Pleural Effusions

and a little bit about other pleural disease:

An overview

Dr. Robert Aaronson

Normal pleura
Two layers:
Visceral
Parietal - accounts for most secretion and
absorption of pleural fluid.
Normal values:
volume: 7-10ml
protein: 15g/L
cells: 1500/ uL

Pathogenesis of pleural effusion

Elevated capillary hydrostatic pressure - cardiac
failure.
Reduced capillary oncotic pressure hypoalbuminemia.
Enhanced capillary permeability - inflammation.
Obstructed lymphatics - tumor.
Movement of fluid from extrathoracic site pancreatitis.

Clinical manifestations
Symptoms:
asymptomatic
pain- "pleuritic" or "dull ache"
cough
dyspnea
Physical examination:
enlarged hemithorax
reduced vocal fremitus
dullness to percussion
decreased breath sounds, friction-rub

Approach to a pleural effusion

Plain chest X-ray Distribution is determined by gravity.
Obliteration of lateral costophrenic angle
Fluid higher laterally (PA film) and
semicircular meniscus on lateral films.
Detects > 175ml of fluid
May be subpulmonic, loculated or
"pseudotumor"

Clinical approach- cont.

Decubitus x-rays
Ultrasound
Computerized tomography, MRI
Pleural tap!!
Closed pleural biopsy
Thoracoscopy
Open pleural biopsy

Narrowing the Differential of

Pleural Effusions

Transudative
Etiology
Imbalance between hydrostatic/oncotic
forces

Exudative
Etiology
Local factors influencing accumulation
of pleural fluid affected

Modified Lights Criteria

Pleural fluid protein
Pleural cholesterol
Pleural LDH

> 2.9 g/dL

> 45 mg/dL
> 60 % ULN

Any ONE of the following defines an

exudate.
(Traditional Lights criteria:

Pro P/S > 0.5

LDH P/S > 0.6
LDH > 2/3 ULN)

Albumin Gradient
Lights criteria tend to overcall exudates
Especially in transudaive effusions after
diuresis
If difference between albumin in serum
minus pleural fluid is > 1.2 than more likely
a true transudate
May misidentify 13%

Exudative or Transudative
Sensitivity of Tests to Distinguish Exudative from Transudative Effusions

Light, R. W. N Engl J Med 2002;346:1971-1977

Transudates = ultra filtrate of

serum
CARDOSIS (CHF) due to increased
pulmonary venous pressures, usually bilateral
(R > L), usually resolves in 48 hours after
diuresis
NEPHROSIS low oncotic pressures
CIRRHOSIS can preferentially form in pleural
space, hepatic-hydrothorax

Other Transudates
Atelectasis increased negative pleural
pressure Congestive cardiac failure
Peritoneal dialysis
Glomerulonephritis
Urinothorax
Myxedema
Pulmonary embolism
Sarcoidosis.

Differential diagnosis- exudate

Parapneumonic effusion
Malignancy - lung, breast, lymphoma,
mesothelioma
Tuberculosis
Pulmonary emboli
Abdominal disease
Esophageal perforation
Collagen vascular disease

Differential diagnosis- exudates

Drugs- nitrofurantoin,
bromocryptine,amiodarone, methtrexate.
Asbestos
Dressler's syndrome
Meig's syndrome, Yellow-nail syndrome,
Sarcoidosis, Uremia, Myxedema

Total and Differential Cell Counts

Neutrophil predominance (>50%)
Implies acute process*
21 of 26 parapneumonic effusions (81 percent)
4 of 5 effusions secondary to pulmonary embolus (80
percent)
4 of 5 effusions secondary to pancreatitis (80 percent)
But only 7 of 43 malignant effusions (16 percent) and
none of 14 tuberculous effusions contained more than
50 percent neutrophils.

Light RW, Erozan YS, Ball WC Jr. Cells in pleural fluid: their value in differential diagnosis. Arch Intern
Med 1973;132:854-860.

Total and Differential Cell Counts

Lymphocyte predominance (>50%)
Implies chronic process
Cancer, TB, or post CABG
The combined data from two series*show that:
90 of 96 exudative pleural effusions consisting of more
than 50 percent lymphocytes (94 percent) were due to
cancer or tuberculosis.
In these series, 90 of 116 tuberculous pleural effusions (78
percent) contained more than 50 percent lymphocytes.

*Yam LT. Diagnostic significance of lymphocytes in pleural effusions. Ann Intern Med 1967;66:972-982

Total and Differential Cell Counts

Eosinophilia predominance
2/3 blood or air in pleural space (repeated thoracentesis)
Drug reactions
Dantrolene
Bromocriptine
Nitrofurantoin
Exposure to asbestos, paragonimiasis,
ChurgStrauss syndrome.

Pleural Fluid Glucose

< 60 mg/dl
Rheumatoid pleural effusions can be < 10
mg/dl. May have Increased cholesterol from cell
debris.
Empyema/ Complicated Parapneumonic
Effusions
Esophageal rupture high level of salivary
amylase & very low pH
Malignancy
Rarely: ChurgStrauss syndrome,Paragonimiasis
(lung fluke),Lupus pleuritis.

Pleural Fluid pH
Normal pleural fluid ph 7.5 7.6
Usually occurs in same situations as low
fluid glucose.
Often implies empyema (esp. if pH < 7.0)
Lowest pH found in esophageal rupture:
pH 6.0
The lower the pH, the worse the prognosis
with malignant effusions

Pleural-fluid Tests for Cancer

One of the more common causes of exudative effusions esp. in the
elderly
Any tumor can metastasize to the pleura but the commonest are:
lung, breast, lymphoma, ovary, stomach
Is more fluid better?
6cc vs 36 vs 400 vs 1200cc*

Cytologic analysis sensitivity:

Metastatic adenocarcinoma 70%

Mesothelioma-- 10%
Squamous-cell carcinoma-- 20%
Lymphoma-- 25-50%
Do flow Cytometry

Sarcoma involving the pleura-- 25%

Measuring tumor markers is probably worthless

Sallach. Volume of Pleural Fluid Required For Diagnosis of Pleural Malignancy. Chest. Dec 2002.

Analysis of pleural fluid.

Other tests:
Cancer markers- CEA, Ca 15-3 etc.
Usually not helpful (i.e., DONT DO)

Immunological markers - RF, ANF,

complement.
Other serologies
Coccidioides complement fixation

Smears and Cultures

Gram stain will identify infection
Inoculate where?1
PF culture was positive by the conventional method in 8
episodes (33 percent) and by the modified method (blood
culture inoculation) in 18 (75 percent)

Fungi/TB
Fungi may be revealed
M. TB rarely positive2 unless the patient has a tuberculous
empyema or AIDS
1. Xiol X, Spontaneous bacterial empyema in cirrhotic patients: a prospective study. Hepatology
1996;23:719-723
2. Valdes L, Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998;158:2017-2021

Pleural Effusion in Tuberculosis

Untreated TB effusion
Resolves!
HOWEVER, 50% subsequently develop
pulmonary or extrapulmonary TB

Cell count with 90-95% lymphocytes

Fluid protein level > 4.0 gms.
No mesothelial cells

Diagnosing TB Effusions
ADA > 40, TB

Cheap, quick
High prevalence countries, good PPV
Low prevalence countries, good NPV
Therefore, in USA, good test to confidently r/o TB in
lymphocytic predominate exudate

IFN- similar to ADA, but expensive

MTB DNA may be detected by PCR
Closed pleural biopsy has a 60 % yield
VATS

Other Tests on the Pleural Fluid

Amylase
Esophageal Rupture
Pancreatitis

Triglycerides: for chylous effusions

Exudative Effusions by
Appearance
Turbid milky suggest chylothorax or
gross pus equals empyema

Thoracic Duct
Above T5 Left

Below T5
Right

Chylothorax and Empyema

Chylothorax:
TG > 110mg/ dl or chylomicrons in fluid
Tumor (lymphoma), trauma,
lymhangiomyomatosis.
Pseudochylothorax
Empyema - "pus" in the pleural space
"Complicated pleural effusion":
Thick pus
pH < 7.00 or glucose < 60mg/ dl
Positive gram stain or culture
pH <7.2 and LDH >1000U

Hemothorax
Defined as pleural fluid hematocrit of 50%
of blood hematocrit
Will coagulate & may lead to loculation
with complications of fibrothorax &
possible empyema
If small, may defibrinate & remain free
flowing

Exudative Effusions & Cell Count

Review
> 50% lymphocytes cancer, TB
> 10% eosinophils blood or air in pleural
space, drug reactions, asbestos exposure,
paragonimiasis
> 10% basophils leukemic infiltration
> 50% neutrophils acute process
> 5% mesothelial cells TB less likely

Unknown Etiology
What % of the time is no diagnosis made even
after video assisted thoracic surgery (VATS)?
15%

When else to worry..

Empyema means gross pus is present
Complicated parapneumonic effusion is
defined by pH < 7.1 or glucose < 40 or
positive Gram stain or cultures
Borderline complicated is fluid with pH >
7.1 & < 7.2 or glucose > 40 or LDH > 1000
& Gram stain & cultures negative needs
RETAP

Asbestos exposure
Mining mostly occurs in Russia, Quebec & South
Africabut ALSO lots of other places!
Primarily used in the manufacture of textiles,
cement, paper & insulation products
Secondary exposures: new construction, repair
& demolition of old construction, automotive
repair of gaskets, brake lining & undercoating.
Also, naval shipyards!

Indications for Thoracentesis

When is it safe to watch a pleural effusion*?
CHF presentation
Especially if bilateral pleural effusions
If above, THEN DIURESE
Should resolve or at least significantly improve
within 48h

*Light RW. Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure. Am J Med 1990;88:230-234

Light, R. W. N Engl J Med 2002;346:1971-1977

Ultrasound
Indications
Difficulty is encountered in obtaining pleural fluid
Small effusion
How small is small?

Does it decrease rate of pneumothorax?

Uncertain
Experience is probably more important than whether
ultrasonography is used.*

*Light RW. Pleural diseases. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001.

Treatment of pleural effusion

Treat underlying cause
Thoracocentesis
Chemical pleurodesis - talc or other
Pleuro-abdominal shunt
Streptokinase/TPA etc.?
Surgery

Post Procedure CXR

Not routine
Indications:

Air during thoracentesis

Coughing
Chest pain
Dyspnea

In one series of 506 thoracenteses, pneumothorax was

present in 13 of the 18 patients with one or more of
these symptoms (72 percent) but in only 5 of 488
patients with none of these symptoms (1 percent).*

Aleman C, The value of chest roentgenography in the diagnosis of pneumothorax after thoracentesis. Am J Med 1999;107:340343

Tests Indicated, According to the Appearance of the Pleural Fluid

Light, R. W. N Engl J Med 2002;346:1971-1977

Light, R. W. N Engl J Med 2002;346:1971-1977

Pneumothorax
Air in the pleural space.
Spontaneous, iatrogenic, traumatic.
Causes: primary or secondary
(Emphysema, Interstitial fibrosis, LAM,
Histiocytosis, necrotising pneumonia)
Primary spontaneous pneumothorax:
young, thin, smoking males.

Pleural Plaques

Asbestos Pleural Disease

Pleural Plaques marker of exposure along
parietal pleura. If > 4 cm. Has increased risk of
mesothelioma
Benign Asbestos Pleurisy earliest sign of
exposure.Usually asymptomatic with increased
eosinophils. Can recur & resolve with residual
thickening
Rounded atelectasis trapped lung adjacent to
fibrotic pleural surface.

Rounded atelectasis

Pulmonary Asbestosis

Mesothelioma
Patients present with constitutional symptoms,
dyspnea & chest pain
Usually widespread in the pleural space at
diagnosis can be bilateral
Latency period of 30 40 yrs. after exposure.
Asbestos acts as a complete carcinogen. No
contribution by tobacco
Radiographically nodularity of pleura
Diagnose via VATS
Treatment is of uncertain benefit

Mesothelioma

Mesothelioma

Case 1
67 y o man with RA on MTX, prednisone
Has subtle decrease in exercise tolerance & dry
cough
PE: stable deformities, no nodes, no JVP, no
edema dullness on left with crackles at base
Chest Xray reticular interstitial markings & left
pleural effusion
Thoracentesis: protein 4.5, glucose 30
PFTs: mild restriction, nl DLCO

Case 1
Which of the following is most likely true
regarding the patients lung disease?
A) crackles suggest CHF
B) Patient has an empyema & needs
immediate drainage
C) has recurrent aspiration pneumonia
D) consistent with RA associated ILD

Case 2
35 y o man is evaluated for 2 wk history of low
grade fevers, fatigue, cough, pleuritic pain &
DOE
Patient is a construction worker & having
difficulty doing work
10 pack years cigarette smoking
Temp 38.2, pulse - 112, rr - 20
Chest Xray moderate right pleural effusion
WBC 9K, 80% PMNs, 15% lymphs

Case 2
Thoracentesis:
Minimally turbid, yellow
3K cells : 85% lymphs, 5% polys, 1% macs
Pleural fluid protein: 5.2
Pleural fluid LDH 230
Pleural fluid glucose 80
Pleural fluid ph 7.36
AFB & Gram stains are negative
Cytology is negative for malignant cells

PPD is negative

Case 2
Which is the most likely diagnosis?
A) TB pleurisy
B) Lung cancer
C) Parapneumonic effusion
D) Pulmonary embolism
E) Benign asbestos effusion

Case 3
56 y o construction worker, heavy smoker,
sustains severe trauma to left chest
In ER two hours later, chest Xray & CBC are
WNL
Goes to South America for a week long vacation
& has intermittant chest discomfort & gradually
increasing DOE
Comes home repeat Xray large left sided
effusion with minimal contralateral shift

Case 3
Thoracentesis:
Cell count 4000 with 10% polys, 30% lymphs, 15% macs,
45% eosinophils
Pleural fluid hematocrit 10%
Pleural fluid protein 4
PF LDH 200
PF glucose 80
Ph 7.35
Cytology negative

Pain meds prescribed & two weeks later CBC is

9K with 20% eos. Chest Xray shows much less
effusion

Case 3
Which of the following is the most likely
diagnosis?
A) benign asbestos pleural effusion
B) Paragonimiasis
C) Post-traumatic hemothorax
D) Lung cancer
E) Pulmonary infarction

Case 4
60 y o man evaluated for a six weeks of
progressive DOE, fatigue, decreased appetitie &
weight loss
Tobacco- 30 pack yrs, drinks 2-3 cocktails per
day
PE: afebrile, dullness to percussion right side
Chest Xray pleural effusion occupying 40% of
hemithorax without obvious parenchymal lesions
or mediastinal nodes, fluid not loculated

Case 4
Thoracentesis:
Cell count: 2.8K, 10% polys, 50% lymphs,
30% macs, 10% mesothelial cells
PF protein 3.8
PF LDH 210
PF amylase 30
PF glucose 50
Ph 7.26

Case 4
Which of the following is the most likely
diagnosis?
A) Complicated parapneumonic effusion
B) Esophageal rupture
C) Rheumatoid pleurisy
D) Acute pancreatitis
E) Malignant effusion

Case 5
60 y o man with history of heavy ETOH
abuse, has insidious onset of DOE
No cough, chest or abdominal pain
Smoked 1.5 packs for 25 yrs quit 4 yrs
ago
Moderate right effusion with minimal
contralateral shift
Serum albumin is 2.4, INR 1.5, nl U/A
Echo is normal

Case 5
Thoracentesis:
Cell count - .5K, 10% polys, 25 % lymphs,
60% macs, 5% meso
PF protein 1.1
Ratio pleural fluid/ serum protein 0.2
Ratio PF/ serum LDH 0.35
Ph 7.45
PF glucose - 100

Case 5
Which of the following is the most likely
diagnosis?
A) CHF
B) hepatic hydrothorax
C) chronic pancreatitis
D) Lung cancer
E) Nephrotic syndrome