Empyema or Complicated Parapneumnia Effusion

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 7.60 transudate 7.40-7.55 exudate 7.30-7.45 pH 7.00- 7.20 & 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.

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

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

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.

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

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

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.

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

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.

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 2002. We present our experience with alteplase of 8 years.

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

UK Controlled Trial Streptokinase Placebo Rel Risk Death or Surgery 64/206 31% 60/221 27% 1.14 Radiography no benefit LOS median 13 D 12 D no dif Side effects 7% 3% 2.49 (chest pain, fever, allergy)

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.

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.

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.

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 12.9. CXR left basilar density.

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.

Lung and Pleural Disease Patients lung and pleural disease 13 pneumonias & pleural effusion 5 pneumonias & empyema 2 lung abscess & empyema 3 loculated effusion, no pneumonia 1 lung abscess & effusion 24 total

Pleural Fluid Characteristics PH > 7.20 5 patients 7.20-6.90 5 <6.90 7 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

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

Length of Hospital Stay (LOS) days Total LOS pre-Alteplase post-Alteplase Mean 16 D 7.2 D 8.7 D Median 13 6 6.5

Chest Tube Drainage Before Alteplase After Alteplase Mean 668 ml (SE 176) 1308 (SE 207) Median 500 ml 1050 ml

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

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 24-48 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.

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.

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?