Acute respiratory distress syndrome (ARDS) is a common complication of critical illness or injury associated with significant morbidity and mortality. The pathogenesis of ARDS involves mechanical and inflammatory injury to the lungs, which causes marked derangement in alveolar-capillary permeability and the passage of protein-rich edema fluid into the air spaces. ARDS usually occurs in a context of uncontrolled response to local or systemic inflammation. The clinical pathogenesis is often multifactorial with complex interaction of risk factors and risk modifiers ( Fig. 12-1 ).
Predisposing Conditions
Sepsis, pneumonia, and shock are the most common conditions predisposing to ARDS. However, only a minority of these patients actually have ARDS ( Fig. 12-2 ). Other typical predisposing conditions include aspiration, trauma, and massive blood product transfusion. Atypical respiratory infections, including viral ( influenza ) and fungal ( Pneumocystis jiroveci , Histoplasma spp., Blastomyces spp.) infections, are unusual but important causes of ARDS, especially in patients with compromised immune systems. Several emerging pathogens, such as severe acute respiratory syndrome, Middle East respiratory syndrome-coronavirus, and epidemic H1N1 influenza, also confer increased risk for ARDS. Additional patient risk factors include gastroesophageal reflux disease, chronic silent aspiration, and drug exposures.
Certain host genetic variants have been associated with development of sepsis and ARDS. These abnormalities include mutations in the surfactant protein-B. Genetic associations have been generally difficult to replicate, and the role of genetic predisposition in development of ARDS is presently unclear.
Risk Modifiers
Sepsis in alcoholics is associated with a distinctly high risk of ARDS. Chronic alcohol use carries a twofold to threefold increase in ARDS development. The exact mechanism of this association remains unknown, but it may be related to a reduction in the antioxidant capacity of the lung. In addition, acute and chronic consumption of alcohol cause an increase in the systemic levels of adenosine and a dose-dependent reduction in alveolar fluid clearance through stimulation of the adenosine type 1 receptor, adding to the lung injury. A recent study in trauma patients demonstrated that the risk of ARDS increased in direct proportion to the blood alcohol content.
A history of tobacco exposure (including second-hand smoking) has been associated with an increased risk of ARDS in trauma patients. Another study found an independent dose–response association between current cigarette smoking and subsequent development of ARDS.
Hypoalbuminemia is a well-known marker of acute or chronic illness or malnutrition and poor surgical outcomes. It was also found to be an independent risk factor for ARDS. This appears to be mediated by decreases in plasma oncotic pressure with increased pulmonary permeability in the critically ill, independent of underlying cause and fluid status.
Hypercapnic acidosis protects against ventilator-induced lung injury in several animal models of ARDS. However, low pH and, in particular, metabolic acidosis have been associated with increased risk of ARDS.
Obesity is also an independent risk factor for the development of ARDS. Although the effects of body position and compression atelectasis may in part explain the observed association, additional mechanisms have been proposed. These include an imbalance between proinflammatory and anti-inflammatory cytokines, which increases lung inflammation and injury through the tumor necrosis factor-α and interleukin-6 pathways.
Diabetes mellitus seems to be associated with a lower risk of ARDS in septic shock. Indeed, a recent meta-analysis that included a total of 12,794 adult patients suggested that diabetes protected against ARDS. Although the exact mechanism is not known, one possible explanation is that diabetic patients have impaired activation of the inflammatory cascade in the lungs.
An alternative hypothesis for ARDS pathogenesis has been proposed, suggesting that surfactant dysfunction may be a critical step in ARDS progression. Both spontaneous and mechanical hyperventilation can induce surfactant dysfunction, leading to higher surface tension and atelectasis. This injury is augmented by supine position and sedation, and this effect can be particularly pronounced in obese patients. However, trials administering surfactant in ARDS patients did not show a mortality benefit.
Risk Prediction Models
The Lung Injury Prediction Score (LIPS) was created in 2011 with the intent to facilitate the design and conduct of ARDS prevention studies. The model includes risk factors and risk modifiers present at the time of hospital admission, before ARDS occurs. It was later validated and refined ( Table 12-1 ). A simplified model, the Early Acute Lung Injury Score, predicts ARDS on the basis of oxygen requirement, respiratory rate, and presence of immunosuppression in patients with bilateral infiltrates on chest imaging.
| LIPS Points | Examples | |
|---|---|---|
| Predisposing conditions | (1) Patient with history of alcohol abuse with septic shock from pneumonia requiring Fio 2 > 0.35 in the emergency room: Sepsis + shock + pneumonia + alcohol abuse + Fio 2 > 0.35 1 + 2 + 1.5 + 1 + 2 = 7.5 | |
| Shock | 2 | |
| Aspiration | 2 | |
| Sepsis | 1 | |
| Pneumonia | 1.5 | |
| High-risk surgery ∗ | ||
| Orthopedic spine | 1 | |
| Acute abdomen | 2 | |
| Cardiac | 2.5 | |
| Aortic vascular | 3.5 | |
| High-risk trauma | (2) Motor vehicle accident with traumatic brain injury, lung contusion, and shock requiring Fio 2 > 0.35 Traumatic brain injury + lung contusion + shock + Fio 2 > 0.35 2 + 1.5 + 2 + 2 = 7.5 | |
| Traumatic brain injury | 2 | |
| Smoke inhalation | 2 | |
| Near drowning | 2 | |
| Lung contusion | 1.5 | |
| Multiple fractures | 1.5 | |
| Risk modifiers | (3) Patient with history of diabetes mellitus and urosepsis with shock 1 + 2 − 1 = 2 | |
| Alcohol abuse | 1 | |
| Obesity (BMI > 30) | 1 | |
| Hypoalbuminemia | 1 | |
| Chemotherapy | 1 | |
| Fio 2 > 0.35 (> 4 L/min) | 2 | |
| Tachypnea (RR > 30) | 1.5 | |
| SpO 2 < 95% | 1 | |
| Acidosis (pH < 7.35) | 1.5 | |
| Diabetes mellitus † | −1 |
∗ Add 1.5 points if emergency surgery.
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