1. Empyema or Complicated Parapneumnia Effusion

2. Evaluation of Pleural Effusion
Exudate vs transudate
Light’s criteria for exudate vs transudate
Protein: pleural fluid protein/serum protein >0.5
LDH: pleural fluid LDH/ serum LDH >0.6
pleural fluid LDH >2/3 upper limit normal
PH: should be measured in ABG syringe
normal transudate
exudate
pH & LDH >1000 IU/L likely to be complicated. Chest tube should be considered.
pH < 7.00 and glucose <40 mg/dl: very likely to be complicated. Chest tube should be inserted.

3. Evaluation of Pleural Effusion
Glucose <60 mg/dL
Glucose pleural fluid/serum glucose <0.5
Complicated parapneumonic effusion or empyema
Rheumatoid pleurisy
Tuberculous pleurisy
Lupus pleuritis
Esophageal rupture

4. Empyema
Definition: obvious pus, or pleural fluid demonstrating bacteria on gram stain or growing bacteria in culture.
Bacteriology (Bartlett, Feingold)
Anaerobes
Aerobes

5. Bacteriology of Empyemas
Anaerobic bacteria in 36-76%
Putrid odor of empyema is considered diagnostic.
Gram stains: unique morphology of anaerobic gram negative rods.
Anaerobes in combination with microaerophilic or aerobic streptococci, all components of normal oral flora.

6. Empyema Management
Antibiotics
Drainage of pus
Surgically placed tube drainage
3 tubes sign
When tube drainage is unsuccessful:
Decortication
Fibrinolytic Therapy

7. Fibrinolytic Therapy
Streptokinase
Urokinase
Alteplase
DNAase
Which agent? Is it efficacious?

8. Basic Knowledge of Complicated Effusion
Learn about cells, bacteriology, chemistry including pH, glucose, LDH, cytokines
Antibiotics
Watch the natural course of resolution.
Learn the factors associated with poor resolution. Incomplete knowledge now
Assumption of poor outcome of all complicated effusions.

9. Basic Knowledge
Those effusions with risk of complications should be subject to therapeutic interventions in randomized prospective studies.
Alteplase
VATS

10. Current Practice at Jacobi
CXR, pleural component is suspected--
Chest CT
Thoracentesis, drain as much as possible by thin wall catheter. (aim: complete drainage)
IR places a pigtail catheter into the largest locule and drain as much as possible.
Drainage volume and CXR show inadequate drainage, instill TPA (Alteplase) 25 mg x 1 for 2 hours and drain overnight.
Assess drainage and CXR. Usually 1 dose is adequate.

11. Background
Loculated pleural effusions and empyema usually require a chest tube drainage or, sometimes, surgical lysis of locule(s) and decortication.
Intrapleural instillation of fibrinolytic agents, such as streptokinase and urokinase, is widely practiced worldwide although their efficacy is debated.
We resorted to use of alteplase (recombinant tissue plasminogen activator) for intrapleural fibrinolysis when streptokinase was withdrawn from US market in We present our experience with alteplase of 8 years.

12. UK Controlled Trial of Intrapleural Streptokinase for Pleural Infection (NEJM 2005; 352:865-74)
Double blind trial, 454 patients with pleural infection
Streptokinase 250,000 IU 2X/D for 3 D or placebo
Antibiotics, chest tube drain, surgery and other routine care.
Primary end point: death or surgical drain in 3 mo
Secondary end point: death rate, surgical rate, radiographical outcome, LOS

13. UK Controlled Trial Streptokinase Placebo Rel Risk
Death or Surgery 64/ % 60/ % 1.14
Radiography no benefit
LOS median 13 D 12 D no dif
Side effects 7% %
(chest pain, fever, allergy)

16. Jacobi Current Practice
If drainage after the first dose of alteplase is inadquate (insufficient volume drained or CXR abnormality not resolved), a second dose of alteplase 25 mg is instilled and drain again.
May need another catheter inserted into a second locule not drained by the first.

17. Case 1
76 yo woman with asthma, DM, CAD had a recent asthma exacerbation, treated with a course of prednisone. She then had a recurrence of shortness of breath and cough productive of green sputum, right sided chest pain, in the right lower posterior aspect.
T 102.6, p110, WBC 24K
Sputum grew MRSA. Pleural fluid also grew MRSA sens to gentamycin, linezolid, vanco, rifampin, bactrim. She was treated with vanco.

18. Case 2
42 yo man was admitted to NCB Hosp for cough productive of yellow sputum, SOB, left sided chest pain of pleuritic nature. WBC 16K. CXR LLL density. Treated with ceftriaxone and azithromycin. Follow up CXR showed persistent LLL density. Chest CT: loculated effusion in the left lower chest. Attempts at thoracentesis unsuccessful. WBC 21K. Transferred to Jacobi for pigtail catheter by IR.

19. Case 3
42 yo woman with hx DM, seizure disorder, menorrhagia presented with 1 week hx of fever, chills, cough productive of yellow sputum, back and chest pain. T 101.3, WBC CXR left basilar density.

20. Intrapleural Catheter Placement
A pig-tail catheter, French size 8-12, was inserted into the largest pocket under CT guidance by an interventional radiologist, or a chest tube was inserted by a surgeon at bedside, or a trocar catheter was inserted by a pulmonary fellow at bedside.
Drainage was carried out under -20 cm water pressure and monitored daily. The catheter was flushed once or twice daily with 5 ml of normal saline.
Chest x-ray examined daily for resolution.
Chest CT was repeated when the resolution was inadequate, and the pigtail catheter may be repositioned or another catheter may be inserted into another location.

21. Lung and Pleural Disease
Patients lung and pleural disease
pneumonias & pleural effusion
5 pneumonias & empyema
2 lung abscess & empyema
3 loculated effusion, no pneumonia
1 lung abscess & effusion
24 total

22. Pleural Fluid Characteristics
PH > patients
<
Glucose > 10 mg/dl 10
< 10 mg/dl 7
Protein > 5 gm 5
< 5 gm 5
LDH > 1000 u 10
< 1000 u 8
Gram stain+/Culture + 7

23. Patients 8 female and 16 male age range 24-90. 20 had co-morbidities
5 COPD/asthma
7 HTN
6 DM
2 CVA
2 Schizophrenia
2 Dysphagia
2 Cirrhosis of liver
5 Alcohol or drug abuse
1 Seizure disorder

24. Length of Hospital Stay (LOS) days
Total LOS pre-Alteplase post-Alteplase
Mean 16 D 7.2 D 8.7 D
Median

25. Chest Tube Drainage Before Alteplase After Alteplase
Mean 668 ml (SE 176) 1308 (SE 207)
Median 500 ml ml

26. Chest Tubes and # Alteplase Instillations
16 had one pigtail catheter Fr size 8-12.
3 had two pigtail catheters.
7 had one chest tube inserted at bedside.
2 had one pigtail and one chest tube.
Alteplase dose ranged between 100mg -5mg per instillation. Median dose 25 mg
6 received two doses two to three days apart

27. Conclusions
7 empyemas and 17 loculated pleural effusions were managed with a pig-tail catheter placed under CT guidance. (44 by Jan 2010)
When drainage in hours was deemed inadequate, alteplase 25 mg was instilled through the catheter, clamped for 2 hours and released.
Subsequent drainage ranged between 150 ml to 4000 ml in the next 2 days.
CXR and chest CT showed excellent outcome in 20 and fair outcome in 4. None required a surgical intervention, VATS or open thoracotomy.
Alteplase instilled into the loculated pleural effusion was effective fibrinolytic agent with minor side effects.

28. Is Alteplase More Effective than Streptokinase?
We found it more effective than streptokinase. A randomized prospective study is ongoing in UK.
More expensive. One or two doses of Alteplase vs several doses of streptokinase.
Chest CT is invaluable in assessing the pleural process, underlying lung disease and selection of site for catheter placement.
CT guided placement of a small bore catheter, Fr 8-12, is well tolerated by patient.
Alteplase related complications were few, fewer than with streptokinase.

29. Conclusions
Are we doing too much? Pleural loculation may resolve with time. If not, then what?
Could we hasten the process? During the diagnostic thoracentesis, if the fluid return is inadquate, alteplase can be instilled then and drain 2 hours later. Save one day.
Should we resort to VATS earlier?