This presentation is the property of its rightful owner.
Sponsored Links
1 / 6

Neumo PowerPoint PPT Presentation


Download Presentation


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript



Pleural disease

Key points

Oliver J Bintcliffe

Point-of-care ultrasound guidance should be used for all pleural

procedures involving fluid

If the pleural fluid protein concentration is 25e35 g/litre, Light’s

criteria can be used to differentiate exudates from transudates



Only 60% of malignant effusions can be diagnosed by cytology

Image-guided pleural biopsy has a higher diagnostic yield than

blind pleural biopsy for malignancy

Indwelling pleural catheters are increasingly being used to

manage symptomatic malignant pleural effusions, reducing

hospitalization and enabling management in the community

Pleural fluid specimens for microbiology should be sent in both

a sterile tube (for Gram stain, acid- and alkali-fast bacilli and

culture of Mycobacterium tuberculosis) and blood culture bot-

tles to increase the microbiological yield

Combination treatment with intrapleural tissue-type plasmin-

ogen activator and DNase may be beneficial in patients with

pleural infection resistant to standard medical therapy

Heimlich valves allow ambulatory treatment for selected pa-

tients with pneumothorax


Amelia O Clive


Nick A Maskell



Pleural disease encompasses a wide range of pathological processes,

many of which are common and increasing in incidence. Patients with

pleural disease are encountered by both respiratory specialists and

general physicians, and a systematic approach to their management

helps in targeting investigation and optimizing patient care. Research

has led to recent advances in diagnostic strategies and therapeutic

techniques in these patients. This review focuses on the clinical

assessment, diagnosis and management of patients with pleural effu-

sions, malignant pleural disease, pleural infection and pneumothorax,

and provides practical suggestions regarding investigation and


Keywords Empyema; malignant pleural effusion; parapneumonic

effusion; pleural disease; pleural effusion; pneumothorax







Investigating pleural effusions

a heparinized syringe (to measure pH using a blood gas analyser)

and sent for the following tests:

? biochemistry e lactate dehydrogenase (LDH), total pro-

tein, glucose

? microbiology e Gram stain, identification of acid- and

alcohol-fast bacilli (AAFB) and microbiological culture

? cytology

? pH.

Pleural effusions are a common medical problem (Table 1).

There are several underlying mechanisms, including:

? increased permeability of the pleural membrane

? increased pulmonary capillary pressure

? excess negative intrapleural pressure

? reduced tissue oncotic pressure

? obstructed lymphatic flow.

The differential diagnosis is wide, so a systematic approach to

investigation is necessary.1This should start with an accurate

history, including a drug history (Table 2), and examination.

Distinguishing pleural fluid exudate and transudate: in most

cases, a pleural fluid total protein of less than 25 g/litre represents

a transudate and more than 35 g/litre an exudate. However, if the

serum total protein is low or the pleural fluid protein concentra-

tion lies between these figures, differentiating the two can be

more difficult. In these cases, measurement of serum and pleural

fluid LDH and total protein allows Light’s criteria to be used to

distinguish exudates and transudates more accurately (Table 4).

Light’s criteria have good sensitivity and specificity (as high

as 98% in some series). However, a small number of patients

with malignancy will be categorized as having a transudate; in

addition, patients with cardiac failure taking diuretics may have a

higher fluid protein concentration, so the pleural fluid may be

mislabelled as an exudate.

Pleural aspiration: a diagnostic pleural fluid sample should be

collected using a fine-bore (21 G) needle and a 50-ml syringe,

using ultrasound guidance to locate a safe site to perform the

procedure (Table 3).1

The appearance and odour of the fluid should be noted. The

sample should be placed in sterile vials, blood culture bottles and

Oliver J Bintcliffe MRCP is a Specialist Registrar in Respiratory and

General Medicine and Clinical Research Fellow in pleural disease at

the University of Bristol, UK. His research interests include pneu-

mothorax and non-malignant pleural effusions. Competing interests:

none declared.

Differential cell counts: a differential count of a pleural fluid

sample can be useful in narrowing the differential diagnosis, but

the results are not disease-specific. Lymphocytic effusions are

commonly seen in malignancy and tuberculosis (TB), after coro-

nary artery bypass graft and with cardiac failure and chronic

pleural effusions.

Neutrophilic effusions usually signify a more acute disease

process, such as pulmonary emboli (PEs) or parapneumonic


Amelia O Clive PhD is a Specialist Registrar in Respiratory and

General Medicine at North Bristol NHS Trust, UK. Her research

interests include the management of malignant pleural disease.

Competing interests: none declared.

Nick A Maskell DM FRCP is a Professor in Respiratory Medicine at the

University of Bristol, UK. His clinical and research interests include

malignant pleural disease and pleural infection. Competing interests:

Professor Maskell has received research funding from Care Fusion,

Roche and Novartis.


? 2016 Elsevier Ltd. All rights reserved.




Pleural procedures1

Causes of transudative and exudative pleural effusions



Pleural procedures should not take place out of hours except in

an emergency

Pleural aspirations and chest drain should be inserted in a clean

environment using full aseptic technique

Bedside thoracic ultrasound guidance is strongly recommended

for all pleural procedures involving pleural fluid

The preferred site for pleural interventions is the triangle of safety

(see below)

Non-urgent pleural procedures should be avoided in anti-

coagulated patients until the international normalized ratio is


Pleural fluid aspiration should be stopped when no more fluid

can be aspirated or the patient becomes symptomatic, to reduce

the risk of re-expansion pulmonary oedema. The total amount

aspirated is often limited to 1.5 litres in the elderly.



Left ventricular failure



Peritoneal dialysis

Less common


Renal impairment

Mitral stenosis

Pulmonary embolism


Constrictive pericarditis

Superior vena cava obstruction

Ovarian hyperstimulation



Parapneumonic effusions

Less common

Pulmonary infarction

Rheumatoid arthritis

Autoimmune diseases

Benign asbestos effusion

Post-myocardial infarction syndrome


Yellow nail syndrome

Drugs (Table 2)






Table 1

pH: a low pleural fluid pH (<7.2) can indicate pleural infection

requiring chest tube drainage. Other causes of low pH effusions

include advanced malignancy, rheumatoid arthritis, TB, collagen

vascular disease and oesophageal perforation. Pleural fluid

glucose concentration correlates with pleural fluid pH and can be

a useful alternative if pH cannot be measured.

Cytology: malignant effusions can be diagnosed from a single

pleural fluid cytology specimen in about 60% of cases. A second

cytology specimen increases the yield slightly. Certain malignant

cell types are diagnosed more readily by experienced cytologists,

using immunocytochemistry; a cytological diagnosis is more

likely in a malignant pleural effusion due to metastatic adeno-

carcinoma than in mesothelioma for instance.

Identify the ‘safe triangle for drain placement, as demarcated by

the outer border of the pectoralis major, the anterior border of the

latissimus dorsi and a horizontal line that meets the nipple

anteriorly. In general, the drain should be sited in the 4th or 5th

intercostal space within this triangle.

Table 3

Pleural imaging: effusions greater than 200 ml can be detected

on a postero-anterior chest radiograph, although smaller vol-

umes can be detected using thoracic ultrasound. Ultrasound

scanning can also differentiate more clearly between pleural fluid

and thickening, assess septations and loculations within an

effusion and help to identify a safe site for pleural procedures.

Computed tomography (CT) can help to characterize pleural

abnormalities further. Contrast enhancement aids differentiation

between benign and malignant pleural thickening and is often

visualized more clearly if some pleural fluid is still present

(Figure 1). In addition, CT can identify other underlying causes of

a pleural effusion, such as PEs, infection or tumours. Up to 40%

of patients with PEs have a small pleural effusion with no specific

biochemical characteristics; a high index of suspicion is required

to make this diagnosis, and CT pulmonary angiography should

be requested if the diagnosis is considered.

Magnetic resonance imaging (MRI) is developing as an im-

aging modality for pleural disease and can be useful in selected

cases where clear soft tissue differentiation is required.

Drug causes of pleural effusion

Light’s criteria



Pleural fluid is an exudate if one or more of the following criteria

are met:

Pleural fluid protein:serum protein ratio >0.5

Pleural fluid LDH:serum LDH ratio >0.6

Pleural fluid LDH more than two-thirds of upper limit of normal

serum LDH















LDH, lactate dehydrogenase.

Table 2

Table 4


? 2016 Elsevier Ltd. All rights reserved.




failure of pleurodesis. Cytological analysis identifies tumour cells

in 60% of malignant effusions, so histology is often required for

diagnosis. This is particularly the case with suspected mesothe-

lioma, in which pleural fluid cytology is frequently non-


Blind pleural biopsies have a lower diagnostic yield and

higher complication rate than CT-guided biopsy and are now

rarely used. Use of local anaesthetic thoracoscopy is increasing

and allows for complete drainage of the pleural effusion, tissue

sampling for histology and pleurodesis in the same procedure. It

provides an alternative to VATS under general anaesthetic if a

less invasive approach is preferred, particularly for elderly pa-

tients for whom a general anaesthetic can be more risky. In some

cases, where the lung is tethered or the effusion heavily septated,

a surgical procedure via multiple ports may be needed to release

the trapped lung, break down septations and obtain tissue for


CT is mandatory for identifying the primary source and for

staging (Figure 1). The precise role of other imaging modalities,

such as MRI and positron emission tomography CT has yet to be


Figure 1 Contrast-enhanced thoracic CT of an exudative pleural

effusion, showing enhancement of the pleural tumour.

Pleural biopsy techniques

A pleural biopsy should be considered in patients who have a

pleural effusion of unknown cause after initial investigations,

particularly if malignancy or TB is suspected. The biopsy can be

performed percutaneously, or at thoracoscopy.

A blind pleural biopsy using an Abrams’ biopsy needle can be

considered if TB pleuritis is suspected, as the pleural abnormality

is more diffuse than in malignancy. However, at least four

samples should be taken to maximize the diagnostic yield. If TB

is suspected, the sample should be sent in saline for TB culture as

well as for histology.

If malignancy is suspected, however, pleural biopsy using an

image-guided cutting needle has a higher diagnostic yield than

blind pleural biopsy. Four samples should still be taken to opti-

mize the diagnostic accuracy.

Thoracoscopy is gaining popularity in the investigation and

management of pleural disease as it is both diagnostic and thera-

peutic.1It allows direct visualization of the pleura and can be per-





thoracoscopic surgery (VATS)) anaesthesia. The sensitivity for ma-

lignancy and TB is over 90%. During the procedure, all the pleural

fluid can be removed and pleurodesis performed if necessary.


The treatment modalities available to patients with malignant

pleural effusions are expanding and depend on patient choice,

clinical condition and availability.1Aside from treatment of the

underlying malignancy, management strategies focus on fluid

removal and prevention of reaccumulation. No current therapies

target the underlying problem of excess fluid production directly,

but this is the subject of continuing research. Treatment of the

underlying malignant process can help to reduce pleural fluid

production, particularly in chemoresponsive tumours such as

breast cancer.

Thoracocentesis allows instant relief of symptoms, but reac-

cumulation frequently necessitates more definitive treatment.

Chest drain insertion and pleurodesis is a well-established

method of removing fluid and preventing recurrence. Talc is

the preferred agent in pleurodesis and is effective in about 70%

of patients. It can be given in the form of talc slurry through a

chest tube, or as a ‘talc poudrage’ during thoracoscopy. The ef-

ficacy of these procedures is the subject of a large, randomized

controlled trial (TAPPS). Pleurodesis is unlikely to be successful

when the lung is unable to fully re-expand (‘trapped lung’),

because of a visceral pleural ‘peel’ of tumour or endobronchial


Indwelling pleural catheters (Figure 2) are gaining popularity

in the management of malignant effusions, particularly in pa-

tients with trapped lung or those who wish to avoid hospital

admission.2The catheters are small chest tubes tunnelled under

the skin that allow regular pleural fluid drainage to be carried out

in the community. Spontaneous pleurodesis occurs in up to one-

half of patients, after which the catheter can be removed. The

combination of talc and an indwelling pleural catheter can in-

crease the rate of pleurodesis; this is the subject of a randomized

controlled trial (IPC-PLUS).

The role of prophylactic radiotherapy in mesothelioma to

prevent metastases along the procedure track following pleural

interventions is not established but is the subject of two large

multicentre randomized controlled trials (SMART, PIT).




Malignant pleural effusion

Malignant pleural effusion can result in disabling breathlessness

for patients with advanced malignancy and confers a poor

prognosis. It can be caused by mesothelioma (a primary pleural

tumour) or metastatic disease. Lung, breast, ovarian, haemato-




commonly metastasize to the pleura.

Other conditions associated with an underlying malignant

process can also cause a pleural effusion. These include PEs,

superior vena cava obstruction, nodal enlargement restricting

pleural fluid resorption and hypoalbuminaemia.






Initial assessment with blood and pleural fluid analysis assists

with diagnosis. Imaging using CT and ultrasound is also used.

Malignant pleural effusions are exudates in 90% of cases. A low

pleural fluid pH indicates extensive disease and helps to predict


? 2016 Elsevier Ltd. All rights reserved.




Figure 2 (a) An indwelling pleural catheter, commonly used for the management of recurrent, symptomatic, malignant pleural effusions. (b) Trocar

and cannula.

Parapneumonic effusions and empyema

choice of antibiotic. Prolonged courses of antibiotics may be

required to ensure complete resolution.

First-line antibiotic treatment for community-acquired pleural

infection should include an aminopenicillin (e.g. amoxicillin) to

cover organisms such as Streptococcus pneumoniae and Haemo-

philus influenzae, as well as metronidazole or a b-lactamase in-

hibitor (e.g. clavulanic acid), to ensure penicillin-resistant

aerobes and anaerobes are covered.1

In hospital-acquired empyema broader cover is required for




Gram-negative and anaerobic organisms.1

More than 65,000 patients develop pleural infection in the USA

and UK each year. Mortality is about 15%. Hospital-acquired

infection, particularly with Gram-negative bacteria, has a

particularly poor prognosis. The microbiology of hospital-

acquired infection also differs from that of community-acquired

empyema (Figure 3), and they should be considered as sepa-

rate entities in terms of epidemiology and recommended therapy.




Pleural infection can occur at any age, but is most common in

elderly patients and children. Men are affected twice as often as

women, and the incidence (particularly of infection caused by

Staphylococcus aureus) is increasing. The incidence is higher in

patients with diabetes, rheumatoid arthritis or coincidental

chronic lung disease, and in alcohol and substance abusers. Poor

dentition is associated with anaerobic infection.


In all suspected cases, pleural fluid aspiration and analysis

should be undertaken. Biochemical pleural fluid markers (low

pH, high LDH, predominant neutrophils, low glucose) are central

in establishing a diagnosis.

Gram staining and culture can aid antibiotic choice, although

40% of infected pleural effusions are culture-negative. Use of

blood culture bottles increases the microbiological yield over

universal containers alone and can aid assessment of poly-

microbial infection.

A pleural pH <7.2 identifies effusions requiring chest tube

drainage. pH should be measured routinely in any potentially

infectedpleuralfluid sample,unless itis obviouslypurulent. A low

pleural fluid glucose concentration (<2.2 mmol/litre indicates the


Tuberculous effusions are usually unilateral and more than

50% will show evidence of parenchymal TB. These effusions are

usually sterile, unless secondarily infected. Smears for acid-fast

bacilli on pleural fluid are positive in only 5e10% of cases,

and only 25e50% are positive on culture. A pleural biopsy is

often required to confirm the diagnosis.


Antibiotics: the clinical setting, pleural fluid culture results and

local antibiotic prescribing policies help to inform the initial

Figure 3


? 2016 Elsevier Ltd. All rights reserved.





pleural fluid pH less than 7.2, septated appearances on ultrasound,

positive pleuralfluidmicrobiologyorpurulentpleuralfluid.1Small

Seldinger tubes are as effective as larger ones and are more

comfortable for the patient; however, they need regular flushing

with sodium chloride 0.9% (20 ml 8-hourly) to prevent blockage.


anutritionalassessmentanddietarysupplementation ifnecessary.

Intrapleural fibrinolytics: there has been much debate about the

role of intrapleural fibrinolytics in pleural infection, to break

down fibrin septae and reduce the pleural rind, and thus improve

fluid drainage and lung expansion.

The MIST-2 trial, which assessed the use of intrapleural

tissue-type plasminogen activator and DNase, showed that

combined treatment improved drainage, reduced hospital stay

and decreased referrals for thoracic surgery.3This treatment can

have a role in patients who do not respond to standard therapy,

or in those not fit for surgery, although its precise role has yet to

be fully established.

Figure 4 A chest X-ray showing a left-sided primary spontaneous



line treatment and can prevent a hospital admission. However,

simple aspiration fails in 20e25% of patients, and insertion of a

chest tube is then warranted in those who are symptomatic.

Clinically stable patients with a large primary pneumothorax

can also be appropriate for conservative treatment without

aspiration; this hypothesis is the subject of a currently recruiting

trial in Australia and New Zealand.

Heimlich valves offer the potential for an outpatient-based

treatment of pneumothorax, which may be appropriate in

selected patients. These devices are the subject of a currently

recruiting randomized controlled trial (RAMPP study).

Recurrence of PSP occurs in about 40% of patients, usually

within 5 years of the first event. If a recurrence occurs, patients

should be referred to a thoracic surgeon for consideration of a

definitive procedure such as pleurodesis or pleurectomy to

prevent further events.4

Surgery: surgical referral may be necessary in patients with

continuing signs of sepsis or failure of the effusion to resolve

despite medical management. The aims of surgery are to treat

infection by draining any residual fluid completely and to allow

adequate lung re-expansion. Several surgical options are avail-

able, including open thoracotomy with decortication, mini-

thoracotomy, VATS and rib resection with open drainage (if

patients are not fit enough for a more definitive procedure).


Pneumothorax is defined as air in the pleural space and can be

spontaneous or traumatic (including iatrogenic). Recommended

management depends on the size of pneumothorax and patient

symptoms and whether the pneumothorax is primary or sec-

ondary (Figure 5). Chest radiographs confirm the diagnosis

(Figure 4) but do not accurately quantify pneumothorax size. CT

is sometimes required to differentiate a pneumothorax from a

subpleural bulla and confirm tube placement, particularly if the

radiographic images are obscured by surgical emphysema.1

Secondary pneumothorax

Secondary pneumothoraces occur in the presence of underlying

lung pathology (particularly chronic obstructive pulmonary

disorder (COPD)); symptoms are often more severe than in PSP

because of a pre-existing impairment of respiratory function.

If the patient develops a small secondary pneumothorax

(<2 cm) and is asymptomatic, inpatient observation is reason-

able. If symptoms are minimal, simple aspiration can be

attempted, although this has a lower success rate than in PSP;

inpatient observation for at least 24 hours after the aspiration is


Many patients with a secondary pneumothorax need inter-

costal drain insertion. A small (<14 F) chest tube is usually

sufficient, but if there is a persistent air leak (continuous

bubbling of the drain >48 hours after insertion), significant

surgical emphysema or the patient is mechanically ventilated, a

larger bore chest tube may be indicated. Suction may also be

helpful if the pneumothorax is slow to resolve and should be

slowly titrated to a more negative pressure, depending on the

patient’s symptoms, down to ?20 cmH2O.

Primary spontaneous pneumothorax (PSP)

PSPs occur in individuals without underlying lung disease.

Subpleural blebs and bullae are found in up to 90% of patients at

thoracoscopy and are thought to have a role in the pathogenesis

of PSP. Smoking is a risk factor; the lifetime risk of PSP is 12% in

men who smoked heavily compared with 0.1% in non-smoking

men. Patients with primary pneumothorax tend to be taller

than controls.

The aim of treatment is to reduce symptoms and prevent

recurrence. Administration of high-flow oxygen (10 litres/minute)

can accelerate resorption of the pneumothorax by reducing the

partial pressure of nitrogen in the pleural space. Observation alone


edge and chest wall) without significant breathlessness, as resorp-

tion will occur over time. If the patient is symptomatic or the


? 2016 Elsevier Ltd. All rights reserved.




Suggested management of pneumothorax






Known lung disease or



smoking history?

Consider symptoms,

pneumothorax size

and clinical stability

Requires admission


Size >2 cm and/or





Consider Heimlich

valve + ambulatory

management if available


with cannula

Aspiration or observation.

(observe for minimum

24 hours)



Chest drain


Discharge home


surgical referral

Early outpatient review as required


Ongoing air leak

Figure 5 Adapted from the British Thoracic Society Pleural Disease Guideline 2010.

Tension pneumothorax: immediate intervention is necessary. A

large-bore cannula should be inserted promptly into the second

intercostal space in the mid-clavicular line and left in place until

a chest tube can be positioned.

Patients should be advised about smoking cessation and

should not fly until the pneumothorax has entirely resolved on

chest radiograph. Unless they undergo a definitive surgical pro-

cedure, patients should not dive.


Iatrogenic pneumothorax: the incidence of iatrogenic pneumo-

thorax is high and increasing. Percutaneous lung biopsy, trans-

bronchial needle aspiration, pleural biopsy, thoracocentesis and

central venous puncture are the principal causes. COPD and lung

fibrosis are important risk factors. In most patients, the pneu-

mothorax will resolve with observation alone, but others can

require aspiration.


1 British Thoracic Society Pleural Disease Guideline Group. BTS

pleural disease guideline 2010. Thorax 2010; 65(suppl 2):


2 Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling

pleural catheter vs chest tube and talc pleurodesis for relieving

dyspnea in patients with malignant pleural effusion: the TIME2

randomized controlled trial. J Am Med Assoc 2012; 307: 2383e9.

3 Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue

plasminogen activator and DNase in pleural infection. N Engl J Med

2011; 365: 518e26.

4 Tschopp JM, Bintcliffe O, Astoul P, et al. ERS task force statement:

diagnosis and treatment of primary spontaneous pneumothorax.

Eur Respir J 2015; 46: 321e35.

Referral for surgery: open surgery with thoracotomy and pleur-

ectomy is an effective method to reduce recurrence rates, though

minimally invasive VATS with surgical talc pleurodesis or

mechanical abrasion is now usually the preferred approach on

account of reduced postoperative pain and shorter hospital stays.

Indications for a surgical referral for pneumothorax include:

? persistent air leak (patients should be referred early,

ideally within 5 days)

? second ipsilateral pneumothorax

? first contralateral pneumothorax

? bilateral spontaneous pneumothorax

? certain at-risk professions (e.g. pilots, divers).

Patients with recurrent secondary pneumothorax who are not

fit for surgery can be given alternative treatments including

chemical pleurodesis (although the recurrence rate is high) or an

ambulatory Heimlich valve.


Bintcliffe OJ, Hallifax RJ, Edey A, et al. Spontaneous pneumothorax:

time to rethink management? Lancet Respir Med 2015; 3: 578e88.

Clive AO, Bhatnagar R, Psallidas I, Maskell NA. Individualised manage-


Corcoran JP, Wrightson JM, Belcher E, DeCamp MM, Feller-

Kopman D, Rahman NM. Pleural infection: past, present, and future

directions. Lancet Respir Med 2015; 3: 563e77.


? 2016 Elsevier Ltd. All rights reserved.


  • Login