Pleural Fluid

Pneumothorax

When supine, pneumothorax gas migrates along the anterior surface of the lung, making detection on the anteroposterior radiograph problematic. The base, lateral chest wall, and juxtacardiac area should be carefully visualized for evidence of pneumothorax. Accumulation of air along the mediastinal parietal pleura may simulate pneumomediastinum.⁵ An erect or decubitus (suspected hemithorax up) radiograph should be obtained to assess for the presence of a pneumothorax. US is sensitive for the detection of pneumothorax by determining the presence or absence of “lung sliding.”⁶ In individuals without pneumothorax, the lung–chest wall interface, which represents a to-and-fro movement synchronized with respiration, can be identified. US visualization of lung sliding is correlated with the absence of pneumothorax, and from this sign alone, at least anterior pneumothorax can be excluded rapidly at the bedside of a mechanically ventilated patient. However, absence of lung sliding may be caused by the presence of large bullae or pleural symphysis caused by previous pleurodesis or pleural adhesions due to previous pleural disease. Hence, the absence of lung sliding is not specific for pneumothorax, but detection of lung sliding reliably excludes the presence of pleural air in the examined area.

The most common radiographic signs of tension pneumothorax are contralateral mediastinal shift, ipsilateral diaphragmatic depression, and ipsilateral chest wall expansion. Underlying lung disease may prevent total lung collapse even if tension is present; in patients on mechanical ventilation, little or no midline mediastinal shift may result from the tension.⁷ In the latter, a depressed ipsilateral diaphragm is a more reliable sign of tension than mediastinal shift.

In patients with acute respiratory distress syndrome (ARDS), barotrauma can result in a localized tension pneumothorax with a subtle contralateral mediastinal shift, flattening of the cardiac contour, and depression of the ipsilateral hemidiaphragm.⁸ Pleural adhesions and relative compressibility and mobility of surrounding structures, in addition to the supine position, probably account for these loculated tension pneumothoraces.

In a study of 88 critically ill patients with 112 pneumothoraces, the anteromedial and subpulmonic recesses were involved in 64% of patients in the supine and semierect position.⁹ Furthermore, in 30% of the pneumothoraces in this study that were not initially detected by the clinician or radiologist, half the patients progressed to tension pneumothorax. Therefore, a high index of suspicion is necessary to avoid catastrophic situations.

Factors that may contribute to an improved ability to diagnose this potentially lethal problem include familiarity with atypical locations of pneumothoraces in critically ill patients, usually due to the supine or semierect position; the consequence of underlying cardiopulmonary disease; and knowledge of other risk factors contributing to misdiagnosis (e.g., mechanical ventilation, altered mental status, prolonged ICU stay, and development of pneumothorax after peak physician staffing hours).¹⁰

Diagnostic Thoracentesis

Therapeutic Thoracentesis

Atelectasis

Atelectasis is a common cause of small pleural effusions in comatose, immobile, pain-ridden patients in ICUs²⁶ and after upper abdominal surgery.^27,28 Other causes include major bronchial obstruction from lung cancer or a mucous plug. Atelectasis causes pleural fluid because of decreased pleural pressure. With alveolar collapse, the lung and chest wall separate further, creating local areas of increased negative pressure. This decrease in pleural pressure favors the movement of fluid into the pleural space, presumably from the parietal pleural surface. The fluid accumulates until the pleural or parietal-pleural interstitial pressure gradient reaches a steady state.

Pleural fluid from atelectasis is a serous transudate with a low number of mononuclear cells, a glucose concentration equivalent to serum, and pH in the range of 7.45 to 7.55. When atelectasis resolves, pleural fluid dissipates during several days.

Congestive Heart Failure

CHF is the most common cause of transudative pleural effusions and a common cause of pleural effusions in ICUs. Pleural effusions due to CHF are associated with increases in pulmonary venous pressure.²⁹ Most patients with subacute or chronic elevation in pulmonary venous pressure (pulmonary capillary wedge pressure of at least 24 mm Hg) have evidence of pleural effusion on US or lateral decubitus radiograph. Isolated increases in systemic venous pressure tend not to produce pleural effusions. Thus, patients with chronic obstructive pulmonary disease (COPD) and cor pulmonale rarely have pleural effusions, and the presence of pleural fluid implies another cause.

Most patients with pleural effusions secondary to CHF have the classic signs and symptoms. The chest radiograph shows cardiomegaly and bilateral small to moderate pleural effusions of similar size (right slightly greater than left). There is usually radiographic evidence of pulmonary congestion, with the severity of pulmonary edema correlating with the presence of pleural effusion.²⁹

The effusion associated with CHF is a transudate, with mesothelial cells and lymphocytes accounting for the majority of the less than 1,000 cells per µL.¹² Acute diuresis can raise the pleural fluid protein and lactate dehydrogenase into the range of an exudate.^30,31 In the patient with secure clinical diagnosis of CHF, observation is appropriate. Thoracentesis should be performed if the patient is febrile, has pleural effusions of disparate size, has a unilateral pleural effusion, does not have cardiomegaly, has pleuritic chest pain, or has a PaO₂ inappropriate for the degree of pulmonary edema.

Treatment consists of decreasing venous hypertension and improving cardiac output with diuretics, digitalis, and afterload reduction. In successfully managed heart failure, the effusions resolve during days to weeks after the pulmonary edema has cleared.

Hepatic Hydrothorax

Pleural effusions occur in approximately 6% of patients with cirrhosis of the liver and clinical ascites. The effusions result from movement of ascitic fluid through congenital or acquired diaphragmatic defects.^32–34

The patient usually has the classic stigmata of cirrhosis and clinically apparent ascites. The usual chest radiograph shows a normal cardiac silhouette and a right-sided pleural effusion, which can vary from small to massive; effusions are less likely isolated to the left pleural space or are bilateral.^32–35 Rarely, a massive pleural effusion may be found without clinical ascites (demonstrated only by US), implying the presence of a large diaphragmatic defect. The pleural fluid is a serous transudate with a low nucleated cell count and a predominance of mononuclear cells, pH greater than 7.40, and a glucose level similar to that of serum.¹² The fluid can be hemorrhagic due to an underlying coagulopathy or rupture of a diaphragmatic bleb. Demonstrating that pleural and ascitic fluids have similar protein and lactate dehydrogenase concentrations substantiates the diagnosis.³² If the diagnosis is problematic, injection of a radionuclide into the ascitic fluid, with detection on chest imaging within 1 to 2 hours, supports a pleuroperitoneal communication through a diaphragmatic defect³⁶; delayed demonstration of the tracer suggests that the pathogenesis of the effusion is via convection through the mesothelium.

Hepatic hydrothorax may be complicated by spontaneous bacterial empyema (SBE), which is analogous to spontaneous bacterial peritonitis. The criteria for diagnosis of SBE are similar to those for the diagnosis of spontaneous bacterial peritonitis. SBE must be considered in the differential diagnosis of the infected cirrhotic patient, even in the absence of clinical ascites.^37,38 The pleural fluid culture and analysis may reveal positive culture, a total neutrophil count of more than 500 cells per µL, and a serum to pleural fluid albumin gradient greater than 1.1. The chest radiograph should not show a pneumonic process. Treatment of SBE is conservative with antibiotics unless purulence is present, in which case tube thoracostomy must be considered.

Treatment of hepatic hydrothorax is directed at resolution of the ascites, using sodium restriction and diuresis. The effusion frequently persists unchanged until all ascites is mobilized. If the patient is acutely dyspneic or in respiratory failure, therapeutic thoracentesis should be done as a temporizing measure. Care should be exercised with paracentesis or thoracentesis, because hypovolemia can occur with rapid evacuation of fluid. Chest tube insertion should be avoided, as it can cause infection of the fluid, and prolonged drainage can lead to protein and lymphocyte depletion and renal failure. Chemical pleurodesis via a chest tube is often unsuccessful owing to rapid movement of ascitic fluid into the pleural space. Treatment options in hepatic hydrothorax refractory to medical management include transjugular intrahepatic portal systemic shunt and video-assisted thoracoscopy to patch the diaphragmatic defect, followed by pleural abrasion or talc poudrage in the properly selected patient.^39,40

Hypoalbuminemia

Many patients admitted to a medical ICU have a chronic illness and associated hypoalbuminemia. When the serum albumin level falls below 1.8 g/dL, pleural effusions may be observed.⁴¹ Because the normal pleural space has an effective lymphatic drainage system, pleural fluid tends to be the last collection of extravascular fluid that occurs in patients with low oncotic pressure. Therefore, it is unusual to find a pleural effusion solely due to hypoalbuminemia in the absence of anasarca. Patients with hypoalbuminemic pleural effusions tend not to have pulmonary symptoms unless there is underlying lung disease, since the effusions are rarely large. Chest radiograph shows small to moderate bilateral effusions and a normal heart size. The pleural fluid is a serous transudate with less than 1000 nucleated cells per µL, predominantly lymphocytes and mesothelial cells. The pleural fluid glucose level is similar to that of serum, and the pH is in the range of 7.45 to 7.55. Diagnosis is presumptive if other causes of transudative effusions can be excluded. The effusions resolve when hypoalbuminemia is corrected.

Iatrogenic Causes

Extravascular migration of a central venous catheter can cause pneumothorax, hemothorax, chylothorax, or a transudative pleural effusion.^42–44 Its incidence is estimated at less than 1% but may be considerably higher. Malposition of the catheter on placement should be suspected if there is absence of blood return or questionable central venous pressure measurements. The immediate postprocedure chest radiograph should be assessed for proper catheter placement; a catheter placed from the right side should not cross the midline. If the catheter is not in the appropriate vessel, phlebitis, perforation of a vein or the heart, or instillation of fluid into the mediastinum or pleural space can occur. In the alert patient, acute infusion of intravenous fluid into the mediastinum usually results in new-onset chest discomfort and dyspnea. Depending on the volume and the rate at which it is introduced into the mediastinum, tachypnea, worsening respiratory status, and cardiac tamponade may ensue. The chest radiograph shows the catheter tip in an abnormal position,^45,46 a widened mediastinum, and evidence of unilateral or bilateral pleural effusions. The effusion can have characteristics similar to those of the infusate (milky if lipid is being given) and may be hemorrhagic and neutrophil-predominant due to trauma and inflammation. The pleural fluid to serum glucose ratio is greater than 1.0 if glucose is being infused.⁴³ The pleural fluid glucose concentration can fall rapidly after glucose infusion into the pleural space, probably explaining the relatively low glucose concentrations in pleural fluid compared to the infusate.⁴⁷ Extravascular migration of a central venous catheter appears to be more common with placement in the external jugular vein, particularly on the left side. Left-sided catheters appear to put the patient at increased risk of perforation because of the horizontal orientation of the left compared to the right brachiocephalic vein. When catheters are introduced from the left side, they should be of adequate length for the tip to rest in the superior vena cava.

Free flow of fluid and proper fluctuation in central venous pressure during the respiratory cycle may not be reliable indicators of intravascular placement. This is probably because intrathoracic pressure changes are transmitted to the mediastinum and thus the venous pressure catheter. Aspiration of blood or retrograde flow of blood when the catheter is lowered below the patient’s heart level should confirm intravascular catheter placement. If blood cannot be aspirated and the effusate is aspirated instead, extravascular migration is assured. The central venous catheter should be removed immediately. If there is a small effusion, observation is warranted. If the effusion is large, causing respiratory distress, or a hemothorax is discovered, thoracentesis or tube thoracostomy should be performed.

Parapneumonic Effusions

Community-acquired or nosocomial pneumonia is common in critically ill patients. The classic presentation is fever, chest pain, leukocytosis, purulent sputum, and a new alveolar infiltrate on chest radiograph. In the elderly debilitated patient, however, many of these findings may not be present. The chest radiograph commonly shows a small to large ipsilateral pleural effusion.^4,8,48–50 When the effusion is free flowing and anechoic on ultrasound, and thoracentesis shows a nonpurulent, polymorphonuclear (PMN) predominant exudate with a pH of 7.30 or greater, it is highly likely that the effusion will resolve during 7 to 14 days without sequelae with antibiotics alone (uncomplicated effusion). If the chest radiograph or CT demonstrates loculation and pus is aspirated, the diagnosis of empyema is established and immediate drainage is needed. In the free-flowing nonpurulent fluid, if Gram stain or culture is positive or pH is less than 7.30, the likelihood of a poor outcome increases, and the pleural space should be drained.

Although a meta-analysis found that low-risk patients with fluid pH between 7.20 and 7.30 may be managed without tube drainage, the patient admitted to the ICU typically cannot be considered low risk, and pH values of less than 7.30 should prompt drainage in most cases.^51–53 Drainage can be accomplished by standard chest tube or small-bore catheter. When loculations occur, pleural space drainage should be accomplished by placement of image-guided tubes or catheters with fibrinolytics or empyectomy and decortication.^54,55 Most thoracic surgeons routinely begin with thoracoscopy and, if not successful, proceed directly to a standard thoracotomy for empyectomy and decortication.^56–59

Pancreatitis

Pleuropulmonary abnormalities are commonly associated with pancreatitis, largely owing to the close proximity of the pancreas to the diaphragm. Approximately half of patients with pancreatitis have an abnormal chest radiograph, with pleural effusions in 3% to 17%.^60,61 Mechanisms that may be involved in the pathogenesis of pancreatic pleural effusion include direct contact of pancreatic enzymes with the diaphragm (sympathetic effusion), transfer of ascitic fluid via diaphragmatic defects, communication of a fistulous tract between a pseudocyst and the pleural space, and retroperitoneal movement of fluid into the mediastinum with mediastinitis or rupture into the pleural space.^60,62 Ascitic amylase moves into the pleural space via the previously mentioned mechanisms. The pleural fluid/serum amylase ratio is greater than one in pancreatitis because of slower lymphatic clearance from the pleural space compared with more rapid renal clearance.

The effusion associated with acute pancreatitis is usually small and left-sided (60%) but may be isolated to the right side (30%) or be bilateral (10%).⁶⁰ The patient usually presents with abdominal symptoms of acute pancreatitis. Diagnosis is confirmed by an elevated pleural fluid amylase concentration greater than that in serum. A normal pleural fluid amylase may be found early in acute pancreatitis but increases on serial measurements. The fluid is a polymorphonuclear (PMN)-predominant exudate with glucose values approximating those of serum. Leukocyte counts may reach 50,000 cells per µL. The pleural fluid pH is usually 7.30 to 7.35.

No specific treatment is necessary for the pleural effusion of acute pancreatitis; the effusion resolves as the pancreatic inflammation subsides. Drainage of the pleural space does not appear to affect residual pleural damage. If the pleural effusion does not resolve in 2 to 3 weeks, pancreatic abscess or pseudocyst should be excluded.

Pulmonary Embolism

The presence of a unilateral pleural effusion may suggest pulmonary embolism or obscure the diagnosis by directing attention to a primary lung or cardiac process. Pleural effusions occur in approximately 40% of patients with pulmonary embolism.⁶³ These effusions result from several different mechanisms including increased pleural capillary permeability, imbalance in microvascular and pleural space hydrostatic pressures, and pleuropulmonary hemorrhage.^63,64 Ischemia from pulmonary vascular obstruction, in addition to release of inflammatory mediators from platelet-rich thrombi, can cause capillary leak into the lung and, subsequently, the pleural space, explaining the usual finding of an exudative effusion. Transudates, described in approximately 20% of patients with pulmonary embolism, result from atelectasis.⁶⁴

With pulmonary infarction, necrosis and hemorrhage into the lung and pleural space may result. More than 80% of patients with infarction have bloody pleural effusions, but more than 35% of patients with pulmonary embolism without radiographic infarction also have hemorrhagic fluid.⁶³ The presence of a pleural effusion does not alter the signs or symptoms in patients with pulmonary embolism. Chest pain, usually pleuritic, occurs in most patients with pleural effusions complicating pulmonary embolism and is invariably ipsilateral.⁶³ The chest radiograph virtually always shows a unilateral effusion that occupies less than one-third of the hemithorax.⁶³ An associated pulmonary infiltrate (infarction) is seen in approximately half of patients with pulmonary embolism and effusion.

Pleural fluid analysis is variable and nondiagnostic.⁶⁴ The pleural fluid is hemorrhagic in two-thirds of patients, but the number of red blood cells exceeds 100,000 per µL in less than 20%.⁶⁴ The nucleated cell count ranges from less than 100 (atelectatic transudates) to greater than 50,000 per µL (pulmonary infarction).⁶⁴ There is a predominance of PMNs when a thoracentesis is performed near the time of the acute injury and of lymphocytes with later thoracentesis. The effusion due to pulmonary embolism is usually (92%) apparent on the initial chest radiograph and reaches a maximum volume during the first 72 hours.⁶³ Patients with pleural effusions that progress with therapy should be evaluated for recurrent embolism, hemothorax secondary to anticoagulation, an infected infarction, or an alternate diagnosis. When consolidation is absent on chest radiograph, effusions usually resolve in 7 to 10 days; with consolidation, the resolution time is 2 to 3 weeks.⁶⁴

The association of pleural effusion with pulmonary embolism does not alter therapy. Furthermore, the presence of a bloody effusion is not a contraindication to full-dose anticoagulation because hemothorax is a rare complication of heparin therapy.⁶⁵ An enlarging pleural effusion on therapy necessitates thoracentesis to exclude hemothorax, empyema, or another cause. Active pleural space hemorrhage necessitates discontinuation of anticoagulation, tube thoracostomy, and placement of a vena cava filter.

Post–Cardiac Injury Syndrome

Post–cardiac injury syndrome (PCIS) is characterized by fever, pleuropericarditis, and parenchymal infiltrates 3 weeks (2 to 86 days) after injury to the myocardium or pericardium.^66–68 PCIS has been described after myocardial infarction, cardiac surgery, blunt chest trauma, percutaneous left ventricular puncture, and pacemaker implantation. The incidence after myocardial infarction has been estimated at up to 4% of cases,⁶⁶ but with more extensive myocardial and pericardial involvement, it may be higher. It occurs with greater frequency (up to 30%) after cardiac surgery.⁶⁹ The pathogenesis of PCIS remains obscure; an autoimmune response in patients with myocardial or pericardial injury and possibly concomitant viral illness has been speculated.⁷⁰

The diagnosis of PCIS remains one of exclusion, for no specific criteria exist. It is important to diagnose or exclude PCIS presumptively. Failure to diagnose accurately could lead to iatrogenic complications from inappropriate therapy, such as cardiac tamponade from anticoagulation for presumed pulmonary embolism and adverse effects related to antimicrobial therapy for presumed pneumonia.

Pleuropulmonary manifestations are the hallmark of PCIS. The most common presenting symptoms are pleuritic chest pain, found in virtually all patients, and fever, pericardial rub, dyspnea, and rales, which occur in half of patients.⁶⁸ Rarely, hemoptysis occurs, an important differential point when pulmonary embolism with infarction is in the differential diagnosis. Fifty percent of patients have leukocytosis, and almost all have an elevated erythrocyte sedimentation rate (average, 62 mm per hour).⁶⁸

The chest radiograph is abnormal in virtually all patients, with the most common abnormality being left-sided and bilateral pleural effusions; a unilateral right effusion is unusual.⁶⁸ Pulmonary infiltrates are present in 75% of patients and are most commonly seen in the left lower lobe.⁶⁶ The pleural fluid is a serosanguineous or bloody exudate with a glucose level above 60 mg per dL and pleural fluid pH above 7.30. Nucleated cell counts range from 500 to 39,000 per µL, with a predominance of PMNs early in the course.⁶⁸ Pericardial fluid on echocardiogram is an important finding suggesting PCIS. The pleural fluid characteristics should help differentiate PCIS from a parapneumonic effusion and CHF, but do not exclude pulmonary embolism.

PCIS is usually self-limited and may not require therapy if symptoms are trivial. It usually responds to aspirin or nonsteroidal antiinflammatory agents, but some patients require corticosteroid therapy for resolution. In those who respond, the pleural effusion resolves within 1 to 3 weeks.

Esophageal Sclerotherapy

Pleural effusions are found in approximately 50% of patients 48 to 72 hours after esophageal sclerotherapy with sodium morrhuate and in 19% of patients after absolute alcohol sclerotherapy.^71–73 Effusions may be unilateral or bilateral, with no predilection for side. Effusion appears more likely with larger total volumes of sclerosant injected and larger volume injected per site.^71–72 The effusions tend to be small, serous exudates with variable nucleated (90 to 38,000 per µL) and red cell counts (126 to 160,000 per µL) and glucose concentration similar to that of serum.⁷¹ These effusions probably result from an intensive inflammatory reaction after extravasation of the sclerosant into the esophageal mucosa, resulting in mediastinal and pleural inflammation. The effusion not associated with fever, chest pain, or evidence of perforation is of little consequence, requires no specific therapy, and resolves during several days to weeks.^71,72 However, late perforation may evolve in patients with apparent innocuous effusions. In patients with symptomatic effusions for 24 to 48 hours, diagnostic thoracentesis should be done and an esophagram considered.

Acute Respiratory Distress Syndrome

The presence of pleural effusions in ARDS has not been well appreciated. In a retrospective study of 25 patients with ARDS, a 36% incidence of pleural effusions was found, a percentage similar to that found with hydrostatic pulmonary edema.⁷⁴ All patients had extensive alveolar pulmonary edema and endotracheal tube fluid that was compatible with increased permeability edema. Several experimental models of increased permeability pulmonary edema, including α-naphthyl thiourea, oleic acid, and ethchlorvynol, have been shown to produce pleural effusions. In the oleic acid and ethchlorvynol models, the development of pleural effusions lagged behind interstitial and alveolar edema by several hours. In the oleic acid model, 35% of the excess lung water collected in the pleural spaces. It appears that the pleura act as a reservoir for excess lung water in increased permeability and hydrostatic pulmonary edema. These effusions tend to be underdiagnosed clinically because the patient has bilateral alveolar infiltrates and the radiograph is taken with the patient in a supine position. Experimentally, the effusion is serous to serosanguineous, with a predominance of PMNs. These effusions usually require no specific therapy and resolve as ARDS resolves. However, in a series of positive end-expiratory pressure (PEEP)-unresponsive patients with ARDS, drainage of pleural effusion via tube thoracostomy has been shown to result in improved oxygenation.⁷⁵ The decision to proceed to pleural space drainage in ARDS should be approached on a case-by-case basis and is not generally recommended.

Spontaneous Esophageal Rupture

Esophageal rupture, a potentially life-threatening event, requires immediate diagnosis and therapy. The history in spontaneous esophageal rupture is usually severe retching or vomiting or a conscious effort to resist vomiting. In some patients, the perforation may be silent. Early recognition of spontaneous rupture depends on interpretation of the chest radiograph. Several factors influence chest radiograph findings: the time between perforation and chest radiograph examination, site of perforation, and mediastinal pleural integrity.⁷⁶ A chest radiograph taken within minutes of the acute injury is usually unremarkable. Mediastinal emphysema probably requires at least 1 to 2 hours to be demonstrated radiographically and is present in less than half of patients; mediastinal widening may take several hours.⁷⁷ Pneumothorax, present in 75% of patients with spontaneous rupture, indicates violation of the mediastinal pleura; 70% of pneumothoraces are on the left, 20% are on the right, and 10% are bilateral.⁷⁷ Mediastinal air is seen early if pleural integrity is maintained, whereas pleural effusion secondary to mediastinitis tends to occur later. Pleural fluid, with or without associated pneumothorax, occurs in 75% of patients. A presumptive diagnosis should immediately be confirmed radiographically. Esophagrams are positive in approximately 90% of patients.⁷⁸ In the upright patient, rapid passage of the contrast material may not demonstrate a small rent; therefore, the study should be done with the patient in the appropriate lateral decubitus position.⁷⁹

Pleural fluid findings depend on the degree of perforation and the timing of thoracentesis from injury. Early thoracentesis without mediastinal perforation shows a sterile, serous exudate with a predominance of PMNs, a pleural fluid amylase less than serum, and pH greater than 7.30.⁸⁰ Once the mediastinal pleura tears, amylase of salivary origin appears in the fluid in high concentration.⁸¹ As the pleural space is seeded with anaerobic organisms from the mouth, the pH falls rapidly and progressively to approach 6.0.^80,82 Other pleural fluid findings suggestive of esophageal rupture include the presence of squamous epithelial cells and food particles. The diagnosis of spontaneous esophageal rupture dictates immediate operative intervention. If diagnosed and treated appropriately within the first 24 hours with primary closure and drainage, survival is greater than 90%.⁷⁷ Delay from the time of initial symptoms to diagnosis results in a reduced survival with any form of therapy.

Hemothorax

Hemothorax (blood in the pleural space) should be differentiated from a hemorrhagic pleural effusion, because the latter can be the result of only a few drops of blood in pleural fluid. An arbitrary but practical definition of a hemothorax with regard to therapy is a pleural fluid/blood hematocrit ratio greater than 30%. The majority of hemothoraces result from penetrating or blunt chest trauma.⁸³ Hemothorax can also result from invasive procedures such as placement of central venous catheters, thoracentesis, and pleural biopsy, as well as from pulmonary infarction, malignancy, or ruptured aortic aneurysm. Bleeding can occur from vessels of the chest wall, lung, diaphragm, or mediastinum. Blood that enters the pleural space clots, rapidly undergoes fibrinolysis, and becomes defibrinogenated; thus, it rarely causes significant pleural fibrosis.

Hemothorax should be suspected in any patient with blunt or penetrating chest trauma. If a pleural effusion is found on the admitting chest radiograph, thoracentesis should be performed immediately and the hematocrit measured on the fluid. The hemothorax may not be apparent on the initial chest radiograph, which may be due to the supine position of the patient. Because bleeding may be slow and not appear for several hours, it is imperative that serial radiographs be obtained in these patients. The incidence of concomitant pneumothorax is high (approximately 60%).⁸³ Patients with traumatic hemothorax should be treated with immediate tube thoracostomy.^83–85 Large-diameter chest tube drainage evacuates the pleural space, may tamponade the bleeding (especially if the origin is from a pleural laceration), allows monitoring of the bleeding, and decreases the likelihood of subsequent fibrothorax.^85,86 If bleeding continues without signs of slowing, thoracotomy should be performed, depending on the individual circumstance.⁸⁵ Pleural effusions occasionally occur after removal of the chest tube from traumatic hemothoraces.⁸⁷ A diagnostic thoracentesis is indicated to exclude empyema. If empyema is excluded, the pleural effusion usually resolves without specific treatment and without residual pleural fibrosis.

Hemothorax is a rare complication of anticoagulation and has been reported in patients receiving heparin and warfarin. Coagulation studies are usually within the therapeutic range. The hemothorax tends to occur on the side of the pulmonary embolism. Anticoagulation should be discontinued immediately, a chest tube inserted to evacuate the blood, and a vena cava filter considered.

Coronary Artery Bypass Surgery

A small, left pleural effusion is virtually always present after coronary artery bypass surgery. This is associated with left lower lobe atelectasis and elevation of the left hemidiaphragm on chest radiograph. Left diaphragm dysfunction is secondary to intraoperative phrenic nerve injury from cold cardioplegia, stretch injury, or surgical trauma.^88–90 The larger and grossly bloody effusions tend to be associated with internal mammary artery grafting, which causes marked exudation from the bed where the internal mammary artery was harvested.⁹¹

The pleural fluid is a hemorrhagic exudate with a low nucleated cell count, a glucose level similar to that of serum, and a pH greater than 7.40. Rarely, a loculated hemothorax may develop with trapped lung, resulting in clinically significant restriction.⁹² If there is a large effusion that qualifies as a hemothorax (see previous section), the fluid should be drained by tube thoracostomy. It is also prudent to drain moderately large, bloody effusions to avoid later necessity for decortication.

Abdominal Surgery

Approximately half of the patients who undergo abdominal surgery develop small unilateral or bilateral pleural effusions within 48 to 72 hours of surgery.^27,28 The incidence is higher after upper abdominal surgery, in patients with postoperative atelectasis, and in patients who have free ascitic fluid at the time of surgery.²⁷ Larger left-sided pleural effusions are common after splenectomy.²⁷ The effusion is usually an exudate with less than 10,000 nucleated cells per µL. The glucose level is similar to that of serum, and pH is usually greater than 7.40.²⁷ The effusion usually is related to diaphragmatic irritation or atelectasis. Small effusions generally do not require diagnostic thoracentesis, are of no clinical significance, and resolve spontaneously. Pleural effusion from subphrenic abscess or pulmonary embolism is unlikely to occur within 2 to 3 days of surgery. The only indication for diagnostic thoracentesis would be to exclude infection if the effusion is relatively large or loculated.

Chylothorax

Trauma from surgery accounts for approximately 25% of cases of chylothorax, second only to lymphoma. Most series estimate an incidence of chylothorax of less than 1% after thoracic surgery,⁹³ but a 3% incidence has been reported after esophagectomy.⁹⁴ Virtually all intrathoracic procedures, including lobectomy, pneumonectomy, and coronary artery bypass grafting, have been reported to cause chylothorax. Other iatrogenic chylothoraces can be caused by complications of prolonged central vein catheterization. Nonsurgical trauma, such as penetrating and nonpenetrating neck, thoracic, and upper abdominal injuries, also has been associated with chylothorax.

When the thoracic duct is torn by stretching during surgery, chyle leaks into the mediastinum and subsequently ruptures through the mediastinal pleura. In the nonsurgical setting, penetrating injuries and fractures may directly tear the thoracic duct. Chylothorax from a central venous catheter usually involves venous thrombosis. Other rare causes of chylothorax include sclerotherapy of esophageal varices and translumbar aortography.^95–97

The patient may be asymptomatic if the effusion is small and unilateral, or may present with dyspnea with a large unilateral effusion or bilateral effusions. The pleural fluid is usually milky, but 12% can be serous or serosanguineous,⁹⁸ with less than 7000 nucleated cells per µL, virtually all lymphocytes. The pleural fluid pH is alkaline (7.40–7.80), and triglyceride levels are greater than plasma levels. Finding a pleural fluid triglyceride concentration of greater than 110 mg/dL makes the diagnosis of chylothorax highly likely.⁹⁸ If the triglyceride level is less than 50 mg/dL, chylothorax is highly unlikely. Triglyceride levels of 50 to 110 mg/dL indicate the need for lipoprotein electrophoresis⁹⁸; the presence of chylomicrons confirms a chylothorax. The thoracic duct defect after trauma usually closes spontaneously within 10 to 14 days, with chest tube drainage as well as bed rest and total parenteral nutrition to minimize chyle formation. A pleuroperitoneal shunt relieves dyspnea, recirculates chyle, and prevents malnutrition and immunocompromise.

Duropleural Fistula

Disruption of the dura and parietal pleura by surgical and nonsurgical trauma may result in a duropleural fistula with subsequent development of a pleural effusion.^99–102 The pleural fluid characteristics depend on the severity of the trauma and the delay between the trauma and the pleural fluid analysis. Pleural fluid due to a chronic duropleural fistula is usually a colorless transudate with low mononuclear cell count; a duropleural fistula associated with recent trauma may be a transudate or an exudate.^101,102 The diagnosis may even be delayed because of a coexisting process such as hemothorax. The diagnosis of duropleural fistula is established by the detection of β₂-transferrin in the pleural fluid.¹⁰³ Confirmation of the fistula by conventional or radionuclide myelography is recommended if surgical management is contemplated.

Definition and Classification

Pneumothorax refers to air in the pleural space. Free air may also be found in the adventitial planes of the lung or the mediastinum (pneumomediastinum). Spontaneous pneumothorax occurs without an obvious cause as a consequence of the natural course of a disease process. Primary spontaneous pneumothorax occurs without clinical findings of lung disease. Secondary spontaneous pneumothorax occurs as a consequence of clinically manifest lung disease, the most common being COPD. Traumatic pneumothorax results from penetrating or blunt chest injury. Iatrogenic pneumothorax occurs as an inadvertent consequence of diagnostic or therapeutic procedures.

Pathophysiology

Pressure in the pleural space is subatmospheric throughout the normal respiratory cycle, averaging approximately −9 mm Hg during inspiration and −5 mm Hg during expiration. Owing to airway resistance, pressure in the airways is positive during expiration (+3 mm Hg) and negative (−2 mm Hg) during inspiration. In normal breathing, airway pressure is greater than pleural pressure throughout the respiratory cycle. Airway pressure may be increased markedly with coughing or strenuous exercise; however, pleural pressure rises concomitantly so that the transpulmonary pressure gradient is usually not substantially changed.

When there are rapid fluctuations in intrathoracic pressure, however, a large transpulmonary pressure gradient occurs transiently. Bronchial and bronchiolar obstruction, resulting in air trapping, can significantly increase the transpulmonary pressure gradient. The alveolar walls and visceral pleura maintain the pressure gradient between the airways and pleural space. When the pressure gradient is transiently increased, alveolar rupture may occur; air enters the interstitial tissues of the lung and may enter the pleural space, resulting in a pneumothorax. If the visceral pleura remain intact, the interstitial air moves toward the hilum, resulting in pneumomediastinum.^104–105 Because mean pressure within the mediastinum is always less than in the periphery of the lung, air moves proximally along the bronchovascular sheaths to the hilum and mediastinal soft tissues.

The development of pneumomediastinum after alveolar rupture requires continual cyclic respiratory efforts, which result in slow movement of air from the ruptured alveolus along a pressure gradient to the mediastinum.¹⁰⁵ Mediastinal air may decompress into the cervical and subcutaneous tissues or the retroperitoneum. With abrupt rise in mediastinal pressure or insufficient decompression to subcutaneous tissue, the mediastinal pleura may rupture, causing pneumothorax. Inadequate decompression of the mediastinum, rather than direct rupture of subpleural blebs into the pleural space, may be the major cause of pneumothorax.¹⁰⁴

When pneumothorax occurs, the elasticity of the lung causes it to collapse. Lung collapse continues until the pleural defect seals or pleural and alveolar pressures equalize. When a ball-valve effect occurs at the site of communication between the pleural space and the alveolus, permitting only egress of air from the lung, there is a progressive accumulation of air within the pleural space, which can result in markedly increased positive pleural pressure, producing a tension pneumothorax. Tension pneumothorax compresses mediastinal structures, resulting in impaired venous return to the heart, decreased cardiac output, and at times, fatal cardiovascular collapse.^106–107 Rarely, tension along the bronchovascular sheaths and in the mediastinum can cause collapse of the pulmonary arteries and veins, resulting in cardiovascular collapse.¹⁰⁴

Patients with primary spontaneous pneumothorax have a decrease in vital capacity and an increase in the P(A-a)O₂ gradient; they usually present with hypoxemia due predominantly to the development of an intrapulmonary shunt and areas of low ventilation/perfusion in the atelectatic lung.^108,109 Hypercapnia does not occur because there is adequate function in the uninvolved lung to maintain necessary alveolar ventilation. Patients with secondary spontaneous pneumothorax, in contrast, commonly develop hypercapnia because the gas exchange abnormality caused by the pneumothorax is superimposed on lungs with preexisting abnormal pulmonary gas exchange.

Pneumothorax in the Intensive Care Unit

Patients with secondary spontaneous pneumothorax may be admitted to an ICU because they develop severe hypoxemic and, at times, hypercapnic respiratory failure. Patients with primary spontaneous pneumothorax rarely require ICU admission because the contralateral lung can maintain necessary alveolar ventilation, and the hypoxemia can be managed with supplemental oxygen. The most common causes of pneumothoraces in ICU patients are invasive procedures and barotrauma.

Definition and Causes

Communication between the bronchial tree and the pleural space is a dreaded complication of mechanical ventilation.^131,132 There are three presentations of bronchopleural fistula (BPF): (1) failure to reinflate the lung despite chest tube drainage, or continued air leak after evacuation of pneumothorax in the setting of chest trauma; (2) complication of a diagnostic or therapeutic procedure such as thoracic surgery; and (3) complication of mechanical ventilation, usually for ARDS.¹⁰⁶ In ARDS, often a pneumothorax occurs under tension and is later associated with empyema, multiple sites of leakage, and a poor prognosis. A large air leak through a BPF can result in failure of lung reexpansion, loss of a significant amount of each delivered tidal volume, loss of the ability to apply PEEP, inappropriate cycling of the ventilator,¹³³ and inability to maintain alveolar ventilation (Table 65-3).

TABLE 65-3 Consequences of a Large Bronchopleural Fistula

If there is a continued air leak for longer than 24 hours after the development of pneumothorax, then a BPF exists. The main factors that perpetuate BPF are high airway pressures that increase the leak during inspiration, increased mean intrathoracic pressures throughout the respiratory cycle (PEEP, inflation hold, high inspiratory/expiratory ratio) that increase the leak throughout the breath, and high negative suction. In severe ARDS, all these factors are present because they usually are necessary to support gas exchange and lung inflation.

Management

Given the frequency of barotrauma in BPF in mechanically ventilated patients, intensivists are called to give advice on the management of these difficult patients. Definitive therapy of BPF frequently involves invasive surgical approaches that include thoracoplasty, mobilization of the pectoralis or intercostal muscles, bronchial stump stapling, and decortication.^134–139 Although some of these techniques are still used today, there is a trend toward more conservative management of acute and chronic BPF, using innovations of standard techniques and new modalities that include chest tube management, drainage systems, ventilatory support, and definitive nonoperative therapy (Table 65-4). Even insertion of an endobronchial valve designed for the treatment of emphysema may be considered in selected patients.¹⁴⁰ Nonoperative therapy provides an alternative to the surgical approaches in patients who are poor operative candidates. Each patient with a BPF is unique and requires individual management based on the specific clinical setting. Attention to the basics of medical care of patients with BPF should not be neglected in the face of the potentially dramatic events related to the BPF. Nutritional status must be maintained, appropriate antibiotics used for the infected pleural space, and the space adequately drained.

TABLE 65-4 Management of Bronchopleural Fistula in Patients Requiring Mechanical Ventilation

Chest Tubes

The initial therapy for pneumothorax in a patient on mechanical ventilation is placement of a chest tube in an attempt to reexpand the lung. The chest tube is initially necessary, can be detrimental later, and may play a role more important than that of a passive conduit. Air leaks in the setting of BPF range from less than 1 to 16 L per minute¹⁴¹; therefore, a chest tube that permits prompt and efficient drainage of this level of airflow is required. Gas moves through a tube in a laminar fashion and is governed by Poiseuille’s law (v = [π r⁴ P/8lV]t). In the clinical setting, the gas moving through a chest tube is moist; therefore, it is subject to turbulent flow and governed by the Fanning equation (v = [π r² r⁵ P/fl]).^141–143 Therefore, both the length (l) and, even more so, the radius (r) are important when choosing a chest tube and connecting tubing to evacuate a BPF adequately (as flow varies exponentially to the fifth power of the radius of the tube). The smallest internal diameter that allows a maximum flow of 15.1 L per minute at −10 cm H₂O suction is 6 mm^141,142 (a 32 French chest tube has an internal diameter of 9 mm). A chest tube with a diameter adequate to convey the potentially large airflow of the BPF must be considered. A chest tube with too small a diameter can lead to lung collapse and tension pneumothorax in the setting of a mobile mediastinum.

Not only can the chest tube be used to drain pleural air, it can also be used to limit the air leak in certain situations. One modality is the application of intrapleural pressure equivalent to the level of PEEP during the expiratory phase of ventilation.^144–146 With positive intrapleural pressure applied through the chest tube, the air leak persists during the inspiratory phase of ventilation but decreases during expiration, allowing maintenance of PEEP in patients in whom it is necessary for adequate oxygenation. Synchronized closure of the chest tube during the inspiratory phase has also been used to control the air leak.^147,148 A combination of these techniques has been suggested for patients with significant BPF air leaks during both the inspiratory and expiratory phases of mechanical ventilation.^131,148 These techniques pose potential hazards, including increased pneumothorax and tension pneumothorax,^131,147 necessitating extremely close patient monitoring when such manipulations are used.

Instillation of chemical agents through the chest tube may potentially help close the BPF if the anatomic defect is small and single, but it is unlikely to be successful if the fistula is large or if there are multiple fistulas. Various agents have been successful in preventing recurrent pneumothoraces in patients who are not on mechanical ventilation,^149–152 but BPF in the setting of mechanical ventilation is a different situation. One study compared the recurrence of pneumothorax in 39 patients with BPF randomized to intrapleural tetracycline or placebo groups.¹⁵³ There was no evidence that intrapleural tetracycline facilitated closure of the BPF. No adverse effects were encountered from the instillation of tetracycline in patients with persistent air leaks.

The chest tube may be associated with adverse effects in patients with BPF. The gas escaping through the chest tube represents part of the minute ventilation delivered to the patient and makes maintenance of an effective tidal volume problematic.^154,155 Maintenance of a specific level of ventilation is not only affected by the amount of gas escaping through the fistula. The escaping gas does not passively flow from the airways into the BPF but is involved in physiologic gas exchange.^154,155 Approximately 25% of the minute ventilation has been found to escape via the BPF in patients with ARDS, with more than 20% of CO₂ excretion occurring by this route in half of the patients.¹⁵⁵ The role of the BPF in active CO₂ exchange is complex; proposed mechanisms include drainage of gas from alveoli in the area of the BPF and removal of gas from remote alveolar areas by pressure gradients created by the BPF.¹⁵⁶

Carbon dioxide excretion and a reduction in minute ventilation occur to a lesser extent in BPF trauma victims.¹⁵⁴ In these patients, variable CO₂ excretion and loss of minute ventilation were dynamic and dependent on the level of chest tube suction. The difference between trauma and ARDS patients may have been due to the variability of lung compliance and the use of different ventilators.¹⁵⁵ Also, BPF may affect oxygen use, which generally decreases the use of inspired oxygen before it escapes through the fistula.¹⁵⁴ This relationship is variable but requires consideration in patients with oxygenation problems.

Negative pressure applied to the chest tube may be transmitted beyond the pleural space and into the airways, creating inappropriate cycling of the ventilator.^133,156 The increased flow through a BPF can occur with increased negative pleural pressure and may interfere with closure and healing of the fistulous site.¹³¹ Therefore, the least amount of chest tube suction that keeps the lung inflated should be maintained in patients with BPF. The chest tube is a potential source of infection, both at the insertion site and within the pleural space.

Drainage Systems

As with the chest tube, the resistance of flow of gases is a consideration in the choice of the drainage system for the patient with a BPF.¹⁴¹ The size of the air leak and the flow the drainage system can accommodate are necessary considerations. In an experimental model of BPF that simulated the type of air leak seen clinically (mean maximal flow, 5 L per minute), four pleural drainage units (PDU)—Emerson Post-Operative Pump (Emerson), Pleur-Evac (Teleflex Medical), Sentinel Seal (Tyco), and Thora-Klex (Avilor)—were tested at water seal, −20 cm H₂O, and −40 cm H₂O suction.¹⁴¹ Compared to the water seal, −20 cm H₂O suction significantly increased the ability of all four PDUs to evacuate air via the chest tube, but an increase in suction to −40 cm H₂O did not significantly alter flow. When the air leak reached 4 to 5 L per minute, use of the Thora-Klex or Sentinel Seal became clinically impractical. The Pleur-Evac can handle flow rates up to 34 L per minute, but its use with rates over 28 L per minute is impractical owing to intense bubbling in the suction control chamber.¹¹² Air leaks of this magnitude are infrequent clinically in BPF and are likely to be seen only with major airway disruption or diffuse parenchymal leak secondary to ARDS with severe barotraumas.¹⁵⁶ In the latter situations, the low-pressure, high-volume Emerson suction pump remains the only PDU capable of handling the air leak.¹⁴¹ The choice of PDU should be influenced by its physiologic capabilities and the type of BPF air leak encountered.

Mechanical Ventilation

Flexible Bronchoscopy

The flexible bronchoscope can be valuable in the diagnosis of BPF.^167–169 Bronchoscopic therapy of BPF has several potential advantages, including low cost, shortened hospital stay, and relative noninvasiveness, particularly in poor operative candidates^167–169 (see Chapter 9). Proximal fistulas, such as those associated with lobectomy or pneumonectomy or stump breakdown, can be directly visualized through the bronchoscope. Distal fistulas cannot be visualized directly and require bronchoscopic passage of an occluding balloon to localize the bronchial segment leading to the fistula.^170–172 A balloon is systematically passed through the working channel of the bronchoscope and into each bronchial segment in question and then inflated; a reduction in air leak indicates localization of a bronchial segment communicating with the BPF. Once the fistula has been localized, various materials can be passed through a catheter in the working channel of the bronchoscope and into the area of the fistula.^167–176 Direct application of a sealant through the working-channel catheter onto the fistula site is the method generally used for directly visualized proximal fistulas. For distal fistulas, a multiple-lumen Swan-Ganz catheter has been used to localize the BPF and pass the occluding material of choice.¹⁷⁰

Several agents have been used through the bronchoscope in an attempt to occlude BPF. These include fibrin agents,^169–170 cyanoacrylate-based agents,¹⁶⁷ absorbable gelatin sponge (Gelfoam [Pfizer]), blood-tetracycline,¹⁷¹ and lead shot.¹⁷² The reports on all of these agents are limited to only a few patients. The cyanoacrylate-based and fibrin agents have received the most attention but still have had less than 20 total cases reported. These patients have had at least a 50% reduction of fistula flow, and most had closure of the fistula subsequent to sealant application, although multiple applications were necessary in some patients. These agents appear to work in two phases, with the agent initially sealing the leak by acting as a plug and subsequently inducing an inflammatory process with fibrosis and mucosal proliferation permanently sealing the area.¹⁶⁷ They are not useful with large proximal tracheal or bronchial ruptures or multiple distal parenchymal defects.¹⁷⁰