AUTHOR \200\231S TIP If whilst aspirating a primary pneumothorax air is still easily remove d after 2.5l have been aspirated, success is unlikely. Give up. Re-X-ray and consider inter costal tube drainage. If simple aspiration fails and less than 2.5l of air have been aspirated a second attempt i s worth considering and may succeed in up to one third of cases. However in most cases if a spiration is unsuccessful, inter- costal tube drainage is usually recommended. Small bore c atheters (approx. 14F) may also be used for aspiration and attached to a Heimlich valve or water seal device until the lung re-expands. New but expensive catheter kits with integral Heimlich type valves may also be equally effective and allow out patient management. There is likely to be an increasing trend to earlier use of de \201 nitive thoracoscopic surgery . There is no relationship between the risk of a future recur- rence and either the size of a primary pneumothorax or the initial method of treatment. Signs Abnormal signs usually require the presence of a moder- ate/large pneumothorax. Hyper -resonance, reduced chest expansion, reduced vocal fremitus and reduced/absent breath sound s may all occur on the affected side. In a mediastinal air leak a clicking/crunching sound may be heard or palpated, which the patient themselves may also sense. Subcutaneous emphyse ma rarely occurs and causes a pal- pable sub-cutaneous crepitus. Tension pneumothorax is as sociated with tachycardia, hypotension, mediastinal shift, and respiratory failure. Radiology of pneumothorax A standard PA chest radiograph taken in full inspiration is suf \201 cient. There is no evidence that routine use of additional expira- tory or lateral \201 lms increases the diagnostic yield for expe- rienced clinicians. In cases of bullous l ung disease a CT scan may be needed to differentiate pneumothorax from bullae. CT scanning may be necessary if the plain radiograph is obscured by surgical emphysema. Secondary (Fig. 14.3.5) The majority of cases will be breathless and require a drainage pro cedure. AUTHOR \200\231S TIP In COPD and emphysema the symptoms and signs of sec- ondary pneumothor ax may be wrongly attributed to the underlying lung disease so that the presence of a pneu- mothorax is overlooked. Examine the CXR carefully. J HARVEY 334 If the pneumothorax is \200\230small \200\231 and the symptoms mild, sim- ple aspiration c an be tried and the patient admitted for observation. All \200\230large \200\231 secondary pneumothoraces and all those with signi \201 cant dyspnoea should be treated with interco stal tube drainage (see algorithm). Failure of lung expansion or persistent air leak following intercostal tube drainage \200 Check tube position on x-ray. Is it kinked or blocked by partially expanded lung? If tube i s in a good position try high volume/low pressure suction ( \200\22310 to \200\22320cm H2O ). If the lung fails to expand or air leak persists discuss early (3 \200\2235 days) with t horacic surgeons. For those patients who are considered too high risk for VATS or thoracic surgery, consider chemical pleurodesis (see Chapter 14.6). Fig. 14.3.5 Algorithm for the management of secondary pneumothorax. (Courtesy of Thorax /BM J Publishing Group Ltd.) Suction \200 There is no evidence that routine use of suction is of value. Suction may be of use in reso lving a persistent air leak, particularly in secondary pneumothoraces. This is debated! Ear ly use of suction, especially in large primary pneu- mothoraces may precipitate re-expansio n pulmonary oedema. Clamping of chest drains \200 This is controversial. Some experts favor clamping prior to chest drain removal in order to detect the persistence of an air leak despite radiological evidence of lung re-expansion a nd therefore prevent unnecessary re-insertion of a chest drain. More commonly chest drains are removed without clamping once full expansion of the lung for 24 hours has been con \201 rmed radiologically. Clamping a chest drain, particularly on non- specialist wards or for patient transfer, may allow the develop- ment of a tension pneumothorax. Fig. 14.3.4 Algorithm for the management of primary pneumothorax. (Courtesy of Thorax /BMJ Publishing Group Ltd.) CHAPTER 14.3 Pneumothorax 335 Spontaneous haemopneumothorax Fortunately this is rare, as it can be associated with severe blood loss, which may be life threatening. The bleeding usually comes from torn vessels in adhesions within the parietal pleura (Fig 14.3.6). AUTHOR \200\231S TIPS Simple aspiration \200 \200 Double check correct side with a colleague. Palpate and mark a spot for aspiration at the s econd intercostal space, mid clavicular line. In \201 ltrate just ABOVE the rib with gener ous amounts of local anesthetic (10ml, 1% lignocaine) and aspirate to con \201 rm the pres ence of air. Connect a 50ml syringe to a 3-way tap (attaching a tube to the exit port with the other end placed under water in a jug will ensure correct direction of air \202 ow). I nsert medium bore cannula (14 \200\22316G) then remove inner needle and connect to 50ml syr inge for aspiration. As the collapsed lung re-expands the patient often coughs and aspirati on becomes dif \201 cult or impossible. AUTHOR \200\231S TIPS Intercostal tube drainage \200 Double check correct site of insertion with a col- league. Obtain written consent. Use the safe triangle whenever possible (Fig. 14.3.8). Be generous with local anesthetic (20ml of 1 % is safe for a 70Kg patient) In most cases consider IV sedation (midazolam and/or diamorph ine). Monitor oxygen saturation. Never insert a drain or guide wire with force. For pneumot horax aim drain towards lung apex. If the drain falls out, it \200\231s your fault! Secure it with deep subcutaneous sutures, transparent dressing and a dressing with an \200\230ome ntal tag \200\231. Fig. 14.3.6 Thoracoscopic view of an apical bulla in a young man with recurrent pneumothora x. Note the adhesions from the parietal pleura (rarely these can bleed when torn, causing a haemo-pneumothorax) The subclavian artery can be seen running behind the parietal pleura. (Picture courtesy of Mr. T. Batchelor). \200 \200 Early referral to a thoracic surgeon is indicated for repair, which can be undertaken throu gh a thoracoscopic approach. \200 \200 Catamenial pneumothorax \200 Catamenial pneumothorax is a rare form of pneumotho- rax occurring in association with mens truation. Usually recurrent and predominantly right-sided it typically affects 30 \200\2234 0-year-old females. The majority of cases have associated pelvic endometri- osis with depos its of endometrial tissue on the diaphrag- matic and visceral pleural surfaces. Defects in the diaphragm that allow air to travel into the pleural space from the abdomen during menst ruation may also be important aetiologically. Treatment consists of suppression of ovulatio n or thora- coscopic pleurodesis and patching of any diaphragmatic defects. Size of chest drains \200 Size doesn \200\231t matter. There is no evidence that large (24 \200\22328F) chest drains offer any advantage over smaller ones (14 \200\22318F) in the management of pneumothorax. L arge bore drains may be required in cases of broncho- pleural \201 stula with a large air leak, typically in secondary pneumothorax and in patients receiving positive pressure vent ilation. Iatrogenic pneumothorax This is the commonest form of pneumothorax. The usual causes are tr ansthoracic needle biopsies, central venous line insertion, pleural aspiration of \202 ui d, pleural biopsy, transbronchial biopsy, and positive pressure ventilation. Acupuncture an d aspiration of breast or thyroid nodules have also been implicated! \200 Other types of pneumothorax Tension pneumothorax This is a medical emergency. A \202 ap o f tissue causes a valve effect, allowing air to leak IN but not OUT of the pleural space. A rapid build up of pleural pressure follows, causing shift of the mediastinal structures, i mpaired venous return, hypotension, shock and dyspnoea. Unless recognized and treated swift ly it may prove fatal. \200 Most cases will resorb without the need for interven- tion. Simple aspiration with a small bore catheter (8F) will treat most cases. Resorting to intercostal tube drain- age should r arely be necessary except for patients on positive pressure ventilation who should always h ave a chest drain inserted. Look for reduced/absent breath sounds on the affected side and the trachea pushed away from the affected side. Remember that a tension pneumothorax can occur in a patient who already has a chest drain in place (that becomes blocked or is inappropriately clamped) and might also be the cause of a sudden, unexplained deterio- ration in a patient receiving positive pressure ventilation. Treat by inserting a large bore cannula into the pleural space throug h the second intercostal space in the mid- clavicular line. There should be a loud hiss as the air under pressure escapes. A formal intercostal chest drain should then be inserted th rough the triangle of safety. AUTHOR \200\231S TIP Iatrogenic pneumothorax Don \200\231t add insult to injury by inserting a chest drain. The majority of cases, espec ially those patients without un- derlying lung disease either do not need any treatment or will respond to simple aspiration. J HARVEY 336 Complications of pneumothorax Surgical emphysema This is caused by air tracking from the pl eural space into the subcutaneous tissues. Although unpleasant for the patient this does no t usually cause problems and resolves spontaneously within a few days. It may be precipitat ed by a blocked or kinked drain or a poorly positioned drain with some of the drain holes l ying subcutaneously. Rarely, surgical emphysema can compromise ventilation and lead to resp iratory failure. \200 of the high recurrence and the increased risk of respiratory failure due to the associated underlying lung disease. Pleurodesing techniques Surgical pleurodesis Whatever technique is used it should involve t he 2 princi- ples of: 1 resecting or suturing any visible blebs or bullae usually found on the visceral pleura at the lung apex 2 thoroughly abrading the visceral pleural surface in order to obliterate sub-pleural emphy sema-like changes together with varying degrees of resection of the pari- etal pleura (pleu rectomy) in order to seal the two layers of pleura together. \200 High \202 ow oxygen (when safe) and subcutaneous drains or incisions are rarely used in t roublesome cases (beware infection risk). Re-positioning of the chest drain or re-insertion of a large bore chest drain may be necessary. Very rarely tra- cheostomy may be required. Surgical emphysema will be more severe and harder to treat in patients with pneumothoraces who are receiving positive pressure ventilation. Both procedures can be achieved through a VATS procedure. Mini (transaxillary) thoracotomy and open thoracot- omy may result in slightlly fewer recurrences than a VATS procedure and may be the preferred approach in secondary pneumothorax. Re-expansion pulmonary oedema This probably results from alveolar capillaries damaged by th e presence of a pneumothorax becoming traumatized as the lung re-expands causing a capillar y leak. Mild forms are quite common after pneumothorax and are more of a radiological pheno menon than a clinical problem. Re-expansion pulmonary oedema is thought to be com- mon afte r a large primary pneumothorax in younger patients, particularly in cases where the lung ha s been collapsed for several days. Symptoms are usually mild and include cough, breath- les sness, and a tight sensation experienced as the lung re-expands. Rarely, there may be signi \201 cant pulmonary oedema and respiratory failure, which can even include the other lung such that positive pressure ventilation is required. To mini- mise the risk of re-expansio n pulmonary oedema avoid suction, particularly in the early management of a large pneumotho rax, especially if the lung may have been collapsed for several days. Chemical pleurodesis This is reserved for those who are not \201 t for thoracic surgery \200\223 usually older patients with secondary pneumo- thoraces. Talc (2 \200\2235g) calibr ated to remove small particles should be used as this minimizes the chance of systemic abso rption and is therefore unlikely to cause ARDS which has been described following the use o f uncalibrated talc Tetracycline (1500mg) has also been used extensively in the past, but i s becoming less available and has a higher recurrence rate than talc. Using 50 \200\223100m l of a patient \200\231s own blood as a pleurodesing agent has been tried successfully in t he management of air leaks following lung resection and may also have a role in pneumothora x. Talc poudrage at thoracoscopy or the insertion of talc slurry down a chest drain has a s uccess rate of around 90%. Success is most likely if the lung is re-expanded despite a pers istent air leak, as this will encourage apposition of the chemically in \202 amed pleural surfaces so encouraging pleurodesis. With continued partial collapse of the lung chemical p leurodesis combined with suction can still be attempted as a last resort in those who are u n \201 t for surgery. Preventing recurrence of a pneumothorax Primary Smoking greatly increases the risk of recur rence and should be discouraged. Recent developments in VATS have led to some experts recom mending VATS pleurodesis for the \201 rst episode of primary pneumothorax. This seems ext reme since at least half of all cases (more in non-smokers) will never recur. Individual pa tient \200\231s wishes and lifestyle, however, may sometimes dictate the need for a VATS pl eurodesis after the \201 rst episode. In most cases VATS pleurodesis should be recommende d following a second pneumothorax ( \201 rst recurrence) and for a \201 rst contra-later al pneumothorax. Advice to patients on discharge \200 Don \200\231t smoke! Smoking greatly increases the risk of recurrence. Return to hospital i mmediately if breathlessness recurs. Sporting activities There is no clear evidence on which to base advice. It is probably safe to resume sports immediately, although many physicians advise a 6-week interval between ra dio- graphic resolution of a pneumothorax and resumption of sporting activities \200\223 p articularly contact sports. Secondary As with primary pneumothorax smoking should be dis- couraged because of the very high association with recur- rence as well as the risk of exacerbating the underlying lung disease. If a patient is \201 t for surgery, referral for a surgical pleurod- esis after the \201 rst episode should be considered because Flying Once again, there is no clear evidence on which to base advice, but most lung specia lists and airlines advise an arbitrary 6-week interval between radiographic resolution of a pneumothorax and \202 ying. CHAPTER 14.3 Pneumothorax 337 Diving Developing a pneumothorax whilst diving may have seri- ous, even life threatening co nsequences. After successful treatment for pneumothorax diving should only be consid- ered for those who have undergone the most effective surgical pleurodesing technique, i.e. pleur ectomy and pleural abrasion at open/mini thoracotomy. Each case should be reviewed individu ally and this may involve CT assessment of the lungs and pleural space. Fig. 14.3.8 The safe triangle. The boundaries are formed by the anterior border of latissim us dorsi, the lateral border of pectoralis major and a line superior to the horizontal leve l of the nipple. The apex is just below the axilla. (Courtesy of Thorax /BMJ Publishing Gro up Ltd.) Further reading Baumann MH, Strange C, Heffner JE, et al. Management of sponta- neous pneum othorax: an American College of Chest Physicians Delphi Consensus Statement. Chest 2001; 11 9: 590 \200\223602. Coker RK, Boldy DAR, Buchdahl R, et al. Managing passengers with respiratory disease planni ng air travel: British Thoracic Society recommendations. Thorax 2002; 57: 289 \200\223304. Godden D, Currie GP, Denison D, et al. British Thoracic Society guidelines on respiratory a spects of \201 tness for diving. Thorax 2003; 58: 3 \200\22311. Henry M, Arnold T, Harvey J. BTS guidelines for the management of spontaneous pneumothorax. Thorax 2003; 58(suppl ii): 39 \200\22352. Noppen M, Schramel F. Pneumothorax in European R espiratory Monograph. Pleural diseases 2002; 22: 279 \200\223296. Schramel FM, Postmus PE, Vanderschueren RG.Current aspects of pneumothorax. Eur Resp J (1997); 10: 1372 \200\2231379. Fig. 14.3.7 This large primary pneumothorax can be successfully treated by a simple aspirat ion technique or even just observed and be allowed to resolve spontaneously. R FINN 338 14.4 Exudative pleural effusions (excluding malignancy) Introduction Pleural effusions are common and have a wide variety of causes. Classi \201 c ation into transudate or exudate assist the clinician in choosing the most appropriate rang e of tests to secure a diagnosis. These criteria identify more than 99% of exudates cor- rectly but will misclassify approxim ately 20% of transudates as exudates. If there is concern, then the difference between the serum and pleural \202 uid protein (the protein gradient) should be measured. If the grad ient is >3.1g/dl, then it is a transudate. Pathophysiology Exudates accumulate secondary to factors local to the pleura. There is a di sruption in the balance between pleural \202 uid production and absorption. The mechanism depends on the underlying disease (e.g. obstructed lymphatic \202 ow due to malignant in \201 ltration). Pulmonary infarction Pulmonary embolism is a common disease and approxi- mately 30% of case s are associated with a pleural effusion. The majority of these are small and unilateral, o nly causing blunting of the costophrenic angle on the chest radio- graph. The pleural \202 uid is generally an exudate, but can rarely be a transudate. Undiagnosed exudative ple ural effusions should be investi- gated for pulmonary embolism. This is best assessed with a high-sensitivity D-dimer assay and a CT pulmonary angiogram. Drainage may be required to alleviate symptoms, but cau- tion is advised as the patient will require anticoagulation to treat the underlying pulmonary embolism. Etiology Causes of an exudative pleural effusion are listed in Table 14.4.1. The majority a re due to malignancy or infection. A drug history is also important. Pneumotox.com lists a number of medications that have been associated with exudative pleural effusions. Table 14. 4.3 lists the more commonly associated. Table 14.4.1 Causes of an exudative pleural effusion Common: Malignancy Parapnuemonic effusion Pulmonary infarction Rheumatoid arthritis Mesothe lioma Tuberculous pleural effusion Tuberculous pleuritis results from infection of the pleura wit h Mycobacterium tuberculosis. Pleural TB is one of the most common extra-pulmonary manifest ations of tuber- culosis and coexists with pulmonary infection in 34 \200\22350% of cases. Since the introduction of public health measures and effective anti-tuberculous agents, the incidence of TB has decreased signi \201 cantly in the developed world. Unfortu- nately i t continues to be a major health issue globaly. Ac- cording to the World Health Organizatio n (WHO), 8 mil- lion new cases of TB and 1.6 million deaths occur each year. Co-infection w ith HIV contributes to this. In the UK, tuberculous pleuritis is more likely to be due to r eactivation of disease than primary infection. The clinical presentation is usually acute o r sub-acute i.e. < 1 month from onset of symptoms to diagnosis. Symptoms include cough, dys pnoea, fever and chest pain. Co-infection with HIV produces a more insidious onset of sympt oms. Pleural aspiration shows a clear yellow or serosanguineous \202 uid. This is an exud ate and is predominantly lymphocytic. In the very early stages the \202 uid may be neutro phillic. Pleural \202 uid culture for TB is usually only positive in 20 \200\22330% of ca ses. In areas with a high prevalence of TB, pleural \202 uid levels of adenosine deaminas e (ADA) >35 IU/L in association with a lymphocytic effusion are virtually diagnostic of tub ercu- lous pleuritis. In areas with a low prevalence of TB, pleural biopsy via thoracoscopy is the gold standard. When microscopy and culture for TB and histological examination for necrotising granulomas are combined there is a high diagnostic sensi- tivity and speci \201 city. Therapeutic drainage of the effusion can signi \201 cantly improve symptoms. In most cases, pleural TB will resolve spontane- ously within 2-4 months without treatment. H owever, 65% Less common: Empyema Tuberculosis SLE Other autoimmune conditions Benign asbestos pleural e ffusion Pancreatitis Post cardiac injury syndrome (Dresslers) Post coronary artery bypass g rafting Hepatic/splenic/sub-phrenic abscess Oesophageal rupture Cardiac failure treated wit h diuretics Rare: Yellow nail syndrome Chylothorax Drugs Sarcoidosis Fungal infection Meigs syndrome Hy pothyroidism Investigations In clinical practice, pleural \202 uid protein levels <25g/l repre- sents a transudate and >35g/l an exudate. In borderline cases (protein level 25 \200\22335g/l) Li ght \200\231s criteria should be applied (Table 14.4.2). Table 14.4.2 Light \200\231s criteria Pleural \202 uid protein/serum protein >0.5 Pleural \202 uid LDH/serum LDH >0.6 Pleural \202 uid LDH >2/3 upper limit of normal serum LDH. The pleural \202 uid is an exudate in the presence of one or more of the above criteria. CHAPTER 14.4 Exudative pleural effusions (excluding malignancy) 339 will experience a recurrence of either pulmonary or pleu- ral TB. Treatment is aimed at pre venting this. Standard treatment includes: \200 \200 The most common cause of drug-associated pleural effusions is drug-induced lupus pleuritis. While more than 80 drugs have been connected to this syndrome, de \201 nite evidence only exists for a handful including: \200 \200 \200 \200 \200 \200 \200 Isoniazid, rifampicin and pyrazinamide for 2 months. Isoniazid and rifampicin for a further 4 months. Procainamide. Hydralazine. Isoniazid. Methyldopa. Chlorpromazine. D-penicillamine. Quinidin e. If a patient comes from an area of isoniazid resistance, then ethambutol should be added un til the results of sensitivity testing are known. Currently, there is insuf \201 cient evi dence to justify the rou- tine addition of corticosteroids. Pleural thickening is a common complication in up to 43% of cases. There are no known predictive factors. Empyema is a rar e complication that requires pleural drainage. Patients with drug-induced lupus pleuritis are symptomatic with fever, pleuritic chest pain , myalgia and arthralgia. The chest radiograph commonly shows bilateral effusions while the pleural \202 uid is exudative with varying nucleated cell counts. The presence of lupus cells in the \202 uid, although rare, strongly suggests the diagnosis. Serum antinuclear antibody (ANA) titres are elevated. The majority of drug-associated pleural effusions resol ve upon withdrawal of the drug. Drug associated pleural effusion Although a rare cause of pleural effusion, drugs should al ways be considered. A detailed medication history is required as patients may not reveal th e use of a drug unless speci \201 cally asked. Most cases of drug induced pleural effusion are associated with bilateral pulmonary in \201 ltrates and are predominantly eosinophili c. Key points \200 Pulmonary embolism should be considered in all cases of undiagnosed exudative pleural effus ion. A detailed drug history is important. Cardiac failure treated with diuretics can produ ce an exudative effusion and may be unilateral. Table 14.4.3 Drugs most commonly associated with pleural effusion \200 Amiodarone Cyclophosphamide Nitrofurantoin L-tryptophan Further reading www.pneumotox.com www.who.int/mediacentre/factsheets/fs104/en/ Light RW, Le e YCG, Textbook of Pleural Diseases. 2nd edn. London: Phenytoin Carbergoline Sodium valproate Pergolide Methotrexate Propranolol Hodder Arnold 2008 Penicillamine Clozapine Carbamazepine Simvastin A ARNOLD & R TEOH 340 14.5 Transudative pleural effusions Introduction Pleural effusions can be classi \201 ed into transudates or exu- dates. This distinction can assist in determining the etiology of the pleural effusion. Atypical features include: \200 \200 \200 the absence of cardiomegaly on the chest radiograph; unexplained pyrexia; clinical suspicio n of pulmonary embolism. Pleural \202 uid which is watery is very suggestive of a transu- date, but most transudat es are straw-colored, and may even be tinged with blood. Additional tests are therefore req uired to differentiate between a transudate and exu- date. Pathophysiology A transudative pleural effusion is caused by an imbalance of the hydrostati c or osmotic pressure gradient between the pulmonary capillaries and the pleural space, and the rate of pleural \202 uid drainage by the lymphatics (Fig. 14.5.1). Differentiating between a transudate and exudate Traditionally a transudate is de \201 ned as pleural \202 uid with a protein level <30g/L, whereas an exudate is de \201 ned as p leural \202 uid with a protein level of >30g/L, in the presence of a normal serum protein . However in borderline cases (when the protein level is between 25 \200\22335g/L) Light \200\231s criteria should be used to dis- tinguish between transudates and exudates (Table 14.5.2). Hydro- static pres- sure Lym- phatic drainage Pleural space Oncotic pressure Fig. 14.5.1 Increased hydrostatic pressure or reduced colloid osmotic pressure within the p ulmonary vasculature tends to cause leakage of \202 uid into the pleural space. If the pl eural lymphatics are unable to keep up with the \202 uid in \202 ux then a transudative pleural effusion develops. Table 14.5.2 Light \200\231s criteria Pleural \202 uid protein/serum protein < 0.5 Pleural \202 uid LDH/serum LDH < 0.6 Etiology The causes of a transudative pleural effusion in the UK are shown in Table 14.5.1. Most are secondary to increased hydrostatic pressure, such as in congestive cardiac failur e, or to low protein states (decreased oncotic pressure) such as hepatic cirrhosis or nephr otic syndrome. Most, though not all, are bilateral. Pleural \202 uid LDH < 2/3 upper limit of normal serum LDH. The pleural \202 uid is a transudate in the presence of one or more of the above criteria . Treatment The treatment of a transudative pleural effusion depends on it etiology. For exam ple, transudative pleural effusions due to conges- tive cardiac failure usually resolve wit hin 48 hours after initiation of diuretic therapy. However, one should be aware that a pleu ral effusion due to congestive cardiac failure partially treated with diuretics may develop the characteristics of an exudate if diagnostic aspiration is subsequently performed. Tran sudative pleural effusions due to hepatic cirrhosis should not be treated by serial therape utic thoracocente- sis as they reaccumulate rapidly. Instead diuretic therapy, a low salt d iet, and drainage of tense ascites, should be performed in the \201 rst instance. The tre atment of a pleural effusion associated with the nephrotic syndrome is to minimize protein loss in the urine so as to increase plasma protein levels. Even if the diagnostic aspiratio n indicates a transudate, the possi- bility of pulmonary embolism needs to be considered du e to the increased risk of thromboembolism in nephrotic syndrome. Thus, in most cases, ther apeutic drainage of a transudative effusion is not appropriate. However, in selected patien ts, large transudative pleural effusions require chest tube drainage for rapid relief of sy mptoms, followed by pleurodesis to reduce the likeli- hood of recurrence. Table 14.5.1 Causes of a transudative pleural effusion Common: Congestive cardiac failure Hepatic cirrhosis Hypoalbuminaemia Nephrotic syndrome Less common: Constrictive pericarditis Peritoneal dialysis Myxoedema Ovarian hyperstimulati on syndrome SVCO Post-operative basal atelectasis Sarcoidosis Although pleural effusions due to pulmonary emboli are usually exudative, they occasionally present as transudates. Investigation Unexplained unilateral pleural effusion, or bilateral pleural effusions that are greatly disparate in size, require a diag- nostic pleural aspiration. Pleural aspiratio n may be deferred in the presence of bilat- eral pleural effusions in a clinical setting su ggestive of con- gestive cardiac failure, unless there is failure to resolve with appropria te treatment, or atypical features are present. CHAPTER 14.5 Transudative pleural effusions 341 Further reading Light RW. Pleural Diseases 4th edn. Philadelphia: Lippincott Williams AUTHOR \200\231S TIPS \200 Bilateral pleural effusions associated with clinical fea- tures of congestive cardiac failu re do not require aspi- ration unless there are atypical features or there is failure to re solve with diuretic therapy. Beware of ascribing all bilateral pleural effusions to congest ive cardiac failure as up to 25% of cases have an alternative cause. When the pleural \202 uid protein level is borderline (25 \200\22335g/L), or in the presence of a low plasma protein level, Light \200\231s criteria should be used to accurately clas- sify a pleural effusion into a transudate or exudates. Pleural effusions secondary to pulmonary embolism a re occasionally transudates. & Wilkins, 2001. Maskell NA. BTS Guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 2003; 58(suppl. II):8 \200\22317. J PORCEL AND F RODRIGUEZ-PANADERO 342 14.6 Malignant effusions \200 Epidemiology Malignant pleural effusion (MPE) is the leading cause of exudative effusions s ubjected to thoracentesis. Pleural ma- lignancy can occur without the presence of effusion. Bilateral effusions with normal heart size (15%). The absence of contralateral mediastinal shift in a large MPE indicates: \200 Ipsilateral bronchial obstruction with lung collapse (e.g. lung cancer). Fixation of the me diastinum by malignant lymph nodes. Extensive pleural involvement (e.g. malignant mes- othe lioma, trapped lung). Causes The majority of MPE are the result of metastases to the pleura from other sites: \200 \200 \200 \200 \200 \200 Lung (30%). Breast (18%). Unknown site (10%). Lymph nodes (9%). Gastrointestinal tract (7%) . Ovary (6%). CT scan Features that favor the diagnosis of MPE are: \200 \200 \200 \200 Pleural nodularity. Parietal pleural thickening greater than 1 cm. Mediastinal and circumfe rential pleural thickening. Liver metastases. Primary pleural neoplasms (mesothelioma) account for approximately 10% of all MPE. More than half of CT scans in MPE do not show any pleural \201 nding other than the pleur al effusion. Pathogenesis Potential mechanisms of metastatic pleural involvement include one or more of the following: \200 AUTHOR \200\231S TIP Chest CT should be done before the effusion is com- pletely drained to ensure optimal diagnostic utility. Pulmonary artery invasion with microscopic tumor embolization to the visceral pleura and su bsequent seeding to the parietal pleura (e.g. lung cancer). Pleural invasion from contiguou s structures (e.g. dia- phragm \200\223 ovary carcinoma, lung, mediastinum, breast). Hemat ogenous spread (e.g. breast, ovary). Diagnosis Pleural \202 uid analysis Pleural \202 uid characteristics in MPE are: \200 \200 \200 \200 \200 \200 \200 Once malignant cells nest on pleural surfaces, the main mechanism of pleural fluid accumula tion is increased vascular permeability, probably in combination with the obstruction of ly mphatic vessels by the parietal pleural metastases. Patients with cancer may also develop e ffusions from causes unrelated to direct pleural involvement by tumor ( \200\230paramaligna nt \200\231 effusions) such as: \200 \200 \200 Exudate according to Light \200\231s criteria in 98%. Bloody appearance (>10.000 RBC/mm3) i n >40%. Lymphocytes predominance in 80%. Reduced glucose levels (<3.3 mmol/L) in 10 \200 \22330%. Low pH (<7.3) in 20 \200\22335%. Adenosine deaminase (ADA) levels <40 U/L in 95%. Positive panel of tumor markers (CEA>50 ng/mL or CA15.3>75 U/mL or CA125>2800 U/mL or CYFRA 21 \200\2231>175 ng/mL) in about half the cases. Notably, one- third of cytology-negative MPE can be identi \201 ed by at least one of these markers. Positive cytological examinati on in 50% after a single tap attempt; a repeat aspiration is helpful in an additional 10% o f cases. This is the most common way of diagnosing MPE. Post-obstructive pneumonia or atelectasis. Pulmonary embolism. Lymphatic mediastinal blocka de or thoracic duct obstruction (chylothorax). SVCO. Malignant pericardial effusion and car diac tamponade. Post-radio- or chemotherapy. Hypoalbuminemia. \200 \200 \200 Cytological yield depends on: \200 \200 Number of submitted specimens. Type of tumor (e.g. lower positive results with squa- mous c ell carcinomas, mesotheliomas and sarcomas). Tumor burden in the pleural space. Expertise o f the cytophatologist. Clinical features \200 \200 \200 \200 Dyspnoea (the most common symptom). Constitutional symptoms. Cough. Chest pain (particularl y in mesothelioma). \200 In contrast, the volume of pleural \202 uid analyzed does not impact the yield of cytolog ic diagnosis (submission of 5 \200\22310 ml may suf \201 ce). Mean age of patients with MPE is 65 years. AUTHOR \200\231S TIP A pleural effusion in a woman with breast cancer is malignant until pr oven otherwise. AUTHOR \200\231S TIP Pleural \202 uid \202 ow cytometry should be ordered when lymphoma is a consideration. Imaging Chest radiographs (see also Chapter 3.8) Typical radiological appearance of MPE: \200 Closed (blind) pleural biopsy \200 45% sensitivity for MPE. \200 Establish the diagnosi s of malignancy only in 15% of patients with false-negative cytology. Large unilateral pleural effusion (60%). Malignancy is the most common cause of massive ple ural effusions. CHAPTER 14.6 Malignant effusions 343 The most widely used sclerosants are: \200 CT-guided biopsy of the pleura \200 Talc, which is the most effective agent (>90% success rate). Dose: 4g. Doxycycline (effecti veness of 75%). Dose: 0.5g. High diagnostic yield (85%) in the presence of pleural thickening or nodularity. Consider a lso if only a small effusion is present and pleu- ral \202 uid cytology is negative. Pleurodesis can be performed: \200 Insuf \202 ating dry powder talc (poudrage) through a thora- coscope. Instilling, at the b edside, doxycycline or talc (slurry) mixed with saline via a chest tube. Medical thoracoscopy \200 \200 >95% sensitivity for MPE. The recommended procedure when the cytological analysis is negati ve and a substantial amount of pleural \202 uid exists in patients who are \201 t enoug h. The choice of the pleurodesis procedure will depend upon: \200 Thoracoscopy allows: \200 The patient \200\231s characteristics (e.g. bedside pleurodesis would be preferred in those with poor performance sta- tus or contralateral pleuro-pulmonary involvement). The availab ility of an expert thoracoscopist. Biopsies from the chest wall, diaphragm, lung and mediastinum. Staging in lung cancer and m esothelioma. Removal of all pleural fluid and talc pleurodesis if macroscopic tumor is obvi ous. \200 Pleurodesis with doxycycline Insert a small-bore catheter (10 \200\22314F). \200 \200 Prognosis \200 Drain in a controlled fashion. Confirm full lung re-expansion with a chest radiograph. Inje ct 500 mg of doxycycline in 100ml of saline into the pleural space. Clamp chest tube for 1 \200\2232 hours, and then open it for drainage. Remove chest tube within 12 \200\22324 hour s, in the absence of excessive \202 uid drainage (>250 ml/day); otherwise, a second dose of the sclerosing agent can be adminis- tered. The entire pleurodesis procedure can be acco mplished within <24 to 72 hours. Median survival depends upon the site of the primary tumor (5 months, with the shortest in lung and the longest in breast primaries and mesothelioma). A pleural \202 uid pH <7.3 is associated with far advanced disease of the pleural space and a decreased response to pleu rodesis. Treatment Systemic therapy \200 May control effusions in chemo- radio- or hormone-ther- apy responsive tumors, such as lymp homa, SCLC and breast cancer. Some experts favor early pleurodesis in chemo-sensitive tumor s. At least, proceed to aspirate symptomatic pleural effusions before chemotherapy. AUTHOR \200\231S TIP A trial of intrapleural \201 binolytics may be a useful adjunct ther apy for patients with multiloculated MPE who fail to drain adequately, before attempting pl eurodesis. Observation \200 Indicated in asymptomatic patients or when there is no recurrence of symptoms after an init ial therapeutic tho- racentesis (uncommon). Complications of pleurodesis: \200 \200 Therapeutic thoracentesis \200 Pleuritic chest pain and fever (10 \200\22330%). Rarely, acute respiratory failure (ARDS) f ollowing talc administration. Where grade large-particle talc (most particles <10 m remov ed) is used, this com- plication has not been reported. Consider the possibility of an unre cognized air leak if ARDS develops post pleurodesis. Recommended for the palliation of dyspnoea in patients with a very short live expectancy (K arnofsky perform- ance scale score \211 40). Caution should be taken if removing more than 1.5 \200\2232 litres on a single occasion. AUTHOR \200\231S TIP Dyspnoea that does not improve after pleural aspiration suggests pulmo nary carcinomatous lymphangitis, atel- ectasis, pulmonary or tumor embolism, or COPD. Indwelling pleural catheters \200 A chronic indwelling 15.5F pleural catheter is the treat- ment of choice in patients with t rapped lung and is also an effective option if pleurodesis fails. Indwelling pleural cathet er allows patients to drain pleural \202 uid regularly or on an \200\230as required \200 \231 basis at home. A spontaneous pleurodesis will occur in almost 45% of patients. The cat heter remains in place for a median of 2 months, until death or removal. The expensive drai nage supplies (suction bottles) counterbalance hospital cost-savings. Pleurodesis through t he indwelling pleural catheter needs to be explored in future. Pleurodesis With pleurodesis, a chemical irritant is injected into the pleural space, creat ing an intense pleural in \202 ammation, which ultimately leads to the fusion of the visce ral and parietal pleura. Prerequisites for pleurodesis: \200 \200 \200 Symptomatic (dyspnoea) MPE. Reasonable survival expectancy (>1 month). Absence of trapped l ung (de \201 ned as lung failure to re-expand after drainage of an effusion because of mec hanical restriction of the visceral pleura) or main- stem bronchial obstruction. J PORCEL AND F RODRIGUEZ-PANADERO 344 Further reading Janssen JP, Collier G, Astoul P, et al. Safety of pleurodesis with talc pou drage in malignant pleural effusions: a prospective cohort study. Lancet 2007; 369: 1535 \200\2231539. Other options \200 