Topic Editor: Becky Box, MBBS
Review Date: 9/20/2012
Definition
- Acute respiratory distress syndrome (ARDS) is defined as refractory hypoxemia due to impaired gas exchange from non-cardiogenic pulmonary edema.
- To diagnose ARDS, the following four items must be present:
- Acute onset - within 7 days of initial symptoms
- New bilateral pulmonary infiltrates on imaging
- Severe hypoxemia with reduced PaO2/FIO2 ratio 200
- No evidence of raised left ventricular pressure (i.e. Cardiogenic etiology)
Description
- The hallmark of ARDS is impaired gas exchanged due to increased capillary permeability resulting in protein rich interstitial and alveolar edema
- The pattern of lung injury, progressing from interstitial/alveolar edema to a proliferative and then a fibrotic phase, is consistent despite the inciting/initiating event
- The intensity of the syndrome varies depending on factors related to the underlying illness and the host response
- Primary pneumonia is the most common cause of ARDS, followed closely by severe sepsis. Other precipitants include aspiration, trauma associated massive hemorrhage, pancreatitis, transfusion related lung injury and drug interactions
Epidemiology
Incidence/Prevalence
- It is estimated that approximately 5% of mechanically ventilated patients have ARDS
- In 2005 the reported incidence was approximately 200,000 patients/year (U.S.)
- Cohort studies across the world report varying incidence, with the being in the U.S., of 65-79 cases/per 100,000 person years, and the lowest being in Spain, of 7.2 cases/per 100,000 person years
- Some literature supports a higher age-adjusted incidence, with one source reporting 86.2/100,000 person years
- The mortality rate associated with ARDS is approximately 40%
Age
- The incidence of ARD increases with age, with 16 cases/100,000 person years in people aged 15 to 19 years, as compared to 306 cases/100,000 person years in those aged 75 to 84 years
Gender
- There is generally no significant gender predominance
- One prospective cohort study found a statistically significant increase in the incidence of ARDS in females compared with males following serious trauma
Risk factors
Non-modifiable
- Disease severity at time of admission
- Advanced age
- Co-morbidities
- Hypoproteinemia
Modifiable
- Alcohol abuse
- Cigarette smoking
- Diseases associated with an acute inflammatory response such as:
- Aspiration of gastric contents
- Burns
- Fat embolism
- Large volume or multiple blood transfusions
- Pancreatitis
- Pneumonia
- Sepsis
- Toxic inhalation
- Traumatic brain injury
- Failure of early administration of antibiotics in patients with septic shock
- Failure to adequately fluid resuscitate in patients with septic shock
- Obesity
Etiology
- ARDS is initiated and perpetuated by proteins involved in both the inflammatory and coagulation cascades
- The development of ARDS and ARDS severity is unpredictable between individuals, even when comparing those with similar illnesses and disease severity scores
- The heterogeneity of this syndrome is likely a result of its multifactorial etiology along with varied host response - due to both genetic and environmental influences
- Multiple studies have shown several sepsis associated genes and proteins. These relate to ARDS susceptibility resulting in ‘unchecked' inflammatory response. They include:
- Angiotensin converting enzyme (ACE)
- Interleukin 2 & 6 (IL2, IL6)
- Tumor Necrosis Factor alpha and beta (TNFa/TNFß)
- Mannose Binding Lectin-2 (MBL-2)
- Plasminogen activator inhibitor 1
- Surfactant protein B
- Von Willebrand's factor antigen
- These genes relate to ARDS susceptibility resulting in an ‘unchecked' inflammatory response
- The primary insult is damage to the alveolar epithelial lining resulting in increased alveolar permeability with the alveoli becoming poorly functioning, including impaired activity of type 2 pneumocytes, which are essential to alveolar fluid transport and surfactant production. The result is a severe ventilation-perfusion mismatch with intrapulmonary shunting causing clinically significant hypoxemia and a marked reduction in lung compliance
- ARDS is thought to develop due to an imbalance between pro- and anti-inflammatory mediators, pro & anticoagulants and neutrophil/protease activators and inhibitors
- Both direct lung injury or indirect injury can lead to the unchecked systemic inflammatory response that is directly implicated in the pathogenesis of ARDS
- Direct lung injury:
- Aspiration of gastric contents
- Fat emboli
- Inhalation injury
- Multiple blood transfusions
- Near-drowning
- Pneumonia
- Reperfusion pulmonary edema
- Pulmonary contusion
- Indirect lung injury:
- Acute pancreatitis
- Burns
- Cardiopulmonary bypass
- Drug overdose
- Multiple trauma
History
- Patient history typically includes development of acute dyspnea and hypoxemia within hours to days of the precipitating event
- In ARDS, there is refractory hypoxemia which is out of proportion to the underlying disease process
Physical findings on examination
- Patients with ARDS present with progressive clinical findings that usually occur within 24-48 hours from the time of the inciting event. To be classified as ARDS, it must occur within 7 days of the inciting event
- Tachypnea, tachycardia and increased work of breathing are the initial clinical findings
- Findings on thoracic examination include increased use of accessory muscles, reduced air entry, bilateral crepitation, and central/peripheral cyanosis despite oxygen supplementation
- Systemic findings may include fever/hypothermia, agitation/confusion (secondary to hypoxemia or hypocapnea) or distress
- Other findings of the underlying disease process may be evident, particularly associated with sepsis, this may include hypotension and peripheral vasoconstriction with altered GCS
- Signs of congestive cardiac failure, such as elevated JVP, peripheral edema, cardiac murmur/gallop or hepatomegaly should be absent, as these signs would indicate an underlying cardiac etiology for the acute pulmonary edema
Blood Tests findings
- Arterial blood gases (ABG): Aa Gradient
- Respiratory alkalosis (initially) with severe hypoxemia is evident on ABG
- The PaO2/FIO2 ratio can be used to distinguish between Acute Lung Injury (ALI) and ARDS, indicating the degree of impaired gas exchange
- ARDS has a PaO2/FIO2 ratio 200
- ALI has a PaO2/FIO2 ratio 300
- For example, in ARDS, a patient on 60% O2 must have a PaO2120 mmHg. For example, if this patient had a PaO2 of 100, this would be 100/0.6 = 167, thus meeting criteria for ARDS
- Hypercapnia occurs as the disease progresses resulting in a respiratory acidosis and indicating impending respiratory failure
- B-type natriuretic peptide (BNP) value: Can help differentiate ARDS from cardiogenic pulmonary edema. Level of 100 pg/mL in patients with bilateral infiltrates and hypoxemia favors the diagnosis of ARDS/ALI
Radiographic findings
- Chest X-ray:
- Clinical findings often precede changes on chest x-ray
- Bilateral diffuse alveolar infiltrates are typical
- With disease progression into the exudative phase, diffuse fluffy alveolar infiltrates are seen
- In the later stages, reticular opacities may occur, suggestive of the development of interstitial fibrosis
- Importantly, there should be an absence of cardiomegaly, pleural effusions and vascular redistribution that are typical of cardiogenic pulmonary edema
- Computed tomographic (CT) of the chest:
- Bilateral alveolar opacities are seen during the acute phase of ARDS. These changes are distributed heterogeneously, more pronounced in the dependent, posterior lung zones and sparing the anterior lung fields
- During the fibroproliferative stage, there are bilateral reticular opacities, reduced lung volume and occasionally, large bullae
- Two-dimensional echocardiography:
- Expect to see normal cardiac function, without an obvious primary cardiac etiology to the pulmonary findings
- Right-to-left shunting across a patent foramen ovale may occur as a result of pulmonary hypertension, and positive-pressure mechanical ventilation. In such cases, it is reasonable to follow up with transesophageal echocardiography
Other diagnostic test findings
- Pulmonary artery wedge pressure (PAWP)
18 mm Hg (now rarely obtained due to limited use of pulmonary arterial catheters), or absence of evidence of left atrial hypertension suggests ARDS - Bronchoscopy can be useful to diagnose co-existing illness such as acute infection, presence of alveolar hemorrhage or eosinophilic pneumonia.
Bronchoalveolar lavage, when performed, can be analyzed for culture, cell counts, gram stain, silver stain and PCR - Histopathologic findings: vary according to disease stage
- Exudative phase – thickening of alveolar-capillary membrane due to dense inflammatory infiltrate and hyaline membrane formation
- Proliferative phase – growth of type 2 pneumocytes within alveolar walls and infiltration of the interstitium by myofibroblasts, fibroblasts and collagenous proteins
- Fibrotic phase – thickening of alveolar walls due to deposition of connective tissue
General treatment items
- Early and aggressive management of the underlying cause reduces mortality associated with ARDS
- Care should be optimized for the prevention of complications such as nosocomial infection, gastrointestinal bleeding and thromboembolism
- It is not uncommon for patients to die from sepsis, so early treatment of any infection at presentation, or nosocomial infection is vital
- Prophylaxis for stress gastrointestinal ulcers is advised for all patients with ARDS
- Some form of prophylaxis is indicated for deep vein thrombosis in most patients with ARDS
- Nutritional support is required, with enteral feeding preferred over parenteral nutrition as this route reduces the risk of catheter-induced sepsis
- Fluid restriction strategies are currently advocated in ARDS. A recent trial (2006) by the National Heart, Lung and Blood Institute ARDS Clinical Trials network showed a clinically significant improvement in lung function and duration of mechanical ventilation in patients managed with fluid restriction strategies. These strategies use the minimal amount of fluid used whilst still maintaining adequate systemic perfusion
Pharmacotherapy:
- Nitric Oxide – multiple studies have failed to show benefit in mortality rate or number of ventilator days with use of inhaled nitric oxide as a pulmonary vasodilator in ARDS. Currently, this can only be recommended as rescue therapy in patients with refractory hypoxemia
- Corticosteroids - has been evaluated in ALI and ARDS with unclear results. There is some suggestion that there may be benefit if instituted seven days after the diagnosis. Conversely, there are findings of adverse effects, such as increased risk of infection and increased incidence of myopathy. As there is no compelling reason to use these agents, they are not routinely recommended
- Surfactant-replacement therapy is effective in infants with neonatal respiratory distress syndrome. Similar agents used in children and adults have failed to demonstrate any benefit, and are thus not recommended
Non-invasive Ventilation
- Noninvasive ventilation such as BiPAP or CPAP (Bi-level or Continuous Positive Airway Pressure) can be trialed, and may occasionally suffice to provide adequate oxygenation to patients with acute lung injury. More often than not, noninvasive ventilation is used as a bridge to maintain oxygenation while preparing for intubation
Ventilation
- Ventilatory support:
- General principles are:
- Tidal Volume (TV) of 6 mL/kg – based on ideal body weight
- Aim to maintain Plateau Pressure (Pplat) at 30 mmHg; the tidal volume and rate may require adjustment to achieve this goal. Usual adjustment is a decrease in TV (minimum 4 mL/kg) with a concomitant increase in respiratory rate
- Use the minimum oxygen necessary to ensure adequate oxygenation with a goal of PaO2 of 55-80 mmHg or SpO2 of 88-95%. It is crucial, when possible to minimize oxygen toxicity by maintaining FIO2 60%
- Permissive hypercapnia is acceptable, while maintaining pH > 7.2
- PEEP(positive end-expiratory pressure) should be utilized to ensure maximal recruitment of alveoli
- A recent study by Acute Respiratory Distress Syndrome network in 2000 supports the ventilation parameters listed above, with a 22% reduction in mortality using low tidal volumes and limited plateau pressures. Other recent studies suggest a mortality reduction or 25-40% when utilizing protective lung ventilation
- High PEEP is felt to splint open collapsed alveoli (reducing stress trauma), and improve oxygenation while preventing intra-pulmonary shunting
Alternate Therapeutic approaches
- Other promising approaches being researched include partial liquid ventilation, and high-frequency oscillatory ventilation
- Prone positioning has been proposed as a means of improving oxygenation by reducing edema and atelectasis. Prone position allows the typically dependent posterior lung zones to be under less hydrostatic pressure, thereby improving ventilation-perfusion mismatch. A recent randomized, prospective trial failed to show a decrease in mortality with prone position Tracheostomy: May be necessary in cases requiring prolonged mechanical ventilation
Dietary or Activity restrictions
- Nutritional support is recommended within 48-72 hours of initiation of mechanical ventilation. Enteral nutrition is preferred
- Enteral diets enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA ), and antioxidants have shown improved outcomes in patients with ARDS
- Elevation of the head of the bed to 45-degrees reduces risk of ventilator-associated pneumonia
Disposition
Admission criteria
- Admit all patients with ARDS to ICU – preferably to a tertiary care center given the high mortality rate of this condition
Discharge criteria
- Hemodynamically stable
- Oxygenation adequate, and stable, on room air or supplemental oxygen
- Adequate nutrition
- Plan with family and patient for immediate return if there are signs or symptoms of respiratory distress
- Follow-up arranged
Prevention
- Appropriate measures to avoid aspiration pneumonitis which is a risk factor for ARDS
- Avoidance of high-tidal volumes in patients on mechanical ventilation as this is a risk factor for ARDS. Small tidal volumes are advised for patients with established ALI
- Careful fluid management in high-risk patients
Prognosis
- Mortality rate is approximately 40%
- Both failure to improve within the first week and the presence of extensive injury to the alveolar epithelium are poor prognostic factors
- Generally speaking, survivors of ARDS tend to be younger and gradually regain pulmonary function over the ensuing 12 months
- Patients who survive may have pulmonary sequelae including:
- Restrictive/obstructive lung disease
- Impaired gas exchange/diffusion at rest or with exercise
Associated conditions
Pregnancy/Pediatric effects on condition
- Though uncommon, ARDS can occur during pregnancy. Maternal, delivery, and fetal factors are essential considerations in the treatment plan
Synonyms/Abbreviations
Synonyms
- Adult respiratory distress syndrome
- Respiratory distress syndrome (RDS)
Abbreviations
ICD-9-CM
- 518.82 Other pulmonary insufficiency, not elsewhere classified
ICD-10-CM
- J80 Acute respiratory distress syndrome
