Pleural Effusion-Parapneumonic

Definitions

Parapneumonic Effusion

Definitions

Parapneumonic Pleural Effusion: effusion which occurs in association with bacterial pneumonia, lung abscess, or bronchiectasis (although an infected pleural effusion may rarely develop without an adjacent pneumonia)
- Uncomplicated Parapneumonic Effusion: occurs with movement of lung interstitial fluid and neutrophils across the visceral pleural into the pleural space
  - Exudate with pH >7.2
- Complicated Parapneumonic Effusion: occurs when there is bacterial invasion of the pleural space, neutrophil influx, and pleural space acidosis (due to anaerobic utilization of glucose by the neutrophils and bacteria)
  - Exudate with pH <7.2
  - Higher Incidence of Complicated Parapneumonic Effusion in HIV/AIDS (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])

Empyema

Definitions

Vianna Definition of Empyema (JAMA, 1971) [MEDLINE]: positive pleural fluid culture or WBC >15,000/mm3 and protein >3.0 g/dL
Weese Definition of Empyema (Arch Intern Med, 1973) [MEDLINE]: >500 WBC/mm3, protein >2.5 g/dL, or specific gravity >1.018
Modern Definition: presence of pus in the pleural space and/or positive Gram stain of pleural fluid
- Positive Pleural Fluid Cultures are Not Required for the Diagnosis of Empyema, Since Pleural Fluid Cultures May Be Negative for Multiple Reasons
  - Anaerobic Organisms are Difficult to Culture
  - Insensitivity of Bacterial Culture Methods
  - Pleural Fluid Sampling Often Occurs After a Patient Has Already Received Antibiotics
  - Pleural Fluid Sampling Errors May Occur Due to Loculations with Aspiration of a Sterile Fluid Pocket, Adjacent to an Infected Fluid Pocket

Epidemiology

Parapneumonic Effusion

Prevalence of Parapneumonic Effusion: parapneumonic effusion occurs in approximately 40% of hospitalized patients with bacterial pneumonia [MEDLINE]

Risk Factors for Parapneumonic Effusion

Delay in Receiving Medical Care
Cholethorax (see Pleural Effusion-Cholethorax, [[Pleural Effusion-Cholethorax]])
Inadvertent Placement of Nasogastric (NG) Tube Into Pleural Space with Enteral Tube Feeding Infusion (see Nasogastric Tube, [[Nasogastric Tube]])
Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]]): likely has increased risk of empyema

Protective Effect of Inhaled Corticosteroids Against the Development of Parapneumonic Pleural Effusion (see Corticosteroids, [[Corticosteroids]])

Clinical Efficacy
- Spanish Study of the Effect of Prior Inhaled Corticosteroids (in Both Asthma and COPD) on the Risk of Developing Parapneumonic Effusion in Association with Pneumonia (Am J Respir Crit Care Med, 2013) [MEDLINE]
  - Prior Use of Inhaled Corticosteroids Decreased the Risk of Parapneumonic Effusion in Association with Pneumonia
  - Prior Use of Inhaled Corticosteroids was Associated with Higher Pleural pH, Higher Pleural Glucose, Lower Pleural Protein, and Lower Pleural LDH

Empyema

Risk Factors for Empyema

Diabetes Mellitus (DM) (see Diabetes Mellitus, [[Diabetes Mellitus]])
- Epidemiology: increases risk for Klebsiella Pneumoniae Empyema
Influenza (see Influenza Virus, [[Influenza Virus]])
- Predominant Etiologies of Bacterial Superinfection and Empyema Following Influenza (J Infect Dis, 2008) [MEDLINE]
  - Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
  - Streptococcus Pneumoniae (see Streptococcus Pneumoniae, [[Streptococcus Pneumoniae]])
  - Streptococcus Pyogenes (Group A β-Hemolytic Streptococcus) (see Streptococcus Pyogenes, [[Streptococcus Pyogenes]])

Etiology

Pneumonia (see Pneumonia, [[Pneumonia]])
- Epidemiology
  - Parapneumonic Effusion Occurs in 40% of Bacterial Pneumonias Cases (Am J Med, 1980) [MEDLINE]
  - Pneumonia Accounts for 55% of Parapneumonic Effusion Cases
Esophageal Perforation (see Esophageal Perforation, [[Esophageal Perforation]])
- Epidemiology: xxx
- Clinical: usually produces an infected effusion
Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])
- Epidemiology: xxx
- Physiology: probably due to formation of bronchopleural fistula via rupture of necrotic subpleural nodules
Sepsis (see Sepsis, [[Sepsis]])
- Epidemiology: xxx
- Physiology: xxxx
Spontaneous Pneumothorax (see Pneumothorax, [[Pneumothorax]])
- Epidemiology: xxx
Subdiaphragmatic Infection
- Types of Subdiaphragmatic Infection
  - Abdominal Abscess (see Abdominal Abscess, [[Abdominal Abscess]])
  - Pyogenic Liver Abscess (see Pyogenic Liver Abscess, [[Pyogenic Liver Abscess]])
Thoracentesis (see Thoracentesis, [[Thoracentesis]])
- Epidemiology
- Physiology: xxx
Thoracic Surgery
- Epidemiology: accounts for 21-25% of cases
  - Incidence of Post-Pneumonectomy Empyema: 2-10%
Trauma (see Trauma-General, [[Trauma-General]])
- Epidemiology: accounts for 6% of cases
Idiopathic Parapneumonic Effusion
- Epidemiology: accounts for 7% of cases

Microbiology

General Comments

Animal Studies Indicate that a Mixed Pleural Space Infection with Both Aerobes and Anerobes is More Likely to Produce an Empyema than Infection with a Single Organism (J Pediatr Surg, 1994) [MEDLINE]
- Mixed Aerobic and Anaerobic Empyema was Found in 23% of Cases (Chest, 1993) [MEDLINE]: mixed microaerophilic or aerobic Streptococci with anaerobes are a common combination (as these are all components of normal oral flora)
- For These Reasons, Isolation of an Aerobic Organism Alone Does Not Eliminate the Need to Cover for Unrecovered Anaerobic Organisms
Microbiology of Pleural Space Infection Appears to Be Changing (Respirology, 2011) [MEDLINE]
- Different Organisms Predominate in Pediatric vs Adult Cases
- Different Organisms Predominate in Community-Acquired vs Hospital-Acquired Cases
- Pneumococcal Vaccination Has Altered Streptococcus Pneumoniae Serotypes in Empyema

Organisms

Anerobes: anaerobes are present in 36-76% of empyemas (Chest, 1993) [MEDLINE]
- Bacteroides Fragilis (see Bacteroides Fragilis, [[Bacteroides Fragilis]])
- Fusobacterium Nucleatum (see Fusobacterium Nucleatum, [[Fusobacterium Nucleatum]])
- Peptostreptococcus (see Peptostreptococcus, [[Peptostreptococcus]])
- Prevotella (see Prevotella, [[Prevotella]])
Actinomycosis (see Actinomycosis, [[Actinomycosis]])
- Epidemiology: pleural space involvement occurs in >50% of thoracic Actinomycosis cases
Bacillus (see Bacillus, [[Bacillus]])
- Bacillus Anthracis (see Anthrax, [[Anthrax]])
  - Epidemiology: xxx
- Bacillus Cereus (see Bacillus Cereus, [[Bacillus Cereus]])
  - Epidemiology: uncommon etiology of parapneumonic effusion
Clostridium (see Clostridium, [[Clostridium]])
- Epidemiology: uncommon etiology of parapneumonic effusion
Enterobacteriaceae (Selected Organisms) (see Enterobacteriaceae, [[Enterobacteriaceae]])
- Citrobacter (see Citrobacter, [[Citrobacter]])
- Enterobacter (see Enterobacter, [[Enterobacter]])
- Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]]): aerobic Gram-negative rod
- Klebsiella (see Klebsiella, [[Klebsiella]]): aerobic GNR
- Proteus (see Proteus, [[Proteus]])
- Salmonella (see Salmonella, [[Salmonella]])
- Serratia (see Serratia, [[Serratia]])
Francisella Tularensis (see Tularemia, [[Tularemia]])
- Epidemiology: uncommon etiology of parapneumonic effusion
Haemophilus (see Haemophilus, [[Haemophilus]])
- Haemophilus Influenzae (see Haemophilus Influenzae, [[Haemophilus Influenzae]])
- Haemophilus Parainfluenzae (see Haemophilus Parainfluenzae, [[Haemophilus Parainfluenzae]])
Legionella (see Legionellosis, [[Legionellosis]])
Listeria Monocytogenes (see Listeriosis, [[Listeriosis]])
- Epidemiology: uncommon etiology of parapneumonic effusion
Pseudomonas (see Pseudomonas, [[Pseudomonas]])
Staphylococcus (see Staphylococcus, [[Staphylococcus]])
- Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
  - Methicillin-Sensitive Staphylococcus Aureus (MSSA)
  - Methicillin-Resistant Staphylococcus Aureus (MRSA)
- Staphylococcus Epidermidis (see Staphylococcus Epidermidis, [[Staphylococcus Epidermidis]])
Streptococcus (see Streptococcus, [[Streptococcus]])
- Streptococcus Anginosus Group (Formerly Streptococcus Milleri Group) (see Streptococcus Anginosus Group, [[Streptococcus Anginosus Group]])
- Streptococcus Pneumoniae (see Streptococcus Pneumoniae, [[Streptococcus Pneumoniae]])
- Streptococcus Pyogenes (Group A β-Hemolytic Streptococcus) (see Streptococcus Pyogenes, [[Streptococcus Pyogenes]])
Mycobacterium Tuberculosis (see Tuberculosis, [[Tuberculosis]])
- Tuberculous Empyema is a Rare Manifestation in which Tuberculous Infection Results in a Neutrophil-Predominant Empyema: in contrast, tuberculous pleurisy is a lymphocytic-predominant effusion which occurs due an immunologic response to tuberculous proteins

Physiology

Exudative Stage: rapid accumulation of sterile fluid (with low WBC, low LDH, normal glucose, normal pH) in pleural space (probably from interstitium in lung/possibly some originates from visceral pleural capillaries also)
- Progression can be arrested at this stage if treated with antibiotics alone
Fibropurulent Stage: accumulation of neutrophils, bacteria, fibrin, and cellular debris in pleural space (with resultant decrease in pH and glucose/increase in LDH/formation of loculations in space)
Organization Stage: fibroblasts grow into exudate from visceral and parietal pleura, creating an inelastic pleural peel
- Thick exudate may drain through the chest wall (empyema necessitatis) or into the lung (bronchopleural fistula)

Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

Leukocytosis
- Leukocytosis with Aerobic Bacterial Pneumonia
  - Mean WBC in Cases without Parapneumonic Effusion: 17,100
  - Mean WBC in Cases with Parapneumonic Effusion: 17,800
- Leukocytosis with Anerobic Bacterial Pneumonia and Parapneumonic Effusion
  - Median WBC: 23,500
Mild Anemia (see Anemia, [[Anemia]]): common in anerobic cases

Serum Procalcitonin (see Serum Procalcitonin, [[Serum Procalcitonin]])

Rationale
- Serum Procalcitonin Has Proved Useful in Diagnosing Bacterial Pneumonia
Clinical Efficacy
- Study of Serum Procalcitonin in Differentiating Parapneumonic Effusion from Malignant/Tuberculous Effusion (Clin Biochem, 2013) [MEDLINE]
  - Serum Procalcitonin >0.18 ng/mL: 83.3% sensitivity/81.0% specificity in determining if a pleural effusion has a bacterial infectious etiology
  - Serum Procalcitonin Performed Better than Pleural Fluid Procalcitonin
Other Considerations
- Serum Procalcitonin Does Not Have Utility in Determining the Need for Pleural Chest Tube Drainage

Pleural Fluid (see Thoracentesis, [[Thoracentesis]])

Indications for Thoracentesis in the Setting of Parapneumonic Effusion (Chest, 2000) [MEDLINE]

Free-Flowing Pleural Fluid Which Layers >25 mm on a Lateral Decubitus Chest X-Ray or Chest CT
Pleural Fluid Loculations
Thickened Parietal Pleural on Intravenous Contrast-Enhanced Chest CT: this is suggestive of empyema

Technique

Ultrasound Guidance is Standard

Appearance

Example: empyema (purulent drainage) in pleurevac container

Odor

Foul-Smelling Odor: indicates the presence of anaerobic infection

Pleural Fluid Cell Count and Differential

xxx

Pleural Fluid pH

Decreased: pleural fluid pH >7.20 is considered the recommended threshold for pleural chest tube drainage (Chest, 2000) [MEDLINE]
- Pleural Fluid pH is the Most Sensitive Indicator for Pleural Chest Tube Drainage (Am J Respir Crit Care Med, 1995) [MEDLINE]
Technique
- Improper Processing of Pleural Fluid pH Samples Occurs in 30-50% of Labs in the US (Curr Opin Pulm Med, 2013) [MEDLINE]
  - Potential Errors in pH Measurement in Pleural Fluid Samples: exposure of sample to air, delay in measurement, use of pH meter instead of a blood gas machine
Other Conditions May Also Present with Pleural Fluid Acidosis and/or Low Pleural Fluid Glucose (see Pleural Effusion-Glucose + pH Patterns, [[Pleural Effusion-Glucose + pH Patterns]])

Pleural Fluid Glucose

Decreased: pleural fluid glucose <60 mg/dL is considered the threshold for pleural chest tube drainage
- Diagnostic Accuracy of Pleural Fluid Glucose for Parapneumonic Effusion is Less Sensitive than Pleural Fluid pH (Am J Respir Crit Care Med, 1995) [MEDLINE]: however, it may be useful when pleural fluid pH is not available

Pleural Fluid Total Protein

Pleural Fluid Total Protein/Serum Total Protein Ratio >0.5
- Exudative (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])

Pleural Fluid Lactate Dehydrogenase (LDH)

Pleural Fluid LDH/Serum LDH Ratio >0.6
- Exudative (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])
- Pleural Fluid LDH is Increased Due to the Lysis of Neutrophils
- Pleural Fluid LDH >66% of Upper Limit of Normal Range for Serum LDH
- Pleural Fluid LDH May Be >1000 IU/L in Some Cases

Serum-Pleural Albumin Gradient (SPAG)

Serum-Pleural Albumin Gradient (SPAG) <1.2 g/dl
- If Fluid Clinically Appears to be a Transudate and SPAG >1.2, but Light’s Criteria Suggest Exudate, Pleural Fluid Can Be Assumed to Be a Transudate: due to the fact that albumin is lower molecular weight than other proteins and crosses capillary walls more easily

Pleural Fluid Cholesterol

Pleural Fluid Cholsterol: elevated >55-60 mg/dL
- Seen in All Exudates
Pleural Cholesterol/Serum Cholesterol Ratio: elevated
- Seen in All Exudates

Staining

Gram-Stain: useful to identify etiologic organism
Acid-Fast Bacteria (AFB) Stain: useful to identify etiologic organism

Pleural Fluid Culture

Sensitivity of Pleural Fluid CUlture
- Pleural Fluid Culture is Often Negative in Empyema: since animal models demonstrate that bacteria are typically cleared rapidly from the pleural space (Ann Thoracic Surg, 1987) [MEDLINE]
- Anerobic Organisms are Difficult to Isolate by Pleural Fluid (and Blood) Culture: increased sensitivity for detection of anaerobes may be provided by molecular methods (Chest, 2011) [MEDLINE]
- Use of Blood Culture Bottles to Culture Pleural Fluid: use of blood culture bottles (in addition to standard culture) improves the sensitivity of pleural fluid culture (Thorax, 2011) [MEDLINE]

Molecular Analysis of Pleural Fluid

PCR or Rapid Antigen Assay for Streptococcus Pneumioniae: these increase sensitivity for detection of Streptococcus Pneumioniae (Clin Infect Dis, 2006) [MEDLINE]

Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]])

Indications
- Quantification of Pleural Fluid: using upright and lateral decubitus chest x-ray to determine the extent of layering
- Detection of Pleural Fluid Loculation: may be seen on chest x-ray in some cases

Chest CT with Intravenous Contrast (see Chest Computed Tomography, [[Chest Computed Tomography]])

Technique
- Intravenous Contrast Accentuates the Pleural Line: this aids in the differentiation of parenchymal consolidation vs a pleural collection
Indications
- Quantification of Pleural Fluid
- Identification of Endobronchial Lesions
- Identification of Associated Pneumonia/Lung Abscess (see Pneumonia, [[Pneumonia]] and Lung Abscess, [[Lung Abscess]])
- Detection of Pleural Fluid Loculation and Localization for Potential CT-Guided Chest Tube Placement
  - Example: red arrow indicates loculated posterior pleural effusion which was amenable to single CT-guided chest tube drainage

Findings
- “Split Pleura Sign” (with Chest CT with Intravenous Contrast): thickening of the visceral and parietal pleura with >30 mm of separation of the pleural surfaces
- Pleural Fluid Loculation
- Pleural Fluid Microbubbles: presence of microbubbles within the pleural fluid collection (which presumably are introduced via a prior thoracentesis) suggest that the fluid will be more resistant to chest tube drainage (Clin Radiol, 2006) [MEDLINE]
CT Findings Which Allow Differentiation of Empyema from Lung Abscess (see Lung Abscess, [[Lung Abscess]])
- CT Features Suggestive of Empyema
  - Angles: “ball under the carpet” appearance (obtuse angles between fluid collection and chest wall)
  - Shape: lenticular shape
  - Internal Surface: typically smooth internal surface of fluid collection
  - Displacement: displacement of lung and mediastinum, as empyema pushes adjacent structures toward contralateral side
  - “Split Pleura Sign”: separation of parietal and visceral pleura
  - Air-Fluid Level: may be seen in cases with an associated bronchopleural fistula (see Bronchopleural Fistula, [[Bronchopleural Fistula]])
- CT Features Suggestive of Lung Abscess (see Lung Abscess, [[Lung Abscess]])
  - Angles: acute angles between fluid collection and chest wall
  - Shape: typically round shape
  - Internal Surface: typically thick, irregular internal surface of fluid collection
  - Displacement: lack of displacement of lung and mediastinum, as abscess tends to destroy adjacent lung, rather than displace it
  - Air-Fluid Level: may be seen

Thoracic Ultrasound (see Thoracic Ultrasound, [[Thoracic Ultrasound]])

Indications
- Quantification of Pleural Fluid
- Detection of Pleural Fluid Loculation
  - Example: red arrow indicates loculations within pleural effusion

Other Pleural Fluid Assays

Pleural Fluid VEGF and IL-8 Levels
- Study of Angiogenic Cytokines in Pleural Fluid (PLoS One. 2013) [MEDLINE]
  - Higher Pleural Fluid VEGF and IL-8 Levels Identified Complicated Parapneumonic Effusions
  - Higher VEGF Level or Larger Effusion was Associated with Decreased Fibrinolytic Activity, Development of Pleural Fluid Loculation and Fibrosis, and Higher Risk of Medical Treatment Failure

Clinical-Light Classification Scheme for Parapneumonic Effusion/Empyema

Class 1 (Non-Significant Parapneumonic Effusion)
- Small
- Layering Pleural Fluid <1 cm Thick on Decubitus Chest X-Ray
Class 2 (Typical Parapneumonic Effusion)
- Layering Pleural Fluid >1 cm Thick on Decubitus Chest X-Ray
- Pleural Fluid Glucose <40
- Pleural Fluid pH >7.2
- Negative Pleural Fluid Gram Stain and Culture
Class 3 (Borderline Complicated Parapneumonic Effusion)
- Pleural Fluid pH 7.0-7.2
- Pleural Fluid LDH >1000
- Pleural Fluid Glucose <40
- Negative Pleural Fluid Gram Stain and Culture
Class 4 (Simple Complicated Parapneumonic Effusion)
- Pleural Fluid pH <7.0
- Pleural Fluid Glucose <40
- Positive Pleural Fluid Gram Stain and Culture
- Pleural Fluid Not Loculated or Frank Pus
Class 5 (Complex Complicated Parapneumonic Effusion)
- Pleural Fluid pH <7.0
- Pleural Fluid Glucose <40
- Positive Pleural Fluid Gram Stain or Culture
- Multiloculated
Class 6 (Simple Empyema)
- Frank Pus
- Single Locule or Free Flowing
Class 7 (Complex Empyema)
- Frank Pus
- Multiple Locules

Clinical Manifestations

General Comments

Time Course of Presentation: depends on underlying organism, immunocompetence of the host, and timing of the patient’s presentation for medical care
- Anerobic Emypema: may present after a longer time course (may be as long as weeks in duration)
Renal/Age/Purulence/Infection Source/Dietary Factors (RAPID) Score: used to risk-stratify patients with pleural space infection at presentation
- Study of RAPID Score in Patients (from the UK MIST1 Trial) with Pleural Space Infection at Presentation with Pneumonia (Chest, 2014) [MEDLINE]
  - Increased Age, Hospital-Acquired Infection, Non-Purulence Predicted Poor Outcome
  - Increased RAPID Score Predicted Mortality and Increased Hospital Length of Stay
- Study of RAPID Score to Predict Long-Term Outcome in Pleural Space Infection at Presentation for Pneumonia (Ann Am Thorac Soc, 2015)
  - Increased RAPID Score Predicted Mortality Rate at 3 mo and 1/3/5 yrs
  - Factors Associated with High-Risk RAPID Scores: Gram-negative rod infections, heart disease, diabetes mellitus, lung disease, and increased length of stay

Pulmonary Manifestations

Symptoms Related to Underlying Pneumonia

Cough with Sputum Production (see Cough, [[Cough]])
Dyspnea (see Dyspnea, [[Dyspnea]])
Fever (see Fever, [[Fever]])
Pleuritic Chest Pain (see Chest Pain, [[Chest Pain]])
Physical Exam Findings
- Crackles
- Egophony (E to A Changes)
- Increased Tactile Fremitus

Symptoms Related to Parapneumonic Pleural Effusion/Empyema

Dyspnea (see Dyspnea, [[Dyspnea]])
Empyema Necessitatis: spontaneous drainage of empyema via fistula through the chest wall
Fever (see Fever, [[Fever]])
Pleuritic Chest Pain (see Chest Pain, [[Chest Pain]])
Weight Loss (seeWeight Loss, [[Weight Loss]])
Physical Exam Findings
- Decreased Breath Sounds
- Decreased Tactile Fremitus
- Dullness to Percussion

Symptoms in Cases of Post-Pneumonectomy Empyema

Fever (see Fever, [[Fever]])
Shift of Mediastinum to Contralateral Side: normally, mediastinum shifts to ipsilateral side as it fills with fluid over days-weeks post-procedure
Expectoration of Large Amounts of Pleural Fluid
Presence of Air-Fluid Level within the Pneumonectomized Space
Drainage of Purulent Material from Surgical Incisions

Treatment

Treatment Recommendations by Class

Class 1: no thoracentesis required
Class 2: antibiotics alone
Class 3: antibiotics + serial thoracentesis
Class 4: antibiotics + chest tube
Class 5: chest tube + thrombolytics (rarely requires VATS pleural space drainage)
Class 6: chest tube + VATS pleural space drainage
Class 7: chest tube + thrombolytics (often requires thoracoscopy or decortication)

Treatment Recommendations by Category (ACCP Consensus Guidelines) (Chest, 2000) [MEDLINE]

Category 1: very low risk of poor outcome -> drainage not recommended
- Minimal Free Flowing and <10 mm on Lateral Decubitus CXR: A0
- Pleural Fluid Gram Stain and Culture Results Unknown: Bx
- Pleural Fluid pH Unknown: Cx
Category 2: low risk of poor outcome -> drainage not recommended
- Small-Moderate Free Flowing and <10 mm on Lateral Decubitus CXR and Less than 50% of the Hemithorax: A1
- Negative Pleural Fluid Gram Stain and Culture: B0
- Pleural Fluid pH ≥7.20: C0
Category 3: moderate risk of poor outcome -> drainage recommended
- Large Free Flowing (≥50% of Hemithorax), Loculated Effusion, or Effusion with Thickened Parietal Pleura: A2
- Positive Pleural Fluid Gram Stain or Culture: B1
- Pleural Fluid pH <7.20
Category 4: high risk of poor outcome -> drainage recommended
- Large Free Flowing (≥50% of Hemithorax), Loculated Effusion, or Effusion with Thickened Parietal Pleura: A2
- Pus: B2
- Pleural Fluid pH <7.20

Antibiotics

Should Be Directed at Etiology of Underlying Pneumonia (see Pneumonia, [[Pneumonia]])

Chest Tube (Tube Thoracostomy) (see Chest Tube, [[Chest Tube]])

Indications: as noted above
Clinical Efficacy
- xxxx

Intrapleural Deoxyribonuclease (DNase) (see Dornase Alfa, [[Dornase Alfa]])

General Comments

Rationale: DNA is the main contributor to the viscosity of empyema fluid

Administration

DNase
- Administration (MIST2 Trial) NEJM, 2011) [MEDLINE]: 5 mg intrapleural BID x 3 days

Clinical Efficacy

See Below

Intrapleural Thrombolytics (see Thrombolytics, [[Thrombolytics]])

Agents

Streptokinase (see Streptokinase, [[Streptokinase]]): 250k IU
- Pre-existing Anti-SK Ab (from strep/staph infection, previous systemic or IP SK use,etc) can render SK ineffective
Urokinase: 100k IU
Alteplase (see Alteplase, [[Alteplase]])
- Administration (MIST2 Trial) NEJM, 2011) [MEDLINE]: 10 mg BID x 3 days
  - Sterile preparation of alteplase 10 mg in 25 mL normal saline in 60 mL catheter-tip syringe
  - With two chest tube clamps in place, unclamp chest tube and instill alteplase
  - Flush with sterile 25 ml saline in 60 mL catheter-tip syringe
  - Clamp chest tube for 2 hrs, then place chest tube back to suction

Clinical Efficacy

First Multicenter Intrapleural Sepsis Trial (MIST1) (NEJM, 2005) [MEDLINE]
- Intrapleural Streptokinase Did Not Improve Mortality, Rate of Surgery, or Length of Hospital Stay in Patients with Pleural Space Infection
MIST2 Trial Comparing Intrapleural Tissue Plasminogen Activator with/without DNase in Pleural Space Infection (NEJM, 2011) [MEDLINE]: n = 210 patients (blinded 2 x 2 factorial trial)
- Intrapleural tPA + DNase Therapy: improved drainage, decreased the frequency of surgical referral, and decreased the duration of hospital stay
- Treatment with Either tPA + DNase Alone: no clinical benefit
  - DNase Treatment Alone Resulted in a 3x Increase in the Number of Surgical Referrals Due to Worsening Infection

Video-Assisted Thoracoscopic Surgery (VATS) (see Video-Assisted Thoracoscopic Surgery, [[Video-Assisted Thoracoscopic Surgery]])

Indications
- Failure of Chest Tube Drainage
Procedures
- Pleural Space Drainage: VATS pleural drainage is the standard treatment for patients who fail chest tube drainage
  - Conversion Rate to Thoracotomy: 3% (Ann Thorac Surg, 2006) [MEDLINE]
- Decortication (see Decortication, [[Decortication]]): considered when symptomatic restriction of lung expansion (due to fibrothorax) is still present >6 mo after initial event

Prognosis

Study of Impact of Parapneumonic Effusion Associated with Pneumonia at Hospital Admission on Outcome (Chest, 2016) [MEDLINE]
- Presence of Pleural Effusion at Emergency Department Presentation with Pneumonia Predicts an Increasing Likelihood of Being Admitted, Longer Hospital Stay, and Increased 30-Day Mortality Rate

References

General

Nontuberculous bacterial empyema in patients with and without underlying diseases. JAMA. 1971 Jan 4;215(1):69-75 [MEDLINE]
Empyema of the thorax then and now. A study of 122 cases over four decades. Arch Intern Med. 1973 Apr;131(4):516-20 [MEDLINE]
Parapneumonic effusions. Am J Med. 1980;69(4):507 [MEDLINE]
Experimental aerobic-anaerobic thoracic empyema in the guinea pig. Ann Thorac Surg. 1987;43(3):298 [MEDLINE]
Aerobic and anaerobic microbiology of empyema. A retrospective review in two military hospitals. Chest. 1993;103(5):1502 [MEDLINE]
A bacteriologic basis for the evolution and severity of empyema. J Pediatr Surg. 1994;29(5):667 [MEDLINE]
Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis. Am J Respir Crit Care Med. 1995;151(6):1700 [MEDLINE]
Microbiological diagnosis of empyema in children: comparative evaluations by culture, polymerase chain reaction, and pneumococcal antigen detection in pleural fluids. Clin Infect Dis. 2006;42(8):1135 [MEDLINE]
Prevalence and clinical significance of pleural microbubbles in computed tomography of thoracic empyema. Clin Radiol. 2006;61(6):513 [MEDLINE]
Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis. 2008;198(7):962 [MEDLINE]
Blood culture bottle culture of pleural fluid in pleural infection. Thorax. 2011;66(8):658 [MEDLINE]
A higher significance of anaerobes: the clone library analysis of bacterial pleurisy. Chest. 2011;139(3):600 [MEDLINE]
Pleural infection: changing bacteriology and its implications. Respirology. 2011 May;16(4):598-603 [MEDLINE]
Influence of previous use of inhaled corticoids on the development of pleural effusion in community-acquired pneumonia. Am J Respir Crit Care Med. 2013;187(11):1241 [MEDLINE]
Clinical importance of angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusions. PLoS One. 2013;8(1):e53169. Epub 2013 Jan 7 [MEDLINE]
Procalcitonin as a diagnostic marker in differentiating parapneumonic effusion from tuberculous pleurisy or malignant effusion. Clin Biochem. 2013;46(15):1484 [MEDLINE]
Do we measure pleural fluid pH correctly? Curr Opin Pulm Med. 2013 Jul;19(4):357-61 [MEDLINE]
A clinical score (RAPID) to identify those at risk for poor outcome at presentation in patients with pleural infection. Chest. 2014 Apr;145(4):848-55 [MEDLINE]
Predicting Long-Term Outcomes in Pleural Infections. RAPID Score for Risk Stratification. Ann Am Thorac Soc. 2015 Sep;12(9):1310-6 [MEDLINE]
Pleural Effusions at First ED Encounter Predict Worse Clinical Outcomes in Patients With Pneumonia. Chest. 2016;149(6):1509 [MEDLINE]

Treatment

Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline. Chest. 2000 Oct;118(4):1158-71 [MEDLINE]
MIST1 Trial. U.K. Controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med. 2005 Mar 3;352(9):865-74 [MEDLINE]
Video-assisted thoracic surgery for pleural empyema. Ann Thorac Surg. 2006;81(1):309 [MEDLINE]
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