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ii1 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 ............................................................................................................................. 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 ....................... www.thoraxjnl.com ii2 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] www.thoraxjnl.com BTS guidelines for the management of pleural disease ii3 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] www.thoraxjnl.com ii4 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] www.thoraxjnl.com BTS guidelines for the management of pleural disease ii5 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] www.thoraxjnl.com ii6 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] www.thoraxjnl.com BTS guidelines for the management of pleural disease ii7 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] www.thoraxjnl.com 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 ............................................................................................................................. 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. www.thoraxjnl.com ii10 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] www.thoraxjnl.com 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 www.thoraxjnl.com 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] www.thoraxjnl.com ii14 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 www.thoraxjnl.com 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 ii15 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 www.thoraxjnl.com 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 REFERENCES 1 Boutin C, Rey F, Viallat JR. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. A randomized trial of local radiotherapy. Chest 1995;108:754–8. [Ib] 2 Scheurich JW, Keuer SP, Graham DY. Pleural effusion: comparison of clinical judgment and Light’s criteria in determining the cause. South Med J 1989;82:1487–91. [IIb] 3 Light RW. Pleural effusion due to pulmonary emboli. Curr Opin Pulm Med 2001;7:198–201. [IV] 4 Chetty KG. Transudative pleural effusions. Clin Chest Med 1985;6:49–54. [IV] 5 Light RW. Diagnostic principles in pleural disease. Eur Respir J 1997;10:476–81. [IV] 6 Ferrer A, Osset J, Alegre J, et al. Prospective clinical and microbiological study of pleural effusions. Eur J Clin Microbiol Infect Dis 1999;18:237–41. [IIb] 7 Boddington M. Serous effusions. In: Coleman DV, ed. Clinical cytotechnology. London: Butterworths, 1989: 271–5. [IV] 8 Sahn S. Pleural fluid analysis: narrowing the differential diagnosis. Semin Respir Med 1987;9:22–9. [IV] 9 Light RW, Erozan YS, Ball WCJ. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med 1973;132:854–60. [III] 10 Light RW, MacGregor MI, Luchsinger PC, et al. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972;77:507–13. [III] 11 Gil S, Martinez M, Cases V, et al. Pleural cholesterol in differentiating transudates and exudates. A prospective study of 232 cases. Respiration 1995;62:57–63. [III] 12 Hamm H, Brohan U, Bohmer R, et al. Cholesterol in pleural effusions. A diagnostic aid. Chest 1987;92:296–302. [IV] 13 Ortega L, Heredia JL, Armengol R, et al. The differential diagnosis between pleural exudates and transudates: the value of cholesterol. Med Clin (Barc) 1991;96:367–70. [III] 14 Roth B. The serum-effusion albumin gradient. Chest 1990;98:546–9. [IV] 15 Heffner JE, Brown LK, Barbieri CA. Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Primary Study Investigators. Chest 1997;111:970–80. [IIa] 16 Heffner JE. Evaluating diagnostic tests in the pleural space. Differentiating transudates from exudates as a model. Clin Chest Med 1998;19:277–93. [IV] 17 Light RW. Pleural diseases. 3rd ed. Baltimore: Williams and Wilkins, 1995. [III] 18 Wysenbeek AJ, Lahav M, Aelion JA, et al. Eosinophilic pleural effusion: a review of 36 cases. Respiration 1985;48:73–6. [III] www.thoraxjnl.com Maskell, Butland 19 Adelman M, Albelda SM, Gottlieb J, et al. Diagnostic utility of pleural fluid eosinophilia. Am J Med 1984;77:915–20. [III] 20 Martinez-Garcia MA, Cases-Viedma E, Cordero-Rodriguez PJ, et al. Diagnostic utility of eosinophils in the pleural fluid. Eur Respir J 2000;15:166–9. [III] 21 Levine H, Metzger W, Lacera D, et al. Diagnosis of tuberculous pleurisy by culture of pleural biopsy specimen. Arch Intern Med 1970;126:269–71. [III] 22 Ansari T, Idell S. Management of undiagnosed persistent pleural effusions. Clin Chest Med 1998;19:407–7. [IV] 23 Light RW, Rogers JT, Cheng D, et al. Large pleural effusions occurring after coronary artery bypass grafting. Cardiovascular Surgery Associates, PC. Ann Intern Med 1999;130:891–6. [III] 24 Good JT Jr, Taryle DA, Maulitz RM, et al. The diagnostic value of pleural fluid pH. Chest 1980;78:55–9. [III] 25 Hamm H, Light RW. Parapneumonic effusion and empyema. Eur Respir J 1997;10:1150–6. [IV] 26 Heffner JE, Brown LK, Barbieri C, et al. Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis. Am J Respir Crit Care Med 1995;151:1700–8. [IIb] 27 Rodriguez P, Lopez M. Low glucose and pH levels in malignant pleural effusions. Diagnostic significance and prognostic value in respect to pleurodesis. Am Rev Respir Dis 1989;139:663–7. [IIb] 28 Sahn SA, Good JTJ. Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications. Ann Intern Med 1988;108:345–9. [IIb] 29 Sahn SA. Pathogenesis and clinical features of disease associated with a low pleural fluid glucose. In: The pleura in health and disease. New York, 1985: 267–85. [IV] 30 Light RW, Ball WCJ. Glucose and amylase in pleural effusions. JAMA 1973;225:257–9. [III] 31 Sahn SA. The pleura. Am Rev Respir Dis 1988;138:184–234. [IV] 32 Houston MC. Pleural fluid pH: diagnostic, therapeutic, and prognostic value. Am J Surg 1987;154:333–7. [IV] 33 Potts DE, Willcox MA, Good JT Jr, et al. The acidosis of low-glucose pleural effusions. Am Rev Respir Dis 1978;117:665–71. [IV] 34 Ende N. Studies of amylase activity in pleural effusions and ascites. Cancer 1960;13:283–7. [III] 35 Sherr HP, Light RW, Merson MH, et al. Origin of pleural fluid amylase in esophageal rupture. Ann Intern Med 1972;76:985–6. [IV] 36 Kramer M. High amylase levels in neoplasm-related pleural effusion. Ann Intern Med 1989;110:567–9. [IV] 37 Light RW. Pleural effusions. Med Clin North Am 1977;61:1339–52. [IV] 38 Lankisch PG, Droge M, Becher R. Pleural effusions: a new negative prognostic parameter for acute pancreatitis. Am J Gastroenterol 1994;89:1849–51. [IV] 39 Hirsch A. Pleural effusion: laboratory tests in 300 cases. Thorax 1979;34:106–12. [III] 40 Salyer WR, Eggleston JC, Erozan YS. Efficacy of pleural needle biopsy and pleural fluid cytopathology in the diagnosis of malignant neoplasm involving the pleura. Chest 1975;67:536–9. [IV] 41 Nance KV, Shermer RW, Askin FB. Diagnostic efficacy of pleural biopsy as compared with that of pleural fluid examination. Mod Pathol 1991;4:320–4. [III] 42 Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clin Proc 1985;60:158–64. [IV] 43 Garcia L. The value of multiple fluid specimens in the cytological diagnosis of malignancy. Mod Pathol 1994;7:665–8. [III] 44 Dekker A, Bupp PA. Cytology of serous effusions. An investigation into the usefulness of cell blocks versus smears. Am J Clin Pathol 1978;70:855–60. [III] 45 Pettersson T, Froseth B, Riska H, et al. Concentration of hyaluronic acid in pleural fluid as a diagnostic aid for malignant mesothelioma. Chest 1988;94:1037–9. [III] 46 Whitaker D. The cytology of malignant mesothelioma. Cytopathology 2000;11:139–51. [IV] 47 Dejmek A, Hjerpe A. Reactivity of six antibodies in effusions of mesothelioma, adenocarcinoma and mesotheliosis: stepwise logistic regression analysis. Cytopathology 2000;11:8–17. [IIb] 48 Brown RW, Clark GM, Tandon AK, et al. Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma. Hum Pathol 1993;24:4–54. [III] 49 Blackmore CC, Black WC, Dallas RV, et al. Pleural fluid volume estimation: a chest radiograph prediction rule. Acad Radiol 1996;3:103–9. [IV] 50 O’Moore PV, Mueller PR, Simeone JF, et al. Sonographic guidance in diagnostic and therapeutic interventions in the pleural space. AJR 1987;149:1–5. [IV] 51 Ruskin JA, Gurney JW, Thorsen MK, et al. Detection of pleural effusions on supine chest radiographs. AJR 1987;148:681–3. [III] 52 Armstrong P, Wilson AG, Dee P, et al. Imaging of diseases of the chest. 3rd ed. Mosby, 2001. [IV] 53 Eibenberger KL, Dock WI, Ammann ME, et al. Quantification of pleural effusions: sonography versus radiography. Radiology 1994;191:681–4. [III] 54 Gryminski J, Krakowka P, Lypacewicz G. The diagnosis of pleural effusion by ultrasonic and radiologic techniques. Chest 1976;70:33–7. [IV] 55 Yang PC, Luh KT, Chang DB, et al. Value of sonography in determining the nature of pleural effusion: analysis of 320 cases. AJR 1992;159:29–33. [IV] BTS guidelines for the investigation of a unilateral pleural effusion in adults 56 Wu RG, Yang PC, Kuo SH, et al. “Fluid color” sign: a useful indicator for discrimination between pleural thickening and pleural effusion. J Ultrasound Med 1995;14:767–9. [III] 57 Wu RG, Yuan A, Liaw YS, et al. Image comparison of real-time gray-scale ultrasound and color Doppler ultrasound for use in diagnosis of minimal pleural effusion. Am J Respir Crit Care Med 1994;150:510–4. [IIb] 58 Lipscomb DJ, Flower CD, Hadfield JW. Ultrasound of the pleura: an assessment of its clinical value. Clin Radiol 1981;32:289–90. [IV] 59 McLoud TC. CT and MR in pleural disease. Clin Chest Med 1998;19:261–76. [IV] 60 Leung AN, Muller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. AJR 1990;154:3–92. [III] 61 Scott EM. Diffuse pleural thickening: percutaneous CT-guided cutting needle biopsy. Radiology 1995;194:867–70. [III] 62 Traill ZC, Davies RJ, Gleeson FV. Thoracic computed tomography in patients with suspected malignant pleural effusions. Clin Radiol 2001;56:193–6. [III] 63 Muller NL. Imaging of the pleura. Radiology 1993;186:297–309. [IV] 64 McLoud TC, Flower CD. Imaging the pleura: sonography, CT, and MR imaging. AJR 1991;156:1145–53. [IV] 65 Falaschi F, Battolla L, Mascalchi M, et al. Usefulness of MR signal intensity in distinguishing benign from malignant pleural disease. AJR 1996;166:963–8. [IIb] 66 Morrone N, Algranti E, Barreto E. Pleural biopsy with Cope and Abrams needles. Chest 1987;92:1050–2. [IIb] 67 Mungall IP, Cowen PN, Cooke NT, et al. Multiple pleural biopsy with the Abrams needle. Thorax 1980;35 :600–2. [IV] 68 Tomlinson JR. Closed pleural biopsy. A prospective study of dual biopsy sites. Am Rev Respir Dis 1900;133:56A. [III] 69 Tomlinson JR. Invasive procedures in the diagnosis of pleural disease. Semin Respir Med 1987;9:30– 6. [IIb] 70 Sahn SA. Pleural manifestations of pulmonary disease. Hosp Pract Hosp Ed 1981;16:73–9, 83. [IV] 71 Escudero BC, Garcia CM, Cuesta CB, et al. Cytologic and bacteriologic analysis of fluid and pleural biopsy specimens with Cope’s needle. Study of 414 patients. Arch Intern Med 1990;150:1190–4. [III] 72 Poe RH, Israel RH, Utell MJ, et al. Sensitivity, specificity, and predictive values of closed pleural biopsy. Arch Intern Med 1984;144:325–8. [III] 73 Chertien J. Needle pleural biopsy. The pleura in health and disease. New York: Marcel Dekker, 1985: 631–42. [IV] 74 McAleer JJ, Murphy GJ, Quinn RJ. Needle biopsy of the pleura in the diagnosis of pleural effusion. Ulster Med J 1987;56:54–7. [III] 75 Canto A, Rivas J, Saumench J, et al. Points to consider when choosing a biopsy method in cases of pleurisy of unknown origin. Chest 1983;84:176–9. [IV] 76 Maskell NA, Gleeson FV, Davies RJO. Standard pleural biopsy versus CT-guided cutting-needle biopsy for the diagnosis of pleural malignancy in pleural effusions: A randomised controlled trial. Lancet 2003 (in press). [IIa] 77 Adams RF, Gleeson FV. Percutaneous image-guided cutting needle biopsy of the pleura in the diagnosis of malignant mesothelioma. Chest 2001;120:1798–802. [III] 78 Adams RF, Gleeson FV. Percutaneous image-guided cutting-needle biopsy of the pleura in the presence of a suspected malignant effusion. Radiology 2001;219:510–4. [III] 79 Harris RJ, Kavuru MS, Rice TW, et al. The diagnostic and therapeutic utility of thoracoscopy. A review. Chest 1995;108:828–41. [IV] 80 Page RD. Thoracosopy: a review of 121 consecutive surgical procedures. Ann Thorac Surg 1989;48:66–8. [IV] 81 Loddenkemper R. Thoracoscopy: state of the art. Eur Respir J 1998;11:213–21. [IV] 82 Viskum K, Enk B. Complications of thoracoscopy. Poumon Coeur 1981;37:25–8. [IV] 83 Heaton RW, Roberts CM. The role of fibreoptic bronchoscopy in the investigation of pleural effusion. Postgrad Med J 1988;64:581–2. [IV] 84 Upham JW, Mitchell CA, Armstrong JG, et al. Investigation of pleural effusion: the role of bronchoscopy. Aust N Z J Med 1992;22:41–3. [III] 85 Feinsilver SH, Barrows AA, Braman SS. Fiberoptic bronchoscopy and pleural effusion of unknown origin. Chest 1986;90:516–9. [III] ii17 86 Chang SC, Perng RP. The role of fiberoptic bronchoscopy in evaluating the causes of pleural effusions. Arch Intern Med 1989;149:855–7. [IIb] 87 Turton CW. Troublesome pleural fluid. Br J Dis Chest 1987;81:217–24. [IV] 88 Ferrer S. Pleural tuberculosis: incidence, pathogenesis, diagnosis, and treatment. Curr Opin Pulm Med 1996;2:327–34. [IV] 89 Hillerdal G. Chylothorax and pseudochylothorax. Eur Respir J 1997;10:1150–6. [IV] 90 Ferguson GC. Cholesterol pleural effusion in rheumatoid lung disease. Thorax 1966;21:577–82. [IV] 91 Hillerdal G. Chyliform (cholesterol) pleural effusion. Chest 1985;88:426–8. [IV] 92 Romero S, Martin C, Hernandez L, et al. Chylothorax in cirrhosis of the liver: analysis of its frequency and clinical characteristics. Chest 1998;114:154–9. [IV] 93 Berkman N, Liss H, Kramer MR. Pyelonephritis as a cause of pleural effusion. Respiration 1996;63:384–6. [IV] 94 Miller KS, Wooten S, Sahn SA. Urinothorax: a cause of low pH transudative pleural effusions. Am J Med 1988;85:448–9. [IV] 95 Stark DD, Shanes JG, Baron RL, et al. Biochemical features of urinothorax. Arch Intern Med 1982;142:1509–11. [IV] 96 Garcia-Pachon E, Padilla-Navas I. Pleural effusion due to pyelonephritis or urinothorax? Respiration 1997;64:392. [IV] 97 Berger HW, Mejia E. Tuberculous pleurisy. Chest 1973;63:88–92. [IV] 98 Idell S. Evaluation of perplexing pleural effusions. Ann Intern Med 1994;110:567–9. [IV] 99 Gakis C. Adenosine deaminase (ADA) isoenzymes ADA1 and ADA2: diagnostic and biological role. Eur Respir J 1996;9:632–3. [IV] 100 Valdes L, Alvarez D, San Jose E, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998;158:2017–21. [III] 101 Burgess LJ, Maritz FJ, Le Roux I, et al. Use of adenosine deaminase as a diagnostic tool for tuberculous pleurisy. Thorax 1995;50:672–4. [IV] 102 van Keimpema AR, Slaats EH, Wagenaar JP. Adenosine deaminase activity, not diagnostic for tuberculous pleurisy. Eur J Respir Dis 1987;71:15–8. [IV] 103 Hsu WH, Chiang CD, Huang PL. Diagnostic value of pleural adenosine deaminase in tuberculous effusions of immunocompromised hosts. J Formos Med Assoc 1993;92:668–70. [III] 104 Epler GR, McLoud TC, Gaensler EA. Prevalence and incidence of benign asbestos pleural effusion in a working population. JAMA 1982;247:617–22. [IIb] 105 Hillerdal G, Ozesmi M. Benign asbestos pleural effusion: 73 exudates in 60 patients. Eur J Respir Dis 1987;71:113–21. [III] 106 Robinson BW, Musk AW. Benign asbestos pleural effusion: diagnosis and course. Thorax 1981;36:896–900. [III] 107 Joseph J, Sahn SA. Connective tissue diseases and the pleura. Chest 1993;104:262–70. [IV] 108 Pettersson T, Klockars M, Hellstrom PE. Chemical and immunological features of pleural effusions: comparison between rheumatoid arthritis 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 57 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. www.thoraxjnl.com 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. www.thoraxjnl.com 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 www.thoraxjnl.com 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 www.thoraxjnl.com 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 REFERENCES 1 Berger HA, Morganroth ML. Immediate drainage is not required for all patients with complicated parapneumonic effusions. Chest 1990;97:731–5. [III] 2 Strange C, Sahn SA. The clinician’s perspective on parapneumonic effusions and empyema. Chest 1993;103:259–61. [IIb] 3 Sahn SA. Management of complicated parapneumonic effusions. Am Rev Respir Dis 1993;148:813–7. [IV] 4 Ferguson AD, Prescott RJ, Selkon JB, et al. Empyema subcommittee of the Research Committee of the British Thoracic Society. The clinical course and management of thoracic empyema. Q J Med 1996;89:285–9. [III] 5 Heffner JE, McDonald J, Barbieri C, et al. Management of parapneumonic effusions. An analysis of physician practice patterns. Arch Surg 1995;130:433–8. [III] 6 Light RW, MacGregor MI, Ball WCJ, et al. Diagnostic significance of pleural fluid pH and PCO2. Chest 1973;64:591–6. [IIb] 7 Matsumoto AH. Image guided drainage of complicated pleural effusions and adjunctive use of intrapleural urokinase. Chest 1995;108:1190–1. [III] 8 Parmar JM. How to insert a chest drain. Br J Hosp Med 1989;42:231–3. [IV] 9 Wait MA, Sharma S, Hohn J, et al. A randomized trial of empyema therapy. Chest 1997;111:1548–51. [Ib] 10 LeMense GP, Strange C, Sahn SA. Empyema thoracis. Therapeutic management and outcome. Chest 1995;107:1532–7. [III] 11 Storm HK, Krasnik M, Bang K, et al. Treatment of pleural empyema secondary to pneumonia: thoracocentesis regimen versus tube drainage. Thorax 1992;47:821–4. [III] 12 Mackenzie JW. Video-assisted thoracoscopy: treatment for empyema and hemothorax. Chest 1996;109:2–3. [IV] 13 Galea JL, De Souza A, Beggs D, et al. The surgical management of empyema thoracis. J R.Coll Surg Edinb 1997;42:15–18. [III] 14 Wallenhaupt SL. Surgical management of thoracic empyema. J Thorac Imaging 1991;6:80–8. [III] 15 Meyer JA. Gotthard Bulau and closed water-seal drainage for empyema, 1875–1891. Ann Thorac Surg 1989;48:597–9. [IV] 16 Peters RM. Empyema thoracis: historical perspective. Ann Thorac Surg 1989;48:306–8. [IV] 17 Heffner JE. Diagnosis and management of thoracic empyemas. Curr Opin Pulmon Med 1996;2:198–205. [IV] 18 Bartlett JG. Anaerobic bacterial infections of the lung and pleural space. Clin Infect Dis 1993;16(Suppl 4):S248–55. [IV] 19 Stiles QR, Lindesmith GG, Tucker BL, et al. Pleural empyema in children. Ann Thorac Surg 1970;10:37–44. [III] 20 Alfageme I, Munoz F, Pena N, et al. Empyema of the thorax in adults. Etiology, microbiologic findings, and management. Chest 1993;103:839–43. [III] 21 Tillett WS, Sherry S. The effect in patients of streptococcal fibrinolysin (streptokinase) and streptococcal desoxyribonuclease on fibrinous, purulent, and sanguinous pleural exudations. J Clin Invest 1949;28:173–90. [III] 22 Macfarlane JT. Pneumonia and other acute infections: acute respiratory infections in adults. In: Brewis RAL, Corrin B, Geddes DM, Gibson GJ, eds. Respiratory medicine. London: W B Saunders, 1995: 705–46. [IV] 23 Taryle DA, Potts DE, Sahn SA. The incidence and clinical correlates of parapneumonic effusions in pneumococcal pneumonia. Chest 1978;74:170–3. [III] 24 Light RW, Girard WM, Jenkinson SG, et al. Parapneumonic effusions. Am J Med 1980;69:507–12. [IIb] www.thoraxjnl.com Davies, Gleeson, Davies, et al 25 Wang N. Anatomy of the pleura. Clin Chest Med 1998;19:229–40. [IV] 26 Agostini E, Zocchi L. Mechanical coupling and liquid exchanges in the pleural space. Clin Chest Med 1998;19:241–60. [IV] 27 American Thoracic Society. Management of nontuberculous empyema: a statement of the subcommittee on surgery. Am Rev Respir Dis 1962;935–6. [IV] 28 Kroegel C, Anthony VB. Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. Eur Respir J 1997;10:2411–8. [IV] 29 Good JT Jr, Taryle DA, Maulitz RM, et al. The diagnostic value of pleural fluid pH. Chest 1980;78:55–9. [III] 30 Sasse SA, Causing LA, Mulligan ME, et al. Serial pleural fluid analysis in a new experimental model of empyema. Chest 1996;109:1043–8. [IIb] 31 Potts DE, Taryle DA, Sahn SA. The glucose-pH relationship in parapneumonic effusions. Arch Intern Med 1978;138:1378–80. [IIb] 32 Potts DE, Levin DC, Sahn SA. Pleural fluid pH in parapneumonic effusions. Chest 1976;70:328–31. [IIb] 33 Idell S, Girard W, Koenig KB, et al. Abnormalities of pathways of fibrin turnover in the human pleural space. Am Rev Respir Dis 1991;144:187–94. [IIb] 34 Sahn SA, Reller LB, Taryle DA, et al. The contribution of leukocytes and bacteria to the low pH of empyema fluid. Am Rev Respir Dis 1983;128:811–5. [IIb] 35 Hughes CE, Van Scoy RE. Antibiotic therapy of pleural empyema. Semin Respir Infect 1991;6:94–102. [IV] 36 Bartlett JG, Gorbach SL, Thadepalli H, et al. Bacteriology of empyema. Lancet 1974;338–40. [III] 37 Brook I, Frazier EH. Aerobic and anaerobic microbiology of empyema: a retrospective review in two military hospitals. Chest 1993;103:1502– 7. [III] 38 Ashbaugh DG. Empyema thoracis. Factors influencing morbidity and mortality. Chest 1991;99:1162–5. [III] 39 Landreneau RJ, Keenan RJ, Hazelrigg SR, et al. Thoracoscopy for empyema and hemothorax. Chest 1996;109:18–24. [III] 40 Varkey B, Rose HD, Kutty CP, et al. Empyema thoracis during a ten-year period. Analysis of 72 cases and comparison to a previous study (1952 to 1967). Arch Intern Med 1981;141:1771–6. [III] 41 Ali I, Unruh H. Management of empyema thoracis. Ann Thorac Surg 1990;50:355–9. [III] 42 Smith JA, Mullerworth MH, Westlake GW, et al. Empyema thoracis: 14-year experience in a teaching center. Ann Thorac Surg 1991;51:39–42. [III] 43 Sherman MM, Subramanian V, Berger RL. Management of thoracic empyema. Am J Surg 1977;133:474–9. [III] 44 Mandal AK, Thadepalli H. Treatment of spontaneous bacterial empyema thoracis. J Thorac Cardiovasc Surg 1987;94:414–8. [III] 45 Mavroudis C, Symmonds JB, Minagi H, et al. Improved survival in management of empyema thoracis. J Thorac Cardiovasc Surg 1981;82:49–57. [III] 46 Van Way C3, Narrod J, Hopeman A. The role of early limited thoracotomy in the treatment of empyema. J Thorac Cardiovasc Surg 1988;96:436–9. [III] 47 Lemmer JH, Botham MJ, Orringer MB. Modern management of adult thoracic empyema. J Thorac Cardiovasc Surg 1985;90:849–55. [III] 48 Lawrence DR, Ohri SK, Moxon RE, et al. Thoracoscopic debridement of empyema thoracis. Ann Thorac Surg 1997;64:1448–50. [III] 49 Civen R, Jousimies-Somer H, Marina M, et al. A retrospective review of cases of anaerobic empyema amd update of bacteriology. Clin Infect Dis 1995;20(Suppl):S224–9. [III] 50 Stavas J, van Sonnenberg E, Casola G, et al. Percutaneous drainage of infected and noninfected thoracic fluid collections. J Thorac Imaging 1987;2:80–7. [IV] 51 Eibenberger KL, Dock WI, Ammann ME, et al. Quantification of pleural effusions: sonography versus radiography. Radiology 1994;191:681–4. [IIb] 52 Yang PC, Luh KT, Chang DB, et al. Value of sonography in determining the nature of pleural effusion: analysis of 320 cases. AJR 1992;159:29–33. [III] 53 Kearney SE, Davies CW, Davies R, et al. Computerised tomography and ultrasound correlation in parapneumonic effusions and empyema. Clin Radiol 2000;55:542–7. [III] 54 Stark DD, Federle MP, Goodman PC, et al. Differentiating lung abscess and empyema: radiography and computed tomography. AJR 1983;141:163–7. [III] 55 Muller NL. Imaging of the pleura. Radiology 1993;186:297–309. [IV] 56 Aquino SL, Webb WR, Gushiken BJ. Pleural exudates and transudates: diagnosis with contrast-enhanced CT. Radiology 1994;192:803–8. [III] 57 Waite RJ, Carbonneau RJ, Balikian JP, et al. Parietal pleural changes in empyema: appearances at CT. Radiology 1990;175:145–50. [III] 58 Takasugi JE, Godwin JD, Teefey SA. The extrapleural fat in empyema: CT appearance. Br J Radiol 1991;64:580–3. [III] 59 Davies CWH, Kearney SE, Gleeson FV, et al. Predictors of outcome and long term survival in patients with pleural infection. Am J Respir Crit Care Med 1999;160:1682–7. [III] 60 Poe RH, Marin MG, Israel RH, et al. Utility of pleural fluid analysis in predicting tube thoracostomy/decortication in parapneumonic effusions. Chest 1991;100:963–7. [III] 61 Himelman RB, Callen PW. The prognostic value of loculations in parapneumonic pleural effusions. Chest 1986;90:852–6. [III] 62 Light RW. A new classification of parapneumonic effusions and empyema. Chest 1995;108:299–301. [IV] BTS guidelines for the management of pleural infection 63 Heffner JE, Brown LK, Barbieri C, et al. Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis. Am J Respir Crit Care Med 1995;151:1700–8. [Ia] 64 Mattison LE, Coppage L, Alderman DF, et al. Pleural effusions in the medical ICU: prevalence, causes, and clinical implications. Chest 1997;111:1018–23. [III] 65 Hamm H, Light RW. Parapneumonic effusion and empyema. Eur Respir J 1997;10:1150–6. [IV] 66 Lesho EP, Roth BJ. Is pH paper an acceptable, low-cost alternative to the blood gas analyzer for determining pleural fluid pH? Chest 1997;112:1291–2. [IIa] 67 Cheng D, Rodriguez M, Rogers J, et al. Comparison of pleural fluid pH values obtained using blood gas machine, pH meter, and pH indicator strip. Chest 1998;114:1368–72. [IIa] 68 Jimenez-Castro D, Diaz G, Perez-Rodriguez E, et al. Modification of pleural fluid pH by local anaesthesia. Chest 1999;116:399–402. [IIa] 69 Huang HC, Chang HY, Chen CW, et al. Predicting factors for outcome of tube thoracostomy in complicated parapneumonic effusion or empyema. Chest 1999;115:751–6. [III] 70 Cham CW, Haq SM, Rahamim J. Empyema thoracis: a problem with late referral? Thorax 1993;48:925–7. [IV] 71 Sasse S, Nguyen TK, Mulligan M, et al. The effects of early chest tube placement on empyema resolution. Chest 1997;111:1679–83. [Ib] 72 Neild JE, Eykyn SJ, Phillips I. Lung abscess and empyema. Q J Med 1985;57:875–82. [III] 73 Bartlett JG. Antibiotics in lung abscess. Semin Respir Infect 1991;6:103–11. [IV] 74 Minton EJ, Macfarlane JT. Antibiotic resistant Streptococcus pneumoniae. Thorax 1996;51(Suppl 2):S45–50. [IV] 75 Wong CA, Donald F, Macfarlane JT. Streptococcus milleri pulmonary disease: a review and clinical description of 25 patients. Thorax 1995;50:1093–6. [III] 76 Jerng JS, Hsueh PR, Teng LJ, et al. Empyema thoracis and lung abscess caused by viridans streptococci. Am J Respir Crit Care Med 1997;156:1508–14. [III] 77 Taryle DA, Good JT, Morgan EJ, et al. Antibiotic concentrations in human parapneumonic effusions. Antimicrob Agents Chemother 1981;7:171–7. [IIb] 78 Scaglione F. Serum protein binding and extravascular diffusion of methoxyimino cephalosporins. Time courses of cefotaxime and ceftriaxone in serum and pleural exudate. J Antimicrob Agents Chemother 1990;26(Suppl A):1–10. [IIb] 79 Shohet I, Yellin A, Meyerovitch J, et al. Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model. Antimicrob Agents Chemother 1987;31:982–5. [IIb] 80 Huchon G, Woodhead M. Guidelines for management of adult community-acquired lower respiratory tract infections. European Study on Community-acquired Pneumonia (ESOCAP) Committee. Eur Respir J 1998;11:986–91. [IV] 81 Hammond JM, Potgieter PD, Hanslo D, et al. The etiology and antimicrobial susceptibility patterns of microorganisms in acute community-acquired lung abscess. Chest 1995;108:937–41. [III] 82 Shinzato T, Saito A. A mechanism of pathogenicity of “Streptococcus milleri group” in pulmonary infection: synergy with an anaerobe. J Med Microbiol 1994;40:118–23. [IIb] 83 Shinzato T, Saito A. The Streptococcus milleri group as a cause of pulmonary infections. Clin Infect Dis 1995;21(Suppl 3):S238–43. [III] 84 Finegold SM, Wexler HM. Present studies of therapy for anaerobic infections. Clin Infect Dis 1996;23(Suppl 1):S9–14. [IV] 85 Kroboth FJ. Clinicoradiographic correlation with extent of Legionnaires’ disease. AJR 1983;141:263–8. [IIb] 86 Randolph KA. Legionnaires’ disease presenting with empyema. Chest 1979;75:404–6. [III] 87 Fine NL, Smith LR, Sheedy PF. Frequency of pleural effusions in mycoplasma and viral pneumonias. N Engl J Med 1970;283:790–3. [III] 88 Mansel JK, Rosenow ECI, Smith TF, et al. Mycoplasma pneumoniae pneumonia. Chest 1989;95:639–46. [III] 89 Silverman SG, Mueller PR, Saini S, et al. Thoracic empyema: management with image-guided catheter drainage. Radiology 1988;169:5–9. [III] 90 Crouch JD, Keagy BA, Delany DJ. “Pigtail” catheter drainage in thoracic surgery. Am Rev Respir Dis 1987;136:174–5. [III] 91 van Sonnenberg E, Nakamoto SK, Mueller PR, et al. CT- and ultrasound-guided catheter drainage of empyemas after chest-tube failure. Radiology 1984;151:349–53. [III] 92 Hunnam GR, Flower CD. Radiologically-guided percutaneous catheter drainage of empyemas. Clin Radiol 1988;39:121–6. [III] 93 Ulmer JL, Choplin RH, Reed JC. Image-guided catheter drainage of the infected pleural space. J Thorac Imaging 1991;6:65–73. [IV] 94 Westcott JL. Percutaneous catheter drainage of pleural effusion and empyema. AJR 1985;144:1189–93. [III] 95 Merriam MA, Cronan JJ, Dorfman GS, et al. Radiographically guided percutaneous catheter drainage of pleural fluid collections. AJR 1988;151:1113–6. [III] 96 Klein JS, Schultz S, Heffner JE. Interventional radiology of the chest: image-guided percutaneous drainage of pleural effusions, lung abscess, and pneumothorax. AJR 1995;164:581–8. [IV] 97 Lee KS, Im JG, Kim YH, et al. Treatment of thoracic multiloculated empyemas with intracavitary urokinase: a prospective study. Radiology 1991;179:771–5. [III] 98 Munnell ER. Thoracic drainage. Ann Thorac Surg 1997;63:1497–502. [IV] ii27 99 Miller KS, Sahn SA. Chest tubes. Indications, technique, management and complications. Chest 1987;91:258–64. [IV] 100 Moulton AL. Surgical definition of pleural peel. Radiology 1991;178:889–900. [IV] 101 Neff CC, van Sonnenberg E, Lawson DW, et al. CT follow-up of empyemas: pleural peels resolve after percutaneous catheter drainage. Radiology 1990;176:195–7. [III] 102 Robinson LA, Moulton AL, Fleming WH, et al. Intrapleural fibrinolytic treatment of multiloculated thoracic empyemas. Ann Thorac Surg 1994;57:803–13. [III] 103 Bilaceroglu.S, Cagerici.U, Cakan A. Management of complicated parapneumonic pleural effusions with image-guided drainage and intrapleural urokinase or streptokinase: a controlled randomized trial. Eur Respir J 1997;10:325S. [Ib] 104 Henke CA, Leatherman JW. Intrapleurally administered streptokinase in the treatment of acute loculated nonpurulent parapneumonic effusions. Am Rev Respir Dis 1992;145:680–4. [III] 105 Aye RW, Froese DP, Hill LD. Use of purified streptokinase in empyema and hemothorax. Am J Surg 1991;161:560–2. [III] 106 Temes RT, Follis F, Kessler RM, et al. Intrapleural fibrinolytics in management of empyema thoracis. Chest 1996;110:102–6. [III] 107 Ogirala RG, Williams MHJ. Streptokinase in a loculated pleural effusion. Effectiveness determined by site of instillation. Chest 1988;94:884–6. [III] 108 Willsie Ediger SK, Salzman G, Reisz G, et al. Use of intrapleural streptokinase in the treatment of thoracic empyema. Am J Med Sci 1990;300:296–300. [III] 109 Jerjes Sanchez C, Ramirez Rivera A, Elizalde JJ, et al. Intrapleural fibrinolysis with streptokinase as an adjunctive treatment in hemothorax and empyema: a multicenter trial. Chest 1996;109:1514–9. [III] 110 Chin NK, Lim TK. Controlled trial of intrapleural streptokinase in the treatment of pleural empyema and complicated parapneumonic effusions. Chest 1997;111:275–9. [IIa] 111 Fraedrich G, Hofmann D, Effenhauser P, et al. Instillation of fibrinolytic enzymes in the treatment of pleural empyema. Thorac Cardiovasc Surg 1982;30:36–8. [III] 112 Porter J, Banning AP. Intrapleural streptokinase. Thorax 1998;53:720. [III] 113 Taylor RFH, Rubens MB, Pearson MC, et al. Intrapleural streptokinase in the management of empyema. Thorax 1994;49:856–9. [III] 114 Mitchell ME, Alberts WM, Chandler KW, et al. Intrapleural streptokinase in management of parapneumonic effusions. Report of series and review of literature. J Fla Med Assoc 1989;76:1019–22. [III] 115 Roupie E, Bouabdallah K, Delclaux C, et al. Intrapleural administration of streptokinase in complicated purulent pleural effusion: a CT-guided strategy. Intensive Care Med 1996;22:1351–3. [III] 116 Laisaar T, Puttsepp E, Laisaar V. Early administration of intrapleural streptokinase in the treatment of multiloculated pleural effusions and pleural empyemas. Thorac Cardiovasc Surg 1996;44:252–6. [III] 117 Bouros D, Schiza S, Panagou P, et al. Role of streptokinase in the treatment of acute loculated parapneumonic pleural effusions and empyema. Thorax 1994;49:852–5. [III] 118 Godley PJ, Bell RC. Major hemorrhage following administration of intrapleural streptokinase. Chest 1984;86:486–7. [III] 119 Davies CWH, Lok S, Davies RJ. The systemic fibrinolytic activity of intrapleural streptokinase. Am J Respir Crit Care Med 1998;157:328– 30. [IIb] 120 Bergh NP, Ekroth R, Larsson S, et al. Intrapleural streptokinase in the treatment of haemothorax and empyema. Scand J Thorac Cardiovasc Surg 1977;11:265–8. [III] 121 Berglin E, Ekroth R, Teger Nilsson AC, et al. Intrapleural instillation of streptokinase. Effects on systemic fibrinolysis. Thorac Cardiovasc Surg 1981;29:124–6. [IIb] 122 Ryan JM, Boland GW, Lee MJ, et al. Intracavitary urokinase therapy as an adjunct to percutaneous drainage in a patient with a multiloculated empyema. AJR 1996;167:643–7. [III] 123 Park CS, Chung WM, Lim MK, et al. Transcatheter instillation of urokinase into loculated pleural effusion: analysis of treatment effect. AJR 1996;167:649–52. [III] 124 Cohen ML, Finch IJ. Transcatheter intrapleural urokinase for loculated pleural effusion. Chest 1994;105:1874–6. [III] 125 Pollak JS, Passik CS. Intrapleural urokinase in the treatment of loculated pleural effusions. Chest 1994;105:868–73. [III] 126 Bouros D, Schiza S, Tzanakis N, et al. Intrapleural urokinase in the treatment of complicated parapneumonic pleural effusions and empyema. Eur Respir J 1996;9:1656–9. [III] 127 Moulton JS, Benkert RE, Weisiger KH, et al. Treatment of complicated pleural fluid collections with image- guided drainage and intracavitary urokinase. Chest 1995;108:1252–9. [III] 128 Moulton JS, Moore PT, Mencini RA. Treatment of loculated pleural effusions with transcatheter intracavitary urokinase. AJR 1989;153:941–5. [III] 129 Davies RJO, Traill ZC, Gleeson FV. Randomised controlled trial of intra-pleural streptokinase in community acquired pleural infection. Thorax 1997;52:416–21. [Ib] 130 Bouros D, Schiza S, Patsourakis G, et al. Intrapleural streptokinase versus urokinase in the treatment of complicated parapneumonic effusions: a prospective, double-blind study. Am J Respir Crit Care Med 1997;155:291–5. [Ib] 131 Bouros D, Schiza S, Tzanakis N, et al. Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. Am J Respir Crit Care Med 1999;159:37–42. [Ib] www.thoraxjnl.com ii28 132 Thomson AH, Hull J, Kumar R, et al. A randomised trial of intrapleural urokinase in the treatment of childhood empyema. Thorax 2002; 57; 343–7. [Ib] 133 Strange C, Allen ML, Harley R, et al. Intrapleural streptokinase in experimental empyema. Am Rev Respir Dis 1993;147:962–6. [IIb] 134 Bouros D, Schiza S, Patsourakis G, et al. Intrapleural streptokinase versus urokinase in the treatment of complicated parapneumonic effusions. Am J Respir Crit Care Med 1997;155:291–5. [Ib] 135 Jennings K. Antibodies to streptokinase. BMJ 1996;312:393–4. [IV] 136 Lynch M, Littler WA, Pentecost BL, et al. Immunoglobulin response to intravenous streptokinase in acute myocardial infarction. Br Heart J 1991;66:139–42. [IIb] 137 Patel S, Jalihal S, Dutka DP, et al. Streptokinase neutralisation titres up to 866 days after intravenous streptokinase for acute myocardial infarction. Br Heart J 1993;70:119–21. [III] 138 Jalihal S, Morris GK. Antistreptokinase titres after intravenous streptokinase. Lancet 1990;335:184–5. [IIb] 139 Elliott JM, Cross DB, Cederholm Williams SA, et al. Neutralizing antibodies to streptokinase four years after intravenous thrombolytic therapy. Am J Cardiol 1993;71:640–5. [IIb] 140 Buchalter MB, Suntharalingam G, Jennings I, et al. Streptokinase resistance: when might streptokinase administration be ineffective? Br Heart J 1992;68:449–53. [IIb] 141 Fears R, Ferres H, Glasgow E, et al. Monitoring of streptokinase resistance titre in acute myocardial infarction patients up to 30 months after giving streptokinase or anistreplase and related studies to measure specific antistreptokinase IgG. Br Heart J 1992;68:167–70. [IIb] www.thoraxjnl.com Davies, Gleeson, Davies, et al 142 Lee HS, Cross S, Davidson R, et al. Raised levels of antistreptokinase antibody and neutralization titres from 4 days to 54 months after administration of streptokinase or anistreplase. Eur Heart J 1993;14:84–9. [IIb] 143 Alfageme I, Vazquez R. Ventricular fibrillation after intrapleural urokinase. Intensive Care Med 1997;23:352. [III] 144 Frye MD, Jarratt M, Sahn SA. Acute hypoxemic respiratory failure following intrapleural thrombolytic therapy for hemothorax. Chest 1994;105:1595–6. [III] 145 Light RW, Nguyen T, Mulligan ME, et al. The in vitro efficacy of varidase versus streptokinase or urokinase for liquefying thick purulent exudative material from loculated empyema. Lung 2000;178:13–18. [IIb] 146 Simpson G, Roomes D, Heron M. Effects of streptokinase and deoxyribonuclease on viscosity of human surgical and empyema pus. Chest 2000;117:1728–33. [IIb] 147 Naidich DP, Lee JJ, Garay SM, et al. Comparison of CT and fiberoptic bronchoscopy in the evaluation of bronchial disease. AJR 1987;148:1–7. [IIb] 148 Naidich DP, Harkin TJ. Airways and lung: correlation of CT with fiberoptic bronchoscopy. Radiology 1995;197:1–12. [IIb] 149 Millar AB, Boothroyd AE, Edwards D, et al. The role of computed tomography (CT) in the investigation of unexplained haemoptysis. Respir Med 1992;86:39–44. [III] 150 Woodring JH. Determining the cause of pulmonary atelectasis: a comparison of plain radiography and CT. AJR 1988;150:757–63. [III] 151 Pothula V, Krellenstein DJ. Early aggressive surgical management of parapneumonic empyemas. Chest 1994;105:832–6. [III] 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 www.thoraxjnl.com 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 REFERENCES 1 Chernow B, Sahn SA. Carcinomatous involvement of the pleura. Am J Med 1977;63:695–702. [IV] 2 Sears D, Hajdu SI. The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions. Acta Cytol 1987;31:85–97. [III] 3 Molengraft van de FJJM, Vooijs GP. Survival of patients with malignancy-associated effusions. Acta Cytol 1989;33:911–6. [III] 4 Bonnefoi H, Smith IE. How should cancer presenting as a malignant effusion be managed? Br J Cancer 1996;74:832–5. [IV] 5 Abbruzzese JL, Abbruzzese MC, Hess KR, et al. Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 1994;12:1272–80. [III] 6 DiBonito L, Falconieri G, Colautti I, et al. The positive pleural effusion. A retrospective study of cytopathologic diagnoses with autopsy confirmation. Acta Cytol 1992;36:329–32. [III] 7 Salyer WR, Eggleston JC, Erozan YS. Efficacy of pleural needle biopsy and pleural fluid cytopathology in the diagnosis of malignant neoplasm involving the pleura. Chest 1975;67:536–9. [III] 8 Johnston WW. The malignant pleural effusion. A review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer 1985;56:905–9. [III] 9 Hsu C. Cytologic detection of malignancy in pleural effusion: a review of 5255 samples from 3811 patients. Diagn Cytopathol 1987;3:8–12. [III] 10 Miserocchi G. Physiology and pathophysiology of pleural fluid turnover. Eur Respir J 1997;10:219–25. [IV] 11 Negrini D, Pistolesi M, Miniati M, et al. Regional protein absorption rates from the pleural cavity in dogs. J Appl Physiol 1985;58:2062–7. [III] 12 Miserocchi G, Venturoli D, Negrini D, et al. Intrapleural fluid movements described by a porous flow model. J Appl Physiol 1992;73:2511–6. [IIb] BTS guidelines for the management of malignant pleural effusions 13 Meyer PC. Metastatic carcinoma of the pleura. Thorax 1966;21:437–43. [III] 14 Rodriguez-Panadero F, Naranjo FB, Lopez-Mejias J. Pleural metastatic tumours and effusions. Frequency and pathogenic mechanisms in a post-mortem series. Eur Respir J 1989;2:366–9. [III] 15 Fentiman IS, Reubens RD, Hayward JL. Control of pleural effusions in patients with breast cancer. A randomized trial. Cancer 1983;2:737–9. [Ib] 16 Kraft A, Weindel K, Ochs A, et al. Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer 1999;85:178–87. [III] 17 Hott JW, Yu L, Antony VB, et al. Role of vascular endothelial growth factor (VEGF) in the formation of malignant pleural effusions. Am J Respir Crit Care Med 1999;159:A212. [III] 18 Maher GG, Berger HW. Massive pleural effusion: malignant and nonmalignant causes in 46 patients. Am Rev Respir Dis 1972;105:458–60. [III] 19 Judson MA, Sahn SA. Pulmonary physiologic abnormalities caused by pleural disease. Semin Respir Crit Care Med 1995;16:346–53. [IV] 20 Stretton F, Edmonds P, Marrinan M. Malignant pleural effusions. Eur J Palliative Care 1999;6:5–9. [IV] 21 Lambert C, Shah HH, Urschel HC Jr, et al. The treatment of malignant pleural effusions by closed trocar tube drainage. Ann Thorac Surg 1967;3:1–5. [IIb] 22 Anderson CB, Philpott GW, Ferguson TB. The treatment of malignant effusions. Cancer 1974;33:916–22. [III] 23 Sorensen PG, Svendsen TL, Enk B. Treatment of malignant pleural effusion with drainage, with and without instillation of talc. Eur J Respir Dis 1984;65:131–5. [Ib] 24 Groth G, Gatzemeier U, Haubingen K, et al. Intrapleural palliative treatment of malignant pleural effusions with mitoxantrone versus placebo (pleural tube alone). Ann Oncol 1991;2:213–5. [Ib] 25 Izbicki R, Weyhing BT, Baker L, et al. Pleural effusion in cancer patients. A prospective randomized study of pleural drainage with the addition of radioactive phosphorus to the pleural space versus pleural drainage alone. Cancer 1975;36:1511–8. [Ib] 26 Zaloznik AJ, Oswald SG, Langin M. Intrapleural tetracycline in malignant pleural effusions. Cancer 1983;51:752–5. [Ib] 27 Antony VB. Pathogenesis of malignant pleural effusions and talc pleurodesis. Pneumologie 1999;10:493–8. [IV] 28 Antony VB, Rothfuss KJ, Godbey SW, et al. Mechanism of tetracycline-hydrochloride-induced pleurodesis. Am Rev Respir Dis 1992;146:1009–13. [III] 29 Rodriguez-Panadero F, Segado A, Juan JM, et al. Failure of talc pleurodesis is associated with increased pleural fibrinolysis. Am J Respir Crit Care Med 1995;151:785–90. [IIb] 30 Xie C, Teixeira LR, McGovern JP, et al. Systemic corticosteroids decrease the effectiveness of talc pleurodesis. Am J Respir Crit Care Med 1999;157:1441–4. [IIa] 31 Belani CP, Einarson TR, Arikian SR, et al. Cost-effectiveness analysis of pleurodesis in the management of malignant pleural effusion. J Oncol Manag 1995;4:24–34. [IIb] 32 Hausheer FH, Yarbro JW. Diagnosis and treatment of malignant pleural effusion. Semin Oncol 1985;12:54–75. [IV] 33 Owen S, Gould D. Underwater seal chest drains: the patient’s experience. J Clin Nurs 1997;6:215–25. [IIb] 34 Parker LA, Charnock GC, Delany DJ. Small bore catheter drainage and sclerotherapy for malignant pleural effusions. Cancer 1989;64:1218– 21. [III] 35 Morrison MC, Mueller PR, Lee MJ, et al. Sclerotherapy of malignant pleural effusion through songraphically placed small-bore catheters. AJR 1992;158:41–3. [III] 36 Seaton KG, Patz EF Jr, Goodman PC. Palliative treatment of malignant pleural effusions: value of small-bore catheter thoracostomy and doxycycline sclerotherapy. AJR 1995;164:589–91. [IIb] 37 Patz EF Jr, McAdams HP, Erasmus JJ, et al. Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage. Chest 1998;113:1305– 11. [Ib] 38 Clementsen P, Evald T, Grode G, et al. Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study. Respir Med 1998;92:593–6. [Ib] 39 Patz EF Jr, McAdams HP, Goodman PC, et al. Ambulatory sclerotherapy for malignant pleural effusions. Radiology 1996;199:133–5. [IIb] 40 Adler RH, Sayek I. Treatment of malignant pleural effusion: a method using tube thoracostomy and talc. Ann Thorac Surg 1976;22:8–15. [IIb] 41 Villanueva AG, Gray AW Jr, Shahian DM, et al. Efficacy of short term versus long term tube thoracostomy drainage before tetracycline pleurodesis in the treatment of malignant pleural effusions. Thorax 1994;49:23–5. [Ib] 42 Kennedy L, Rusch VW, Strange C, et al. Pleurodesis using talc slurry. Chest 1994;106:342–6. [III] 43 Robinson L A, Fleming WH, Galbraith TA. Intrapleural doxycycline control of malignant pleural effusions. Ann Thorac Surg 1993;55:1115–21. [III] 44 Tarver RD, Broderick LS, Conces DJ. Reexpansion pulmonary edema. J Thorac Imag 1996;11:198–209. [IV] 45 Mahfood S, Hix WR, Aaron BL, et al. Reexpansion pulmonary edema. Ann Thorac Surg 1988;45:340–5. [IV] 46 Nakamura H, Ishizaka A, Sawafuji M, et al. Elevated levels of interleukin-8 and leukotriene B4 in pulmonary edema fluid of a patient with reexpansion pulmonary edema. Am J Respir Crit Care Med 1994;149:1037–40. [IV] ii37 47 Pulsiripunya C, Youngchaiud P, Pushpakom R, et al. The efficacy of doxycycline as a pleural sclerosing agent in malignant pleural effusion: a prospective study. Respirology 1996;1:69–72. [IIb] 48 Wooten SA, Barbarash RA, Strange C, et al. Systemic absorption of tetracycline and lidocaine following intrapleural instillation. Chest 1988;94:960–3. [III] 49 Sherman S, Grady KJ, Seidman JC. Clinical experience with tetracycline pleurodesis of malignant pleural effusions. South Med J 1987;80:716–9. [III] 50 Whitwam JG, Wang C. Sedation and sedoanalgesia. In: Whitwam J G. Day-case anaesthesia and sedation. London: Blackwell Scientific Publications, 1994: 262–74. [IV] 51 McAlpine LG, Hulks G, Thomson NC. Management of recurrent malignant pleural effusion in the United Kingdom: survey of clinical practice. Thorax 1990;45:699–701. [IV] 52 Heffner JE, Unruh LC. Tetracycline pleurodesis: adios, farewell, adieu. Chest 1992;101:64–6. [IV] 53 Bayly TC, Kisner DL, Sybert A, et al. Tetracycline and quinacrine in the control of malignant pleural effusions. A randomized trial. Cancer 1978;41:1188–92. [Ib] 54 Landvater L, Hix WR, Mills M, Siegel RS, et al. Malignant pleural effusion treated by tetracycline sclerotherapy. A comparison of single vs repeated instillation. Chest 1988;93:1196–8. [Ib] 55 Martinez-Moragon E, Aparicio J, Rogado MC, et al. Pleurodesis in malignant pleural effusions: a randomized study of tetracycline versus bleomycin. Eur Respir J 1997;10:2380–3. [Ib] 56 Gravelyn TR, Michelson MK, Gross BH, et al. Tetracycline pleurodesis for malignant pleural effusions. A 10-year retrospective study. Cancer 1987;59:1973–7. [III] 57 Kessinger A, Wigton RS. Intracavitary bleomycin and tetracycline in the management of malignant pleural effusions: a randomized study. J Surg Oncol 1987;36:81–3. [Ib] 58 Evans TR, Stein RC, Pepper JR, et al. A randomized prospective trial of surgical against medical tetracycline pleurodesis in the management of malignant pleural effusions secondary to breast cancer. Eur J Cancer 1993;29A:316–9. [Ib] 59 Fentiman IS, Rubens RD, Hayward JL. A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer. Eur J Cancer Clin Oncol 1986;22:1079–81. [Ib] 60 McAlpine LG, Kay JW, Thomson NC, et al. Tetracycline pleurodesis in malignant pleural effusion: a comparison of needle aspiration with intercostal tube drainage. Thorax 1995;50:437P. [Ib] 61 Bethune N. Pleural poudrage: new technique for deliberate production of pleural adhesions as a preliminary to lobectomy. J Thorac Surg 1935;4:251–61. [IV] 62 Marom EM, Patz EF Jr., Erasmus JJ, et al. Malignant pleural effusions: treatment with small-bore catheter thoracostomy and talc pleurodesis. Radiology 1999;210:277–81. [IIb] 63 Thompson RL, Yau JC, Donnelly RF, Gowan DJ, et al. Pleurodesis with iodized talc for malignant effusions using pigtail catheters. Ann Pharmacother 1998;32:739–42. [IIb] 64 Webb WR, Ozmen V, Moulder PV, et al. Iodized talc pleurodesis for the treatment of pleural effusions. J Thorac Cardiovasc Surg 1992;103:881–5. [III] 65 Weissberg D, Ben-Zeev I. Talc pleurodesis. Experience with 360 patients. J Thorac Cardiovasc Surg 1993;106:689–95. [III] 66 Lynch TJ Jr, Kalish L, Mentzer SJ, et al. Optimal therapy of malignant pleural effusions: report of a randomized trial of bleomycin, tetracycline and talc and a meta-analysis. Int J Oncol 1996;8:183–90. [Ib] 67 Zimmer PW, Hill M, Casey K, Harvey E, et al. Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions. Chest 1997;112:430–4. [Ib] 68 Yim AP, Chung SS, Lee TW, et al. Thoracoscopic management of malignant pleural effusions. Chest 1996;109:1234–8. [III] 69 Rinaldo JE, Owens GR, Rogers RM. Adult respiratory distress syndrome following intrapleural installation of talc. J Thorac Cardiovasc Surg 1983;85:523–6. [IV] 70 Ferrer J, Villarino MA, Tura JM, et al. Talc preparations used for pleurodesis vary markedly from one preparation to another. Chest 2001;119:1901–5. [IV] 71 Alberts DS, Chen HSG, Mayersohn M, et al. Bleomycin pharmacokinetics in man II: Intracavitary administration. Cancer Chemother Pharmacol 1979;2:127–32. [III] 72 Bitran JD, Brown C, Desser RK, et al. Intracavitary bleomycin for the control of malignant effusions. J Surg Oncol 1981;16:273–7. [III] 73 Ostrowski MJ, Halsall GM. Intracavitary bleomycin in the management of malignant effusions: a multicenter study. Cancer Treatment Reports 1982;66:1903–7. [III] 74 Ruckdeschel JC, Moores D, Lee JY, et al. Intrapleural therapy for malignant pleural effusions. A randomized comparison of bleomycin and tetracycline. Chest 1991;100:1528–35. [Ib] 75 Hartman DL, Gaither JM, Kesler KA, et al. Comparison of insufflated talc under thoracoscopic guidance with standard tetracycline and bleomycin pleurodesis for control of malignant pleural effusions. J Thorac Cardiovasc Surg 1993;105:743–7. [Ib] 76 Goff BA, Mueller PR, Muntz HG, et al. Small chest-tube drainage followed by bleomycin sclerosis for malignant pleural effusions. Obstet Gynecol 1993;81:993–6. [III] 77 Hsu WH, Chiang CD, Chen CY, et al. Ultrasound-guided small-bore Elecath tube insertion for the rapid sclerotherapy of malignant pleural effusion. Jpn J Clin Oncol 1998;28:187–91. [III] 78 Mansson T. Treatment of malignant pleural effusion with doxycycline. Scand J Infect Dis 1988;53(Suppl):29–34. [III] www.thoraxjnl.com ii38 79 Heffner JE, Standerfer RJ, Torstveit J, et al. Clinical efficacy of doxycyline for pleurodesis. Chest 1994;105:1743–7. [III] 80 Prevost A, Nazeyrollas P, Milosevic D, et al. Malignant pleural effusions treated with high dose intrapleural doxycycline: clinical efficacy and tolerance. Oncol Reports 1998;5:363–6. [III] 81 Hatta T, Tsubuota N, Yoshimura M, et al. Effect of intrapleural administration of minocycline on postoperative air leakage and malignant pleural effusions. Kyobu Geka 1990;43:283–6. [III] 82 Light RW, Sassoon CS, Vargas FS, et al. Comparison of the effectiveness of tetracycline and minocycline as pleural sclerosing agents in rabbits. Am Rev Respir Dis 1992;145:A868. [III] 83 Webb HE, Oaten SW, Pike CP. Treatment of malignant ascitic and pleural effusions with Corynebacterium parvum. BMJ 1978;1:338–40. [III] 84 McLeod DT, Calverley PM, Millar JW, et al. Further experience of Corynebacterium parvum in malignant pleural effusion. Thorax 1985;40:515–8. [IIb] 85 Millar JW, Hunter AM, Horne NW. Intrapleural immunotherapy with Corynebacterium parvum in recurrent malignant pleural effusions. Thorax 1979;35:856–8. [Ib] 86 Leahy BC, Honeybourne D, Brear SG, et al. Treatment of malignant pleural effusions with intrapleural Corynebacterium parvum or tetracycline. Eur J Respir Dis 1985;66:50–4. [Ib] 87 Ostrowski MJ, Priestman TJ, Houston RF, et al. A randomized trial of intracavitary bleomycin and Corynebacterium parvum in the control of malignant pleural effusions. Radiother Oncol 1989;14:19–26. [Ib] 88 Foresti V. Intrapleural Corynebactrium parvum for recurrent malignant pleural effusions. Respiration 1995;62:21–6. [III] 89 Bilaceroglu S, Cagirici U, Perim K, et al. Corynebacterium parvum pleurodesis and survival is not significantly influencd by pleural pH and glucose level. Monaldi Arch Chest Dis 1998;53:14–22. [IIb] 90 Rosso R, Rimoldi R, Salvati F, et al. Intrapleural natural beta interferon in the treatment of malignant pleural effusions. Oncology 1988;45:253–6. [III] 91 Lissoni P, Barni S, Tancini G, et al. Intracavitary therapy of neoplastic effusions with cytokines: comparison among interferon alpha, beta and interleukin-2. Supportive Care in Cancer 1995;3:78–80. [Ib] 92 Davis M, Williford S, Muss HB, et al. A phase I-II study of recombinant intrapleural alpha interferon in malignant pleural effusions. Am J Clin Oncol 1992;15:328–30. [III] 93 Goldman CA, Skinnider LF, Maksymiuk AW. Interferon instillation for malignant pleural effusions. Ann Oncol 1993;4:141–5. [III] 94 Wilkins HE, Connolly MM, Grays P, et al. Recombinant interferon alpha-2b in the management of malignant pleural effusions. Chest 1997;111:1597–9. [IIb] 95 Viallat JR, Boutin C, Rey F, et al. Intrapleural immunotherapy with escalating doses of interleukin-2 in metastatic pleural effusions. Cancer 1993;71:4067–71. [III] 96 Masotti A, Fumagalli L, Morandini GC. Intrapleural administration of recombinant interleukin-2 in non-small cell lung cancer with neoplastic pleural effusion. Monaldi Arch Chest Dis 1997;52:225–8. [III] 97 Rusch VW, Figlin R, Godwin D, et al. Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial. J Clin Oncol 1991;9:313–9. [IIb] 98 Morales M, Exposito MC. Intrapleural mitoxantrone for the palliative treatment of malignant pleural effusions. Supportive Care in Cancer 1995;3:147–9. [III] 99 Aasebo U, Norum J, Sager G, et al. Intrapleurally instilled mitoxantrone in metastatic pleural effusions: a phase II study. J Chemother 1997;9:106–11. [III] 100 Lorch DG, Gordon L, Wooten S, et al. Effect of patient positioning on distribution of tetracycline in the pleural space during pleurodesis. Chest 1988;93:527–9. [III] 101 Dryzer SR, Allen ML, Strange C, et al. A comparison of rotation and nonrotation in tetracycline pleurodesis. Chest 1993;104:1763–6. [Ib] 102 Sahn SA. Pleural diseases related to metastatic malignancies. Eur Respir J 1997;10:1907–13. [IV] 103 Yim AP, Chan AT, Lee TW, et al. Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion. Ann Thorac Surg 1996;62:1655–8. [Ib] www.thoraxjnl.com Antunes, Neville, Duffy, et al 104 Lynch TJ Jr. Management of malignant pleural effusions. Chest 1993;103(Suppl):385–9S. [IV] 105 Jones FL Jr. Subcutaneous implantation of cancer: a rare complication of pleural biopsy. Chest 1970;57:189–90. [IV] 106 Berger L, Dargan EL, Huang BL. Dissemination of cancer cells by needle biopsy of the lung. J Thorac Cardiovasc Surg 1972;63:430–2. [IV] 107 Kumar UN, Varkey B. Case report: subcutaneous metastasis. Rare complication of drainage of malignant pleural fluid. Postgrad Med 1976;60:253–5. [IV] 108 Yim AP. Port-site recurrence following video-assisted thoracoscopic surgery. Surg Endosc 1995;9:1133–5. [IV] 109 Boutin C, Rey F, Viallat JR. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. Chest 1995;108:754–8. [Ib] 110 Tillet WS, Sherry S. The effect in patients of streptococcal fibrinolysin (streptokinase) and streptococcal deoxyribonuclease on fibrinous, purulent and sanguinous pleural exudations. J Clin Invest 1949;28:173–90. [IIb] 111 Godley PJ, Bell RC. Major hemorrhage following administration of intrapleural streptokinase. Chest 1984;86:486–7. [IV] 112 Jerjes-Sanchez C, Ramirez-rivera A, Elizalde JJ, et al. Intrapleural fibrinolysis with streptokinase as an adjunctive treatment in hemothorax and empyema. Chest 1996;109:1514–9. [IIb] 113 Davies CWH, Traill ZC, Gleeson FV, et al. Intrapleural streptokinase in the management of malignant multiloculated pleural effusions. Chest 1999;115:729–33. [III] 114 Gilkeson RC, Silverman P, Haaga JR. Using urokinase to treat malignant pleural effusions. AJR 1999;173:781–3. [III] 115 Menzies R Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med 1991;114:271–6. [IIb] 116 Harris R J, Kavuru MS, Rice TW, et al. The diagnostic and therapeutic utility of thoracoscopy. Chest 1995;108:828–41. [IV] 117 Loddenkemper R. Thoracoscopy: state of the art. Eur J Respir 1998;11:213–21. [IV] 118 Canto A, Blasco E, Casillas M, et al. Thoracoscopy in the diagnosis of pleural effusion. Thorax 1977;32:550–4. [III] 119 Yim AP, Chung SS, Lee TW, et al. Thoracoscopic management of malignant pleural effusions. Chest 1996;109:1234–8. [IV] 120 Viallat JR, Rey F, Astoul P, et al. Thoracoscopic talc poudrage pleurodesis for malignant effusions. A review of 360 cases. Chest 1996;110:1387–93. [III] 121 Colt HG. Therapeutic thoracoscopy. Clin Chest Med 1998;19:383–94. [IV] 122 Viskum K, Enk B. Complications of thoracoscopy. Poumon Coeur 1981;37:25–8. [IV] 123 Milanez de Campos JR, Vargas FS, Werebe EC, et al. Thoracoscopy talc poudrage. A 15-year experience. Chest 2001;119:801–6. [IV] 124 Putnam JB, Light RW, Rodriguez RM, et al. A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer 1999;86:1992–9. [Ib] 125 Warren WH, Faber LP. Clinical experience with Pleurx catheters for malignant pleural effusions. Chest 2000;118(Suppl):130S. [III] 126 Little AG, Ferguson MK, Golomb HM, et al. Pleuroperitoneal shunting for malignant pleural effusions. Cancer 1986;58:2740–3. [III] 127 Wong PS, Goldstraw P. Pleuroperitoneal shunts. Br J Hosp Med 1993;50:16–21. [IV] 128 Petrou M, Kaplan D, Goldstraw P. Management of recurrent malignant pleural effusions. The complementary role of talc pleurodesis and pleuroperitoneal shunting. Cancer 1995;75:801–5. [III] 129 Lee KA, Harvey JC, Reich H, et al. Management of malignant pleural effusions with pleuroperitoneal shunting. J Am Coll Surg 1994;178:586–8. [III] 130 Martini N, Bains MS, Beattie EJ Jr. Indications for pleurectomy in malignant effusion. Cancer 1975;35:734–8. [III] 131 Fry WA, Khandekar JD. Parietal pleurectomy for malignant pleural effusions. Ann Surg Oncol 1995;2:160–4. [III] 132 Waller DA, Morritt GN, Forty J. Video-assisted thoracoscopic pleurectomy in the management of malignant pleural effusion. Chest 1995;107:1454–6. [IIb] 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 www.thoraxjnl.com 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. www.thoraxjnl.com 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 www.thoraxjnl.com 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 www.thoraxjnl.com 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 www.thoraxjnl.com 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- ii47 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 www.thoraxjnl.com 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 www.thoraxjnl.com 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 www.thoraxjnl.com 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 REFERENCES 1 Light RW. Pneumothorax. In: Pleural diseases. 3rd ed. Baltimore: Williams and Wilkins, 1995: 242–77. 2 Laennec RTH. Trait de l’auscultation mediate et des maladies des poumons et du coeur. Tome Second. Paris, 1819. 3 Kjaergard H. Spontaneous pneumothorax in the apparently healthy. Acta Med Scand (Suppl) 1932;43:1–159. 4 Melton LJ, Hepper NCG, Offord KP. Incidence of spontaneous pneumothorax in Olmsted County, Minnesota: 1950–1974. Am Rev Respir Dis 1979;29:1379–82. [III] 5 Bense L, Wiman LG, Hedenstierna G. Onset of symptoms in spontaneous pneumothorax: correlations to physical activity. Eur J Respir Dis 1987;71:181–6. [III] 6 Gupta D, Hansell A, Nichols T, et al. Epidemiology of pneumothorax in England. Thorax 2000;55:666–71. [III] 7 Donahue DM, Wright CD, Viale G, et al. Resection of pulmonary blebs and pleurodesis for spontaneous pneumothorax. Chest 1993;104:1767–9. [IIb] www.thoraxjnl.com 8 Lesur O, Delorme N, Frogamet JM, et al. Computed tomography in the aetiological assessment of idiopathic spontaneous pneumothorax. Chest 1990;98:341–7. [IIa] 9 O’Hara VS. Spontaneous pneumothorax. Milit Med 1978;143:32–5. [III] 10 Jansveld CA, Dijkman JH. Primary spontaneous pneumothorax and smoking. BMJ 1975;4:559–60. [IIa] 11 Bense L, Eklund G, Odont D, et al. Smoking and the increased risk of contracting pneumothorax. Chest 1987;92:1009–12. [IIa] 12 Schramel FM, Meyer CJ, Postmus PE. Inflammation as a cause of spontaneous pneumothorax and emphysematous-like changes: results of bronchoalveolar lavage. Eur Respir J 1995;8:397s. [IIb] 13 Withers JN, Fishback M.E, Kiehl PV, et al. Spontaneous pneumothorax. Am J Surg 1964;108:772–6. [IV] 14 Sadikot RT, Greene T, Meadows K, et al. Recurrence of primary pneumothorax. Thorax 1997;52:805–9. [III] 15 West JB. Distribution of mechanical stress in the lung, a possible factor in localisation of pulmonary disease. Lancet 1971;i:839–41. [IIb] 16 Smit HJM, Chatrou M, Postmus PE. The impact of spontaneous pneumothorax and its treatment on the smoking behaviour of young adult smokers. Respir Med 1998;92:1132–6. [III] 17 Lippert HL, Lund O, Blegrad S, et al. Independent risk factors for cumulative recurrence rate after first spontaneous pneumothorax. Eur Respir J 1991;4:324–31. [III] 18 Videm V, Pillgram-Larsen J, Ellingsen Ø, et al. Spontaneous pneumothorax in chronic obstructive pulmonary disease: complications, treatment and recurrences. Eur J Respir Dis 1987;71:365–71. [III] 19 Miller AC, Harvey JE. Guidelines for the management of spontaneous pneumothorax. BMJ. 1993;307:114–6. [IV] 20 Soulsby T. British Thoracic Society guidelines for the management of spontaneous pneumothorax: do we comply with them and do they work? J Accid Emerg Med 1998;15:317–21. [III] 21 Selby CD, Sudlow MF. Deficiencies in the management of spontaneous pneumothoraces. Scot Med J 1994;39:75–6. [III] 22 Yeoh JH, Ansari S, Campbell IA. Management of spontaneous pneumothorax : a Welsh survey. Postgrad Med J 2000;76:496–9. [III] 23 Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluation. Lancet 1993;342:1317–21. [IIb] 24 Bero LA, Grilli R, Grimshaw JM, et al. Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings. BMJ 1998;317:465–8. [Review] 25 Grilli R, Lomas J. Evaluating the message: the relationship between compliance rate and the subject of a practice guideline. Med Care 1994;32:202–13. [IV] 26 Woolf SH, Grol R, Hutchinson A, et al. Potential benefits, limitations and harms of clinical guidelines. BMJ 1999;318:527–30. 27 Agency for Health Care Policy and Research. Acute pain management, operative or medical procedures and trauma. Clinical practice guidelines. Publication no. 92-0032. Rockville, Maryland, USA: Agency for Healthcare Policy and Research Publications, 1992. 28 Petrie GJ, Barnwell E, Grimshaw J, on behalf of the Scottish Intercollegiate Guidelines Network. Clinical guidelines criteria for appraisal for national use. Edinburgh: Royal College of Physicians, 1995. 29 Vail WJ, Alway AE, England NJ. Spontaneous pneumothorax. Dis Chest 1963;38:512–5. [III] 30 Serementis MG. The management of spontaneous pneumothorax. Chest 1970;57:65–8. [III] 31 Wait MA, Estrera A. Changing clinical spectrum of spontaneous pneumothorax. Am J Surg 1992;164:528–31. [III] 32 Tanaka F, Itoh M, Esaki H, et al. Secondary spontaneous pneumothorax. Ann Thorac Surg 1993;55:372–6. [III] 33 Pavlin DJ, Cheney FW Jr. Unilateral pulmonary edema in rabbits after re-expansion of collapsed lung. J Appl Physiol 1979;46:31–5. [IIb] 34 Miller WC, Toon R, Palat H, et al. Experimental pulmonary edema following re-expansion of pneumothorax. Am Rev Respir Dis 1973;108:664–6. [Ib] 35 Norris RM, Jones JG, Bishop JM. Respiratory gas exchange in patients with spontaneous pneumothorax. Thorax 1968;23:427–33. [IIb] 36 Light RW, O’Hara VS, Moritz TE, et al. Intrapleural tetracycline for the prevention of recurrent spontaneous pneumothorax: results of a Department of Veterans Affairs Co-operative Study. JAMA 1990;264:2224–30. [Ib] 37 Schramel FM, Wagenaar M, Sutedja TA, et al. Diagnosis of pneumothorax not improved by additional roentgen pictures of the thorax in the expiratory phase. Ned Tijdschr Geneesk 1995;139:131–3. [IIb] 38 Schramel FM, Golding RP, Haakman CD, et al. Expiratory chest radiographs do not improve visibility of small apical pneumothoraces by enhanced contrast. Eur Resp J 1996;9:406–9. [IIb] 39 Glazer H, Anderson DJ, Wilson BS, et al. Pneumothorax: appearances on lateral chest radiographs. Radiology 1989;173:707–11. [III] 40 Carr JJ, Reed JC, Choplin RH, et al. Plain and computed radiography for detecting experimentally induced pneumothorax in cadavers: implications for detection in patients. Radiololgy 1992;183:193–9. [IIb] 41 Bourgouin P, Cousineau G, Lemire P, et al. Computed tomography used to exclude pneumothorax in bullous lung disease. J Can Ass Radiol 1985;36:341–2. [IV] 42 Collins CD, Lopez A, Mathie A, et al. Quantification of pneumothorax size on chest radiographs using intrapleural distances: regression analysis based on volume measurements from helical CT. AJR 1995;165:1127–30. [III] BTS guidelines for the management of spontaneous pneumothorax 43 Engdahl O, Toft T, Boe J. Chest radiograph: a poor method for determining the size of a pneumothorax. Chest 1993;103:26–9. [IIb] 44 Philips GD, Trotman-Dickenson B, Hodson ME, et al. Role of CT in the management of pneumothorax in patients with complex cystic lung disease. Chest 1997;112:275–8. [IV] 45 Jordan KG, Kwong JS, Flint J, et al. Surgically treated pneumothorax. Radiologic and pathologic findings. Chest 1997;111:280–5. [III] 46 Stradling P, Poole G. Conservative management of spontaneous pneumothorax. Thorax 1966;21:145–9. [III] 47 Flint K, Al-Hillawi AH, Johnson NM. Conservative management of spontaneous pneumothorax. Lancet 1984;ii: 687–8. [III] 48 O’Rourke JP, Yee ES. Civilian spontaneous pneumothorax: treatment options and long term results. Chest 1989;96:1302–6. [III] 49 Northfield TC. Oxygen therapy for spontaneous pneumothorax. BMJ 1971;4:86–8. [IIa] 50 Kirchen LT Jr, Swartzel RL. Spontaneous pneumothorax and its treatment. JAMA 1954;155:24–9. [III] 51 Archer GJ, Hamilton AAD, Upadhyag R, et al. Results of simple aspiration of pneumothoraces. Br J Dis Chest 1985;79:177–82. [III] 52 Ng AWK, Chan KW, Lee SK. Simple aspiration of pneumothorax. Singapore Med J 1994;35:50–2. [IIb] 53 Noppen M, Alexander P, Driesen P, et al. Manual aspiration versus chest tube drainage in first episodes of primary spontaneous pneumothorax. Am J Respir Crit Care Med 2002;165:1240–4. [Ib] 54 Spencer-Jones J. A place for aspiration in the treatment of spontaneous pneumothorax. Thorax 1985;40:66–7. [III] 55 Andrivert P, Djedaim K, Teboul J-L, et al. Spontaneous pneumothorax: comparison of thoracic drainage vs immediate or delayed needle aspiration. Chest 1995;108:335–40. [Ib] 56 Harvey J, Prescott RJ. Simple aspiration versus intercostal tube drainage for spontaneous pneumothorax in patients with normal lungs. BMJ 1994;309:1338–9. [Ib] 57 Vallee P, Sullivan M, Richardson H, et al. Sequential treatment of a simple pneumothorax. Ann Emerg Med 1988;17:936–47. [IIb] 58 Delius RE, Obeid FN, Horst HM, et al. Catheter aspiration for simple pneumothorax. Arch Surg 1989;124:833–6. [IIb] 59 Laub M, Milman N, Müller D. Role of small calibre chest tube drainage for iatrogenic pneumothorax. Thorax 1990;45:748–9. [IIb] 60 Playfair EE. Case of empyema treated by aspiration and subsequently by drainage. BMJ 1875;1:45–50. [IV] 61 Graham EA, Bell RD. Open pneumothorax: its relation to the treatment of empyema. Am J Med Sci 1918;156:839–43. [IV] 62 Kenyon JH. Traumatic haemothorax: siphon drainage. Ann Surg 1916;64:728–9. [IV] 63 Symbas PN. Chest drainage tubes. Surg Clin North Am 1989;69:41–6. [IV] 64 Harriss DR, Graham TR. Management of intercostal drains. Br J Hosp Med 1991;45:383–6. [IV] 65 Baumann MH, Strange C, Heffner JE, et al. Management of spontaneous pneumothorax. An American College of Chest Physicians Delphi Consensus Statement. Chest 2001;119:590–602. 66 Seaton D, Yoganathan K, Coady T, et al. Spontaneous pneumothorax: marker gas technique for predicting outcome of manual aspiration. BMJ 1991;302:262–5. [IIb] 67 Engdahl O, Boe J, Sandstedt S. Intrapleural bupivocaine for analgesia during chest drainage treatment for pneumothorax. A randomised double blind trial. Acta Anaesthesiol Scand 1993;37:149–53. [Ib] 68 Sherman S, Ravikrishnan KP, Patel A, et al. Optimum anaesthesia with intrapleural lidocaine during chemical pleurodesis with tetracycline. Chest 1993;3:533–6. [IIb] 69 Curtin JJ, Goodman LR, Quebbeman EJ, et al. Thoracostomy tubes after acute chest injury: relationship between location in a pleural fissure and function. AJR 1994;163:1339–42. [IIb] 70 Holden MP, ed. Management of intercostal drainage tubes. In: Practice of cardiothoracic surgery. Bristol: John Wright, 1982: 3. 71 Daly RC, Mucha P, Pairolero PC, et al. The risk of percutaneous chest tube thoracostomy for blunt thoracic trauma. Ann Emerg Med 1985;14:865–70. [IV] 72 Iberti TJ, Stern PM. Chest tube thoracostomy. Crit Care Clin 1992;14:879–95. [IV] 73 Miller KS, Sahn FA. Chest tubes: indications, technique, management and complications. Chest 1987;91:258–64. [Review] 74 Chan L, Reilly KM, Henderson C, et al. Complication rates of tube thoracostomy. Am J Emerg Med 1997;15:368–70. [III] 75 Baldt MM, Bankier AA, Germann PS, et al. Complications after emergency tube thoracostomy: assessment with CT. Radiology 1995;195:539–43. [III] 76 Brunner RG, Vinsant GO, Alexander RH, et al. The role of antibiotic therapy in the prevention of empyema in patients with an isolated chest injury: a prospective study. J Trauma 1990;30:1148–53. [Ib] 77 Nichols RI, Smith JW, Muzik AC, et al. Preventative antibiotic usage in traumatic injuries requiring chest tube thoracostomy. Chest 1994;106:1493–8. [Ib] 78 Maunder RJ, Pierson DJ, Hudson LD. Subcutaneous and mediastinal emphysema. Pathophysiology, diagnosis and management. Arch Intern Med 1984;144:1447–53. [Review] 79 Conetta R, Barman AA, Lakovou C, et al. Acute ventilatory failure from massive subcutaneous emphysema. Chest 1993;104:978–80. [IV] 80 So SY, Yu DY. Catheter drainage of spontaneous pneumothorax: suction or no suction, early or late removal ? Thorax 1982;37:46–8. [IIb] 81 Bevelaqua FA, Aranda C. Management of spontaneous pneumothorax with small lumen catheter manual aspiration. Chest 1982;81:693–5. [III] ii51 82 Conces Jr DJ, Tarrer RD, Cory Gray W, et al. Treatment of pneumothoraces utilising small calibre chest tubes. Chest 1988;94:55–7. [III] 83 Minami H, Saka H, Senda K, et al. Small calibre catheter drainage for spontaneous pneumothorax. Am J Med Sci 1992;304:345–7. [IIb] 84 Tattersall DJ, Traill ZC, Gleeson FV. Chest drains: Does Size Matter? Clin Radiol 2000;55:415–21. [IV] 85 Sharma TN, Agrihotri SP, Jain NK, et al. Intercostal tube thoracostomy in pneumothorax: factors influencing re-expansion of lung. Ind J Chest Dis Allied Sci 1988;30:32–5. [III] 86 Mathur R, Cullen J, Kinnear WJM, et al. Time course of resolution of persistent air leak in spontaneous pneumothorax. Respir Med 1995;89:129–32. [IIb] 87 Enerson DM, McIntyre RN. A comparative study of the physiology and physics of pleural drainage systems. J Thorac Cardiovasc Surg 1966;52:40–4. [IIb] 88 Munnell E. Thoracic drainage. Ann Thorac Surg 1997;63:1497–502. [IV] 89 Roe BB. Physiologic principles of drainage of the pleural space. Am J Surg 1958;96:246–9. [Review] 90 Pierson DJ. Persistent bronchopleural air-leak during mechanical ventilation: a review. Respir Care 1982;27:408–15. [Review] 91 Granke K, Fischer CR, Gago O, et al. The efficacy and timing of operative intervention for spontaneous pneumothorax. Ann Thorac Surg 1986;42:540–2. [IIa] 92 Schonenberger RA, Haefeli HA, Weiss P, et al. Timing of invasive procedures for primary and secondary spontaneous pneumothorax. Arch Surg 1991;126:764–66. [III] 93 Shah SS, Cohen AS, Magee PG, et al. Surgery remains a late and under-utilised option in the management of spontaneous pneumothorax: should the British Thoracic Society guidelines be revisited ? Thorax 1998;53(Suppl 4):A52. [III] 94 Pavlin DJ, Nessly MC, Cheney FW. Increased pulmonary vascular permeability as a cause of re-expansion pulmonary edema in rabbits. Am Rev Respir Dis 1981;124:422–7. [IIa] 95 Mafhood S, Hix WR, Aaron BI, et al. Re-expansion pulmonary edema. Ann Thorac Surg 1988;45:340–5. [IV] 96 Matsuura Y, Nomimura T, Nurikami H, et al. Clinical evidence of re-expansion pulmonary edema. Chest 1991;100:1562–6. [III] 97 Almind M, Lange P, Viskum K. Spontaneous pneumothorax: comparison of simple drainage, talc pleurodesis and tetracycline pleurodesis. Thorax 1989;44:627–30. [Ib] 98 Olsen PS, Anderson HO. Long term results after tetracycline pleurodesis in spontaneous pneumothorax. Ann Thorac Surg 1992;53:1015–7. [IIb] 99 Massard G, Thomas P, Wihlm J-M. Minimally invasive management for first and recurrent pneumothorax. Ann Thorac Surg 1998;66:592–9. [Review] 100 Torre M, Grassi M, Nerli FP, et al. Nd-Yag lasar pleurodesis via thoracoscopy. Chest 1994;106:338–41. [IIb] 101 Vargas FS, Wang N-S, Lee HM, et al. Effectiveness of bleomycin in comparison to tetracycline as pleural sclerosing agents in rabbits. Chest 1993;104:1582–4. [IIb] 102 Van den Brande P, Staelans I. Chemical pleurodesis in primary spontaneous pneumothorax. J Thorac Cardiovasc Surg 1989;37:180–2. [Ib] 103 Alfageme I, Moreno L, Heurtas C, et al. Spontaneous pneumothorax: long term results with tetracycline pleurodesis. Chest; 1994: 106:347–50. [IIa] 104 Light RW, Wang N-S, Sassoon CS, et al. Comparison of the effectiveness of tetracycline and minocycline as pleural sclerosing agents in rabbits. Chest 1994;106:577–82. [IIb] 105 Hurewitz AN, Lidonicci K, Wu CL, et al. Histologic changes of doxycycline pleurodesis in rabbits. Chest 1994;106:1241–5. [IIb] 106 Wang YT, Ng KY, Poh SC. Intrapleural tetracycline for spontaneous pneumothorax with persistent air leak. Singapore Med J 1988;29:72–3. [IV] 107 Macoviak JA, Stephenson LW, Ochs R, et al. Tetracycline pleurodesis during active pulmonary-pleural air leak for prevention of recurrent pneumothorax. Chest 1982;81:78–81. [Ib] 108 Chee CB, Abishaganaden J, Yeo JK, et al. Persistent air-leak in spontaneous pneumothorax - clinical course and outcome. Respir Med 1998;92:757–61. [III] 109 Thévenet F, Gamondès JP, Bodzongo D, et al. Spontaneous and recurrent pneumothorax. Surgical review of 278 cases. Ann Chir 1992;46:165–9. [III] 110 Weedon D, Smith GH. Surgical experience in the management of spontaneous pneumothorax, 1972–1982. Thorax 1983;38:737–43. [IV] 111 Körner H, Anderson KS, Strangeland L, et al. Surgical treatment of spontaneous pneumothorax by wedge resection without pleurodesis or pleurectomy. Eur J Cardiothorac Surg 1996;10:656–9. [III] 112 Thomas P, Le Mee F, Le Hors H, et al. Results of surgical treatment of persistent or recurrent pneumothorax. Ann Chir 1993;47:136–40. [III] 113 Waller DA, McConnell SA, Rajesh PB. Delayed referral reduces the success of video-assisted thoracoscopic surgery for spontaneous pneumothorax. Respir Med 1998;92:246–9. [III] 114 Inderbitzi RG, Leiser A, Furrer M, et al. Three years experience in video-assisted thoracic surgery (VATS) for spontaneous pneumothorax. J Thorac Cardiovasc Surg 1994;107:1410–5. [III] 115 Cran IR, Rumball CA. Survey of spontaneous pneumothorax in the Royal Air Force. Thorax 1967;22:462–5. [IV] 116 Parry GN, Juniper ME, Dussek JE. Surgical intervention in spontaneous pneumothorax. Respir Med 1992;86:1–2. [Review] www.thoraxjnl.com ii52 117 Gaensler EA. Parietal pleurectomy for recurrent spontaneous pneumothorax. Surg Gynecol Obstet 1956;102:293–308. [IV] 118 Claggett OT. The management of spontaneous pneumothorax. J Thorac Cardiovasc Surg 1968;55:761–2. [IV] 119 Tyson MD, Crandall WB. The surgical treatment of recurrent idiopathic spontaneous pneumothorax. J Thorac Surg 1941;10:566–70. [III] 120 Waller DA, Forty J, Morritt GN. Video-assisted thoracoscopic surgery versus thoracotomy for spontaneous pneumothorax. Ann Thorac Surg 1994;58:373–7. [IIb] 121 Waller DA. Video-assisted thoracoscopic surgery (VATS) in the management of spontaneous pneumothorax. Thorax 1997;52:307–8. [Review] 122 Naunheim KS, Mack MJ, Hazelrigg SR, et al. Safety and efficacy of video-assisted thoracic surgical techniques for the treatment of spontaneous pneumothorax. J Thorac Cardiovasc Surg 1995;109:1198–204. [III] 123 Horio H, Nomori H, Fuyuno G, et al. Limited axillary thoracotomy vs video-assisted thoracoscopic surgery for spontaneous pneumothorax. Surg Endosc 1998;12:1155–8. [III] 124 Simansky DA, Yellin A. Pleural abrasion via axillary thoracotomy in the era of video assisted thoracic surgery. Thorax 1994;49:922–3. [III] 125 Deslauriers J, Beaulieu M, Després JP, et al. Transaxillary pleurectomy for treatment of spontaneous pneumothorax. Ann Thorac Surg 1980;30:567–74. [III] 126 Kennedy L, Sahn SA. Talc pleurodesis for the treatment of pneumothorax and pleural effusion. Chest 1994;106:1215–22. [Ia] 127 Dumont P, Diemont F, Massard G, et al. Does a thorascopic approach for surgical treatment of spontaneous pneumothorax represent progress ? Eur J Cardiothorac Surg 1997;11:22–31. [III] 128 Tschopp JM, Brutsche M, Frey JG. Treatment of complicated pneumothorax by simple talc pleurodesis under thoracoscopy and local anaesthesia. Thorax 1997;52:329–32. [III] 129 Liu H-P, Lin PJ, Hsieh M-J, et al. Thoracoscopic surgery as a routine procedure for spontaneous pneumothorax. Chest 1995;107:559–62. [IV] 130 Verschoof AC, TenVelde GP, Greve LH, et al. Thorascopic pleurodesis in the management of spontaneous pneumothorax. Respiration 1988;53:197–200. [IIb] 131 Hansen AK, Nielsen PH, Møller NG, et al. Operative pleurodesis in spontaneous pneumothorax. Scand J Thorac Cardiovasc Surg 1989;23:279–81. [IV] 132 Webb WR, Ozman V, Moulder PV, et al. Iodized talc pleurodesis for the treatment of pleural effusions. J Thorac Cardiovasc Surg 1992;103:881–6. [IV] 133 Rinaldo JE, Owens GR, Roger RM. Adult respiratory distress syndrome following intrapleural instillation of talc. J Thorac Cardiovasc Surg 1983;85:523–6. [IV] 134 Kennedy L, Rusch VW, Strange C, et al. Pleurodesis using talc slurry. Chest 1994;106:342–6. [IV] 135 Hamed H, Fentiman IS, Chaudary MA, et al. Comparison of bleomycin and talc for the control of pleural effusions secondary to carcinoma of the breast. Br J Surg 1989;76:1266–7. [IIb] 136 Becker RM, Munro DD. Transaxillary minithoracotomy: the optimal approach for certain pulmonary and mediastinal lesions. Ann Thorac Surg 1976;22:254–9. [IV] 137 Kim KH, Kim HK, Han JY, et al. Transaxillary minithoracotomy versus video-assisted thoracic surgery for spontaneous pneumothorax. Ann Thorac Surg 1996;61:1510–2. [Ib] 138 Mouroux J, Elkaïm D, Padavoni B, et al. Video-assisted thoracoscopic treatment of spontaneous pneumothorax: technique and results of one hundred cases. J Thorac Cardiovasc Surg 1996;112:385–91. [IV] 139 Rämö OJ, Salo JA, Mattila SP. Video-assisted thoracoscopic pleurectomy in the treatment of recurrent spontaneous pneumothorax. Ann Chir Gynaecol 1995;84:272–5. [IIb] 140 Nathanson LK, Shimi SM, Wood RA, et al. Videothorascopic ligation of bullae and pleurectomy for spontaneous pneumothorax. Ann Thorac Surg 1991;52:316–9. [IV] 141 Fosse E, Fjeld NB, Brockmeier V, et al. Thoracoscopic pleurodesis. Scand J Thor Cardiovasc Surg 1993;27:117–9. [IV] 142 Bertrand PC, Regnard JP, Spaggiari L, et al. Immediate and long term results after surgical treatment of primary spontaneous pneumothorax by VATS. Ann Thorac Surg 1996;61:1641–5. [III] 143 Gebhard FT, Becker HP, Gerngross H, et al. Reduced inflammatory response in minimally invasive surgery of pneumothorax. Arch Surg 1996;131:1079–82. [IIb] 144 Cole Jr FH, Cole FH, Khandekar A, et al. Video-assisted thoracic surgery: primary therapy for spontaneous pneumothorax? Ann Thorac Surg 1995;60:931–5. [IIb] 145 Sekine Y, Miyata Y, Yamada H, et al. Video-assisted thoracoscopic surgery does not deteriorate postoperative pulmonary gas exchange in spontaneous pneumothorax patients. Eur J Cardiothorac Surg 1999;16:48–53. [Ib] 146 Waller DA, Forty J, Soni AK, et al. Videothoracoscopic operation for secondary spontaneous pneumothorax. Ann Thorac Surg 1994;57:1612–5. [IV] www.thoraxjnl.com Henry, Arnold, Harvey 147 British Thoracic Society Standards of Care Committee. Managing passengers with respiratory disease planning air travel: British Thoracic Society recommendations. Thorax 2002;57:289–304. 148 Ziser A, Vaananen A, Melamed Y. Diving and chronic spontaneous pneumothorax. Chest 1985;87:264–5. [IV] 149 British Thoracic Society Fitness to Dive Group. BTS guidelines on respiratory aspects of fitness for diving. Thorax 2003;58:3–11. 150 Light RW, Hamm H. Pleural disease and acquired immune deficiency syndrome. Eur Respir J 1997;10:2638–43. [IV] 151 Sepkowitz KA, Telzac EE, Gold JW, et al. Pneumothorax in AIDS. Ann Intern Med 1991;114:455–9. [III] 152 Gerein AN, Brumwell ML, Lawson LM, et al. Surgical management of pneumothorax in patients with acquired immune deficiency syndrome. Arch Surg 1991;126:1272–7. [IV] 153 Delorenzo LT, Huang CT, Maguire GP, et al. Roentgenographic patterns of Pneumocystis carinii in 104 patients with AIDS. Chest 1987;91:323–7. [IV] 154 Suster B, Akerman M, Grenstein M, et al. Pulmonary manifestations of AIDS: review of 106 episodes. Radiology 1986;161:87–93. [IV] 155 Eng RH, Bishburg E, Smith SM. Evidence for destruction of lung tissue during Pneumocystis carinii infection. Arch Intern Med 1987;147:746–9. [IV] 156 Fenerstein IM, Archer A, Pluda JM. Thin walled cavities, cysts and pneumothorax in Pneumocystis carinii pneumonia; further observation and histopathological correlation. Radiology 1990;174:197–202. [IIb] 157 Wait MA, Dal Nogare AR. Treatment of AIDS-related spontaneous pneumothorax: a decade of experience. Chest 1994;106:693–6. [IV] 158 Metersky ML, Colt HG, Olson LK, et al. AIDS-related spontaneous pneumothorax. Risk factors and treatment. Chest 1995;108:946–51. [IIb] 159 Joe L, Gordin F, Parker RH. Spontaneous pneumothorax with Pneumocystis carinii infection. Arch Intern Med 1986;146:1816–7. [IV] 160 Beers MF, Sohn M, Swartz M. Recurrent pneumothorax in AIDS patients with pneumocystis pneumonia. Chest 1990;98:266–70. [IV] 161 Coker RJ, Peters MB, McCarthy M, et al. Pneumothorax in patients with AIDS. Respir Med 1993;87:43–7. [IV] 162 Asboe D, Fisher M, Nelson MR et al. Pneumothorax in AIDS: case reviews and proposed clinical management. Genitourinary Med 1996;72:258–60. [III] 163 Spector ML, Stern SC. Pneumothorax in cystic fibrosis. Ann Thorac Surg 1989;47:204–7. [IV] 164 Tribble G, Selden R, Rodgers B. Talc poudrage in the treatment of spontaneous pneumothoraces in patients with cystic fibrosis. Ann Surg 1986;204:677–80. [III] 165 Davis P, di Santi’Agnese PA. Diagnosis and treatment of cystic fibrosis: an update. Chest 1984;85:802–9. [Review] 166 Schuster SR, McLaughlin J, Matthews WJ, et al. Management of pneumothorax in adults with cystic fibrosis. J Pediatr Surg 1983;18:492–7. [IV] 167 Penketh A, Knight RK, Hodson ME, et al. Management of pneumothorax in cystic fibrosis. Thorax 1982;37:850–3. [IV] 168 Noyes BE, Orenstein DM. Treatment of pneumothorax in cystic fibrosis in the era of lung transplantation. Chest 1992;101:1187–8. [III] 169 Light RW. Tension pneumothorax. Intensive Care Med 1994;20:468–9. [IV] 170 Baumann MH, Sahn SA. Tension pneumothorax: diagnostic and therapeutic pitfalls. Crit Care Med 1994;22:896. [IV] 171 Tocino IM, Miller MH, Fairfax WR. Distribution of pneumothorax in the supine and semi-recumbent critically ill adult. AJR 1985;144:901–4. [III] 172 American College of Surgeons Committee On Trauma. Thoracic trauma. In: Advanced Trauma Life Support programme for physicians: instructor manual. Chicago: American College of Surgeons, 1993. 173 Britten S, Palmer SH, Snow TM. Needle thoracocentesis in tension pneumothorax: insufficient cannula length and potential failure. Injury 1996;27:321–2. [III] 174 Bristol JB. Harvey JE. Safer insertion of pleural drains. BMJ 1983;286:348–9. [IV] 175 Sassoon CS, Light RW, O’Hara VS, et al. Iatrogenic pneumothorax: aetiology and morbidity. Respiration 1992;59:215–20. [IV] 176 Despars JA, Sassoon CS, Light RW. Significance of iatrogenic pneumothoraces. Chest 1994;105:1147–50. [IV] 177 Poe RH, Kullay MC, Wicks CM, et al. Predicting risk of pneumothorax in needle biopsy of the lung. Chest 1984;85:232–5. [III] 178 Berger R, Smith D. Efficacy of the lateral decubitus position in preventing pneumothorax after needle biopsy of the lung. South Med J 1988;81:1140–3. [IIa] 179 Anderson CL, Crespo JC, Lie TH. Risk of pneumothorax not increased by obstructive lung disease in percutaneous needle biopsy. Chest 1994;105:1705–8. [IV] 180 Pollack MM, Fields AI, Holbrook PR. Pneumothorax and pneumomediastinum during pediatric mechanical ventilation. Crit Care Med 1979;7:536–9. [IV] 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) www.thoraxjnl.com 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 www.thoraxjnl.com 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 www.thoraxjnl.com 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. www.thoraxjnl.com 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] www.thoraxjnl.com 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 REFERENCES 1 American College of Surgeons Committee on Trauma. In: Thoracic trauma. Advanced Trauma Life Support program for physicians: instructor manual. Chicago: AmericanCollege of Surgeons, 1993. [IV] 2 Miller KS, Sahn SA. Review. Chest tubes. Indications, technique, management and complications. Chest 1987;91:258–64. [IV] 3 Parmar JM. How to insert a chest drain. Br J Hosp Med 1989;42:231–3. [IV] 4 Treasure T, Murphy JP. Pneumothorax. Surgery 1989;75:1780–6. [IV] 5 Westaby S, Brayley N. Thoracic trauma – I. BMJ 1990;330:1639–44. [IV] 6 Harriss DR, Graham TR. Management of intercostal drains. Br J Hosp Med 1991;45:383–6. [IV] 7 Iberti TJ, Stern PM. Chest tube thoracostomy. Crit Care Clin 1992;8:879–95. [IV] 8 Quigley R.L. Thoracentesis and chest tube drainage. Crit Care Cli 1995;11:111–26. [IV] 9 Tomlinson MA. Treasure T. Insertion of a chest drain : how to do it. Br J Hosp Med 1997;58:248–52. [IV] 10 Collop NA, Kim S, Sahn SA. Analysis of tube thoracostomy performed by pulmonologists at a teaching hospital. Chest 1997;112:709–13. [III] 11 Luketich JD, Kiss MD, Hershey J, et al. Chest tube insertion: a prospective evaluation of pain management. Clin J Pain 1998;14:152–4. [IIa] 12 Reinhold C, Illescas FF, Atri M, et al. The treatment of pleural effusions and pneumothorax with catheters placed percutaneously under image guidance. AJR 1989;152:1189–91. [III] 13 Ward EW, Hughes TE. Sudden death following chest tube insertion: an unusual case of vagus nerve irritation. J Trauma 1994;36:258–9. [IV] 14 Boland GW, Lee MJ, Silverman S, et al. Review. Interventional radiology of the pleural space. Clin Radiol 1995;50:205–14. [IV] 15 Klein JS, Schultz S, Heffner JE. Intervential radiology of the chest: image-guided percutaneous drainage of pleural effusions, lung abscess, and pneumothorax. AJR 1995;164:581–8. [IV] 16 Rosenberg ER. Ultrasound in the assessment of pleural densities. Chest 1983;84:283–5. [IV] 17 Harnsberger HR, Lee TG, Mukuno DH. Rapid, inexpensive real time directed thoracocentesis. Radiology 1983;146:545–6. [IV] 18 Holden MP. Management of intercostal drainage tubes. In: Practice of cardiothoracic surgery. Bristol: John Wright, 1982: 3. [IV] 19 Aslam PA, Hughes FA. Insertion of an apical tube. Surg Gynecol Obstet 1970;130:1097. [IV] 20 Galvin IF, Gibbons JRP, Magout M, et al. Placement of an apical chest tube by a posterior approach. Br J Hosp Med 1990;44:330–1. [IV] 21 Hyde J, Sykes T, Graham T. Reducing morbidity from chest drains. BMJ 1997;311:914–5. [IV] 22 Clementsen P, Evald T, Grode G, et al. Treatment of malignant pleural effusion : pleurodesis using a small bore catheter. A prospective randomized study. Respir Med 1998;92:593–6. [Ib] 23 Patz EF, Goodman PC, Erasmus JJ. Percutaneous drainage of pleural collections. J Thorac Imaging 1998;13:83–92. [IV] 24 Henderson AF, Banham SW, Moran F. Re-expansion pulmonary oedema: a potentially serious complication of delayed diagnosis of pneumothorax. BMJ 1985;29:593–4. [IV] 25 Thomas RJ, Sagar SM. What size pleural tube for pleural effusions (letter)? Br J Hosp Med 1990;43:184. [IV] 26 Taylor PM. Catheters smaller then 24 French gauge can be used for chest drains (letter). BMJ 1997;315:186. [IV] 27 Conces DJ, Tarver RD, Gray WC, et al. Treatment of pneumothoraces utilizing small caliber chest tubes. Chest 1988;94:55–7. [III] 28 Parker LA, Charnock GC, Delany DJ. Small bore catheter drainage and sclerotherapy for malignant pleural effusions. Cancer 1989;64:1218– 21. [III] 29 Morrison MC, Mueller PR, Lee MJ, et al. Sclerotherapy of malignant pleural effusion through sonographically placed small-bore catheters. AJR 1992;158:41–3. [III] ii59 30 Goff BA, Mueller PR, Muntz HG, et al. Small chest tube drainage followed by bleomycin sclerosis for malignant pleural effusions. Obstet Gynecol 1993;81:993–6. [III] 31 Seaton KG, Patz EF, Goodman PC. Palliative treatment of malignant pleural effusions: value of small-bore catheter thoracostomy and doxycycline sclerotherapy. AJR 1995;164:589–91. [IIb] 32 Thompson RL, Yau JC, Donnelly RF, et al. Pleurodesis with iodized talc for malignant effusions using pigtail catheters. Ann Pharmacother 1998;32:739–42. [IIb] 33 Van Le L, Parker LA, DeMars LR, et al. Pleural effusions: outpatient management of pigtail catheter chest tubes. Gynecol Oncol 1994;54:215–7. [IV] 34 Matsumoto AH. Image-guided drainage of complicated pleural effusions and adjunctive use of intrapleural urokinase. Chest 1995;108: 1190–1. [IV] 35 Moulton JS, Benkert RE, Weisiger KH, et al. Treatment of complicated pleural fluid collections with image guided drainage and intra cavitary urokinase. Chest 1995;108:1252–9. [III] 36 Parry GW, Morgan WE, Salama FD. Management of haemothorax. Ann R Coll Surg Engl 1996;78:325–6. [IV] 37 Millikan JS, Moore EE, Steiner E, et al. Complications of tube thoracostomy for acute trauma. Am J Surg 1980;140:738–41. [III] 38 Davis JW, MacKersie RC, Hoyt DB, et al. Randomised study of algorithms for discontinuing tube thoracostomy drainage. J Am Coll Surg 1994;179:553–7. [Ib] 39 Fallon WF, Wears RL. Prophylactic antibiotics for the prevention of infectious complications including empyema following tube thoracoscopy for trauma: results of a meta-analysis. J Trauma 1992;33:110–7. [Ia] 40 LeBlanc KA, Tucker WY. Prophylactic antibiotics and closed tube thoracostomy. Surg Gynecol Obstet 1985;160:259–63. [Ib] 41 Wooten SA, Barbarash RA, Strange C, et al. Systemic absorption of tetracycline following intrapleural instillation. Chest 1988;94:960–3. [IIa] 42 Mellor DJ. A new method of chest drain insertion. Anaesthesia 1996;51:713–4. [IV] 43 Haggie JA. Management of pneumothorax: chest drain trocar is unsafe and unnecessary. BMJ 1993;307:443. [IV] 44 Rashid MA, Wikstrom T, Ortenwall P. A simple technique for anchoring chest tubes. Eur Respir J 1998;12:958–9. [IV] 45 Baumann MH, Strange C, Heffner JE, et al. Management of spontaneous pneumothorax. An American College of Chest Physicians Delphi Consensus Statement. Chest 2001;119:590–602. 46 Trapnell DH, Thurston JGB. Unilateral pulmonary oedema after pleural aspiration. Lancet 1970;i:1367–9. [IV] 47 Rozenman J,Yellin A, Simansky DA, et al. Re-expansion pulmonary oedema following pneumothorax. Respir Med 1996;90:235–8. [IV] 48 Henderson AK. Further advice on inserting a chest drain (letter and reply). Br J Hosp Med 1990;43:82. [IV] 49 Mafhood S, Hix WR, Aaron BI, et al. Re-expansion pulmonary oedema. Ann Thorac Surg 1988;45:340–5. [IV] 50 Mills M, Balsch B. Spontaneous pneumothorax : a series of 400 cases. Ann Thorac Surg 1965;1:286. [IV] 51 Brooks J. Open thoracotomy in the management of spontaneous pneumothorax. Ann Surg 1973;177:798. [IV] 52 Hall M, Jones A. Clamping may be appropriate to prevent discomfort and reduce risk of oedema (letter). BMJ 1997;315:313. [IV] 53 Roegela M, Roeggla G, Muellner M, et al. The cost of treatment of spontaneous pneumothorax with the thoracic vent compared with conventional thoracic drainage (letter). Chest 1996;110:303. [Ib] 54 Ponn RB, Siverman HJ, Federico JA. Outpatient chest tube management. Ann Thorac Surg 1997;64:1437–40. [III] 55 Mainini SE, Johnson FE. Tension pneumothorax complicating small-caliber chest tube insertion. Chest 1990; 97:759–60. [IV] 56 Matthews HR, Mcguigan JA. Closed chest drainage without an underwater seal. Thorax 1988;41:804P. [IV] 57 Graham ANJ, Cosgrove AP, Gibbons JRP, et al. Randomised clinical trial of chest drainage systems. Thorax 1992;47:461–2. [Ib] 58 Bar-El Y, Leiberman Y, Yellin A. Modified urinary collecting bag for prolonged underwater chest drainage. Ann Thorac Surg 1992;54:995–6. [IIb] 59 Sharma TN, Agrihotri SP, Jain NK, et al . Intercostal tube thoracostomy in pneumothorax : factors influencing re-expansion of lung. Ind J Chest Dis Allied Sci 1988;30:32–5. [III] 60 So SY, Yu DY. Catheter drainage of spontaneous pneumothorax: suction or no suction, early or late removal? Thorax 1982;37:46–8. [Ib] 61 Williams T. To clamp or not to clamp. Nursing Times 1992;88:33. [IV] 62 Curtin JJ, Goodman LR, Quebberman EJ, et al. Thoracostomy tubes after acute chest injury: relationship between location in a pleural fissure and function. AJR 1994;163:1339–42. [IIa] 63 Peek GJ, Firmin RK, Arsiwala S. Chest tube insertion in the ventilated patient. Injury 1995;26:425–6. [IV] 64 Main A. As few sharp objects as possible should be used on entering pleural space (letter). BMJ 1998;316:68. [IV] www.thoraxjnl.com