CHAPTER 92 ACUTE RESPIRATORY DISTRESS SYNDROME
There have not been many topics in critical care medicine that have received as much as attention as the acute respiratory distress syndrome (ARDS). Recently, there has been significant medical progress in this area—due in part to a better understanding of the pathophysiology of ARDS as well as earlier diagnosis and initiation of therapy. The “open lung” concept of mechanical ventilation has revolutionized the management of these patients. Newer modes of ventilation and novel strategies to improve oxygenation and reduce lung compliance have also contributed substantially.1 Despite these advances, a 30%–40% mortality can be attributed to ARDS.2 ARDS can occur directly from traumatic chest trauma or as a sequela of a host of disease processes (sepsis, fat emboli syndrome, pneumonia, severe blunt chest trauma, and so on). Therefore, a thorough understanding of the clinical presentation and treatment options for ARDS is essential for every practitioner who manages critically ill patients.
EPIDEMIOLOGY
The first estimate of the incidence of ARDS, 75 cases per 100,000 person per year population correlating with 150,000 cases per year in this country, was published in an expert panel report by the National Institute of Health in 1972.3 The American European Consensus Conference (AECC) redefined ARDS in 1992. Recent studies based on the AECC criteria found incidence rates that varied from 4.9 to 22 per person years. More recent studies reported high incidence rate of ARDS among ventilated patients. In a large multicenter study including 5183 mechanically ventilated patients, 9% of patients met ARDS criteria at the beginning or over the course of the ventilatory support.4 In a more recent prospective study, Estenssoro et al.5 found that 8% of patients admitted to an intensive care unit (ICU) and 20% of mechanically ventilated patients fulfilled criteria for ARDS.
The reported rate of mortality from ARDS ranges from 31% to 74%. Several investigators have observed a reduction in mortality rates over time, from more than 60% in the 1980s to less than 40% in the 1990s.2,6 Most studies have indicated that nonsurvivors of ARDS usually die of nonrespiratory causes. In 1985, Montgomery et al.7 highlighted that only 16% of deaths were caused by respiratory failure. In most cases, early death was caused by underlying disease, whereas late death was caused by sepsis. Recently, Bersten et al.8 showed that respiratory failure was the cause of death in only 9% of ARDS cases. Thus, ARDS is a systemic disease and the main cause of death is related to multiorgan failure. It is interesting that degree of hypoxemia is unimportant in terms of predicting mortality. Valta et al.9 showed that age, right ventricular dysfunction, and the presence of acute renal failure were found to have important prognostic value.
DEFINITION AND CLINICAL DIAGNOSIS
The definition of ARDS has been simplified over the past few years, allowing clinicians to identify patients earlier. Ashbaugh’s 1967 original description consisted of respiratory distress, cyanosis, decreased lung compliance, and bilateral infiltrates on chest radiograph.10 In 1988, Murray and Mathay devised a four-point scoring system that included the level of positive end expiratory pressure (PEEP), the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), lung compliance, and chest x-ray findings.11 In 1994, the AECC modified the 1988 definition and their new definition included the following major components12:
Acute respiratory distress syndrome presents with dyspnea, usually developing within 72 hours of the initial insult. Some patients may progress to moderate or severe respiratory failure necessitating intubation. Stable patients with mild to moderate ALI can be cautiously managed with a trial of noninvasive ventilation.13 Arterial blood gas will often reveal hypoxia with respiratory alkalosis. The diagnosis is confirmed by chest x-ray, which shows bilateral infiltrates resembling pulmonary congestion. Infrequently, the chest x-ray will have an atypical pattern that will be asymmetric or unilateral. Computer tomography of the chest, if obtained, shows consolidation with atelectasis in the dependent zones.14
Acute respiratory distress syndrome is associated with several clinical disorders, sepsis being the most common among them (40%).5 Two clinical disorders often found in trauma patients are pulmonary contusion and multiple blood transfusions, which can lead to ARDS. Pulmonary contusion is a direct insult to the lung parenchyma, leading to the accumulation of blood and proteinaceous fluid at the alveolar-capillary interface.15 This will lead to ALI in many patients, with some patients progressing to ARDS. Trauma patients requiring multiple transfusions of packed red cells are at risk for ARDS. Transfusion-related ALI (TRALI) accounts for a small percentage of cases of ARDS. The exact mechanism of TRALI is still unclear.
PATHOPHYSIOLOGY
Acute respiratory distress syndrome is a devastating form of acute respiratory failure that frequently develops in patients with pulmonary and nonpulmonary organ failure. Experimental and clinical data regarding the pathogenesis of disease have evolved significantly over the past decade. ARDS is an extremely severe form of ALI that occurs as a result of systemic inflammation caused by either direct or indirect lung injury. Direct lung injury is associated with high mortality rate. Some causes of direct lung injury include pneumonia, aspiration, and pulmonary contusion. Common causes of indirect lung injury are sepsis, multiple blood transfusion, shock, and acute pancreatitis.16 Regardless of the initial etiology, ARDS is characterized histologically by diffuse alveolar damage with interstitial and alveolar infiltration with neutrophils and macrophages. On the other hand, it is a progressive disease and has indistinct stages with different histologic features.
The acute exudative phase is manifested by the rapid onset of respiratory failure. Arterial hypoxemia that is refractory to oxygen is a characteristic feature. Pathologically, this picture is characterized by injury of the alveolar-capillary membrane and accumulation of protein-rich fluid with neutrophils, macrophages, and disruption of the endothelial-epithelial barrier—ending with the development of the pulmonary interstitial edema secondary to microcapillary circulatory injury.17 The resulting interstitial accumulation of fluid and protein impairs diffusion capacity and thus oxygenation. These changes are responsible for the decreasing pulmonary compliance and hypoxemia. Disruption of the alveolar epithelium and loss of types 1 and 2 pneumocytes lead to loss of the mechanical barrier integrity, leading to bacterial translocation and sepsis.
The key role of the activated neutrophils and macrophages has been established based on analyses of bronchoalveolar (BAL) fluid in the acute phase of ARDS.18 Several recent studies stressed that activated neutrophils and macrophages produce cytokines, including TNF-α, interleukins IL-1βm IL-6, IL-8, and IL-10 (all of these playing essential roles in pathophysiology of ARDS).19 Recovery from ARDS is characterized by the resolution of the alveolar edema and recuperation of the alveolar epithelial barrier. During the acute phase of inflammation, alveolar epithelial cells undergo apoptosis. Once recovery begins, type 2 cells proliferate—producing surfactant. The type 2 cells then differentiate to type 1 cells. After the acute phase, some patients make uncomplicated and rapid recovery—whereas others progress to the fibrotic stage, which has been observed early in the course of disease.20 The alveolar space filled with mesenchymal cells (producing procollagen 3 peptide, collagen, and fibronectin, along with new blood vessels) gives a histologic picture of fibrosing alveolitis associated with poor outcome and an increased risk of death.21
