Pleural Empyema Management Benoit Guery Maladies Infectieuses Philippe Ramon Service d’endoscopie Respiratoire CHRU Lille

Empyema formation Exudative stage Fibrinopurulent stage fibrinous material forms on both pleural surfaces. As more fibrin is deposited Fibrinopurulent stage may last several weeks pleural surfaces may be joined by fibrinous septae which cause the fluid to become loculated Organisational stage Proliferation of fibroblasts on the pleural surfaces, which form an inelastic covering preventing adequate lung expansion (fibrothorax).

Goals of the treatment Treat the infection Drain the purulent effusion adequately and completely Re-expand the lung to fill the pleural space Eliminate complications and avoid chronicity

The infection

Bacteriological data Pleural Ponction : Results Exsudate Direct analysis, Gram stain Aerobic and anaerobic cultures (Bactec) If possible before antibiotic treatment Results Mono or polymicrobial ( 4-30%) Variations between series Variations between underlying conditions

Wait et al, Chest 1997 Cheng et al, Chest 2005

Maskell et al, NEJM 2005

Bacteriological data. Streptococcus pneumoniae: 15-20% Increased resistance Staphylococcus:15-30% Streptococcus spp Gram Negative: 20-50% Klebsiella, Enterobacter, Pseudomonas, Hemophilus, E.Coli Anaerobes: Fusobacterium, Bacteroides fragilis

Microbiological diagnosis techniques 3 methods - Standard culture - PCA: Pneumococcal capsular antigen - 16S rDNA PCR confirmed by pneumolysin PCR Le Monnier et al, Clin Inf Dis 2006

Microbiological diagnosis techniques Latex antigen detection Se: 90% Sp: 95% Le Monnier et al, Clin Inf Dis 2006

Antibiotic treatment As soon as the bacteriologic sample are recovered Pneumonia Amoxicillin, 3GC or 3GC +/- Metronidazole Amox-clavulanic acid Dosage of the molecule Nosocomial Tazobactam or Imipenem +/- Aminoglycoside or Quinolone Not Pneumococcus directed molecules Adapted to the laboratory results

Adequate drainage Available techniques

Primary treatment options Antibiotics alone; Recurrent thoracocentesis Insertion of chest drain alone or in combination with fibrinolytics VATS. Open decortication

Thoracocenthesis Big caliber needle Mostly diagnosis technique Therapeutically used if the liquid remains fluid Theoretically allows pleural lavage

Chest Tube As soon as the liquid is thick Localization Size: 20 à 24 free: axillary loculated: Chest imaging using ultrasonography and/or computed tomography Size: 20 à 24 Bedside

Pleural Lavage Isotonic saline +/- Noxyflex (noxytioline) Modalités 3 way stopcock Directly through the CT: 250 to 500 ml Cautiously if suspicion of broncho-pleural fistula Timing: Immediately after CT placement+++ Once a day until the liquid is clear

NOXYFLEX (noxytioline) Local disinfectant (formaldéhyde) 2,5 g diluted in a least 100ml isotonic saline Maximum: 5g/day Incompatible with iodine polyvidone,chlorhexidin, chlorine solution, lactic acid

Fibrinolytics Urokinase: 100 000 or 300 000 IU conditioning Streptokinase: 250000 IU conditioning 250.000 IU in 10-20 ml isotonic saline Don’t evacuate before 24 to 48 heures Constantly associated with fever (38-39°C) Then evacuate Pleural lavage clamp 4h ( Chest 1996)

Video-assisted thoracic surgery Collection<10 cm: unusual Visual control of the CT position 5 mm introducer, 4 mm optical Collection>10 cm 10 mm introducer Two or three ports are made in the chest One port is utilised for the camera and the others for grasping instruments Free fluid is evacuated and loculations drained under thoracoscopic visualisation. Fibrinous adhesions are separated and the pleural debris removed from the pleural lining using endoscopic grasping forceps or by extensive irrigation and suction. Following the procedure, one or two chest drains are then placed in the portholes.

Local antibiotics Usually Rifampin or Colimycin Still debated Do not replace systemic treatment

Physiotherapy Key to a correct evolution After CT removal Often and for a long time….. Decrease surgery Decrease long term pain and functionnal limitations

Therapeutic choices

Guidelines to predict which patients with non-purulent parapneumonic effusions warrant chest tube drainage 240 patients with PPE 85 uncomplicated PPE 67 complicated PPE 88 empyema Porcel et al, Respir Med 2006

BTS and ACCP criteria BTS: non purulent PPE is complicated if any of the following pH<7.2 LDH> 1000 IU/L Glucose <40mg/dL Positive culture ACCP: Positive culture pH<7.2 Glucose <60mg/dL Effusion>half of the hemithorax Porcel et al, Respir Med 2006

Porcel et al, Respir Med 2006

Compare Chest Tube + Streptokinase (n=9) vs VATS (n=11) B score on the Cochrane analysis with methodological concerns: Small number Patient selection Unclear allocation and outcome assessor blinding But: VATS is superior to CT for large loculated pleural empyemas Duration CT LOS Wait et al, Chest 1997 Cochrane 2005

Prospective study between 1997 and 2004 2 groups I: video-assisted thoracoscopy (chest tube, fibrin debrided) II: chest tube without VAT Surgical decortication Group I: 17.1% Group II: 37.1% LOS Group I: 8.3 days Group II: 12.8 days Bilgin et al, ANZ J Surg 2006

Randomized double blind study Hypothesis: Urokinase is effective through the lysis and not the volume effect Randomized double blind study UK (15 patients) for 3 days, 100 000 IU in 100 ml NS Control (16 patients), 100 ml NS for 3 days Complete drainage UK: 13/15 (86%) NS: 4/16 (25%) All patients had inadequate drainage Bouros et al, AJRCCM 1999

Cochrane analysis 2007

Cochrane analysis 2007

Cochrane analysis 2007

Cochrane analysis 2007

Cochrane analysis 2007

Cochrane analysis 2007

Prospective study from 2001 to 2004 Cause: bacterial pneumonia 2 groups: A: CT (70) B: CT + SK (57) Multivariate analysis: the use of fibrinolysis is the only independent factor associated with a favorable outcome Misthos et al, Eur J Car Thor Surg 2005

452 patients with pleural infection Sk 250 000 IU twice daily for 3 days Placebo No difference in mortality, rate of surgery, radiographic outcomes, LOS Serious adverse events more common with Sk (chest pain, allergy, fever) Maskell et al, NEJM 2005

Meta-analysis with 5 properly randomized trials comparing fibrinolytic agents to placebo 575 patients Tokuda et al, Chest 2006

Only one study analyzed… no differences observed on the parameters Cochrane analysis 2007

Fibrinolytics vs VATS 60 children matched No difference LOS after intervention Failure rate Radiologic outcome at 6 month Treatment cost with UK ($6 914)< VATS ($10 146) Sonnappa et al, AJRCCM 2006

Case report 1 50 yo Left Pneumococcus empyema Admitted on the 4th day D2 streptase instillation D3 VATS+2 CT CT removal on D8 Discharged on D12

Case report 2 76 yo March 96: Pneumonia April 96 : Left lung effusion No fever, CRP 29, fibrinogen 7g/l Exsudate, LDH 7200, glucose 0,24g/l cytology PMN, negative direct examination

Pleural lavage (Noxyflex) CT removal on 2/5/96 VATS (25/4/96): loculated Removed debris and liquid (600ml) Posterior CT n°24 Pleural lavage (Noxyflex) CT removal on 2/5/96

Indications Thoracocentesis Clear liquid Not clear or purulent effusion pH>7.20 pH<7.20 Not loculated Loculated No intervention Reccurent thoracocentesis Drainage Pleural lavage Drainage Pleural lavage Fibrinolytics Failure VATS Surgery Hamm et al, ERJ 1997

Indications Thoracocentesis Clear liquid Not clear or purulent effusion pH>7.20 pH<7.20 Not loculated Loculated No intervention Reccurent thoracocentesis Drainage Pleural lavage Fibrinolytics 24-48h Drainage Fibrinolytics Pleural lavage VATS Drainage Pleural lavage Failure VATS Surgery Failure Surgery