60 - Tuberculous and Fungal Infections of the Pleura
Editors: Shields, Thomas W.; LoCicero, Joseph; Ponn, Ronald B.; Rusch, Valerie W.
Title: General Thoracic Surgery, 6th Edition
Copyright 2005 Lippincott Williams & Wilkins
> Table of Contents > Volume I - The Lung, Pleura, Diaphragm, and Chest Wall > Section XII - Thoracic Trauma > Chapter 72 - Acute Respiratory Distress Syndrome
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Chapter 72
Acute Respiratory Distress Syndrome
Joseph LoCicero III
Originally described by Ashbaugh and associates in 1967, adult respiratory distress syndrome (ARDS) is a condition of noncardiogenic pulmonary dysfunction following some type of physiologic insult and is characterized by refractory hypoxemia, decreased pulmonary compliance, and diffuse interstitial infiltrates on chest radiography. Our understanding and management of this devastating syndrome have changed in the last 40 years. Many studies performed during that time have claimed varying success in changing the usual dismal outcomes. One of the reasons for discrepancy among studies was the lack of a clear definition of the syndrome. The American European Consensus Conference (AECC) on ARDS reported by Bernard and associates (1994a, 1994b) took on the task of redefining the syndrome. They accommodated by addressing a broader spectrum of pulmonary dysfunction and defining two clinical entities: acute lung injury and ARDS (Table 72-1).
Acute lung injury is defined by the following:
Acute onset
Pao2/Fio2 less than 300 mm Hg regardless of the level of positive end-expiratory pressure (PEEP)
Bilateral infiltrates on frontal chest radiography
Pulmonary artery occlusion pressure less than 18 mm Hg (if measured) or no evidence of left atrial hypertension
ARDS is defined by the following:
Acute onset
Pao2/Fio2 less than 200 mm Hg regardless of the level of PEEP
Bilateral infiltrates on frontal chest radiography
Pulmonary artery occlusion pressure less than 18 mm Hg (if measured) or no evidence of left atrial hypertension
With the adoption of these definitions, a uniform standard is now present to characterize the natural history, pathogenesis, and management outcomes of ARDS. A prospective comparison by Moss and associates (1995a) of the definition proposed by the AECC and two alternative definitions, the Lung Injury Severity Score (LISS), which is defined later, and the Modified Lung Injury Severity Score, found that similar patients were identified by all three definitions. The LISS and the AECC definition were compared subsequently in a series of patients by a Canadian consortium reported by Meade and colleagues (2001) and showed reasonable correlation.
Although ARDS is a relatively common clinical entity, its prevalence is not well established. It was estimated by Bernard and associates (1994b) that 100,000 to 150,000 patients develop ARDS in the United States per year (approximately 40 per 100,000 patients). Murray and colleagues in 1977 estimated that the rate of ARDS ranges from 5 to 50 cases per 100,000 patients. In 2003, the ARDS Network did an intensive review of the registry and of data from the American Hospital Association to estimate the incidence of acute lung injury in the United States; many such cases go on to ARDS. The findings reported by Goss and colleagues (2003) were that the incidence is much higher than previously thought. Acute lung injury currently occurs at a rate of 64.5 cases per 100,000 patients, or 64.5 cases per 105 patient years.
BRIEF HISTORY
Although references to an ARDS-like pulmonary dysfunction were made as early as World War I, it was not until 1967 that Ashbaugh and associates definitively described an ARDS in adults. Petty and Ashbaugh (1971) later named the dysfunction adult respiratory distress syndrome. In the 1960s and early 1970s, significant advances in resuscitation and ventilatory support led to a greater recognition of respiratory failure in patients with sepsis, shock, aspiration pneumonia, pancreatitis, and severe traumatic injuries. A number of terms, including shock lung, wet lung, Da Nang lung, postperfusion lung and traumatic wet lung, were used to describe the pulmonary dysfunction that developed in these patients.
ARDS, however, is not a new entity. In 1925, Osler observed that uncontrolled septicemia leads to a frothy pulmonary
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edema that resembles serum, not the sanguinous transudative edema fluid seen in dropsy or congestive heart failure. Early observations of the association between pulmonary dysfunction and trauma were made by Burford and Burbank in 1945 when they reported acute respiratory failure ( traumatic wet lung ) after thoracic injury and noted its association with increased interstitial and intraalveolar fluid. Mallory and colleagues (1950) subsequently described some of the classic features of pulmonary pathology in necropsy cases of traumatic shock from World War II. In 1950, Jenkins and associates used the term congestive atelectasis to refer to the respiratory failure seen in patients with sepsis, trauma, and peritonitis.
Table 72-1. Acute Lung Injury and Acute Respiratory Distress Syndrome | ||||||||||||||||||||
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Ashbaugh and co-workers provided the first detailed clinical and histopathologic description of ARDS in 1967. They reported findings in 12 patients with respiratory insufficiency after trauma, severe viral infection, acute pancreatitis, and shock. Histopathologic features of this syndrome included hemorrhagic interstitial and intraalveolar edema, atelectasis, hyaline membrane formation, and the presence of numerous alveolar macrophages. They further noted that the characteristics of the syndrome described resembled those of fat embolism syndrome, respiratory distress syndrome in infants, congestive atelectasis, and postperfusion lung. These seminal observations indicated that the respiratory dysfunction seen in ARDS was associated with an acute inflammatory response in the lung. It has since become apparent, as noted by Montgomery (1985) and Carrico (1986) and their associates, that uncontrolled systemic inflammation, whether elicited by sterile or infectious insult, is capable of producing acute dysfunction in other organ systems.
RISK FACTORS AND BIOCHEMICAL MARKERS
Clinical risk factors, physiologic responses, and biochemical markers have been used to identify patients at risk for developing ARDS. It has long been recognized that both direct and indirect causes of pulmonary injury are associated with the development of ARDS (Table 72-2). The studies of Bernard (1994a, 1994b), Hudson (1995), Fowler (1983) and Pepe (1982) and their colleagues have noted that the most common causes of ARDS due to direct lung injury are pulmonary contusion, gastric aspiration, and pulmonary infection, whereas ARDS due to indirect lung injury most commonly results from sepsis, severe trauma, and prolonged shock. Webster (1988) and Fowler (1983) and their associates have noted that nearly 80% of patients who develop ARDS have one or more of these risk factors. Moreover, Fowler (1983) and Pepe (1982) and their associates have pointed out that the risk of developing ARDS ranges from 2% to 40% in patients with a single risk factor. These same authors, as well as Hudson and colleagues (1995), note that patients with uncontrolled sepsis, pulmonary contusion, aspiration pneumonia, prolonged shock, and severe polytrauma are at greatest risk for ARDS. Fowler (1983) and Pepe (1982) and their colleagues reported that the probability of developing ARDS is disproportionately increased when more than one risk factor is present. The latter authors also recorded that the percentage of patients who develop ARDS is increased 2.3-fold when two risk factors are present and 4.7-fold with three risk factors.
Table 72-2. Clinical Risk Factors for Acute Respiratory Distress Syndrome | ||
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ARDS risk also depends on the magnitude of the physiologic insult, as indicated by correlation with the systemic inflammatory response syndrome, the injury severity score (ISS), and the acute physiology and chronic health evaluation (APACHE) score (Table 72-3). The systemic inflammatory response syndrome, an early nonspecific index of systemic inflammation according to Rangel-Frausto and associates (1995), is associated with a modest increased risk of ARDS. This risk increases with the number of systemic inflammatory response syndrome criteria met, but only 2% to 6% of patients with systemic inflammatory response syndrome develop ARDS. Similarly, ARDS risk increases with increasing ISS and APACHE II scores. Webster and co-workers (1988) have observed that 50% of patients with an ISS greater than 49 and 44% of patients with an APACHE II score greater than 29 develop ARDS.
Early changes in oxygenation have been shown by Weigelt (1981), Pepe (1983), and T. J. Donnelly (1994) and their colleagues to predict ARDS. Weigelt and associates (1981) reported a 95% probability of developing ARDS in patients with a Pao2 less than 100 mm Hg on 40% O2 or a Pao2 less than 350 mm Hg on 100% O2. T. J. Donnelly and co-workers (1994) found significant differences in the Pao2/Fio2 ratios of patients who developed ARDS as early as 4 hours postinjury. Pepe and associates (1983) have used these differences in the initial Pao2/Fio2 ratio, combined with clinical risk factors and ISS, to create a scoring system that estimates ARDS risk.
A number of biochemical markers have been examined as potential indicators of the cellular or humoral events that precede clinically apparent lung injury. Miller and colleagues (1992, 1996) have found that interleukin-8 (IL-8), an important neutrophil chemoattractant implicated in lung injury, is elevated in the lung lavage of patients with ARDS and has been correlated with clinical outcomes. Retrospective analysis of lung lavage IL-8 by S. C. Donnelly and associates (1993) and Reid and Donnelly (1996) showed a positive predictive index of 80%. Soluble forms of intracellular adhesion molecule-1 (ICAM-1) and the endothelial adhesion molecules E selectin and P selectin have not been shown to predict ARDS by Sakamaki (1995), Sessler (1995) and Boldt (1995) and their colleagues, but do correlate with outcomes and may therefore have prognostic value. Another marker of endothelial injury, von Willebrand's factor antigen, has been shown to be elevated in patients with acute respiratory failure but has a positive predictive value of only 65% in patients with nonpulmonary sepsis syndrome and no predictive value in patient populations with more diverse risk factors in the studies of Carvalho (1982), Rubin (1990) and Moss (1995b) and their associates. Abnormalities in surfactant and surfactant-associated proteins have been detected by Hallman (1982) and Pison (1992) and their co-workers in patients with respiratory failure. Additional studies will be necessary to determine whether these alterations can be used to accurately predict the development of ARDS.
Table 72-3. Acute Respiratory Distress Syndrome Risk | ||||||||||||||||||||||||||||||||||||||
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A variety of neutrophil products have been examined as potential predictors of ARDS. Elastase, soluble L selectin, and CD11b/CD18 are increased in patients with ARDS, as reported in the studies of S. C. Donnelly (1994, 1995) and Laurent (1994) and their associates, as well as by Simms and D'Amico (1991), but have not yet been studied prospectively to establish their predictive value. Although complement activation is an important humoral component of systemic inflammatory responses, the presence of activated complement proteins such as C3a and C5a does not reliably predict ARDS according to Duchateau (1984) and Tennenberg (1987) and their colleagues.
Most recently, Sharkey and colleagues (1999) have suggested that early elevation in transferrin is an indicator for the development of ARDS, but the range of values (from 12 to 4,500) makes the predictive value suspect. To date, biochemical markers of ARDS have relatively low predictive value for any given individual but may be useful in characterizing patient populations at risk.
PATHOGENESIS
Studies of the pathogenesis of ARDS have had to accommodate three simple, yet challenging observations. First, the characteristics of ARDS are remarkably consistent despite its diverse clinical causes. The earliest accounts of ARDS highlighted the similarity of lung injuries produced by such diverse insults as sepsis, shock, fat embolism, gastric aspiration, and pulmonary contusion. This suggested
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the presence of a final common pathway or pathways of lung injury that could be elicited by a heterogeneous group of primary stimuli. Second, inflammatory stimuli presenting on either side of the alveolar capillary membrane produce the same syndrome of pulmonary dysfunction. Because both direct and indirect insults produce ARDS, the final common pathway or pathways involved in lung injury must be elicited by either intravascular or intraalveolar stimuli. Third, identical insults do not produce lung injury in all individuals. This last and most challenging observation requires that hypotheses involving the pathogenesis of ARDS provide an explanation for the heterogeneity of individual responses to a given stimulus.
Initial clinical and histologic investigations by Ashbaugh (1967) and Jenkins (1950) and their colleagues suggested that the refractory hypoxemia characteristic of ARDS was directly related to increased pulmonary capillary permeability and extravascular lung fluid. Intraalveolar and interstitial edema are consistent early features of ARDS, and, as noted by Mitchell and associates (1992), extravascular lung water is increased from three to eight times normal, but it is the cellular process that produces the original observations. The presence of leukocyte and platelet microthrombi, according to Bachofen and Weibel (1977), indicates that ARDS is associated with an acute intravascular inflammatory process. A number of critical proinflammatory events associated with the development of ARDS, including macrophage activation, neutrophil recruitment and activation, endothelial injury, platelet aggregation and degranulation, the activation of plasma proteins, and alveolar epithelial injury, have been identified in the studies of Weiland (1986), Groeneveld (1997) and Heffner (1987) and their colleagues, as well as Tate and Repine (1983) (Table 72-4).
Table 72-4. Pathogenesis of Acute Respiratory Distress Syndrome | |
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Macrophage Activation
Pulmonary interstitial and alveolar macrophages are key signaling and effector cells in acute lung injury. These resident leukocytes of the lung are ideally positioned to initiate local inflammatory responses. They do so by elaborating a variety of secreted and membrane-associated mediators, including cytokines, reactive oxygen intermediates, eicosanoids, tissue factor, and HLA-DR antigen. Macrophage activation promotes neutrophil recruitment, antigen presentation, phagocytosis, and sequestration at the inflammatory site. In addition to providing these beneficial actions, a number of macrophage products, including reactive oxygen intermediates, tumor necrosis factor (TNF), and IL-1, have been implicated in acute lung injury by Brackett and McCay (1994), Simpson and Casey (1989), and Koy and associates (1996). Meduri and colleagues (1995) have reported that TNF, IL-1, and IL-8 are elevated in bronchoalveolar lavage fluid from patients with ARDS and correlate with mortality. Studies by Molloy and co-workers (1993) examining altered macrophage function in acute lung injury suggest that a failure of counterregulatory mechanisms that normally limit inflammatory responses may result in the pathologic release of proinflammatory substances that contribute to lung injury.
Neutrophil Recruitment and Activation
Neutrophil participation in ARDS has been established by the studies of Harlan (1987), Idell and Cohen (1985) and Weiland (1986) and Hinson (1983) and their associates. These investigators demonstrated the presence of activated neutrophils in the lungs of patients with ARDS, the ability of neutrophil-derived mediators to induce lung injury, and the attenuation of lung injury following neutrophil depletion or blocking experiments. Simms and D'Amico (1991) have reported that neutrophil margination and transendothelial migration are mediated by chemoattractants and the upregulation of neutrophil endothelial binding. S. C. Donnelly (1993), Hammerschmidt (1980) and Garcia (1988) and their colleagues have observed that the neutrophil chemoattractants IL-8, LTB4, and C5a are increased in acute lung injury. IL-8 concentrations have been shown by Goodman and co-workers (1996) to correlate with the number of neutrophils present in the bronchoalveolar lavage fluid of patients with ARDS. Expression of neutrophil and endothelial adhesion molecules is also increased in acute lung injury. Simms and D'Amico (1991), as well as O'Leary (1996) and Wang (1997) and their associates, reported that proinflammatory mediators, including TNF, IL-1, and endotoxin released during conditions that predispose to ARDS, upregulate neutrophil expression of a number of adhesion molecules, including CD11b/CD18, ICAM-1, and L selectin.
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In addition to their role in neutrophil margination, Shappell and colleagues (1990) have suggested that integrins may further contribute to lung injury by inducing the release of reactive oxygen species. Blockade of CD11/CD18 on neutrophils or ICAM-1 on endothelial cells with monoclonal antibodies, as noted by Horgan and associates (1990, 1992), attenuates pulmonary neutrophil sequestration and lung injury. Janoff (1985) and Weiland and co-workers (1986), as well as B. O. Anderson and associates (1991), have observed that activated neutrophils produce reactive oxygen intermediates, elastase, gelatinases, and collagenase all capable of producing lung injury.
Despite the evidence that neutrophils play an important role in the pathogenesis of ARDS, neutrophil-independent mechanisms also appear to be involved in lung injury. Acute lung injury has been demonstrated in severely neutropenic patients by Ognibene and colleagues (1986) and in animal models with impaired neutrophil adherence or attenuated neutrophil function by Carraway and associates (1998).
Endothelial Injury
Pulmonary capillary injury is a hallmark of ARDS. Ashbaugh and colleagues (1967) initially stated that the early evidence of this injury included hemorrhagic interstitial and intraalveolar edema, microvascular occlusion with platelet and neutrophil aggregates, and the loss of normal endothelial histocytologic architecture; these features were confirmed by Hasleton (1983). More recently, biochemical markers of endothelial cell activation and injury (e.g., von Willebrand's factor antigen and tissue factor pathway inhibitor) have been shown by Sabharwarl and associates (1995) to be elevated in patients with ARDS. Grau and co-workers (1996) have reported that expression of TNF receptor p75 and adhesion molecules ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) is also increased in pulmonary microvascular endothelial cells from patients with ARDS. It is hypothesized that neutrophil adherence and the creation of a protected microenvironment between the neutrophil and endothelial cell are prerequisites for neutrophil-mediated injury to endothelium. Inflammatory mediators released in response to injury or infection induce the expression of endothelial adhesion molecules. Chuluyan and colleagues (1995) have noted that IL-1 upregulates E selectin, ICAM-1, and VCAM-1 expression. TNF and IL-1 have been shown by Shalaby and associates (1987) to enhance endothelial injury by neutrophils and reactive oxygen intermediates. Minamiya and colleagues (1995) have observed that bacterial lipopolysaccharides also promote neutrophil endothelial adherence and release of hydrogen peroxide into the pulmonary microcirculation.
Endothelial injury associated with neutrophil adherence and activation is accompanied by a loss of endothelial integrity that is characterized by cytoskeletal changes, increased permeability, and proteolytic injury to endothelial surface elements. Recovery of a number of endothelial membrane associated proteins from extracellular fluids is increased. In patients with ARDS, these include thrombomodulin and soluble E selectin, as noted by MacGregor (1997) and Ruchaud-Sparagano (1998) and their associates. The latter investigators also have noted that release of soluble E selectin may further exacerbate endothelial injury by decreasing neutrophil chemotaxis and increasing the production of reactive oxygen intermediates and integrin-mediated adhesion.
Platelet Aggregation and Degranulation
Platelet aggregation and microvascular thrombosis normally act to sequester and limit inflammatory responses. In contrast, disseminated platelet activation contributes to pulmonary dysfunction by redistributing microvascular blood flow, increasing capillary permeability, and activating leukocytes. In the mid-1970s, thrombocytopenia and pulmonary platelet sequestration were noted in patients with ARDS by Bone (1976) and Hill (1976) and their associates. These findings were associated with extensive microvascular thrombosis, pulmonary hypertension, and pulmonary edema. According to the studies of Heffner and co-workers (1987), platelet activation is initiated by bacterial lipopolysaccharides, platelet-activating factor, thromboxane, and thrombin. These authors also reported that degranulation further amplifies the local inflammatory response, producing vasoconstriction and neutrophil recruitment by the release of platelet-activating factor, thromboxane, serotonin, and platelet-derived growth factor.
Activation of Plasma Protein Systems
A number of important plasma protein systems are activated in ARDS. Craddock (1977) and Hammerschmidt (1980) and their colleagues observed that complement activation is a common feature of ARDS and has been used experimentally to produce lung injury. Complement fragments, as described by Duchateau and associates (1984), are potent activators of neutrophils, stimulating aggregation, chemokinesis, and adhesion to endothelium. However, both Flick (1986) and Dehring (1987) and their colleagues have shown that depletion of complement does not prevent septic lung injury, indicating that other mechanisms contribute.
A second plasma protein system commonly activated in ARDS is the coagulation cascade, as reported by Bone and co-workers (1976). Dorinsky and Gadek (1989) have recorded that clinically evident coagulopathy is present in 26% of patients with ARDS. Intravascular and intraalveolar fibrin deposition are also frequent findings, according to Idell and associates (1987). Coagulation is promoted by the
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upregulation of endothelial and monocyte and macrophage tissue factor. In a study by Johnson and colleagues (1983), the infusion of thrombin in animals results in increased microvascular permeability and lung injury, suggesting that rather than being a consequence of lung injury, coagulation is involved in the pathogenesis of lung injury. Saldeen (1983) reported that the inhibition of fibrinolysis contributes to the hypercoagulation seen in ARDS. The inhibition of intraalveolar fibrinolytic activity is caused in part by increased plasminogen-activator inhibitor type 1 release, according to the investigations of Bertozzi and co-workers (1990).
Alveolar Epithelial Injury
Although alveolar epithelial injury is evident in histopathologic and ultrastructural studies of patients with ARDS, biochemical assessment and quantification of epithelial injury has been lacking because of the absence of markers of epithelial injury. The identification of an alveolar epithelial type I cell specific protein has been used as a marker of epithelial cell injury by McElroy and associates (1995) in an animal model of pneumonia. A second potential marker of epithelial injury, epithelial cell derived neutrophil activator-78, has been shown by Goodman and colleagues (1996) to be elevated in the bronchoalveolar fluid of patients with ARDS. Evidence of functional injury has previously been demonstrated by Hallman and associates (1982) and more recently by Lewis and Jobe (1993) by abnormalities in epithelial surfactant. Gunther and colleagues (1996) have shown that lung lavages of patients with ARDS contain decreased total phospholipids, decreased large surfactant aggregates, and decreased surfactant protein A and have increased surface tension. Abnormalities in surfactant may not directly reflect injury to the type II epithelial cell. Plasma proteins with access to the alveolus because of capillary injury are known to influence surfactant activity and may be responsible for some alterations in surfactant activity, as Seeger and co-workers (1985) have observed. It is also true, however, that epithelial cells are subject to injury by many of the same macrophage- and neutrophil-derived mediators implicated in endothelial cell injury, as shown by Sulkowska (1997). Bacteria and bacterial products (e.g., exoenzyme S and phospholipase A) can injure alveolar epithelium, as demonstrated by the studies of Wiener-Kronish and associates (1991, 1993).
The initial sequence of cellular events that precede ARDS depends on the nature and site of the insult. Well-recognized differences in the nature of insults (e.g., sterile vs. infectious) activate distinct inflammatory pathways. Recognition of the importance of the site of the primary insult in determining early inflammatory responses has increased. For example, indirect pulmonary insults (e.g., sepsis, shock, pancreatitis) involve systemic mediators that upregulate adhesion molecule expression, neutrophil adherence and activation, and the activation of plasma protein systems as early events. In contrast, insults presented via the tracheobronchial tree (e.g., gastric aspiration, pneumonia, inhalation burn) first produce a local inflammatory response mediated in large part by alveolar macrophages. Subsequent diffuse lung injury appears to depend on a failure of regulatory mechanisms to contain or localize the inflammatory response. In this setting the participation of intravascular components of the inflammatory response, including neutrophil recruitment and activation, occurs as a secondary event. The failure of initial attempts to treat ARDS by modifying inflammatory responses is in large part because of an incomplete understanding of the complexity of the factors that dictate host responses to injury and infection.
The primary pathophysiologic correlates of the cellular events that result in ARDS are an increase in transcapillary fluid flux, interstitial edema, decreased pulmonary compliance, impaired oxygenation, and increased work of breathing, as enumerated by Iliff and colleagues (1972). Zapol and Snider (1977) also noted that the release of vasoactive substances from platelets, neutrophils, and macrophages is accompanied by a period of pulmonary hypertension. Initial injury to the alveolar capillary membrane is compounded by diminished surfactant activity. The redistribution of intrapulmonary blood flow because of microvascular thrombosis and altered vasomotor responses, in conjunction with the loss of alveolar gas-exchange units because of collapse and intraalveolar fluid accumulation, leads to ventilation-perfusion mismatching, an increase in the shunt fraction Qs/Qt, and decreased functional residual capacity.
DIAGNOSIS
The diagnoses of acute lung injury and ARDS are made using the criteria established by the AECC (see Table 72-1).
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A number of scoring systems have been developed to further stratify the severity of lung injury. The most widely accepted scoring system is the LISS developed by Murray and associates (1988) (Table 72-5). This system is particularly useful for studies that seek to quantify the progression of pulmonary dysfunction and is commonly used in natural history studies and clinical efficacy trials.
Table 72-5. Lung Injury Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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MANAGEMENT
Traditional management of ARDS consists of the identification and treatment of the primary cause or causes of respiratory failure and supportive ventilatory care (Table 72-6). A number of different strategies have been used in an attempt to provide adequate ventilatory support while preventing iatrogenic lung injury. However, proven therapies, pharmacologic or mechanical, that directly affect the outcomes of ARDS by attenuating or reversing acute inflammatory lung injury have not been identified. It is essential therefore to identify and treat the primary causes of ARDS. Because sepsis is the most common cause of ARDS, septic foci must be sought out and treated. Both Fry (1980) and Montgomery (1985) and their colleagues, among others, have pointed out that intraabdominal infection is the most frequent source of infection in surgical patients with sepsis-related ARDS.
Conventional Ventilatory Management
Ventilator management is covered in detail in Chapter 40. Some of the key points are emphasized here. All patients with acute respiratory insufficiency require attention to pulmonary toilet to minimize the risks of atelectasis, endobronchial mucus plugging, and pneumonia. However, it has not been possible to prevent or reverse ARDS with early ventilatory support. It has become progressively clearer that the objective of ventilatory management is to maintain adequate oxygenation and ventilation while preventing ventilator-induced lung injury and maintaining adequate tissue perfusion (see Table 72-6). This usually has been accomplished with supplemental oxygen, pressure-limited positive-pressure ventilation, and PEEP.
Table 72-6. Management of Adult Respiratory Distress Syndrome | |
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Patients with ARDS should be placed on a ventilatory mode that minimizes the work of breathing. This can be accomplished with either volume- or pressure-cycled, assist control modes. Controversy regarding the use of pressure-cycled versus volume-cycled ventilatory modes is based largely on differences in the rate at which positive pressure and gas flow develop in these two modes. Older volume-cycled ventilators produced rapid, sustained flows that stopped abruptly (square wave flow pattern), which may be detrimental by increasing maldistribution of ventilation and producing barotrauma. Davis and associates (1996) have noted that the newer ventilators allow the regulation of flow rates in volume-cycled ventilatory modes and have largely eliminated this concern. Small tidal volumes of 6 to 10 mL/kg and limited peak airway pressures of less than 40 to 45 cm H2O, as suggested by Gammon and co-workers (1992) as well as by Dreyfuss and Saumon (1992), are used to minimize the risk of iatrogenic lung injury. PEEP is applied to minimize the need for supplemental oxygen to an Fio2 of 0.6 or less. By attenuating progressive atelectasis and increasing functional residual capacity, PEEP partially corrects ventilation-perfusion mismatching in the lung and thus improves oxygenation. Valta and associates (1993) have noted that alveolar recruitment by PEEP, previously cited as a cause of improved oxygenation, is minimal.
Ventilator and fluid management are closely linked in patients with ARDS. In contrast to normal negative-pressure ventilation, which augments cardiac venous return, the increased mean airway pressures that accompany the application of PEEP result in increased intrathoracic pressure and may decrease venous return. Thus, positive-pressure ventilation can decrease left ventricular end-diastolic volume, increase pulmonary vascular resistance, and significantly impair cardiac performance. Appropriate fluid management depends on the recognition that adequate filling pressures must be maintained to ensure optimal cardiac performance and tissue perfusion. Excessive fluid administration exacerbates hypoxemia in these patients with pulmonary capillary injury and increased permeability. The pulmonary artery catheter provides valuable information in this setting and should be used as soon as it is apparent that the severity of respiratory dysfunction requires increasing PEEP and mean airway pressures in order to maintain oxygenation.
Permissive Hypercapnia
Permissive hypercapnia, or pressure-targeted ventilation, is a lung-protective strategy suggested by Hickling and colleagues (1990) in which hypoventilation and hypercapnia are accepted to avoid peak airway pressures above 40 to 45 cm
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H2O. The pathophysiologic consequences of hypercapnia (i.e., central nervous system dysfunction, neuromuscular weakness, and intracranial hypertension) are primarily related to the magnitude and the rate of change of intracellular pH. Arterial partial pressures of CO2 in the range of 80 to 100 mm Hg and even respiratory acidosis with pH in the range of 7.05 to 7.15 that develop over several hours are remarkably well tolerated if oxygenation is preserved. An increase of 10 to 20 mm Hg per hour in the Pco2 allows compensatory mechanisms to maintain intracellular pH. Sodium bicarbonate is commonly administered for an acidosis of less than 7.2.
Although permissive hypercapnia is regarded by many as an experimental approach, in practice it is relatively common to accept hypercapnia when minute ventilation becomes rate limited because of low lung volumes and high airway pressures. However, given the effect of hypercapnia on cerebral vessels, the use of permissive hypercapnia in patients with head injuries should be avoided until its use in this group of patients has been thoroughly examined.
Inverse Ratio Ventilation
Inverse ratio ventilation (IRV) is a labor-intensive ventilatory technique that improves oxygenation by increasing the fraction of inspiratory time in the respiratory cycle. Normal inspiratory expiratory ratios of 1:3 are increased to 2:1, 3:1, or 4:1. Indications for its use are high peak airway pressures and persistent hypoxemia despite maximal conventional ventilatory support. Gurevitch and colleagues (1986) have reported that improved oxygenation is achieved by prolonging the period of inhalation and thus the interval of positive airway pressure. This maintains alveolar gas-exchange units at lower levels of PEEP and lower peak airway pressures than can be achieved with conventional techniques but increases mean airway pressure. It also has been suggested by Marcy and Marini (1991) that increasing the inspiratory expiratory ratio promotes alveolar recruitment, decreases dead-space ventilation, and improves gas mixing.
Patients ventilated using IRV should be sedated and pharmacologically paralyzed. IRV can be initiated with either pressure- or volume-controlled ventilatory modes. Volume-cycled IRV is achieved by decreasing the inspiratory flow rate or adding a pause after inspiration. An important practical point to remember when using IRV is that as the ventilatory rate increases, the amount of time allowed for exhalation decreases and effective ventilation decreases. At high inspiratory expiratory ratios and ventilatory rates, Pco2 increases dramatically as ventilatory rate increases.
High-Frequency Ventilation
High-frequency ventilation is being investigated as an alternative ventilatory technique in patients with ARDS. This technique uses ventilatory rates from 60 to 3,600 cycles per minute combined with continuous positive airway pressures. The high ventilatory frequency promotes rapid gas mixing throughout the lung despite low tidal volumes. This technique appears to be most applicable to patients with large thoracostomy tube air leaks and possibly to patients with severe ARDS who fail conventional techniques and IRV. A preliminary study of patients with ARDS caused by sepsis, trauma, and gastric aspiration by Fort and co-workers (1997) demonstrated improvement in oxygenation with high-frequency ventilation while mean airway pressures were maintained around 30 cm H2O. Concerns that the increased mean airway pressures used in high-frequency ventilation would impair cardiac function were not borne out in this study. No significant changes in cardiac function were observed, although many patients had an early, transient increase in pulmonary artery pressure.
Despite multiple trials, confusion remains because of the uncertainties of interpretation of data on regional lung function. Hubmayr (2002) argues that fluid in the interstitium and dependent edema account for the diffusion defects and that collapse does not occur to any great extent. In a health policy report, Steinbrook (2003) summarized the serious issues of patient safety surrounding all of the recent trials. The National Heart, Lung, and Blood Institute of the National Institutes of Health has suspended all trials while it decides how to resolve this controversial issue.
Surfactant
Surfactant is a type II alveolar epithelial cell derived phospholipid that decreases alveolar surface tension and opening pressure. Neonatal respiratory distress syndrome has been treated successfully with surfactant. The role of replacement surfactant therapy in ARDS is unclear. Human and animal studies by Lewis and Jobe (1993) and by Pison (1989) and Gregory (1991) and their colleagues have shown that surfactant activity is impaired in acute lung injury and that these abnormalities correlate with the severity of respiratory dysfunction. But although preliminary studies using bovine or synthetic surfactant showed promising results, subsequent trials have had mixed results, according to the studies of Walmrath (1996) and Anzueto (1996) and their associates. This is in part because of differences in the formulations of surfactant that have been used. The activity of surfactant depends on its association with apoproteins: surfactant proteins A, B, and C. One of the experimental agents, Exosurf, used in early studies evaluating the efficacy of surfactant replacement therapy in patients with ARDS contained only the phospholipid component. Although the results of these early studies have left many people skeptical about the efficacy of surfactant, additional work is needed to determine whether a biologically active form of surfactant can improve pulmonary function.
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Inhalational Nitric Oxide
Nitric oxide is a locally active vasodilator that can be delivered directly to ventilated areas of the lung to improve perfusion. Frostell and colleagues (1993) have reported that inhaled nitric oxide at concentrations of 5 to 80 ppm results in selective pulmonary vasodilation without systemic hypotension. In addition to its direct effects on vasomotor tone, Gries and associates (1998) have suggested that nitric oxide may decrease lung inflammation by inhibiting platelet aggregation. The studies of Rossaint (1993), Gerlach (1993) and McIntyre (1995) and their co-workers show that nitric oxide reduces the pulmonary hypertension associated with early acute lung injury but that its effects on oxygenation are less consistent. Improved oxygenation and decreased shunt are observed in 60% to 65% of patients, but no survival benefit has been shown in the experience of Rossaint and associates (1995). The efficacy of nitric oxide in patients with ARDS is currently being evaluated in prospective randomized clinical trials.
Extracorporeal Membrane Oxygenation and Partial Liquid Lung Ventilation
Extracorporeal membrane oxygenation and extracorporeal CO2 removal were evaluated as salvage techniques in patients with severe refractory hypoxemia as early as 1979 by Zapol and colleagues and more recently by Morris and associates (1994). Early experiences with extracorporeal membrane oxygenation showed prohibitive complication rates and mortality, but technical improvements such as those reported by Gattinoni and co-workers (1986) have resulted in fewer complications and improved survival. A 47% survival rate was reported in a subset of patients enrolled in a phase I trial of extracorporeal membrane oxygenation by H. Anderson and colleagues (1993). Neither technique has shown survival benefit in prospective randomized studies.
Partial liquid lung ventilation exploits the low surface tension of perfluorocarbons and their unique ability to dissolve large quantities of respiratory gases. Perfluorocarbons have been studied in animal models of severe lung injury and show modest improvement in pulmonary compliance and oxygenation. Partial liquid ventilation uses conventional ventilatory modes with a volume of perfluorocarbon equivalent to the functional residual capacity. Preliminary work by Hirschl (1996) and Gauger (1996) and their colleagues indicates improvements in oxygenation, compliance, and shunt. Additional studies are needed to establish the role of partial liquid lung ventilation as a salvage technique in patients with severe lung injury unresponsive to conventional management.
Antiinflammatory Agents
Numerous antiinflammatory agents have been investigated in acute lung injury and sepsis. Antioxidant therapy using allopurinol, superoxide dismutase, catalase, vitamin E, and N-acetylcysteine has shown mixed results in animal and human studies conducted by Warner (1986) and Kunimoto (1987) and their associates, as well as by Bernard (1991). Antibody and receptor antagonist therapies directed at blocking the biological activities of endotoxin, TNF, IL-1, and cell adhesion molecules have been examined primarily in sepsis, the major cause of ARDS. An early report of decreased respiratory failure in patients with gram-negative sepsis treated with endotoxin antibody has not been supported by subsequent studies reported by Greenman (1991), Ziegler (1991) and McCloskey (1994) and their colleagues. Anticytokine therapies have produced mixed results. Although animal studies often indicate significant survival benefits, controlled clinical studies fail to confirm these findings. The IL-1 receptor antagonist study reported by Fisher and associates (1994a), for example, failed to show improved survival in septic patients, but a posthoc subset analysis by the same authors (1994b) showed benefit. Inhibitors of eicosanoid synthesis and phosphodiesterase inhibitors have shown beneficial antiinflammatory actions in animal models but do not have clinically proven benefit in preventing or treating sepsis or ARDS, as shown by Haupt (1991) and Ardizzoia (1993) and their colleagues. Similarly, Bone and associates (1989) have shown that prostaglandin E1 treatment has failed to improve survival in patients with ARDS.
Corticosteroids have potent antiinflammatory effects and have been shown to decrease pulmonary capillary injury when administered before lung injury in experimental models, as noted in the review of Metz and Sibbald (1991), but have not been shown to improve clinical outcomes when administered during the early phase of ARDS in the studies of Bernard (1987), Bone (1987) and Luce (1988) and their colleagues. Corticosteroids may have applications in the later phases of acute lung injury. Several studies reported by Ashbaugh and Maier (1985), Hooper and Kearl (1990), and Meduri and associates (1991, 1998) indicate a benefit of corticosteroids administered during the fibroproliferative phase of ARDS when infection is absent. Meduri and associates (2002) recommend a prolonged course of methylprednisolone at 2 mg/kg per day tapering slowly over 30 days. Despite intensive efforts to identify antiinflammatory agents effective in the prevention or treatment of ARDS, to date no prospective randomized trial has demonstrated benefit from any of the agents studied. Intensive investigation continues in this area.
OUTCOMES
Mortality from acute respiratory distress syndrome is 40% to 60%. The mortality was virtually unchanged from the syndrome's description in 1967, when Ashbaugh and colleagues reported a 58% mortality, to 1987 when Artigas and co-workers (1991) of the European Collaborative Study reported a 59% mortality. Large series in the 1990s
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have shown similar mortality, but several studies of Hudson (1995), Suchyta (1992) and Milberg (1995) and their associates suggest a reduction in ARDS mortality to approximately 40%.
Montgomery (1985), Bell (1983) and Gee (1990) and their colleagues note that mortality is influenced by a variety of factors, including the underlying cause of ARDS, preexisting medical conditions, and patient age. Deaths that occur within 72 hours of developing ARDS, according to Montgomery and associates (1985), are typically caused by the primary disease process, whereas late deaths are from sepsis and multiple organ failure. Irreversible respiratory failure is infrequently the primary cause of death, with only 16% of deaths attributable to fulminant respiratory failure. ARDS is a relatively frequent manifestation of severe inflammatory insults that produce organ dysfunction, but it is the combined failure of other organ systems that is responsible for the high mortality of ARDS.
Herridge and colleagues of the Canadian University Health Network and the Canadian Critical Care Trials Group (2003) reported a landmark study of 1-year survivors of ARDS. The initial group of patients had a hospital mortality of 40%. They followed 109 survivors who had a 1-year survival rate of 89%. These patients had an average 18% weight loss from baseline by the time of discharge, and their weight only approached baseline at 1 year. Table 72-7 lists the pulmonary function tests over the year of follow-up. Lung volumes and diffusion capacity did not change appreciably from relatively normal values. FEV1 did continue to improve over the year. Table 72-8 lists the functional outcomes. Even at 1 year after discharge, these patients had a very low exercise capacity, only achieving a median of 422 m in 6 minutes. Other measures from the SF-36 general health survey showed gradual improvement in physical functioning, physical role, pain, and emotional role, whereas little change was seen in general health, vitality, and mental health. Social functioning improved over the first 6 months and then plateaued.
Table 72-7. Recovery of Pulmonary Function among Patients with Acute Respiratory Distress Syndrome during the First 12 Months After Discharge from the Intensive Care Unit | ||||||||||||||||||||||||||||
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Several investigators have looked for early predictors of poor outcome. Monchi and associates (1998) studied prospectively all ventilated patients, of whom 259 developed ARDS. The overall mortality rate was 65%. Simplified acute physiologic score (SAPS-II), the severity of the underlying medical conditions, the oxygenation index (mean airway pressure Fio2 100/Pao2), the length of mechanical ventilation prior to ARDS, the mechanism of lung injury, cirrhosis, and occurrence of right ventricular dysfunction were independently associated with an elevated risk of death. Thus, the prognosis of ARDS seems to be related to the triggering risk factor, the severity of the respiratory illness, and the occurrence of a right ventricle dysfunction, after adjustment for a general physiologic severity score.
FUTURE DIRECTIONS
The National Heart, Lung, and Blood Institute convened a workshop to recommend the directions of future research, which was reported by Matthay and colleagues (2003). The attendees arrived at several conclusions. High-quality multicenter clinical trials must be supported to address issues of comorbidities of renal failure and sepsis. Proteomic and genomic evaluations in animal studies are likely to uncover important molecules and genes to target. It would be beneficial to know of biological markers and genetic factors for susceptibility and of earlier prognostic indicators. A national lung tissue biobank for the study of ARDS was recommended, as was continuing investigation into the cellular and molecular mechanisms of ARDS, including cell-to-cell communication that occurs with the progression of ARDS. The lung's response to bacterial and viral genetics is poorly understood and requires better elucidation. It is
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necessary to investigate methods to modulate inflammatory cell responses, to study lung remodeling and clearance of edema fluid, and to study soluble and insoluble proteins. Progress in decreasing the continued high mortality rate in this disease will only come with a major commitment from the National Heart, Lung, and Blood Institute to focus on this condition.
Table 72-8. Ability to Exercise and Return to Work and Health-Related Quality of Life among Patients with Acute Respiratory Distress Syndrome during the First 12 Months After Discharge from the Intensive Care Unit | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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REFERENCES
Anderson BO, Brown JM, Harken AH: Mechanisms of neutrophil-mediated tissue injury. J Surg Res 51:170, 1991.
Anderson H 3rd, et al: Extracorporeal life support for adult cardiorespiratory failure. Surgery 114:161, 1993.
Anzueto A, et al: Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med 334:1417, 1996.
Ardizzoia A, et al: Respiratory distress syndrome in patients with advanced cancer treated with pentoxifylline: a randomized study. Support Care Cancer 1:331, 1993.
Artigas A, et al: Clinical presentation, prognostic factors, and outcome of ARDS in the European Collaborative Study (1985 1987). In Zapol WM, Lemaire F (eds): Adult Respiratory Distress Syndrome. New York: Marcel Dekker, 1991, p. 37.
Ashbaugh DG, Maier RV: Idiopathic pulmonary fibrosis in adult respiratory distress syndrome. Arch Surg 120:530, 1985.
Ashbaugh DG, et al: Acute respiratory distress in adults. Lancet 2:319, 1967.
Bachofen M, Weibel ER: Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116:589, 1977.
Bell RC, et al: Multiple organ system failure and infection in adult respiratory distress syndrome. Ann Intern Med 99:293, 1983.
Bernard GR: N-acetylcysteine in experimental and clinical acute lung injury. Am J Med 91(suppl 3c):54, 1991.
Bernard GR, et al: High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 317:1565, 1987.
Bernard GR, et al: The American European consensus conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818, 1994a.
Bernard GR, et al: Report of the American European consensus conference on acute respiratory distress syndrome. J Crit Care 9:72, 1994b.
Bertozzi P, et al: Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med 322:890, 1990.
Boldt J, et al: Do plasma levels of circulating soluble adhesion molecules differ between surviving and non surviving critically ill patients? Chest 107:787, 1995.
Bone RC, Francis PB, Pierce AK: Intravascular coagulation associated with the adult respiratory distress syndrome. Am J Med 61:585, 1976.
Bone RC, et al: Early methylprednisolone treatment for septic syndrome and the adult respiratory distress syndrome. Chest 92:1032, 1987.
Bone RC, et al: Randomized double-blind, multicenter study of prostaglandin E1in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group. Chest 96:114, 1989.
Brackett DJ, McCay PB: Free radicals in the pathophysiology of pulmonary injury and disease. Adv Exp Med Biol 366:147, 1994.
Burford TH, Burbank B: Traumatic wet lung. J Thorac Cardiovasc Surg 14:415, 1945.
Carraway MS, et al: Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons. Am J Respir Crit Care Med 157: 938, 1998.
Carrico CJ, et al: Multiple organ failure syndrome. Arch Surg 121:196, 1986.
Carvalho ACA, et al: Altered factor VIII in acute respiratory failure. N Engl J Med 307:1113, 1982.
Chuluyan HE, et al: IL-1 activation of endothelium supports VLA-4 (CD49d/CD29)-mediated monocyte transendothelial migration to C5a, MIP-1a, RANTES, and PAF but inhibits migration to MCP-1: a regulatory role for endothelium-derived MCP-1. J Leukoc Biol 58:71, 1995.
Craddock PR, et al: Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med 296:769, 1977.
Davis K Jr, et al: Comparison of volume control and pressure control ventilation: is flow waveform the difference? J Trauma 41:808, 1996.
Dehring DJ, et al: Complement depletion in a porcine model of septic acute respiratory disease. J Trauma 27:615, 1987.
Donnelly SC, et al: Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341:643, 1993.
Donnelly SC, et al: Role of selectins in development of adult respiratory distress syndrome. Lancet 344:215, 1994.
Donnelly SC, et al: Plasma elastase levels and the development of the adult respiratory distress syndrome. Am J Respir Crit Care Med 151: 1428, 1995.
Donnelly TJ, et al: Cytokine, complement, and endotoxin profiles associated with the development of the adult respiratory distress syndrome after severe injury. Crit Care Med 22:768, 1994.
Dorinsky PM, Gadek JE: Mechanisms of multiple nonpulmonary organ failure in ARDS. Chest 96:885, 1989.
Dreyfuss D, Saumon G: Barotrauma is volutrauma, but which volume is the one responsible? Intensive Care Med 18:139, 1992.
Duchateau J, et al: Complement activation in patients at risk of developing the adult respiratory distress syndrome. Am Rev Respir Crit Care Med 130:1058, 1984.
Enright PL, Sherrill DL: Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med 158:1384, 1998.
Fisher CJ Jr, et al: Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. The IL-IRA Sepsis Syndrome Study Group. Crit Care Med 22:12, 1994a.
Fisher CJ Jr, et al: Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-Ira Sepsis Syndrome Study Group. JAMA 271:1836, 1994b.
Flick MR, et al: Reduction of total hemolytic complement activity with Naja haje cobra venom factor does not prevent endotoxin-induced lung injury in sheep. Am Rev Respir Dis 133:62, 1986.
Fort P, et al: High-frequency oscillatory ventilation for adult respiratory distress syndrome a pilot study. Crit Care Med 25(5 pt 1):937, 1997.
Fowler AA, et al: Adult respiratory distress syndrome: risk with common predispositions. Ann Intern Med 98:593, 1983.
Frostell CG, et al: Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology 78:427, 1993.
Fry DE, et al: Multiple system organ failure: the role of uncontrolled infection. Arch Surg 115:136, 1980.
Gammon RB, Shin MS, Buchalter SE: Pulmonary barotrauma in mechanical ventilation: patterns and risk factors. Chest 102:568, 1992.
Garcia JGN, et al: Inflammatory events after fibrin microembolization alterations in alveolar macrophage and neutrophil function. Am Rev Respir Dis 137:630, 1988.
Gauger PG, et al: Initial experience with partial liquid ventilation in pediatric patients with the acute respiratory distress syndrome. Crit Care Med 24:16, 1996.
Gee MH, et al: Physiology of aging related to outcome in the adult respiratory distress syndrome. J Appl Physiol 69:822, 1990.
Gerlach H, et al: Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur J Clin Invest 23:499, 1993.
Goodman RB, et al: Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med 154:602, 1996.
Goss CH, et al: ARDS Network: incidence of acute lung injury in the United States. Crit Care Med 31:1607, 2003.
Grau GE, et al: Phenotypic and functional analysis of pulmonary microvascular endothelial cells from patients with acute respiratory distress syndrome. Lab Invest 74:761, 1996.
Greenman RL, et al: A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA 266:1097, 1991.
Gregory TJ, et al: Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest 88:1976, 1991.
Gries A, et al: Inhaled nitric oxide inhibits human platelet aggregation p-selectin expression, and fibrinogen binding in vitro and in vivo. Circulation 97:1481, 1998.
P.993
Groeneveld ABJ, et al: Systemic coagulation and fibrinolysis in patients with or at risk for the adult respiratory distress syndrome. Thromb Haemost 78:1444, 1997.
Gunther A, et al: Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema. Am J Respir Crit Care Med 153:176, 1996.
Gurevitch MJ, et al: Improved oxygenation and lower peak airway pressure in severe adult respiratory distress syndrome. Treatment with inverse ratio ventilation. Chest 89:211, 1986.
Hallman M, et al: Evidence of lung surfactant in respiratory failure study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity, and plasma myoinositol. J Clin Invest 70:673, 1982.
Hammerschmidt DE, et al: Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome. Lancet 1:947, 1980.
Harlan JM: Neutrophil-mediated vascular injury. Acta Med Scand Suppl 715:123, 1987.
Hasleton PS: Adult respiratory distress syndrome a review. Histopathology 7:307, 1983.
Haupt MT, et al: Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. Crit Care Med 19:1339, 1991.
Heffner JE, Sahn SA, Repine JE: The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders. Am Rev Respir Dis 135:482, 1987.
Herridge MS, et al: One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 348:683, 2003.
Hickling KG, Henderson SJ, Jackson R: Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 16:372, 1990.
Hill JD, et al: Pulmonary pathology in acute respiratory insufficiency: lung biopsy as a diagnostic tool. J Thorac Cardiovasc Surg 71:64, 1976.
Hinson JM, et al: Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep. J Appl Physiol 55:92, 1983.
Hirschl RB, et al: Evaluation of gas exchange, pulmonary compliance, and lung injury during total and partial liquid ventilation in the acute respiratory distress syndrome. Crit Care Med 24:1001, 1996.
Hooper RG, Kearl RA: Established ARDS treated with a sustained course of adrenocortical steroids. Chest 97:138, 1990.
Hopman WM, et al: Canadian normative data for the SF-36 health survey. Canadian Multicentre Osteoporosis Study Research Group. CMAJ 163: 265, 2000.
Horgan MJ, Wright SD, Malik AB: Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung vascular injury. Am J Physiol 259:L315, 1990.
Horgan MJ, et al: Role of ICAM-1 in neutrophil-mediated lung and vascular injury after occlusion and reperfusion. Am J Physiol 261:H1578, 1992.
Hubmayr RD: Perspective on lung injury and recruitment: a skeptical look at the opening and collapse story. Am J Respir Crit Care Med 165:1647, 2002.
Hudson LD, et al: Clinical risk for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med 151:293, 1995.
Idell S, Cohen AB: Bronchoalveolar lavage in patients with the adult respiratory distress syndrome. Clin Chest Med 6:459, 1985.
Idell S, et al: Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome: contribution of tissue factor associated with factor VII. Am Rev Respir Dis 136:1466, 1987.
Iliff LD, Greene RE, Hughes JMB: Effect of interstitial edema on distribution of ventilation and perfusion in isolated lung. J Appl Physiol 33:462, 1972.
Janoff A: Elastase in tissue injury. Annu Rev Med 36:207, 1985.
Jenkins MT, et al: Congestive atelectasis a complication of the intravenous infusion of fluids. Ann Surg 132:327, 1950.
Johnson A, Tahamont MV, Malik AB: Thrombin-induced lung vascular injury. Am Rev Respir Dis 128:38, 1983.
Koy Y, et al: Tumor necrosis factor induced lung leak in rats: less than with interleukin-1. Inflammation 20:461, 1996.
Kunimoto F, et al: Inhibition of lipid peroxidation improves survival rate of endotoxemic rats. Circ Shock 21:15, 1987.
Laurent T, et al: CD11B/CD18 expression, adherence, and chemotaxis of granulocytes in adult respiratory distress syndrome. Am J Respir Crit Care Med 149:1534, 1994.
Lewis JF, Jobe AH: Surfactant and the adult respiratory distress syndrome. Am Rev Respir Dis 147:218, 1993.
Luce JM, et al: Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 138:62, 1988.
MacGregor IR, et al: Modulation of human endothelial thrombomodulin by neutrophils and their release products. Am J Respir Crit Care Med 155:47, 1997.
Mallory TB, et al: The general pathology of traumatic shock. Surgery 27: 629, 1950.
Marcy TW, Marini JJ: Inverse ratio ventilation in ARDS: rationale and implementation. Chest 100:494, 1991.
Matthay MA, et al: Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 167:1027, 2003.
McCloskey RV, et al: Treatment of septic shock with human monoclonal antibody HA-1A: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 121:1, 1994.
McElroy MC, et al: A type I cell-specific protein is a biochemical marker of epithelial injury in a rat model of pneumonia. Am J Physiol 268: L181, 1995.
McIntyre RC, et al: Inhaled nitric oxide variably improves oxygenation and pulmonary hypertension in patients with acute respiratory distress syndrome. J Trauma 39:418, 1995.
Meade MO, et al: Agreement between alternative classifications of acute respiratory distress syndrome. Am J Respir Crit Care Med 163:490, 2001.
Meduri GU, et al: Fibroproliferative phase of ARDS: clinical findings and effects of corticosteroids. Chest 100:943, 1991.
Meduri GU, et al: Inflammatory cytokines in the BAL of patients with ARDS. Chest 108:1303, 1995.
Meduri GU, et al: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome. A randomized controlled trial. JAMA 280:159, 1998.
Meduri GU, et al: Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med 165:983, 2002.
Metz C, Sibbald WJ: Anti-inflammatory therapy for acute lung injury. A review of animal and clinical studies. Chest 100:1110, 1991.
Milberg JA, et al: Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983 1993. JAMA 273:306, 1995.
Miller EJ, Cohen AB, Matthay MA: Increased interleukin-8 concentrations in the pulmonary edema fluid of patients with acute respiratory distress syndrome from sepsis. Crit Care Med 24:1448, 1996.
Miller EJ, et al: Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 146:427, 1992.
Minamiya Y, et al: Endotoxin-induced hydrogen peroxide production in intact pulmonary circulation of rat. Am J Respir Crit Care Med 152:348, 1995.
Mitchell JP, et al: Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis 145:990, 1992.
Molloy RG, et al: Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. J Immunol 151:2142, 1993.
Monchi M, et al: Early predictive factors of survival in the acute respiratory distress syndrome: a multivariate analysis. Am J Resp Crit Care Med 158:1076, 1998.
Montgomery AB, et al: Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132:485, 1985.
Morris AH, et al: Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 149:295, 1994.
Moss M, et al: Establishing the relative accuracy of three new definitions of the adult respiratory distress syndrome. Crit Care Med 23:1629, 1995a.
Moss M, et al: Von Willebrand factor antigen levels are not predictive for the adult respiratory distress syndrome. Am J Respir Crit Care Med 151:15, 1995b.
Murray JF, and the staff of the Division of Lung Diseases, National Heart, Lung and Blood Institute: Mechanisms of acute respiratory failure. Am Rev Respir Dis 115:1071, 1977.
P.994
Murray JF, et al: An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138:720, 1988.
Ognibene FP, et al: Adult respiratory distress syndrome in patients with severe neutropenia. N Engl J Med 315:547, 1986.
O'Leary EC, Marder P, Zuckerman SH: Glucocorticoid effects in an endotoxin-induced rat pulmonary inflammation model: differential effects on neutrophil influx, integrin expression, and inflammatory mediators. Am J Respir Cell Molec Biol 15:97, 1996.
Osler W: The Principles and Practice of Medicine, Designed for the Use of Practitioners and Students of Medicine. 10th Ed. thoroughly revised by Thomas McCrae. New York: Appleton, 1925. In Wiedemann HP, Tai DY: Adult respiratory distress syndrome: current management, future directions. Cleve Clin J Med 64:365, 1997.
Pepe PE, et al: Clinical predictors of the adult respiratory distress syndrome. Am J Surg 144:124, 1982.
Pepe PE, et al: Early prediction of the adult respiratory distress syndrome by a simple scoring method. Ann Emerg Med 12:749, 1983.
Petty TL, Ashbaugh DG: The adult respiratory distress syndrome: clinical features, factors influencing prognosis and principles of management. Chest 60:233, 1971.
Pison U, et al: Surfactant abnormalities in patients with respiratory failure after multiple trauma. Am Rev Respir Dis 140:1033, 1989.
Pison U, et al: Surfactant protein a (A-SP-A) is decreased in acute parenchymal lung injury associated with polytrauma. Eur J Clin Invest 22: 712, 1992.
Rangel-Frausto MS, et al: The natural history of the systemic inflammatory response syndrome (SIRS). JAMA 273:117, 1995.
Reid PT, Donnelly SC: Predicting acute respiratory distress syndrome and intrapulmonary inflammation. Br J Hosp Med 55:499, 1996.
Rossaint R, et al: Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328:399, 1993.
Rossaint R, et al: Efficacy of inhaled nitric oxide in patients with severe ARDS. Chest 107:1107, 1995.
Rubin DB, et al: Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 86:474, 1990.
Ruchaud-Sparagano MH, et al: Potential pro-inflammatory effects of soluble E-selectin upon neutrophil function. Eur J Immunol 28:80, 1998.
Sabharwarl AK, et al: Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. Am J Respir Crit Care Med 151:758, 1995.
Sakamaki F, et al: Soluble form of p-selectin in plasma is elevated in acute lung injury. J Respir Crit Care Med 151:1821, 1995.
Saldeen T: Clotting microembolism, and inhibition of fibrinolysis in adult respiratory distress. Surg Clin N Am 63:285, 1983.
Seeger W, et al: Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer. J Appl Physiol 58:326, 1985.
Sessler CN, et al: Circulating ICAM-1 is increased in septic shock. Am J Respir Crit Care Med 151:1420, 1995.
Shalaby MR, et al: Receptor binding and activation of polymorphonuclear neutrophils by tumor necrosis factor-alpha. J Leukoc Biol 41:196, 1987.
Shappell SB, et al: Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils. J Immunol 144:2702, 1990.
Sharkey RA, et al: Initial serum ferritin levels in patients with multiple trauma and the subsequent development of acute respiratory distress syndrome. Am J Respir Crit Care Med 159:1506, 1999.
Simms HH, D'Amico R: Increased PMN CD11b/CD18 expression following post-traumatic ARDS. J Surg Res 50:362, 1991.
Simpson SQ, Casey LC: Role of tumor necrosis factor in sepsis and acute lung injury. Crit Care Clin 5:27, 1989.
Steinbrook R: How best to ventilate? Trial design and patient safety in studies of the acute respiratory distress syndrome. N Engl J Med 348: 1393, 2003.
Suchyta MR, et al: The adult respiratory distress syndrome: a report of survival and modifying factors. Chest 101:1074, 1992.
Sulkowska M: Effect of human recombinant tumor necrosis factor-alpha and pentoxifylline on the ultrastructure of type II alveolar epithelial cells in pregnant and nonpregnant rabbits. J Comp Pathol 117:227, 1997.
Tate RM, Repine JE: Neutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis 128:552, 1983.
Tennenberg SD, Jacobs MP, Solomkin JS: Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome. Clarification with radioaerosol lung scans. Arch Surg 122: 26, 1987.
Valta P, et al: Does alveolar recruitment occur with positive end expiratory pressure in adult respiratory distress syndrome patients? J Crit Care 8: 34, 1993.
Walmrath D, et al: Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis. Am J Respir Crit Care Med 154:57, 1996.
Wang JH, et al: Intercellular adhesion molecule-1 (ICAM-1) is expressed on human neutrophils and is essential for neutrophil adherence and aggregation. Shock 8:357, 1997.
Warner BW, Hasselgren P-O, Fischer JE: Effect of allopurinol and superoxide dismutase on survival rate in rats with sepsis. Curr Surg 43:292, 1986.
Webster NR, Cohen AT, Nunn JF: Adult respiratory distress syndrome how many cases in the UK? Anaesthesia 43:923, 1988.
Weigelt JA, Snyder WH, Mitchell RA: Early identification of patients prone to develop adult respiratory distress syndrome. Am J Surg 142: 687, 1981.
Weiland JK, et al: Lung neutrophils in the adult respiratory distress syndrome: clinical and pathophysiologic science. Am Rev Respir Dis 133: 218, 1986.
Wiener-Kronish JP, Albertine KH, Matthay MA: Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coliendotoxin. J Clin Invest 88:864, 1991.
Wiener-Kronish JP, et al: Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits. J Appl Physiol 75:1661, 1993.
Zapol WM, Snider MT: Pulmonary hypertension in severe acute respiratory failure. N Engl J Med 296:476, 1977.
Zapol WM, et al: Extracorporeal membrane oxygenation in severe acute respiratory failure. JAMA 242:2193, 1979.
Ziegler EJ, et al: Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med 324:429, 1991.
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