Acute respiratory distress syndrome (ARDS) is a clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure.

ARDS is caused by diffuse lung injury from many underlying medical and surgical disorders. The lung injury may be direct, as occurs in toxic inhalation, or indirect, as occurs in sepsis (Table 322-1). The clinical features of ARDS are listed in Table 322-2. By expert consensus, ARDS is defined by three categories based on the degrees of hypoxemia (Table 322-2). These stages of mild, moderate, and severe ARDS are associated with mortality risk and with the duration of mechanical ventilation in survivors.

 

ARDS is a diffuse, acute, inflammatoryalveolar injury manifested by severe hypoxia and bilateral radiographic infiltrates of noncardiogenic etiology. It can result from either direct pulmonary injury or in response to a systemic insult. Imaging plays an important role in the diagnosis of ARDS and may help determine its underlying etiology.

 ARDS is defined by timing (within 1 wk of clinical insult or onset of respiratory symptoms); radiographic changes (bilateral opacities not fully explained by effusions, consolidation, or atelectasis); origin of edema (not fully explained by cardiac failure or fluid overload); and severity based on the PaO2/FIO2 ratio on 5 cm of continuous positive airway pressure (CPAP). The 3 categories are mild (PaO2/FIO2 200-300), moderate (PaO2/FIO2 100-200), and severe (PaO2/FIO2 ≤100).¹

 

 Acute respiratory distress syndrome (ARDS) is the archetypal example of increased-permeability edema. While the underlying pathophysiology is complex, the fundamental mechanism is an inflammation-mediated disruption of the alveolar capillary barrier. Through loss of endothelial and epithelial barrier integrity, the normal homeostatic mechanisms of fluid balance are disrupted, and protein-rich fluid accumulates in the alveolar space. This loss of integrity may result from direct injury to the alveolar epithelium following the local activation of inflammation by inhaled toxins or pulmonary infection. Or it may occur after injury to the pulmonary capillary endothelium following the systemic activation of inflammation by circulating toxins, as, for example, in sepsis or pancreatitis. Whether the injury occurs directly or indirectly, the insult activates the innate immune response through resident immune cells such as the alveolar macrophage. These cells recognize both exogenous factors, such as those derived from microorganisms, and endogenous factors, elaborated by local or distant cellular injury, through “pattern recognition” receptors (eg, toll-like receptors). Receptor activation stimulates pro-inflammatory responses. Through the release of cytokines and chemokines such as IL-1B, TNFα, IL-6, and IL-8, circulating inflammatory cells including neutrophils and monocytes are recruited to the lung and undergo activation, which further potentiates the pro-inflammatory signal. The propagation of this inflammatory cascade results in direct and indirect tissue injury through the release of a variety of factors, including other cytokines and chemokines, proteases, eicosanoids, and reactive oxygen species. Loss of the barrier integrity as a result of injury to both the alveolar epithelium and capillary endothelium ultimately leads to the leakage of protein-rich fluid into the alveolar spaces throughout the lung. There, the edema fluid inactivates surfactant, increasing surface tension with resultant alveolar instability and atelectasis. Increased surface tension also decreases the interstitial hydrostatic pressure, further favoring fluid movement into the alveolus. The loss of surfactant activity and the filling of airspaces cause the significant physiologic derangements that characterize ARDS, including decreases in both lung compliance and lung volume, resulting in severe hypoxemia (secondary to low V̇/Q̇ and shunt).

C. The severe hypoxia found in ARDS is due to several factors. Damage to endothelial and epithelial cells causes increased vascular permeability and reduced surfactant production and activity. These abnormalities lead to interstitial and alveolar pulmonary edema, alveolar collapse, a significant increase in surface forces, markedly reduced pulmonary compliance, and hypoxemia. As the process worsens, there may be a further fall in compliance and disruption of pulmonary capillaries, leading to areas of true shunting and refractory hypoxemia. The combination of increased work of breathing and progressive hypoxemia usually requires mechanical ventilation. The underlying process is heterogeneous, with normal-appearing lung adjacent to atelectatic or consolidated lung. Therefore, ventilating patients at typical tidal volumes may overdistend normal alveoli, reduce blood flow to areas of adequate ventilation, and precipitate further lung injury (“volu-trauma”). Hypoxemia can be profound in ARDS, typically followed days later by hypercapnia owing to increasing dead space ventilation.

Limiting pulmonary edema or accelerating its resorption through the modulation of fluid intake or oncotic pressure could be beneficial.

 

Focus efforts on preventing secondary insults and avoiding ventilator-associated lung injury.

Low tidal volume approach entails use of a tidal volume of 6 mL/kg of predicted body weight with respiratory rate adjusted to achieve adequate minute ventilation.

The goal is to achieve plateau pressures of ≤ 30 cm water. The PEEP ladder below  guides PEEP settings according to FIO2.

From The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:1301–1308.

PEEP, Positive end-expiratory pressure

Complications of Injecting Drug Use

• Local problems—Abscess (Figures 240-2 
  

  A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

  and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
  • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
  • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
• IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
  • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.