Human studies Reliable data on the volume and cellular content of pleural \202 uid in nor mal humans are scarse, because of the obvious dif \201 culties in retrieving this small am ount of \202 uid without \200\230disturbing \200\231 the pleural environment. The \201 rst study ad- dressing this issue was that of Yamada, published in 1933, who punctured the 9th or 10th intercostal space on the dorsal axillary line in a group of healthy Japanese s oldiers. In about 30% of cases some \202 uid was aspirated after a period of rest, wherea s in about 70% of cases some \202 uid was retrieved after exercise. Usually only a few dr ops of foam was aspirated but in a few cases up to 20 ml could be retrieved. Total white bl ood cell count was 4500 L-1 (range 1700 \200\223 6200). Differential cell count showed 5 3.7% cells similar to monocytes, 10.2% lymphocytes, 3% meso- thelial cells, 3.6% granulocyt es, and 29.5% \200\230deteriorated cels of dif \201 cult classi \201 cation \200\231. Mo re recently, a pleural lavage technique was used to retrieve the few milliliters of pleural \202 uid present in the pleural space of otherwise healthy participants undergoing thora coscopic sympathec- tomy for the treatment of essential hyperhidrosis. In anal- ogy with br onchoalveolar lavage (a technique enabling retrieval of small volumes of epithelial lining \202 uid from the lung), 150 ml of prewarmed saline was injected in, and immediately aspi rated from the right pleural space, after induction of a pneumothorax in the setting of a t horaco- scopic sympathectomy performed for the treatment of CHAPTER 14.1 Normal physiologic \202 uid volume and cellular contents CHAPTER 00 CHAPTER TITLE 323 Table 14.1.1 Species Mean volume (right & left pleural space) ml.kg-1 Total white blood cell count, L-1 Macrophages (%) Monocytes (%) Mesothelial Cells (%) Lymphocytes (%) Rabbits 0.2 2442 595 NR 60.8 31.8 7.4 Dogs 0.15 2208 734 NR 28.2 69.8 8.2 Rabbits 0.13 1503 281 7.6 to 16 38.6 to 70.1 3.7 to 25.4 10 to 10.6 Rabbits 0.13 1503 414 7.5 1.5 70.1 3.6 8.9 1.6 10.6 1.8 Rabbits NR NR 9.25 66.5 8 9.75 Rabbits NR NR 5 60.17 10 11 Rabbits 0.1 1216 800 NR NR NR NR Rabbits 0.09 NR NR NR NR NR Rabbits 0.22 NR NR NR NR NR Dogs 0.1 NR NR NR NR NR Sheep 0.12 NR NR NR NR NR Sheep 0.04 NR NR NR NR NR Rats 0.6 NR NR NR NR NR Puppies 1.33 NR NR NR NR NR Cats 0.28 NR NR NR NR NR Pigs 0.22 NR NR NR NR NR essential hyperhidrosis. With urea used as an endogeneous marker of dilution, measured mean right-sided pleural \202 uid volume was 8.4 4.3 ml. In a subgroup of subjects, right- and leftsided pleural \202 uid volumes were shown to be similar. Expressed per kg of bod y mass, total pleural \202 uid volume in non-smoking, healthy subjects is 0.26 ml.kg-1, w hich corresponds well with values obtained in animal studies. Total white blood cell count in the pleural \202 uid of normal non-smoking subjects was 1716 cells L-1. Differ- enti al cell count yielded a predominance of macrophages (median 75%, interquartile range 16%) a nd lymphocytes (median 23%, interquartile range 18%). Mesothelial cells, neutrophils, and e osinophils were only marginally present. A typical image of a cell smear is shown in Fig. 1 4.1.1. In a second study using a similar lavage technique, lymphocyte subtyping showed a lo wer proportion of CD4 positive T cells (30% vs 45.8 %) and a higher proportion of CD8 posti tve T cells (11.78 vs 9.6 %) and regulatory T cells (CD4+CD25high) in pleural \202 uid in normal subjects as compared to blood which may suggest that previously described abnormali ties in lymphocyte subsets in pleural effusions may not only be a result of the pleural dis ease itself but also be characteristic of the pleural compartment itself. Interestingly, a small but statistically signi \201 cant in- crease in pleural \202 uid neutrophils was o bserved in smoking subjects. In addition to revealing the volume and cellular composition o f normal pleural \202 uid (which may be helpful in understanding cellular events occurrin g in disorders characterized by pleural effusions), this pleural lavage tech- nique allows to study the pathophysiological events in pleural disorders which typically are not associa ted with pleural effusions, such as pneumothorax and asbestos- related pleurisy. Fig. 14.1.1 A typical cell smear of a pleural lavage sample in a normal, non-smoking subjec t. M NOPPEN 324 Miserocchi G, Agostoni E. Contents of pleural space. J Appl Physiol KEY ISSUES \200 1971; 30: 208 \200\223213S. In normal animals and humans, the pleural space con- tains a small volume of pleural \202 uid. In different animal species this volume varies between 0.04 and 0.20 ml.kg-1. In norm al humans, the pleural \202 uid volume is 0.26ml.kg-1. This \202 uid has the solute cha racteristics of all intersti- tial \202 uids, and contains a total of 1000 to 2500 white blood cells per L. Macrophages/monocytes and lym- phocytes are the predominant cell types . Pleural lavage is a safe and simple technique allowing the study of normal pleural \202 uid, and of pleural dis- ease which is not characterized by pleural effusions. Miserocchi G. Physiology and pathophysiology of pleural \202 uid turnover. Eur Respir J 1997; 10: 219 \200\223225. Noppen M, De Waele M, Li R, et al. Volume and cellular content of normal pleural \202 uid in humans examined by pleural lavage. Am J Respir Crit Care Med 2001;7:180 \200\223182. Noppen M, Herregodts P, D \200\231haese J, et al. A simpli \201 ed thoracosco- pic sympath icolysis technique for essential hyperhidrosis: results in 100 consecutive patients. J Lapa roendosc Surg 1996; 6:151 \200\223159. Noppen M. Normal volume and cellular contents of ple ural \202 uid. Curr Opin Pulm Med 2001;7:180 \200\223182. Further reading Broaddus VC, Araya M, Carlton DP, et al. Developmental changes in pleural l iquid protein concentration in sheep. Am Rev Respir Dis 1991; 143: 38 \200\22341. MiserocchiG, Negrini D, Mortola J. Comparative features of Starling-lymphatic interaction a t the pleural level in mammals. J Appl Physiol 1984; 56:1151-1156. This page intentionally left blank H DAVIES & R DAVIES 326 14.2 Assessment and investigation of an undiagnosed pleural effusion (including thoracoscop y) Introduction Pleural effusions are a common medical problem, affecting over 3000 people per million population annually. They are a manifestation of over 50 underlying diseases, some pleuro-pulmonary and some systemic. The commonest causes of pleural effusion in the USA an d UK are heart failure, pneumonia, and malignancy. The approach to the patient with a pleur al effusion requires a structured approach to formulate the likely diagnosis, minimize inva sive investigations and guide treatment. (urinothorax), bile or CSF may also result in pleural effusion. History A thorough history should determine previous asbestos exposure, risk factors for he art failure, tuberculosis expo- sure, pack-years smoking history, features of malignancy or infection. A drug history is also important as a number of medications have been associate d with exudative pleural effusions (Table 14.2.1); http://www.pneumotox.com is a useful res ource for further information. Table 14.2.1 Pathophysiology The normal pleural cavity contains approximately 0.13 \200\223 0.06ml/kg bo dy mass of \202 uid for lubrication during respira- tion. Pleural effusions arise when th e balance between pleural \202 uid production and its absorption has been dis- turbed. Tr ansudative effusions occur due to an increase in hydrostatic pressure or reduction in tissu e oncotic pressure; whereas exudates accumulate secondary to increased pleural permeability or impaired absorption (e.g. obstructed lymphatic \202 ow). Transdiaphragmatic pas- sage of ascites or peritoneal dialysate from the abdomen, chyle (chylothorax), blood (haemothor ax) or rarely urine Drugs most commonly associated with pleural effusion \200 Amiodarone \200 Nitrofurantoi n \200 Phenytoin \200 Methotrexate \200 Penicillamine \200 Carbamazepine \200 Cyc lophosphamide \200 Cabergoline \200 Pergolide History, clinical examination and chest radiography Clinical presentation suggests heart failure Yes Treat cause No improvement No Thoracentesis: request protein, LDH, white cell differential count ( pH / glucose, MCS, A AFB, cytology if clinically indicated) Pleural analysis confirms diagnosis Yes Treat cause No Contrast enhanced CT thorax Obtain pleural biopsy: send for histology and culture Repeat pleural fluid analysis for cyt ology Is the diagnosis evident? Yes Treat cause No Reconsider thoracoscopy Reconsider PE and TB Etiology unknown in 10 \200\22315% Follow up surveillance, \200\230watchful waiting \200\231 Fig. 14.2.1 Diagnostic algorithm for the patient with an undiagnosed unilateral pleural eff usion. CHAPTER 14.2 Assessment and investigation of an undiagnosed pleural effusion 327 Clinical features Patients may be asymptomatic but often present with dysp- noea, chest pai n or cough. Dyspnoea arises as a consequence of altered diaphragm mechanics (secondary to i ncreased pleural pressure) as well as decreased chest wall compli- ance and impaired underl ying lung function. Pleuritic chest pain indicates irritation of the parietal pleural surfa ce, ribs or chest wall. Cough is a non-speci \201 c symptom, although expectoration of pur ulent sputum indicates an infective etiology. The presence of constitutional symptoms such as weight loss, night sweats, anorexia, and malaise typically occur with infective causes o r malignancy, and joint, skin or eye symptoms may indicate underlying connective tissue dis ease. Physical examination reveals a stony dull percussion note with decreased fremitus and absent breath sounds. Clinical detection of less than 250 \200\223300ml of pleural \202 uid is dif \201 cult. Features of heart failure, malignancy and connective tissue disease should be sought. Milky pleural \202 uid occurs in chylothorax, pseudochylotho- rax or empyema. Putrid odor suggests anaerobic infection and an ammonia smell is characteristic of urinothorax. The pr esence of food particles is indicative of oesophageal rupture. Is the \202 uid a transudate or exudate? Differentiation between exudative and transudati ve effu- sions aids diagnosis (Table 14.2.3), and all initial pleural \202 uid samples sh ould be sent for measurement of protein and lactate dehydrogenase (LDH). In clinical practi ce, pleural \202 uid protein levels <27g/l repre- sent a transudate and >35g/l an exudate . In borderline cases, pleural \202 uid is an exudate if any of Light \200\231s criteria apply: \200 \200 \200 Pleural \202 uid to serum protein ratio >0.5. Pleural \202 uid to serum LDH >0.6. Pleur al \202 uid LDH >2/3 the upper limit of normal serum LDH. Light \200\231s criteria are very sensitive in determining exudative effusions however misc lassi \201 cation may occur particularly in patients with heart failure taking diuretic th erapy or in those with two separate diagnoses such as cancer and heart failure. Investigation In most cases, the underlying diagnosis is determined by the clinical history and examination supplemented by chest radiography and pleural \202 uid analysis. A syste matic diag- nostic approach is outlined in Fig. 14.2.1. Table 14.2.3 Causes of pleural effusions Transudates Exudates Pleural \202 uid analysis Thoracentesis Thoracentesis (pleural aspiration) is indicated i n patients with a newly discovered pleural effusion except where there is a secure diagnosi s of heart failure. Diagnostic pleu- ral \202 uid aspiration using a 21F bore needle is s afe and few contraindications exist. Ultrasound guidance should be used if the \202 uid v olume is small or heavily loculated. Ther- apeutic aspiration of 1-2L of \202 uid can rel ieve breathless- ness but complete drainage should not be performed prior to CT imaging as superior images are obtained with pleural \202 uid present. Table 14.2.2 lists recommende d initial pleural \202 uid tests for effusions of unknown etiology. Common causes Common causes Left ventricular failure Liver cirrhosis \200\230hepatic hydrothorax \200\231 Hypoalbumina emia Peritoneal dialysis Malignancy Parapneumonic effusions Pulmonary infarction Rheumatoid arthritis Mesothelioma Less common causes Less common causes Nephrotic syndrome Hypothyroidism Mitral stenosis Empyema Tuberculosis SLE Pulmonary embolism (10 \200\22320%) Other autoimmune diseases Benign asbestos pleural effusion Pancreatitis Post cardiac injury syndrome (Dressler \200 \231s) Post coronary artery bypass grafting Hepatic/Splenic/Subphrenic abscess Oesophageal rupture Table 14.2.2 Biochemistry Protein Lactate dehydrogenase (LDH) Glucose pH (if no blood gas analyzer available) Rare causes Rare causes Cytology Cytological analysis Differential white cell count Constrictive pericarditis Urinothorax Meigs \200\231 syndrome Ovarian hyperstimulation synd rome SVCO Malignancy (up to 5% are transudates) Yellow nail syndrome Chylothorax Drugs Sarcoidosis Microbiology Grams \200\231 stain and culture Acid fast bacilli stain and culture Fungal infections Following diagnostic aspiration note: Appearance and odor Pleural \202 uid may be serous (straw colored) or blood stained (sero sanguineous). Blood stained \202 uid may occur in malignancy, tuberculosis, pulmonary inf arction, trauma, benign asbestos pleural effusion (BAPE) or post cardiac in- jury surgery ( PCIS). A true haemothorax ( \202 uid haematocrit >50% blood haematocrit) is usually relate d to trauma. Differential cell count The predominant cellular population within a pleural aspi- rate is determined by the nature of the pleural insult and timing of thoracentesis relative to the injury. H DAVIES & R DAVIES 328 Acute in \202 ammation produces a typically neutrophilic pleu- ral \202 uid e.g. infecti on, whereas in chronic pleural effusion, e.g. malignancy or tuberculosis, mononuclear cells prevail. Lymphocytic effusions are common in chronic diseases of insidious onset such as t uberculosis (usually over 80%) or malignancy. Eosinophilic (>10% of total leukocytes) pleur al \202 uid is often diagnostically unhelpful and occurs in both benign (e.g. air or bloo d in pleural cavity, drug reactions or Churg \200\223 Strauss syndrome) and malignant condi tions. Other pleural \202 uid analysis Pleural \202 uid amylase levels higher than the normal range for serum, or a pleural-to-serum ratio >1, are seen in effusions associated with acut e pancreatitis, oesophageal rupture, and malignancy (especially adenocarcinoma). Isoenzyme analysis differentiates between amylase of pancreatic or salivary origin. Pleural \202 ui d cholesterol and triglyceride levels should be requested if chylothorax or pseudochylothor ax is sus- pected. Simple bench centrifugation of turbid/cloudy pleural \202 uid can aid differentiation from empyema when there is diagnostic doubt. A clear supernatant is seen in empyema as the cell debris sediments whereas a chylous effusion remains milky. The presenc e of chylomicrons or a triglyceride concentration >1.24mmol/L (110mg/dL) confirms the diagn osis of chylothorax. Whereas the detection of cholesterol crystals at microscopy or a cho- lesterol level >5.18mmol/l (200mg/dL) is diagnostic of a pseudochylothorax. Raised adenosin e deaminase (ADA) levels are very sensi- tive for tuberculous pleural effusion however, its speci \201 city is limited. Therefore, measurement is not routinely recom- mended except in TB endemic areas where low pleural \202 uid ADA levels effectively exclude tuberculous effusions. Elevated pleural \202 uid creatinine ( \202 uid: serum ratio >1) is diagnost ic of urinothorax, a condition which arises ipsilat- eral to an obstructed kidney as a cons equence of the passage of urine through retroperitoneal space into the pleural space. Measu rement of pleural \202 uid rheumatoid factor and anti- nuclear antibodies is unhelpful di agnostically as levels mir- ror serum values. The presence of lupus erythematosus ( \200 \230LE \200\231) cells in pleural \202 uid is diagnostic of systemic lupus erythematosus (SLE) related pleuritis. Detection of B-transferrin, found in cerebrospinal \202 uid, con \201 rms the presence of a duro-pleural \201 stula. Pleural \202 uid pH and glucose Pleural \202 uid pH should be measured in all cases of sus- pected pleural infection. All non-purulent samples can be heparinised (in an arterial blood gas syringe) and the pH measured in a standard blood gas analyzer. Care must be taken , during pleural aspiration, to avoid contamination with local anesthetic, e.g. lidocaine, which is acidic and can produce a falsely low pH reading. Normal pleural \202 uid pH is a round 7.6 (as a result of bicar- bonate accumulation in the pleural space). Pleural pH <7.3 re \202 ects a substantial amount of lactic acid production and is seen with intense pleu ral in \202 ammation. Low pleural \202 uid glucose (<3.3mmol/l) is seen with a similar s pectrum of dis- ease re \202 ecting metabolic activity within the pleural space. Causes of exudative effusions with low pleural \202 uid pH and glucose concentration include: comp licated parapneu- monic effusion and empyema, rheumatoid pleuritis, malig- nancy, tuberculo us pleuritis, oesophageal rupture and lupus pleuritis. Urinothorax is the only transudative effusion to be, rarely, associated with a low pleural \202 uid pH. Clinically a pleural \202 uid pH <7.2 in the context of pleural infection indicates a need for urgent pleural drainage. Some data suggest that in malignant pleural effusion, pleu- ral \202 uid pH <7. 3 is associated with a poorer prognosis and lower pleurodesis success rate. A high pleural \202 uid pH (>7.6) may be seen with Proteus- related pleural infection. Imaging CXR Most pleural effusions are revealed with an erect plain pos- terior-anterior (P A) 9 lateral chest radiograph. Blunting of the costophrenic angle occurs with approximately 200ml of \202 uid. If the patient is imaged supine (e.g. if ventilated on ICU) hazy opac i \201 cation of the hemithorax is seen. Subpul- monic effusions can be dif \201 cult to diagnose with an erect PA CXR but a lateral view may demonstrate a \202 attened posterior hemi-diaphragm. Evidence of the underlying cause may become apparent i.e. bilateral effusi ons with car- diomegaly in heart failure or presence of concomitant lobar collapse or a par enchymal mass in malignant disease. Microbiology Send samples in a sterile pot and blood culture bottles (may improve the yield of bacterial culture). Frank pus, turbid pleural \202 uid, Grams \200\231 stain and/or c ulture positive \202 uid or a pleural pH <7.2 in the context of clinical infection secure the diagnosis of pleural infection and indi- cate a need for prompt pleural drainage. Pleu ral \202 uid culture is negative in 40% of those with pleural infection however; ampli \201 cation of bacterial DNA can provide a diagnosis in a proportion of these cases. In cas es of tuberculous pleuritis direct smears of pleural \202 uid for acid-fast bacilli (AFB) are positive in <20%, and pleural \202 uid culture sensitivity <50%. This re \202 ects the low mycobacterial load. Demonstration of granulomata histo- logically is often required to establish the diagnosis. Ultrasound Ultrasound is safe and easy to perform. It will con \201 rm the presence of ple ural \202 uid in borderline CXR cases with a sensitivity of almost 100%, and should be us ed to guide aspiration of small or heavily septated effusions. Cytology Pleural \202 uid cytology has a sensitivity of approximately 60%, dependent on c ell type and experience of the cytologist. Yield is increased with detection of a further 2 7% of cases with analysis of a second, but not third, pleural aspirate. Immunocytochemistry can improve accuracy of cell type diagnosis and \202 ow cytometry should be requested if lymphoma is a possibility. CT Contrast enhanced CT imaging, with pleural \202 uid in situ and allowing time for cont rast medium to enter the tissue phase, allows effective delineation of the pleural surface. Nodular, circumferential or mediastinal pleural thickening and parietal pleural thickening >1cm, all favor malignant disease with sensitivities approaching 100%. CHAPTER 14.2 Assessment and investigation of an undiagnosed pleural effusion 329 Pleural empyema may be differentiated from lung abscess with thoracic CT. The \200\230spli t pleura \200\231 sign is often demon- strated in empyema with enhancement of the visceral and parietal pleural surfaces evident. A lenticular shape and compression of surrounding pa renchyma is also seen with empyema. Coincidental endobronchial disease or asbestos related lung pathology may be discovered. MRI Although MR imaging is as sensitive as CT for de \201 ning pleural disease it is not r outinely used for cost and acces- sibility reasons. However, MR is preferred in patients wh ere minimisation of radiation dose is important e.g. young women with susceptible breast ti ssue and benign pleural disease. PET PET is not routinely indicated in the investigation of pleural effusion however, may ai d differentiation of malignant from benign pleural disease. Fig. 14.2.3 Thoracoscopic biopsy via two-port technique (mesothelioma) (see Plate 14). Contraindications include an obliterated pleural space, sig- ni \201 cant pleural adhesion s, bleeding diathesis, unstable car- diovascular disease or hypoxia (oxygen saturations <92 % on room air). Medical thoracoscopy is conducted under sedation with local anesthetic and may be carried out as a day-case. A short stay in hospital can be expected if therapeutic t alc poudrage has been performed. For details of the procedure see Chapter 69 of the Oxford Handbook of Respiratory Medicine. Thoracoscopy is safe and complications rare. Intra-pleura l hemorrhage and air/gas embolism on pneumothorax induction occur in approximately 0.1%. Em pyema, local skin infection and port-site pain, which may persist for several weeks, are al so recognized. Mortality rates are low (<0.01%). Closed blind pleural biopsies are performe d using an Abrams \200\231 biopsy needle. They are indicated in cases of sus- pected pleura l tuberculosis where diffuse granulomatous pleural involvement is seen. Diagnostic sensitiv ity is around 90% when both pleural histology and culture are analyzed. Closed biopsies are less sensitive when pleural involve- ment is patchy i.e. malignancy. At least four biopsie s are recommended from a single site, and the samples should be placed in sterile saline (f or AFB smear and culture) and 10% formaldehyde (for histological examination). Complication s are uncommon but include chest pain, pneumothorax (approximately 1% of patients require c hest drain insertion) and vasovagal reactions. Imaging-guided (CT or ultrasound) biopsy is superior to closed biopsies in patients with suspected malignant pleu- ral disease as focal areas of pleural thickening can be tar- geted (sensitivity 87% for CT-guided biopsy vs 47% for Abrams \200\231 biopsy). Bronchoscopy has no role in the routine investigation of an u ndiagnosed pleural effusion; however, should be consid- ered if endobronchial pathology is detected during the diagnostic work-up (usually with CT scanning). Pleural biopsy In cases where pleural \202 uid analysis is non-diagnostic, pleural biopsy for histological examination should be considered. Tissue can be obtained under direct vis ion at thoracoscopy or via closed (blind) or imaging-guided percutaneous biopsy. Thoracosco pic biopsy techniques are most sensitive and should be the method of choice where possible. Thoracoscopy with pleural biopsy Thoracoscopy is indicated for patients with undiagnosed cy tology negative exudative pleural effusions. It can be per- formed under local or general a nesthesia, using a single port or two-port technique. Thoracoscopy allows direct visualizat ion of the pleural surface, biopsy of areas which appear abnormal and thera- peutic maneuve rs such as complete \202 uid drainage pleu- rodesis during the same procedure (Figs. 1 4.2.2 and 14.2.3). The diagnostic rate is approximately 90% for malignant pleural disease a nd approaches 100% in tuberculous pleurisy. Fig. 14.2.2 Normal thoracoscopic appearance of parietal pleural surface (see Plate 13). The persistent undiagnosed pleural effusion Despite thorough investigation about 15% of exu dative pleural effusions remain undiagnosed. In approximately 15% of these underlying malig nancy is eventually proven. H DAVIES & R DAVIES 330 Important diagnoses to reconsider in cases of unexplained pleural effusion include pulmonar y embolism and tubercu- losis as speci \201 c treatment is available to prevent ongoing pa tient morbidity. Hansen M, Faurschou P, Clementsen P. Medical thoracoscopy, results and complications in 146 patients: a retrospective study. Respir Med 1998; 92: 228 \200\223232. Menzies R,.Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med 1991; 114: 271 \200\223276. Further reading Diacon AH, Van de Wal BW, Wyser C, et al. Diagnostic tools in tuberculous p leurisy: a direct comparative study. Eur Respir J 2003; 22: 589 \200\223591. Rodriguez-Panadero F, Lopez MJ. Low glucose and pH levels in malignant pleural effusions. D iagnostic signi \201 cance and prognos- tic value in respect to pleurodesis. Am Rev Respir Dis 1989; 139: 663 \200\223667. Sahn SA,.Good JT, Jr. Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications. Ann Intern Med 1988; 108:345 \200\223349. Garcia LW, Ducatman BS, Wang HH. The value of multiple \202 uid specimens in the cytologi cal diagnosis of malignancy. Mod Pathol. 1994; 7: 665 \200\223668. This page intentionally left blank J HARVEY 332 14.3 Pneumothorax De \201 nition \200 \200 factors including higher smoking rates, tall thin body habi tus and different lung mechanic s. Other reported associa- tions of primary pneumothorax include, loud music ( The Pink Flo yd Effect !) type A personality angen, phases of the moon, and falls in humidity and ambien t air pressure! Pneu- mothorax has been reported in families with an autosomal dominance wi th variable penetrance. Recognized genetic conditions associated with pneumothorax include collagen disorders such as Ehlers \200\223Danlos syndrome, cystic \201 brosis, homocystin uria, and alpha 1 antitrypsin de \201 ciency. Pneumothorax literally means air in the chest . Air becomes trapped between the lung (visc eral pleura) and the chest wall (parietal pleura) causing varying degrees of lung collapse. Pneumothoraces are divided into Primary (the under- lying lung is normal) and Secondary (a ssociated with lung disease \200\223 e.g. COPD and emphysema, interstitial lung disease, c ystic \201 brosis, infections, etc). Pneumothorax may also be Iatrogenic (eg transtho- ra cic needle biopsy, central line insertion, acupuncture) or Traumatic (e.g. rib fracture, ch est trauma, penetrat- ing or blast injury). Tension pneumothorax occurs when air enters but cannot leave the pleural space, causing a progressive build up of pressure, compromise of the mediastinal structures, impairment of venous return, shock and risk of death Etiology Primary Rupture of pleural blebs and bullae probably plays a role in pathogenesis as they are more frequently seen on CT scans and at thoracoscopy in cases of pneumothorax. \200 Subpleural emphysema-like changes are also thought to be important in the etiology of pneum othorax (Fig. 14.3.2). In \202 ammatory changes typically caused by smoking, in small dist al airways cause obstruction and increased pressure in the distal lung parenchyma. This lea ds to rup- ture of the visceral pleura and may also cause mediasti- nal pleural leaks that are also likely to be important aetiologically. Smoking confers a 22-fold increase in rela- tive risk of developing pneumothorax for men and a 9-fold increased risk for women. Prevalence The annual consulting rate for primary and secondary pneu- mothoraces combined i s approximately 24/100,000 (men) and 10/100,000 (women). Hospital admission rates are aroun d 17/100,000 (men) and 6/100,000 (women). Mortality rates are low at 1.3/million (men) and 0.6/million(women). Epidemiology Over half of all pneumothoraces are traumatic in origin (trauma or iatrogenic) . There is a bimodal age distribution the peaks being attributable to primary (15 \200\2233 4 years) and secondary (over 55 years). Pneumothorax is commoner in men with a ratio of abo ut 3:1 due to a number of possible Secondary \200 Almost any lung disease has been reported as causing secondary pneumothorax. Common causes include:- \200 Airway diseases (e.g. COPD, acute severe asthma, cystic \201 brosis). Infections (pneumoc ystis, tuberculosis, abscess form- ing organisms, e.g. Staphylococcus) (Fig. 14.3.3). Inter stitial lung disease (sarcoid, pulmonary \201 brosis, histiocytosis X, lymphangioleiomyom atosis). Connective tissue disease (Rheumatoid, Marfans, and Ehlers \200\223Danlos). Tumors (lung cancer, sarcoma). Fig. 14.3.2 Emphysema-like changes just beneath the visceral pleura. (Courtesy of Journal o f Bronchology). Fig. 14.3.1 A bulla on the apex of the lung viewed thoracoscopically. (Courtesy of Mr T Mor gan). CHAPTER 14.3 Pneumothorax 333 Estimating the size of a pneumothorax The clinical status of the patient rather than the es timated size of a pneumothorax should be the main criteria for treatment decisions. A large primary pneumothorax may not require any inter- vention whilst a small secondary pneumotho rax may require urgent drainage. The most accurate assessment of the volume of a pneu- moth orax requires CT scanning. This is not necessary for the majority of patients. The best met hod of estimating the size of a pneumothorax is much debated! It is not an exact science, s ince the lung often collapses leaving an uneven edge. One reasonable approach classi \201 es pneumothoraces as \200\230small \200\231 or \200\230large \200\231 depending on whethe r the distance be- tween the lateral chest wall and collapsed lung edge is <2cm or >2cm. Th e actual volume of a 2cm pneumothorax is approxi- mately 50%. Management of pneumothorax Fig. 14.3.3 This pneumothorax is due to multiple septicaemic staphylococcal abscesses in a young diabetic girl. One of the abscesses has ruptured through the visceral pleura to cause a pyo-pneumothorax. A chest drain is needed. Primary (Fig. 14.3.4 and 14.3.5) Those with no or minimal symptoms can safely be treated by observation alone and discharged home with review at 2 weeks. They should be provided with verb\al and written instructions to return immediately if they become breath- less. Patien ts with marked dyspnoea and/or a \200\230large \200\231 pneu- mothorax should undergo simp le aspiration (see algo- rithm). Clinical features Symptoms Primary pneumothorax may not cause any symptoms and may be an in cidental radiological \201 nding. Usually patients will experience a sharp pleuritic pain with or without dyspnoea. Small pneumothoraces may be overlooked and the symp- toms attrib uted to pleurisy, pneumonia, musculo-skeletal pain, pulmonary embolism or angina. Dyspnoea is invariably present in secondary pneumotho- rax and may be severe and associated with res piratory failure even with small pneumothoraces. 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 