A more recent report, based on the so-called, “Berlin definition,”2 recommends identification of three categories of ARDS, based upon the degree of hypoxemia alone:

(1) mild ARDS (200 O2/FIO2 ≤300 mm Hg);

(2) moderate ARDS (100 O2/FIO2 ≤200 mm Hg); or

(3) severe ARDS (PaO2/FIO2 ≤100 mm Hg).2 




Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair.



Acute lung injury is similarly defined; it differs only in the degree of hypoxemia (P/F ratio ≤ 300).


The causes of ARDS are multifactorial and include but are not limited to:

  • Trauma
  • Sepsis
  • Aspiration
  • Pneumonia
  • Severe pancreatitis
  • Severe burns
  • Transfusion-related acute lung injury
  • Chemical pneumonitis or inhalational injury


Management of ARDS is generally supportive. Focus efforts on preventing secondary insults and avoiding ventilator-associated lung injury. The ARDS Network 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 in Table 20–8 guides PEEP settings according to FIO2.




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

This syndrome is defined by acute onset (≤1 week) of bilateral opacities on chest imaging that are not fully explained by cardiac failure or fluid overload and of shunt physiology

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




is an acute, diffuse, inflammatory lung injury

ARDS is particularly characterized by pulmonary edema caused by an increase in pulmonary capillary permeability.

This review discusses the principal clinical studies that have made it possible to progress in the optimization of the fluid state during ARDS. Notably, a randomized, multicenter study has suggested that fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, it is accepted that patients with hemodynamic failure must undergo early and adapted vascular filling. Liberal and conservative filling strategies are therefore complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, although albumin treatment has been suggested to improve oxygenation transiently in ARDS patients, no sufficient evidence justifies its use to mitigate pulmonary edema and reduce respiratory morbidity. Finally, the resorption of alveolar edema occurs through an active mechanism, which can be pharmacologically upregluated. In this sense, the use of beta-2 agonists may be beneficial but further studies are needed to confirm preliminary promising results.+++++++++++++++++++ARDS is caused by diffuse lung injury from many underlying medical and surgical disorders.1

Acute respiratory distress syndrome (ARDS): severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure. ++++++++++++++++++++ARDS is the final common pathway of a number of different serious medical conditions, all of which lead to increased pulmonary capillary leak.

The natural history of ARDS is marked by three phases—exudative, proliferative, and fibrotic.

Image not available.

Diagram illustrating the time course for the development and resolution of ARDS. The exudative phase is notable for early alveolar edema and neutrophil-rich leukocytic infiltration of the lungs, with subsequent formation of hyaline membranes from diffuse alveolar damage. Within 7 days, a proliferative phase ensues with prominent interstitial inflammation and early fibrotic changes. Approximately 3 weeks after the initial pulmonary injury, most patients recover. However, some patients enter the fibrotic phase, with substantial fibrosis and bullae formation.


What are the main pathophysiologic factors in ARDS that cause an accumulation of extravascular fluid in the lungs?

 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).




What accounts for the severe hypoxia often found in ARDS, despite the use of mechanical ventilation and high concentrations of oxygen?

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.


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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.

PEEP Ladder
Fio2 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.0
PEEP 5 5–8 8–10 10 10–14 14 14–18 18–22

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 
    Image not available.

    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.


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You are managing a patient admitted to the medical ICU for severe acute respiratory distress syndrome due to necrotizing pancreatitis. The patient has an ideal body weight of 70 kg. The patient’s ventilator is set on a volume control with a respiratory rate of 28 bpm, tidal volume of 420 mL, FiO2 of 0.7, and PEEP of 8 cmH2O. The patient is hypoxemic with an SaO2 of 86% on these settings. You review the static pressure-volume curve for the respiratory system. The lower inflection point is at 12 cmH2O. The upper inflection point is at 30 cmH2O. Measured pressure with an inspiratory hold is 26 cmH2O. Which of the following is the best choice to improve oxygenation in this patient?

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The correct answer is D.

 Hypoxemia in ARDS results in shunt physiology with the presence of alveolar and interstitial fluid and loss of surfactant. In turn, there is significant loss of lung compliance and development of alveolar collapse that is worse in the dependent portions of the lungs. During mechanical ventilation, the goal is to minimize overdistention of less affected areas of the lungs while maximizing alveolar recruitment. Positive end-expiratory pressure (PEEP) is used to prevent alveolar collapse at end-expiration. Trials of mechanical ventilation with high-PEEP compared to low-PEEP strategies did not show any differences in outcomes when a low tidal volume ventilation strategy was used. More recently, a trial used a strategy that involved constructing static pressure-volume curves of the lung on the mechanical ventilator. With this strategy, a lower inflection point can be calculated. This point identifies the pressure at which the alveoli open. In ARDS, this point is typically 12–15 cmH2O. In theory, setting the PEEP to this pressure will maximize oxygenation and prevent lung injury. Trials of this mode of ventilation improve lung function and may have an effect on mortality. More recently, strategies employing esophageal pressure catheters to estimate optimal transpulmonary pressure are being studied to determine the effects on oxygenation, duration of mechanical ventilation, and mortality.


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Which of the following conditions is NOT a common cause of the changes featured in the image?

The correct answer is B.

The image depicts hyaline membranes in the lung, characteristic of diffuse alveolar damage (histologic correlate of acute respiratory distress syndrome). Metastatic neoplasms are not a common cause of diffuse alveolar damage.