Acute Respiratory Distress Syndrome Definition, Causes, and Pathophysiology
First successfully described in 1967, acute respiratory distress syndrome has since garnered much interest and debate. Extensive studies and clinical trials have been carried out in efforts to address the associated high mortality; however, it remains a significant burden on health care. Despite the heterogeneous etiologies that lead to the development of acute respiratory distress syndrome, this rapidly progressing form of respiratory failure, characterized by severe hypoxemia and nonhydrostatic pulmonary edema, has a recognizable pattern of lung injury. In this chapter, we will review the clinical manifestations, definitions, causes, and a brief overview of the pathophysiology of this complex syndrome.

Complications and Outcomes of Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) is a disease associated with both short- and long-term complications. Acute complications include refractory respiratory failure requiring prolonged dependence on mechanical ventilation and the subsequent need for tracheostomy and gastrostomy tubes, protracted immobilization, and lengthy stays in the intensive care unit resulting in delirium, critical illness myopathy, and polyneuropathy, as well as secondary nosocomial infections. Chronic adverse outcomes of ARDS include irreversible changes such as fibrosis, tracheal stenosis from prolonged tracheostomy tube placement, pulmonary function decline, cognitive impairment and memory loss, posttraumatic stress disorder, depression, anxiety, muscle weakness, ambulatory dysfunction, and an overall poor quality of life. The degree of disability in ARDS survivors is heterogeneous and can be evident even years after hospitalization. Although survival rates have improved over the past 4 decades, mortality remains significant with rates reported as high as 40%. Despite advancements in management, the causes of death in ARDS have remained relatively unchanged since the 1980s with sepsis/septic shock and multiorgan failure at the top of the list.

Acute Kidney Injury in the Context of Acute Respiratory Distress Syndrome
Acute kidney injury is a heterogeneous syndrome defined by rapid (hours to days) decline in the glomerular filtration rate leading to retention of metabolic waste products including creatinine and urea, resulting in declination of the body's ability to manage fluid status and acid-base regulation. Acute kidney injury is seen commonly in acute respiratory distress syndrome and this article will explore the relationship between the 2 entities.

Prone Positioning in ARDS
Adult respiratory distress syndrome (ARDS) is a clinical entity characterized by hypoxemic respiratory failure in the setting of noncardiogenic pulmonary edema. It is associated with significant morbidity and mortality. Prone positioning is a beneficial strategy in patients with severe ARDS because it improves alveolar recruitment, ventilation/perfusion (V/Q) ratio, and decreases lung strain. The outcome is improved oxygenation, decreased severity of lung injury, and, subsequently, mortality benefit. In this article, we discuss the physiology of prone positioning on chest mechanics and V/Q ratio, the placement and maintenance of patients in the prone position with use of a prone bed and the current literature regarding benefits of prone positioning in patients with ARDS.

Paralytics, Sedation, and Steroids in Acute Respiratory Distress Syndrome
In this article, we discuss the literature behind the use of paralytics, sedation, and steroids in acute respiratory distress syndrome. We explore the controversies and discuss the recommendations for the use of these agents.

Mechanical Ventilation in ARDS
Mechanical ventilation is the primary supportive, invasive measure utilized in patients with acute respiratory distress syndrome. Throughout the years, many large multicenter randomized controlled trials and observational studies were analyzed to determine what ventilator parameters to use that would produce a mortality benefit after initial diagnosis. This article discusses the concepts of ventilator-induced lung injury, permissive hypercapnia, high-versus-low peep strategies, oxygenation goals, and recruitment strategies from a physiologic perspective and the major studies that produced recommendations for each. Newer concepts, such as driving pressure, are also discussed.

Extracorporeal Membrane Oxygenation in ARDS
Extracorporeal membrane oxygenation (ECMO) has become a key tool in the management of cardiac and/or respiratory failure refractory to conventional management. Although ECMO has multiple indications, it has been widely studied for the management of acute respiratory distress syndrome in adults. ECMO provides rest and support while the damaged lungs heal. It is an invasive modality with risks of serious complications; therefore, clinicians should be vigilant during patient selection. Furthermore, users should be familiar with different components of the ECMO machinery and the management of different organ systems while patients are on the circuit. ECMO is a relatively new modality that has shown good results when used in certain circumstance, and its use is becoming more popular across the United States.

Acute Respiratory Distress Syndrome Novel Therapies
Acute respiratory distress syndrome (ARDS) was first described in 1967. Since then, several landmark studies have been published that have greatly influenced the way we diagnose and treat patients with ARDS. Despite extensive research and advancements in ventilator strategies, moderate-severe ARDS has been associated with high mortality rates. Current treatment remains primarily supportive with lung-protective ventilation strategies. Pharmacological therapies that reduce the severity of lung injury in vivo and in vitro have not yet translated into effective clinical treatment options. Currently, the mortality rate of severe ARDS remains in the range of 30% to 40%. To review, the mainstay of ARDS management includes mechanical ventilation with low tidal volumes to decrease barotrauma, prone ventilation, conservative fluid management, and neuromuscular blockade. ARDS survivors tend to have long-term and potentially permanent neuromuscular, cognitive, and psychological symptoms, affecting patient's quality of life posthospitalization. These long-term effects are likely secondary to prolonged hospitalizations, prolonged mechanical ventilation, utilization of prone strategies, utilization of paralytic drugs, and occasionally steroids. Therefore, several novel therapies outside the realm of advanced ventilation and prone positioning methods are being studied. In this article, we discuss a few of these novel therapies including prophylactic aspirin, inhaled nitric oxide, mesenchymal stem cells, and intravenous β-agonists. Steroids and extracorporeal membrane oxygenation have been discussed in a previous article.

Mimics of Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) was first described in 1967 by Ashbaugh and colleagues. Acute respiratory distress syndrome is a clinical syndrome, not a disease, and has no ideal definition or gold standard diagnostic test. There are multiple causes and different pathways of pathogenesis as well as various histological findings. Given these variations, there are many clinical entities that can get confused with ARDS. These entities are discussed in this article as “Mimics of ARDS.” It imperative to correctly identify ARDS and distinguish it from other diseases to implement correct management strategy.