Download Pleural Disease Guidelines 2003

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BTS GUIDELINES
Introduction to the methods used in the generation of the
British Thoracic Society guidelines for the management of
pleural diseases
R J O Davies, F V Gleeson
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Thorax 2003;58(Suppl II):ii1–ii7
D
iseases of the pleura and pleural space are
common and present a significant contribution to the workload of respiratory
physicians. Despite their prevalence and clinical
importance, there is limited consensus on their
management. These guidelines attempt to integrate the available objective evidence with clinical
experience relating to the investigation and treatment of these problems. The guidelines have been
prepared using consistent methods and are
presented in a broadly similar way.
STRUCTURE OF EACH GUIDELINE
The first section of each guideline consists of a
brief introduction that sets an historical and
clinical background for the management guidance itself.
The guidelines are then presented so that they
can be read at three levels. The articles begin with
a flow diagram that is intended to present a
“thumbnail” sketch of management for the
relevant area. These flow diagrams are brief
enough to be used as a wall display in, for
instance, an accident and emergency department
or respiratory ward, or might be added to a junior
doctor’s personal organiser.
At the next level, the reader can look at the
bullet points presented after the flow diagram in
each document. These are structured to follow the
same order as the flow diagram and represent the
“key facts” which underpin the flow diagram.
These bullet points have been rated according to
the strength of evidence that lies behind each
point. This grading is laid out in table 1 and
Table 1 Grading of management
recommendations (“bullet points”)
A
See end of article for
authors’ affiliations
B
.......................
Correspondence to:
Dr R J O Davies, Oxford
Centre for Respiratory
Medicine, Churchill
Hospital Site, Oxford
Radcliffe Hospital,
Headington, Oxford
OX3 7LJ, UK;
robert.davies@
ndm.ox.ac.uk
C
(Supported by paper(s) of levels Ia or Ib).
Requires at least one randomised trial as part of
a body of literature of overall good quality and
consistency addressing the specific
recommendation
(Supported by paper(s) of levels IIa, IIb, III).
Requires the availability of well conducted
clinical studies but no randomised clinical trials
on the topic of recommendation (or
poor/inadequate randomised trials not
supported by sufficient other literature to achieve
grade A).
(Supported by level IV evidence). Requires
evidence from expert committee reports or
opinions and/or clinical experience of respected
authorities. Indicates absence of directly
applicable studies of good quality.
ranges from grade A (based on good quality clinical trial evidence) to grade C (based on expert
opinion alone).
Beneath each set of bullet points is a short
paragraph detailing the literature and the rationale relating to that section’s bullet points. This
text is intended to provide greater detail without
requiring access to the primary literature. The
text is referenced in detail and these references
constitute the bibliography at the end of each
guideline for the reader wishing to explore the
data for themselves. This primary source literature has been individually graded for its methodology and the grading is given alongside each reference. The explanation of this grading system is
presented in table 2.
METHODS USED IN GENERATING THE
GUIDELINES
Each guideline was researched and drafted by a
subgroup of the Pleural Diseases Group (itself a
subcommittee of the BTS Standards of Care Committee). Members of the drafting subgroup of the
Pleural Diseases Group are cited as the primary
authors of each guideline. For each guideline area,
a systematic search of the Medline database was
performed using all identifiable key words relevant
to the disease area of interest. Thereafter, a paper
based exploration of the relevant literature was
pursued from this core dataset. All English
language literature including all clinical trials and
all well formulated clinical case series were identified. Isolated case reports were excluded unless
they seemed particularly relevant. Animal and
basic science research was cited as needed, but no
systematic review of this literature was performed.
All identified publications were reviewed by the
drafting subgroup of the Pleural Diseases Group
Table 2 Grading of primary literature
(the bibliographies)
Ia
Ib
IIa
IIb
III
IV
Meta-analysis of randomised trials
Randomised controlled trial
Well designed controlled study without
randomisation
Another type of well designed
quasi-experimental study
Well designed non-experimental descriptive
studies such as comparative studies, correlation
studies, and case-control studies
Opinion of expert committee reports or opinions
and/or clinical experience of respected
authorities
.......................
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Davies, Gleeson
responsible for that guideline and rated according to the
standard criteria for the calibre of the methodology of the
research published (table 2). An algorithm for clinical
management based on a typical patient’s diagnostic and
therapeutic path was then drafted by the subgroup. This draft
was based, where possible, on the published evidence but this
was then combined with clinical expertise as required. The
resulting draft is therefore a blend of published evidence and
clinical experience. This first draft was reviewed in detail by all
the members of the Pleural Diseases Guideline Group and
thereafter refined by the subgroup. A second detailed review
was then performed by the whole group, with further manuscript alterations as needed. These documents were then submitted to open review and we would like to thank those who
contributed to this process. This open review process included
acknowledged UK and international experts, the membership
of the British Thoracic Society and the Standards of Care
Committee of the British Thoracic Society. The individuals
contributing to this process are listed in the Acknowledgements section below. The manuscripts were then amended in
the light of these comments before submission for blind peer
review and publication.
CONFLICT OF INTEREST
All the members of the Pleural Guidelines Committee submitted a
written record of possible conflicts of interest to the Standards of Care
Committee of the BTS. These are available for inspection on request
from the Chairman of this Committee.
ACKNOWLEDGEMENTS
The Pleural Diseases Guidelines Group would like to thank the
following people who contributed to open review of the guideline
documents: Professor M Bauman, Dr D Crook, Mr J Dussek, Mr W
Fountain, Professor D Geddes, Professor J Heffner, Professor R Light,
Dr J Macfarlane, Dr A Millar, Dr R Miller, Professor S Sahn, Dr T
Seemungal and colleagues, Dr M Slade, Professor C Strange, Mr D
Waller, and Professor K Webb.
Abstracted bullet points from each of the BTS guidelines for the management of pleural disease
In this section the “bullet points” from each of the BTS guidelines for the management of pleural disease are presented together
so that they can be easily reproduced and used for teaching, training, A&E handbooks, etc.
INVESTIGATION OF A UNILATERAL PLEURAL EFFUSION IN ADULTS
Clinical assessment and history
• Aspiration should not be performed for bilateral effusions in a clinical setting strongly suggestive of a pleural transudate, unless
there are atypical features or they fail to respond to therapy. [C]
• An accurate drug history should be taken during clinical assessment. [C]
Pleural aspiration
• A diagnostic pleural fluid sample should be gathered with a fine bore (21G) needle and a 50 ml syringe. The sample should be
placed in both sterile vials and blood culture bottles and analysed for protein, lactate dehydrogenase (LDH, to clarify borderline
protein values), pH, Gram stain, AAFB stain, cytology, and microbiological culture. [C]
Pleural fluid analysis
• The appearance of the pleural fluid and any odour should be noted. [C]
• A pleural fluid haematocrit is helpful in the diagnosis of haemothorax.
• The pleural protein should be measured to differentiate between a transudative and exudative pleural effusion. This will usually suffice if the patient’s serum protein level is normal and pleural protein is less than 25 g/l or more than 35 g/l. If not, Light’s criteria
(see box 5, page ii11) should be used. [B]
• Pleural lymphocytosis is common in malignancy and tuberculosis.
• Eosinophilic pleural effusions are not always benign.
• pH should be performed in all non-purulent effusions. [B]
• In an infected effusion a pH of <7.2 indicates the need for tube drainage. [B]
• Amylase measurement should be requested if acute pancreatitis or rupture of the oesophagus is possible. [C]
• Iso-enzyme analysis is useful in differentiating high amylase levels secondary to malignancy or ruptured oesophagus from those
raised in association with abdominal pathology.
• Malignant effusions can be diagnosed by pleural fluid cytology alone in only 60% of cases.
• If the first pleural cytology specimen is negative, this should be repeated a second time. [B]
• Both cell blocks and fluid smears should be prepared for examination and, if the fluid has clotted, it needs to be fixed and sectioned as a histological section. [B]
Diagnostic imaging
• PA and lateral chest radiographs should be performed in the assessment of suspected pleural effusion. [C]
• Ultrasound guided pleural aspiration should be used as a safe and accurate method of obtaining fluid if the effusion is small or
loculated. [B]
• Fibrinous septations are better visualised on ultrasound than on CT scans.
• CT scans for pleural effusion should be performed with contrast enhancement. [C]
• In cases of difficult drainage, CT scanning should be used to delineate the size and position of loculated effusions. [C]
• CT scanning can usually differentiate between benign and malignant pleural thickening.
Invasive investigations
•
•
•
•
•
•
•
•
Pleural tissue should always be sent for tuberculosis culture whenever a biopsy is performed. [B]
In cases of mesothelioma, the biopsy site should be irradiated to stop biopsy site invasion by tumour. [A]
When using an Abrams’ needle, at least four biopsy specimens should be taken from one site. [C]
When obtaining biopsies from focal areas of pleural nodularity shown on contrast enhanced CT scans, image guidance should be
used. [C]
Image guided cutting needle biopsies have a higher yield for malignancy than standard Abrams’ needle pleural biopsy.
Thoracoscopy should be considered when less invasive tests have failed to give a diagnosis. [B]
Routine diagnostic bronchoscopy should not be performed for undiagnosed pleural effusion. [C]
Bronchoscopy should be considered if there is haemoptysis or clinical features suggestive of bronchial obstruction. [C]
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BTS guidelines for the management of pleural disease
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Abstracted bullet points from each of the BTS guidelines for the management of pleural disease (continued)
Special tests
• If a chylothorax or pseudochylothorax is suspected, pleural fluid should be sent for measurement of triglyceride and cholesterol levels and the laboratory asked to look for the presence of cholesterol crystals and chylomicrons. [C]
• If urinothorax is suspected, the pleural fluid creatinine level should be measured and will be higher than the serum creatinine level.
[C]
• When pleural biopsies are taken, they should be sent for both histological examination and culture to improve the diagnostic sensitivity for tuberculosis. [B]
• There are no specific pleural fluid characteristics to distinguish those caused by pulmonary embolism. This diagnosis should be
pursued on clinical grounds.
• Suspected rheumatoid effusions should have a pleural fluid pH, glucose and complement measured. [C]
• Rheumatoid arthritis is unlikely to be the cause of an effusion if the glucose level in the fluid is above 1.6 mmol/l (29 mg/dl).
• The pleural fluid ANA level should not be measured as it mirrors serum levels and is therefore unhelpful. [C]
• In patients with HIV infection, the differential diagnosis of pleural effusion is wide and differs from the immunocompetent patient.
Management of persistent undiagnosed pleural effusion
• In persistently undiagnosed effusions, the possibility of pulmonary embolism and tuberculosis should be reconsidered since these
disorders are amenable to specific treatment. [C]
• Undiagnosed pleural malignancy proves to be the cause of many “undiagnosed” effusions with sustained observation.
MANAGEMENT OF PLEURAL INFECTION
Diagnostic pleural fluid sampling in parapneumonic pleural effusions
• All patients with a pleural effusion in association with sepsis or a pneumonic illness require diagnostic pleural fluid sampling. [C]
Sampling small parapneumonic pleural effusions
• In the event of a small effusion or a failed previous attempt at pleural fluid sampling, an ultrasound scan and image guided fluid
sampling is recommended. [C]
• Pleural effusions with maximal thickness <10 mm on ultrasound scanning can be observed, with pleural fluid sampling if the effusion enlarges. [C]
When to use chest tube drainage in pleural infection
• Patients with frankly purulent or turbid/cloudy pleural fluid on sampling should receive prompt pleural space chest tube drainage.
[B]
• The presence of organisms identified by Gram stain or culture from non-purulent pleural fluid samples indicates that pleural infection is established and should lead to prompt chest tube drainage. [B]
• Pleural fluid pH should be assessed in all non-purulent, possibly infected effusions. [B]
• pH <7.2 indicates chest tube drainage is required. [B]
• Parapneumonic effusions that do not fulfil these criteria for chest tube drainage should be treated with antibiotics alone provided
clinical progress is good. [B]
• Poor clinical progress during treatment with antibiotics alone should lead to prompt patient review and probably chest tube drainage. [B]
Other indications for chest tube drainage
• Patients with a loculated pleural collection should receive earlier chest tube drainage. [C]
• Large non-purulent effusions should be drained by chest tube for symptomatic benefit. [C]
Referral to a respiratory specialist
• A respiratory physician or thoracic surgeon should be involved in the care of all patients requiring chest tube drainage for a pleural infection. [C]
Antibiotics
•
•
•
•
All patients should receive antibiotics. [B]
Where possible, antibiotics should be guided by bacterial culture results. [B]
Where cultures are negative, antibiotics should cover community acquired bacterial pathogens and anaerobic organisms. [B]
Hospital acquired empyema requires broader spectrum antibiotic cover. [B]
Chest tube drainage
• There is no consensus on the size of the optimal chest tube for drainage.
• If a small bore flexible catheter is used, regular flushing and suction is recommended to avoid catheter blockage. [C]
Cessation of chest tube drainage in the presence of a residual pleural fluid collection
• If the chest tube becomes blocked or pus is unable to drain, it should be flushed with saline to ensure its patency. If poor drainage
persists, a chest radiograph or CT scan should be performed to check drain position. [C]
Intrapleural fibrinolytic drugs
• Intrapleural fibrinolytic drugs (streptokinase 250 000 IU twice daily for 3 days or urokinase 100 000 IU once a day for 3 days)
improve radiological outcome and, in children, hospital stay. Current best evidence favours their use [B], but it is not known if they
reduce mortality and/or the need for surgery. Clinical trials are underway to address this question.
• Patients who receive intrapleural streptokinase should be given a streptokinase exposure card and should receive urokinase or
tissue plasminogen activator (TPA) for subsequent indications. [C]
Persistent sepsis and pleural collection
• Patients with persistent sepsis and a residual pleural collection should undergo further radiological imaging. [C]
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Davies, Gleeson
Abstracted bullet points from each of the BTS guidelines for the management of pleural disease (continued)
Bronchoscopy
• Bronchoscopy should only be performed in patients where there is a high index of suspicion of bronchial obstruction. [C]
Nutrition
• Clinicians should ensure adequate nutritional support commencing as soon as possible after pleural infection is identified. [C]
Referral for surgical treatment
• Failure of chest tube drainage, antibiotics and fibrinolytic drugs should prompt early discussion with a thoracic surgeon.[C]
• Patients should be considered for surgical treatment if they have persisting sepsis in association with a persistent pleural collection,
despite chest tube drainage and antibiotics. [C]
Patients not considered fit for surgery and not improving with chest tube drainage and antibiotics
• In cases of ineffective chest tube drainage and persistent sepsis in patients unable to tolerate general anaesthesia, re-imaging the
thorax and placement of further image guided small bore catheters, large bore chest tubes, or intrapleural fibrinolytic therapy
should be considered. [C]
• Local anaesthetic surgical rib resection should be considered in patients unsuitable for general anaesthesia. [C]
MANAGEMENT OF MALIGNANT PLEURAL EFFUSIONS
Clinical presentation
• Massive pleural effusions are most commonly due to malignancy. [B]
Management by observation alone
• Observation is recommended if the patient is asymptomatic or there is no recurrence of symptoms after initial thoracentesis. [C]
• Advice should be sought from the thoracic malignancy multidisciplinary team for symptomatic or recurrent malignant effusions. [C]
Therapeutic pleural aspiration
•
•
•
•
Repeat pleural aspiration is recommended for the palliation of breathlessness in patients with a very short life expectancy. [C]
Caution should be taken if removing more than 1.5 l on a single occasion. [C]
The recurrence rate at 1 month after pleural aspiration alone is close to 100%. [B]
Intercostal tube drainage without pleurodesis is not recommended because of a high recurrence rate. [B]
Size of intercostal tube
• Small bore (10–14 F) intercostal catheters should be the initial choice for effusion drainage and pleurodesis. [B]
Lung re-expansion, fluid drainage and suction
• Large pleural effusions should be drained in a controlled fashion to reduce the risk of re-expansion pulmonary oedema (RPO). [C]
• Suction to aid pleural drainage before and after pleurodesis is usually unnecessary but, if applied, a high volume, low-pressure
system is recommended. [C]
• In patients where only partial pleural apposition can be achieved, chemical pleurodesis should still be attempted and may provide
symptomatic relief. [B]
• Once effusion drainage and lung re-expansion have been radiographically confirmed, pleurodesis should not be delayed while
the cessation of pleural fluid drainage is awaited. [B]
Analgesia and premedication
• Lignocaine (3 mg/kg; maximum 250 mg) should be administered intrapleurally just prior to sclerosant administration. [B]
• Premedication should be considered to alleviate anxiety and pain associated with pleurodesis. [C]
Selecting a sclerosing agent
•
•
•
•
•
Talc is the most effective sclerosant available for pleurodesis. [B]
A small number of patients (<1%) may develop acute respiratory failure following talc administration. [B]
Tetracycline is modestly effective, has few severe side effects, and is the preferred sclerosant to minimise adverse event rates. [B]
Bleomycin is an alternative sclerosant with a modest efficacy rate but is expensive. [B]
Pleuritic chest pain and fever are the most common side effects of sclerosant administration. [B]
Rotation following pleurodesis
• Patient rotation is not necessary after intrapleural instillation of tetracycline class agents. [A]
Clamping of intercostal tube
• The intercostal tube should be clamped for 1 hour after sclerosant administration. [C]
• In the absence of excessive fluid drainage (>250 ml/day) the intercostal tube should be removed within 12–72 hours of sclerosant
administration. [C]
Malignant seeding at intercostal tube or port site
• Patients with proven or suspected mesothelioma should receive prophylactic radiotherapy to the site of biopsy or chest drain insertion. [A]
Intrapleural fibrinolytics
• Intrapleural instillation of fibrinolytic drugs is recommended for the relief of distressing dyspnoea due to multiloculated malignant
effusion resistant to simple drainage. [C]
Thoracoscopy in malignant pleural effusion
• Thoracoscopy should be considered for the diagnosis of suspected but unproven malignant pleural effusion. [B]
• Thoracoscopy should be considered for the control of recurrent malignant pleural effusion. [B]
• Thoracoscopy is a safe procedure with low complication rates. [B]
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BTS guidelines for the management of pleural disease
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Abstracted bullet points from each of the BTS guidelines for the management of pleural disease (continued)
Long term indwelling pleural catheter drainage
• Chronic indwelling pleural catheters are effective in controlling recurrent and symptomatic malignant effusions in selected patients.
[B]
Pleuroperitoneal shunting
• Pleuroperitoneal shunts are an alternative and effective option in patients with a trapped lung or failed pleurodesis. [B]
MANAGEMENT OF SPONTANEOUS PNEUMOTHORAX
Smoking
• Strong emphasis should be placed on the relationship between the recurrence of pneumothorax and smoking in an effort to
encourage patients to stop smoking. [B]
Clinical evaluation and imaging
• Expiratory chest radiographs should not be used for the routine diagnosis of pneumothorax. [B]
• A lateral chest or lateral decubitus radiograph should be performed if the clinical suspicion of pneumothorax is high, but a PA
radiograph is normal. [B]
• CT scanning is recommended when differentiating a pneumothorax from complex bullous lung disease, when aberrant tube placement is suspected, and when the plain chest radiograph is obscured by surgical emphysema. [C]
• The clinical history is not a reliable indicator of pneumothorax size. [C]
Size of pneumothorax
• The previous classification of the size of a pneumothorax tends to underestimate its volume. In these new guidelines the size of a
pneumothorax is divided into “small” or “large” depending on the presence of a visible rim of <2 cm or >2 cm between the lung
margin and the chest wall.
Treatment by observation alone
• Observation should be the treatment of choice for small closed pneumothoraces without significant breathlessness. [B]
• Patients with small (<2 cm) primary pneumothoraces not associated with breathlessness should be considered for discharge with
early outpatient review. These patients should receive clear written advice to return in the event of worsening breathlessness. [B]
• If a patient with a pneumothorax is admitted overnight for observation, high flow (10 l/min) oxygen should be administered, with
appropriate caution in patients with COPD who may be sensitive to higher concentrations of oxygen. [B]
• Breathless patients should not be left without intervention regardless of the size of the pneumothorax on a chest radiograph. [C]
Simple aspiration
• Simple aspiration is recommended as first line treatment for all primary pneumothoraces requiring intervention. [A]
• Simple aspiration is less likely to succeed in secondary pneumothoraces and, in this situation, is only recommended as an initial
treatment in small (<2 cm) pneumothoraces in minimally breathless patients under the age of 50 years. [B]
• Patients with secondary pneumothoraces treated successfully with simple aspiration should be admitted to hospital and observed
for at least 24 hours before discharge. [C]
Repeat aspiration and catheter aspiration of simple pneumothorax
• Repeated aspiration is reasonable for primary pneumothorax when the first aspiration has been unsuccessful (i.e. patient still
symptomatic) and a volume of <2.5 l has been aspirated on the first attempt. [B]
• Catheter aspiration of pneumothorax (CASP) can be used where the equipment and experience is available. [B]
• Catheter aspiration kits with an integral one way valve system may reduce the need for repeat aspiration. [C]
Intercostal tube drainage
• If simple aspiration or catheter aspiration drainage of any pneumothorax is unsuccessful in controlling symptoms, then an intercostal tube should be inserted. [B]
• Intercostal tube drainage is recommended in secondary pneumothorax except in patients who are not breathless and have a very
small (<1 cm or apical) pneumothorax. [B]
• A bubbling chest tube should never be clamped. [B]
• A chest tube which is not bubbling should not usually be clamped. [B]
• If a chest tube for pneumothorax is clamped, this should be under the supervision of a respiratory physician or thoracic surgeon,
the patient should be managed in a specialist ward with experienced nursing staff, and the patient should not leave the ward environment. [C]
• If a patient with a clamped drain becomes breathless or develops subcutaneous emphysema, the drain must be immediately
unclamped and medical advice sought. [C]
Size of chest tube
• There is no evidence that large tubes (20–24 F) are any better than small tubes (10–14 F) in the management of pneumothoraces.
The initial use of large (20–24 F) intercostal tubes is not recommended, although it may become necessary to replace a small chest
tube with a larger one if there is a persistent air leak. [B]
Referral to respiratory specialists
• Pneumothoraces which fail to respond within 48 hours to treatment should be referred to a respiratory physician. [C]
Chest drain suction
• Suction to an intercostal tube should not be applied directly after tube insertion, but can be added after 48 hours for persistent air
leak or failure of a pneumothorax to re-expand. [B]
• High volume, low pressure (–10 to –20 cm H2O) suction systems are recommended. [C]
• Patients requiring suction should only be managed on lung units where there is specialist medical and nursing experience. [C]
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Davies, Gleeson
Abstracted bullet points from each of the BTS guidelines for the management of pleural disease (continued)
Chemical pleurodesis
• Chemical pleurodesis can control difficult or recurrent pneumothorax [A] but should only be attempted if the patient is either unwilling or unable to undergo surgery. [B]
• Medical pleurodesis for pneumothorax should be performed by a respiratory specialist. [C]
Referral to thoracic surgeons
• In cases of persistent air leak or failure of the lung to re-expand, the managing respiratory specialist should seek an early (3–5
days) thoracic surgical opinion. [C]
• Open thoracotomy and pleurectomy remains the procedure with the lowest recurrence rate for difficult or recurrent pneumothoraces. Minimally invasive procedures, thoracoscopy (VATS), pleural abrasion, and surgical talc pleurodesis are all effective alternative strategies.
Surgical chemical pleurodesis
• Surgical chemical pleurodesis is best achieved with 5 g sterile talc. Side effects such as ARDS and empyema are reported but rare.
[A]
Discharge and follow up
• Patients discharged without intervention should avoid air travel until a chest radiograph has confirmed resolution of the pneumothorax. [C]
• Diving should be permanently avoided after a pneumothorax, unless the patient has had a surgical pleurectomy. [C]
• Primary pneumothorax patients treated successfully by simple aspiration should be observed for 4–6 hours before discharge. Secondary pneumothorax patients who are successfully treated with simple aspiration should be admitted for 24 hours before
discharge to ensure no recurrence. [C]
Pneumothorax and AIDS
• Early and aggressive treatment of pneumothoraces in HIV patients, incorporating intercostal tube drainage and early surgical
referral, is recommended. [B]
Pneumothorax and cystic fibrosis
• Early and aggressive treatment of pneumothoraces in cystic fibrosis is recommended. [C]
• Surgical intervention should be considered after the first episode, provided the patient is fit for the procedure. [C]
Tension pneumothorax
• If tension pneumothorax is present, a cannula of adequate length should be promptly inserted into the second intercostal space in
the mid clavicular line and left in place until a functioning intercostal tube can be positioned. [B]
INSERTION OF A CHEST DRAIN
Training
• All personnel involved with insertion of chest drains should be adequately trained and supervised. [C]
Pre-drainage risk assessment
• Risk of haemorrhage: where possible, any coagulopathy or platelet defect should be corrected prior to chest drain insertion but
routine measurements of platelet count and/or prothrombin time should only be performed in patients with known risk factors. [C]
• The differential diagnosis between a pneumothorax and bullous disease requires careful radiological assessment. Similarly, it is
important to differentiate between the presence of collapse and a pleural effusion when the chest radiograph shows a unilateral
“whiteout”.
• Lung densely adherent to the chest wall throughout the hemithorax is an absolute contraindication to chest drain insertion. [C]
• The drainage of a post pneumonectomy space should only be carried out by or after consultation with a cardiothoracic surgeon.
[C]
Consent and premedication
• Prior to commencing chest tube insertion the procedure should be explained fully to the patient and consent recorded in accordance with national guidelines. [C]
• Unless there are contraindications to its use, premedication (benzodiazepine or opioid) should be given to reduce patient distress.
[B]
Confirming site of drain insertion
• A chest tube should not be inserted without further image guidance if free air or fluid cannot be aspirated with a needle at the time
of anaesthesia. [C]
• Imaging should be used to select the appropriate site for chest tube placement. [B]
• A chest radiograph must be available at the time of drain insertion except in the case of tension pneumothorax. [C]
Drain size
• Small bore drains are more comfortable for the patient than larger bore tubes, [B] but there is no evidence that either is therapeutically superior.
• Large bore drains are recommended for drainage of acute haemothorax to monitor further blood loss. [C]
Aseptic technique
• Aseptic technique should be employed during catheter insertion. [C]
• Prophylactic antibiotics should be given in trauma cases. [A]
Anaesthesia
• Local anaesthetic should be infiltrated prior to insertion of the drain. [C]
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BTS guidelines for the management of pleural disease
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Abstracted bullet points from each of the BTS guidelines for the management of pleural disease (continued)
Insertion of chest tube
• Chest drain insertion should be performed without substantial force. [C]
• Insertion of a small bore drain under image guidance with a guidewire does not require blunt dissection.
• Blunt dissection into the pleural space must be performed before insertion of a large bore chest drain. [C]
Incision
• The incision for insertion of the chest drain should be similar to the diameter of the tube being inserted. [C]
Position of tube tip
• The position of the tip of the chest tube should ideally be aimed apically for a pneumothorax or basally for fluid. However, any
tube position can be effective at draining air or fluid and an effectively functioning drain should not be repositioned solely because
of its radiographic position. [C]
Securing the drain
• Large and medium bore chest drain incisions should be closed by a suture appropriate for a linear incision. [C]
• “Purse string” sutures must not be used. [C]
Clamping of chest drains
• A bubbling chest tube should never be clamped. [C]
• Drainage of a large pleural effusion should be controlled to prevent the potential complication of re-expansion pulmonary oedema.
[C]
• In cases of pneumothorax, clamping of the chest tube should usually be avoided. [B]
• If a chest tube for pneumothorax is clamped, this should be under the supervision of a respiratory physician or thoracic surgeon,
the patient should be managed in a specialist ward with experienced nursing staff, and the patient should not leave the ward environment. [C]
• If a patient with a clamped drain becomes breathless or develops subcutaneous emphysema, the drain must be immediately
unclamped and medical advice sought. [C]
Closed system drainage
• All chest tubes should be connected to a single flow drainage system e.g. under water seal bottle or flutter valve. [C]
• Use of a flutter valve system allows earlier mobilisation and the potential for earlier discharge of patients with chest drains.
Suction
• When chest drain suction is required, a high volume/low pressure system should be used. [C]
• When suction is required, the patient must be nursed by appropriately trained staff. [C]
Ward instructions
• Patients with chest tubes should be managed on specialist wards by staff who are trained in chest drain management. [C]
• A chest radiograph should be performed after insertion of a chest drain. [C]
Removal of a chest tube
• In cases of pneumothorax, the chest tube should not be clamped at the time of its removal. [B]
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ii8
BTS guidelines for the investigation of a unilateral pleural
effusion in adults
N A Maskell, R J A Butland, on behalf of the British Thoracic Society Pleural Disease
Group, a subgroup of the British Thoracic Society Standards of Care Committee
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Thorax 2003;58(Suppl II):ii8–ii17
1 INTRODUCTION
Pleural effusions, the result of the accumulation
of fluid in the pleural space, are a common medical problem. They can be caused by several
mechanisms including increased permeability of
the pleural membrane, increased pulmonary capillary pressure, decreased negative intrapleural
pressure, decreased oncotic pressure, and obstructed lymphatic flow. The pathophysiology of
pleural 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 is
wide, a systematic approach to investigation is
necessary. The aim is to establish a diagnosis
swiftly while minimising unnecessary invasive
investigation. This is particularly important as the
differential diagnosis includes malignant mesothelioma in which 40% of needle incisions for
investigation are invaded by tumour.1 A 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
See end of article for
authors’ affiliations
.......................
Correspondence to:
Dr N A Maskell, Oxford
Centre for Respiratory
Medicine, Churchill
Hospital Site, Oxford
Radcliffe Hospital,
Headington, Oxford
OX3 7LJ, UK;
[email protected]
.......................
www.thoraxjnl.com
• Aspiration should not be performed for
bilateral effusions in a clinical setting
strongly suggestive of a pleural transudate, unless there are atypical features
or they fail to respond to therapy. [C]
• An accurate drug history should be taken
during 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 physical
examination. The biochemical analysis of pleural
fluid is considered later (section 5).
Clinical assessment alone is often capable of
identifying transudative effusions. In a series of
33 cases, all 17 transudates were correctly
predicted by clinical assessment, blind of the
results of pleural fluid analysis.2 Therefore, in an
appropriate clinical setting such as left ventricular
failure with a confirmatory chest radiograph,
these effusions do not need to be sampled unless
there are atypical features or they fail to respond
to treatment.
Approximately 75% of patients with pulmonary embolism and pleural effusion have a
history of pleuritic pain. These effusions tend to
occupy less than a third of the hemithorax and
the dyspnoea is often out of proportion to its size.
As tests on the pleural fluid are unhelpful in
diagnosing pulmonary embolism, a high index of
suspicion is required to avoid missing the
diagnosis.3
The patient’s 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 with
their frequencies. Useful resources for more
detailed information include the British National
Formulary and the website pneumotox.com.
3 CAUSES OF A PLEURAL EFFUSION
Pleural effusions are classified into transudates
and 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 fluid
accumulation. 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 are
altered.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 frequency.
4 PLEURAL ASPIRATION
• A diagnostic pleural fluid sample should
be gathered with a fine bore (21G) needle
and a 50 ml syringe. The sample should be
placed in both sterile vials and blood culture bottles and analysed for protein, lactate dehydrogenase (LDH, to clarify borderline protein values), pH, Gram stain,
AAFB stain, cytology, and microbiological
culture. [C]
This is the primary means of evaluating pleural
fluid and its findings are used to guide further
investigation. Diagnostic taps are often performed
in the clinic or by the bedside, although small
Box 1 Drugs known to cause pleural
effusions
Over 100 reported cases globally*
•
•
•
•
Amiodarone
Nitrofurantoin
Phenytoin
Methotrexate
20–100 reported cases globally*
•
•
•
•
•
•
•
Carbamazepine
Procainamide
Propylthiouracil
Penicillamine
GCSF
Cyclophosphamide
Bromocriptine
*pneumotox.com (2001)
BTS guidelines for the investigation of a unilateral pleural effusion in adults
ii9
Diagnostic algorithm for the investigation of a pleural effusion
History, clinical examination and chest radiography
Does the clinical picture
YES
suggest a transudate? e.g.
Treat
YES
Resolved?
the cause
LVF, hypoalbuminaemia, dialysis
STOP
(section 2)
NO
Pleural aspiration.
NO
Send for: cytology, protein, LDH, pH
Gram stain, culture and sensitivity, AAFB stains and culture
See
box 1
YES
Do you suspect an
empyema, chylothorax
or haemothorax?
NO
YES
Is it a transudate?
(section 5.2)
Treat
the cause
NO
Have the fluid analysis
YES
and chemical features
Treat
appropriately
given a diagnosis?
NO
Box 1: Additional pleural fluid tests
Refer to a chest physician
Suspected disease
Request contrast enhanced CT thorax (fig 2) (section 6.3)
Chylothorax
Tests
cholesterol and
triglyceride
centrifuge
Obtain pleural tissue, either by ultrasound/CT
guided biopsy, or by closed pleural biopsy or
Haemothorax
haematocrit
Empyema
centrifuge
thoracoscopy.
Send these for histology and TB culture together
with a repeat pleural aspiration for cytology,
_
microbiological studies +/ special tests
Box 2: Pleural fluid tests which may be
(see box 2) (sections 7.1 and 7.2)
useful in certain circumstances
Suspected disease
YES
Cause found?
Rheumatoid disease
Tests
glucose
complement
NO
Pancreatitis
Reconsider thoracoscopy
Cause found?
YES
amylase
Treat
appropriately
NO
Reconsider PE and TB.
Wait for diagnosis to evolve. (section 9)
Figure 1 Flow diagram of the investigation pathway for a unilateral pleural effusion of unknown aetiology.
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Maskell, Butland
Box 2 Causes of transudative pleural effusions
Very common causes
•
•
•
•
Left ventricular failure
Liver cirrhosis
Hypoalbuminaemia
Peritoneal dialysis
Less common causes
•
•
•
•
Hypothyroidism
Nephrotic syndrome
Mitral stenosis
Pulmonary embolism
Rare causes
•
•
•
•
•
Constrictive pericarditis
Urinothorax
Superior vena cava obstruction
Ovarian hyperstimulation
Meigs’ syndrome
Box 4 Key facts when investigating undiagnosed
pleural effusions
• If the pleural fluid protein is between 25 and 35 g/l, then
Light’s criteria are advised to differentiate accurately
exudates from transudates.
• Pleural fluid pH should be performed in all non-purulent
effusions if infection is suspected.
• When sending a pleural fluid specimen for microbiological
examination, it should be sent in both a sterile tube (for
Gram stain, AAFB and TB culture) and in blood culture bottles to increase the diagnostic yield.
• Only 60% of malignant effusions can be diagnosed by
cytological examination.
• A contrast enhanced CT scan of the thorax is best
performed with the fluid present. This will enable better
visualisation of pleura and can identify the best site for
pleural biopsy if cytological examination is unhelpful.
Table 1
Appearance of pleural fluid
Box 3 Causes of exudative pleural effusions
Fluid
Suspected disease
Common causes
Putrid odour
Food particles
Bile stained
Milky
“Anchovy sauce” like fluid
Anaerobic empyema
Oesophageal rupture
Cholothorax (biliary fistula)
Chylothorax/pseudochylothorax
Ruptured amoebic abscess
• Malignancy
• Parapneumonic effusions
Less common causes
•
•
•
•
•
•
Pulmonary infarction
Rheumatoid arthritis
Autoimmune diseases
Benign asbestos effusion
Pancreatitis
Post-myocardial infarction syndrome
Rare causes
• Yellow nail syndrome
• Drugs (see box 1)
• Fungal infections
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 to
be sent directly for microbiological, biochemical, and cytological analysis.
Microscopic examination of Gram stained pleural fluid
sediment is necessary for all fluids and particularly when a
parapneumonic effusion is suspected. If some of the microbiological specimen is sent in blood culture bottles the yield is
greater, especially for anaerobic organisms.6
20 ml of pleural fluid is adequate for cytological examination and the fresher the sample when it arrives at the laboratory the better. If part of the sample has clotted, the cytologist
must fix and section this and treat it as a histological section
as 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 stored
at 4°C for up to 4 days.7
5 PLEURAL FLUID ANALYSIS
5.1 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 odour
of the pleural fluid should be noted. The unpleasant aroma of
anaerobic infection may guide antibiotic choice. The appearance can be divided into serous, blood tinged, frankly bloody,
www.thoraxjnl.com
or purulent. If the pleural fluid is turbid or milky it should be
centrifuged. 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 or
pseudochylothorax 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 the
patient’s peripheral blood haematocrit, the patient has a
haemothorax. If the haematocrit on the pleural fluid is less
than 1%, the blood in the pleural fluid is not significant.9
Grossly bloody pleural fluid is usually due to malignancy, pulmonary embolus with infarction, trauma, benign asbestos
pleural effusions, or post-cardiac injury syndrome (PCIS).9
5.2 Differentiating between a pleural fluid exudate and
transudate
• The pleural protein should be measured to differentiate between a transudative and exudative pleural
effusion. This will usually suffice if the patient’s
serum protein is normal and pleural protein is less
than 25 g/l or more than 35 g/l. If not, Light’s criteria
(see box 5) should be used. [B]
The classical way of separating a transudate from an exudate
is by pleural fluid protein, with exudates having a protein level
of >30 g/l and transudates a protein level of <30 g/l. Care
should be taken in interpreting this result if the serum total
protein is abnormal. Unfortunately, the protein level often lies
very close to the 30 g/l cut off point, making clear differentiation difficult. In these cases, measurement of serum and pleural fluid lactate dehydrogenase (LDH) and total protein levels
will allow the use of Light’s criteria to distinguish between
these two more accurately (box 5).10
A considerable number of other biochemical markers have
been compared with Light’s criteria. These include measuring
pleural fluid cholesterol, albumin gradient, and serum/pleural
fluid bilirubin ratio.11–15 The accuracy of these different indices
BTS guidelines for the investigation of a unilateral pleural effusion in adults
Box 5 Light’s criteria
The pleural fluid is an exudate if one or more of the following criteria are met:
• Pleural fluid protein divided by serum protein >0.5
• Pleural fluid LDH divided by serum LDH >0.6
• Pleural fluid LDH more than two-thirds the upper limits of
normal serum LDH
in differentiating exudates and transudates has been examined in a meta-analysis of 1448 patients from eight studies.15
Light’s criteria performed best with excellent discriminative
properties. Further analysis suggests a cut off value of LDH
levels in pleural fluid of >0.66, the upper limits of the laboratory normal might be a better discriminator (“modified Light’s
criteria”).16
In summary, Light’s criteria appear to be the most accurate
way of differentiating between transudates and exudates. The
weakness of these criteria is that they occasionally identify an
effusion in a patient with left ventricular failure on diuretics
as 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 and
tuberculosis.
• Eosinophilic pleural effusions are not always benign.
When polymorphonuclear cells predominate, the patient has
an acute process affecting the pleural surfaces. If there is concomitant parenchymal shadowing, the most likely diagnoses
are 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 presence
of 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.18–20 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 eosinophilic effusions were due to cancer.20
If the pleural fluid differential cell count shows a predominant lymphocytosis, the most likely diagnoses are tuberculosis
and malignancy. Although high lymphocyte counts in pleural
fluid raise the possibility of tuberculous pleurisy,9 as many as
10% 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 pleural effusions which can usually be treated conservatively.
Large symptomatic effusions can occur in up to 1% of patients
in the postoperative period. These are predominantly left sided
and the differential cell count can help to clarify the situation.
Bloody effusions are usually eosinophilic, occur early, and are
related to bleeding into the pleural cavity from the time of
surgery. Non-bloody effusions tend to have small lymphocytes
as 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 effusions. [B]
• In an infected effusion a pH of <7.2 indicates the
need for tube drainage. [B]
ii11
A pleural fluid pH of <7.2 with a normal blood pH is found in
the same diagnoses as a low pleural fluid glucose.24 A pH of
<7.2 represents a substantial accumulation of hydrogen ions,
as normal pleural pH is about 7.6 because of bicarbonate
accumulation in the pleural cavity. The main clinical use for
the measurement of pleural pH is the identification of pleural
infection.25 26 This is covered in detail in the guideline on pleural infection (page ii18). Other diseases causing an exudative
pleural effusion with a low pH are collagen vascular diseases
(particularly rheumatoid arthritis), oesophageal rupture, and
malignancy.24
A prospective study of the value of pH in malignant pleural
effusions by Rodriguez and Lopez27 in 77 patients undergoing
thoracoscopy showed that a pH of <7.3 was associated with
more extensive malignancy, a 90% chance of positive cytology,
and a 50% chance of failed pleurodesis. Sahn and Good
showed that a reduced pH (<7.3) predicted poor survival in
malignant pleural disease (pH >7.3, median survival 9.8
months; pH <7.3, survival 2.1 months).28
5.5 Glucose
A pleural glucose level of less than 3.3 mmol/l is found in exudative pleural effusions secondary to empyema, rheumatoid
disease, lupus, tuberculosis, malignancy, or oesophageal
rupture.29 The lowest glucose concentrations are found in
rheumatoid effusions and empyema.29–32 In pleural infection,
pH discriminates better than glucose.26 33 Rheumatoid arthritis
is unlikely to be the cause of an effusion if the glucose level in
the fluid is above 1.6 mmol/l (see section 8.6.1).30
5.6 Amylase
• Amylase measurement should be requested if acute
pancreatitis or rupture of the oesophagus is possible.
[C]
• Iso-enzyme analysis is useful in differentiating high
amylase levels secondary to malignancy or ruptured
oesophagus from those raised in association with
abdominal pathology.
Pleural fluid amylase levels can be useful in the evaluation of
an exudative effusion. Pleural fluid amylase levels are elevated
if they are higher than the upper limits of normal for serum or
the pleural fluid/serum ratio is >1.0.31 This suggests acute
pancreatitis, pancreatic pseudocyst, rupture of the oesophagus, ruptured ectopic pregnancy, or pleural malignancy
(especially adenocarcinoma).9 Approximately 10% of malignant effusions have raised pleural amylase levels.34
Iso-enzyme analysis can be useful in suspected cases of
oesophageal rupture as this will show the amylase is of
salivary origin.35 If the salivary amylase is raised and oesophageal rupture is not suspected, malignancy is most likely. Pleural effusions associated with pancreatic disease usually
contain pancreatic amylase.36
In a prospective study of 176 patients, 10 had an amylase
rich effusion. Of these, four had pancreatitis which had not
previously been suspected. The rest were due to nonpancreatic diseases of which lung cancer was predominant.37
The incidence of pleural effusion with acute pancreatitis
exceeds 50%. Patients with acute pancreatitis and a pleural
effusion tend to have more severe disease and a higher likelihood of subsequently developing a pseudocyst than those
without effusions.38
5.7 Cytology
• Malignant effusions can be diagnosed by pleural fluid
cytology alone in only 60% of cases.
• If the first pleural cytology specimen is negative, this
should be repeated a second time. [B]
• Both cell blocks and fluid smears should be prepared
for examination and, if the fluid has clotted, it needs
to be fixed and sectioned as a histological section. [B]
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ii12
Maskell, Butland
Table 2 Sensitivity of pleural fluid cytology in
malignant pleural effusion
Reference
No of patients
No caused by
malignancy
% diagnosed by
cytology
Salyer et al40
Prakash et al42
Nance et al41
Hirsch39
Total
271
414
385
300
1370
95
162
109
117
371
72.6
57.6
71.0
53.8
61.6
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 sensitivity of pleural cytology are shown in table 2.39–42 These sensitivities vary from 40% to 87%, with a mean of about 60%. Of 55
cases 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 the
second, 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 in
combination with pleural biopsy.42 The final causes of the
effusion were malignancy in 281 patients (68%). The presence
of 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 having
malignancy. 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 cell
carcinoma, 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 from
adenocarcinoma.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 glandular markers for CEA, B72.3 and Leu-M1 together with calretinin and cytokeratin 5/6 will often help to distinguish
adenocarcinoma from mesothelioma.46–48
6 DIAGNOSTIC IMAGING
6.1 Plain radiography
• PA and lateral chest radiographs should be performed in the assessment of suspected pleural
effusion. [C]
The plain chest radiographic features of pleural effusion are
usually characteristic. The PA chest radiograph is abnormal in
the presence of about 200 ml pleural fluid. However, only
50 ml of pleural fluid can produce detectable posterior costophrenic 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, differentiating
between pleural thickening and free fluid.50
In the intensive care setting, patients are often imaged
supine where free pleural fluid will layer out posteriorly. Pleural fluid is often represented as a hazy opacity of one
hemithorax with preserved vascular shadows on the supine
radiograph. Other signs include the loss of the sharp
silhouette of the ipsilateral hemidiaphragm and thickening of
the minor fissure. The supine chest radiograph will often
underestimate the volume of pleural fluid.51
Subpulmonic effusions occur when pleural fluid accumulates 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
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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 flat
appearance 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 used
as a safe and accurate method of obtaining fluid if
the effusion is small or loculated. [B]
• Fibrinous septations are better visualised on ultrasound 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 effusion, ultrasound guided aspiration yields fluid in 97% of
cases.50 In a series of 320 patients, Yang et al55 found that pleural effusions with complex septated, complex non-septated, or
homogeneously echogenic patterns are always exudates,
whereas hypoechoic effusions can be either transudates or
exudates. Ultrasound is also useful in demonstrating fibrinous
loculation and readily differentiates between pleural fluid and
pleural thickening.56 57 Ultrasound also has the added advantage 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 performed
with contrast enhancement. [C]
• In cases of difficult drainage, CT scanning should be
used to delineate the size and position of loculated
effusions. [C]
• CT scanning can usually differentiate between benign and malignant pleural thickening.
There are features of contrast enhanced thoracic CT scanning
which can help differentiate between benign and malignant
disease (fig 2). In a study of 74 patients, 39 of whom had
malignant disease, Leung et al60 showed that malignant disease
is favoured by nodular pleural thickening, mediastinal pleural
thickening, parietal pleural thickening greater than 1 cm, and
circumferential pleural thickening. These features have
specificities 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 the
33 cases of pleural malignancy were identified correctly on the
basis of the presence of one or more of Leung’s criteria. When
investigating a pleural effusion a contrast enhanced thoracic
CT 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 radiographs in the differentiation of pleural from parenchymal disease. It is particularly helpful in the assessment and management 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 than
CT scanning.59 64 65
7 INVASIVE INVESTIGATIONS
7.1 Percutaneous pleural biopsy
• Pleural tissue should always be sent for tuberculosis
culture whenever a biopsy is performed. [B]
• In cases of mesothelioma, the biopsy site should be
irradiated 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
BTS guidelines for the investigation of a unilateral pleural effusion in adults
ii13
Figure 2 (A) Computed tomographic scan of the thorax without
contrast enhancement showing a large undiagnosed cytologically
negative pleural effusion. (B) The same patient after administration of
intravenous contrast which reveals malignant nodular pleural
thickening. This illustrates the value of contrast enhancement for the
definition of pleural nodularity. The performance of imaging before
complete drainage of the pleural fluid allows the identification of
pleural nodularity and retains the opportunity for low risk image
guided needle biopsy. (C) Image of the pleural abnormality being
biopsied with a cutting needle. Histological examination showed this
to be due to a mesothelioma.
pleura. They are performed on patients with undiagnosed
exudative effusions, with non-diagnostic cytology, and a clinical suspicion of tuberculosis or malignancy. Occasionally, a
blind pleural biopsy may be performed at the same time as the
first 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 on
a 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.
AAFB smear, culture, biopsy histology, and culture are
performed in concert, the diagnostic yield is 80–90%.21 70–72
Complications of Abrams’ pleural biopsy include site pain
(1–15%), pneumothorax (3–15%), vasovagal reaction (1–5%),
haemothorax (<2%), site haematoma (<1%), transient fever
(<1%) and, very rarely, death secondary to haemorrhage. If a
pneumothorax is caused, only 1% require chest
drainage.69 70 72–75
7.1.1 Blind percutaneous pleural biopsies
• Image guided cutting needle biopsies have a higher
yield for malignancy than standard Abrams’ needle
pleural biopsy.
The contrast enhanced thoracic CT scan of a patient with a
pleural effusion will often show a focal area of abnormal
pleura. An image guided cutting needle biopsy allows that
focal area of abnormality to be biopsied. It has a higher yield
than that of blind pleural biopsy in the diagnosis of
malignancy.76 This technique is particularly useful in patients
who are unsuitable for thoracoscopy.
Pleural malignant deposits tend to predominate close to the
midline and diaphragm, which are areas best avoided when
performing an Abrams’ biopsy. However, it is possible to take
biopsy specimens safely from these anatomical regions under
radiological imaging.76–78 In a recent prospective study 33
patients with a pleural effusion and pleural thickening, demonstrated on contract enhanced CT scanning, underwent percutaneous image guided pleural biopsy. Correct histological
• When using an Abrams’ needle, at least four biopsy
specimens 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 et
al66 compared these two needles in a small randomised study
of 24 patients; the diagnostic yield was similar but samples
were larger with an Abrams’ needle. The yield compared with
pleural fluid cytology alone is increased by only 7–27% for
malignancy.40–42 At least four samples need to be taken to optimise diagnostic accuracy,67 and these should be taken from
one site as dual biopsy sites do not increase positivity.68 The
biopsy 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 examinations performed between 1958 and 1985 (published in 14
papers) showed a diagnostic rate of 75% for tuberculosis and
57% for carcinoma.69 In tuberculous effusions, when fluid
7.1.2 Image guided cutting needle pleural biopsies
• When obtaining biopsies from focal areas of pleural
nodularity shown on contrast enhanced CT scans,
image guidance should be used. [C]
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Maskell, Butland
diagnosis was made in 21 of 24 patients (sensitivity 88%, specificity 100%) including 13 of 14 patients with mesothelioma
(sensitivity 93%).77 In a larger retrospective review of image
guided pleural biopsy in one department by a single
radiologist, 18 of 21 mesothelioma cases were correctly identified (sensitivity 86%, specificity 100%).78 The only published
complications to date are local haematoma and minor haemoptysis.
7.2 Thoracoscopy
• Thoracoscopy should be considered when less invasive 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 who underwent thoracoscopy over a 5 year period and
showed 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 negative pleural cytological specimens. A similar sensitivity for
malignant disease was described by Page80 in 121 patients with
undiagnosed effusion.
In addition to obtaining a tissue diagnosis, several litres of
fluid can be removed during the procedure and the
opportunity is also provided for talc pleurodesis. Thoracoscopy
may 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 vessel trauma.81 In a series of 566 examinations by Viskum and
Enk82 the most common side effect was subcutaneous emphysema (6.9%), with cardiac dysrhythmia occurring in 0.35%,
one air embolism, and no deaths.
7.3 Bronchoscopy
• Routine diagnostic bronchoscopy should not be performed for undiagnosed pleural effusion. [C]
• Bronchoscopy should be considered if there is
haemoptysis or clinical features suggestive of bronchial obstruction. [C]
Heaton and Roberts83 reviewed the case records of 32 patients
who had bronchoscopy for undiagnosed pleural effusion. In
only six did it yield a diagnosis and in four of these the diagnosis was also established by less invasive means. The other
two had radiographic abnormalities suggestive of bronchial
neoplasm. Upham et al84 studied 245 patients over 2 years and
Feinsilver et al85 studied 70. Both also found positive yields of
<5% in patients with a pleural effusion, but no haemoptysis or
pulmonary abnormality on the chest radiograph. Chang et al86
performed bronchoscopy, thoracentesis, and pleural biopsy on
140 consecutive patients with pleural effusion. In the patient
group with an isolated pleural effusion, with no haemoptysis
or pulmonary abnormality on the chest radiograph, the yield
from bronchoscopy was only 16% whereas pleural investigation yielded a positive diagnosis in 61%. If bronchoscopy is
deemed necessary, it should be performed after pleural drainage in order to perform adequate bronchoscopy without
extrinsic airway compression by pleural fluid.
Table 3
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Box 6 Causes of chylothorax and pseudochylothorax
Chylothorax
• Neoplasm: lymphoma, metastatic carcinoma
• Trauma: operative, penetrating injuries
• Miscellaneous: tuberculosis, sarcoidosis, lymphangioleiomyomatosis, cirrhosis, obstruction of central veins, amyloidosis
Pseudochylothorax
• Tuberculosis
• Rheumatoid arthritis
• Poorly treated empyema
In summary, bronchoscopy has a limited role in patients
with an undiagnosed pleural effusion. It should be reserved
for patients whose radiology suggests the presence of a mass,
loss of volume or when there is a history of haemoptysis or
possible aspiration of a foreign body.
8 SPECIAL TESTS
8.1 Chylothorax and pseudochylothorax
• If a chylothorax or pseudochylothorax is suspected,
pleural fluid should be sent for measurement of triglyceride and cholesterol levels and the laboratory
asked to look for the presence of cholesterol crystals
and chylomicrons. [C]
True chylous effusions result from disruption of the thoracic
duct or its tributaries. This leads to the presence of chyle in the
pleural space. Approximately 50% are due to malignancy
(particularly lymphoma), 25% trauma (especially during surgery), and the rest are miscellaneous causes such as tuberculosis, sarcoidosis, and amyloidosis (box 6).87 88
Chylothorax must be distinguished from pseudochylothorax or “cholesterol pleurisy” which results from the
accumulation of cholesterol crystals in a long standing pleural
effusion. In these cases the pleura is usually markedly
thickened and fibrotic.89 In the past, the most common causes
of a pseudochylous effusion were tuberculosis and artificial
pneumothorax. Chronic rheumatoid pleurisy is now the usual
cause.90 91
Chylothorax and pseudochylothorax can be discriminated
by lipid analysis of the fluid. A true chylothorax will usually
have a high triglyceride level, usually >1.24 mmol/l (110 mg/
dl), and can usually be excluded if the triglyceride level is
<0.56 mmol/l (50 mg/dl). The biochemistry laboratory should
be asked to look for the presence of chylomicrons between
these values. In a pseudochylothorax the cholesterol 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 confused with chylothorax. They can be distinguished by bench
centrifugation which leaves a clear supernatant in empyema
as the cell debris is separated. The chylous effusion remains
milky.
Laboratory differentiation of chylothorax and pseudochylothorax
Feature
Pseudochylothorax
Chylothorax
Triglycerides
Cholesterol
Cholesterol crystals
Chylomicrons
<0.56 mmol/l (50 mg/dl)
>5.18 mmol/l (200 mg/dl)
Often present
Absent
>1.24 mmol/l (110 mg/dl)
<5.18 mmol/l (200 mg/dl)
Absent
Present
BTS guidelines for the investigation of a unilateral pleural effusion in adults
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8.2 Urinothorax
• If urinothorax is suspected, the pleural fluid creatinine level should be measured and will be higher
than 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 the
same 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 pleural
fluid creatinine level is greater than the serum creatinine level.
The pleural fluid is a transudate and has a low pH.95 96
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 screening test.30 80% of rheumatoid pleural effusions have a pleural
fluid glucose to serum ratio of <0.5 and a pH <7.30.109 110
However, in acute rheumatoid pleurisy the glucose level and
pH may by normal.107 Measurement of C4 complement in
pleural fluid may be of additional help, with levels below
0.04 g/l in all cases of rheumatoid pleural disease and in only
two of 118 controls reported in one study.108 Rheumatoid factor can be measured on the pleural fluid and often has a titre
of >1:320. However, it can be present in effusions of other
aetiology and often mirrors the serum value, adding little
diagnostically.108 111
8.3 Tuberculous pleurisy
• When pleural biopsies are taken, they should be sent
for both histological examination and culture to
improve the diagnostic sensitivity for tuberculosis.
[B]
8.6.2 Systemic lupus erythematosus
Smears for acid fast bacilli are only positive in 10–20% of
tuberculous effusions and are only 25–50% 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 tends
to be higher with tuberculosis than in other exudates.100–102
However, ADA levels are also raised in empyema, rheumatoid
pleurisy, and malignancy, which makes the test less useful in
countries with a low prevalence of tuberculosis. Importantly,
ADA levels may not be raised if the patient has HIV and
tuberculosis.103
8.4 Pleural effusion due to pulmonary embolism
• There are no specific pleural fluid characteristics to
distinguish 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 22 A pleural fluid red blood
cell count of more than 100 000/mm3 is suggestive of
malignancy, pulmonary infarction, or trauma.9 Lower counts
are unhelpful.3 Effusions associated with pulmonary embolism have no specific characteristics and the diagnosis should
therefore be pursued on clinical grounds with the physician
retaining a high index of suspicion for the diagnosis.22
8.5 Benign asbestos pleural effusion
Benign asbestos pleural effusions are commonly diagnosed in
the 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 and
asymptomatic, often with pleural fluid which is
haemorrhagic.105 106 There is a propensity for the effusion to
resolve within 6 months, leaving behind residual diffuse pleural thickening.105 106 As there are no definitive tests, the
diagnosis can only be made with certainty after a prolonged
period of follow up.
8.6 Connective tissue diseases
8.6.1 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 an
effusion if the glucose level in the fluid is above
1.6 mmol/l (29 mg/dl).
Pleural involvement occurs in 5% of patients with rheumatoid
arthritis.107 The majority of patients with rheumatoid pleural
effusions 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
• The pleural fluid ANA level should not be measured
as it mirrors serum levels and is therefore unhelpful.
[C]
Up to 50% of patients with systemic lupus erythematosus
(SLE) will have pleural disease at some time in the course of
their disease.107 The presence of LE cells in pleural fluid is
diagnostic of SLE.107 112 Khare et al111 measured ANA levels in 82
consecutive pleural effusions. Six of the eight samples
collected from patients with SLE were ANA positive with a
homogenous staining pattern; the two effusions that were
negative for ANA had other reasons for their effusions
(pulmonary embolism and left ventricular failure). However,
eight (10%) of the effusions where the patients had no clinical
evidence of SLE were ANA positive. In five of these eight
patients the underlying cause of the effusion was malignancy.
Other studies have shown similar results and, as the pleural
ANA levels often mirror serum levels, the test is of limited
diagnostic value.108 112 113
8.7 Pleural effusions in HIV infection
• In patients with HIV infection, the differential
diagnosis of pleural effusion is wide and differs from
the immunocompetent patient.
A pleural effusion is seen in 7–27% of hospitalised patients
with HIV infection. Its three leading causes are Kaposi’s
sarcoma, parapneumonic effusions, and tuberculosis.114 In one
prospective study of 58 consecutive patients with HIV
infection and radiographic evidence of a pleural effusion, the
causes of the effusion were Kaposi’s sarcoma in one third of
the cases, parapneumonic effusion in 28%, tuberculosis in
14%, Pneumocystis carinii pneumonia in 10%, and lymphoma in
a further 7%.115
In a large prospective series of 599 HIV infected patients
over 3 years, 160 had a pleural effusion during an inpatient
admission; 65% were small effusions, 23% moderate, and 13%
large. In this series the most common cause was bacterial
pneumonia and the overall in-hospital mortality was high at
10%.116
9 MANAGEMENT OF PERSISTENT UNDIAGNOSED
PLEURAL EFFUSION
• In persistently undiagnosed effusions the possibility
of pulmonary embolism and tuberculosis should be
reconsidered since these disorders are amenable to
specific treatment. [C]
• Undiagnosed pleural malignancy proves to be the
cause of many “undiagnosed” effusions with sustained observation.
The cause of the pleural effusion is undetermined after
repeated cytology and pleural biopsy in around 15% of cases.39
It is sensible to reconsider diagnoses with a specific
treatment—for example, tuberculosis, pulmonary embolism,
fungal infection.87 A tuberculin skin test is positive in about
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ii16
Audit points
• The gross appearance of the pleural fluid and its odour
should always be recorded.
• Pleural fluid pH should be performed in every case of suspected 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 diagnostic yield.
• Pleural biopsy specimens should be placed in both saline
and formalin and sent for histological examination and culture.
• Diagnostic bronchoscopy is not indicated in the assessment
of an undiagnosed effusion unless the patient has haemoptysis or features suggestive of bronchial obstruction.
70% of patients with tuberculous pleurisy and the combination 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 embolism
should 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’ affiliations
N A Maskell, Oxford Centre for Respiratory Medicine, Churchill Hospital
Site, Oxford Radcliffe Hospital, Headington, Oxford OX3 7LJ, UK
R J A Butland, Department of Thoracic Medicine, Gloucestershire Royal
Hospital, Gloucester GL1 3NN, UK
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and other diseases. Thorax 1982;37:354–61. [IV]
109 Hunder GG, McDuffie FC, Huston KA, et al. Pleural fluid complement,
complement conversion, and immune complexes in immunologic and non
immunologic diseases. J Lab Clin Med 1977;90:971–80. [IV]
110 Good JT Jr, King TE, Antony VB, et al. Lupus pleuritis. Clinical features
and pleural fluid characteristics with special reference to pleural fluid
antinuclear antibodies. Chest 1983;84:714–8. [IV]
111 Khare V, Baethge B, Lang S, et al. Antinuclear antibodies in pleural
fluid. Chest 1994;106:866–71. [III]
112 Salomaa ER, Viander M, Saaresranta T, et al. Complement components
and their activation products in pleural fluid. Chest 1998;114:723–30.
[III]
113 Chandrasekhar AJ. Antibody deposition in the pleura: a finding in
drug-induced lupus. J Allergy Clin Immunol 1978;61:399–402. [IV]
114 Afessa B. Pleural effusions and pneumothoraces in AIDS. Curr Opin Pulm
Med 2001;7:202–9. [IV]
115 Miller RF, Howling SJ, Reid AJ, et al. Pleural effusions in patients with
AIDS. Sex Transm Infect 2000;76:122–5. [IIb]
116 Afessa B. Pleural effusion and pneumothorax in hospitalized patients
with HIV infection: the pulmonary complications, ICU support, and
prognostic factors of hospitalized patients with HIV (PIP) study. Chest
2000;117:1031–7. [III]
www.thoraxjnl.com
ii18
BTS guidelines for the management of pleural infection
C W H Davies, F V Gleeson, R J O Davies, on behalf of the BTS Pleural Disease Group,
a subgroup of the BTS Standards of Care Committee
.............................................................................................................................
Thorax 2003;58(Suppl II):ii18–ii28
T
here is great variation worldwide in the management of patients with pleural infection,
and approaches differ between physicians.1–14
In the UK up to 40% of empyema patients come to
surgery due to failed catheter drainage4 and, overall, 20% of patients with empyema die.4 The process of rapid evaluation and therapeutic intervention appears to reduce morbidity and mortality, as
well as health care costs.
This paper presents the results of a peer
reviewed systematic literature review, combined
with expert opinion, of the preferred management of pleural infection. The clinical guidelines
generated from this process are shown in fig 1.
The guidelines are aimed predominantly at physicians involved in general and respiratory medicine, and specifically do not cover in detail the
complex areas of surgical management or the
management of post pneumonectomy empyema.
1 HISTORICAL PERSPECTIVE,
PATHOPHYSIOLOGY AND
BACTERIOLOGY OF PLEURAL INFECTION
This section provides background information for
reference, interest, and to set the management
guidelines in context.
See end of article for
authors’ affiliations
.......................
Correspondence to:
Dr R J O Davies, Oxford
Centre for Respiratory
Medicine, Churchill
Hospital Site, Oxford
Radcliffe Hospital,
Headington, Oxford
OX3 7LJ, UK;
robert.davies@
ndm.ox.ac.uk
.......................
www.thoraxjnl.com
1.1 Historical perspective
Pleural infection was first described by Hippocrates in 500BC. Open thoracic drainage was the only
treatment for this disorder until the 19th century
when closed chest tube drainage was first
described but not adopted.15 This technique
became widely practised during an influenza epidemic in 1917–19 when open surgical drainage
was associated with a mortality rate of up to
70%.16 This high mortality was probably due to
respiratory failure produced by the large open
pneumothorax left by open drainage.16 This was
particularly true of Streptococcus haemolyticus infections which produce streptokinase and probably
reduce adhesion formation.16 A military commission investigated this high mortality rate and
produced recommendations that remain the basis
for treatment today. They advocated adequate pus
drainage with a closed chest tube, avoidance of
early open drainage, obliteration of the pleural
space, and proper nutritional support. These
changes reduced the mortality rate to 3.4% during
the later stages of the epidemic.
The introduction of antibiotics both reduced
the incidence of empyema and changed its bacteriology. Before antibiotics 60–70% of cases were
caused by Streptococcus pneumoniae, which now
accounts for about 10% of culture positive cases.17
The prevalence of Staphylococcus aureus rose and
the development of staphylococcal resistance in
the 1950s increased complications and
mortality.18 19 More recently, the reported prevalence of anaerobic infections14 18 20 and Gram
negative organisms14 20 has risen. Intrapleural
fibrinolytic therapy was first introduced in
1949,21 but the impure agents used caused adverse
reactions. Most recently, thoracoscopic surgery
has introduced the early use of video assisted
thoracoscopic (VATS) pleural debridement.9
1.2 Pathophysiology of pleural infection
Pneumonia leads to about 50 000 hospital admissions each year in the UK.22 Up to 57% of patients
with pneumonia develop pleural fluid23 24 and
there are about 60 000 cases of pleural infection
in the USA per year.3 A significant proportion of
cases are related to community and hospital
acquired pneumonia, or are secondary to iatrogenic causes. Pleural infection may also develop
without evidence of pneumonia—so called primary empyema. Most forms of pleural infection
represent a progressive process that transforms a
fluid self-resolving parapneumonic pleural effusion into a complicated multiloculated fibrotic
and purulent collection which significantly impairs respiratory reserve and is only amenable to
surgical drainage.
1.3 Normal pleural fluid physiology
In health, the volume of pleural fluid in humans
is small (<1 ml), forming a film about 10 µl thick
between the visceral and parietal pleural
surfaces.25 Pleural fluid contains protein at concentrations similar to the interstitial fluid, a small
number of cells (predominantly mesothelial cells,
macrophages and lymphocytes), and some large
molecular weight proteins such as lactate dehydrogenase (LDH). Compared with serum, pleural
fluid in health also contains higher levels of
bicarbonate, lower levels of sodium, and similar
levels of glucose.26 These parameters change when
disease processes affecting the adjacent lung or
vascular tissue activate an immune response.
Water and small molecules pass freely between
mesothelial cells, while larger particles may be
transported by cytoplasmic transport mechanisms or via the pleurolymphatic communication.
The pleurolymphatic communication is poorly
documented but probably consists of a series of
stomas in selected areas of pleura overlying
connective tissue and a series of dilated lymphatic
channels with regulatory valves.25
1.4 Pleural effusion development with
pneumonia
The development of empyema in association with
pneumonia is a progressive process that moves
from a simple exudate to a fibrinopurulent stage
and later to an organising stage with scar tissue
formation.27 The stage when the pleural fluid is a
straightforward exudate is often called a “simple
parapneumonic effusion”. The early fibrinopurulent stage when the pleural fluid has developed
BTS guidelines for the management of pleural infection
ii19
Diagnostic algorithm for the management of patients with pleural infection
History, examination and chest radiograph
Pleural effusion and evidence
of infection?
YES
Antibiotics (section 2.3, 2.8)
Failed sampling?
Diagnostic fluid sampling
Small effusion?
YES
Ultrasound scan with
Section
sampling of any fluid
2.4
Pus?
NO
Pleural fluid pH
and microbiology
Section 2.5
Gram stain and/or
NO
Observe unless
culture positive
clinical indication
and/or pH <7.2
for chest tube
YES
YES
Involve respiratory physician
Insert chest tube
Section 2.7
Section 2.9
Is the
patient better?
YES
(fluid drained and
sepsis improved)
NO
1. Check tube position on chest radiograph
2. Consider CT scan for residual collection
Sections 2.10, 2.11, 2.12
3. Consider intrapleural fibrinolytics
4. Consider change to large bore chest tube
Is the
patient better at 5–7 days?
YES
(fluid drained and
sepsis improved)
NO
1. Review diagnosis
2. Consult with cardiothoracic surgeon
Section 2.15
Remove tube
Figure 1 Flow diagram describing the management of pleural infection.
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ii20
Davies, Gleeson, Davies, et al
Table 1
Characteristics of parapneumonic pleural effusions
Stages
Macroscopic appearance
Pleural fluid characteristics
Comments
Simple parapneumonic
Clear fluid
Will usually resolve with antibiotics alone.
Perform chest tube drainage for symptom relief if
required
Complicated parapneumonic
Clear fluid or cloudy/turbid
Empyema
Frank pus
pH >7.2
LDH <1000 IU/l
Glucose >2.2 mmol/l
No organisms on culture or Gram stain
pH <7.2
LDH >1000 IU/l
Glucose >2.2 mmol/l
May be positive Gram stain/culture
May be positive Gram stain/culture
Requires chest tube drainage
Requires chest tube drainage
No additional biochemical tests necessary on
pleural fluid (do not measure pH)
LDH=lactate dehydrogenase.
features of infection but is not yet overtly purulent is termed a
“complicated parapneumonic effusion”. Frank pus is termed
“empyema”. The features of these three stages are summarised in table 1.
In the early exudative stage there is fluid movement into the
pleural space due to increased capillary vascular permeability,
accompanied by the production of proinflammatory
cytokines.28 These produce active changes in the pleural mesothelial cells to facilitate fluid entry into the pleural cavity.
Initially the fluid is a free flowing exudate characterised by a
low white cell count, a lactate dehydrogenase (LDH) level less
than half that in the serum, normal pH and glucose levels, and
does not contain bacterial organisms.6 24 29–32 Treatment with
antibiotics at this stage is likely to be adequate and most effusions of this type do not require chest tube drainage.6 24 32
1.5 Development of complicated parapneumonic
effusion and empyema
Parapneumonic effusions in the exudative stage progress to
the fibrinopurulent stage with increasing fluid accumulation
and bacterial invasion across the damaged endothelium. Bacterial invasion accelerates the immune reaction, promoting
further migration of neutrophils and also activation of the
coagulation cascade leading to increased procoagulant and
depressed fibrinolytic activity.28 33 This favours fibrin deposition and allows septations to form within the fluid. Neutrophil
phagocytosis and bacterial death fuel the inflammatory process by the release of more bacteria cell wall derived fragments
and proteases.28 This combination of events leads to increased
lactic acid production, associated with a fall in pleural fluid
pH,34 accompanied by increased glucose metabolism and a rise
in LDH levels due to leucocyte death leading to the characteristic biochemical features of a fibrinopurulent collection (pH
<7.20, glucose <2.2 mmol/l, LDH >1000 IU/l).
The organising stage follows with the proliferation of
fibroblasts.28 As a solid fibrous pleural peel replaces the soft
fibrin, the re-expansion of lung is prevented, impairing lung
function and creating a persistent pleural space with continuing potential for infection.
1.6 Bacteriology of pleural infection
Currently, aerobic organisms are those most frequently identified from empyemas. Gram positive organisms from the streptococcal species, including the S milleri group of organisms,
and
Staphylococcus
aureus
are
most
commonly
found.10 11 13 20 35–47 Most patients with S aureus have postoperative or nosocomial empyemas or are immunocompromised.42 S
aureus is seen frequently in patients following trauma and
surgery.38 45 Gram negative organisms are also the most
commonly found aerobic bacteria in pleural infection, including Escherichia coli, Pseudomonas spp, Haemophilus influenzae,
and Klebsiella spp.11 13 20 36 37 40 42–44 46–48 These organisms are commonly part of mixed growths with other Gram negative
organisms or with anaerobes11 20 38 39 41–45 and rarely occur in
isolation.
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The frequency of anaerobic isolates is rising and anaerobes
may be present in up to 76% of cases.18 36 37 49 However, most
series report anaerobes in 12–34% of positive pleural fluid
cultures.4 10 11 13 20 39 41 43 44 47 Anaerobes may cause empyema
without other aerobic co-pathogens in about 14% of culture
positive cases.10 18 20 41 44 Infections with anaerobes are more
likely to have an insidious clinical onset,36 with less fever,
greater weight loss, and are more common following possible
aspiration pneumonia and with poor dental hygiene.36
2 IDENTIFICATION AND RADIOLOGICAL
ASSESSMENT OF PNEUMONIA ASSOCIATED
PLEURAL EFFUSION
This section presents the detail of the literature evidence and
expert opinion behind the guideline presented in fig 1.
2.1 Identification
A pleural effusion may be obvious on the chest radiograph50
and the co-existence of pulmonary infiltrates and fluid should
alert the clinician to the possibility of a parapneumonic
collection. Empyema should be suspected in patients who are
failing to respond to appropriate antibiotic therapy. Lateral
chest radiographs may confirm pleural fluid not suspected on
the posteroanterior chest radiograph.24 Ultrasound scanning,
which is now readily available, is the preferred investigation
and enables exact location of any fluid collection and allows
guided diagnostic aspiration if required.50 51
Occasionally, pleural sepsis is caused by oesophageal
rupture and this diagnosis should be suspected in patients
who develop a pleural effusion soon after significant retching
or vomiting. Oesophageal imaging and the detection of an
oesophageal leak should prompt immediate referral to a
surgeon with expertise in the management of oesophageal
rupture.43
2.2 Radiological assessment
Ultrasound may help to identify exudative pleural effusions;
in a study of 320 cases of pleural effusion52 all echogenic effusions were caused by exudates and homogeneous echogenic
effusions were due to either empyema or haemorrhage. In a
review of both ultrasound and computed tomographic (CT)
appearances in a group of patients with parapneumonic effusion requiring drainage, the appearances at ultrasound
(septations, echogenicity, fig 2) did not correlate with the
length of history, presence or absence of purulence, or the biochemical staging of pleural infection, but pleural thickness on
contrast enhanced CT scanning was greater in those with
frankly purulent effusions.53
In cases of diagnostic difficulty, contrast enhanced CT scanning may help to differentiate pleural empyema from a parenchymal lung abscess. Empyemas are usually lenticular in
shape and compress the lung parenchyma, while lung
abscesses often have an indistinct boundary between the lung
parenchyma and collection.54 55 The “split pleura” sign, caused
BTS guidelines for the management of pleural infection
ii21
Figure 3 Typical contrast enhanced CT appearances of pleural
empyema. The image shows a multiloculated pleural collection
forming separate lenticular pleural opacities. The “split pleura sign”
with enhancing pleural tissue visible on both the visceral and parietal
pleural surfaces is shown. Note that the septation within individual
locules that is seen on ultrasound (fig 2A) is not seen on CT
scanning.
Figure 2 (A) Typical pleural ultrasound appearance of pleural
infection and (B) the macroscopic appearances of pleural fibrinous
septation. The pleural ultrasound image (A) shows the pleural space
divided into a multi-septated collection with varying echogenic
appearances within the divided fluid indicating varying degrees of
fluid purulence. The pleural photograph (B) is taken at thoracoscopy
and shows the macroscopic appearance of fibrinous pleural
septation, in this case an infected malignant pleural effusion.
by enhancement of both parietal and visceral pleural surfaces
(fig 3), and their separation in empyema is characteristic of a
pleural collection. Pleural thickening is seen in 86–100% of
empyemas56–58 and 56% of exudative parapneumonic
effusions.56 The absence of pleural thickening indicates a likely
simple parapneumonic effusion.56 In pleural infection there is
pleural enhancement with CT contrast studies,57 and the
extrapleural subcostal fat is of increased attenuation.55–58
2.3 Which patients with a parapneumonic effusion
need diagnostic pleural fluid sampling?
• All patients with a pleural effusion in association
with sepsis or a pneumonic illness require diagnostic
pleural fluid sampling. [C]
It is currently impossible to clinically differentiate patients
with a complicated parapneumonic effusion requiring chest
tube drainage from those with a simple effusion that may
resolve with antibiotics alone, and there are no specific data
relating to which patients with a parapneumonic effusion can
be managed without diagnostic pleural fluid sampling. There
are no differences in age, white cell count, peak temperature,
incidence of pleural pain, or the degree of radiological
infiltrate between those requiring chest tube drainage for
resolution of symptoms and those who may resolve with antibiotics alone.24 In patients with pneumococcal pneumonia the
development of parapneumonic effusions may be associated
with a longer duration of symptoms and the presence of
bacteraemia,23 but the majority of these patients will have a
“simple parapneumonic effusion” and will not require chest
tube drainage. Similarly, there are no reliable clinical59 60 or
radiological59 characteristics that will predict which patients
with pleural infection will come to surgery.
Pleural fluid characteristics remain the most reliable
diagnostic test to guide management6 24 29 32 60–63 and diagnostic
pleural fluid sampling is therefore recommended in all
patients with a pleural effusion in association with a
pneumonic illness or recent chest trauma or surgery. Patients
in an intensive care (ICU) setting frequently develop pleural
effusions that are not caused by pleural infection.64 It is probably safe to observe such patients with hypoalbuminaemia,
heart failure, or atelectasis who are at low risk of infection
while treating the underlying condition.64 Pleural fluid should
be sampled if there are features of sepsis, possibly under
ultrasound guidance if patients are receiving positive pressure
ventilation.
2.4 Patients with a small pleural effusion or who have
failed diagnostic pleural fluid sampling
• In the event of a small effusion or a failed previous
attempt at pleural fluid sampling, an ultrasound scan
and image guided fluid sampling is recommended.
[C]
• Pleural effusions with maximal thickness <10 mm
on ultrasound scanning can be observed, with pleural
fluid sampling if the effusion enlarges. [C]
In the event of a small effusion, failure of an attempt to gather
a pleural fluid sample, or an inexperienced operator, an ultrasound scan and image guided pleural fluid sampling is simple
and will reduce patient discomfort.50 Small effusions of
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ii22
<10 mm thickness on a decubitus chest radiograph will usually resolve with antibiotics alone.24 32 As ultrasound is used in
preference to decubitus chest radiography in the UK, it seems
reasonable to observe any effusion where maximal thickness
is <10 mm on ultrasound scanning. An increase in the size of
the effusion should warrant re-evaluation and a diagnostic
pleural fluid sample if clinically indicated.
2.5 When to use chest tube drainage in pleural
infection
• Patients with frankly purulent or turbid/cloudy pleural fluid on sampling should receive prompt pleural
space chest tube drainage. [B]
The presence of frankly purulent or turbid/cloudy fluid on
pleural aspiration indicates the need for prompt chest tube
drainage.24 32 62 63 Purulent fluid is more frequent in patients
who fail chest tube drainage and require surgery or in those
who die.59
• The presence of organisms identified by Gram stain
or culture from non-purulent pleural fluid samples
indicates that pleural infection is established and
should lead to prompt chest tube drainage. [B]
The presence of organisms identified by positive Gram
staining indicates bacterial invasion and implies progression
from a simple effusion into empyema and hence the need for
chest tube drainage.24 32 62 63 Some frankly purulent or culture
positive parapneumonic effusions due to pneumococcus may
resolve without chest tube drainage,23 60 but clinicians should
be aware of the common co-existence of anaerobes not readily
cultured in the laboratory before making a therapeutic
decision not to drain a frank empyema.
• Pleural fluid pH should be assessed in all nonpurulent, possibly infected effusions. [B]
• pH <7.2 indicates chest tube drainage is required. [B]
• Parapneumonic effusions that do not fulfil these criteria for chest tube drainage should be treated with
antibiotics alone provided clinical progress is good.
[B]
• Poor clinical progress during treatment with antibiotics alone should lead to prompt patient review and
probably chest tube drainage. [B]
Parapneumonic pleural effusions are inflammatory exudates
dominated by polymorphonuclear leucocytes. The absolute
protein values are of no value in determining the likelihood of
spontaneous resolution of the effusion or chest tube drainage
requirements.6 24 31 60 The pleural fluid leucocyte count shows a
wide variation in values between simple effusions and frankly
purulent empyemas,32 and a predominance of lymphocytes in
an exudate should raise the possibility of malignancy or
tuberculosis. Some non-purulent collections will show biochemical evidence of infection and are likely to need chest
tube drainage for resolution of sepsis.24 29–32 34 61–63 The development of a pleural fluid acidosis associated with a rising pleural level of LDH and a falling glucose level are characteristic
and constitute the biochemical criteria for pleural
infection.24 32 63
These biochemical criteria have been reviewed in a systematic meta-analysis of the data justifying their use.63 This report
showed that pleural fluid pH is the most useful index predicting the need for chest tube drainage and that the pleural LDH
and glucose levels did not further improve diagnostic clarity. A
pleural pH of about 7.2 was identified as best indicating the
need for pleural drainage while previous studies had favoured
a lower action threshold (∼7.00).65 The increased mortality
associated with older age and co-morbid disease should be an
indication for more aggressive management and earlier chest
tube drainage.63
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Davies, Gleeson, Davies, et al
Pleural fluid for pH should be collected anaerobically with
heparin and then measured in a blood gas analyser. It is not
advisable, and should not be necessary, to put frank pus
through a blood gas analyser as this already indicates a need
for chest tube drainage of the effusion. However, where there
is uncertainty whether a turbid/cloudy fluid is infected, pH
can be measured safely using a blood gas analyser. Extensive
clinical experience of this technique, particularly in the US,
has shown that it does not damage the blood gas analyser.
Measurement of pleural fluid pH is unreliable when analysed
by pH litmus paper or a pH meter, and these should not be
considered as acceptable alternatives to a blood gas
analyser.66 67 Physicians should be aware that lignocaine is
acidic and can depress measured pH if given in large volumes
or left in the same syringe used for local anaesthetic
administration.68
Parapneumonic pleural effusions that do not fulfil these
criteria for chest tube drainage may be observed and are likely
to resolve with antibiotics alone. However, some patients with
an initial pleural pH of >7.2 will fail to resolve their sepsis
syndrome and will require surgery despite chest tube
drainage.59 These occasional cases confirm that, while pleural
pH is specific in predicting the need for pleural drainage, it is
less than 100% sensitive59 and does not accurately predict
eventual need for surgery.59 62 Unsatisfactory clinical progress
therefore indicates the need for repeated pleural fluid
sampling and possible chest tube drainage. When needle aspiration is straightforward, it may occasionally be possible to
remove all the fluid at initial thoracocentesis. In some cases
the fluid will not then return and no further intervention will
be required.
2.6 Other indications for chest tube drainage
• Patients with a loculated pleural collection should
receive earlier chest tube drainage. [C]
• Large non-purulent effusions should be drained by
chest tube for symptomatic benefit. [C]
The presence of loculation on the chest radiograph or
ultrascan is associated with a poorer outcome and may be an
additional indication for early chest tube drainage.32 61 69 Larger
pleural collections (>40% of the hemithorax) may be more
likely to require surgery,4 69 and non-purulent effusions without acidosis can be drained with a chest tube if indicated for
symptomatic benefit.
2.7 Respiratory specialist
• A respiratory physician or thoracic surgeon should be
involved in the care of all patients requiring chest
tube drainage for a pleural infection. [C]
In view of the substantial mortality associated with pleural
infection, the small number of cases seen annually in a single
centre and the need for prompt effective treatment, it is
appropriate to focus the care of this disorder in specialist
hands. Delay to chest tube drainage of the pleural space is
probably associated with increased morbidity and duration of
hospital stay,5 10 13 38 59 70 71 and may lead to increased
mortality.38 Misdiagnosis, inappropriate antibiotics, and inappropriate chest tube placement have been cited as important
factors contributing to the progression of pleural infection.70
An appropriate physician requires the skills to identify
patients for surgery and experience in assessing thoracic surgical risk as well as expertise in managing the substantial
co-morbidity in these patients. A respiratory physician best
combines these skills as well as having the advantage of an
established liaison with a thoracic surgeon. In centres with
thoracic surgery immediately available, care may be under a
surgeon and a surgical opinion is appropriate after approximately 7 days in any patient not settling with drainage and
antibiotics.
BTS guidelines for the management of pleural infection
Table 2
ii23
Illustrative antibiotic regimens for the initial treatment of culture negative pleural infection
Origin of infection
Intravenous antibiotic treatment
Oral antibiotic treatment
Community acquired culture
negative pleural infection
Cefuroxime 1.5 g tds iv + metronidazole 400 mg tds orally or
500 mg tds iv
Benzyl penicillin 1.2 g qds iv + ciprofloxacin 400 mg bd iv
Meropenem 1 g tds iv + metronidazole 400 mg tds orally or
500 mg tds iv
Amoxycillin 1 g tds + clavulanic acid 125 mg
tds
Amoxycillin 1 g tds + metronidazole 400 mg tds
Clindamycin 300 mg qds
Hospital acquired culture negative
pleural infection
Piperacillin + tazobactam 4.5 g qds iv
Ceftazidime 2 g tds iv
Meropenem 1 g tds iv ± metronidazole 400 mg tds orally or 500
mg tds iv
Not applicable
No particular regimen is the single “ideal” choice. Drug doses should be appropriately adjusted in the presence of renal or hepatic failure.
2.8 Antibiotics
• All patients should receive antibiotics. [B]
• Where possible, antibiotics should be guided by bacterial culture results. [B]
• Where cultures are negative, antibiotics should cover
community acquired bacterial pathogens and
anaerobic organisms. [B]
• Hospital acquired empyema requires broader spectrum antibiotic cover. [B]
All patients should receive antibiotic therapy as soon as pleural infection is identified, and where possible, antibiotics
should be chosen based on the results of pleural fluid culture
and sensitivities. A significant proportion of both aerobes and
anaerobes isolated from pleuropulmonary infections may be
resistant to penicillin,18 72 73 but beta-lactams remain the drugs
of choice for pneumococcal74 and the S milleri group
infections.75 76 Both penicillins and cephalosporins show good
penetration of the pleural space,35 77 78 and there is no need to
administer antibiotics directly into the pleural space.
Aminoglycosides should be avoided as they have poor
penetration into the pleural space and may be inactive in the
presence of pleural fluid acidosis.35 79
In the absence of positive culture results, antibiotics should
be chosen to cover the likely organisms that may cause pleural
infection. There are a considerable number of reasonable drug
combinations and the chosen regimen should reflect whether
the infection was contracted in the community or in hospital.
The actual regimen choice should reflect local hospital policy.
In community acquired infection, empirical treatment with
a second generation cephalosporin (e.g. cefuroxime) or an
aminopenicillin (e.g. amoxycillin) will cover expected organisms such as Pneumococcus, Staphylococcus aureus, and Haemophilus influenzae.80 A beta-lactamase inhibitor or metronidazole
should also be given because of the frequent co-existence of
penicillin resistant aerobes and anaerobes.18 72 81 Clindamycin
can combine this spectrum into a single agent. Intravenous
benzyl penicillin combined with a quinolone also has an
appropriate spectrum and may be associated with a reduced
incidence of Clostridium difficile diarrhoea.
There is evidence for a probable synergistic role of
anaerobes with the S milleri group of organisms82 83 and
patients with these mixed infections have a higher mortality
from empyema.76 Patients with an allergy to penicillin can be
treated by clindamycin alone18 80 or in combination with a
cephalosporin.3 Chloramphenicol, carbapenems such as meropenem, third generation cephalosporins, and broad spectrum
antipseudomonal penicillins such as piperacillin also have
good anti-anaerobic activity and are alternative agents.73 84
Pleural effusions may occur in patients with Legionella
pneumonia and are usually self-resolving.85 Legionella has
rarely been reported as a cause of empyema86 and a macrolide
should only be added in suspected cases. Similarly, pleural
effusions may occur in 5–20% of patients with pneumonia due
to Mycoplasma pneumoniae,87 88 but these are usually small reac-
tive effusions. Most will resolve with suitable antibiotics such
as a macrolide, but diagnostic pleural fluid sampling should be
performed to ensure that a complicated parapneumonic effusion is not present. In all cases antibiotic regimens should be
adjusted according to the results of subsequent culture results
(while remembering that anaerobic pathogens are difficult to
grow).
In hospital acquired empyema, usually secondary to
nosocomial pneumonia, trauma or surgery, the antibiotics
should be chosen to treat both Gram positive and Gram negative aerobes and also anaerobes. Postoperative and trauma
related empyema requires antistaphylococcal cover. Recommended antibiotics include antipseudomonal penicillins
(piperacillin-tazobactam and ticarcillin-clavulinic acid),
carbapenems
(meropenem),
or
third
generation
cephalosporins.35
The duration of treatment for pleural infection has not been
assessed in detailed clinical trials and remains controversial.
Antibiotics are often continued for several weeks, based on the
experience of clinicians managing this and other purulent
pulmonary diseases such as lung abscess3 18 72 but, providing
there is adequate pleural drainage, long term treatment may
not be necessary. Treatment for about 3 weeks is probably
appropriate. When prolonged treatment is used, the antibiotic
regimen is usually changed to an oral combination after the
fever and sepsis syndrome has settled.
Suggested antibiotic regimens for the initial treatment of
culture negative community and hospital acquired pleural
infections are shown in table 2.
2.9 Chest tube drainage
• There is no consensus on the size of the optimal
chest tube for drainage.
• If a small bore flexible catheter is used, regular flushing and suction is recommended to avoid catheter
blockage. [C]
Chest tube drainage is usually performed in one of three ways:
tube insertion under radiological guidance, tube insertion
without radiological guidance, and tube insertion at time of
surgical debridement. Traditionally, the closed chest tube
drainage of pus from the pleural cavity has been via the insertion of a large bore chest tube, inserted without radiological
guidance. More recently, flexible small bore catheters which
seem less traumatic to insert and more comfortable for the
patient have been employed. These smaller catheters are usually inserted under ultrasound or CT guidance.
There are no controlled trials comparing the use of
traditional large bore chest tubes with smaller catheters and
no clinical consensus on the optimal choice. Most of the published data relate to the use of image guided small bore catheters and suggest these can have a good outcome as a primary
drainage procedure50 89 93–95 or as a rescue treatment when
larger tubes have failed.50 89–95 10–14 Fr catheters are popular in
these series and have a low complication rate.50 89 91–93 96 There is
www.thoraxjnl.com
ii24
also a substantial body of opinion that considers large bore
tubes to be more effective for draining thick pus, based on
clinical experience. Sound clinical trials are needed to clarify
the optimal size of chest tube.
There is no controlled evidence about optimal drain
management regarding issues such as drain flushing and
drain suction. In most of the studies with small bore catheters,
both catheter flushing and suction were used50 89–95 97 and regular flushing (30 ml saline every 6 hours via three-way tap) is
therefore recommended for small catheters. To ensure
reliability, trained nurses should ideally perform this task.
Flushing larger bore drains is technically more difficult as
these do not have three-way taps and disconnection for
irrigation might introduce secondary infection. There are no
studies to suggest any advantage from the regular flushing of
large drains and it is therefore not recommended routinely.
Suction (20 cm H2O) is employed in the belief it improves
drainage but there is no sound evidence or clinical consensus
on which to base specific guidelines in this area.98 99
2.10 Management of cessation of chest tube drainage
in the presence of a residual pleural fluid collection
• If the chest tube becomes blocked or pus is unable to
drain, it should be flushed with saline to ensure its
patency. If poor drainage persists, a chest radiograph
or CT scan should be performed to check drain position. [C]
In the event that the chest tube should become blocked or pus
is unable to drain, it may be flushed with 20–50 ml normal
saline to ensure its patency. If poor drainage persists, imaging
should be performed to check chest tube position and tube
distortion and to look for undrained locules. Kinks may occur
at the skin with smaller drains which can be repositioned and
redressed. A number of commercial dressings are now
available to secure small drains to reduce kinking and which
have a low fall out rate. If the chest tube is permanently
blocked, it should be removed and a further chest tube
inserted if indicated.
Contrast enhanced CT scanning is the most useful imaging
modality in patients failing chest tube drainage to provide
anatomical detail such as locules and to ensure accurate chest
tube placement. Pleural thickening seen on contrast enhanced
CT scanning represents a “fibrinous” peel, which may prevent
lung re-expansion despite adequate drainage of the pleural
space.100 Contrast enhanced CT scanning cannot accurately
differentiate early and late fibrinopurulent stage disease,57 and
pleural thickness on the CT scan does not appear to predict the
outcome from tube drainage.59 Pleural peel may resolve over
several weeks in patients spared surgery.101 Residual
calcification,57 thickening of extrapleural tissues,57 and pleural
scarring101 may persist long after empyema treatment. Both
ultrasound and chest radiography may also be useful in
patients failing to drain.
2.11 Intrapleural fibrinolytic drugs
• Intrapleural fibrinolytic drugs (streptokinase 250 000
IU twice daily for 3 days or urokinase 100 000 IU once
a day for 3 days) improve radiological outcome and
current best evidence recommends their use. [B] It is
not known if they reduce mortality and/or the need
for surgery and clinical trials are underway to
address this question.
• Patients who receive intrapleural streptokinase
should be given a streptokinase exposure card and
should receive urokinase or tissue plasminogen activator (TPA) for subsequent indications. [C]
Intrapleural fibrinolytic therapy was first used in 1949.21
The agents used initially were impure and produced side
effects due to immunological events such as fever, leucocytosis
www.thoraxjnl.com
Davies, Gleeson, Davies, et al
and general malaise,21 and these agents fell out of use. More
recently, intrapleural fibrinolytic drugs have been reassessed.
Several observational series suggest improved pleural drainage with these agents,21 102–128 and these reports have been supplemented by small controlled trials.110 129–132
There are four small randomised trials of intrapleural fibrinolytic agents. The first129 reported 24 patients randomised to
streptokinase or saline placebo. Pleural drainage was improved
on radiographic criteria. The study was not large enough to
address surgery rates, mortality or safety. The second study131
compared urokinase and a saline placebo in 31 patients with
pleural infection. Patients were randomised after failed chest
tube drainage alone. Successful pleural drainage was significantly more frequent in those receiving urokinase, but again
the study was not powered for mortality, surgery rates or
safety. The third study103 is currently only reported in abstract
form and included 128 patients with loculated parapneumonic pleural effusion randomised to receive either intrapleural urokinase, streptokinase, or control flushes. As with the
other studies,129 131 groups who received fibrinolytic therapy
drained more fluid and had improved radiology. The fourth
study is in children and shows that urokinase reduces hospital stay compared with placebo. Again it was not powered to
assess the main clinical end points of mortality and surgery
frequency.132
In these studies, drained pleural fluid volume is uninterpretable since intrapleural streptokinase increases pleural
fluid production.133 The current literature is therefore encouraging but does not establish benefit for the primary end points
of clinical interest: patient mortality, surgery rates, and
residual lung function. The Medical Research Council and
British Thoracic Society are currently recruiting to a multicentre study to assess definitively the efficacy of intrapleural
streptokinase.
Most reported adverse events due to intrapleural fibrinolytic agents are immunological and occur with intrapleural
streptokinase. Fever has been noted,103 115–117 134 but only in subjects receiving fibrinolytics for pneumonia associated pleural
infection where the varying fever of the primary illness makes
it difficult to quantify this effect reliably. Systemically administered streptokinase generates a systemic antibody response
that can neutralise later administration of streptokinase.135–142
It is not yet known whether intrapleurally administered fibrinolytic agents produce a similar response. In the absence of
such data it is advisable to manage patients as if they had
received their initial fibrinolytic systemically, with urokinase
or tissue plasminogen activator (TPA) being used for later
myocardial infarction or pulmonary embolism.
Two studies of small patient groups suggest that intrapleural streptokinase does not produce systemic fibrinolysis up to
a total cumulative dose of 1.5 million IU.119 There are isolated
reports of local pleural haemorrhage106 112 116 and systemic
bleeding118 associated with intrapleural fibrinolytic use. There
have also been reports of nose bleeds,116 pleural pain,109 116 121
and transient disorientation (without evidence of intracerebral bleeding on CT brain scan).109 Urokinase is non-antigenic
but may still cause acute reactions (due to immediate
hypersensitivity and histamine release) with fever124 and
cardiac arrhythmia.143 There is a report of adult respiratory
distress syndrome (ARDS) in a patient who received both
streptokinase and urokinase for empyema drainage.144 The
true incidence of these occasional but major side effects is not
known and will be clarified by the currently recruiting MRC/
BTS trial.
Streptokinase 250 000 IU daily,21 103–119 121 129 or 250 000 IU 12
hourly,119 or urokinase 100 000 U daily131 134 retained for 2–4
hours in the pleural space are the usual regimens. Their use
may be most beneficial in high risk patients of an older age or
with co-morbidity where surgery has a greater risk.
Recently, there has been interest in other intrapleural
agents including combination drugs consisting of streptokinase and streptodornase-α, DNase.145 146 In an experimental
BTS guidelines for the management of pleural infection
setting in which fluid viscosity was assessed, this combination
reduced the amount of non-liquefied material and therefore
viscosity compared with streptokinase alone.145 146 These in
vitro studies suggest that it is the DNA content of pus that
determines the viscosity and that, if it is effective, streptokinase may work predominantly by breaking down loculations
and not by changing pus viscosity. Clinical trials will be
required to assess whether DNase compounds are effective
adjuncts in pleural drainage, and their use in patients cannot
yet be recommended.
2.12 Persistent sepsis and pleural collection
• Patients with persistent sepsis and a residual pleural
collection should undergo further radiological imaging. [C]
In patients who do not respond to medical treatment and who
have sepsis in association with a persistent pleural collection,
the diagnosis should be reviewed and a further chest
radiograph performed. Thoracic CT scanning will identify
chest tube position, pleural thickening, and anatomy of the
effusion, and may also identify endobronchial obstruction of
the bronchi by malignancy147–150 or foreign body, and pathology
in the mediastinum when there is inadequate resolution of
pleural sepsis following drainage.
2.13 Bronchoscopy
• Bronchoscopy should only be performed in patients
where there is a high index of suspicion of bronchial
obstruction. [C]
The role of bronchoscopy in patients with empyema has not
been addressed specifically by any studies, but it is clear from
the BTS empyema series4 that British chest physicians
consider bronchoscopy an important investigation in patients
with pleural infection. In this series,4 43 of 119 patients (40%)
underwent bronchoscopy, usually to exclude a tumour predisposing to empyema; tumour was only found in five patients,
less than 4% of the total sample. Bronchoscopy is usually performed at the time of surgery by most thoracic surgeons, but
only a small number of these patients have obstructing
tumour predisposing to empyema.43 In view of the small
number of patients in whom bronchoscopy is helpful, it is only
recommended where there is a high index of suspicion for
bronchial obstruction. Features that should raise this suspicion include a mass or loss of volume on radiographic imaging
or a history of possible aspiration/inhalation.
2.14 Nutrition
• Clinicians should ensure adequate nutritional support commencing as soon as possible after pleural
infection is identified. [C]
Poor nutrition was identified during the First World War as
one of the important determinants of outcome from pleural
empyema,16 but is still sometimes overlooked. Patients with
empyema suffer the catabolic consequences of chronic
infection which may lead to further immunodeficiency and
slow recovery. Clinicians should provide adequate nutritional
support from the time the diagnosis is made. Hypoalbuminaemia is associated with a poor outcome from pleural
infection.4
2.15 Referral for surgical treatment
• Failure of chest tube drainage, antibiotics and
fibrinolytic drugs should prompt early discussion
with a thoracic surgeon. [C]
• Patients should be considered for surgical treatment
if they have persisting sepsis in association with a
persistent pleural collection, despite chest tube
drainage and antibiotics. [C]
ii25
Audit points
• Pleural fluid should be sampled for diagnostic purposes
within 24 hours in over 95% of cases of suspected pleural
infection.
• Pleural fluid pH should be measured with a blood gas analyser at the first diagnostic pleural fluid tap in all cases
unless the pleural fluid sample is visibly purulent.
• All pleural fluid samples assessed in a blood gas analyser
must be heparinised.
• All patients treated for pleural infection should receive
appropriate antibiotic treatment.
• Unless there is a clear contraindication to chest drainage,
all pleural effusions being treated as infected should be
drained by a chest tube.
• All patients should have had an assessment of the effectiveness of the drainage of the pleural fluid collection and the
resolution of their fever and sepsis 5–8 days after starting
chest tube drainage and antibiotics for pleural infection.
The result of this assessment should be recorded in the clinical notes.
• All patients who have not achieved effective pleural drainage at the outcome assessment described above should be
discussed with a thoracic surgeon to consider surgical
drainage of the infected collection.
The decision to operate to achieve empyema drainage is
subjective, and there are no established objective criteria to
define the point at which a patient should proceed to surgery.
Patients with purulent fluid59 and/or loculations69 at presentation are more likely to require surgical drainage, although
many patients settle without surgery. Patients should be considered for surgery if they have a residual sepsis syndrome in
association with a persistent pleural collection, despite drainage and antibiotics. Failure of sepsis to begin resolution within
7 days45 151 is suggested as an appropriate period after which a
surgical opinion should be sought.
A number of surgical approaches are available including
video assisted thoracoscopic surgery (VATS), open thoracic
drainage, or thoracotomy and decortication. The type of
procedure performed will depend on many factors including
patient age and co-morbidity, and surgical preference including the local availability of video assisted surgical techniques.
The choice of surgical procedure is beyond the remit of these
guidelines and is not considered further.
One small trial has directly compared surgical and medical
treatment. Wait et al9 randomised 20 patients with pleural
infection who were suitable for general anaesthesia to receive
immediate VATS or intrapleural streptokinase for 3 days
instilled into a chest tube. Chest tubes were not inserted under
radiological guidance in the medical group and were inserted
by junior resident medical staff. The surgical group had higher
primary treatment success (10/11 patients) and all medical
failures (5/9 patients) were salvaged by surgery without
requiring thoracotomy. Surgical patients required shorter
drainage time (5.8 v 9.8 days) and had a shorter stay in hospital (8.7 v 12.8 days). The results of this study need to be interpreted in the light of the small sample size and the unusually
high failure rate in the control limb (55%). Further appropriately powered studies are needed.
2.16 Patients not considered fit for surgery and not
improving with chest tube drainage and antibiotics
• In cases of ineffective chest tube drainage and
persistent sepsis in patients unable to tolerate
general anaesthesia, re-imaging the thorax and
placement of further image guided small bore
catheters, large bore chest tubes, or intrapleural
fibrinolytic therapy should be considered. [C]
www.thoraxjnl.com
ii26
• Local anaesthetic surgical rib resection should be
considered in patients unsuitable for general anaesthesia. [C]
Ineffective chest tube drainage and persistent sepsis in
patients unfit for general anaesthesia can be approached by a
number of “less invasive” options. Re-imaging the thorax and
placement of further image guided small bore catheters may
drain loculated collections50 89–91 93 94 and large bore chest tubes
can be tried for “thick” pus.96 Alternatively, patients may proceed to surgical rib resection and open drainage under local
anaesthesia.
.....................
Authors’ affiliations
C W H Davies, Department of Respiratory Medicine, Battle and Royal
Berkshire Hospitals, Oxford Road, Reading RG30 1AG, UK
F V Gleeson, Department of Radiology, Churchill Hospital Site, Oxford
Radcliffe Hospital, Headington, Oxford OX3 7LJ, UK
R J O Davies, Oxford Centre for Respiratory Medicine, Churchill
Hospital Site, Oxford Radcliffe Hospital, Headington, Oxford OX3 7LJ,
UK
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ii29
BTS guidelines for the management of malignant pleural
effusions
G Antunes, E Neville, J Duffy, N Ali, on behalf of the BTS Pleural Disease Group,
a subgroup of the BTS Standards of Care Committee
.............................................................................................................................
Thorax 2003;58(Suppl II):ii29–ii38
1 INTRODUCTION
The discovery of malignant cells in pleural fluid
and/or parietal pleura signifies disseminated or
advanced disease and a reduced life expectancy in
cancer patients.1 Median survival following diagnosis ranges from 3 to 12 months and is dependent on the stage and type of the underlying
malignancy. The shortest survival time is observed in malignant effusions secondary to lung
cancer and the longest in ovarian cancer, while
malignant effusions due to an unknown primary
have an intermediate survival time.2–5
Currently, lung cancer is the most common
metastatic tumour to the pleura in men and
breast cancer in women.6 Together, both malignancies account for approximately 50–65% of all
malignant effusions (table 1). Lymphomas, tumours of the genitourinary tract and gastrointestinal tract as a group account for a further
25%.5 7–9 Pleural effusions from an unknown
primary are responsible for 7–15% of all malignant pleural effusions.3 7 8
An algorithm for the management of malignant pleural effusions is shown in fig 1.
2 PATHOPHYSIOLOGY
The pleura consists of five main anatomical compartments (fig 2): the parietal systemic circulation (branches of the intercostal and internal
mammary arteries), the parietal interstitial space,
the pleural space lined on either side by mesothelial cells, the pulmonary interstitium, and the visceral circulation (bronchial and pulmonary arterioles).
Pleural fluid is filtered in the parietal pleural
compartment from the systemic capillaries down
a small pressure gradient into the pleural space.
Under normal conditions the visceral pleura plays
an insignificant role in pleural fluid turnover.10
Experiments using radioactive albumin and
other labelled proteins have shown that pleural
fluid secretion is greatest at the apex and absorption is increased towards the diaphragm and
mediastinum.11 12 Pleural fluid is drained out of
Table 1
See end of article for
authors’ affiliations
.......................
Correspondence to:
Dr G Antunes, Department
of Respiratory Medicine,
James Cook University
Hospital, Marton Road,
Middlesborough TS4 3BW,
UK; george.antunes@
stees.nhs.uk
.......................
the pleural space predominantly through the stomata of the parietal lymphatics lying between the
parietal mesothelial cells. The number of parietal
lymphatics is greatest at the diaphragm and
mediastinum. These stomata merge into small
lymphatic channels which, in turn, form larger
vessels ultimately draining into the mediastinal
lymph nodes.
Any disruption or obstruction by tumour cells
along this intricate lymphatic network may result
in a pleural effusion. This mechanism for pleural
fluid accumulation has been confirmed by necroscopic studies which reveal that involvement of
the regional lymph nodes is usually associated
with the presence of a pleural effusion.1 13
Typically, adenocarcinoma of the lung spreads to
the parietal pleura from the visceral pleura along
existing pleural adhesions. This is preceded by
migration of tumour cells to the visceral pleura
from underlying pulmonary capillaries—that is,
haematogenous spread.14 Pleural metastases from
a primary site other than the lung result from
haematogenous or lymphatic spread. Malignant
effusions secondary to breast cancer arise either
through chest wall lymphatics or via hepatic
metastases resulting in either contralateral or
bilateral effusions.15
Haemorrhagic malignant effusions usually result from invasion of blood vessels directly and/or
tumour induced angiogenesis.13 Vascular endothelial growth factor (VEGF), a cytokine
possessing potent angiogenic activity and promoting endothelial permeability, may play a
significant role in the formation of malignant
effusions and local tumour growth.16 17
3 CLINICAL PRESENTATION
• Massive pleural effusions are most commonly due to malignancy. [B]
• The majority of malignant effusions are
symptomatic. [C]
Massive pleural effusions, defined as complete or
almost complete opacification of a hemithorax on
Primary tumour site in patients with malignant pleural effusion
Primary
tumour site
Salyer7
(n=95)
Chernow1
(n=96)
Johnston8
(n=472)
Sears2
(n=592)
Hsu9
(n=785)
Total (%)
Lung
Breast
Lymphoma
GI tract
GU tract
Other
Unknown primary
42
11
11
–
–
14
17
32
20
–
13
13
5
13
168
70
75
28
57
26
48
112
141
92
32
51
88
76
410
101
56
68
70
15
65
764
343
234
141
191
148
219
(37.5)
(16.8)
(11.5)
(6.9)
(9.4)
(7.3)
(10.7)
GI=gastrointestinal; GU=genitourinary.
www.thoraxjnl.com
ii30
Antunes, Neville, Duffy, et al
Proven
malignant
effusion
Recurrence/
NO
Observe
symptomatic?
YES
Seek specialist opinion from a member
of the thoracic malignancy
multidisciplinary team
Intercostal tube
insertion and
drainage
Consider:
Chest radiograph:
NO
complete lung
1. Thoracoscopy (section 4.4)
2. Long term indwelling
catheter (section 4.5)
re-expansion?
3. Pleuroperitoneal shunt
(section 4.6)
YES
Chemical
pleurodesis
Consider:
1. Repeated pleurodesis
(section 4.3)
2. Thoracoscopy (section 4.4)
Recurrence of
effusion?
YES
3. Long term indwelling
catheter (section 4.5)
4. Pleuroperitoneal shunt
(section 4.6)
NO
5. Palliative repeated
thoracentesis (section 4.2)
STOP
Figure 1 Algorithm for the management of malignant pleural effusions.
www.thoraxjnl.com
BTS guidelines for the management of malignant pleural effusions
Parietal
Visceral
pleura
pleura
intervention during the course of treatment. Common and
less common management options will be discussed below.
Basal lamina
4.1 Observation
Pleural
Extrapleural
Pulmonary
space
s.c.
parietal
interstitium
p.c.
interstitium
Parietal
Alveolus
lymphatic
Stoma
Pulmonary lymphatic
• Observation is recommended if the patient is asymptomatic or there is no recurrence of symptoms after
initial thoracentesis. [C]
• Advice should be sought from the thoracic malignancy multidisciplinary team for symptomatic or
recurrent malignant effusions. [C]
The majority of these patients will become symptomatic in
due course and require further intervention. There is no
evidence that initial thoracentesis carried out according to
standard technique will reduce the chances of subsequent
effective pleurodesis.
4.2 Therapeutic pleural aspiration
Microvilli
• Repeat pleural aspiration is recommended for the
palliation of breathlessness in patients with a very
short life expectancy. [C]
Unidirectional
valve
Figure 2 Schematic diagram of pleural anatomy; s.c.=systemic
capillary; p.c.=pulmonary capillary. Modified from Miserocchi10 with
permission.
the chest radiograph, are more commonly associated with a
malignant aetiology.18 However, a modest number of patients
(up to 25%) are asymptomatic at presentation—that is, they
are found incidentally with physical examination or by chest
radiography.1 Dyspnoea is the most common presenting
symptom and is occasionally accompanied by chest pain and
cough. Dyspnoea is due to a combination of reduced
compliance of the chest wall, depression of the ipsilateral diaphragm, mediastinal shift, and reduction in lung volume
stimulating neurogenic reflexes. Chest pain is usually related
to involvement of the parietal pleura, ribs, and other intercostal structures.19 Constitutional symptoms including weight
loss, malaise, and anorexia also generally accompany respiratory symptoms. The diagnosis of a malignant pleural effusion
is discussed in the section on the investigation of a unilateral
pleural effusion (page ii8).
4 MANAGEMENT OPTIONS
Treatment options for malignant pleural effusions are
determined by several factors: symptoms and performance
status of the patient, the primary tumour and its response to
systemic therapy, and lung re-expansion following pleural
fluid evacuation (table 2). Although small cell lung cancer,
lymphoma, and breast cancer usually respond to chemotherapy, associated secondary pleural effusions may require
Table 2
ii31
• Caution should be taken if removing more than 1.5 l
on a single occasion. [C]
• The recurrence rate at 1 month after pleural
aspiration alone is close to 100%. [B]
• Intercostal tube drainage without pleurodesis is not
recommended because of a high recurrence rate. [B]
Repeated therapeutic pleural aspiration provides transient
relief of symptoms and avoids hospitalisation for patients with
limited survival expectancy and poor performance status. This
option is appropriate for frail or terminally ill patients but
individual patient preference may also dictate its use in
patients who have had a previous failed intercostal tube and
pleurodesis.20 The amount of fluid evacuated will be guided by
patient symptoms (cough, chest discomfort) and should be
limited to 1–1.5 l (see section 4.3.2). Pleural aspiration alone
and intercostal tube drainage without instillation of a sclerosant are associated with a high recurrence rate and a small risk
of iatrogenic pneumothorax and empyema.21–26
4.3 Intercostal tube drainage and intrapleural
instillation of sclerosant
Pleurodesis requires a diffuse inflammatory reaction and local
activation of the coagulation system with fibrin deposition.27
Antony and colleagues have demonstrated increased growth
factor-like activity in mesothelial cells exposed to tetracycline
leading to fibroblast proliferation. This activity gradually
decays once the tetracycline is removed.28 Increased pleural
fibrinolytic activity is associated with failure of pleurodesis.
Rodriguez-Panadero showed that rapid reduction in fibrinolytic activity within 24 hours using pleural D-dimer levels was
Treatment options for malignant pleural effusions
Management approach
Commonly used Observation
options
Therapeutic thoracentesis
Less commonly
used options
Advantages
Disadvantages
Indicated for small and asymptomatic effusions
Chest tube insertion with
intrapleural sclerosant
Thoracoscopy with talc poudrage
Effusions will usually increase in size and need
intervention
Transient and rapid relief of dyspnoea; minimally High recurrence rate; risk of iatrogenic empyema
invasive; suitable for outpatient setting
and pneumothorax
Success rate >60%; low incidence of
Side effects of sclerosants (see text)
complications
High success rate (90%)
Invasive procedure and may be unavailable
Long term indwelling catheter
drainage
Pleuroperitoneal shunt
Suitable for outpatient setting; modest success
rate
Useful for intractable effusions and trapped lung
Pleurectomy
Very low recurrence rate
Local infection; risk of tumour seeding in
mesothelioma
Good performance status required to manage
shunt (WHO 0,1); occlusion; infection
Invasive procedure; significant morbidity and
mortality
www.thoraxjnl.com
ii32
Box 1 Chemical pleurodesis
(1) Insert small bore intercostal tube (10–14 F).
(2) Controlled evacuation of pleural fluid.
(3) Confirm full lung re-expansion and position of intercostal
tube with chest radiograph.
(4) Administer premedication prior to pleurodesis.
(5) Instill lignocaine solution (3 mg/kg; maximum 250 mg)
into pleural space followed by sclerosant of choice (for
sclerosants, see text).
(6) Clamp tube for 1 hour and consider patient rotation for
talc slurry.
(7) Remove intercostal tube within 12–72 hours if lung
remains fully re-expanded and there is satisfactory evacuation of pleural fluid.
associated with good outcome of talc pleurodesis. In contrast,
the group in whom the D-dimer level took longer to return to
baseline (>24 hours) had a greater number of treatment
failures.29
In animals the effectiveness of pleurodesis may be reduced
by concomitant use of corticosteroids. Recent evidence in rabbits has shown reduced pleural inflammatory reaction and, in
some cases, prevention of pleurodesis with administration of
corticosteroids at the time of talc pleurodesis.30 The administration of non-steroidal anti-inflammatory agents at the time
of pleurodesis is more contentious and, at present, evidence
against their use is lacking.
Belani and colleagues, using a simulation model, compared
the cost effectiveness of intercostal tube insertion and chemical
pleurodesis (tetracycline, doxycyline and bleomycin) with
operative talc poudrage. The cost of symptom free days was used
to determine cost effectiveness. Intercostal tube insertion and
chemical pleurodesis was found to be more cost effective than
talc poudrage where theatre time and personnel contributed
significantly to the extra cost.31 The method of chemical
pleurodesis will be discussed below and is summarised in box 1.
4.3.1 Size of intercostal tube
• Small bore (10–14 F) intercostal catheters should be
the initial choice for effusion drainage and pleurodesis. [B]
Conventional large bore intercostal tubes (24–32 F) have been
employed in most studies involving sclerosing agents.32 They
have traditionally been used because they are thought to be
less prone to obstruction by clots, but there is little published
evidence to confirm this. The placement of large bore tubes is
perceived to be associated with significant discomfort33 and
this has led to the assessment of smaller bore tubes (10–14 F)
for the drainage and administration of sclerosing agents.
Studies using small bore intercostal tubes with commonly
used sclerosants have reported similar success rates to large
bore tubes.34–38 The small bore tubes in these studies were
inserted either at the patient’s bedside by a physician or under
radiological guidance.
Comparison between small bore and large bore intercostal
tubes has been considered in two studies. Clementsen et al,38 in
a randomised study using tetracycline as a sclerosing agent,
compared a small bore tube (10 F) placed at bedside with a
large bore tube (24 F). Although no significant difference in
success rate was observed between the two groups, the small
bore catheter was associated with less discomfort. Small bore
tubes (10 F) were also considered more successful than large
bore tubes (32–38 F) in a non-randomised study .34 Both studies recruited only a small number of patients and larger
randomised studies are necessary to support these findings.
Small bore tubes have been used for ambulatory or
outpatient pleurodesis. Patz et al39 used a fluoroscopically
placed tube (10 F) connected to a closed gravity drainage bag
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Antunes, Neville, Duffy, et al
system for this purpose. Bleomycin was the preferred sclerosing agent and the pleurodesis success rate approached 80%.
Six patients complained of mild chest pain during insertion of
the intercostal tube. Two of the intercostal tubes became
blocked but were successfully cleared with a guidewire.
In view of the potential advantages (reduced patient
discomfort, ease of placement, and comparable pleurodesis
success rates), small bore tubes (10–14 F) should be considered initially for the drainage of malignant effusions.
4.3.2 Lung re-expansion, fluid drainage, and suction
• Large pleural effusions should be drained in a
controlled fashion to reduce the risk of re-expansion
pulmonary oedema (RPO). [C]
• Suction to aid pleural drainage before and after pleurodesis is usually unnecessary but, if applied, a high
volume, low pressure system is recommended. [C]
• In patients where only partial pleural apposition can
be achieved, chemical pleurodesis should still be
attempted and may provide symptomatic relief. [B]
• Once effusion drainage and lung re-expansion have
been radiographically confirmed, pleurodesis should
not be delayed while the cessation of pleural fluid
drainage is awaited. [B]
The most important requirement for successful pleurodesis is
satisfactory apposition of the parietal and visceral pleura, confirmed radiologically.32 40 41 Incomplete lung re-expansion may
be due to a thick visceral peel (“trapped lung”), pleural loculations, proximal large airway obstruction, or a persistent air
leak. Most studies indicate that the lack of a response following instillation of a sclerosant is predominantly due to incomplete lung expansion.41 42 Where complete lung re-expansion
or pleural apposition is not achieved and the patient is unsuitable for surgical intervention, pleurodesis should still be
attempted. Robinson and colleagues,43 in a study using doxycycline as a sclerosing agent, reported a favourable response in
nine out of 10 patients with partial re-expansion of the lung.
The amount of pleural fluid drained per day before the
instillation of a sclerosant (<150 ml/day) is less relevant for
successful pleurodesis than radiographic confirmation of fluid
evacuation and lung re-expansion. In a randomised study, a
shorter period of intercostal tube drainage and hospital stay
was seen in the group in whom sclerotherapy was undertaken
as soon as complete lung re-expansion was documented
(majority <24 hours) than in the group in whom pleurodesis
was attempted only when the fluid drainage was <150 ml/
day. The success rate in both groups approached 80%.41
Large pleural effusions should be drained in a controlled
fashion avoiding evacuation of more than 1–1.5 l at one time
or slowed to about 500 ml/hour, and aspiration discontinued if
the patient develops chest discomfort, persistent cough, or
vasovagal symptoms. Re-expansion pulmonary oedema (RPO)
is a well described but rare complication following rapid
expansion of a collapsed lung through evacuation of large
amounts of pleural fluid at a single time and the use of early
and excessive pleural suction.44 45 Putative pathophysiological
mechanisms include reperfusion injury of the underlying
hypoxic lung, increased capillary permeability, and local
production of neutrophil chemotactic factors such as interleukin (IL)-8.46 Suction may be required for incomplete lung
expansion and a persistent air leak. When suction is applied,
the use of high volume, low pressure systems is recommended
with a gradual increment in pressure to about –20 cm H2O.
4.3.3 Analgesia and premedication
• Lignocaine (3 mg/kg; maximum 250 mg) should be
administered intrapleurally just prior to sclerosant
administration. [B]
BTS guidelines for the management of malignant pleural effusions
Table 3
ii33
Sclerosing agents available in UK
Sclerosing agent
Recommended
dose
Average
success rate
Common
side effects
Serious
complications
Approx cost
per treatment
Manufactured
in UK
No of
treatments
Tetracycline
1–1.5 g
65%49 53–55
None
1.5 g: £13.95†
No
1
Sterile talc
(slurry or poudrage)
Bleomycin
2–5 g
90%42 64 65 68
Chest pain,
fever, cough
Chest pain,
fever
Chest pain,
fever, nausea
Chest pain,
fever
Respiratory
failure/ARDS
None
5 g: £1.60
Yes*
1
60 units: £68.75
Yes
1
None
500 mg: £29.50
No‡
>1
Doxycycline
60 units
500 mg
61%
56 67 72–74
43 47 78 79
76%
ARDS=adult respiratory distress syndrome.
*Produced in Germany and available via international wholesalers.
†Produced under manufacturer’s licence in UK.
‡Not available or licensed for use in the UK.
• Premedication should be considered to alleviate
anxiety and pain associated with pleurodesis. [C]
Intrapleural administration of sclerosing agents is associated
with chest pain and the incidence varies from 7% in the case
of talc to 40% with doxycycline.43 47 Lignocaine is the best
studied local anaesthetic for intrapleural administration. The
onset of action of lignocaine is almost immediate and it should
therefore be administered just before the sclerosant. The issue
of safety has been highlighted in two studies. Wooten et al48
showed that the mean peak serum concentration of lignocaine
following 150 mg of intrapleural lignocaine was 1.3 µg/ml,
well below the serum concentration associated with central
nervous system side effects (that is >3 µg/ml). In an earlier
study of 20 patients larger doses of lignocaine were necessary
to achieve acceptable levels of local anaesthesia. The patients
receiving 250 mg lignocaine had more frequent pain-free episodes than those given 200 mg, while serum levels remained
within the therapeutic range. Side effects were limited to
transient paraesthesia in a single patient.49 The reason for the
significant difference in analgesia between the two groups
with only a small increment in the lignocaine dose was
unclear.
In the context of pleurodesis, premedication and sedation is
poorly studied and no evidence based guidelines exist.
Pleurodesis is an uncomfortable procedure and is associated
with anxiety for the patient. The use of sedation may be helpful to allay such fears and induce amnesia. The level of sedation using either an opioid (with a suitable anti-emetic) or
benzodiazepine should be appropriate—that is, maintenance
of verbal communication and cooperation. Sedation employed
before pleurodesis should be conducted with continuous
monitoring with pulse oximetry and in a setting where resuscitation equipment is available.50
esis until death, and a partial response as partial reaccumulation of fluid radiographically but not requiring
further pleural intervention such as aspiration. An ideal sclerosing agent must possess several essential qualities: a high
molecular weight and chemical polarity, low regional clearance, rapid systemic clearance, a steep dose-response curve,
and be well tolerated with minimal or no side effects. The
choice of a sclerosing agent will be determined by the efficacy
or success rate of the agent, accessibility, safety, ease of
administration, number of administrations to achieve a complete response, and cost (table 3). Sclerosing agents available
for routine use will be discussed first.
• Talc is the most effective sclerosant available for
pleurodesis. [B]
• A small number of patients (<1%) may develop acute
respiratory failure following talc administration. [B]
• Tetracycline is modestly effective, has few severe side
effects, and is the preferred sclerosant to minimise
adverse event rates. [B]
• Bleomycin is an alternative sclerosant with a modest
efficacy rate but is expensive. [B]
• Pleuritic chest pain and fever are the most common
side effects of sclerosant administration. [B]
Tetracycline
Until recently, tetracycline had been the most popular and
widely used sclerosing agent in the UK.51 The manufacturer of
parenteral tetracycline discontinued production and distribution of the agent in the US in 1993 and a similar fate may follow in the UK.52 However, currently the parenteral preparation
is available in Germany and may be imported via international
wholesalers. These suppliers state that supplies are expected to
remain available for the foreseeable future. The advantages of
tetracycline are its reasonable efficacy, excellent safety profile,
ease of administration, and low cost. Success rates (complete
and partial response rates) from the larger studies have varied
from 50% to 92% with a mean of 65%.41 49 53–55 Side effects
include fever (10%) and pleuritic chest pain (30%), which are
usually transient and respond readily to antipyretics and
analgesia. The optimal dose for intrapleural administration is
1.0–1.5 g or 20 mg/kg. Studies using smaller doses such as
500 mg have reported lower response rates, while there is no
evidence to support the use of larger doses of tetracycline.56 57
Thoracoscopic instillation of tetracycline has been studied
in two randomised trials for malignant effusions in breast
cancer. Evans et al compared thoracoscopic instillation of
500 mg tetracycline with 1.5 g via chest tube. The complete
response rate at 1 month for both groups was 76%.58 Fentiman
et al,59 on the other hand, compared talc poudrage with thoracoscopically administered tetracycline (500 mg). The talc
group was found to be superior with a successful palliation at
1 month of 92% compared with 48% for the tetracycline group.
Tetracycline pleurodesis may also be attempted using a needle
aspiration technique where the agent is administered after
draining an effusion to dryness. A recent randomised study
employing this method reported a disappointingly low
pleurodesis success rate of 29% at 6 weeks compared with 80%
with intercostal tube drainage.60
Despite the evaluation of a wide variety of agents, to date no
ideal sclerosing agent exists. Comparison of sclerosing agents
is hampered by the lack of comparative randomised trials, different eligibility criteria, and disparate criteria for measuring
response and end points. A complete response is usually
defined as no re-accumulation of pleural fluid after pleurod-
Sterile talc
Talc (Mg3Si4O10(OH)2) is a trilayered magnesium silicate sheet
that is inert and was first used as a sclerosing agent in 1935.61
Talc used for intrapleural administration is asbestos-free and
sterilised effectively by dry heat exposure, ethylene oxide, and
4.3.4 Selecting a sclerosing agent
www.thoraxjnl.com
ii34
gamma radiation. It may be administered in two ways: at thoracoscopy using an atomiser termed “talc poudrage” or via an
intercostal tube in the form of a suspension termed “talc
slurry”.62 63
Success rates (complete and partial response) for talc slurry
range from 88% to 100% with a mean of 90%.24 42 64 65 The
majority of studies have used talc slurry alone and only a limited number of comparative studies have been published. A
truncated randomised study by Lynch and colleagues66
compared talc slurry (5 g) with bleomycin (60 units) and tetracycline (750 mg). Although the study was terminated early
because of the removal of tetracycline from the US market,
analysis of the data to that point revealed no differences
between the three treatment groups 1 month after pleurodesis. In a recent randomised trial between talc slurry (5 g) and
bleomycin (60 units), 90% of the talc group achieved a
complete response at 2 weeks compared with 79% of the bleomycin group, which was statistically insignificant.67 Yim et al68
compared talc slurry (5 g) with talc poudrage (5 g) and found
no significant difference between the two groups with respect
to complete response rate (both over 90%), chest drainage
duration, length of hospital stay, and complication rate.
Talc slurry is usually well tolerated and pleuritic chest pain
and mild fever are the most common side effects observed. A
serious complication associated with the use of talc is adult
respiratory distress syndrome (ARDS) or acute pneumonitis
leading to acute respiratory failure. The mechanism of acute
talc pneumonitis is unclear and has been reported with both
talc poudrage and slurry.42 69 The dose of talc and the physical
characteristics (size and type) appear to be the most
important determinants for the development of this
complication.70 In a case series reported by Kennedy et al42 five
patients developed respiratory failure with talc slurry pleurodesis (10 g). Three patients required mechanical ventilation
but were later successfully extubated. Studies using lower
doses (2–5 g) have reported excellent complete response rates
with a lower incidence of serious adverse effects including
acute respiratory failure.64 65 The diagnosis of talc pneumonitis
is made after exclusion of other possible mechanisms for pulmonary infiltrates and respiratory failure—that is, reexpansion pulmonary oedema and lymphangitis carcinomatosa.
Bleomycin
Bleomycin is the most widely used antineoplastic agent for the
management of malignant pleural effusions. Its mechanism of
action is predominantly as a chemical sclerosant similar to talc
and tetracycline. Although 45% of the administered bleomycin
is absorbed systemically, it has been shown to cause minimal
or no myelosuppression.71 Bleomycin is an effective sclerosant
with success rates after a single administration ranging from
58% to 85% with a mean of 61%.56 67 72–74 Large comparative
trials have found it to be superior to tetracycline.56 74 75 It has an
acceptable side effect profile with fever, chest pain, and nausea
the most common adverse effects. The recommended dose is
60 units mixed in normal saline. Bleomycin has also been used
in studies evaluating small bore intercostal tubes placed under
radiological guidance with similar efficacy rates.37 39 76 77 The
major disadvantages of bleomycin are the cost per treatment
compared with other sclerosants and that it needs to be
performed by trained personnel familiar with the administration of cytotoxic drugs (table 3).
Rarely used and historical agents
(1) Doxycyline: Although doxycycline is widely used in the US
and is available in Continental Europe, it is not available or
licensed for intrapleural administration in the UK. It has been
evaluated in several small trials with success rates varying
from 65% to 100% with a mean of 76%.43 47 78 79 All but one of
the trials used a dose of 500 mg mixed in normal saline.
www.thoraxjnl.com
Antunes, Neville, Duffy, et al
Prevost et al80 used doses in excess of 2 g with a reported success rate of 82%. Side effects are similar to those with
tetracycline—that is, fever (30%) and mild to moderate pleuritic chest pain (up to 60%). Doxycycline has been used with
small bore tubes in two studies. Patz et al37 in a large
randomised study compared bleomycin with doxycycline
(500 mg) in 106 patients. The complete response rate at 1
month for doxycycline was 79%. In a similar study, Seaton et
al36 reported a complete response rate of 81% with a low incidence of side effects. The major disadvantage of doxycycline is
the need for repeated instillations to obtain a satisfactory success rate. This may lead to prolonged catheter or intercostal
tube indwelling times with a potential increase in infection,
patient discomfort, and overall cost in treatment.
(2) Minocycline: Minocycline has been used as a sclerosing
agent but experience in humans is limited to a single small
and uncontrolled study.81 A recent study in rabbits suggests
that it may be as effective as tetracycline at inducing
pleurodesis.82 Minocycline is not available or licensed for
intrapleural administration in the UK.
(3) Other sclerosants: Corynebacterium parvum extract,83–89
interferons (interferon-α and -β),90–94 interleukins (IL-2),95 96
and several chemotherapeutic drugs (cisplatin, cytosine
arabinoside, and mitoxantrone)97–99 have been used for
pleurodesis with variable and usually disappointing efficacy
rates. Most of the trials have been uncontrolled and recruited
small numbers of patients. Corynebacterium parvum, interferons, and interleukins require multiple administrations, while
significant toxicity is encountered with the use of the chemotherapeutic drugs.
4.3.5 Rotation following pleurodesis
• Patient rotation is not necessary after intrapleural
instillation of tetracycline class agents. [A]
Rotation of the patient following intrapleural administration
of a sclerosing agent is described in most pleurodesis studies
in order to achieve adequate distribution of the agent over the
pleura. However, patient rotation is time consuming and may
cause further discomfort for these patients. A study using
radiolabelled tetracycline has shown that tetracycline is
dispersed throughout the pleural space within seconds and
rotation of the patient did not influence the distribution of the
agent.100 A subsequent randomised trial using tetracycline,
minocycline, and doxycycline revealed no significant difference in the success rate of the procedure or duration of fluid
drainage between the rotation and non-rotation groups.101
Patient rotation is still required when using talc slurry until
further evidence is available.
4.3.6 Clamping of intercostal tube
• The intercostal tube should be clamped for 1 hour
after sclerosant administration. [C]
• In the absence of excessive fluid drainage (>250 ml/
day) the intercostal tube should be removed within
12–72 hours of sclerosant administration. [C]
Clamping of the intercostal tube following intrapleural
administration of the sclerosant should be brief (1 hour). This
will prevent the sclerosant from immediately draining back
out of the pleural space, although this may not be
important.100 Intercostal tube removal has been recommended
when fluid drainage reached less than 150 ml/day, but there is
a lack of evidence to support this action.102–104 In the absence of
any evidence that protracted drainage is beneficial, and given
the discomfort associated with prolonged drainage, we
arbitrarily recommend removal of the intercostal tube within
12–72 hours after the instillation of the sclerosant provided
the lung remains fully re-expanded and there is satisfactory
evacuation of pleural fluid on the chest radiograph. Where
excessive fluid drainage persists (>250 ml/day), repeat pleurodesis may be attempted with an alternative sclerosant. In
BTS guidelines for the management of malignant pleural effusions
ii35
the event of incomplete lung expansion any treatable cause for
this should be excluded and the drain may then be removed as
pleurodesis is unlikely to succeed.
4.3.7 Malignant seeding at intercostal tube or port site
• Patients with proven or suspected mesothelioma
should receive prophylactic radiotherapy to the site
of biopsy or chest drain insertion. [A]
Local tumour recurrence or seeding following diagnostic and
therapeutic pleural aspiration, pleural biopsy, intercostal tube
insertion, and thoracoscopy is uncommon in nonmesothelioma malignant effusions.105–108 However, in mesothelioma 40% of patients may develop malignant seeding at the
site of diagnostic pleural procedures. In a randomised study
Boutin et al109 found that local metastases were prevented in
patients who received radiotherapy to the thoracoscopic tract
site. All the patients received radiotherapy within 2 weeks of
thoracoscopy. It should be noted that further clinical trials of
procedure site radiotherapy in mesothelioma are currently
recruiting. The role of prophylactic radiotherapy following
pleural procedures in non-mesothelioma malignant effusions
has not been established and therefore cannot be recommended.
4.3.8 Intrapleural fibrinolytics
• Intrapleural instillation of fibrinolytic drugs is recommended for the relief of distressing dyspnoea due
to multiloculated malignant effusion resistant to
simple drainage. [C]
The use of fibrinolytic agents represents an advance in the
management of multiloculated malignant effusions. Immune
mediated or haemorrhagic complications have rarely been
described with the administration of intrapleural fibrinolytics
in contrast to systemic administration of these agents.110 111
Jerjes-Sanchez et al112 administered intrapleural streptokinase (250 000 IU) in an open study to four patients with
multiloculated malignant effusions not considered suitable for
pleurodesis at the time. In three of the four patients
fibrinolytic administration allowed radiographic improvement
and led to successful pleurodesis. A more recent study found
that intrapleural streptokinase increased pleural fluid drainage and led to radiographic improvement and amelioration of
symptoms in 10 patients with multiloculated or septated
malignant effusions. Intrapleural streptokinase was well
tolerated and no allergic or haemorrhagic complications were
reported.113 Gilkeson et al114 preferred urokinase in their
prospective but non-randomised study. Twenty two malignant
pleural effusions were treated with urokinase resulting in
substantial increase in pleural fluid output in patients both
with and without radiographic evidence of loculations. The
majority then underwent pleurodesis with doxycycline resulting in a complete response rate of 56%. Similarly, no allergic or
haemorrhagic complications were encountered.
None of these studies is large enough to accurately describe
the safety profile of fibrinolytic drugs in this setting. The physician should therefore use these agents with caution,
carefully considering the risk/benefit balance for the individual patient. An appropriately experienced specialist should
be involved in the care of all patients receiving this treatment.
4.4 Thoracoscopy in malignant pleural effusion
• Thoracoscopy should be considered for the diagnosis
of suspected but unproven malignant pleural effusion. [B]
• Thoracoscopy should be considered for the control of
recurrent malignant pleural effusion. [B]
• Thoracoscopy is a safe procedure with low complication rates. [B]
Figure 3 (A) CT scan and (B) thoracoscopic appearance of pleural
malignancy (breast carcinoma metastases).
Thoracoscopy (under sedation or general anaesthesia) has
grown in popularity as a diagnostic and therapeutic tool for
malignant effusions.115–117 The thoracoscopic appearance of
pleural malignancy and a thoracic CT scan from the same
patient are shown in fig 3. The diagnostic yield and accuracy of
thoracoscopy for malignant effusions is greater than
90%.55 117 118 Patients with exudative pleural effusions of
unknown aetiology after pleural fluid cytological and microbiological examination should proceed to pleural tissue biopsy
(see guideline on the investigation of pleural effusions, page
ii8).
The therapeutic role of thoracoscopy has been evaluated
extensively. Talc poudrage is an effective method for controlling malignant effusions with a mean pleurodesis success rate
of more than 90%.115 116 119 120 Patient selection for thoracoscopy
and talc poudrage is important in view of the invasive nature
of the procedure and cost. The role of surgical thoracoscopy in
patients with trapped lung is less clear. The procedure can
facilitate breaking up of loculations and release of adhesions
www.thoraxjnl.com
ii36
and thereby aid lung re-expansion and apposition of the
pleura for talc poudrage.121
Thoracoscopy is a safe and well tolerated procedure with a
low perioperative mortality rate (<0.5%).116 122 The most common major complications are empyema and acute respiratory
failure secondary to infection or re-expansion pulmonary
oedema.115 123
4.5 Long term indwelling pleural catheter drainage
• Chronic indwelling pleural catheters are effective in
controlling recurrent and symptomatic malignant
effusions in selected patents. [B]
Insertion of a long term tunnelled pleural catheter is an alternative method for controlling recurrent and symptomatic
malignant effusions including patients with trapped lung. A
specific catheter has been developed for this purpose and the
published studies employing this catheter have reported
encouraging results.124 125
In the only randomised and controlled study to date,
Putnam and colleagues124 compared a long term indwelling
pleural catheter with doxycycline pleurodesis via a standard
intercostal tube. The length of hospitalisation for the indwelling catheter group was significantly shorter (1 day) than that
of the doxycycline pleurodesis group (6 days). Spontaneous
pleurodesis was achieved in 42 of the 91 patients in the
indwelling catheter group. A late failure rate (defined as reaccumulation of pleural fluid after initial successful control) of
13% was reported compared with 21% for the doxycycline
pleurodesis group. There was a modest improvement in the
quality of life and dyspnoea scores in both groups. The
complication rate was higher (14%) in the indwelling catheter
group and included local cellulitis (most common) and, rarely,
tumour seeding of the catheter tract.
An indwelling pleural catheter is therefore an effective
option for controlling recurrent malignant effusions when
length of hospitalisation is to be kept to a minimum (reduced
life expectancy) and expertise and facilities exist for
outpatient management of these catheters.
Antunes, Neville, Duffy, et al
Audit points
• Performance status at time of chemical pleurodesis.
• Use of small bore catheters in the management of malignant
pleural effusions.
• Assessment of lung re-expansion prior to pleurodesis.
• Assessment of pain during and after pleurodesis using a
pain scale or score.
• Complete and partial response rates of sclerosing agents.
• Surgical referral rates for the management of malignant
pleural effusions.
Future potential areas for research
• Large prospective randomised trials comparing small bore
catheters and large bore intercostal tubes for pleural fluid
drainage and pleurodesis in malignant pleural effusions.
• Role of premedication before pleurodesis in malignant
pleural effusion.
• Clinical trials of promising new sclerosants such as
transforming growth factor beta (TGFβ) and iodopovidone.
• Place of suction after pleurodesis in terms of duration of
fluid drainage and length of hospital stay.
empyema, haemorrhage, and cardiorespiratory failure (operative mortality rates of 10–13%). Patient selection is therefore
important and this method should be reserved for those who
have failed to respond to other forms of treatment.130 131 The
advent of video assisted thoracic surgery (VATS) has enabled
parietal pleurectomy to be performed without a formal thoracotomy. A study of 19 patients (13 with mesothelioma, six
with metastatic adenocarcinoma) found this thoracoscopic
method to be safe and associated with an effusion recurrence
rate of 10%. The median postoperative stay was 5 days and all
patients were discharged home.132
.....................
Authors’ affiliations
4.6 Pleuroperitoneal shunting
• Pleuroperitoneal shunts are an alternative and effective option in patients with a trapped lung or failed
pleurodesis. [B]
In selected patients with trapped lung and large effusions
refractory to chemical pleurodesis, pleuroperitoneal shunting
is an acceptable palliative option. The shunt consists of a
valved chamber (containing two unidirectional valves) with
fenestrated pleural and peritoneal catheters attached at either
end. The device is pressure activated but spontaneous flow will
also occur when the pressure gradient between the pleural
and peritoneal space is more than 1 cm H2O. More often the
pressure gradient is low and requires manual compression of
the pump chamber percutaneously, sometimes over 400 times
per day.126 127 The insertion of the shunt is facilitated by thoracoscopy or a mini-thoracotomy and the duration of hospital
stay varies between 4 and 6 days. The procedure is usually well
tolerated and postoperative morbidity and mortality are
low.128
Complications include shunt occlusion, infection, and
tumour seeding or implantation into the peritoneal cavity.
Shunt occlusion rates vary from 12% to 25% and normally
requires replacement of the shunt.128 129 The presence of pleural
infection, multiple pleural loculations, and inability to
compress the pump chamber are contraindications to pleuroperitoneal shunting.
4.7 Pleurectomy
Pleurectomy is an effective but invasive method for treating
malignant pleural effusions. Complications may include
www.thoraxjnl.com
G Antunes, Department of Respiratory Medicine, James Cook University
Hospital, Middlesborough TS4 3BW, UK
E Neville, Respiratory Centre, St Mary’s Hospital, Portsmouth PO3 6AD,
UK
J Duffy, Cardiothoracic Surgery Department, Nottingham City Hospital,
Nottingham NG5 1PB, UK
N Ali, Kings Mill Centre, Sutton in Ashfield, Nottingham NG17 4LJ, UK
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85 Millar JW, Hunter AM, Horne NW. Intrapleural immunotherapy with
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93 Goldman CA, Skinnider LF, Maksymiuk AW. Interferon instillation for
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94 Wilkins HE, Connolly MM, Grays P, et al. Recombinant interferon
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97 Rusch VW, Figlin R, Godwin D, et al. Intrapleural cisplatin and
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98 Morales M, Exposito MC. Intrapleural mitoxantrone for the palliative
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99 Aasebo U, Norum J, Sager G, et al. Intrapleurally instilled mitoxantrone
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100 Lorch DG, Gordon L, Wooten S, et al. Effect of patient positioning on
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ii39
BTS guidelines for the management of spontaneous
pneumothorax
M Henry, T Arnold, J Harvey, on behalf of the BTS Pleural Disease Group, a subgroup
of the BTS Standards of Care Committee
.............................................................................................................................
Thorax 2003;58(Suppl II):ii39–ii52
1 INTRODUCTION
Pneumothorax is defined as air in the pleural
space—that is, between the lung and the chest
wall.1 Primary pneumothoraces arise in otherwise
healthy people without any lung disease. Secondary pneumothoraces arise in subjects with underlying lung disease. The term pneumothorax was
first coined by Itard, a student of Laennec, in
1803,2 and Laennec himself described the clinical
picture of pneumothorax in 1819.2 He described
most pneumothoraces as occurring in patients
with pulmonary tuberculosis, although he recognised that pneumothoraces also occurred in
otherwise healthy lungs, a condition he described
as “pneumothorax simple”. The modern description of primary spontaneous pneumothorax
occurring in otherwise healthy people was provided by Kjaergard in 1932.3 Primary pneumothorax remains a significant global problem, occurring in healthy subjects with a reported incidence
of 18–28/100 000 per year for men and 1.2–6/
100 000 per year for women.4 5 Secondary pneumothorax is associated with underlying lung disease, whereas primary pneumothorax is not. By
definition, there is no apparent precipitating
event in either. Hospital admission rates for combined primary and secondary pneumothorax are
reported in the UK at between 5.8/100 000 per
year for women and 16.7/100 000 per year for
men. Mortality rates in the UK were 0.62/million
per year for women and 1.26/million per year for
men between 1991 and 1995.6 This guideline
describes the management of spontaneous primary and secondary pneumothorax. It excludes
the management of trauma. Algorithms for the
management of spontaneous primary and secondary pneumothorax are shown in figs 1 and 2.
• Strong emphasis should be placed on the
relationship between the recurrence of
pneumothorax and smoking in an effort
to encourage patients to stop smoking.
[B]
Despite the absence of underlying pulmonary
disease in patients with primary pneumothorax,
subpleural blebs and bullae are likely to play a role
in the pathogenesis since they are found in up to
90% of cases of primary pneumothorax at thoracoscopy or thoracotomy and in up to 80% of cases
on CT scanning of the thorax.7 8 The aetiology of
See end of article for
such bullous changes in otherwise apparently
authors’ affiliations
healthy lungs is unclear. Undoubtedly, smoking
.......................
plays a role9–11; the lifetime risk of developing a
pneumothorax in healthy smoking men may be
Correspondence to:
Dr M Henry, The General
as much as 12% compared with 0.1% in nonInfirmary at Leeds, Great
smoking men.11 This trend is also present, though
George Street, Leeds
to a lesser extent, in women.11 There does not
LS1 3EX, UK;
[email protected] appear to be any relationship between the onset
. . . . . . . . . . . . . . . . . . . . . . . of pneumothorax and physical activity.5 Small
airway obstruction, mediated by an influx of
inflammatory cells, often characterises pneumothorax and may become manifest in the smaller
airways of men at an earlier stage.12 Patients with
primary pneumothoraces tend to be taller than
control patients.13 14 The gradient in pleural
pressure increases from the lung base to the
apex,1 thus alveoli at the lung apex in tall
individuals are subject to significantly greater
distending pressure than those at the base of the
lung and, theoretically, are more predisposed to
the development of subpleural blebs.15 Strong
emphasis should be placed on the relationship
between smoking and pneumothorax in an effort
to deter those smokers who have developed a
pneumothorax from smoking. Despite the apparent relationship between smoking and pneumothorax, 80–86% of young patients continue to
smoke after their first primary pneumothorax.16
The risk of recurrence of primary pneumothorax
is 54% within the first 4 years, with isolated risk
factors including smoking, height in male
patients,14 17 and age over 60 years.17 Risk factors
for secondary pneumothorax recurrence include
age, pulmonary fibrosis, and emphysema.17 18
In an effort to standardise treatment of
primary and secondary pneumothoraces, the
British Thoracic Society (BTS) published guidelines for the treatment of both in 1993.19 Several
studies suggest that compliance with the 1993
guidelines, though improving, remains at only
20–40% among non-respiratory and A&E
staff.20–22 Clinical guidelines have been shown to
improve clinical practice23 24; compliance with
guidelines is related to the complexity of practical
procedures that are described25 and is strengthened by an evidence base.26 Steps in the 1993
guidelines which may need clarification include:
(1) simple aspiration (thoracocentesis) versus
intercostal tube drainage (tube thoracostomy) as
the first step in the management of primary and
secondary pneumothoraces, (2) treatment of elderly pneumothorax patients or patients with
underlying lung disease, (3) when to refer
patients with a difficult pneumothorax to a chest
physician or thoracic surgeon for persistent air
leak or failure of re-expansion of the lung, and (4)
treatment of the recurrent pneumothorax. This
guideline addresses these issues. Its purpose is to
provide a comprehensive evidence based review
of the epidemiology, aetiology, and treatment of
pneumothorax to complement the summary
guidelines for diagnosis and treatment.
2 CLINICAL EVALUATION AND IMAGING
• Expiratory chest radiographs are not recommended for the routine diagnosis of
pneumothorax. [B]
www.thoraxjnl.com
ii40
Henry, Arnold, Harvey
Primary
pneumothorax
Start
NO
Breathless and/or rim of air > 2 cm
on chest radiograph
?
(section 4.1)
YES
Aspiration
YES
?Successful
(section 4.2)
NO
Consider repeat
aspiration
YES
?Successful
(section 4.2.1)
NO
Intercostal drain
?Successful
YES
(section 4.3)
Remove 24 hours after
full re-expansion/cessation
of air leak without clamping
NO
Referral to chest physician within 48 hours
?Suction (section 4.4.1)
Referral to thoracic surgeon
after 5 days (section 4.5)
Figure 1 Recommended algorithm for the treatment of primary pneumothorax.
www.thoraxjnl.com
Consider
discharge
(section 4.6)
BTS guidelines for the management of spontaneous pneumothorax
ii41
Secondary
pneumothorax
Start
Aspiration
NO
Breathless + age > 50 years
?Successful
+ rim of air > 2 cm
on chest radiograph
(section 4.2)
?
(section 4.1)
NO
YES
YES
Intercostal drain
Admit to
hospital for
?Successful
(section 4.3)
24 hours
YES
NO
Referral to chest
physician after 48 hours
?Suction (section 4.4.1)
YES
Remove 24 hours after
Consider
full re-expansion/cessation
discharge
of air leak
(section 4.6)
?Successful
NO
Early discussion with
surgeon after 3 days
(section 4.5)
Figure 2 Recommended algorithm for the treatment of secondary pneumothorax.
www.thoraxjnl.com
ii42
Henry, Arnold, Harvey
• A lateral chest or lateral decubitus radiograph
should be performed if the clinical suspicion of
pneumothorax is high, but a PA radiograph is
normal. [B]
• CT scanning is recommended when differentiating a
pneumothorax from complex bullous lung disease,
when aberrant tube placement is suspected, and
when the plain chest radiograph is obscured by
surgical emphysema. [C]
methods of estimating size from PA chest radiographs are
cumbersome and generally used only as a research tool.42 The
size of a pneumothorax, in terms of volume, is difficult to
assess accurately from a chest radiograph which is a two
dimensional image. In the 1993 guidelines19 pneumothoraces
were classified into three groups:
• “small”: defined as a “small rim of air around the lung”;
• The clinical history is not a reliable indicator of
pneumothorax size. [C]
• “complete”: defined as “airless lung, separate from the diaphragm”.
Clinical history and physical examination usually suggest the
presence of a pneumothorax, although clinical manifestations
are not reliable indicators of size.29 30 In general, the clinical
symptoms associated with secondary pneumothoraces are
more severe than those associated with primary pneumothoraces, and most patients with a secondary pneumothorax
complain of breathlessness which is out of proportion to the
size of the pneumothorax.31 32 Many patients, particularly
those with primary pneumothoraces, do not seek medical
advice for several days, 46% waiting more than 2 days with
symptoms.9 This feature is important because the occurrence
of re-expansion pulmonary oedema (RPO) after re-inflation
may be related to the length of time the lung has been
collapsed (see section 4.4.1).33 34
Arterial blood gas measurements are frequently abnormal
in patients with pneumothorax with the arterial oxygen tension (PaO2) being less than 10.9 kPa (80 mm Hg) in 75% of
patients.35 The presence of underlying lung disease along with
the size of pneumothorax predicts the degree of
hypoxaemia.35 Arterial PaO2 was below 7.5 kPa (55 mm Hg)
and PaCO2 above 6.9 kPa (50 mm Hg) in 16% of cases of
secondary pneumothorax in the largest reported series.36 Pulmonary function tests are weakly sensitive measures of the
presence or size of pneumothorax and are not
recommended.8
In both primary and secondary spontaneous pneumothorax
the diagnosis is normally established by plain chest radiography. In general, expiratory radiographs add little and are
not indicated as a routine investigation, even in the case of a
suspected small apical pneumothorax.37 38 When a pneumothorax is suspected but not confirmed by standard posteroanterior (PA) chest radiographs, lateral radiographs provide
added information in up to 14% of cases.39 The lateral decubitus radiograph is superior to the erect or supine chest
radiograph and is felt to be as sensitive as CT scanning in
pneumothorax detection.40 The upright lateral or lateral decubitus radiograph is clinically helpful where findings on the
upright PA radiograph are unclear. While such small
pneumothoraces may not have much clinical relevance in
patients without underlying lung disease, in patients with
suspected secondary pneumothoraces, even small pneumothoraces may have significant implications and here lateral or
lateral decubitus radiographs are probably valuable. In
patients with severe bullous lung disease CT scanning will differentiate emphysematous bullae from pneumothoraces and
save the patient an unnecessary and potentially dangerous
aspiration.41
This attempt to quantify a pneumothorax tends to underestimate the volume of anything greater than the smallest of
pneumothoraces.1 Since the volume of a pneumothorax
approximates to the ratio of the cube of the of the lung diameter to the hemithorax diameter, a pneumothorax of 1 cm on
the PA chest radiograph occupies about 27% of the hemithorax
volume if the lung is 9 cm in diameter and the hemithorax
10 cm: (103 – 93)/103 = 27%. Similarly, a 2 cm radiographic
pneumothorax occupies 49% of the hemithorax on the same
basis (fig 3).
In view of the proximity of the lung surface to the chest wall
in a pneumothorax of <1 cm, aspiration using a sharp needle
may not be advisable. However, given that the actual volume of
a 2 cm pneumothorax approximates to a 50% pneumothorax,
this should be considered large in size and can be treated
safely by aspiration when circumstances dictate. For the purposes of these new guidelines, “small” is therefore regarded as
a pneumothorax of <2 cm and “large” as a pneumothorax of
>2 cm.
If accurate size estimates are required, CT scanning is the
most robust approach.43 Otherwise, it is only recommended for
difficult cases such as patients in whom the lungs are obscured
by overlying surgical emphysema, or to differentiate a
pneumothorax from a suspected bulla in complex cystic lung
disease.44 The routine use of CT scans preoperatively in
patients with pneumothorax and suspected emphysema or
isolated bullae adds little to the plain PA chest radiograph
from the point of view of management of the patient.45
• “moderate”: defined as lung “collapsed halfway towards
the heart border”; and
4 TREATMENT OPTIONS FOR SPONTANEOUS
PNEUMOTHORAX
4.1 Observation
• Observation should be the treatment of choice for
small closed pneumothoraces without significant
breathlessness. [B]
• Patients with small (<2 cm) primary pneumothoraces not associated with breathlessness should be
considered for discharge with early outpatient
review. These patients should receive clear written
advice to return in the event of worsening breathlessness. [B]
1993:
Small secondary pneumothorax
Tx suggested: simple
aspiration
3 SIZE OF PNEUMOTHORAX
• The previous classification of the size of a pneumothorax tends to underestimate its volume. In these
new guidelines the size of a pneumothorax is divided
into “small” or “large” depending on the presence of
a visible rim of <2 cm or >2 cm between the lung
margin and the chest wall.
The plain PA radiograph is a poor method of quantifying the
size of a pneumothorax as it usually underestimates it. Exact
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9.5 cm
12 cm
2003:
Volume_of pneumothorax
(123 9.53) /123 = 50%
Tx suggested: intercostal tube
drainage
Figure 3 Quantitation of size of pneumothorax: 1993 versus 2003
guidelines.
BTS guidelines for the management of spontaneous pneumothorax
• If a patient with a pneumothorax is admitted
overnight for observation, high flow (10 l/min) oxygen should be administered, with appropriate caution in patients with COPD who may be sensitive to
higher concentrations of oxygen. [B]
• Breathless patients should not be left without intervention regardless of the size of the pneumothorax
on a chest radiograph. [C]
4.1.1 Primary pneumothoraces, minimal symptoms
Observation alone is advised for small, closed, mildly symptomatic spontaneous pneumothoraces.21 30 46–48 70–80% of pneumothoraces estimated at smaller than 15% have no persistent
air leak and recurrence in those managed with observation
alone is less than in patients treated with intercostal tube
drainage.48 Patients with small primary pneumothoraces and
minimal symptoms do not require hospital admission, but it
should be stressed before discharge that they should return
directly to hospital in the event of developing breathlessness.
Most patients in this group who fail this “treatment” and
require intercostal tube drainage have secondary
pneumothoraces.48
4.1.2 Secondary pneumothoraces, minimal symptoms
Observation alone is only recommended in patients with small
secondary pneumothoraces of less than 1 cm depth or isolated
apical pneumothoraces in asymptomatic patients. Hospitalisation is recommended in these cases. All other cases will
require active intervention (aspiration or chest drain insertion, see later sections).
4.1.3 Symptomatic pneumothoraces, primary or
secondary
Observation alone is inappropriate and active intervention is
required. Marked breathlessness in a patient with a small
(<2 cm) primary pneumothorax may herald tension
pneumothorax.48 If a patient is hospitalised for observation,
supplemental high flow (10 l/min) oxygen should be given
where feasible.49 Inhalation of high concentrations of oxygen
may reduce the total pressure of gases in pleural capillaries by
reducing the partial pressure of nitrogen. This should increase
the pressure gradient between the pleural capillaries and the
pleural cavity, thereby increasing absorption of air from the
pleural cavity. The rate of resolution/reabsorption of spontaneous pneumothoraces is 1.25–1.8% of the volume of hemithorax every 24 hours.47 50 In a group of 11 patients with
pneumothoraces ranging in size from 16% to 100%, the mean
rate of re-expansion was 1.8% per day and full re-expansion
occurred at a mean of 3.2 weeks.47 A 15% pneumothorax
would therefore take 8–12 days to resolve fully. The addition of
high flow oxygen therapy has been shown to result in a fourfold increase in the rate of pneumothorax reabsorption during
periods of oxygen supplementation.49
4.2 Simple aspiration
• Simple aspiration is recommended as first line treatment for all primary pneumothoraces requiring
intervention. [A]
• Simple aspiration is less likely to succeed in secondary pneumothoraces and, in this situation, is only
recommended as an initial treatment in small
(<2 cm) pneumothoraces in minimally breathless
patients under the age of 50 years. [B]
• Patients with secondary pneumothoraces treated
successfully with simple aspiration should be admitted to hospital and observed for at least 24 hours
before discharge. [C]
The 1993 BTS guidelines19 recommended simple aspiration as
first line treatment in all primary pneumothoraces where
ii43
there is complete collapse of the lung, and in smaller primary
pneumothoraces in which patients complain of significant
breathlessness. Simple aspiration was also recommended as
initial treatment in secondary pneumothoraces where there is
moderate or complete collapse of the lung and in smaller secondary pneumothoraces where significant breathlessness is
present. Small was defined as a “small rim of air around the
lung”, moderate as “lung collapsed halfway towards the heart
border”, and complete as “airless lung, separate from the diaphragm”.
A study describing treatment practices for pneumothoraces
after the 1993 guidelines showed that only 17 of 43 decisions
to aspirate pneumothoraces by A&E staff, perhaps because of
unfamiliarity with the technique, and nine of 26 similar decisions made by medical staff seemed appropriate.20 A similar
study undertaken in Scotland and completed before the publication of the 1993 guidelines reported that only three of 38
spontaneous pneumothoraces (one primary, two secondary)
were treated initially by aspiration alone and all three were
successful.21 It would seem, therefore, that many medical staff
are unaware of the guidelines in this respect, or are unwilling
or unable to aspirate.
Successful re-expansion of the lung is less likely after simple aspiration in secondary pneumothorax (33–67%) than in
primary (59–83%).51–53 However, several larger series which
used this technique found that 59–73% of all pneumothoraces
requiring intervention could be successfully aspirated.51 52 54–56
Successful aspiration in these series depended on age (under
50 years: 70–81% success, over 50 years: 19–31% success), the
presence of chronic lung disease (27–67% success), and the
size of the pneumothorax (<3 l aspirated: 89% success, >3 l:
no success; >50% on chest film: 62% success, <50% on chest
film: 77% success). In a prospective randomised trial to compare simple aspiration and tube drainage of pneumothoraces,
Andrivert and colleagues55 found a 20% recurrence rate at 3
months after simple aspiration of primary pneumothoraces
and a 28% recurrence rate after tube drainage demonstrating
that simple aspiration is no less effective from the point of
view of recurrence than the more invasive intercostal tube
drainage. In a more recent randomised controlled trial Noppen
and coworkers53 showed that simple aspiration was as
successful in treating first primary pneumothoraces as immediate intercostal tube drainage (59% versus 63%). Patients
treated with simple aspiration were less likely to be hospitalised and less likely to suffer a recurrence of the pneumothorax
over the next 12 months. Harvey and Prescott,56 on behalf of
the British Thoracic Society, confirmed that simple aspiration
of primary pneumothoraces is as effective as tube drainage
when recurrence of pneumothorax at 12 months was taken as
an end point. Further advantages of simple aspiration over
intercostal tube drainage are a reduction in total pain scores
during hospitalisation and shorter hospital stays.56 In centres
where the experience and equipment is available, consideration should be give to using small bore catheter aspiration kits
(CASP, see below) to aspirate pneumothoraces as the catheter
may be left in place until full re-expansion of the lung is confirmed. Otherwise, repeat aspiration or connection to an
underwater seal system may be facilitated through these
indwelling small bore catheters.
Large secondary pneumothoraces (>2 cm), particularly in
patients over the age of 50, should be considered a high risk of
failure for simple aspiration and recurrence and therefore tube
drainage is recommended as appropriate initial treatment. If
simple aspiration is considered in patients with secondary
pneumothoraces, admission for observation for at least 24
hours should be undertaken, with prompt progression to tube
drainage if needed. Active treatment of the underlying lung
disorder will also be necessary.
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ii44
4.2.1 Repeat aspiration and catheter aspiration of simple
pneumothorax
• Repeated aspiration is reasonable for primary pneumothorax when the first aspiration has been unsuccessful (i.e. patient still symptomatic) and a volume
of <2.5 l has been aspirated on the first attempt. [B]
• Catheter aspiration of pneumothorax (CASP) can be
used where the equipment and experience is available. [B]
• Catheter aspiration kits with an integral one way
valve system may reduce the need for repeat aspiration. [C]
Failure to re-expand a primary pneumothorax with aspiration
can be successfully corrected by a second aspiration in over
one third of cases, particularly where the initial attempt failed
because of a kinked or displaced catheter.51 Despite this, the
tendency is to treat aspiration failures with tube
drainage.20 51 52 A second attempt at simple aspiration of the
pneumothorax should be considered unless >2.5 l was
aspirated during the unsuccessful first attempt.56 Catheter
aspiration of simple pneumothorax (CASP) involves a small
(8 F) catheter being passed over a guidewire into the pleural
space. A three way stopcock is attached and air may be
aspirated via a 50 ml syringe. This controls up to 59% of all
pneumothoraces. Addition of a Heimlich valve and suction
may improve success rates further.57–59
4.3 Intercostal tube drainage
• If simple aspiration or catheter aspiration drainage
of any pneumothorax is unsuccessful in controlling
symptoms, then an intercostal tube should be
inserted. [B]
• Intercostal tube drainage is recommended in secondary pneumothorax except in patients who are not
breathless and have a very small (<1 cm or apical)
pneumothorax. [B]
• A bubbling chest tube should never be clamped. [B]
• A chest tube which is not bubbling should not usually
be clamped. [B]
• If a chest tube for pneumothorax is clamped, this
should be under the supervision of a respiratory physician or thoracic surgeon, the patient should be
managed in a specialist ward with experienced nursing staff, and the patient should not leave the ward
environment. [C]
• If a patient with a clamped drain becomes breathless
or develops subcutaneous emphysema, the drain
must be immediately unclamped and medical advice
sought. [C]
Underwater seal drainage using a chest tube was introduced
in 1875.60 Widespread closed tube drainage was first adopted
during the 1917 influenza epidemic.61 Intercostal tube
drainage or underwater seal drainage in its modern form has
been in use since 1916 when Kenyon62 described a “siphon”
method of draining traumatic haemothorax. This treatment,
despite being extremely effective, has many potential disadvantages ranging from chest and abdominal visceral trauma
from sharp trocars in the hands of inexperienced operators63 to
the bulkiness of the underwater seal bottle system which must
be kept upright.
Likewise it may be hazardous to clamp a chest drain that is
still bubbling, thereby potentially converting simple pneumothoraces into life threatening tension pneumothoraces.64 Such
instances are anecdotal, and there is no evidence of which we
are aware that clamping the tube improves success rates or
prevents recurrence. Almost identical success rates have been
recorded for the maintenance of full re-expansion of the lung
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Henry, Arnold, Harvey
after 24 hours whether the tube is clamped or not before
removal.80 However, many experienced physicians still support
the use of clamping of chest drains before their removal to
detect small air leaks not immediately obvious at the bedside.
By clamping the chest drain for several hours and performing
a chest radiograph, a minor or intermittent air leak may be
detected, potentially avoiding the need for chest tube reinsertion. In the ACCP Delphi consensus statement65 about half the
consensus group supported clamping and half did not, and
this seems similar to the UK spread of opinion. Drain clamping is therefore not generally recommended for safety reasons,
but is acceptable under the supervision of nursing staff who
are trained in the management of chest drains and who have
instructions to unclamp the chest drain in the event of any
clinical deterioration. Patients with a clamped chest drain
inserted for pneumothorax should not leave the specialist
ward area.
Despite these risks, tube drainage remains an effective
treatment for pneumothorax although it is not proven that
tube drainage should be performed as the initial treatment in
any pneumothorax. Simple aspiration should be considered as
the primary treatment for all primary pneumothoraces
requiring intervention but not considered to be under tension.
In secondary pneumothoraces in patients over 50 years with
pneumothorax >50%, primary failure rates for aspiration are
estimated at >50%.51 52 66 Age alone is a strong predictor of
failure of simple aspiration (>50 years, success 27–67%),51 52
although in those over the age of 50 years with no evidence of
pre-existing lung disease there is no evidence that tube drainage should be recommended before simple aspiration as
primary treatment.
Analgesic use during the insertion of intercostal tubes
remains poorly studied. The injection of intrapleural local
anaesthetic (20–25 ml = 200–250 mg, 1% lignocaine) given as
a bolus and at eight hourly intervals as necessary after the
insertion of the drain significantly and safely reduced pain
scores without affecting blood gas measurements, either with
or without chemical pleurodesis. There are no data detailing
the incidence of pleural infection with this technique.67 68
Chest tubes frequently (59%) end up in fissures,69 but these
tubes seem to retain their effectiveness. Step by step
guidelines to chest drain insertion are described elsewhere in
these guidelines (page ii53).
4.3.1 Complications of intercostal tube drainage
The complications of intercostal tube drainage include
penetration of the major organs such as lung, stomach, spleen,
liver, heart and great vessels, and are potentially fatal.63 70–73
These complications occur more commonly when a sharp
metal trocar is inappropriately applied during the
procedure.63 72 73
In the largest series reviewing complications of tube drainage in recent times, Chan and colleagues74 identified
complications in 18% of chest drain insertions for all
indications; 64% of these chest tubes (n=373) were inserted
for treatment of pneumothorax. However, 15% of the “complications” identified involved failure of resolution of the
pneumothorax and only 4% involved aberrant tube placement. Notably, complications related to tube placement
occurred most commonly on medical wards. CT assessment
suggests a higher rate of incorrect tube placement. Baldt and
colleagues75 identified 3% of tubes placed extrathoracically
and 6% placed within the lung during the treatment of pneumothoraces. This highlights the need for correct training in
chest tube placement. In some circumstances, thoracic CT
scanning is valuable for assessing chest tube position—for
example, when misplacement is suspected but not confirmed
on a plain radiograph.75
Pleural infection is another complication of intercostal tube
drainage. The rate of empyema after chest tube insertion has
BTS guidelines for the management of spontaneous pneumothorax
been estimated as 1%.74 Other series have reported an
incidence of up to 6% of chest tube related empyema in
trauma cases and suggested that the administration of
prophylactic antibiotics should be considered, particularly
where a prolonged period of chest tube drainage might be
anticipated.76 77 This highlights the need for full aseptic
technique in the insertion or manipulation of any chest drainage system.
Finally, surgical emphysema is a well recognised complication of intercostal tube drainage.78 This is generally of cosmetic
importance only, subsiding after a few days. The development
of surgical emphysema associated with pneumothorax involves an air filled space, not formerly in communication with
the subcutaneous tissue, being brought into communication
with the subcutaneous tissues. This may occur in the presence
of a malpositioned, kinked, blocked, or clamped tube.
Likewise, a small tube in the presence of a very large leak may
potentially cause surgical emphysema. Occasionally, the
resulting acute airway obstruction or thoracic compression
may lead to respiratory compromise.78 79 The treatment is
usually conservative but, in life threatening situations,
tracheostomy, skin incision decompression, and insertion of
large bore modified subcutaneous chest drains have all been
used.78
4.3.2 Size of tube
• There is no evidence that large tubes (20–24 F) are
any better than small tubes (10–14 F) in the management of pneumothoraces. The initial use of large
(20–24 F) intercostal tubes is not recommended,
although it may become necessary to replace a small
chest tube with a larger one if there is a persistent air
leak. [B]
Although one study suggested that success rates for the treatment of pneumothoraces with small chest tubes (13 F) were
poor and that larger sized catheters should be used,80
subsequent studies have not confirmed this and suggest that
smaller calibre chest tubes are just as effective.81–84 Primary
success rates of 84–97% were recorded in these studies using
drains of 7–9 F gauge. Recent technical developments have
allowed the addition of a Heimlich flutter valve to small tubes
as well as to larger bore tubes.
Factors which might predispose to small tube failure, thus
favouring the choice of a larger tube, would be the presence of
pleural fluid and the presence of a large air leak which exceeds
the capacity of the smaller tubes.82 The use of an indwelling
small lumen Teflon catheter (2 mm) inserted “over needle and
guidewire” attached to a flutter valve after partial aspiration
with a 60 ml syringe proved successful in 27 of 28 patients
with a mean drainage time of 48 hours.59 Using a small calibre
chest drain system, the median duration of drainage ranged
from 2 to 4 days, which compares very favourably with larger
intercostal tube drainage systems.59 82 83 Difficulties with tube
blockage were not encountered in any of these studies.
Chemical pleurodesis is still possible through smaller tubes
including indwelling catheter systems.
If the decision is made to insert a chest drain, small
(10–14 F) systems should be used initially. The use of catheter
over guidewire systems (Seldinger technique) may prove to be
as safe and effective as small calibre tubes, although they are
more expensive. They are being used with increasing
frequency, but further evidence is required before they can be
recommended for initial use.
4.4 Referral to respiratory specialists
• Pneumothoraces which fail to respond within 48
hours to treatment should be referred to a respiratory physician. [C]
Failure of a pneumothorax to re-expand or a persistent air leak
exceeding 48 hours duration should prompt referral to a res-
ii45
piratory physician. Such patients may require sustained chest
drainage with complex drain management (suction, chest
drain repositioning) and thoracic surgery decisions. These
issues will be better managed by physicians with specific
training and experience in these problems and established
relationships with a thoracic surgeon. Drain management is
also best delivered by nurses with substantial experience in
this area.
4.4.1 Chest drain suction
• Suction to an intercostal tube should not be applied
directly after tube insertion, but can be added after
48 hours for persistent air leak or failure of a
pneumothorax to re-expand. [B]
• High volume, low pressure (–10 to –20 cm H2O)
suction systems are recommended. [C]
• Patients requiring suction should only be managed
on lung units where there is specialist medical and
nursing experience. [C]
There is no evidence to support the routine initial use of suction applied to chest drain systems in the treatment of spontaneous pneumothorax.80 85 A persistent air leak, with or without incomplete re-expansion of the pneumothorax on a chest
radiograph, is the usual reason for applying suction to an
intercostal tube system. A persistent air leak is usually
arbitrarily defined as a continued air bubbling through an
intercostal tube 48 hours after insertion. Mathur and
colleagues86 retrospectively reviewed 142 cases of spontaneous
pneumothorax requiring chest drain insertion. The median
time to resolution was 8 days (19 days in those with
underlying lung disease), which was not related to the initial
size of the pneumothorax. Most of the patients (30/43) with a
persistent air leak had suction applied, but without standardisation of the degree of suction or of the point of initiation (the
first 4 days in the majority). Normal intrapleural pressures are
–8 cm H2O during inspiration and –3.4 cm H2O during expiration. During intercostal tube drainage various factors influence the amount of suction applied to the pleural space.63 87 It
has been suggested that, because the magnitude of these
physiological factors varies, it is desirable to apply –10 to
–20 cm H2O suction to all pneumothoraces which are slow to
re-expand, and the system used should have the capacity to
increase the suction with an air flow volume of 15–20 l/min.88
Over 40 years ago Roe89 stressed the importance of high
volume vacuums to drain the pleural space during pneumothoraces. The use of high pressure, high volume suction is not,
however, recommended because of the ease with which it can
generate high air flow suction which may lead to air stealing,
hypoxaemia, or the perpetuation of persistent air leaks.90 Likewise, high pressure, low volume systems should be avoided.64
High volume, low pressure systems such as a VernonThompson pump or wall suction with an adaptor to reduce
pressure are recommended. Unfortunately, due to the lack of
more recent randomised controlled trials examining the role
of suction with intercostal tube systems, evidence based
recommendations cannot be applied. The best practice from
previous studies to date, as above, suggests that suction should
be applied after 48 hours, but that surgical referral for a
persistent air leak in those without pre-existing lung disease
should be made at 5–7 days. Significantly, earlier referral (2–4
days) should be considered in those with underlying disease,
a large persistent air leak, or failure of the lung to
re-expand.91–93 If suction is to be applied to a chest drain, it is
recommended that the patient should be situated in an area
where specialist nursing experience is available.
The addition of suction too early after the insertion of a
chest tube, particularly in the case of a primary pneumothorax which may have been present for a few days, may
precipitate re-expansion pulmonary oedema (RPO) and is
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ii46
contraindicated. RPO is probably caused by the increased permeability of capillaries damaged during a pneumothorax. This
becomes manifest as oedema during re-expansion due to further mechanical stresses applied to the already “leaky”
capillaries.94 Clinically, these patients manifest symptoms of
coughing and breathlessness or chest tightness after insertion
of the chest tube. In those whose symptoms persist, a repeat
chest radiograph after 24 hours will often show pulmonary
oedema in the treated lung, although pulmonary oedema may
also develop in the contralateral lung.95 The incidence of RPO
may be up to 14% and is higher in those with larger primary
pneumothoraces and in younger patients (<30 years),
although in most cases RPO does not progress beyond a radiological phenomenon.96 However, the clinical relevance of RPO
must not be understated as the outcome has been reported as
fatal in 20% of 53 reported cases who developed a clinical
deterioration as part of an RPO syndrome in one series.95 Particular caution should therefore be exercised in treating young
patients with large pneumothoraces and suction should not be
used immediately in the treatment of a spontaneous
pneumothorax. Even when employed later and it is suspected
that the pneumothorax has been present for a considerable
period of time, the potential development of RPO should be
considered.96
4.4.2 Chemical pleurodesis
• Chemical pleurodesis can control difficult or recurrent pneumothorax [A] but should only be attempted if the patient is either unwilling or unable to
undergo surgery. [B]
• Medical pleurodesis for pneumothorax should be
performed by a respiratory specialist. [C]
Chemical pleurodesis has generally been advocated by chest
physicians experienced in thoracoscopy. The instillation of
substances into the pleural space should lead to an aseptic
inflammation with dense adhesions, leading ultimately to
pleural symphysis. There is a high rate of recurrence of
primary and secondary pneumothoraces,14 and efforts to
reduce these rates by instillation of various sclerosants—
either via chest drains or by surgical means—are regularly
undertaken without clear guidelines to direct physicians in
their use. In the majority of cases, when appropriate, the prevention of further pneumothoraces should be undertaken by
surgical means. The rate of recurrence of pneumothoraces
after surgical intervention either by thoracotomy or VATS,
with or without surgical pleurodesis, is far less than after
medical pleurodesis.36 97–99 A small number of individuals are
either too frail or are unwilling to undergo any definitive surgical treatment to prevent recurrence of their pneumothoraces
and, in these instances, medical chemical pleurodesis may be
appropriate.
During the last decade many sclerosing agents have been
studied.36 97 100–103 Tetracycline is recommended as the first line
sclerosant therapy in both primary and secondary pneumothoraces. It was initially proposed as it proved to be the most
effective sclerosant in animal models.101 104 105 Recently,
parenteral tetracycline for pleurodesis has become more difficult to obtain due to problems with the manufacturing process. The parenteral preparation is currently available in
Germany and may be imported via international wholesalers.
These suppliers state that supplies are expected to remain
available for the foreseeable future. Minocycline and doxycycline have been shown to be reasonable alternatives as
sclerosants in animal models.104 105
The rate of recurrence of pneumothorax is the primary
indicator of success for any sclerosant. Although tetracycline
has been shown significantly to reduce the incidence of early
recurrence, the incidence of late recurrence is 10–20% which is
unacceptably high compared with surgical methods of
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Henry, Arnold, Harvey
pleurodesis.97 99 103 Large randomised controlled studies comparing the use of tetracycline as a sclerosant with standard
management in primary pneumothorax are needed to
determine whether or not tetracycline should be used after
treatment of a first uncomplicated primary pneumothorax to
prevent recurrence. Tetracycline can, however, be recommended for recurrent primary pneumothorax and secondary
pneumothorax when surgery is not an option, and talc may be
used on the grounds that it is the most effective agent in
malignant effusion. There is conflicting evidence as to whether
tetracycline is effective for the treatment of fully expanded
pneumothorax with persistent air leak.36 106 107 The largest of
these studies, the Veterans Administration Study, did not support the use of intrapleural tetracycline to facilitate the closure
of a persistent air leak.36 Macoviak and colleagues107 suggest
that intrapleural tetracycline can facilitate the closure of a
persistent air leak provided that the lung can be kept
expanded so that symphysis can occur. Likewise, there is conflicting evidence as to whether intrapleural tetracycline shortens the length of stay in hospital with pneumothorax.36 97 103
The dosage of intrapleural tetracycline requires clarification. Almind et al97 found a reduction in the incidence of
recurrence in a group receiving 500 mg tetracyline via chest
drains compared with those treated by tube drainage alone.
This reduction was not significant. The Veterans Administration Study,36 which used 1500 mg tetracycline, showed a
significant reduction in the incidence of recurrence of
pneumothorax without significant extra morbidity. This dose
of intrapleural tetracycline is therefore recommended as the
standard dose for medical pleurodesis. While pain was
reported more frequently in the group treated with tetracycline at a dose of 1500 mg,36 others have reported no increase
in pain with tetracycline at a dose of 500 mg provided
adequate analgesia is given.97 Adequate analgesia may be
achieved with administration of intrapleural local anaesthesia. Standard doses (200 mg (20 ml) 1% lignocaine) are
significantly less effective than larger doses (250 mg (25 ml)
1% lignocaine). The higher doses have been shown to increase
the number of pain free episodes from 10% to 70% with no
appreciable toxicity.68
Medical and surgical pleurodesis using talc remain effective
alternatives to tetracycline pleurodesis. There are no controlled trials comparing talc and tetracycline as sclerosants in the
treatment of pneumothorax. The issue of talc pleurodesis will
be dealt with later in the surgical section of this review as most
trials using talc tend to focus on surgical talc pleurodesis.
Since medical pleurodesis is recognised to be “second best”
care and its use will imply a “difficult” case, it is recommended
that medical pleurodesis be undertaken only by respiratory
specialists or thoracic surgeons.
4.5 Referral to thoracic surgeons
• In cases of persistent air leak or failure of the lung to
re-expand, the managing respiratory specialist
should seek an early (3–5 days) thoracic surgical
opinion. [C]
• Open thoracotomy and pleurectomy remains the
procedure with the lowest recurrence rate for
difficult or recurrent pneumothoraces. Minimally
invasive procedures, thoracoscopy (VATS), pleural
abrasion, and surgical talc pleurodesis are all effective alternative strategies.
The timing of surgical intervention for pneumothorax has
recently been challenged and remains contentious. There is no
evidence based justification for the arbitrary but widely advocated cut off point of 5 days for surgery for a persistent air
leak.48 Chee and colleagues108 showed that 100% of primary
pneumothoraces treated by tube drainage with persistent air
leaks for more than 7 days had resolved their air leaks by 14
days and 79% of those with secondary pneumothoraces and
BTS guidelines for the management of spontaneous pneumothorax
persistent air leaks had resolved their air leaks by 14 days with
no mortality. However, considering the efficacy and relatively
low levels of morbidity and recurrence associated with surgery
for pneumothorax,109–112 earlier surgical intervention has been
advocated for persistent air leak or failure of re-expansion,
particularly in cases of secondary pneumothorax.92 113 Several
authors have recommended operative referral/intervention as
early as 3 days for a persistent air leak. However, these studies
were not controlled.91 93 Despite the reduction in the incidence
of late recurrence of pneumothorax in many of these studies,
surgical referral for a persistent air leak in a first primary
pneumothorax within the first 4–5 days is not supported by
the literature. However, best practice suggests that protracted
chest tube drainage is not in the patient’s interest. It is therefore recommended that patients with difficult pneumothoraces should receive care from a respiratory physician and that a
thoracic surgical opinion will be an early part of management.
According to the statistical and perceived risk of recurrence,
accepted indications for operative intervention are as follows:
• Second ipsilateral pneumothorax
• First contralateral pneumothorax
• Bilateral spontaneous pneumothorax
• Persistent air leak (>5–7 days of tube drainage; air leak or
failure to completely re-expand)
• Spontaneous haemothorax
• Professions at risk (e.g. pilots, divers)108 110 114–116
4.5.1 Surgical strategies
There are two objectives in the surgical management of a
pneumothorax. The first widely accepted objective is resection
of blebs or the suture of apical perforations to treat the underlying defect. The second objective is to create a pleural
symphysis to prevent recurrences. There is debate between
those who favour surgical pleurodesis or pleural abrasion versus those who favour partial or total pleurectomy as a definitive treatment to prevent recurrence of pneumothorax,109 117 118
although a relatively recent comprehensive review of this area
suggests a slight advantage of pleurectomy over pleural abrasion with a recurrence rate of 0.4% after pleurectomy (n=752)
and 2.3% after pleural abrasion (n=301).109 Operative techniques have tended towards minimally invasive procedures
over the last few years. In order to be considered effective,
these techniques should yield results comparable to the “gold
standard” open thoracotomy procedure—that is, the operative
morbidity should be less than 15% and the pneumothorax
recurrence rate should be less than 1%.37 99 112
Open thoracotomy
In 1941 Tyson and Crandall119 described pleural abrasion as a
treatment for pneumothorax and in 1956 Gaensler117 introduced parietal pleurectomy for recurrent pneumothorax. This
procedure produces uniform adhesions between the pleura
and the chest wall. Both of these techniques are designed to
obliterate the pleural space by creating symphysis between the
two pleural layers or between the visceral pleura and subpleural plane, in the case of parietal pleurectomy. In order to prevent recurrence, however, an appropriate closure at the site of
the pleural air leak is essential either by cauterisation, ligation,
or suture of accompanying blebs.116 Open thoracotomy yields
the lowest postoperative recurrence results. Bulla ligation/
excision, thoracotomy with pleural abrasion, and either apical
or total parietal pleurectomy all have failure rates under
0.5%.48 110 Morbidity from thoracotomy for pneumothorax has
an overall incidence of 3.7%, mostly in the form of sputum
retention and postoperative infection.110 Open thoracotomy is
generally performed using single lung ventilation, a limited
posterolateral thoracotomy allowing parietal pleurectomy,
excision, or stapling of bullae or pleural abrasion.120 Isolated
lung ventilation during open thoracotomy facilitates full visu-
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alisation of the visceral pleura. This may not be possible during a VATS procedure, increasing the risk of missing a leaking
bulla.121–123 Open thoracotomy may be associated with increased postoperative respiratory dysfunction and hospital
stay compared with VATS procedures.120 It is suggested that the
success rates with the open procedure are higher.124 Thus, surgical authorities suggest open thoracotomy in patients with
secondary pneumothoraces who may have extensive pleural
disease requiring more extensive pleurectomy, subpleural
bullectomy, or pleural abrasion.110 114 125
Surgical chemical pleurodesis
• Surgical chemical pleurodesis is best achieved with
5 g sterile talc. Side effects such as ARDS and
empyema are reported but rare. [A]
The use of talc pleurodesis is now a subject of renewed interest because of the potential unavailability of tetracycline, its
low cost, and a record of successful pleurodesis (85–92%) that
is similar to alternative thoracoscopic techniques for complicated pneumothorax.99 114 126 127 While talc slurry inserted under
medical supervision via intercostal tube drainage tends to be
less favoured than thoracoscopic talc poudrage, both methods
have been shown to be effective. The overall success rate for
talc pleurodesis reviewed by meta-analysis is 91%.126 Surgical
pleurodesis with tetracycline is not generally felt to be a satisfactory alternative, with recurrence rates of 16% in a series of
390 patients who underwent surgical pleurodesis using
tetracycline.98 There are no controlled trials comparing pain
during talc pleurodesis with that using other agents, although
it is suggested that talc pleurodesis is no more difficult or
painful a procedure than tetracycline pleurodesis.128–132 Dosages of talc ranging from 2 g to 10 g have been used, but the
suggestion that higher dosages are more effective has not been
established by controlled trials. On the basis of a metaanalysis of uncontrolled data, 5 g talc by VATS is recommended with a success rate of 87%, which is very close to the
success rates using more extensive operative approaches.126
Side effects reported with talc pleurodesis include five cases of
adult respiratory distress syndrome (ARDS), although the risk
of ARDS may be related to the size of talc particles used133;
empyema, although this is rare when properly sterilised talc is
used126 134 135; pneumonia; and respiratory failure.134 In view of
these potential side effects, standard first line usage of talc
poudrage or talc slurry pleurodesis should be approached with
caution since surgery not dependent on introducing a foreign
agent is usually an option. Lower dosages of 2–5 g should be
used until dosage schedules and effectiveness have been clarified. Long term safety does not appear to be an issue if
asbestos-free talc is used. The success rates with talc poudrage
and talc slurry pleurodesis are similar, so either approach can
be recommended. Because of the relatively high failure rates
of over 9% with talc pleurodesis compared with surgical pleural stripping procedures, talc pleurodesis should not be
considered as initial treatment for primary spontaneous
pneumothorax requiring surgical intervention. In those
patients who are either unwilling or too unwell to undergo
general anaesthesia, medical pleurodesis with either tetracycline or talc (via an intercostal tube) is recommended.
Transaxillary minithoracotomy
Becker and Munro136 pioneered this technique in the 1970s.
The procedure is considered a minimally invasive procedure.
The incision in the axillary margin measures 5–6 cm. Apical
pleurectomy or abrasion may be performed and the apex carefully inspected for pleural blebs or bullae which may be
stapled. The largest series examining this technique reported
a mean hospital stay of 6 days, a recurrence rate of 0.4%, and
a complication rate of 10%, most of which were minor.125 These
results make this procedure a realistic alternative to open
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ii48
thoracotomy for the treatment of complicated spontaneous
pneumothorax.
Video assisted thoracoscopic surgery (VATS)
The evaluation of VATS for spontaneous pneumothorax is limited by the small number of randomised trials comparing it
with alternative surgical approaches. To date, there have only
been two randomised studies which have attempted to define
the role of VATS in the treatment of spontaneous
pneumothorax.120 137 In a comprehensive review, Massard and
colleagues99 have suggested that the impression that VATS is
superior to open procedures in terms of morbidity, time in
hospital, and cost may not be wholly correct. Minimally
invasive surgery may have a complication rate similar to open
procedures at about 8–10%.120 122 138 Recurrence rates of
pneumothorax after VATS are 5–10%,114 127 which are higher
than the 1% rates reported after open procedures.110 While
bullectomy, pleurectomy, pleural abrasion, and surgical pleurodesis have all been shown to have reasonable success rates
when carried out thoracoscopically,120 122 128 139–141 there are concerns associated with VATS performed under local anaesthetic
supplemented by nitrous oxide inhalation. These arise from
the inability to obtain isolated single lung ventilation and
include difficulties in inspecting the entire visceral pleural
surface, increasing the risk of missing a leaking bleb or
bulla.123 142 It is also suggested that a less intense pleural
inflammatory reaction is induced by VATS procedures leading
to a less effective pleurodesis.143 Several authors suggest that
VATS offers significant advantages over open thoracotomy
including a shorter postoperative hospital stay,114 120 127 138 142
significantly less postoperative pain,120 125 143 144 and better
pulmonary gas exchange in the postoperative period.145 However, Kim and colleagues in their randomised controlled trial
did not confirm a shorter postoperative stay in the VATS
groups.137
Further randomised trials comparing VATS with transaxillary and open thoracotomies are required and, until these data
are available, VATS cannot be considered to be established as
being superior to thoracotomy.144 Waller and colleagues146 suggested that, while VATS may be the preferred surgical
procedure for young fit people with complicated or recurrent
primary pneumothoraces, it is less reliable in cases of secondary pneumothorax. In cases of secondary pneumothorax, open
thoracotomy and repair is still the recommended approach
and VATS procedures should be reserved for those who might
not tolerate an open procedure because of poor lung function.
4.6 Discharge and follow up
• Patients discharged without intervention should
avoid air travel until a chest radiograph has confirmed resolution of the pneumothorax. [C]
• Diving should be permanently avoided after a pneumothorax, unless the patient has had bilateral surgical pleurectomy. [C]
• Primary pneumothorax patients treated successfully
by simple aspiration should be observed to ensure
clinical stability before discharge. Secondary pneumothorax patients who are successfully treated with
simple aspiration should be admitted for 24 hours
before discharge to ensure no recurrence. [C]
Patients with spontaneous pneumothoraces who are discharged without active intervention should be advised to
return for a follow up chest radiograph after 2 weeks. These
patients should be cautioned against flying until a follow up
chest radiograph confirms full resolution of the pneumothorax. Commercial airlines currently arbitrarily advise that there
should be a 6 week interval between having a pneumothorax
and travelling by air. A recent chest radiograph should confirm
resolution of the pneumothorax. A patient with a current
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Henry, Arnold, Harvey
closed pneumothorax should not travel on a commercial
flight. There is no evidence that air travel precipitates
recurrence of a pneumothorax, but recurrence during a flight
may have serious repercussions. The BTS Air Travel Working
Party stress that patients may travel safely 6 weeks after a
definitive surgical procedure or resolution of the pneumothorax on the chest radiograph. Otherwise, there is still a significant risk of recurrence for up to 1 year, depending on whether
the patient has underlying lung disease or not. Patients,
particularly those who have suffered a secondary spontaneous
pneumothorax, may decide to avoid the risk by avoiding flying
for a year in the absence of a definitive surgical procedure.147
After a pneumothorax, diving should be discouraged permanently unless a very secure definitive prevention strategy such
as surgical pleurectomy has been performed.148 The BTS
guidelines on respiratory aspects of fitness for diving149 deal
with this in greater detail.
Patients with primary pneumothorax treated successfully
by simple aspiration should be observed to ensure clinical stability before discharge. The few patients with secondary
pneumothorax who are successfully treated with simple aspiration should be admitted at least overnight and preferably for
24 hours before discharge to ensure no recurrence. The
mortality rate associated with secondary pneumothorax is
10%, and many of these patients die after the pneumothorax
has resolved.18 32 Most patients with secondary pneumothorax
will require a more protracted admission, including treatment
of their underlying lung disorder.32 All patients discharged
after active treatment or otherwise should be given verbal and
written advice to return to the Accident and Emergency
department immediately should they develop further breathlessness.
5 PNEUMOTHORAX AND AIDS
• Early and aggressive treatment of pneumothoraces
in HIV patients, incorporating intercostal tube
drainage and early surgical referral, is recommended.
[B]
There is evidence that the clinical spectrum of spontaneous
pneumothorax is shifting away from the predominant
subpleural bleb disease as emphasised by most reports since
Kjaergard.3 There are several reports that up to 25% of spontaneous pneumothoraces in large urban settings with a high
prevalence of HIV infection are AIDS related31 32 150; 2–5% of
AIDS patients will develop a pneumothorax.151–153 Pneumocystis
carinii infection should be considered as the most likely
aetiology in any HIV positive patient who develops a
pneumothorax, although the administration of aerosolised
pentamidine has also been suggested as an independent risk
factor.151 Pneumocystis carinii pneumonia (PCP) is associated
with a severe form of necrotising alveolitis in which the subpleural pulmonary parenchyma is replaced by necrotic thin
walled cysts and pneumatoceles.154 155 AIDS related spontaneous pneumothorax is complicated by the refractory nature of
air leaks which tend to occur with the necrotising subpleural
pneumonitis of PCP infection.156 Such is the relationship
between AIDS related pneumothorax and the presence of P
carinii that the occurrence of pneumothorax in AIDS patients
is considered an indicator of treatment for active P carinii
infection.151 AIDS related spontaneous pneumothorax carries
a higher hospital mortality, a higher incidence of bilateral
(40%) and recurrent pneumothoraces, and more prolonged air
leaks.157 Treatment failures may also reflect the degree of
immunocompromise of the impaired host as reflected by the
CD4 counts.157 It has also been suggested that systemic
corticosteroids used to treat PCP may increase the risk of morbidity from AIDS related pneumothorax.158 Because of the
high rate of primary treatment failures and associated short
survival times reported for such patients,159 160 early and
BTS guidelines for the management of spontaneous pneumothorax
aggressive treatment of AIDS related spontaneous
pneumothorax—incorporating early tube drainage and talc
pleurodesis, early VATS assisted talc poudrage, unilateral or
bilateral pleurectomy—is recommended.150 152 157 158 161 162
6 PNEUMOTHORAX AND CYSTIC FIBROSIS
• Early and aggressive treatment of pneumothoraces
in cystic fibrosis is recommended. [C]
• Surgical intervention should be considered after the
first episode, provided the patient is fit for the procedure. [C]
The treatment of pneumothorax for patients with cystic fibrosis (CF) is similar to that for non-CF patients. A pneumothorax is associated with more severe disease and can be life
threatening. Median survival after pneumothorax in patients
with CF is 30 months and the occurrence reflects the severity
of the underlying disease rather than being an independent
risk factor.163 Contralateral pneumothoraces occur in up to 40%
of patients.163 164 A small pneumothorax without symptoms
can be observed or aspirated. Larger pneumothoraces require
treatment with intercostal tube drainage. The leak is usually
from the upper lobes and it is important to site the tube in the
correct place. The collapsed lung can be stiff and take a long
time to re-expand. It is important to commence intravenous
antibiotics at the same time to prevent sputum retention,
which can delay re-expansion of the collapsed lung. Pleurectomy, pleural abrasion, and talc pleurodesis all have markedly
lower reported recurrence rates than observation or tube thoracostomy alone, which has an unacceptably high recurrence
rate of 50%.165–167 Partial pleurectomy has a success rate of 95%
with little reduction in pulmonary function associated with
surgery, and it is generally felt to be the treatment of choice in
CF patients with recurrent pneumothoraces who are fit to
undergo surgery.163 In those patients who are too ill to undergo
surgery, it can take 2–3 weeks for the lung to re-expand with
intubation and suction. In this group, talc instillation or
repeated instillation of the patient’s own blood are effective
alternatives.163 Although not an absolute contraindication to
transplantation, sclerosants can make transplantation more
difficult. It takes longer to remove the lungs, prolonging the
ischaemic time for the donor lungs, and is associated with
excessive bleeding.168
7 TENSION PNEUMOTHORAX
• If tension pneumothorax is present, a cannula of
adequate length should be promptly inserted into
the second intercostal space in the mid clavicular line
and left in place until a functioning intercostal tube
can be positioned. [B]
Tension pneumothorax occurs when the intrapleural pressure
exceeds the atmospheric pressure throughout inspiration as
well as expiration. It is thought to result from the operation of
a one way valve system, drawing air into the pleural space
during inspiration and not allowing it out during expiration.
The development of tension pneumothorax is often, but not
always, heralded by a sudden deterioration in the cardiopulmonary status of the patient related to impaired venous
return, reduced cardiac output, and hypoxaemia.169 170 The
development of tension in a pneumothorax is not dependent
on the size of the pneumothorax and the clinical scenario of
tension pneumothorax may correlate poorly with chest radiographic findings. The clinical status is striking. The patient
rapidly becomes distressed with rapid laboured respiration,
cyanosis, sweating, and tachycardia. It should be particularly
suspected in those on mechanical ventilators or nasal
non-invasive ventilation who suddenly deteriorate or develop
EMD arrest, and is frequently missed in the ICU setting.171 If a
tension pneumothorax occurs, the patient should be given
ii49
high concentration oxygen and a cannula should be introduced into the pleural space, usually in the second anterior
intercostal space mid clavicular line. Air should be removed
until the patient is no longer compromised and then an intercostal tube should be inserted into the pleural space as previously described. Advanced Trauma Life Support guidelines
recommend the use of a cannula 3–6 cm long to perform
needle thoracocentesis for life threatening tension
pneumothorax.172 However, in 57% of patients with tension
pneumothorax the thickness of the chest wall has been found
to be greater than 3 cm. It is therefore recommended that a
cannula length of at least 4.5 cm should be used in needle
thoracocentesis of tension pneumothoraces.173 174 The cannula
should be left in place until bubbling is confirmed in the
underwater seal system to confirm proper function of the
intercostal tube.169
8 IATROGENIC PNEUMOTHORAX
The incidence of iatrogenic pneumothorax is high, outnumbering spontaneous pneumothoraces in several large review
series.175 176 Transthoracic needle aspiration (24%), subclavian
vessel puncture (22%), thoracocentesis (22%), pleural biopsy
(8%), and mechanical ventilation (7%) are the five leading
causes.173 The two primary risk factors related to the development of pneumothorax with transthoracic needle aspiration
are the depth of the lesion and the presence of COPD.177 To
date, no method has been found to prevent pneumothorax
following needle aspiration/thoracocentesis. While it was
hoped that positioning the patient so that the area to be biopsied was dependent might reduce the incidence of such
events, this has not been shown to be the case.178 The
treatment of iatrogenic pneumothorax tends to be simple as
there is less likelihood of recurrence. The majority will resolve
with observation alone. If required, treatment should be by
simple aspiration. Delius and coworkers58 aspirated up to 89%
without resorting to tube drainage using a small 8 F teflon
catheter. Patients with COPD who develop an iatrogenic
pneumothorax are more likely to require tube drainage,179 and
patients who develop a pneumothorax while on positive pressure ventilation should be treated with a chest drain unless
immediate weaning from positive pressure ventilation is possible, as positive pressure ventilation maintains the air leak.180
9 CONCLUDING REMARKS
The 1993 BTS pneumothorax guidelines emphasised the place
of simple observation and aspiration, reminded junior doctors
of the potential hazards of chest drain insertion, and encouraged shorter, safer and less painful treatment paths for many
patients. Despite their usefulness, recent evidence suggests
that adherence to these guidelines may be suboptimal. This
revision endorses the main thrust of these guidelines, with
observation for the least severe cases, simple aspiration as the
initial treatment choice, and chest drain insertion as a last
resort. Recently, the American College of Chest Physicians
(ACCP) has published its own guidelines which were arrived
at by the Delphi consensus method.65 These guidelines are
similar to our proposed guidelines in many respects, although
there are differences such as the emphasis placed on the value
of simple aspiration in the treatment of primary pneumothorax. Both sets of guidelines will undoubtedly stimulate debate.
The evidence for the current BTS recommendations is
incorporated and its weaknesses described. This revision alters
the threshold for aspiration in primary pneumothorax and
suggests a place for re-aspiration. The limitations of aspiration
in secondary pneumothorax are acknowledged, and initial
chest drain insertion is recommended for categories of
patients where aspiration is unlikely to succeed. These issues
are already being revisited as the new “pneumothorax kits”
inserted with a Seldinger technique and containing integral
Heimlich type flutter valves gain popularity. It is likely that
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ii50
Henry, Arnold, Harvey
Audit points
• Proportion of patients treated by (a) simple observation, (b)
aspiration, and (c) chest drains and their appropriateness
(relative to the guidelines) and outcome (in terms of
recurrence rates, complications, and lengths of stay in hospital)
• Number of chest drains clamped and the reasons for this.
• Referral rates to physicians and surgeons and the timing of
such referrals.
• Use of analgesics and local anaesthetics.
• Follow up rates
Future potential areas for research
• Prospective randomised controlled trials comparing:
• simple observation versus aspiration ± tube drainage
for primary pneumothoraces larger than 2 cm on the
chest radiograph;
• use of small catheter/Heimlich valve kits versus intercostal tube drainage following failed aspiration in
primary pneumothoraces;
• small catheter aspiration (CASP) versus conventional
aspiration or tube drainage;
• VATS versus open thoracotomy for the difficult pneumothorax.
• Use of suction with regard to its timing and optimal mode.
• Comparison of “clamping” and “ non-clamping” strategies
after cessation of air leak.
they will prove to be as successful and possibly replace simple
aspiration followed by immediate removal of the catheter as
recommended in these guidelines.
Several aspects of management that were not previously
covered are now included. These include the place of CT scanning in diagnosis, which patients to refer for surgery, a discussion of surgical techniques, and issues such as intercostal tube
size and the place of suction and pleurodesis. Complex
scenarios including tension pneumothorax, subcutaneous
emphysema, pneumothorax in HIV disease and adult CF are
also discussed. It is hoped that these changes build on the
clinical benefits produced by the first set of guidelines
which—if adhered to—should, we calculate, prevent approximately 7000 unnecessary chest drain insertions every year in
the UK.
.....................
Authors’ affiliations
M Henry, Department of Respiratory Medicine, The General Infirmary at
Leeds, Great George Street, Leeds LS1 3EX, UK
T Arnold, Medical Chest Unit, Castle Hill Hospital, Cottingham, North
Humberside HU16 5JQ, UK
J Harvey, Department of Respiratory Medicine, Southmead Hospital,
Bristol BS10 5NB, UK
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ii53
BTS guidelines for the insertion of a chest drain
D Laws, E Neville, J Duffy, on behalf of the British Thoracic Society Pleural Disease
Group, a subgroup of the British Thoracic Society Standards of Care Committee
.............................................................................................................................
Thorax 2003;58(Suppl II):ii53–ii59
1 BACKGROUND
In current hospital practice chest drains are used
in many different clinical settings and doctors in
most specialities need to be capable of their safe
insertion. The emergency insertion of a large bore
chest drain for tension pneumothorax following
trauma has been well described by the Advanced
Trauma and Life Support (ATLS) recommendations in their instructor’s manual1 and there have
been many general descriptions of the step by
step method of chest tube insertion.2–9
It has been shown that physicians trained in the
method can safely perform tube thoracostomy
with 3% early complications and 8% late.10 In these
guidelines we discuss the safe insertion of chest
tubes in the controlled circumstances usually
encountered by physicians. A summary of the
process of chest drain insertion is shown in fig 1.
2 TRAINING
• All personnel involved with insertion of
chest drains should be adequately trained
and supervised. [C]
Before insertion of a chest drain, all operators
should have been adequately trained and have
completed this training appropriately. In all other
circumstances, insertion should be supervised by
an appropriate trainer. This is part of the SHO core
curriculum training process issued by the Royal
College of Physicians and trainees should be
expected to describe the indications and complications. Trainees should ensure each procedure is
documented in their log book and signed by the
trainer. With adequate instruction, the risk of
complications and patient pain and anxiety can
be reduced.11
These guidelines will aid the training of junior
doctors in the procedure and should be readily
available for consultation by all doctors likely to
be required to carry out a chest tube insertion.
3 INDICATIONS
Chest tubes may be useful in many settings, some
of which are listed in box 1.
4 PRE-DRAINAGE RISK ASSESSMENT
See end of article for
authors’ affiliations
.......................
Correspondence to:
Dr D Laws, Department of
Thoracic Medicine, Royal
Bournemouth Hospital,
Castle Lane East,
Bournemouth BH7 7DW,
UK; diane.laws@
rbch-tr.swest.nhs.uk
.......................
• Risk of haemorrhage: where possible, any
coagulopathy or platelet defect should be
corrected prior to chest drain insertion
but routine measurement of the platelet
count and prothrombin time are only recommended in patients with known risk
factors. [C]
• The differential diagnosis between a
pneumothorax and bullous disease requires careful radiological assessment.
Similarly it is important to differentiate
between the presence of collapse and a
Box 1 Indications for chest drain insertion
• Pneumothorax
• in any ventilated patient
• tension pneumothorax after initial needle
relief
• persistent or recurrent pneumothorax
after simple aspiration
• large secondary spontaneous pneumothorax in patients over 50 years
• Malignant pleural effusion
• Empyema and complicated parapneumonic
pleural effusion
• Traumatic haemopneumothorax
• Postoperative—for example, thoracotomy,
oesophagectomy, cardiac surgery
pleural effusion when the chest radiograph shows a unilateral “whiteout”.
• Lung densely adherent to the chest wall
throughout the hemithorax is an absolute
contraindication to chest drain insertion.
[C]
• The drainage of a post pneumonectomy
space should only be carried out by or
after consultation with a cardiothoracic
surgeon. [C]
There is no published evidence that abnormal
blood clotting or platelet counts affect bleeding
complications of chest drain insertion. However,
where possible it is obvious good practice to
correct any coagulopathy or platelet defect prior
to drain insertion. Routine pre-procedure checks
of platelet count and/or prothrombin time are
only required in those patients with known risk
factors. For elective chest drain insertion, warfarin should be stopped and time allowed for its
effects to resolve.
5 EQUIPMENT
All the equipment required to insert a chest tube
should be available before commencing the
procedure and are listed below and illustrated in
fig 2.
• Sterile gloves and gown
• Skin antiseptic solution, e.g. iodine or chlorhexidine in alcohol
• Sterile drapes
• Gauze swabs
• A selection of syringes and needles (21–25
gauge)
• Local anaesthetic, e.g. lignocaine (lidocaine)
1% or 2%
• Scalpel and blade
• Suture (e.g. “1” silk)
• Instrument for blunt dissection (e.g. curved
clamp)
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ii54
Laws, Neville, Duffy
Indication to insert
chest drain
(section 3)
Consent
(section 6)
Premedication
(section 6)
Figure 2
Confirmation of site of insertion
clinically and on radiography
(section 8)
Positioning of
patient
(section 7)
Equipment required for insertion of chest drains.
• Guidewire with dilators (if small tube being used)
• Chest tube
• Connecting tubing
• Closed drainage system (including sterile water if underwater seal being used)
• Dressing
Equipment may also be available in kit form.
6. CONSENT AND PREMEDICATION
Size of chest drain
(sections 10 and 13)
Aseptic technique (section 11)
Local anaesthesia (section 12)
Blunt dissection if required (section 13.3.2)
Securing drain and suture
(section 13.3.4)
Underwater seal (section 14.2)
Clamping instructions (section 14.1)
Decision re suction
(section 14.3)
Removal of drain
(section 14.5)
Figure 1 Summary of chest drain insertion process.
www.thoraxjnl.com
• Prior to commencing chest tube insertion the procedure should be explained fully to the patient and
consent recorded in accordance with national guidelines. [C]
• Unless there are contraindications to its use, premedication (benzodiazepine or opioid) should be
given to reduce patient distress. [B]
Consent should be taken and recorded in keeping with
national guidelines. The General Medical Council (GMC)
guidelines for consent state that it is the responsibility of the
doctor carrying out a procedure, or an appropriately trained
individual with sufficient knowledge of a procedure, to
explain its nature and the risks associated with it. It is within
the rights of a competent individual patient to refuse such
treatment. In the case of an emergency, when the patient is
unconscious and the treatment is lifesaving, treatment may be
carried out but must be explained as soon as the patient is
sufficiently recovered to understand. If possible, an information leaflet should be given before the procedure.
Chest drain insertion has been reported to be a painful procedure with 50% of patients experiencing pain levels of 9–10
on a scale of 10 in one study,11 and therefore premedication
should be given. Despite the apparent common sense of this
approach, there is little established evidence of the effect from
these medications. Premedication could be an intravenous
anxiolytic—for example, midazolam 1–5 mg titrated to
achieve adequate sedation—given immediately before the
procedure or an intramuscular opioid given 1 hour before,
although neither drug has been shown to be clearly superior.
Both these classes of drugs may cause respiratory depression
and patients with underlying lung disease such as COPD
should be observed as reversal agents—for example, naloxone
or flumazenil—are occasionally necessary.
While the use of atropine as part of premedication for fibreoptic bronchoscopy has been assessed, no controlled trial of its
use in chest tube insertion has been identified, although it is
advocated in some centres. Case reports of vasovagal
reactions12 and a death due to vagal stimulation following tube
insertion13 may support its use as premedication.
BTS guidelines for the insertion of a chest drain
Figure 3 Diagram to illustrate the “safe triangle”.
ii55
unsightly scarring. A more posterior position may be chosen if
suggested by the presence of a locule. While this is safe, it is
not the preferred site as it is more uncomfortable for the
patient to lie on after insertion and there is a risk of the drain
kinking.
For apical pneumothoraces the second intercostal space in
the mid clavicular line is sometimes chosen but is not recommended routinely as it may be uncomfortable for the patient
and may leave an unsightly scar. Loculated apical pneumothoraces are not uncommonly seen following thoracotomy and
may be drained using a posteriorly sited (suprascapular) apical tube.19 20 This technique should be performed by an operator experienced in this technique—for example, a thoracic
surgeon. If the drain is to be inserted into a loculated pleural
collection, the position of insertion will be dictated by the site
of the locule as determined by imaging.
7 PATIENT POSITION
The preferred position for drain insertion is on the bed,
slightly rotated, with the arm on the side of the lesion behind
the patient’s head to expose the axillary area.7 9 An alternative
is for the patient to sit upright leaning over an adjacent table
with a pillow or in the lateral decubitus position.14 Insertion
should be in the “safe triangle” illustrated in fig 3. This is the
triangle bordered by the anterior border of the latissimus
dorsi, the lateral border of the pectoralis major muscle, a line
superior to the horizontal level of the nipple, and an apex
below the axilla.
8 CONFIRMING SITE OF DRAIN INSERTION
• A chest tube should not be inserted without further
image guidance if free air or fluid cannot be aspirated
with a needle at the time of anaesthesia. [C]
• Imaging should be used to select the appropriate site
for chest tube placement. [B]
• A chest radiograph must be available at the time of
drain insertion except in the case of tension
pneumothorax. [C]
Immediately before the procedure the identity of the patient
should be checked and the site and side for insertion of the
chest tube confirmed by reviewing the clinical signs and the
chest radiograph. Fluoroscopy, ultrasonography, and CT scanning can all be used as adjunctive guides to the site of tube
placement.15 Before insertion, air or fluid should be aspirated;
if none is forthcoming, more complex imaging than a chest
radiograph is required.
The use of ultrasonography guided insertion is particularly
useful for empyema and effusions as the diaphragm can be
localised and the presence of loculations and pleural thickening defined.16 Using real time scanning at the time of the procedure can help to ensure that the placement is safe despite
the movement of the diaphragm during respiration. The complication rate following image guided thoracocentesis is low
with pneumothoraces occurring in approximately 3% of
cases.17 Success rates of image guided chest tube insertion are
reported to be 71–86%.12 If an imaging technique is used to
indicate the site for drain insertion but the procedure is not
carried out at the time of imaging, the position of the patient
at the time must be clearly documented to aid accurate insertion when the patient returns to the ward. It is recommended
that ultrasound is used if the effusion is very small or initial
blind aspiration fails.
9 DRAIN INSERTION SITE
The most common position for chest tube insertion is in the
mid axillary line,2–9 through the “safe triangle”18 illustrated in
fig 3 and described above. This position minimises risk to
underlying structures such as the internal mammary artery
and avoids damage to muscle and breast tissue resulting in
10 DRAIN SIZE
• Small bore drains are recommended as they are more
comfortable than larger bore tubes [B] but there is
no evidence that either is therapeutically superior.
• Large bore drains are recommended for drainage of
acute haemothorax to monitor further blood loss. [C]
The use of large bore drains has previously been
recommended6 8 21 as it was felt that there was an increase in
the frequency of drain blockage, particularly by thick
malignant or infected fluid. The majority of physicians now
use smaller catheters (10–14 French (F)) and studies have
shown that these are often as effective as larger bore tubes22
and are more comfortable and better tolerated by the
patient.23 There remains intense debate about the optimum
size of drainage catheter24–26 and no large randomised trials
directly comparing small and large bore tubes have been performed.
In pneumothoraces 9 F catheters have been used with success rates of up to 87%, although in a few patients the air leak
seems to exceed the capacity of this small catheter.27 In the
event of failure to drain a pneumothorax due to excessive air
leakage, it is recommended that a larger bore tube be inserted.
There is no evidence to suggest that surgical emphysema rates
vary between the size of drains. Ultrasonographically guided
insertion of pigtail catheters for treatment of malignant pleural effusions for sclerotherapy has been particularly well studied with good effect.28–32 The use of small bore pigtail catheters
has allowed outpatient treatment of malignant pleural
effusions which have not responded to chemotherapy.33
Empyemas are often successfully drained with ultrasonically
placed small bore tubes with the aid of thrombolytic
agents.34 35
In the case of acute haemothorax, however, large bore tubes
(28–30 F minimum) continue to be recommended for their
dual role of drainage of the thoracic cavity and assessment of
continuing blood loss.36
11 ASEPTIC TECHNIQUE
• Aseptic technique should be employed during catheter insertion. [C]
• Prophylactic antibiotics should be given in trauma
cases. [A]
As a chest drain may potentially be in place for a number of
days, aseptic technique is essential to avoid wound site infection or secondary empyema. Although this is uncommon,
estimations of the empyema rate following drain insertions
for trauma are approximately 2.4%.37 While the full sterile
technique afforded by a surgical theatre is usually unnecessary, sterile gloves, gown, equipment and the use of sterile
towels after effective skin cleansing using iodine or chlorhexidine are recommended. A large area of skin cleansing should
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ii56
be undertaken. In a study of chest tubes inserted in trauma
suites using full aseptic technique, there were no infective
complications in 80 cases.38
Studies of the use of antibiotic prophylaxis for chest tube
insertion have been performed but have failed to reach
significance because of small numbers of infectious complications. However, a meta-analysis of these studies has been performed which suggested that, in the presence of chest trauma
(penetrating or blunt), the use of prophylactic antibiotics
reduces the absolute risk of empyema by 5.5–7.1% and of all
infectious complications by 12.1–13.4%.39 The use of prophylactic antibiotics in trauma cases is therefore recommended.
The antibiotics used in these studies were cephalosporins or
clindamycin.
The use of prophylactic antibiotics is less clear in the event
of spontaneous pneumothorax or pleural effusion drainage as
no studies were found which addressed these circumstances.
In one study only one infectious complication (in the chest
tube track) occurred in a series of 39 spontaneous pneumothoraces treated with chest tubes.40
12 ANAESTHESIA
• Local anaesthetic should be infiltrated prior to insertion of the drain. [C]
Local anaesthetic is infiltrated into the site of insertion of the
drain. A small gauge needle is used to raise a dermal bleb
before deeper infiltration of the intercostal muscles and pleural surface. A spinal needle may be required in the presence of
a thick chest wall.
Local anaesthetic such as lignocaine (up to 3 mg/kg ) is
usually infiltrated. Higher doses may result in toxic levels. The
peak concentration of lignocaine was found to be <3 µg/ml
(that is, a low risk of neurotoxic effects) in 85% of patients
given 3 mg/kg intrapleurally.41 The volume given is considered
to be more important than the dose to aid spread of the effective anaesthetic area. The use of adrenaline to aid haemostasis
and localise the anaesthesia is used in some centres but is not
evidence based.
13 INSERTION OF CHEST TUBE
• Chest drain insertion should be performed without
substantial force. [C]
Insertion of a chest tube should never be performed with any
substantial force since this risks sudden chest penetration and
damage to essential intrathoracic structures. This can be
avoided either by the use of a Seldinger technique or by blunt
dissection through the chest wall and into the pleural space
before catheter insertion. Which of these approaches is appropriate depends on the catheter size and is discussed below.
13.1 Small bore tube (8–14 F)
• Insertion of a small bore drain under image guidance
with a guidewire does not require blunt dissection.
Small bore chest tubes are usually inserted with the aid of a
guidewire by a Seldinger technique. Blunt dissection is
unnecessary as dilators are used in the insertion process. After
infiltration with local anaesthesia, a needle and syringe are
used to localise the position for insertion by the identification
of air or pleural fluid. A guidewire is then passed down the hub
of the needle, the needle is removed, and the tract enlarged
using a dilator. A small bore tube can then be passed into the
thoracic cavity along the wire. These have been successfully
used
for
pneumothorax,
effusions,
or
loculated
empyemas.15 23 42
13.2 Medium bore tube (16–24 F)
Medium sized chest drains may be inserted by a Seldinger
technique or by blunt dissection as outlined below. As the
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Laws, Neville, Duffy
incision size should afford a snug fit around the chest tube, it
is not possible to insert a finger to explore the pleura when
inserting this size of tube. Exploration with a finger is felt to be
unnecessary for the elective medical insertion of these
medium sized chest tubes.
13.3 Large bore tube (>24 F)
• Blunt dissection into the pleural space must be
performed before insertion of a large bore chest
drain. [C]
13.3.1 Incision
• The incision for insertion of the chest drain should be
similar to the diameter of the tube being inserted.
[C]
Once the anaesthetic has taken effect an incision is made. This
should be slightly bigger than the operator’s finger and tube.
The incision should be made just above and parallel to a rib.
13.3.2 Blunt dissection
Many cases of damage to essential intrathoracic structures
have been described following the use of trocars to insert large
bore chest tubes. Blunt dissection of the subcutaneous tissue
and muscle into the pleural cavity has therefore become
universal43 and is essential. In one retrospective study only
four technical complications were seen in 447 cases using
blunt dissection.37 Using a Spencer-Wells clamp or similar, a
path is made through the chest wall by opening the clamp to
separate the muscle fibres. For a large chest drain, similar in
size to the finger, this track should be explored with a finger
through into the thoracic cavity to ensure there are no underlying organs that might be damaged at tube insertion.2–9 The
creation of a patent track into the pleural cavity ensures that
excessive force is not needed during drain insertion.
13.3.3 Position of tube tip
• The position of the tip of the chest tube should
ideally be aimed apically for a pneumothorax or
basally for fluid. However, any tube position can be
effective at draining air or fluid and an effectively
functioning drain should not be repositioned solely
because of its radiographic position. [C]
In the case of a large bore tube, after gentle insertion through
the chest wall the trocar positioned a few centimetres from the
tube tip can afford support of the tube and so help its
positioning without incurring organ damage. A smaller clamp
can also be used to direct the tube to its desired position.1 3
If possible, the tip of the tube should be aimed apically to
drain air and basally for fluid. However, successful drainage
can still be achieved when the drain is not placed in an ideal
position,21 so effectively functioning tubes should not be
repositioned simply because of a suboptimal radiographic
appearance.
13.3.4 Securing the drain
• Large and medium bore chest drain incisions should
be closed by a suture appropriate for a linear incision.
[C]
• “Purse string” sutures must not be used. [C]
Two sutures are usually inserted—the first to assist later
closure of the wound after drain removal and the second, a
stay suture, to secure the drain.
The wound closure suture should be inserted before blunt
dissection. A strong suture such as “1” silk is appropriate.6 21 A
“mattress” suture or sutures across the incision are usually
employed and, whatever closure is used, the stitch must be of
a type that is appropriate for a linear incision (fig 4). Complicated “purse string” sutures must not be used as they convert
BTS guidelines for the insertion of a chest drain
ii57
• If a patient with a clamped drain becomes breathless
or develops subcutaneous emphysema, the drain
must be immediately unclamped and medical advice
sought. [C]
Figure 4 Example of stay and closing sutures.
a linear wound into a circular one that is painful for the
patient and may leave an unsightly scar.9 A suture is not usually required for small gauge chest tubes.
The drain should be secured after insertion to prevent it
falling out. Various techniques have been described,44 but a
simple technique of anchoring the tube has not been the subject of a controlled trial. The chosen suture should be stout and
non absorbable to prevent breaking (e.g. “1” silk),6 and it
should include adequate skin and subcutaneous tissue to
ensure it is secure (fig 4).
Large amounts of tape and padding to dress the site are
unnecessary and concerns have been expressed that they may
restrict chest wall movement6 or increase moisture collection.
A transparent dressing allows the wound site to be inspected
by nursing staff for leakage or infection. An omental tag of
tape has been described2 which allows the tube to lie a little
away from the chest wall to prevent tube kinking and tension
at the insertion site (fig 5).
14 MANAGEMENT OF DRAINAGE SYSTEM
14.1 Clamping drain
• A bubbling chest tube should never be clamped. [C]
• Drainage of a large pleural effusion should be
controlled to prevent the potential complication of
re-expansion pulmonary oedema. [C]
• In cases of pneumothorax, clamping of the chest tube
should usually be avoided. [B]
• If a chest tube for pneumothorax is clamped, this
should be under the supervision of a respiratory physician or thoracic surgeon, the patient should be
managed in a specialist ward with experienced nursing staff, and the patient should not leave the ward
environment. [C]
Figure 5 Omental tag to support the tube while allowing it to lie a
little away from the chest wall.
There is no evidence to suggest that clamping a chest drain
prior to its removal increases success or prevents recurrence of
a pneumothorax and it may be hazardous. This is therefore
generally discouraged. Clamping a chest drain in the presence
of a continuing air leak may lead to the potentially fatal complication of tension pneumothorax.3 6 9 A bubbling drain
therefore should never be clamped. However, many experienced specialist physicians support the use of the clamping of
non-bubbling chest drains inserted for pneumothorax to
detect small air leaks not immediately obvious at the bedside.
By clamping the chest drain for several hours, followed by a
chest radiograph, a minor air leak may be detected, avoiding
the need for later chest drain reinsertion. In the ACCP Delphi
consensus statement45 about half the consensus group
supported clamping and half did not, and this seems similar to
the UK spread of opinion. Drain clamping is therefore not
generally recommended for safety reasons, but is acceptable
under the supervision of nursing staff who are trained in the
management of chest drains and who have instructions to
unclamp the chest drain in the event of any clinical deterioration. Patients with a clamped chest drain inserted for
pneumothorax should not leave the specialist ward area.
There have been reports of re-expansion pulmonary
oedema following rapid evacuation of large pleural effusions46
as well as in association with spontaneous pneumothorax.47 48
This has been reported to be fatal in some cases (up to 20% of
subjects in one series of 53 cases49). In the case of spontaneous
pneumothorax this is a rare complication with no cases of
re-expansion pulmonary oedema reported in two large studies
of 400 and 375 patients, respectively.50 51 It is usually associated
with delayed diagnosis and therefore awareness of its
potential occurrence is sufficient.
Milder symptoms suggestive of re-expansion oedema are
common after large volume thoracentesis in pleural effusion,
with patients experiencing discomfort and cough. It has been
suggested that the tube be clamped for 1 hour after draining
1 litre.52 While there is no evidence for actual amounts, good
practice suggests that no more than about 1.5 litres should be
drained at one time, or drainage should be slowed to about
500 ml per hour.
14.2 Closed system drainage
• All chest tubes should be connected to a single flow
drainage system e.g. under water seal bottle or flutter
valve. [C]
• Use of a flutter valve system allows earlier mobilisation and the potential for earlier discharge of
patients with chest drains.
The chest tube is then attached to a drainage system which
only allows one direction of flow. This is usually the closed
underwater seal bottle in which a tube is placed under water
at a depth of approximately 3 cm with a side vent which
allows escape of air, or it may be connected to a suction
pump.2–4 7 This enables the operator to see air bubble out as the
lung re-expands in the case of pneumothorax or fluid evacuation rate in empyemas, pleural effusions, or haemothorax. The
continuation of bubbling suggests a continued visceral pleural
air leak, although it may also occur in patients on suction
when the drain is partly out of the thorax and one of the tube
holes is open to the air. The respiratory swing in the fluid in
the chest tube is useful for assessing tube patency and
confirms the position of the tube in the pleural cavity. The disadvantages of the underwater seal system include obligatory
inpatient management, difficulty of patient mobilisation, and
the risk of knocking over the bottle.
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ii58
The use of integral Heimlich flutter valves has been
advocated in patients with pneumothoraces, especially as they
permit ambulatory or even outpatient management which has
been associated with a 85–95% success rate.53 54 In 176 cases of
pneumothorax treated with small chest tubes and a Heimlich
flutter valve there were only eight failures (hospital admissions for problems with tube function or placement). The
mean length of inpatient stay has been quoted at 5 hours with
a thoracic vent and 144 hours with an underwater seal, with a
cost saving US$5660.53 Case reports of incorrect use (wrong
direction of flow) of such valves have been described, however,
with tension pneumothorax as a result.55 Flutter valves cannot
be used with fluid drainage as they tend to become blocked.
However, in the UK a similar short hospital stay is achieved by
initial aspiration of pneumothoraces (see guidelines on pneumothorax, page ii39).
The use of a drainage bag with an incorporated flutter valve
and vented outlet has been successfully used
postoperatively.56 57 A randomised trial of 119 cases following
elective thoracotomy compared the use of an underwater seal
with the flutter bag and found no difference in drainage volumes, requirement for suction, or complications with the
added advantage of earlier mobilisation with drainage bags.57
In cases of malignant pleural effusion drainage a closed
system using a drainage bag or aspiration via a three way tap
has been described to aid palliation and outpatient
management.33 One report of a modified urinary collecting
bag for prolonged underwater chest drainage has been
described for use with empyemas, bronchopulmonary fistula,
and pneumothorax associated with emphysema with no complications in the 12 patients studied.58
14.3 Suction
• When chest drain suction is required, a high volume/
low pressure system should be used. [C]
• When suction is required, the patient must be nursed
by appropriately trained staff. [C]
The use of high volume/low pressure suction pumps has been
advocated in cases of non-resolving pneumothorax or following chemical pleurodesis,6 but there is no evidence to support
its routine use in the initial treatment of spontaneous
pneumothorax.59 60 If suction is required, this may be
performed via the underwater seal at a level of 10–20 cm H2O.
A high volume pump (e.g. Vernon-Thompson) is required to
cope with a large leak. A low volume pump (e.g. Roberts
pump) is inappropriate as it is unable to cope with the rapid
flow, thereby effecting a situation similar to clamping and
risking formation of a tension pneumothorax. A wall suction
adaptor may also be effective, although chest drains must not
be connected directly to the high negative pressure available
from wall suction.
In the management of pleural infection, the use of suction
is less clear. Most studies are observational and have used suction applied via the chest tube after flushing to prevent blocking and have reported success, but this has not been compared
with cases without suction. This is discussed further in the
guideline on pleural infection (page ii18).
There is no evidence that briefly disconnecting a drain from
suction used for spontaneous pneumothorax or pleural
effusion is disadvantageous. Therefore, as long as adequate
instruction is given to patient, portering and nursing staff
with regard to keeping the underwater seal bottle below the
level of the chest, it is acceptable to stop suction for short periods such as for radiography.
14.4 Ward instructions
• Patients with chest tubes should be managed on
specialist wards by staff who are trained in chest
drain management. [C]
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Laws, Neville, Duffy
Audit points
• The presence and use of an appropriate nursing chest drain
observation chart should be noted.
• The frequency of chest drain complications should be
recorded.
• The use of premedication and analgesics and patient pain
scores relating to chest drain insertion should be recorded.
• The duration of chest tube drainage should be recorded.
• A chest radiograph should be performed after insertion of a chest drain. [C]
Patients should be managed on a ward familiar with chest
tubes. Instruction to and appropriate training of the nursing
staff is imperative. If an underwater seal is used, instructions
must be given to keep the bottle below the insertion site at all
times, to keep it upright, and to ensure that adequate water is
in the system to cover the end of the tube.9 Daily reassessment
of the amount of drainage/bubbling and the presence of respiratory swing should be documented, preferably on a dedicated
chest drain chart. Instruction with regard to chest drain
clamping must be given and recorded.61
Patients should be encouraged to take responsibility for
their chest tube and drainage system. They should be taught
to keep the underwater seal bottle below the level of their
chest and to report any problems such as pulling on the drain
insertion site. Educational material (e.g. leaflets) should be
available on the ward for patients and nursing staff.
A chest radiograph should be performed to assess tube
position, exclude complications such as pneumothorax or surgical emphysema, and assess the success of the procedure in
the volume of fluid drainage or pneumothorax resolution.
Concern has previously been expressed in cases where the
tube enters the lung fissure. In a study of 66 patients with
chest tubes inserted for acute chest trauma, 58% of which
were located within a pulmonary fissure,62 no difference in
outcome was seen between these cases and those in whom the
tube was located outside the fissures.
14.5 Removal of the chest tube
• In cases of pneumothorax, the chest tube should not
be clamped at the time of its removal. [B]
In cases of pneumothorax, there is no evidence that clamping
a chest drain at the time of its removal is beneficial.60
The chest tube should be removed either while the patient
performs Valsalva’s manoeuvre or during expiration with a
brisk firm movement while an assistant ties the previously
placed closure suture.2–4 7 8 The timing of removal is dependent
on the original reason for insertion and clinical progress (see
guidelines for management of pneumothorax (page ii39),
malignant pleural effusions (page ii29), and pleural infections
(page ii18)).
In the case of pneumothorax, the drain should not usually
be removed until bubbling has ceased and chest radiography
demonstrates lung reinflation.4 Clamping of the drain before
removal is generally unnecessary. In one study the removal of
chest tubes after continuous suction was compared with the
removal after a period of disconnection from suction to an
underwater seal. No significant difference was seen between
these two methods with only two of 80 cases (2.5%) requiring
reinsertion of a chest tube.38
15 PATIENTS REQUIRING ASSISTED VENTILATION
During the insertion of a chest tube in a patient on a high
pressure ventilator (especially with positive end expiratory
pressure (PEEP), it is essential to disconnect from the ventilator at the time of insertion to avoid the potentially serious
BTS guidelines for the insertion of a chest drain
complication of lung penetration,63 although as long as blunt
dissection is carried out and no sharp instruments are used,
this risk is reduced.64
ACKNOWLEDGEMENTS
The authors are grateful to Dr Richard Holmes for figs 3, 4, and 5.
.....................
Authors’ affiliations
D Laws, Department of Thoracic Medicine, Royal Bournemouth Hospital,
Bournemouth BH7 7DW, UK
E Neville, Respiratory Centre, St Mary’s Hospital, Portsmouth PO3 6AD,
UK
J Duffy, Cardiothoracic Surgery Department, City Hospital, Nottingham
NG5 1PB, UK
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