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Acute respiratory distress syndrome.

The expression acute respiratory distress syndrome (ARDS) emerged from the American-European Consensus Conference on ARDS in 1994. Previous to that date, the designation adult respiratory distress syndrome, introduced by Ashbaugh in 1967, was used to describe this condition. Before 1967, ARDS was described by numerous terms which included: Da Nang lung, white lung syndrome, pump lung, shock lung, wet lung, stiff lung syndrome, adult hyaline membrane disease, & adult respiratory insufficiency.

In addition to renaming ARDS in 1994, the American-European Consensus Conference on ARDS standardized the definition of this syndrome and established clinical criteria used to differentiate ARDS from acute lung injury (ALI). The criteria used to define ARDS and ALI are listed below.

Clinical Criteria Used to Differentiate ARDS from ALI

Criteria Defining ARDS

* onset: acute

* oxygenation: Pa02/FI02 < 200

* chest radiography: bilateral pulmonary infiltrates

* hemodynamic monitoring: pulmonary capillary wedge pressure

<18 torr, or absence of left atrial hypertension.

Criteria Defining ALI

* onset: acute

* oxygenation: Pa02/FI02 <300

* chest radiography: bilateral pulmonary infiltrates

* hemodynamic monitoring: pulmonary capillary wedge pressure <18 torr, or absence of left atrial hypertension.

Interestingly, the response among patients to injury varies. Some patients develop ARDS and others ALP. Still, others demonstrate no signs and symptoms.

Despite the attention received by ARDS over the years, a dismal clinical outcome continues to be associated with this syndrome. Although its pathophysiology has been extensively studied and researched, mortality rates remain high, i.e., around 50% to 60%. Relatively recent mechanical ventilation strategies such as permissive hypercapnia and the use of low tidal volumes have somewhat improved the prognosis.


According to the American Lung Association, the incidence of ARDS ranges between 1.5 and 75 per 100,000 persons each year in the United States. According to the American-European Consensus Conference on ARDS, approximately 150,000 people in the United States develop ARDS every year.

In light of the high mortality rate associated with ARDS, the actual survivability depends on multiple factors. These factors include predisposing conditions, severity of illness, age, comorbid conditions, and, in patients with trauma, severity of the underlying pulmonary injury.


Acute respiratory distress syndrome is not a disease per se. ARDS is a syndrome, encompassing a complex array of signs and symptoms. It can also be viewed as a life-threatening complication of some other disease or condition.

ARDS is a medical emergency that has multiple causes. The conditions producing ARDS are often classified into two categories: direct lung (pulmonary) injury and indirect lung (nonpulmonary) injury. Causes of ARDS resulting from direct lung injury include the following conditions: pneumonia, aspiration of gastric contents, pulmonary contusion, fat embolism, smoke/chemical inhalation, near-drowning, and re-perfusion pulmonary edema. The lungs are the primary site of injury for these conditions

Conditions that cause ARDS from indirect lung injury include: sepsis, burns, acute pancreatitis, drug overdose, multiple trauma, cardiopulmonary bypass, and multiple blood transfusions. These disparate causes share a commonality in their relationship with ARDS. They all produce acute inflammation of the alveolar-capillary membrane despite a site other than the lungs being the primary location of injury.

Among the causes of ARDS, sepsis is the most common. However, other factors such as blood transfusions, advanced age, and cigarette smoking increase the risk of developing ARDS.


The primary abnormality in ARDS is the disruption of the alveolar-capillary membrane. The breakdown of this barrier results in alveolar and pulmonary capillary permeability. This increased permeability leads to pulmonary interstitial and alveolar edema. This protein-rich fluid floods the alveoli.

Neutrophils and macrophages are summoned to the site of the pulmonary capillary endothelium. There these scavengers cells release cytokines (interleukins and tumor necrosis factor), oxygen radicals, arachidonic acid metabolites (leukotrienes and prostaglandins), and proteolytic enzymes (elastase and collagenase). These mediators produce an inflammatory response and are responsible for damage to the alveolar epithelium and the capillary endothelium, resulting in increased alveolar-capillary permeability.

As a consequence to the cellular damage and the alveolar flooding, pulmonary surfactant is inactivated. The sequel to the inactivation of pulmonary surfactant is an increase in the surface tension within the alveoli. This development causes alveolar collapse, capillary shunting, a decreased functional residual capacity, decreased lung compliance, and an increased work of breathing

The presence of edema fluid in the pulmonary interstitium and in the alveoli increases the distance across which oxygen molecules must diffuse to enter the blood. The patient experiences hypoxemia and hypoxia which further increase the work of breathing. The hypoxemia is not amenable to oxygen therapy. This refractory hypoxemia may be multifactorial, but intrapulmonary shunting with ventilation-perfusion disturbances are considered the primary cause.


Hypercarbia ensues as the work of breathing continues to increase. The hypercarbia along with the hypoxia raise the pulmonary artery pressures. The increased afterload imposed on the right ventricle may produce a lower right and left ventricular output. A decreased cardiac output complicates the oxygenation problem by compromising tissue oxygen delivery.

From a pathophysiologic standpoint, ARDS features three phases: (1) exudative, (2) proliferative, and (3) fibrotic. These phases are often overlapping.

Exudative Phase

The exudative phase tends to last the first week following the onset of the symptoms of ARDS. This phase is characterized by diffuse alveolar and pulmonary capillary damage. Tight junctions between capillary endothelial cells normally fuse, sealing these cells to each other. During this phase, these junctions disrupt and vascular fluid exudes through these openings. Within the first 24 hours of the onset of signs and symptoms, alveolar and pulmonary interstitial fluid are comprised of proteinaceous and hemorrhagic material. Hyaline membrane formation also characterizes the exudative phase. Both the pulmonary capillary endothelium and the alveolar epithelium display regions of damage. Neutrophils are abundant throughout the pulmonary interstitium, alveoli, and pulmonary capillaries.

Proliferative Phase

The proliferative phase often presents during the second to fourth week following the development of ventilatory failure. Alveolar air spaces fill with blood cells such as neutrophils and erythrocytes. Alveolar type II cells become more abundant as they attempt to repair the alveolar surface, destroyed by the loss of type I pneumocytes. This often coincides with the fibrotic phase, as fibroblasts appear in both the pulmonary interstitium and alveoli. Because these fibrotic and proliferative phases often overlap, some researchers elect to consolidate these two phases into what is termed the fibro-proliferative phase.

Fibrotic Phase

The fibrotic phase frequently occurs simultaneously with the proliferative phase. However, clinical evidence has revealed that some ARDS patients achieve complete resolution of their lung injury before progressing into the fibro-proliferative phase; others develop fibrosis.

The fibrotic phase represents tissue repair and features the development of patches of scar tissue forming in and around the pulmonary capillaries and the lung's acini. During this time, bronchoalveolar lavage reveals fewer neutrophils. At the same time, the collagen content of the lungs dramatically increases. Interestingly, elevated levels of procollagen peptides detected early in ARDS is predictive of poor prognosis.

The degree of fibrosis influences pulmonary compliance. The greater the fibrosis, the stiffer the lungs. Additionally, the tidal volume decreases, hypercarbia develops, and the patient's work of breathing increases. These changes also adversely affect oxygenation in the lungs, worsening hypoxemia and hypoxia.

Refractory hypoxemia may be multifactorial, but intrapulmonary shunting with ventilation-perfusion disturbances are believed to be the primary cause. Those who experience such early resolution appear to have a better prognosis than patient's whose ARDS advance to the fibro-proliferative or fibrotic phases.

The mortality associated with ARDS is primarily caused by multiple organ system failure. The mediators that wreck havoc on the lungs enter the systemic circulation and adversely influence other organs throughout the body.

Clinical Manifestations

Although ARDS is an emergency, most patients who develop ARDS do not demonstrate the signs and symptoms of this condition immediately following the original injury or illness. Frequently following the inciting injury or illness, patients experience a 24-to 48-hour latent period. During this time some patients may appear normal, and seem to be recovering from the injury or condition that resulted in their hospitalization. Then, following this latent period, a progression of clinical findings emerges. Sometimes the development of ARDS is concurrent with the predisposing event or illness.

During the first few hours of the onset of ARDS, patients exhibit tachypnea, dyspnea, tachycardia, agitation, and acute respiratory alkalosis. The acute respiratory alkalosis may be accompanied by a metabolic acidosis if the hypoxia is severe enough to cause the buildup of lactic acid resulting from anaerobic respiration.

Often, at this time, the patient's chest reveals normal auscultatory findings and normal radiography. However, within 24 hours normal breath sounds give way to coarse crackles, signifying the presence of pulmonary edema. The classic chest radiograph reveals bilateral, diffuse alveolar infiltrates consistent with alveolar flooding. The absence of cardiomegaly and pleural effusion radiographically distinguishes ARDS from cardiogenic pulmonary edema.

The inflammatory process and pulmonary edema contribute to ventilation-perfusion imbalances and capillary shunting. These pathophysiologic developments (especially the capillary shunting) manifest themselves as refractory hypoxemia when oxygen is administered in an attempt to ameliorate the patient's oxygenation problem. Clinically, the response to oxygen therapy is measured as the Pa02/F102 ratio, which in ARDS is less than 200.

Among the ventilation-perfusion disturbances present, increased alveolar dead space develops. Consequently, the minute ventilation increases to maintain a normal or near-normal PaCO2. Also early during the onset of ARDS, pulmonary compliance decreases severely, contributing to an increased work of breathing and respiratory distress.

Ultimately, the patient develops acute respiratory failure because of the increased work of breathing caused by (1) refractory hypoxemia, (2) increased alveolar dead space, and (3) severely decreased compliance. Arterial blood gas data at this time reflect either an uncompensated respiratory acidosis, or a mixed acidosis (acute respiratory acidosis and lactic acidosis). Lactic acidosis develops if the hypoxia is severe enough to cause anaerobic respiration.


In addition to the treatment of the underlying cause of this syndrome, mechanical ventilation is the mainstay of support for patients with ARDS. The primary goal of mechanical ventilation to ARDS patients is to treat the respiratory failure. This treatment is intended to improve gas exchange, to relieve respiratory distress, to facilitate lung healing, and to reduce the work of breathing. Avoiding pulmonary complications associated with mechanical ventilation such as barotrauma/volutrauma and infection are critical considerations.

Because patients with ARDS experience substantially reduced lung volumes caused by alveolar damage, atelectasis, and alveolar edema, the use of large mechanical tidal volumes are to be avoided to prevent over-distension of the lungs and volutrauma. Alveolar over-distension has been correlated with surfactant degradation, epithelial and endothelial membrane disruption, cytokine release, and pulmonary tissue inflammation. Volutrauma may develop from increased airway pressure with alveolar over-distension, or from shear forces applied during opening and closing of small airways. Therefore, the current trend is to ventilate these patients with tidal volumes based on about 6 ml/kg of ideal body weight and positive end-expiratory pressure (PEEP), along with attempting to achieve plateau pressures of less than 35 cm H20.

ARDS patients generally receive various levels of PEEP to prevent the opening and closing of alveoli during ventilation. PEEP is further added to improve oxygenation and to avoid using high FI02s (i.e., > 0.60) and to prevent alveolar derecruitment.

Inverse ratio ventilation (IRV), e.g., I:E ratio of 2:1, is used to improve oxygenation by increasing the patient's mean airway pressure (mean Paw). During IRV the tidal volume is delivered slowly with a longer inspiratory time and with a lower driving pressure. Expiratory time is shortened and less time is allowed for recruited alveoli to collapse. These strategies have the potential effect of improving oxygenation. Lung injury resulting from high ventilation pressures, i.e., barotrauma, must be avoided. For I:E ratios greater than 1.5:1, neuromuscular blockade of the patient is essential.

Permissive hypercapnia is the intentional reduction of mechanical ventilation for the avoidance of alveolar overdistension, i.e., volutrauma. PaCO2 levels are deliberately allowed to rise to levels as high as 100 torr. The arterial pH is maintained somewhere around 7.20 to 7.25; however, the pH deemed acceptable is determined on an individual basis. The pH is controlled by the patient's renal compensation and the administration of NaH2CO3. The Pa02 is maintained at greater than 60 torr. This ventilatory strategy is generally implemented when the plateau pressure (alveolar pressure) climbs to potentially dangerous levels.

A number of measures are taken to establish permissive hypercapnia. The PaCO2 is permitted to increase, while the pH is allowed to decrease as a result of sedating the patient. Carbon dioxide production is minimized by instituting neuromuscular blockade and sedation, reducing the patient's body temperature, and limiting the patient's intake of glucose. Tracheal gas insufflation may be instituted to flush out carbon dioxide from the patient's anatomic dead space, but studies regarding the effectiveness of tracheal gas insufflation are inconclusive. Permissive hypercapnia should not be used on patients who have an elevated intracranial pressure because the high PaCO2 may increase cerebral perfusion significantly. The use of permissive hypercapnia was advanced by Hickling, et al in the early 1990s, and has been associated with a lower mortality rate among patients with ARDS.

Placing mechanically ventilated ARDS patients in the prone position produces a short-term improvement in the patient's oxygenation status. Long-term influence is uncertain. The physiology underlying this maneuver has not been elucidated. The speculation is the gravitational effects on pulmonary blood flow and the intra-pleural pressure gradient improves ventilation-perfusion ratios.

Prone positioning demands vigilance regarding the displacement of the endotracheal tube and vascular lines. Thoracic compliance sometimes decreases when the patient is placed in the prone position. The consequence is higher airway pressure with volume ventilation, or a decreased tidal volume with pressure ventilation.

Trials of high frequency jet ventilation and high frequency oscillatory ventilation have been conducted. However, the data supporting the use of these methods of mechanical ventilation for ARDS patients are inconclusive.

A variety of pharmacologic agents have been studied within the context of ARDS, but none have demonstrated a reduction in the mortality rate. Inhaled nitric oxide (NO) dilates the pulmonary vasculature, improves ventilation-perfusion mismatching, and improves oxygenation. Yet, the use of NO neither decreases the duration of mechanical ventilation, nor the mortality rate associated with ARDS.

Corticosteroids have been used as anti-inflammatory agents. The administration of corticosteroids before the onset of signs and symptoms of ARDS, or during the early stage of ARDS has not proved efficacious. Similarly, the instillation of pulmonary surfactant into the lungs of ARDS patients has had no significant clinical benefit.

Respiratory therapists must have a firm understanding of the various etiologic factors associated with ARDS and must be vigilant of the signs and symptoms of this syndrome in order to be prepared to take definitive action once the onset of this condition emerges. Once supportive care has been initiated, the respiratory therapist must work to avoid or to minimize the risk of volutrauma/barotrauma, and apply strategies to improve oxygenation and to avert the devastation of multiple organ system failure.

by Bill Wojciechowski, MS, RRT
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Article Details
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Author:Wojciechowski, Bill
Publication:FOCUS: Journal for Respiratory Care & Sleep Medicine
Article Type:Disease/Disorder overview
Geographic Code:4EUUK
Date:Mar 22, 2013
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