Pleural Disease




    • 1.5 million diagnosed annually in US:Most common causes:
      • US causes of pleural effusions:




        Heart failure






        Malignant pleural effusion



        Pulmonary embolism



        Viral illness



        Cirrhosis with ascites



        Post–coronary artery bypass surgery



        Gastrointestinal disease (for example,

        hepatic hydrothorax, pancreatitis, esophageal rupture)









        Benign asbestos disease



    • Dyspnea, pleuritic chest pain, dry cough.
      • Also: weight change, fever, arthralgia, orthopnea.
      • Hx of malignancy, cardiac, abdominal surgery, MI, TB, medications, asbestos
    • Exam:
      • Clubbing
      • Joint Deformities/Synovitis
      • Stigmata of Liver disease or heart failure.
    • Diagnosis:
      • Chest Xray
      • Chest CT: useful for identifying AIR in pleural space and pulmonary infiltrates/masses for cause.
      • Thoracic U/S: can be useful, enhances safety/success of thoracentesis.
        • Helps cause (i.e. septations and fluid echo density = exudative process).
        • Helps fluid vs. lung consolidation.
        • Diaphragmatic dysfunction and pleural thickening.
      • Pleural fluid is rarely diagnostic, but supports/refutes the pre-thoracentesis ddx, points to additional studies.

    Para-pneumonic Effusions

    • Guidelines indicate only drain effusions that occupy more than half of hemithorax or >1cm on lateral decubitus views.
    • Reference:
      • Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest. 2000;118(4):1158-1171. PMID: 11035692


    • Not everyone with fluid needs thoracentesis.
      • NOT INDICATED in small <1cm pleural effusions associated with HF, pneumonia, or heart surgery.
    • If small effusion, heart failure, pneumonia or following heart surgery --> no need to work up further.
    • If unexplained effusions ≥1cm (chest wall - to lung distance), should be worked up with thoracentesis.


    Procedure Notes

    • Landmarking: 5-10cm lateral to the spine, 1-2 ribs below the precussed top of the pleural effusion, and above 9th rib.


    Fluid Testing

    • Exucative vs. Transudative Effusion
      • Fluid protein
      • Fluid LDH
      • Serum protein
      • Serum LDH
    • Also check:
      • pH, glucose, cell count, differential, gram stain, cultures.
    • Additional (if needed):
      • Cytology (If cancer is possibility)
        • SEND LOTS! Pathologists spin sample to make cell block, the more you send the more cells they can screen for cancer.
      • Triglycerides (if suspicious of chylous effusion, due to thoracic duct obstruction).
      • Cholesterol (another exudative/transudative criteria)
      • Amylase (pancreatitis, esophageal rupture)
      • NT-proBNP (CHF)
      • Adenosine Deaminase (TB effusions, highly sensitive and specific)
      • Specific Tumor Markers


    Containers To Use

    • Lavender Tube (EDTA additive):
      • Cell count
      • Differential (incl WBC)
    • Green tube (Heparin additive):  - Chemistry
      • Glucose
      • Protein
      • LDH
      • Albumin (if needed)
      • Triglycerides 
      • Cholesterol
    • Blood gas syringe
      • pH
    • Sterile (i.e. Urine Container - starplex)
      • Culture
      • Gram Stain
    • Sterile (i.e. Urine Container - starplex)
      • Pathology (SEND LOTS, recommended THREE FULL STARPLEX CONTAINERS).


    Pleural Fluid Analysis

    • Initial pleural analysis should focus on characterizing fluid as exudative or transudative.
    • Light's Criteria
    • Light's Criteria:

      • Criteria for Exudative Effusion (one of these)
        1.  Fluid Protein / Serum Total Protein > 0.5
        2.  Fluid LDH / Serum LDH > 0.6  (THIS ONE IS NOT USED IN NEW US GUIDELINES)
        3.  Fluid LDH > 2/3 of ULN of serum level 


      - For Exudate: Need one of the criteria

      - For Transudate: Requires NO criteria be true.

    • NOTE:
      • Challenging to differentiate in context of diuretics. --> if patient responds, can look exudative.
      • Can look at gradient of protein and albumin.
        • Protein Gradient (serum - pleural) > 3.1 g/dL (31 g/L) => transudative
        • Albumin Gradient (serum - pleural)  > 1.2 g/dL (12g/L) => transudative


    (Mostly important in exudative effusions)


    • Erythrocytes
      • Fluid looks red if 5000-10,000 RBCs/uL
      • Hemothorax diagnosed if pleural fluid hematocrit >50% of peripheral hematocrit. (transudates can be tinged with blood).
    • WBC
      • >10,000/uL => infection  (but non-specific/sensitive, can see in non-infection too).
      • <1,000/uL => usually transudative
    • Neutrophilic
      • Acute inflammation or infection.
      • Can get in pneumonia (parapneumonic effusions) [often cell count >10,000/uL]
        • Classified as:
          • Complicated, Uncomplicated, Empyema (see below)
    • Lymphocytic Effusion ≥50% Ddx:
      • Most common causes:
        • Tuberculosis (risk factors?, can do Adenosine Deaminase Test)
        • Malignancy  (flow cytometry)
      • If exudative lymphocytic, and no diagnosis ==> Pleural biopsy indicated!!! (important diagnosis)
      • (Note: this only matters in EXUDATIVE effusions)
      • Pleural fluid for flow cytometry indicated for lymphocytic pleural effusions if lymphoma is considered.
    • Eosinophil Count
      • High >10%
      • Low/absent in TB.
      • Caused by:
        • Air or blood in pleural space.
        • Medications, fungal infections, parasitic disease, eosinophilic pneumonia, vasculitis (Churg-Strauss Syndrome), benign asbestos effusions.
      • Usually thoracentesis itself increases eosinophil count.
      • 1/3 of effusions with eosinophilia will not have identifiable cause.
    • Mesophilial cells:
      • absence in TB pleuritis


    • Glucose level < 60 mg/dL (3.33 mmol/L) 
      • TB, parapneumonic effusion, malignant effusion, rheumatoid disease.
      • If parapneumonic effusion + low glucose ==> CHEST TUBE DRAINAGE
        • Signals "complicated parapneumonic effusion".
      • If malignant effusion + low glucose ==> High yield cytology, poor prognosis, poor pleuridesis.
    • pH < 7.2
      • Same implications as low glucose for parapneunonic and malignant effusions (see low glucose above.)
        • Glucose MORE RELIABLE indicator (pH influenced by sample handling - must run sample on a blood gas analyzer within an hour).
          • Even a tiny bit of air will raise pH, and small amounts of lidocaine (even 0.2 mL) will lower pH
        • However pH drops BEFORE GLUCOSE.
      • Causes:
        • Complicated parapneumonic effusions, esophageal rupture, rheumatoid and tuberculous pleuritis, malignant pleural disease, systemic acidosis, paragonimiasis, lupus pleuritis, urinothorax.
        • NOTE: Urinothorax is only transudative effusion with LOW PH.
      • Correlates with glucose level, but falls before glucose (early!!!)
    • Triglyceride Level > 110 mg/dL (1.2 mmol/L)
      • Do not do routinely, but only when chylothorax is suspected.
      • If low, <50 mg/dL(0.6 mmol/L)--> chylothorax is unlikely.
      • Often see cloudy fluid, but if someone fasting, fluid can look clear but have high TG.
      • Confirmed by chylomicrons on lipoprotein analysis.
    • Adenosine Deaminase (ADA)
      • Highly specific for TB pleuritis
      • If <40 u/L--> highly sensitive (excludes TB pleuritis), NPP = 100%
      • If >70 u/L--> highly specific
      • If ADA is elevated, can start empiric therapy until get pleural biopsy to confirm diagnosis.
      • Pleural biopsy is gold standard
        • Pleural biopsy AFB culture and stain!
        • (Also send pleural fluid).
      • AFB stain or culture --> recommended and necessary, but sensitivity is low.
        • AFB stain positive in less than 5% of cases. (only helpful if positive).
        • AFB culture positive in 24% of cases. 
        • If you do that, recommended to send 3 samples!! (to improve detection)  ADA is much better.


    Transudative Effusions

    • Causes:
      • Causes of Transudative Pleural Effusions



        TRANSUDATIVE EFFUSIONS - Common Causes

        Heart failure

        Most common cause of transudative effusion; diuresis can cause borderline exudative chemical characteristics


        Small effusion caused by negative transpleural pressure

        Hepatic hydrothorax

        Most are right-sided; occurs in 6%-12% of patients with end-stage liver disease and clinical ascites; can occur in the absence of ascites


        Small bilateral effusions with evidence of generalized anasarca, from decreased intravascular oncotic pressure

        Constrictive pericarditis

        Usually bilateral with normal heart size; 95% have jugular venous distention

        Trapped lung

        Unilateral as a result of remote pleural inflammation and resultant unexpandable lung; caused by negative transpleural pressure

        TRANSUDATIVE EFFUSIONS - Uncommon Causes

        Cerebrospinal fluid leak into pleural space (duropleural fistula)

        Caused by trauma or thoracic spinal surgery


        Unilateral effusion caused by ipsilateral obstructive uropathy; the only low-pH transudate


        Caused by a central venous catheter misdirected into the pleural space

        Superior vena cava obstruction

        From acute systemic venous hypertension or lymphatic congestion

        Peritoneal dialysis

        Massive effusion; develops within 48 hours of initiating dialysis due to dialysate crossing into the chest because of congenital or acquired defects

    Exudative Effusions

    • Inflammatory effusions
    • Large List:
      • Tuberculosis (Leading cause worldwide, and 5% of pts with TB, most don't have active parenchymal TB)
      • Pancreatitis
      • Pulmonary Embolism
      • Subphrenic Abscess

    Parapneumonic Effusions

    • Caused by bacteria:
      • CAP: S. pneumoniae
      • Empyema: S. milleri, S. aureus, Enterobacteriae, Anaerobic bacteria isolated in 36-76% of empyemas.
    • Small <1cm free-flowing (not loculated) pleural effusions can be safetly managed with abx, followed serially.
    • Classification:
      • Uncomplicated
        • Influx of interstitial fluid + neutrophils, do not require drainage, resolve with pneumonia.
      • Complicated
        • Bacterial pleural invasion.
        • Treated same as Empyema.
      • Empyema
        • (often considered subset of complicated pleural effusions)
        • Defined by positive gram stain and/or culture.
        • Treated same as complicated pleural effusion.
        • (William Osler died, asked colleagues to autopsy on kitchen table, they found empyema).
    • If small (<1cm distance between chest wall and lung)
      • --> safetly manage with abx and serial CXR. (Assuming it's free-flowing  and not loculated)
    • Complicated pleural effusion defined as:

      • larger effusions, esp if >1/2 of hemithorax
      • Septations / loculation
      • pH < 7.2 
      • glucose < 60 mg/dL (<3.3 mmol/L)
      • Positive fluid gram stain or culture (called "empyema")


      Require antibiotics AND pleural drainage

      - chest tubes are preferred


    • DNAse and TPAse - given through chest tube (NEJM 2011)
      • In the past, many infectious effusions required surgical decortication, with lots of morbidity until a trial showed that instilling DNAse and TPA into the effusion through chest tube.
      • NEJM 2011:
        • Enrolled: Clinical evidence of infection
          • Positive on culture for bacterial infection, or positive for bacteria on Gram’s staining, or pleural fluid that had a pH of less than 7.2 (measured by means of a blood-gas analyzer).
        • TPAse and DNAse (2x2 factorial) together was effective to:
          • Improve pleural drainage
          • Hasten hospital discharge
          • Decrease surgical referrals


    • Most common worldwide cause of exudative effusions.
    • 5% of pts with TB have effusions.
    • 20% have active parenchymal disease at the time.
    • If left alone, will resolve without intervention in 2-4mo, BUT most patients will progress to active TB in 5 years.
    • Treat like active TB!
    • NOTE: lymphocytic exudative fluid, with latent TB (positive TST, IGRA) --> TB until proven otherwise.
    • Diagnosis:
      • Main Dx: pleural biposy
        • (necrotizing granulomas or culture results), positive result in 80-90% of cases.
      • Pleural fluid
        • -> AFB smear of pleural fluid positive in 5% of pts at most
        • -> AFB cultures of pleural fluid positive in 25% of pts with TB
      • Adenosine Deaminase (ADA) of fluid
        • Elevated in a number of inflammatory conditions, but highest in TB (>70 units/L)
        • Good negative predictive value 100% (if not elevated < 40 units/L)
      • Other clues:
        • Absence of mesothelial cells.
        • Absence of eosinophils
        • Protein level >5g/dL (>50 g/L)



    • Typically massive unilateral effusion
    • Diagnostic yield increases with sequential samplings..
      • Cytology from each pleural tap often yields malignant cells in 30% of poor taps.
        • Can increase yield by sending large amounts of fluid (3 starplex containers).
      • A GOOD 1st tap: yield: 65%
        • 2nd tap: adds 27%
        • 3rd tap:  adds 5%
        • additional: no help.
      • Thorascopic pleural biopsy indicated for all undiagnosed exudative pleural effusions following 3 pleural fluid samplings.
      • Thorascopic biopsy is >90% sensitive for pleural malignancy.
      • (Closed pleural biopsy is less sensitive than cytology, and SHOULD NOT BE PERFORMED)
      • Flow cytometry is useful with lymphocyte-predominant effusions when lymphoma is considered.
    • Treatment
      • Palliate symptoms.
      • For slowly accummulating: Serial theraputic thoracentesis.
      • For rapid accumulation:
        • Chemical pleurodesis (done with Telc --> applied via chest tube or thorascopically)
          • Success rate of Telc >90% if lung is re-expanded completely!!
          • Placement of a tunneled indwelling pleural catheter (Pleurex (R) in Canada) --> symptom palliation while avoiding hospitalization.
          • Other rare options: Placement of a pleuro-peritoneal shunt, Surgical pleurectomy

    Long-Term Management

    • Options:
      • Do nothing (if asymptomatic)
      • Serial thoracentesis  (very small infection risk)
      • Tunneled Pleural Catheter (~ 1-5% risk of empyema)
        • Catheter that tunnels under skin a few cm medially with cuff allowing tissue to grow in.
          • Minimizes infection risk --> can keep them in for up to 3 months, some case reports of longer.
        • Eventually will likely pleuridese (catheter irritates pleura).
        • (Talc has much higher pleuridesis rate)
        • CCAC will manage catheters as O/P.
      • Talc Pleuridesis
        • Must have lung completely re-expanded.
        • Takes 1 week in hospital 4-5 days of talc in the pleural space.
          • Quite painful, if has 3 months to live... consider other options.
        • Risks:  Infection (5%), ARDS risk.



    • Classified as:
      • Spontaneous
        • Primary Spontaneous (no underlying lung disease)
        • Secondary Spontaneous (if lung disease is present)
      • Iatrogenic
    • Primary Spontaneous Pneumothorax:
      • Risk Factors:
        • Smoking (most important)
        • Family Predisposition (Marfan's syndrome)
        • Thoracic endometriosis
      • Lifetime recurrence rate 25-50%, most likely in 1st year post-pneumothorax.
    • Secondary Spontaneous Pneumothorax
      • Causes:
        • COPD (most common cause)
        • Cystic Fibrosis
        • TB
        • Pneumocystis Jerovecii
      • Much more severe/symptomatic (less pulmonary reserve).
      • High risk of recurrence.
    • Management:
      • Same regardless of primary/secondary.
      • Supplemental high-flow O2 (replaces air with O2, that is faster resorbled)
      • If large or hemodynamically unstable
        • Drain pneumothorax Emergently!
          • Emergent needle thoracostomy to stabilize patient --> decompress air collection.
          • Followed by placement of chest tube!
      • If Small:
        • Primary Spontaneous:
          • <2cm lung-to-chestWall on CXR + minimal symptoms ---> Observation + F/U CXR.
          • >2cm or symptoms --> Aspiration of air collection OR chest tube (chest tube if reacummulates).
            • When air leak resolves: Remove chest tube.
            • If persistent air leak --> Surgery may be needed.
          • If recurrent --> chemical pleuridesis or thorascopic repair (less recurrence, preferred)
        • Secondary Spontaneous:
          • Admit all secondary pneumos to hospital 
          • >2cm --> aspiration + chest tube placement (like primary)
            • However, high risk of recurrence, so definitive management is often needed.
              • Often chemical pleuridesis (via thoracostomy) (25% recurrence)
              • Thorascopic repair --> (5% recurrence)
    • Tension pneumothorax
      • Defined as high intrathoracic pressure from pneumo causing hemodynamic instability.
        • Can happen in primary or secondary pneumo.  
        • Common in mechanical vents. (predisposes to tension etiology).
      • Venous return to R-heart drops, BP drops.
      • Other findings:
        • JVP distension
        • Tracheal deviation away from pneumo.
        • Subcutaneous air (crepitus)
      • Emergency!! --> Immediate decompression
        • Cannula into pleural space in 2nd intercostal space along mid-clavicular line.  Aspiration from cannula until hemodynamic stability.
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