Pleural Effusion

Abstract

Pleural effusion is an abnormal accumulation of fluid within the pleural space and is a clinical manifestation of conditions such as pyothorax, feline infectious peritonitis, congestive heart failure, intrathoracic neoplasia (e.g., lymphoma, thymoma, pulmonary neoplasia, mesothelioma), chylothorax, heartworm disease, hemothorax, hypoalbuminemia, lung lobe torsion, and diaphragmatic hernia. Pleural effusion is usually suspected from clinical signs and physical findings and is confirmed by thoracentesis or thoracic radiography. ETIOLOGY Pleural effusion occurs when one or, more often, a combination of the factors that determine pleural fluid dynamics are altered so as to increase fluid formation, decrease fluid absorption, or both. For example, pleural effusion is often associated with congestive heart failure (CHF) because increased capillary hydrostatic pressure results in increased pleural fluid formation. Extreme hypoalbuminemia may lower systemic colloidal osmotic pressure sufficiently to cause increased formation and decreased absorption of pleural fluid. Inflammation of the pleura may increase the formation of pleural fluid because of increased blood flow (hydrostatic pressure) and permeability of the pleural capillaries along with increased intrapleural colloidal osmotic pressure due to a higher concentration of protein in the fluid. Pleural effusion may also result from lymphatic insufficiency caused by thoracic duct obstruction, intrathoracic neoplasia, pleural thickening, or lymphatic hypertension secondary to CHF. The major causes of pleural effusion in dogs and cats are listed in Table 164-1 . Table 164-1 CAUSES OF PLEURAL EFFUSION AND CRITERIA FOR DIAGNOSIS Causes of Pleural Effusion Distinguishing Radiographic Findings Fluid Patterns Other Diagnostics Common Diseases Pyothorax Effusion may be unilateral or encapsulated; rounded or collapsed lung lobes (constrictive pleuritis) Septic exudate CBC; fluid culture Feline infectious peritonitis Concurrent abdominal effusion in some cases; rounded or collapsed lung lobes (constrictive pleuritis) Nonseptic exudate (pyogranulomatous) Fluid protein electrophoresis; Serology; PCR, immunostain Congestive heart failure Cardiomegaly; pulmonary edema and venous congestion; dilated caudal vena cava; abdominal effusion (rare) Pure transudate; modified transudate; chylous effusion Echocardiography; electrocardiography; angiocardiography Heartworms (dirofilariasis) Prominent pulmonary arteries; right-sided heart enlargement Modified transudate; chylous effusion Heartworm tests; echocardiography Mediastinal neoplasia (lymphoma, thymoma) Mediastinal mass (widened mediastinum; dorsally displaced trachea; caudally displaced heart and carina; esophageal compression) Neoplastic: modified transudate; nonseptic exudate; chylous effusion Ultrasound; fine-needle aspiration cytology Bronchopulmonary neoplasia (carcinoma) Pulmonary mass or infiltration Neoplastic (variable): modified transudate; nonseptic exudate; chylous effusion; hemorrhage Ultrasound; fine-needle aspiration cytology; thoracotomy Chylothorax Rounded or collapsed lung lobes (constrictive pleuritis); effusion may be unilateral Chylous effusion Fluid triglyceride; lymphangiogram; evaluate for underlying causes Uncommon Diseases Diaphragmatic hernia Other signs of thoracic trauma; loss of diaphragm shadow; displaced abdominal organs; concurrent abdominal effusion Modified transudate; nonseptic exudate Ultrasound; contrast peritoneography Hemothorax Other signs of thoracic trauma Hemorrhage If nontraumatic: coagulation tests; evaluate for underlying causes Lung lobe torsion Opaque lung lobe (right middle or either cranial lobe) Nonseptic exudate; hemorrhage Ultrasound, bronchoscopy; thoracotomy Hypoalbuminemia Concurrent abdominal effusion Pure transudate Evaluate kidneys, liver, and GI tract Mesothelioma No distinguishing characteristics Neoplastic (variable): modified transudate; nonseptic exudate Ultrasound; fine-needle aspiration cytology; thoracotomy Thymic branchial cyst Mediastinal mass (similar appearance to mediastinal neoplasia) Modified transudate; nonseptic exudate Ultrasound; thoracotomy Pancreatitis Concurrent abdominal effusion Nonseptic exudate Abdominal ultrasound; serum pancreatic lipase immunoassay Pulmonary thromboembolism Hypovascularity of lung; blunted pulmonary arteries; right-sided heart enlargement Modified transudate; nonseptic exudate Angiography; pulmonary perfusion scan CLINICAL SIGNS • Dyspnea and exercise intolerance (inactivity) are the most consistent presenting signs of pleural effusion. Dogs and cats generally accommodate to small to moderate increases in the volume of intrapleural fluid by gradually decreasing their level of activity. Thus the signs of early pleural effusion are subtle and often imperceptible to the owner. As the accumulation of intrapleural fluid becomes substantial, however, tachypnea and respiratory distress become apparent during mild exertion and eventually even at rest. • To facilitate breathing, the animal may prefer a sitting or crouched sternal posture, with the head and neck extended and the elbows abducted away from the thorax. An anxious facial expression and open-mouth breathing with forceful abdominal efforts during inspiration may be observed. Cyanosis may be seen in severe cases. Key Point Any struggling or increased distress during examination procedures may worsen dyspnea and induce respiratory arrest because of limited respiratory reserve. • Other clinical signs associated with pleural effusion depend on the underlying cause but may include anorexia, depression, weight loss, dehydration, pallor, fever, hypothermia, or cough. Cough in animals with pleural effusion may indicate tracheal compression by a mediastinal mass (lymphoma, thymoma), intrapulmonary involvement (e.g., lung tumor, pulmonary edema, heartworm disease, pneumonia), or the presence of pleuritis. DIAGNOSIS Suspect pleural effusion on the basis of clinical signs and physical findings. Confirm pleural effusion by thoracentesis (see Chapter 3) or thoracic radiography (see Chapter 159). The cause is often determined through analysis of pleural fluid obtained by thoracentesis, in conjunction with post-thoracentesis radiographs. Depending on the suspected etiology, consider other diagnostic procedures such as laboratory evaluations, cardiac evaluations, ultrasonography, and specialized imaging procedures (contrast radiography, scintigraphy, computed tomography [CT]). Rarely, exploratory thoracotomy is required for definitive diagnosis. Physical Examination Thoracic Auscultation and Percussion • Auscultation generally reveals muffled or inaudible heart and lung sounds ventrally, while breath sounds are preserved dorsally. • On percussion, pleural effusion causes the thorax to sound dull and hyporesonant, and a horizontal fluid line may be demonstrable. Other Physical Findings • Fever suggests an inflammatory, infectious, or neoplastic process. • Jugular venous distention or pulsations and auscultation of murmurs, gallops, and arrhythmias are signs suggestive of cardiogenic pleural effusion. Pleural effusion can be associated with congestive heart failure in cats with hyperthyroidism; thus, palpate the thyroid region for the presence of thyroid gland nodules or enlargement. • Decreased compressibility of the cranial thorax is suggestive of a mediastinal mass, usually lymphoma or thymoma. Mediastinal lymphoma can also compress the esophagus, causing signs of dysphagia and regurgitation; it also can impinge on the sympathetic innervation of the eye, causing Horner syndrome. • Animals with pleural effusion should also be thoroughly examined for evidence of a tumor in any location, since extrathoracic neoplasms may metastasize to the lungs or pleural cavity and cause pleural effusion (e.g., mammary adenocarcinoma). • Ophthalmoscopy may reveal lesions of chorioretinitis in cats with feline infectious peritonitis (FIP). • External signs of trauma may indicate hemothorax or diaphragmatic hernia. Thoracic Radiography Routine thoracic radiography is generally effective for confirming pleural effusion. Key Point If the animal is in extreme respiratory distress, perform pleural drainage to stabilize the patient before radiography. Otherwise, the stress of restraint and manipulation during radiography could prove fatal. The radiographic signs of pleural effusion include separation of the lung lobes from the parietal pleura and sternum by extrapulmonary fluid density (i.e., compression of lung lobes by a pleural fluid density), fluid-filled interlobar fissures producing a scalloped appearance to the edges of the lungs, and obscuring of the cardiac and diaphragmatic shadows, which is referred to as the silhouette sign (see Chapter 159). There is also widening of the mediastinum and blunting or filling of the costophrenic angles by intrapleural fluid density on a ventrodorsal view. In addition, the various causes of pleural effusion may be associated with other radiographic findings of diagnostic significance (see Table 164-1). • A rounded contour to the caudal lobar borders, often accompanied by atelectasis of the cranial and middle lobes, is suggestive of a chronic fibrosing reaction of the visceral pleura that is exerting a constrictive and restrictive effect on the lung lobes (especially in cats with chronic chylothorax). Atelectatic lobes may be mistaken for pulmonary masses, hilar masses, or lung lobe torsion. • Although most pleural effusions are bilateral, unilateral effusion is seen occasionally. This is most suggestive of pyothorax because the natural walling-off response to septic suppuration can cause extensive pleural thickening, which may seal off the mediastinum and limit the effusion to one side. Pleural thickening associated with chylothorax can also result in unilateral effusion. In addition to pyothorax and chylothorax, unilateral effusion is occasionally observed in traumatic hemothorax, diaphragmatic hernia, pulmonary neoplasia, and lung lobe torsion. • Pleural effusion is sometimes found in combination with ascites. Simultaneous pleural and peritoneal effusions (dual-cavity effusion) occur most often in cats with FIP but also in dogs or cats with severe hypoalbuminemia, diaphragmatic hernia, widely disseminated neoplasia, pancreatitis, and CHF. Key Point Because many intrathoracic structures are obscured by the presence of pleural effusion, obtain radiographs after the removal of pleural fluid to facilitate visualization of such abnormalities as mediastinal mass, cardiomegaly, intrapulmonary lesions (masses, infiltrates, vascular changes), lung lobe torsion, or diaphragmatic hernia (see Table 164-1). • Both right and left lateral radiographic views of the thorax may be indicated when a unilateral lesion is suspected (e.g., focal fluid accumulation, pulmonary mass or focal density, lung lobe torsion). Horizontal beam radiography (e.g., standing lateral view) can be used to confirm small-volume effusions, to demonstrate fluid encapsulation, and to facilitate visualization of thoracic structures by shifting fluid away from the structures of interest. Thoracentesis and Fluid Analysis In most animals with pleural effusion, the combination of radiographic findings and fluid analysis establishes the diagnosis or determines the direction for additional diagnostic evaluations. Drainage of the pleural fluid also provides therapeutic benefit and may be lifesaving in patients with hypoxemia. Thoracentesis • Thoracentesis is a safe and generally effective method for removal of fluid from the pleural space. See Chapter 3 for a description of thoracentesis techniques. • Following the collection of diagnostic specimens, enough fluid should be aspirated to relieve respiratory distress. In some animals it may be difficult to obtain an adequate volume of fluid if the fluid is compartmentalized within the pleural space by adhesions or if it is viscid and full of fibrin or debris. In this case, or if repeated pleural drainage is anticipated, place a thoracostomy tube (see Chapter 3). Pleural Fluid Analysis Perform the following analyses on the pleural fluid. • Perform cytologic examination of direct smears and centrifuged cell concentrate smears stained with routine hematologic stains. In scanty aspirates, smears for cytologic examination are the first priority. • Measure total nucleated cell count (differentiates transudates from exudates). • Determine physical and biochemical characteristics, such as color, turbidity (correlates with nucleated cell count in non-chylous fluids), odor (foul odor suggests pyothorax), specific gravity and total protein concentration (differentiates transudates from exudates), viscosity and clot formation (indicates fibrinous exudate as in feline infectious peritonitis [FIP]), and presence of chylomicrons (tests for triglyceride indicate chylous effusion). • Consider non-routine chemical analyses; e.g., pH (<6.9 in pyothorax), glucose (<10 mg/dl in pyothorax), lactic dehydrogenase (>200 IU/L in exudates), adenosine deaminase (elevated in inflammatory exudates), and fibronectin (elevated in neoplastic effusion). • If infection is suspected, consider Gram stain, acid-fast stain, culture and sensitivity testing for aerobic and anaerobic bacteria, and, in some cases, culture for fungi. • If FIP is a possibility, set aside an aliquot of fluid in case protein electrophoresis and a polymerase chain reaction test are later warranted based on preliminary findings (see under Feline Infectious Peritonitis). Classification of Pleural Fluid Patterns On the basis of these analyses, pleural effusions are generally classified into one of several patterns: transudate, modified transudate, nonseptic exudate, septic exudate, chylous effusion, or hemorrhage (Table 164-2 ). In addition, any of these can be subcategorized as neoplastic versus non-neoplastic depending on whether or not neoplastic cells are present on cytologic evaluation. There can be considerable overlap between these various categories; nevertheless, they are helpful for understanding the pathogenesis and determining the cause of pleural effusions. Table 164-2 PLEURAL FLUID ANALYSIS PATTERNS* Fluid Category TP WBC/ml Disease Associations Transudate <1.5 <1,000 CHF (early); hypoproteinemia Modified transudate 2.5–5 1,000–7,000 CHF; neoplasia (e.g., lymphoma); diaphragmatic hernia; pulmonary thromboembolism Nonseptic exudate 3–6 5,000–20,000 FIP; neoplasia; diaphragmatic hernia; lung lobe torsion; pancreatitis; pulmonary thromboembolism Septic exudate 3–7 5,000–300,000 Septic pleuritis (pyothorax) Chylous effusion 2.5–6 1,000–20,000 CHF; lymphoma; thoracic lymphangiectasia; heartworms; jugular vein thrombosis (catheter-induced); diaphragmatic hernia; lung lobe torsion Hemorrhage >3.0 5,000–20,000 Trauma, coagulopathy, neoplasia, lung lobe torsion TP, total protein (g/dl). * The six basic fluid patterns and their most frequent clinical associations are indicated. Any of these can be subcategorized as neoplastic if neoplastic cells are present on cytologic evaluation. Transudate Transudative effusions are generally associated with alteration of capillary hydrostatic pressure caused by CHF or decreased plasma colloidal osmotic pressure caused by hypoalbuminemia. The typical features of a pure transudate are low protein concentration and low cell count consisting predominantly of mesothelial cells; this is comparable to the characteristics of normal pleural fluid. Modified Transudate Long-standing transudative effusions often become modified transudates, as they acquire greater cellularity and protein content. Modified transudates and non-septic exudates can be very similar. Septic Exudate Septic exudates are purulent effusions consisting of numerous degenerating neutrophils, usually in association with intra- and extracellular bacteria. The fluid usually has marked turbidity, high protein concentration, and a foul odor, whereas the color is variable. The presence of a septic exudate within the pleural space indicates septic pleuritis (pyothorax) and is an indication for culture and Gram stain of the effusion (see under Pyothorax). Nonseptic Exudate Nonseptic inflammation and disorders that cause lymphatic or venous obstruction, such as neoplasia, diaphragmatic hernia, lung lobe torsion, pulmonary infarction, and thymic branchial cysts may result in a nonseptic exudative effusion that is difficult to distinguish from a modified transudate. Some clinicians subclassify such effusions as neoplastic effusions if neoplastic cells are evident cytologically. • Feline infectious peritonitis causes a nonseptic pyogranulomatous exudate that has fairly distinctive characteristics—yellow and translucent in appearance with a viscous consistency, high protein concentration (approximating serum levels), high fibrin content, and low-to-moderate cellularity consisting mostly of non-degenerate neutrophils and macrophages (see under Feline Infectious Peritonitis; see also Chapter 10). If FIP is suspected, consider performing protein electrophoresis of the fluid. If gamma globulin is greater than 32% of the protein in effusates, FIP is strongly considered; conversely, if more than 48% of protein is albumin or if the albumin-to-globulin ratio is greater than 0.81, FIP is unlikely. • Eosinophilic effusion (>10% eosinophils) can be either an exudate or modified transudate. The most frequent cause has been intrathoracic neoplasia (e.g., systemic mastocytosis, lymphoma). Eosinophilic pleural effusion has also been associated with heartworm disease, allergy, bronchointerstitial lung disease, eosinophilic granulomatosis, and trauma. Chylous Effusion Chylous effusions are caused by extravasation or leakage of intestinal lymph (chyle) from an obstructed or ruptured thoracic duct. Chylothorax in dogs and cats may be idiopathic or associated with trauma, thoracic lymphangiectasia, intrathoracic neoplasia, heart disease, heartworms, venous thrombosis, diaphragmatic hernia, or lung lobe torsion (see under Chylothorax). The milky white opaque fluid contains mostly lymphocytes accompanied by variable numbers of neutrophils, depending on the duration of the effusion and the extent of the resulting pleuritis (see Table 164-2). Chylous effusions are confirmed by the presence of chylomicrons, which can be demonstrated by the ether clearance test, by the presence of a cream layer on refrigeration, and microscopically by the presence of Sudan-positive orange fat droplets, but these are relatively insensitive methods. Key Point The most reliable test for chylous effusion is the comparison of the triglyceride and cholesterol concentrations measured simultaneously in the fluid and serum. Chylous effusion is characterized by a high triglyceride concentration (usually >300 mg/dl) compared with that of serum and a pleural fluid cholesterol-to-triglyceride ratio of less than 1. The fluid cholesterol concentration is less than or equal to that of serum. Hemorrhagic Effusion Hemorrhage into the pleural space may be associated with trauma, hemostatic abnormalities, or neoplasia. The physicochemical and cytologic features of the effusion are similar to those of defibrinated peripheral blood. The presence of erythrophagocytosis by macrophages confirms that the hemorrhage is not merely the result of a traumatic collection. Laboratory Evaluations Various laboratory evaluations may provide useful diagnostic information depending on the suspected underlying cause of pleural effusion. • The complete blood count may reveal a neutrophilia with a left shift in pyothorax, FIP, lung lobe torsion, and neoplasia. Lymphopenia is common in animals with chylothorax, but it can also be a nonspecific manifestation of stress. Anemia and various other hematologic abnormalities may be associated with lymphoma and feline leukemia virus (FeLV). • Serum protein determinations may reveal hypoalbuminemia, a cause of transudation, or hyperglobulinemia, a common finding in FIP and other conditions of chronic immune stimulation. Severe proteinuria would be expected on the urinalysis of a dog or cat with hypoalbuminemia and transudation associated with nephrotic syndrome. • Diagnostic testing may be indicated for infectious and parasitic diseases that have been associated with pleural effusion, such as FeLV, feline immunodeficiency virus (FIV), FIP, heartworm disease, and aelurostrongylosis. Specific aspects of these various diagnostic tests are described in the appropriate chapters elsewhere in this book. • In cats with cardiogenic pleural effusion, the serum concentrations of thyroxine and taurine may be indicated for the diagnosis of hyperthyroid cardiomyopathy and taurine-deficient cardiomyopathy, respectively (see Chapter 150). Cardiac Evaluations • Echocardiography is the most useful procedure for diagnosis of cardiogenic causes of pleural effusion such as cardiomyopathy (idiopathic, taurine deficiency, hyperthyroidism), pericardial diseases (pericarditis, neoplasia), congenital heart defects, and heartworm disease. • Angiocardiography is also helpful for determining the underlying cardiac abnormality in selected cases of cardiogenic pleural effusion. A detailed discussion of cardiac evaluation is found in Chapters 142 and 143. Ultrasonography The inability of ultrasound to penetrate air-filled structures limits the diagnostic usefulness of ultrasound examination of the lungs; however, in animals with pleural effusion, ultrasonography can provide meaningful information because the pleural fluid provides an “acoustic window” for transmission. Thoracic ultrasonography is possible when an air-filled lung is collapsed, displaced (by fluid, mass, or herniated abdominal viscera), replaced (by neoplastic tissue), or consolidated. Because the presence of pleural fluid actually enhances ultrasound transmission, it is preferable to perform the procedure prior to evacuation of the pleural fluid. • Pleural fluid usually appears as an anechoic or hypoechoic space between the thoracic wall or diaphragm and lung. The fluid in pyothorax and hemothorax may contain internal echoes. • In addition to confirming pleural effusion, ultrasonography is helpful for the diagnosis of pulmonary, mediastinal, and pleural neoplasms; pulmonary abscesses associated with pyothorax; lung lobe torsion; cardiac abnormalities; and diaphragmatic hernia. • Ultrasonography can also be used to guide needle placement accurately for fine-needle aspiration or biopsy of pleural, mediastinal, and pulmonary masses. Specialized Imaging Techniques Depending on the suspected etiology of the pleural effusion and the results of other diagnostic evaluations, specialized imaging techniques may be indicated, such as contrast radiographic procedures (contrast peritoneography for the diagnosis of diaphragmatic hernia, contrast lymphangiography for the diagnosis of chylothorax, contrast pleurography), lymphoscintigraphy, and CT. Positive Contrast Peritoneography When diaphragmatic hernia is suspected but cannot be confirmed on routine thoracic and abdominal radiographs, ultrasonography should be the next approach; however, if ultrasound is unavailable, positive contrast peritoneography is an alternative method for diagnosis of diaphragmatic hernia. Inject an aqueous contrast iodide (Renovist; 1 ml/kg) into the peritoneal cavity, and roll the animal from side to side for several minutes to distribute the contrast agent. Obtain radiographs to determine whether the contrast agent has entered the pleural space through a defect in the diaphragm. Lymphangiography Positive-contrast lymphangiography is used to evaluate the thoracic duct lymphatic channel in dogs and cats with unexplained chylous effusion. This is usually done by catheterizing an intestinal lymphatic just prior to, and in preparation for, surgical ligation of the thoracic duct to treat chylothorax. The reader is directed to surgical clinical literature and texts for a technical description of this procedure. SPECIFIC DISEASES Pyothorax (Septic Pleuritis) Pyothorax is the accumulation of purulent exudate (pus) within the pleural space as a result of intrapleural bacterial infection (septic pleuritis) or, rarely, mycotic infection. Etiology Microorganisms A diversity of microorganisms has been isolated from the pleural fluid of dogs and cats with pyothorax; mixed bacterial infections composed mostly of obligate and facultative anaerobes are found most consistently. • In many cases, the infection consists entirely of anaerobic bacteria. The most frequent isolates are Bacteroides spp., Clostridium spp., Peptostreptococcus spp., Fusobacterium spp., Pasteurella multocida, and Actinomyces spp. The isolates from cats with pyothorax and their relative frequency closely resemble those found in subcutaneous cat bite abscesses and mirror the normal oropharyngeal flora of the cat. • Other bacteria found sporadically include Pseudo-monas spp., Escherichia coli, Klebsiella spp., Proteus spp., Streptococcus spp., Staphylococcus spp., Corynebacterium pyogenes, Nocardia spp., Borrelia spp., Eubacterium spp., and mycoplasmas. • Fungi, such as Cryptococcus neoformans, Blastomyces dermatitidis, and Candida albicans, are rare causes. • In addition, pleuritis has been reported as a rare manifestation of infection with Aelurostrongylus abstrusus, the feline lungworm. Source of Infection The source of infection is not identified in most dogs and cats with pyothorax. Microorganisms may potentially enter the pleural space through penetrating chest wounds (e.g., bite wounds), perforations of mediastinal structures (i.e., esophagus, trachea, bronchi), migrating pleural foreign bodies (e.g., grass awns), and direct extension from the lung in bacterial pneumonia (parapneumonic effusion). Mediastinitis, pleuritis, and pyothorax are frequent complications of esophageal perforation caused by esophageal foreign bodies, especially those with irregular sharp edges, such as plastic, glass, wood, and bone. Iatrogenic esophageal rupture can occur during endoscopic foreign body retrieval or during balloon dilation of esophageal strictures. Intrapleural infection can also result from hematogenous or lymphatic spread from distant infection sites. Clinical Signs Dyspnea is the most consistent sign of pyothorax. Cough is observed in some cases. In addition, nonspecific systemic signs are common, including inactivity, exercise intolerance, fever, depression, anorexia, dehydration, weight loss, and pallor. Advanced cases may present in a moribund state with endotoxic shock and hypothermia. Diagnosis • Physical findings (auscultation and percussion) and radiographic findings in pyothorax are typical of pleural effusion. In some animals with pyothorax, the pleural fluid may become encapsulated or compartmentalized by fibrinous adhesions and fibrosis (walling-off process), producing radiographic signs of unilateral or non-gravitating effusion and rounded lobar edges. • The hematologic findings in pyothorax are typical of a serious septic inflammatory process and support the diagnosis. A neutrophilic leukocytosis with a left shift and with toxic-appearing neutrophils are found in most cases, while a neutropenia with a degenerative left shift may develop terminally. The hemogram also usually reveals a mild to moderate nonregenerative, normochromic, normocytic anemia of chronic infection. • Confirm the diagnosis of pyothorax with pleural fluid analysis, which indicates septic inflammatory (purulent) exudate. The fluid is usually malodorous and cloudy or opaque, with color varying from red to brown to yellow. The fluid also may contain a flocculent sediment of fibrinous and cellular debris. The total protein concentration generally exceeds 4.5 g/dl and there are usually 50,000 to 100,000 or more nucleated cells/μl, consisting of mostly (greater than 85%) degenerating neutrophils. Cytologic examination usually reveals abundant intra- and extracellular bacteria. • Culture the pleural fluid for confirmation of the diagnosis and for determination of optimal antibacterial therapy. In most cases, a mixed infection (see earlier, under Etiology) involving primarily anaerobic bacteria is found. If only routine aerobic culture techniques are used, only the aerobic component of the infection will be identified, and because some dogs and cats with pyothorax have an exclusively anaerobic infection, there may be no growth at all. Thus, perform both aerobic and anaerobic cultures. • Because retroviral status may influence prognosis, test cats with pyothorax for FeLV (see Chapter 8) and FIV (see Chapter 9). Treatment Treat pyothorax with systemic antibiotics, closed-chest drainage, and lavage by means of an indwelling chest tube thoracostomy (see elsewhere for thoracic tube placement). The chest tube provides for repeated drainage and irrigation of the pleural space. Antibiotics Start antibiotic therapy intravenously and then continue orally at home for at least 4 to 6 weeks. Until the results of culture and sensitivity of the effusion are available, assume that a mixed anaerobic and aerobic infection is present (see earlier, under Etiology). Most isolates are susceptible to antibiotics of the penicillin family, such as penicillin G, ampicillin, amoxicillin, or amoxicillin with clavulanate; thus, standard dosages of any one of these are a good initial choice (see Table 164-3 ), although approximately 20% of anaerobes may be resistant to the penicillin-ampicillin group. Other effective antibiotics for anaerobic infections include clindamycin and metronidazole (see Table 164-3). For gram-negative infections, add an aminoglycoside (amikacin), enrofloxacin, or trimethoprim-sulfadiazine. Trimethoprim-sulfadiazine is indicated for Nocardia spp. Table 164-3 USEFUL ANTIBIOTICS FOR TREATMENT OF PYOTHORAX Antibiotic Trade Name Dosage Indications Penicillin G generic 20,000–40,000 U/kg q6–8h IV IM anaerobes,* Pasteurella, Actinomyces Ampicillin Omnipen 20 mg/kg q6–8h IV IM SC anaerobes,* Pasteurella and some other gram negatives Amoxicillin Amoxi-Tabs 20 mg/kg q8–12h PO anaerobes,* Pasteurella and some other gram negatives Amoxicillin/clavulanate Clavamox 20 mg/kg q12h PO anaerobes,† Pasteurella and many other gram negatives Chloramphenicol Chloromycetin 50 mg total/cat q12h IV SC PO anaerobes,† gram-positive and gram-negative aerobes Clindamycin Antirobe 10 mg/kg q12h PO anaerobes† Metronidazole Flagyl 10–15 mg/kg q8–12h PO IV anaerobes† Enrofloxacin§ ¶ Baytril Dogs: 5 mg/kg q12h PO, IV, SC; most gram-negative and gram-positive aerobes Cats: 5 mg/kg q24h PO, IV, SC Trimethoprim-sulfadiazine Tribrissen 15 mg/kg q12h PO Nocardia Amikacin‡ Amiglyde-V 10 mg/kg q8–12h IV IM SC gram negatives§ Cefoxitin Mefoxin 20–30 mg/kg q8h IV IM anaerobes,† gram-negatives Ticarcillin Ticar 30–50 mg/kg q6h IV IM anaerobes,† gram-negatives, Pseudomonas * Excluding Bacteroides fragilis. † Including most penicillin-resistant strains of Bacteroides fragilis. ‡ Caution: uncorrected dehydration may potentiate aminoglycoside nephrotoxicity. § Enrofloxacin and aminoglycosides are ineffective against anaerobes; thus, always use in combination with penicillin or other antibiotic with activity against anaerobes when treating pyothorax. ¶ Doses exceeding 5 mg/kg daily are retinotoxic in cats and may cause blindness. Pleural Drainage and Lavage Place a thoracic drainagetube to drain purulent material from the pleural space and allow lavage of the pleural cavity. Although some animals with severe effusion may require continuous chest drainage, intermittent drainage is adequate for most patients. • Perform thoracic drainage at least twice daily. For pleural lavage use sterile isotonic saline or lactated Ringer's solution warmed to body temperature. Prior to each irrigation procedure, evacuate any fluid that has accumulated since the previous lavage and record the quantity. Warm the irrigation solution to body temperature and infuse 10 to 20 ml/kg body weight slowly over about 5 minutes through the chest tube. If respiratory distress occurs, stop the infusion. • Leave the solution in the thorax for 5 to 10 minutes while the animal is gently rolled to enhance distribution; then aspirate as much as possible. A return of 75% or more of the irrigation solution is expected, which can sometimes be facilitated by repositioning the animal or rolling it from side to side during aspiration. • If the animal is initially dehydrated, rehydration should be accomplished before, or simultaneous to, the first lavage; otherwise, much of the instilled fluid will be absorbed from the pleural space with very little returned on aspiration. • Obtain samples of interlavage fluid for cytologic examination on a daily basis and examine for disappearance of microorganisms and degenerative neutrophils. Remove the chest tube once the interlavage pleural fluid becomes characteristic of a modified transudate (clear in appearance and free of microorganisms and degenerative neutrophils) and the quantity that accumulates is small and can be accounted for merely by the presence of the drain itself (i.e., up to 2-3 ml/kg/day). There should also be radiographic resolution of pleural effusion. • The duration of the pleural drainage phase of therapy in most cases is 4 to 7 days. Monitor serum proteins and electrolytes (especially potassium) because depletion can occur with prolonged lavage. Evaluate thoracic radiographs about 1 week following tube removal to ensure resolution, and continue systemic antibiotics for a minimum of 4 to 6 weeks. Complications Adverse sequelae to pyothorax may include restrictive pleuritis, pleural adhesion formation, and pulmonary abscessation. Occasionally, adhesions render closed-chest drainage and lavage ineffective. In such cases, perform a thoracotomy (see Chapter 167) to manually break down adhesions, drain pockets of exudate, remove debris, and place a drainage tube in the most favorable location for postoperative thoracic lavage. In addition, thoracotomy may be necessary if a migrating pleural foreign body is suspected. Chylothorax Etiology Chylothorax results from the leakage or extravasation of chylomicron-laden intestinal lymph (chyle) into the pleural space from an obstructed, ruptured, or anomalous thoracic duct or its collateral branches. The cause of chylothorax is frequently not apparent; however, chylous pleural effusions in dogs and cats have been associated with lymphangiectasia of intrathoracic lymphatics (resulting from obstruction of thoracic duct inflow into the cranial vena cava), traumatic rupture of the thoracic duct, intrathoracic neoplasia (mediastinal lymphoma, thymoma), heart disease (cardiomyopathy, heartworms, hyperthyroidism, pericarditis), diaphragmatic hernia, peritoneopericardial diaphragmatic hernia, lung lobe torsion, and vena caval thromboembolism (iatrogenic from indwelling jugular venous catheterization). Idiopathic chylothorax has a prediliction for Afghan hounds, Smiba Inus, and Oriental cat breeds (Siamese, Himalayan). Clinical Signs In addition to typical signs of pleural effusion, such as dyspnea and tachypnea, it is noteworthy that dogs and cats with chylothorax often present with coughing. Diagnosis • Confirmation that pleural fluid is chyle depends on demonstration of the presence of chylomicrons. The most reliable criteria for chyle are an increased concentration of triglycerides in the fluid compared with serum and a fluid cholesterol-to-triglyceride ratio of less than 1 (see under Classification of Pleural Fluid Patterns). • In the veterinary literature, many milky effusions have been called pseudochylous (which implies lipid in the form of cholesterol and lecithin derived from degenerating cells) when, in fact, if triglyceride analysis had been performed, these effusions would probably have been true chyle. • The predominant cell in chyle is usually the small lymphocyte. However, over time the irritant effect of chyle results in an influx of inflammatory cells, especially neutrophils. • Once chylothorax is confirmed, use routine radiography and other clinical evaluations (e.g., ultrasonography, echocardiography, heartworm testing) to search for underlying causes, such as heart disease, heartworms, neoplasia, or diaphragmatic hernia. Medical Treatment • If an underlying cause is identified, treatment is directed toward the underlying primary disorder. In the rare case when there is a history of recent thoracic trauma, conservative medical management may be tried for a 2-week period in hopes of spontaneous healing of the injured lymphatic. This consists of (1) pleural drainage by either periodic thoracentesis or continuous chest tube drainage, and (2) decreasing thoracic duct flow by exercise restriction (cage rest). • A fat-restricted diet supplemented with medium-chain triglycerides (MCTs) has been recommended in the past; however, this has not been effective clinically, and in normal dogs it has been shown experimentally that altering dietary fat content or using MCTs does not significantly affect thoracic duct lymph flow and that orally administered MCTs are carried in thoracic duct lymph. • Anecdotal reports have indicated some success with the administration of a benzopyrone compound, Rutin (50 mg/kg PO q8h). The proposed mechanisms of action of rutin include reducing leakage from blood vessels, increasing protein removal by lymphatic vessels, increasing the macrophage phagocytosis of chyle, increasing tissue macrophage numbers, and increasing proteolysis and removal of protein from tissues. However, clinical results from the use of this drug for dogs and cats with chylothorax have been inconsistent. Surgical Treatment • If no underlying medically treatable cause of chylothorax is found, surgical intervention is indicated. The surgical approach to treatment of chylothorax involves ligation of the thoracic duct at the level of the diaphragm in association with evaluation of the thoracic duct and intrathoracic lymphatics by pre- and immediate postoperative contrast lymphangiography. Lymphangiography is performed by cannulating a mesenteric lymphatic vessel via a flank abdominal approach. After delineating the thoracic duct and its branches with the dye study, the duct is ligated via a 10th intercostal space thoracotomy (right side in dogs, left side in cats). Ligate the duct as close to the diaphragm as possible, and be sure to occlude all branches. Postligation lymphangiography then confirms complete occlusion of the thoracic duct system. The details of these procedures are provided in Chapter 167. • The reported success rate of this procedure varies from 20% to 60% in cats and 55-60% in dogs. Commercially available pump devices (e.g., Hakim-Cordis ventricular-peritoneal catheter, Cordis Corporation, Miami, FL; double-valve Denver peritoneal-venous catheter, Denver Biomaterials Inc., Evergreen, CO) are available for active pleuroperitoneal shunting of chylous effusion in refractory chylothorax. Disadvantages of shunt devices are that they are expensive, they are easily occluded, they require considerable owner compliance, and the complication rate is high. • Recent clinical studies have shown improved results of surgical treatment when thoracic duct ligation is combined with partial pericardectomy. Although the reason for treatment successes with pericardectomy are unclear, subtle changes in thoracic venous and/or lymphatic pressures could account for the cessation of effusion due to improved flow through thoracic duct lymphatics. The authors currently create a pericardial window in conjunction with thoracic duct ligation for chylothorax in dogs and cats. • When chylothorax is unresponsive to thoracic duct ligation or shunt procedures, pleurodesis using intrapleural instillation of a sclerosing agent such as tetracycline or sterile talc may be palliative. Pleurodesis is intended to reduce or stop pleural effusion by causing diffuse adhesions between the parietal and visceral pleura. It is an effective technique in humans but has not been efficacious in dogs, either with experimental or spontaneous effusion. Complications Chronic diffuse fibrosing pleuritis is a sequela of chylothorax that may cause constriction and collapse of lung lobes and restrict the expandability of the lungs. Radiographically, fibrosing pleuritis is indicated by rounded lung lobe borders and atelectasis of cranial or middle lobes. The atelectatic lobes may be mistaken for pulmonary masses, hilar masses, or lung lobe torsion. In order to avoid excessive pleural fibrosis, surgical intervention in animals with chylothorax, especially cats, should not be delayed. Surgical removal of the layer of fibrin and fibrotic reaction covering the visceral pleura, a process called decortication, is difficult in cats and usually results in significant laceration of underlying lung tissue that requires continuous pleural drainage for postoperative pneumothorax and effusion. Feline Infectious Peritonitis Etiology Feline infectious peritonitis is a highly fatal chronic progressive coronaviral infection of cats characterized by widespread immune complex-mediated vasculitis and pyogranulomatous inflammation (see Chapter 10 for a comprehensive description of the disease). In the effusive form of FIP, exudative peritonitis or pleuritis may occur. Clinical Signs Pleural involvement is manifested as dyspnea and by other signs of pleural effusion, often accompanied by nonspecific signs such as anorexia, depression, fever, and pallor. Pericardial effusion due to fibrinous pericarditis may accompany pleural FIP and is detectable by echocardiography, but only rarely is this extensive enough to cause cardiac tamponade. Diagnosis • The diagnosis can usually be established by analysis of a specimen of pleural fluid obtained by thoracentesis. The fluid of FIP is a nonseptic exudate, often described as pyogranulomatous or fibrinous. It is typically pale yellow to golden in color, is nearly translucent because of its relatively low cell count (usually 1,000-10,000 nucleated cells/μl), and is foamy because of its high protein content. The fluid of FIP may seem viscous, tenacious, and sticky, and it may contain flecks, strands, or clots of fibrin. The concentration of protein often approaches that of serum, ranging from 4 to 10 g/dl. Fluid protein electrophoresis is a reliable diagnostic indicator of FIP when gamma globulin composes more than 32% of the protein, albumin is less than 48% of the protein, and the albumin-to-globulin ratio is less than 0.81. A somewhat distinctive mixture of inflammatory cells characterizes the pyogranulomatous nature of FIP exudate, with non-degenerate neutrophils and macrophages predominating, but also including plasma cells and lymphocytes. • Ancillary laboratory findings that may support the diagnosis of FIP include neutrophilic leukocytosis, neutropenia, lymphopenia, normocytic-normochromic nonregenerative anemia, and hyperglobulinemia. • A high serum titer of anti-coronaviral antibody indicates the possibility of FIP but is not a confirmatory test. A polymerase chain reaction (PCR) test for coronavirus in pleural fluid is a useful diagnostic aid (low sensitivity but high specificity) providing that a validated assay is used. Also use fluid immunostaining. Treatment In general, the results of treatments for FIP have been disappointing, and the prognosis is considered poor. Nevertheless, occasional remissions have been obtained with immunosuppressive therapy and with drainage of the intrapleural exudate (see Chapter 10). Congestive Heart Failure Etiology Pleural effusion can be a manifestation of CHF in dogs and cats (Chapter 147). It is most commonly associated with cardiomyopathy (see Chapter 150), but also occurs with cardiac arrhythmias, congenital cardiac defects, pericardial diseases, heartworm disease, and hyperthyroid cardiomyopathy. Although pleural effusion is considered primarily a sign of right-sided CHF, animals with severe or chronic left-sided failure also develop pleural effusion. Clinical Signs In animals with pleural effusion due to heart disease, presenting signs often include tachypnea, dyspnea, depression, inactivity, and weakness. Anorexia and vomiting may also be observed. Physical findings that may indicate a cardiogenic cause for pleural effusion include: • Signs of low cardiac output, such as pallor, hypothermia, cold extremities and pinnae, and weak femoral pulses • Jugular venous distention, jugular pulsation, or positive hepatojugular reflex • Concurrent hepatomegaly (due to hepatic congestion) or ascites (although, unlike dogs, cats rarely develop significant ascites from CHF) • Abnormalities of cardiac auscultation, such as murmurs, diastolic gallops, or arrhythmias • Ophthalmoscopic lesions of taurine-deficient retinopathy in cats (see Chapter 138) • A palpable thyroid nodule in hyperthyroid cats Diagnosis The diagnosis of cardiogenic pleural effusion can be difficult because the effusion may muffle the heart sounds on auscultation and obscure the cardiac silhouette on thoracic radiographs. • Radiographic findings that suggest pleural effusion is associated with CHF include cardiomegaly, pulmonary infiltrates (edema), pulmonary venous distention, distended caudal vena cava, and hepatomegaly. In many cases, these findings are more apparent on radiographs taken after fluid has been drained from the pleural space. • Pleural fluid analysis may determine the effusate to be a transudate, modified transudate, or chylous effusion, the predominant cells being erythrocytes, mesothelial cells, and small lymphocytes. • Echocardiography is often and sometimes angiocardiography, may be necessary to confirm and assess cardiac disease. Cardiac arrhythmias and conduction disturbances are evaluated electrocardiographically. Treatment The treatment options for CHF as described in Chapter 147 are used for control of cardiogenic pleural effusion. Intrathoracic Neoplasia Etiology Intrathoracic neoplasia is one of the most common causes of pleural effusion in dogs and cats. Causes of neoplastic pleural effusion include mediastinal lymphoma and thymoma, primary and metastatic pulmonary neoplasia (see Chapter 165), and malignant pleural mesothelioma. The mechanism of pleural effusion in these conditions generally involves hemolymphatic obstruction. Diagnosis • Use radiography (both right and left lateral views) and ultrasonography to characterize or identify the location of an intrathoracic mass (see Chapter 159). • The fluid can vary from modified transudate to nonseptic exudate to chylous effusion. Lymphoma is usually diagnosed cytologically. Confirmation of non-lymphomatous intrathoracic neoplasia can be a diagnostic challenge requiring biopsy by thoracoscopy or thoracotomy. Clumps of reactive mesothelial cells exfoliate into all pleural effusions and are easily mistaken for neoplastic cells, especially carcinoma cells. Ideally, similar-appearing cells should be aspirated from pulmonary or intrathoracic masses before a definitive diagnosis of neoplasia is made. Conversely, many primary and metastatic tumors do not exfoliate cells into pleural fluid; thus, an absence of neoplastic cells in pleural effusion does not necessarily exclude neoplasia as the cause. Treatment Chemotherapy for mediastinal lymphoma is discussed in Chapter 27. The surgical aspects of intrathoracic neoplasia (thoracotomy, lobectomy) are discussed in Chapter 167. Hemothorax Etiology • Hemothorax, the accumulation of blood within the pleural space, may be associated with any form of thoracic trauma that lacerates the lung parenchyma or ruptures intrathoracic vessels (see Chapter 166). It can also be caused by disorders of hemostasis (see Chapter 23) or by intrathoracic neoplasms that rupture or erode into vessels. Lung lobe torsion and pulmonary infarction are rare causes. • The seriousness of hemothorax depends on the rate and volume of blood loss. Bleeding from the venous circulation or the low-pressure pulmonary arterial circulation is usually self-limiting, whereas bleeding from high-pressure systemic arteries, such as the intercostal or bronchoesophageal arteries, may be more severe. Hemorrhage due to injury of the heart or great vessels results in massive hemothorax that is rapidly fatal. • The two major consequences of hemothorax are shock due to loss of circulating blood volume into the pleural space and ventilatory impairment due to fluid compression of the lung. As a general rule, in rapidly developing hemothorax, fatal circulatory failure (exsanguination) occurs before the volume of pleural fluid that accumulates is sufficient to cause serious respiratory compromise. However, blood or fluid replacement therapy in the presence of continued bleeding may lead to greater accumulation of intrapleural fluid, resulting in severe lung compression and ventilatory failure. Clinical Signs Clinical signs of hemothorax are attributed to shock and pleural effusion—dyspnea, tachypnea, weakness, pallor, and weak femoral pulses. Diagnosis • The heart and lung sounds are usually muffled, and percussion of the ventral thorax may be hyporesonant. In the trauma victim, this is distinguished from the hyperresonance of pneumothorax. • Confirm intrapleural fluid radiographically. • Definitive diagnosis is made by aspiration of defibrinated (non-clotting) blood from the pleural space. Blood clots rapidly (within 45 minutes) in the pleural space; thus, unless there is ongoing or very recent bleeding, the aspirated hemorrhagic effusion will not clot or contain platelets. Treatment The treatment of hemothorax involves treatment of shock with intravenous fluids or blood, as well as relief of respiratory distress via thoracentesis if necessary. See Chapter 166 for more details on treatment of hemothorax. Lung Lobe Torsion Etiology Torsions of either the right middle lung lobe or the right or left cranial lung lobe have occasionally been found in dogs and cats with pleural effusions. The mechanism of lung lobe displacement that culminates in torsion is poorly understood. Lung lobe torsion can occur secondary to pleural effusion, or it can be the cause of a serosanguineous effusion. Clinical Signs The signs usually include dyspnea, tachypnea, depression, anorexia, and weight loss. Diagnosis • The diagnosis of lung lobe torsion is suggested by visualization of a consolidated cranial or middle lung lobe on post-thoracentesis radiographs. Radiographic differential diagnoses for lobar consolidation should include pneumonia, edema, hemorrhage, atelectasis, and neoplasia. • The pleural fluid may be nonspecific (i.e., nonseptic exudate), or it may reflect the underlying disease state (i.e., chylous, septic, or neoplastic effusion). • Ultrasonography is helpful for identifying lung lobe torsion in some animals with pleural effusion. • Confirmation of lung lobe torsion can only be made by thoracotomy in many cases. Treatment The treatment is lung lobectomy of the affected lobe (see Chapter 167). Thymic Branchial Cysts Branchial cysts develop from vestiges of the fetal branchial arch system. These are rare, but when they develop in the thymus they produce an encapsulated, multilobulated, multicystic mass in the cranial mediastinum that compresses adjacent structures and usually cause pleural effusion. Pleural fluid is blood-tinged and characteristic of a modified transudate (obstructive pattern) or nonseptic exudate. On the basis of their radiographic appearance, thymic branchial cysts must be differentiated from other cranial mediastinal masses such as lymphoma and thymoma (see under Intrathoracic Neoplasia). Because of their cystic nature, branchial cysts should be distinguishable from solid mediastinal masses by ultrasonography. Treat branchial cysts by surgical resection. Diaphragmatic Hernia Pleural effusion can be a complication of diaphragmatic hernia, especially when the liver or omentum is incarcerated in the hernia. The effusion can complicate the radiographic diagnosis of diaphragmatic hernia. The pleural fluid is usually a modified transudate, but in some cases it may be blood or chyle. Diaphragmatic hernia is discussed further in Chapter 166. Pancreatitis-Associated Effusion Mild transient pleural effusion has occasionally been associated with acute pancreatitis. Accompanying peritoneal effusion may also be present. Pleural effusion is a well-known complication of pancreatitis in humans; the pathogenesis is not fully understood, but it has been attributed to chemical pleuritis associated with toxins and activated pancreatic enzymes such as lipase reaching the pleural cavity via intercommunicating lymphatics. Generalized vascular injury and increased vascular permeability associated with acute pancreatitis may also play a role. The pleural effusion is usually a small volume and self-limiting with resolution of the pancreatitis; thus, no specific treatment is necessary. See Chapter 73 for further discussion of pancreatitis. Pulmonary Thromboembolism Pleural effusion can occur in association with pulmonary thromboembolism whenever it is extensive enough to produce infarction and ischemic necrosis of the lung and inflammation of adjacent pleura. • Clinical signs are unresponsive dyspnea and signs of right-sided heart failure. • Underlying causes of pulmonary thromboembolism include heartworm disease, pulmonary neoplasia, and hypercoagulability caused by septicemia, amyloidosis, hyperadrenocorticism, and immune-mediated hemolysis. • The effusion is usually a modified transudate or nonseptic exudate, but secondary infection of the infarcted lung can result in a septic effusion. • Radiographically, blunted pulmonary arteries, hypovascularity of the affected lung, and evidence of right-sided heart enlargement or failure suggest pulmonary thromboembolism; however, the diagnosis can be difficult to document because radiographic abnormalities may be absent or very subtle. • Specialized procedures such as right ventricular and pulmonary artery pressure measurements, angiography, and radionuclide lung perfusion scan may be required for definitive diagnosis. • Treatment is based on resolving the underlying cause of the thromboembolism (see Chapter 153), providing pleural drainage as needed, supplemental oxygen therapy, and control of secondary bacterial infection.