Epidemiology

ARDS was initially described by Laennec in 1821, as a new syndrome characterized by pulmonary edema without heart failure.⁷ Subsequently, terms such as “double pneumonia” and “shock lung” were used to describe this syndrome, before the term “acute respiratory distress syndrome” was coined by Ashbaugh and colleagues in 1967.⁸ ARDS may result from intrapulmonary or extrapulmonary mechanisms, and indeed the cause is often multifactorial. It develops most commonly in the context of severe bacterial and viral pneumonia, nonpulmonary sepsis, aspiration, and trauma. Some of the less common causes of ARDS are included in Table 18.2. Perioperative lung injury results from a complex interaction between the patient’s physiologic state, the underlying surgical diagnosis and technique, and interaction with the mechanical ventilator. Although ARDS is a common entity, it is important to understand that there are many clinical pathologies that mimic ARDS and should be considered, especially in the absence of an inciting factor (Table 18.3).⁹

Several comorbidities and exposures have been implicated in elevating the risk for developing ALI, and or worse outcomes, including excessive alcohol consumption,¹⁰ cigarette smoking,¹¹ and environmental pollutants.¹² Data from the United States and the United Kingdom suggest there is also an association between mortality, ethnicity, and gender. Black, Asian, and minority ethnicity patients and male patients have a higher than average mortality from ALI than White and female patients.¹³ The biologic cause for such disparities, beyond social inequality, is not clear. Erickson and colleagues concluded that it appeared to be mediated by increased severity of illness at presentation for Black patients but could not explain the increase seen among Hispanics in the United States.¹³

Imaging

The plain chest radiograph appearance that is consistent with ARDS is that of bilateral diffuse alveolar opacification, although it has been demonstrated that there is significant interobserver variability, and the findings may be subtle.¹⁴ As the severity worsens, the consolidation becomes more apparent.¹⁴ Computed tomography (CT) scanning of patients with ARDS reveals a more detailed picture of the heterogeneous nature of the lung injury than chest x-ray. The information gained from the CT scan can help quantify the extent of the abnormalities and localize them.¹⁵

The classic findings of early ARDS on CT scan are: (1) normal (or near-normally) aerated lung regions with minimal pathologic findings, most commonly in the least dependent zones of the lung. These tend to be ventral when the patient is supine; (2) a hazy increase in lung attenuation, with preservation of bronchial and vascular margins, known as ground glass opacification in the middle lung; and (3) consolidative changes in the most dependent (dorsal) zones of the lung, appear as a homogeneous increase in lung attenuation that obscures bronchovascular margins in which air-bronchograms may be present.^15,16

Lung ultrasound (LUS) is being used with increasing frequency to aid in the diagnosis of ARDS, and to help differentiate it from other lung pathologies (see Ch. 54). It has been demonstrated that LUS can identify the principal pathologic findings in ARDS with reasonable sensitivity and specificity.¹⁷ International evidence-based recommendations for the use of LUS were established in 2012.¹⁸ LUS is recommended as a tool to help evaluate and differentiate between fibrotic lung disease, pulmonary edema, and ARDS.¹⁸

The four main patterns that are seen on LUS are summarized from these guidelines as follows:

1. 1. Normally aerated lung, represented by lung sliding and artifactual horizontal repetitions of the pleural line, known as A-lines.
   
2. 2. Alveolar-interstitial syndrome, represented by the presence of three or more discrete laser-like vertical hyperechoic reverberation artifacts arising from the pleural line, extending to the bottom of the screen without fading, and moving synchronously with lung sliding, known as B-lines.
   
3. 3. Consolidation, represented as a subpleural area consisting of tissue-like echodensities interlaced with echo-poor areas which are indicative of dynamic air bronchograms.
   
4. 4. Pleural effusions, represented by an anechoic space between the parietal and visceral pleura, with respiratory movement of the lung within the effusion.^18,19

When compared with CT scanning, LUS has shown reasonable sensitivity and specificity (82.7%–92.3% and 90.2%–98.6%, respectively) in the diagnosis of ARDS.¹⁹ Its portability, lack of radiation, and steep learning curve make it an ideal tool in many situations to assist in diagnosis ARDS.

Genotype

There has been significant investment in research to identify genetic factors that: increase susceptibility to ALI or delineate genetic subtypes. The advantages of identifying the “gene for ALI” would be to determine those at risk and to appropriately match intervention(s) with subtype.

Although no specific gene has been identified for ARDS, there has been some success identifying candidates that are associated with the pathologic mechanisms that in turn confer higher mortality, for example, lung vascular permeability and the angiopoietin 2 gene (ANGPT2).²²

Pathologic Phenotype

The pathologic phenotype of ALI is “diffuse alveolar damage,” (Fig. 18.2). The degree of alveolar epithelial injury and increased vascular permeability, leading to the formation of pulmonary edema, is a valuable predictor of outcome. Biopsies taken from the lungs of patients, within the first 7 days of ALI, display the histologic features of cell death, epithelial hyperplasia, inflammation, disordered coagulation, and fibrinolysis. In addition, there is an alveolar cellular infiltrate, rich with neutrophils, macrophages, and erythrocytes. The normal alveolar epithelium of type I and type II alveolar cells is anatomically and functionally disrupted. The tight barrier that selectively restricts the movement of solutes is denuded and becomes lined by fibrin-rich hyaline exudates.²³

Edema Formation

The reabsorption of fluid in the alveolus depends on the integrity and health of the barrier of type I and type II alveolar cells. This monolayer of cells is linked by tight junctions and adherens junctions, and both are key to the transport of ions and fluid from the airspace. Loss of epithelial integrity and injury to type II cells will disrupt normal fluid and cellular transport; leading to impaired fluid removal from the alveolar space,²⁴ septic shock in patients with pneumonia,²⁵ and impaired surfactant production.²⁶

Surfactant Production

The type II alveolar epithelial cell is the more complex alveolar epithelial cell. It is a highly metabolically active cell, most appreciated for the synthesis and secretion of pulmonary surfactant proteins. There are four such proteins, A to D, responsible for reducing alveolar surface tension, enabling them to remain open. Dysfunction contributes to inhomogeneous airspace collapse, and low levels of protein D are associated with increased mortality.

Surfactant release is initially enhanced by high-volume ventilation. However, the increased surface area of the alveoli increases the rate at which surfactant is released, eventually exceeding the rate of production.²⁷ Higher tidal volumes also increase the conversion of the large aggregate surfactant on epithelial cells. Eventually, the basement membrane gives way, leading to alveolar hemorrhage.²⁸ Finally, the increasing alveolar pulmonary edema fluid contains serum proteins and proteases that disable surfactant proteins.²⁹

The clinical significance of flooding of the alveolar airspaces is that it rapidly impairs adequate ventilation, resulting in hypoxemia from ventilation-perfusion mismatch and intrapulmonary shunt. Additional right-to-left shunt from reabsorption atelectasis, secondary to alveolar denitrogenation, may also contribute when high levels of oxygen are administered.³⁰ In the presence of protein-rich pulmonary edema fluid, cellular infiltrate, and a reduction in functionally active surfactant, will results in a dramatic reduction in thoracic compliance.