1. 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

2. 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

3. 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

4. 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.

5. 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.

6. Historical perspective
500BC. Hippocrates: open thoracic drainage.
: 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

7. 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

8. 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

9. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

10. NICK A MASKELL AND ROBERT JO DAVIES TEXTBOOK OF PLEURAL DISEASE

11. 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.

12. 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)

13. 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)

14. 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)

15. 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 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

16. 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%

17. 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

18. 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

19. 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

20. 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

23. 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

27. 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:

28. 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:

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

30. 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

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

32. 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

35. Intrapleural fibrinolytics
1949 Tillet and Sherry: partial purified streptococcal fibrinolysin
Highly purified streptokinase: IU
Urokinase: IU
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

36. 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

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

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

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

40. 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

41. THANKS FOR YOUR ATTENTION