bright spots as echogenic density within the effusion, and the echogenic shape changed with respiration Center left, IIA = complex nonseptated and relatively hyperechoic pattern: predominant hyperechoic spots visible within the effusion, and the echogenic shape not changed with respiration Center right, III = complex septated pattern: prominent fibrinous septation visible within the effusion Bottom, IV = homogenously echogenic pattern: echogenic spots density evenly distributed within the effusion Tu, C.-Y. et al. Chest 2004;126:1274-1280

Pleural Effusions in Febrile Medical ICU Patients* Chest Ultrasound Study Chih-Yen Tu, MD (Chest. 2004;126:1274-1280.)

Antibiotics Antibiotics 40% culture negative It is not uncommon to need at least 2 weeks of therapy and some times longer. Decisions on the length of treatment can be guided by repeated measurements of serum CRP. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Mark Cohen and Steven A. Sahn Chest, May 2001; 119: 1547.

Chest catheter drainage Optimal size of catheter? Excellent outcomes may be achieved with such small catheter especially when combined with fibrinolytic therapy. Drainage may fail if the fluid is of high viscosity and direct blocks the tube. The balance of forces drawing it down the tube is inadequate. If the fluid is partitioned by fibrinous septaeFig.ppt. The rapidity of chest tube drainage might be improved by increasing the drain size, but the successful drainage is unchanged. Here again, provide that the catheter is patent, its bore is irrelevant. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Intrapleural fibrinolytics 1949 Tillet and Sherry: partial purified streptococcal fibrinolysin Highly purified streptokinase: 250000IU Urokinase: 100000IU It form a complex with plasminogen that converts additional circulating plasminogen to plasmin. Plasmin lyses fresh fibrin clot and digests prothrobin and fibrinogen. Improvement in the chest radiograph and greater volume pleural drainage, not outcome of mortality, surgical frequency, or hospital stay. Tube drainage with streptokinase and early surgical intervention showed reduced length of hospitalization Potential side effect: hemorrhage, pleuritic pain and fever NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Surgery for pleural infecetion No definite data that define the point at which a patient with empyema should proceed to surgical intervention. Open thoracotomy with decortication Mini-thoracotomy Video-assisted thoracoscopic surgery (VATS) Rib resection with open drainage VATS: reduced hospital inpatient time, postoperative complications and length of operating time VATS: failures are with empyema in the organizing stage of the disease NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

Figure 2 Surgical scars: open decortication. Jaffe, A et al. Arch Dis Child 2003;88:839-841 Copyright ©2003 BMJ Publishing Group Ltd.

Figure 1 Surgical scars: VATS. Jaffe, A et al. Arch Dis Child 2003;88:839-841 Copyright ©2003 BMJ Publishing Group Ltd.

Luh, S.-P. et al. Chest 2005;127:1427-1432

Future Directions Increasing resistant micro-organism intrapleural fibrinolytics still no know if they actually reduce mortality and need for surgical intervention. Comparing the use of intrapleural fibrinolytics with early VATS NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

THANKS FOR YOUR ATTENTION