pleura disease effusion

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BTS guidelines for the investigation of a unilateral pleuraleffusion in adultsN A Maskell, R J A Butland, on behalf of the British Thoracic Society Pleural DiseaseGroup, a subgroup of the British Thoracic Society Standards of Care Committee. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .

Thorax2003;58(Suppl II):ii8ii17

1 INTRODUCTIONPleural effusions, the result of the accumulation

of fluid in the pleural space, are a common medi-cal problem. They can be caused by several

mechanisms including increased permeability of

the pleural membrane, increased pulmonary cap-illary pressure, decreased negative intrapleural

pressure, decreased oncotic pressure, and ob-

structed lymphatic flow. The pathophysiology ofpleural effusions is discussed in more detail in the

guideline on malignant effusions (page ii29).Pleural effusions indicate the presence of

disease which may be pulmonary, pleural, or

extrapulmonary. As the differential diagnosis iswide, a systematic approach to investigation is

necessary. The aim is to establish a diagnosis

swiftly while minimising unnecessary invasiveinvestigation. This is particularly important as the

differential diagnosis includes malignant mes-

othelioma in which 40% of needle incisions forinvestigation are invaded by tumour.1A minimum

number of interventions is therefore appropriate.A diagnostic algorithm for the investigation of

a pleural effusion is shown in fig 1.

2 CLINICAL ASSESSMENT AND HISTORY

Aspiration should not be performed forbilateral effusions in a clinical setting

strongly suggestive of a pleural tran-sudate, unless there are atypical featuresor they fail to respond to therapy. [C]

An accurate drug history should be takenduring clinical assessment. [C]

The initial step in assessing a pleural effusion is to

ascertain whether it is a transudate or exudate.

Initially this is through the history and physicalexamination. The biochemical analysis of pleural

fluid is considered later (section 5).

Clinical assessment alone is often capable ofidentifying transudative effusions. In a series of

33 cases, all 17 transudates were correctly

predicted by clinical assessment, blind of theresults of pleural fluid analysis.2 Therefore, in an

appropriate clinical setting such as left ventricularfailure with a confirmatory chest radiograph,

these effusions do not need to be sampled unlessthere are atypical features or they fail to respond

to treatment.

Approximately 75% of patients with pulmo-nary embolism and pleural effusion have a

history of pleuritic pain. These effusions tend to

occupy less than a third of the hemithorax andthe dyspnoea is often out of proportion to its size.

As tests on the pleural fluid are unhelpful in

diagnosing pulmonary embolism, a high index ofsuspicion is required to avoid missing the

diagnosis.3

The patients drug history is also important.Although uncommon, a number of medications

have been reported to cause exudative pleural

effusions. These are shown in box 1, together withtheir frequencies. Useful resources for more

detailed information include the British National

Formulary and the website pneumotox.com.

3 CAUSES OF A PLEURAL EFFUSIONPleural effusions are classified into transudatesand exudates. A transudative pleural effusion

occurs when the balance of hydrostatic forces

influencing the formation and absorption of

pleural fluid is altered to favour pleural fluidaccumulation. The permeability of the capillaries

to proteins is normal.4 In contrast, an exudative

pleural effusion develops when the pleural

surface and/or the local capillary permeability arealtered.5 There are a multitude of causes of

transudates and exudates and these are shown in

boxes 2 and 3, together with a guide to their fre-quency.

4 PLEURAL ASPIRATION

A diagnostic pleural fluid sample shouldbe gathered with a fine bore (21G) needleand a 50 ml syringe. The sample should beplaced in both sterile vials and blood cul-

ture bottles and analysed for protein, lac-tate dehydrogenase (LDH, to clarify bor-derline protein values), pH, Gram stain,AAFB stain, cytology, and microbiologicalculture. [C]

This is the primary means of evaluating pleural

fluid and its findings are used to guide further

investigation. Diagnostic taps are often performedin the clinic or by the bedside, although small

Box 1 Drugs known to cause pleuraleffusions

Over 100 reported cases globally*

Amiodarone Nitrofurantoin Phenytoin Methotrexate

20100 reported cases globally*

Carbamazepine Procainamide Propylthiouracil Penicillamine GCSF Cyclophosphamide Bromocriptine

*pneumotox.com (2001)

See end of article forauthors affiliations. . . . . . . . . . . . . . . . . . . . . . .

Correspondence to:Dr N A Maskell, OxfordCentre for RespiratoryMedicine, ChurchillHospital Site, OxfordRadcliffe Hospital,Headington, OxfordOX3 7LJ, UK;[email protected]. . . . . . . . . . . . . . . . . . . . . . .

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Figure 1 Flow diagram of the investigation pathway for a unilateral pleural effusion of unknown aetiology.

D i a g n o s t i c a l g o r i t h m f o r t h e i n v e s t i g a t i o n o f a p l e u r a l e f f u s i o n

H i s t o r y , c l i n i c a l e x a m i n a t i o n a n d c h e s t r a d i o g r a p h y

D o e s t h e c l i n i c a l p i c t u r e

s u g g e s t a t r a n s u d a t e ? e . g .

L V F , h y p o a l b u m i n a e m i a , d i a l y s i s

( s e c t i o n 2 )

P l e u r a l a s p i r a t i o n .

S e n d f o r : c y t o l o g y , p r o t e i n , L D H , p H

G r a m s t a i n , c u l t u r e a n d s e n s i t i v i t y , A A F B s t a i n s a n d c u l t u r e

R e c o n s i d e r P E a n d T B .

W a i t f o r d i a g n o s i s t o e v o l v e . ( s e c t i o n 9 )

R e f e r t o a c h e s t p h y s i c i a n

R e q u e s t c o n t r a s t e n h a n c e d C T t h o r a x ( f i g 2 ) ( s e c t i o n 6 . 3 )

R e c o n s i d e r t h o r a c o s c o p y

D o y o u s u s p e c t a n

e m p y e m a , c h y l o t h o r a x

o r h a e m o t h o r a x ?

O b t a i n p l e u r a l t i s s u e , e i t h e r b y u l t r a s o u n d / C T

g u i d e d b i o p s y , o r b y c l o s e d p l e u r a l b i o p s y o r

t h o r a c o s c o p y .

S e n d t h e s e f o r h i s t o l o g y a n d T B c u l t u r e t o g e t h e r

w i t h a r e p e a t p l e u r a l a s p i r a t i o n f o r c y t o l o g y ,

m i c r o b i o l o g i c a l s t u d i e s + /

_

s p e c i a l t e s t s

( s e e b o x 2 ) ( s e c t i o n s 7 . 1 a n d 7 . 2 )

H a v e t h e f l u i d a n a l y s i s

a n d c h e m i c a l f e a t u r e s

g i v e n a d i a g n o s i s ?

I s i t a t r a n s u d a t e ?

( s e c t i o n 5 . 2 )

C a u s e f o u n d ?

C a u s e f o u n d ?

R e s o l v e d ?

N O

N O

N O

N O

N O

N O

N O

Y E S

Y E S Y E S

Y E S

Y E S

Y E S

Y E S

S e e

b o x 1

T r e a t

t h e c a u s e

T r e a t

t h e c a u s e

T r e a t

a p p r o p r i a t e l y

T r e a t

a p p r o p r i a t e l y

S T O P

B o x 1 : A d d i t i o n a l p l e u r a l f l u i d t e s t s

5 K I F A ? J A @ @ E I A = I A 6 A I J I

C h y l o t h o r a x

H a e m o t h o r a x

E m p y e m a

c h o l e s t e r o l a n d

t r i g l y c e r i d e

c e n t r i f u g e

h a e m a t o c r i t

c e n t r i f u g e

B o x 2 : P l e u r a l f l u i d t e s t s w h i c h m a y b e

u s e f u l i n c e r t a i n c i r c u m s t a n c e s

5 K I F A ? J A @ @ E I A = I A 6 A I J I

R h e u m a t o i d d i s e a s e

P a n c r e a t i t i s

g l u c o s e

c o m p l e m e n t

a m y l a s e

BTS guidelines for the investigation of a unilateral pleural effusion in adults ii9

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effusions often require radiological guidance. A green needle(21G) and 50 ml syringe are adequate for diagnostic pleural

taps. The 50 ml sample should be split into three sterile pots tobe sent directly for microbiological, biochemical, and cytologi-

cal analysis.

Microscopic examination of Gram stained pleural fluidsediment is necessary for all fluids and particularly when a

parapneumonic effusion is suspected. If some of the microbio-

logical specimen is sent in blood culture bottles the yield isgreater, especially for anaerobic organisms.6

20 ml of pleural fluid is adequate for cytological examina-tion and the fresher the sample when it arrives at the labora-

tory the better. If part of the sample has clotted, the cytologist

must fix and section this and treat it as a histological sectionas it will increase the yield. Sending the cytology sample in a

citrate bottle will prevent clots and is preferred by some

cytologists. If delay is anticipated, the specimen can be storedat 4C for up to 4 days.7

5 PLEURAL FLUID ANALYSIS5.1 Typical characteristics of the pleural fluid The appearance of the pleural fluid and any odour

should be noted. [C] A pleural fluid haematocrit is helpful in the diagnosis

of haemothorax.

After performing pleural aspiration, the appearance and odourof the pleural fluid should be noted. The unpleasant aroma of

anaerobic infection may guide antibiotic choice. The appear-

ance can be divided into serous, blood tinged, frankly bloody,

or purulent. If the pleural fluid is turbid or milky it should becentrifuged. If the supernatant is clear, the turbid fluid was

due to cell debris and empyema is likely. If it is still turbid,this

is because of a high lipid content and a chylothorax orpseudochylothorax are likely.8 Table 1 lists the characteristics

of the pleural fluid in certain pleural diseases.If the pleural fluid appears bloody, a haematocrit can be

obtained if there is doubt as to whether it is a haemothorax. If

the haematocrit of the pleural fluid is more than half of thepatients peripheral blood haematocrit, the patient has a

haemothorax. If the haematocrit on the pleural fluid is lessthan 1%, the blood in the pleural fluid is not significant.9

Grossly bloody pleural fluid is usually due to malignancy, pul-

monary embolus with infarction, trauma, benign asbestospleural effusions, or post-cardiac injury syndrome (PCIS). 9

5.2 Differentiating between a pleural fluid exudate andtransudate

The pleural protein should be measured to differen-tiate between a transudative and exudative pleuraleffusion. This will usually suffice if the patientsserum protein is normal and pleural protein is lessthan 25 g/l or more than 35 g/l. If not, Lights criteria(see box 5) should be used. [B]

The classical way of separating a transudate from an exudateis by pleural fluid protein, with exudates having a protein level

of >30 g/l and transudates a protein level of


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in differentiating exudates and transudates has been exam-ined in a meta-analysis of 1448 patients from eight studies.15

Lights criteria performed best with excellent discriminativeproperties. Further analysis suggests a cut off value of LDH

levels in pleural fluid of >0.66, the upper limits of the labora-

tory normal might be a betterdiscriminator (modified Lightscriteria).16

In summary, Lights criteria appear to be the most accurate

way of differentiating between transudates and exudates. Theweakness of these criteria is that they occasionally identify an

effusion in a patient with left ventricular failure on diureticsas an exudate. In this circumstance, clinical judgement should

be used.

5.3 Differential cell counts on the pleural fluid

Pleural lymphocytosis is common in malignancy andtuberculosis.

Eosinophilic pleural effusions are not always benign.

When polymorphonuclear cells predominate, the patient hasan acute process affecting the pleural surfaces. If there is con-

comitant parenchymal shadowing, the most likely diagnosesare parapneumonic effusion and pulmonary embolism with

infarction. If there is no parenchymal shadowing, more

frequent diagnoses are pulmonary embolism, viral infection,acute tuberculosis, or benign asbestos pleural effusion.9 17

An eosinophilic pleural effusion is defined as the presenceof 10% or more eosinophils in the pleural fluid. The presence

of pleural fluid eosinophilia is of little use in the differential

diagnosis of pleural effusions.9 Benign aetiologies include

parapneumonic effusions, tuberculosis, drug induced pleurisy,benign asbestos pleural effusions, Churg-Strauss syndrome,

pulmonary infarction, and parasitic disease.1820 It is often the

result of air or blood in the pleural cavity.19 However,

malignancy is also a common cause; 11 of a series of 45 eosi-nophilic effusions were due to cancer. 20

If the pleural fluid differential cell count shows a predomi-

nant lymphocytosis, the most likely diagnoses are tuberculosisand malignancy. Although high lymphocyte counts in pleural

fluid raise the possibility of tuberculous pleurisy, 9 as many as10% of tuberculous pleural effusions are predominantly

neutrophilic.21 Lymphoma, sarcoidosis, rheumatoid disease,

and chylothorax can cause a lymphocytic pleural effusion. 22

Coronary artery bypass grafting (CABG) often causes pleu-

ral effusions which can usually be treated conservatively.

Large symptomatic effusions can occur in up to 1% of patients

in thepostoperative period. These arepredominantly left sidedand the differential cell count can help to clarify the situation.

Bloody effusions are usually eosinophilic, occur early, and arerelated to bleeding into the pleural cavity from the time of

surgery. Non-bloody effusions tend to have small lymphocytesas their predominant cell type, occur later, and are generally

more difficult to treat.23

5.4 pH

pH should be performed in all non-purulent effu-sions. [B]

In an infected effusion a pH of


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If malignancy is suspected, cytological examination of the

pleural fluid is a quick and minimally invasive way to obtain a

diagnosis. The results of the major series reporting the sensi-tivity of pleural cytology are shown in table 2. 3942 These sensi-

tivities vary from 40% to 87%,witha mean of about 60%.Of 55cases where malignancy was diagnosed on the basis of

cytological examination, Garcia et al found 65% were

established from the first specimen, a further 27% from thesecond, and only 5% from the third. 43

A retrospective review of 414 patients between 1973 and

1982 compared the diagnostic efficacy of cytology alone and incombination with pleural biopsy.42 The final causes of the

effusion were malignancy in 281 patients (68%). The presenceof pleural malignancy was established by cytology in 162

patients (58%) and, with the addition of a blind pleural biopsy,

a further 20 patients (7%) were classified as havingmalignancy. The yield depends on the skill and interest of the

cytologist and on tumour type, with a higher diagnostic rate

for adenocarcinoma than for mesothelioma, squamous cellcarcinoma, lymphoma and sarcoma. The yield increases if

both cell blocks and smears are prepared.44

Immunocytochemistry, as an adjunct to cell morphology, is

becoming increasingly helpful in distinguishing benign from

malignant mesothelial cells and mesothelioma fromadenocarcinoma.45 46 Epithelial membrane antigen (EMA) is

widely used to confirm a cytological diagnosis of epithelial

malignancy. 46 47 When malignant cells are identified, the glan-

dular markers for CEA, B72.3 and Leu-M1 together with cal-

retinin and cytokeratin 5/6 will often help to distinguishadenocarcinoma from mesothelioma.4648

6 DIAGNOSTIC IMAGING6.1 Plain radiography

PA and lateral chest radiographs should be per-formed in the assessment of suspected pleuraleffusion. [C]

The plain chest radiographic features of pleural effusion are

usually characteristic. The PA chest radiograph is abnormal inthe presence of about 200 ml pleural fluid. However, only

50 ml of pleural fluid can produce detectable posterior costo-phrenic angle blunting on a lateral chest radiograph.49 Lateral

decubitus films are occasionally useful as free fluid gravitates

to the most dependent part of the chest wall, differentiatingbetween pleural thickening and free fluid.50

In the intensive care setting, patients are often imagedsupine where free pleural fluid will layer out posteriorly. Pleu-

ral fluid is often represented as a hazy opacity of one

hemithorax with preserved vascular shadows on the supineradiograph. Other signs include the loss of the sharp

silhouette of the ipsilateral hemidiaphragm and thickening of

the minor fissure. The supine chest radiograph will oftenunderestimate the volume of pleural fluid.51

Subpulmonic effusions occur when pleural fluid accumu-lates in a subpulmonic location. They are often transudates

and can be difficult to diagnose on the PA radiograph and may

require a lateral decubitus view or ultrasound. The PA

radiograph will often show a lateral peaking of an apparently

raised hemidiaphragm which has a steep lateral slope with

gradual medial slope. The lateral radiograph may have a flatappearance of the posterior aspect of the hemidiaphragm with

a steep downward slope at the major fissure.52

6.2 Ultrasound findings

Ultrasound guided pleural aspiration should be usedas a safe and accurate method of obtaining fluid ifthe effusion is small or loculated. [B]

Fibrinous septations are better visualised on ultra-sound than on CT scans.

Ultrasound is more accurate than plain chest radiography for

estimating pleural fluid volume and aids thoracentesis.53 54

After unsuccessful thoracentesis or in a loculated pleural effu-

sion, ultrasound guided aspiration yields fluid in 97% of

cases.50 In a series of 320 patients, Yang et al55 found that pleu-ral effusions with complex septated, complex non-septated, or

homogeneously echogenic patterns are always exudates,

whereas hypoechoic effusions can be either transudates orexudates. Ultrasound is also useful in demonstrating fibrinous

loculation and readily differentiates between pleural fluid and

pleural thickening.56 57 Ultrasound also has the added advan-

tage of often being portable, allowing imaging at the bedside

with the patient sitting or in the recumbent position.58 59

6.3 CT findings

CT scans for pleural effusion should be performedwith contrast enhancement. [C]

In cases of difficult drainage, CT scanning should beused to delineate the size and position of loculatedeffusions. [C]

CT scanning can usually differentiate between be-nign and malignant pleural thickening.

There are features of contrast enhanced thoracic CT scanning

which can help differentiate between benign and malignantdisease (fig 2). In a study of 74 patients, 39 of whom had

malignant disease, Leung et al60 showed that malignant diseaseis favoured by nodular pleural thickening, mediastinal pleural

thickening, parietal pleural thickening greater than 1 cm, andcircumferential pleural thickening. These features havespecificities of 94%, 94%, 88%, and 100%, respectively, and

sensitivities of 51%, 36%, 56% and 41%. Scott et al61 evaluated

these criteria in 42 patients with pleural thickening; 32 of the33 cases of pleural malignancy were identified correctly on the

basis of the presence of one or more of Leungs criteria. When

investigating a pleural effusion a contrast enhanced thoracicCT scan should be performed before full drainage of the fluid

as pleural abnormalities will be better visualised.62

CT scanning has been shown to be superior to plain radio-

graphs in the differentiation of pleural from parenchymal dis-

ease. It is particularly helpful in the assessment and manage-ment of loculated pleural effusions. Loculated effusions on CT

scans tend to have a lenticular shape with smooth margins

and relatively homogeneous attenuation.63

The role of magnetic resonance (MR) imaging is currently

evolving, but generally does not provide better imaging thanCT scanning.59 64 65

7 INVASIVE INVESTIGATIONS7.1 Percutaneous pleural biopsy

Pleural tissue should always be sent for tuberculosisculture whenever a biopsy is performed. [B]

In cases of mesothelioma, the biopsy site should beirradiated to stop biopsy site invasion by tumour. [A]

Percutaneous pleural biopsies are of greatest value in the

diagnosis of granulomatous and malignant disease of the

Table 2 Sensitivity of pleural fluid cytology inmalignant pleural effusion

Reference No of patientsNo caused bymalignancy

% diagnosed bycytology

Salyer et al40 271 95 72.6Prakash et al42 414 162 57.6Nance et al41 385 109 71.0Hirsch39 300 117 53.8Total 1370 371 61.6

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pleura. They are performed on patients with undiagnosedexudative effusions, with non-diagnostic cytology, and a clini-

cal suspicion of tuberculosis or malignancy. Occasionally, a

blind pleural biopsy may be performed at the same time as thefirst pleural aspiration if clinical suspicion of tuberculosis is

high.All aspiration and biopsy sites should be marked with

Indian ink as the site(s) will need local radiotherapy within 1

month if the final diagnosis is mesothelioma. This is based ona small randomised study showing tumour seeding in the

biopsy track in about 40% of the patients who did not receive

local radiotherapy.1 Other clinical trials continue to recruit to

clarify this area.

7.1.1 Blind percutaneous pleural biopsies

When using an Abrams needle, at least four biopsyspecimens should be taken from one site. [C]

The Abrams pleural biopsy needle is most commonly used in

the UK with the Cope needle being less prevalent. Morrone etal66 compared these two needles in a small randomised study

of 24 patients; the diagnostic yield was similar but sampleswere larger with an Abrams needle. The yield compared with

pleural fluid cytology alone is increased by only 727% formalignancy. 4042At least four samples need to be taken to opti-

mise diagnostic accuracy,67 and these should be taken from

one site as dual biopsy sites do not increase positivity. 68 Thebiopsy specimens should be placed in 10% formaldehyde for

histological examination and sterile saline for tuberculosis

culture. A review of the pleural biopsy yield from 2893 exami-nations performed between 1958 and 1985 (published in 14

papers) showed a diagnostic rate of 75% for tuberculosis and57% for carcinoma.69 In tuberculous effusions, when fluid

AAFB smear, culture, biopsy histology, and culture areperformed in concert, the diagnostic yield is 8090%. 21 7072

Complications of Abrams pleural biopsy include site pain

(115%), pneumothorax (315%), vasovagal reaction (15%),

haemothorax (


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diagnosis was made in 21 of 24 patients (sensitivity 88%, spe-

cificity 100%) including 13 of 14 patients with mesothelioma

(sensitivity 93%).77 In a larger retrospective review of imageguided pleural biopsy in one department by a single

radiologist, 18 of 21 mesothelioma cases were correctly identi-

fied (sensitivity 86%, specificity 100%).78 The only published

complications to date are local haematoma and minor haemo-

ptysis.

7.2 Thoracoscopy

Thoracoscopy should be considered when less inva-sive tests have failed to give a diagnosis. [B]

Thoracoscopy is usually used when less invasive techniques(thoracentesis and percutaneous closed pleural biopsy) have

not been diagnostic. Harris et al79 described 182 consecutive

patients whounderwent thoracoscopy over a 5 year period andshowed it to have a diagnostic sensitivity of 95% for

malignancy. Malignancy was shown by thoracoscopy in 66%of patients who had previously had a non-diagnostic closed

pleural biopsy and in 69% of patients who had had two nega-

tive pleural cytological specimens. A similar sensitivity formalignant disease wasdescribedby Page80 in 121patients with

undiagnosed effusion.

In addition to obtaining a tissue diagnosis, several litres offluid can be removed during the procedure and the

opportunity is also provided for talc pleurodesis. Thoracoscopymay therefore be therapeutic as well as diagnostic. 81

Complications of this procedure appear to be few. The most

serious, but rare, is severe haemorrhage caused by blood ves-sel trauma.81 In a series of 566 examinations by Viskum and

Enk82 the most common side effect was subcutaneous emphy-

sema (6.9%), with cardiac dysrhythmia occurring in 0.35%,one air embolism, and no deaths.

7.3 Bronchoscopy

Routine diagnostic bronchoscopy should not be per-formed for undiagnosed pleural effusion. [C]

Bronchoscopy should be considered if there ishaemoptysis or clinical features suggestive of bron-chial obstruction. [C]

Heaton and Roberts83 reviewed the case records of 32 patientswho had bronchoscopy for undiagnosed pleural effusion. In

only six did it yield a diagnosis and in four of these the diag-

nosis was also established by less invasive means. The othertwo had radiographic abnormalities suggestive of bronchial

neoplasm. Upham et al84 studied 245 patients over 2 years andFeinsilver et al85 studied 70. Both also found positive yields of

1.24 mmol/l (110 mg/dl), and can usually be excluded if the triglyceride level is

5.18 mmol/l (200 mg/dl), chylomicrons are not found, and

cholesterol crystals are often seen at microscopy (table 3). 89 92

Occasionally an empyema can be unusually milky and con-

fused with chylothorax. They can be distinguished by bench

centrifugation which leaves a clear supernatant in empyemaas the cell debris is separated. The chylous effusion remains

milky.

Box 6 Causes of chylothorax and pseudochylothorax

Chylothorax

Neoplasm: lymphoma, metastatic carcinoma Trauma: operative, penetrating injuries Miscellaneous: tuberculosis, sarcoidosis, lymphangioleio-

myomatosis, cirrhosis, obstruction of central veins, amy-loidosis

Pseudochylothorax

Tuberculosis Rheumatoid arthritis Poorly treated empyema

Table 3 Laboratory differentiation of chylothorax and pseudochylothorax

Feature Pseudochylothorax Chylothorax

Triglycerides 1.24 mmo l/l (110 mg/dl)Choles terol >5.18 mm ol/l (200 mg/dl)


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8.2 Urinothorax

If urinothorax is suspected, the pleural fluid creati-nine level should be measured and will be higherthan the serum creatinine level. [C]

Urinothorax is a rare complication of an obstructed kidney.

The urine is thought to move through the retroperitoneum to

enter the pleural space, with the effusion occurring on thesame side as the obstructed kidney.93 The pleural fluid smells

like urine and resolves when the obstruction is removed.94 The

diagnosis can be confirmed by demonstrating that the pleuralfluid creatinine level is greater than the serum creatinine level.

The pleural fluid is a transudate and has a low pH. 95 96

8.3 Tuberculous pleurisy

When pleural biopsies are taken, they should be sentfor both histological examination and culture toimprove the diagnostic sensitivity for tuberculosis.[B]

Smears for acid fast bacilli are only positive in 1020% of

tuberculous effusions and are only 2550% positive on pleural

fluid culture.97 98 The addition of pleural biopsy histology and

culture improves the diagnostic rate to about 90%. 21 98

The adenosine deaminase (ADA) level in pleural fluid tendsto be higher with tuberculosis than in other exudates.100102

However, ADA levels are also raised in empyema, rheumatoidpleurisy, and malignancy, which makes the test less useful incountries with a low prevalence of tuberculosis. Importantly,

ADA levels may not be raised if the patient has HIV andtuberculosis.103

8.4 Pleural effusion due to pulmonary embolism

There are no specific pleural fluid characteristics todistinguish those caused by pulmonary embolism.This diagnosis should be pursued on clinical grounds.

Small pleural effusions are present in up to 40% of cases of

pulmonary embolism. Of these, 80% are exudates and 20%

transudates; 80% are bloodstained.3 22A pleural fluid red blood

cell count of more than 100 000/mm3 is suggestive of

malignancy, pulmonary infarction, or trauma.9 Lower countsare unhelpful.3 Effusions associated with pulmonary embo-

lism have no specific characteristics and the diagnosis should

therefore be pursued on clinical grounds with the physicianretaining a high index of suspicion for the diagnosis. 22

8.5 Benign asbestos pleural effusionBenign asbestos pleural effusions are commonly diagnosed inthe first two decades after asbestos exposure. The prevalence is

dose related with a shorter latency period than other asbestos

related disorders.104 The effusion is usually small andasymptomatic, often with pleural fluid which is

haemorrhagic.105 106 There is a propensity for the effusion toresolve within 6 months, leaving behind residual diffuse pleu-

ral thickening.105 106 As there are no definitive tests, the

diagnosis can only be made with certainty after a prolongedperiod of follow up.

8.6 Connective tissue diseases8.6.1 Rheumatoid arthritis associated pleural effusions

Suspected cases should have a pleural fluid pH,glucose and complement measured. [C]

Rheumatoid arthritis is unlikely to be the cause of aneffusion if the glucose level in the fluid is above1.6 mmol/l (29 mg/dl).

Pleural involvement occurs in 5% of patients with rheumatoid

arthritis.107 The majority of patients with rheumatoid pleuraleffusions are men, even though the disease generally affects

more women.108 Pleural fluid can be serous, turbid, yellow

green, milky, or haemorrhagic.109 Rheumatoid arthritis is

unlikely to be the cause of an effusion if the glucose level in

the fluid is above 1.6 mmol/l, so this serves as a useful screen-

ing test.30 80% of rheumatoid pleural effusions have a pleuralfluid glucose to serum ratio of


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70% of patients with tuberculous pleurisy and the combina-tion of a positive tuberculin skin test and an exudative pleural

effusion containing predominantly lymphocytes is sufficient

to justify empirical antituberculous therapy.22 There are no

specific pleural fluid tests for pulmonary embolism so, if there

is a clinical suspicion of the diagnosis, imaging for embolismshould be undertaken. Many undiagnosed pleural effusions

are eventually proved to be due to malignancy. If this

possibility is to be pursued after routine tests have failed,thoracoscopy is advised.

. . . . . . . . . . . . . . . . . . . . .

Authors affiliationsN A Maskell, Oxford Centre for Respiratory Medicine, Churchill HospitalSite, Oxford Radcliffe Hospital, Headington, Oxford OX3 7LJ, UKR J A Butland, Department of Thoracic Medicine, Gloucestershire RoyalHospital, Gloucester GL1 3NN, UK

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Audit points

The gross appearance of the pleural fluid and its odourshould always be recorded.

Pleural fluid pH should be performed in every case of sus-pected parapneumonic effusion.

The diagnostic rate of pleural cytology should be audited. If the first pleural fluid cytology specimen is non-diagnostic,

a second sample should be taken to increase the diagnos-tic yield.

Pleural biopsy specimens should be placed in both salineand formalin and sent for histological examination and cul-ture.

Diagnostic bronchoscopy is not indicated in the assessmentof an undiagnosed effusion unless the patient has haemo-ptysis or features suggestive of bronchial obstruction.

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BTS guidelines for the investigation of a unilateral pleural effusion in adults ii17

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