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

  • xx

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]

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
  • 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]
  • 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]])
  • Francisella Tularensis (see Tularemia, [[Tularemia]])
    • Epidemiology: uncommon etiology of parapneumonic effusion
  • Haemophilus (see Haemophilus, [[Haemophilus]])
  • 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]])
  • 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

PUR PLEURAL

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

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

EMPYEMA CHEST CT

  • 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

LOC PLEUR US

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]
  • Intrapleural administration of Pulmozyme for pleural empyema. Respiratory Medicine CME 2011, Vol.4(3):114–115, doi:10.1016/j.rmedc.2010.12.002
  • MIST2 Trial. Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740 [MEDLINE]
  • Is medical thoracoscopy efficient in the management of multiloculated and organized thoracic empyema? Respiration. 2012;84(3):219 [MEDLINE]
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