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Synopsis
Terminology
Diagnosis
Treatment
Complications and Prognosis
Screening and Prevention

Apr.11.2022

Acute Respiratory Distress Syndrome in Adults

Synopsis

Key Points

Acute respiratory distress syndrome is severe and often fatal acute respiratory failure; characterized by diffuse inflammatory lung injury rapidly progressing to increased pulmonary vascular permeability, increased lung weight, and hypoxemia
Most commonly secondary to pneumonia, nonpulmonary sepsis, and trauma. Worsening respiratory status most commonly develops within 1 week of clinical insult ^r1
Primary diagnostic tools are arterial blood gas levels showing hypoxemia with a PaO₂ to FiO₂ ratio of 300 mm Hg or less and radiograph showing bilateral opacities; echocardiography may be required to ascertain that these opacities are not attributable to cardiogenic pulmonary edema ^r1
Treatment is primarily conventional mechanical ventilation using lung-protective strategies (ie, low-tidal-volume and/or low-pressure ventilation) and a high concentration of inspired oxygen and PEEP
Other supportive care measures include prone positioning during mechanical ventilation, conservative fluid management strategies, and provision of enteral nutrition to prevent respiratory muscle weakness
Additional treatments focus on addressing underlying cause
High mortality rate of up to 46%; survivors commonly have residual lung damage ^r1^r2

Urgent Action

Conventional mechanical ventilation with low tidal volumes, PEEP, and moderate to high oxygen, with the goal of maximizing oxygenation ^r3^r4
Prone positioning decreases mortality ^r3

Pitfalls

Early stages can be difficult to differentiate from cardiogenic pulmonary edema, possibly resulting in delay of critical interventions ^r5
An outbreak of lung injury associated with vaping was identified by CDC in September 2019; be aware that severe lung disease, including acute respiratory distress syndrome, can occur ^r6^r7

Terminology

Clinical Clarification

Acute respiratory distress syndrome is severe and often fatal acute respiratory failure; characterized by diffuse inflammatory lung injury rapidly progressing to increased pulmonary vascular permeability, increased lung weight, and hypoxemia
Preceded by a clinical insult—usually pneumonia, nonpulmonary sepsis, aspiration of gastric contents, or trauma
Berlin definition of acute respiratory distress syndrome includes presence of all following criteria: ^r1^r8
- Timing of acute onset of symptoms (or worsening of nonacute symptoms) within 1 week of a known clinical insult
- Hypoxemia as shown by the PaO₂ to FiO₂ ratio of 300 mm Hg or less with PEEP or CPAP of 5 cm H₂O or greater
- Chest imaging showing bilateral opacities that are not explained by effusions, atelectasis, or nodules, and are not cardiogenic in nature
- Respiratory failure or pulmonary edema not fully explained by cardiac failure or fluid overload

Classification

Under conventional mechanical ventilation, the following apply:
- The 3 categories of acute respiratory distress syndrome are based on degree of hypoxemia, as follows: ^r1^r8
  - Mild: 200 mm Hg < PaO₂/FiO₂ ≤ 300 mm Hg
  - Moderate: 100 mm Hg < PaO₂/FiO₂ ≤ 200 mm Hg
  - Severe: PaO₂/FiO₂ ≤ 100 mm Hg
- A minimum PEEP of 5 cm H₂O is required to make the severity classification; it may be delivered noninvasively with CPAP to classify mild cases ^r1^r8

Diagnosis

Clinical Presentation

History

Recent known clinical insult (usually within 3 days and nearly always within 7 days) of new or worsening respiratory symptoms ^r1^c1^c2^c3
- Known history of (or recent symptoms suggestive of) congestive heart failure can suggest possibility of cardiogenic (rather than noncardiogenic) pulmonary edema ^c4
Symptoms may vary in severity, with some being mild initially; all worsen over a period of several hours
- Dyspnea ^c5
- Cough ^c6
- Chest discomfort ^c7
- Anxiety ^c8

Physical examination

Cyanosis may be evident ^c9
Tachypnea at rest ^c10
Tachycardia at rest ^c11
Hypotension is often present ^c12
Fever may or may not be present, depending on the presence of infection as an underlying cause ^c13
Use of accessory muscles of respiration (usually indicates moderate to severe disease) ^c14
Coarse crepitations of both lungs at presentation ^c15
Cold, mottled extremities with prolonged capillary refill time (longer than 2 seconds) indicates ineffective circulation ^c16^c17^c18
Evaluate carefully for:
- Signs of cardiogenic pulmonary edema (which can both mimic and coexist with acute respiratory distress syndrome), including bilateral crackles, jugular venous distention, S₃/S₄ gallop, hepatomegaly, and dependent edema ^c19^c20^c21^c22^c23^c24
- Signs of underlying infection, including pneumonia (egophony, rales, dullness to percussion), lymphadenopathy, and septic emboli of the skin ^c25^c26^c27^c28

Causes and Risk Factors

Causes

Direct alveolar injury
- Pneumonia ^c29
- Aspiration of gastric contents ^c30
- Near-drowning ^c31
- Noxious inhalation (eg, chlorine, high oxygen) ^c32^c33^c34
- Fat, amniotic fluid, or air emboli ^c35^c36
- Vaping-related injury ^r9^c37
Indirect alveolar injury
- Sepsis (nonpulmonary origin) ^c38
- Trauma ^c39
- Multiple blood transfusions ^c40
- Drug reaction (eg, nitrofurantoin, amiodarone, anticancer drugs) or overdose (eg, opiates) ^c41^c42^c43^c44
- Cardiopulmonary bypass ^c45
- Burns ^c46
- Acute pancreatitis ^c47

Risk factors and/or associations

Age

May occur at any age
In trauma patients, progressive increase in risk up to ages 60 to 69 years, with declining risk thereafter ^r10^c48^c49^c50
In vaping-related pulmonary disease, most patients are aged 18 to 34 years ^r7^c51

Sex

In trauma patients, females are at increased risk ^r11^c52^c53

Ethnicity/race

Mortality rates are higher for Blacks than for Whites in broad epidemiologic studies ^r12^c54^c55
When limited to national (United States) trauma data: ^r13
- Black race is protective (ie, lower incidence of acute respiratory distress syndrome) ^c56
- Hispanic ethnicity is associated with increased acute respiratory distress syndrome–associated mortality ^c57

Other risk factors/associations

Worldwide, sepsis is most common risk factor ^c58
60% to 70% of patients with COVID-19 who require intensive care have (or develop) acute respiratory distress syndrome ^r14^c59
Chronic alcohol use disorder significantly increases risk of acute respiratory distress syndrome in patients with critical illness ^c60

Diagnostic Procedures

Primary diagnostic tools

Use history, physical examination findings, arterial blood gas measurements, and imaging studies to diagnose according to Berlin definition ^r1^c61
- Chest radiography is the initial diagnostic evaluation ^r1^c62
- CT is not routine but is often obtained for more detail ^c63
- Early stages can be difficult to differentiate from cardiogenic pulmonary edema on basis of history and physical examination, possibly resulting in delay of critical interventions; additional evaluation with transthoracic echocardiography may be helpful

Laboratory

Arterial blood gas measurement ^r1^c64
- Indicated for diagnosis and ongoing monitoring of all patients in whom the syndrome is suspected
- Findings include:
  - Varying degrees of hypoxemia
  - Earliest finding is respiratory alkalosis; with progression, respiratory acidosis with hypercapnia
  - Widened alveolar-arterial gradient
- PaO₂ to FiO₂ ratio is used to assess severity, as follows: ^r1^c65
  - Mild: 200 mm Hg < PaO₂/FiO₂ ≤ 300 mm Hg
  - Moderate: 100 mm Hg < PaO₂/FiO₂ ≤ 200 mm Hg
  - Severe: PaO₂/FiO₂ ≤ 100 mm Hg
Routine laboratory tests include CBC, blood chemistries, and coagulation studies; in addition, the following laboratory tests are typically obtained: ^c66^c67^c68
- Brain natriuretic peptide or N-terminal pro–brain natriuretic peptide (to distinguish cardiogenic from noncardiogenic pulmonary edema) ^c69^c70
  - Result below 100 pg/mL has high specificity (about 95%) for acute respiratory distress syndrome; however, higher levels do not exclude the diagnosis ^r15
- Sputum Gram stain and culture ^c71^c72
- Serum amylase or lipase if acute pancreatitis is suspected ^c73^c74
- Consider COVID-19 testing for patients who are at risk ^r8

Imaging

Chest radiography ^c75
- Indicated for diagnosis and ongoing monitoring of all patients in whom acute respiratory distress syndrome is suspected ^r1
  - Within first few hours of precipitating event, lungs may appear normal ^r1
  - Within 24 hours, bilateral airspace opacities are usually evident ^r1
  - In severe acute respiratory distress syndrome, airspace opacities are commonly present in 3 or 4 lung quadrants ^r1
CT ^c76
- Useful for determining root cause of respiratory symptoms in some cases (eg, cancer, chronic interstitial lung diseases, edema) ^r1
  - Widespread patchy or coalescent airspace opacities are consistent with acute respiratory distress syndrome
  - Consider risk versus benefit of moving a critically ill patient for CT scan
Echocardiography ^r1^c77
- Objective aid to clinical judgment for excluding cardiogenic pulmonary edema; however, cardiogenic and noncardiogenic pulmonary edema can coexist
- Findings suggestive of cardiogenic pulmonary edema include significantly reduced left ventricular ejection fraction, diastolic dysfunction, and aortic or mitral valve dysfunction

Differential Diagnosis

Most common

Cardiogenic pulmonary edema ^c78
- Clinical indicators
  - Abnormal findings on cardiac examination
    - Third heart sound (S₃ gallop)
    - Heart murmurs
    - Irregular heart rate
    - Displaced point of maximum impulse of heart
    - Elevated jugular venous pressure
  - Radiographic abnormalities may overlap with findings of acute respiratory distress syndrome; abnormalities include:
    - Pulmonary venous congestion
    - Kerley B lines
    - Cardiomegaly
    - Pleural effusions
- Differentiating features
  - Echocardiography with findings of cardiac dysfunction favors cardiogenic pulmonary edema
  - Plasma brain natriuretic peptide level less than 100 pg/mL favors acute respiratory distress syndrome ^r15^r16
Viral or bacterial pneumonitis ^c79^c80
- Clinical indicators
  - Upper respiratory symptoms may precede illness
  - Fever is likely
- Differentiating features
  - History, physical examination, and diagnostic test findings will not meet Berlin definition^r1
  - Sputum microscopy, culture, and/or rapid antigen detection suggest infection
  - Bronchoalveolar lavage with suggestive cytologic changes favors viral pneumonitis
- In addition to being a possible differential diagnosis, pneumonia is also the most frequent lung condition leading to acute respiratory distress syndrome

Less common

Chronic interstitial lung diseases (eg, idiopathic pulmonary fibrosis, occupational lung diseases, autoimmune diseases) ^c81^c82^c83^c84
- Clinical indicators
  - Dyspnea and cough slowly progressing over months or years, caused by diffuse alveolar damage
    - However, chronic interstitial lung diseases may sometimes worsen rapidly, mimicking acute respiratory distress syndrome
  - Associated signs/symptoms of the underlying disease (eg, arthralgias or arthritis in autoimmune disease)
  - Early radiographs may show subpleural reticular changes mixed with alveolar opacities
- Differentiating features
  - Slower, progressive onset
  - Will not meet Berlin definition^r1
  - CT scan may suggest diagnosis
  - Lung tissue biopsy confirms diagnosis
Acute interstitial pneumonitis ^c85^d1
- Clinical indicators
  - Rapid onset of respiratory failure, which clinically mimics acute respiratory distress syndrome symptomatically and radiologically, but for which no precipitating factor is identified
- Differentiating features
  - Difficult to differentiate; can be thought of as idiopathic acute respiratory distress syndrome
Malignancy ^c86^d2
- Clinical indicators ^d3
  - Rapid, progressive cancer disseminating throughout the lungs may have a presentation similar to that of acute respiratory distress syndrome
  - Usually lymphoma or acute leukemia
- Differentiating features
  - Will not meet Berlin definition^r1
  - Bronchoalveolar lavage may reveal malignant cells
Diffuse alveolar hemorrhage ^c87
- Clinical indicators
  - Syndrome presenting with hemoptysis (two-thirds of patients) evolving over days to weeks with progressive anemia, diffuse alveolar infiltrates, and hypoxemic respiratory failure
  - Most commonly associated with underlying connective tissue disorder and less commonly with toxin inhalation or drug reaction
- Differentiating features
  - Often requires serial bronchoalveolar lavage for diagnosis because symptoms and imaging findings are nonspecific
    - Hemoptysis is absent in one-third of patients and those patients may be indistinguishable from patients with acute respiratory distress syndrome
    - Intra-alveolar RBCs appear in lavage fluid in increasing numbers, with hemosiderin-laden macrophages appearing within 48 to 72 hours
    - CBC shows progressive anemia

Treatment

Goals

Maintain oxygenation via mechanical ventilation with adjustments of FiO₂ and PEEP; ARDS Network goal is PaO₂ of 55 to 80 mm Hg or SpO₂ of 88% to 95% ^r17
Avoid ventilator-induced lung damage by using protective (ie, volume-limited and/or pressure-limited) ventilator settings
Maintain a neutral or net-negative fluid balance in hemodynamically stable patients
- Central venous pressure goal of 4 to 8 mm Hg ^r18
- Urine output of more than 0.5 mL/kg ^r18
- Adequate cardiac output ^r18
Identify and treat or reverse the underlying cause

Disposition

Admission criteria

Criteria for ICU admission

All patients in whom acute respiratory distress syndrome is either confirmed or suspected

Recommendations for specialist referral

Refer to pulmonologist or critical care specialist for ventilator management
Consult infectious disease specialist if infection is suspected

Treatment Options

Mainstay of treatment is supportive care in an ICU setting

Mechanical ventilation using PEEP and a lung-protective strategy of low tidal volumes and airway pressures to mitigate ventilator-induced lung injury ^r19^r20^r21
- Minority of patients may be managed with noninvasive delivery high FiO₂ (ie, humidified high-flow nasal cannula) ^r18^r22
Prone positioning improves mortality in severe cases and should be used as an upfront management strategy rather than as a rescue effort ^r23^r24^r25
Sedatives are typically administered for patient comfort and safety ^r26
- Guidelines recommend using either dexmedetomidine or propofol to achieve light levels of sedation in adults receiving mechanical ventilation and continuous sedation ^r26
- Addition of neuromuscular blockade during mechanical ventilation has been considered as a strategy for moderate to severe acute respiratory distress syndrome ^r27
  - Benefits of neuromuscular blockade include reduced patient–ventilator dyssynchrony, reduced work of breathing, and reduced accumulation of alveolar fluid ^r28
  - However, prolonged administration of neuromuscular blocking agents is associated with later neuromuscular weakness and requires deeper sedation, which can have negative consequences (eg, delirium, coma, long-term cognitive impairment)^r26^r28
  - Large multicenter trial reported early administration of a 48-hour infusion of neuromuscular blockade with deep sedation in patients with moderate to severe acute respiratory distress syndrome resulted in lower mortality than deep sedation without routine neuromuscular blockade ^r29
  - Recent study conducted among patients with moderate to severe acute respiratory distress syndrome who were treated with a high-PEEP strategy demonstrated no significant difference in 90-day mortality between patients who received an early continuous neuromuscular blockade and those who were treated with a usual-care approach with lighter sedation targets ^r28
Fluid management strategies include use of IV crystalloids, vasopressors (eg, norepinephrine), inotropes (eg, dobutamine), and diuretics (eg, furosemide) to maintain effective tissue perfusion
- Conservative fluid management results in more ventilator-free days and fewer days in the ICU compared with liberal fluid management ^r30^r31
- In some cases it may be reasonable to combine a liberal strategy (ie, for resuscitation early in course of disease) with a conservative strategy (ie, later in course of disease) ^r30
- Pulmonary artery catheter–guided fluid management is associated with more complications than central venous catheter–guided management and does not improve outcomes; a pulmonary artery catheter should not be routinely used ^r32
Other supportive care, including nutrition and prophylaxis of expected medical complications (eg, deep venous thrombosis, stress ulcers) ^r33
Venovenous extracorporeal membrane oxygenation is commonly used as rescue therapy for patients with refractory hypoxemia ^r20
- Improved oxygenation, but limited data on effect on mortality; one study reported a significantly lower 28-day mortality compared with lung-protective ventilation ^r20^r25
Cochrane Review concluded that there is insufficient evidence to determine with certainty whether corticosteroids, surfactants, N-acetylcysteine, statins, β‐agonists, or inhaled nitric oxide are effective at reducing mortality or duration of mechanical ventilation in patients with acute respiratory distress syndrome ^r34^r35
- NIH COVID-19 treatment guidelines recommend use of dexamethasone in patients who require supplemental oxygen with or without mechanical ventilation ^r36
- Corticosteroid therapy has been reported in many cases to be useful in vaping-related lung injury ^r9^r37

Drug therapy

Pharmaceutical interventions should aim to:
- Treat root causes (eg, antibiotics for bacterial pneumonia;^r38remdesivir, dexamethasone, tocilizumab for COVID-19^r36) ^c88^c89^c90^c91
- If indicated, maintain blood pressure and effective tissue perfusion and oxygenation (eg, vasopressors, inotropes, diuretics) ^c92^c93^c94

Nondrug and supportive care

Prone positioning ^c95

General explanation
- Prone position for severe cases during conventional mechanical ventilation provides significant survival benefit in meta-analyses, although pressure ulcers and airway problems are increased ^r3^r23^r24
- May be especially helpful in subpopulation of patients who are already receiving low-tidal-volume ventilation without improvement
- Outcomes are best when used in combination with low-tidal-volume ventilation (6 mL/kg) and neuromuscular blockade ^r24
- Prone position is maintained for at least 16 hours per day ^r24
- 2017 American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guidelines recommend prone positioning for more than 12 hours per day in severe acute respiratory distress syndrome ^r19
- NIH guidelines recommend that mechanically ventilated patients with COVID-19 acute respiratory distress syndrome and refractory hypoxemia despite optimized ventilation undergo prone positioning for 12 to 16 hours per day ^r36^c96
  - Nonintubated, spontaneously breathing patients with COVID-19 may also benefit from prone positioning while receiving noninvasive respiratory support; associated with short-term improvement in oxygenation, decrease in respiratory rate and/or dyspnea, and reduction in need for intubation ^r39
- Contraindications include facial/neck trauma, spinal instability, recent sternotomy, large ventral surface burn, elevated intracranial pressure, large-volume hemoptysis, and high risk for requiring cardiopulmonary resuscitation or defibrillation ^r24
Indication
- Patients with severe acute respiratory distress syndrome who do not improve with lung-protective ventilator strategies

Careful fluid management ^c97

Includes optimal use of IV crystalloids (ie, fluid boluses and maintenance IV fluid infusions), use of vasopressors (eg, dobutamine), and use of diuretics (eg, furosemide) to maintain effective central and peripheral tissue perfusion and oxygenation
Various strategies have been studied and are loosely categorized as conservative (aiming for a lower intravascular pressure and resulting in lower positive cumulative fluid balance) or liberal (aiming for a higher intravascular pressure and resulting in higher positive cumulative fluid balance) ^r30^r31
Research-based fluid management protocols for each of these strategies are complex and take into account the goal intravascular pressure (eg, low versus high as measured by central venous pressure or pulmonary artery wedge pressure), mean arterial pressure, urine output, and evidence of adequate peripheral tissue perfusion ^r40
- Details of management used in research studies (including a protocol algorithm)^r41 are available from the NIH National Heart, Lung, and Blood Institute ARDS Network^r40
- Conservative fluid management results in enhanced oxygenation, more ventilator-free days, and fewer days in the ICU compared to liberal fluid management; may also have mortality benefit ^r31
Recent study included 3 levels of fluid management: ^r31
- Conservative: negative cumulative fluid balance of 136 mL ^r31
- Simplified/conservative: positive cumulative fluid balance 1913 mL ^r31
- Liberal: positive cumulative fluid balance positive of mL ^r31
- Simplified/conservative strategy was considered a safe and effective alternative to a conservative strategy, and both appeared preferable to a liberal fluid strategy ^r31

Other supportive care

Nutritional support ^r42^c98
- Initiate nutritional support within 24 to 48 hours after intubation
- Enteral feeding (either gastric or small bowel) is preferred over total parenteral nutrition when the gastrointestinal tract is functional, owing to fewer complications (eg, infection)
- No difference in 6- to 12-month outcomes (eg, physical function, survival, multiple secondary outcomes) with initial trophic (small volume) versus full enteral feeding ^r43
- Polymeric formula is preferred; fluid-restricted formulas are available
- Withhold enteral feedings if patients are hypotensive
Deep vein thrombosis prophylaxis using pharmacologic agents according to established clinical practice guidelines ^r44
Gastrointestinal bleeding prophylaxis for patients receiving mechanical ventilation ^r45^r46

Procedures

Conventional mechanical ventilation using lung-protective strategy ^c99

General explanation

Lung-protective strategies include low-tidal-volume ventilation and/or low-pressure ventilation ^c100^c101

Decreased mortality at 28 days, but evidence is insufficient regarding long-term morbidity and quality of life after protective strategy versus conventional strategy ^r21
2017 American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guidelines recommend mechanical ventilation using lower tidal volumes (4-8 mL/kg predicted body weight) and lower inspiratory pressures (plateau pressure less than 30 cm H₂O) ^r19
Cochrane Review found insufficient evidence to confirm or refute any advantage with low-tidal-volume ventilation as compared with low-pressure ventilation ^r4

Low-tidal-volume ventilation

Tidal volume of about 6 mL/kg (predicted body weight) is considered low volume, in comparison to usual 8 to 15 mL/kg ^r47
Predicted body weight is about 20% lower than measured body weight and is calculated as:
- Males (in kg): 50 + 0.91 (height, 152.4 cm) ^r48
- Females (in kg): 45.5 + 0.91 (height, 152.4 cm) ^r48
6 mL/kg volume is recommended by international guidelines for management of patients who develop acute respiratory distress syndrome due to sepsis ^r47
Permissive hypercapnia (which usually accompanies lower tidal volumes) is considered safe and is associated with improved outcomes; ARDS Network goal is pH of 7.3 to 7.45, but many authors advocate allowing pH as low as 7.2 ^r17^r49

Mechanical ventilation goals in acute respiratory distress syndrome.

Tidal volume	4-6 mL/kg of ideal body weight
Plateau pressure	Ideally less than 30 cm H₂O but lower may be better
pH, respiratory rate, minute ventilation	Depends on patient comorbidities but pH of 7.2 is widely accepted as acceptable permissive hypercapnia; lower may also be acceptable
PEEP	Unknown; higher may be better for severe ARDS
FiO₂	Unknown; titration based on PEEP to FiO₂ table is appropriate

Low-pressure ventilation ^r21
- Plateau pressure 30 cm H₂O or less ^r21

Other evidence-based ventilation strategies
- Use PEEP to improve oxygenation and prevent atelectasis ^r50^c102
  - Set PEEP for at least 5 cm H₂O; higher may be better ^r50
    - Improves oxygenation; however there is no clear mortality benefit of higher PEEP ^r51
    - No significant increase in the risk of barotrauma with higher PEEP ^r51
    - 2017 American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guidelines recommend higher PEEP in patients with moderate or severe acute respiratory distress syndrome ^r19
- Consider using recruitment maneuvers to keep all alveoli open (or to open previously collapsed alveoli) in refractory hypoxemia ^r50
  - 2017 American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guidelines recommend recruitment maneuvers in patients with moderate or severe acute respiratory distress syndrome ^r19
  - Brief intervals (eg, 40 seconds) of increased airway pressure (eg, 40 cm H₂O) may increase oxygenation; however, there is risk for overdistention and consequent shunting ^r48
- Sedation to improve mechanical ventilation tolerance and decrease oxygen requirements ^r48
Specific ventilator protocols
- In response to a shortage of critical care specialists during pandemic situations, the American Thoracic Society has published a step-by-step tutorial with video to assist nonintensivists with selecting reasonable initial ventilator settings^r52 and a guide to troubleshooting problems in ventilated patients for nonintensivists^r53
- NIH ARDS Network ventilator protocol ^r17^c103
  - Calculate predicted body weight
    - Males (in kg) = 50 + 2.3 (height, 60 in) ^r17
    - Females (in kg) = 45.5 + 2.3 (height, 60 in) ^r17
  - Select any ventilator mode
  - Set ventilator settings to achieve initial tidal volume of 8 mL/kg predicted body weight ^r17
    - Reduce by 1 mL/kg at intervals of 2 hours or less until tidal volume equals 6 mL/kg predicted body weight ^r17
  - Set initial rate to approximate baseline minute ventilation (not greater than 35 breaths per minute) ^r17
  - Adjust tidal volume and respiratory rate to achieve pH and plateau pressure goals
  - Plateau pressure goal is 30 cm H₂O or less ^r17
    - Check plateau pressure (0.5 second inspiratory pause) at least every 4 hours and after each change in PEEP or tidal volume
    - If plateau pressure is greater than 30 cm H₂O, decrease tidal volume in increments of 1 mL/kg (maintain minimum of 4 mL/kg) ^r17
    - If plateau pressure is less than 25 cm H₂O and tidal volume is less than 6 mL/kg, increase tidal volume by 1 mL/kg until plateau pressure is greater than 25 cm H₂O or tidal volume equals 6 mL/kg ^r17
    - If plateau pressure is less than 30 cm H₂O and breath stacking or dyssynchrony occurs, increase tidal volume in 1 mL/kg increments to 7 or 8 mL/kg (if plateau pressure remains less than 30 cm H₂O) ^r17
  - Oxygenation goal is PaO₂ of 55 to 80 mm Hg or SpO₂ of 88% to 95% ^r17
    - It has been hypothesized that lower PaO₂ targets could result in lower mortality; however, one study found no significant difference in 90-day mortality between patients treated to lower oxygenation targets (60 mm Hg) compared to those targeting higher levels (90 mm Hg)^r55 and another found a restrictive oxygenation strategy (target PaO₂ 55 to 70 mm Hg; SpO₂ 88 to 92%) could be potentially harmful ^r54
    - Use a minimum PEEP of 5 cm H₂O ^r17
    - Consider use of incremental FiO₂/PEEP combinations to achieve goal using ARDS Network table of combinations^r17

Indication

Acute respiratory distress syndrome of any severity classification

Complications

Hypercapnic respiratory acidosis may develop in some patients

Comorbidities ^c104

Usually related to underlying cause (eg, sepsis, pancreatitis, trauma)

Special populations

Acute respiratory failure in patients with COVID-19 ^d4
- Acute respiratory distress syndrome associated with COVID-19 does not appear to be distinct from the conventional syndrome, and existing therapies should remain the mainstay of treatment ^r27
- Ventilation management of acute respiratory failure secondary to COVID-19 is similar to that of acute respiratory distress syndrome due to other causes, with the following exceptions: ^r56
  - Higher PEEP with broad variation is used in COVID-19 patients
  - Higher FiO₂ is needed in COVID-19 patients
  - Prone positioning is used more often in patients with acute respiratory failure due to COVID-19
- Specific pharmacologic treatments for COVID-19 include antiviral agents, immunosuppressive agents, and immunomodulators ^r36
- Refer to published guidelines for management recommendations specific for COVID-19 ^r36^r57
  - Anticoagulation is recommended for hospitalized, nonpregnant adults with COVID-19 who are receiving supplemental oxygen ^r20^r36

Monitoring

Continuously monitor blood pressure, pulse oximetry, temperature, and respiratory rate (from ventilator) ^c105^c106^c107
Frequently monitor arterial blood gas ^c108
Central venous pressure monitoring is not mandatory but can assist with fluid management; pulmonary artery catheter is not indicated ^c109

Complications and Prognosis

Complications

Common complications that occur in an ICU setting include the following:
- Ventilator-induced lung injury, especially pulmonary edema ^c110^c111
- Ventilator-associated barotrauma (eg, pneumothorax, subcutaneous edema) ^c112^c113^c114
- Ventilator-associated pneumonia ^r8^c115
- Catheter-related infections ^c116
- Poor nutrition and loss of muscle mass ^c117^c118
- Deep vein thrombosis ^c119
- Gastrointestinal bleeding ^c120
- Delirium ^r29^c121
Pulmonary fibrosis develops in roughly two-thirds of patients with acute respiratory distress syndrome; patient may become increasingly reliant on persistent mechanical ventilation ^r58^c122
Cognitive impairment (post-intensive care syndrome) is common (70%-100% at hospital discharge, 46%-80% at 1 year, and 20% at 5 years) ^r20^r59^r60^c123
Depression and posttraumatic stress disorder are common ^r59^c124^c125
Long-term physical disability and neuromuscular weakness ^r20^r60^c126^c127

Prognosis

No specific biomarker is considered predictive of outcome ^r47
Mortality outside of a clinical trial setting remains high and relatively unchanged since the original consensus definition was developed in 1994 ^r20^r61
- Mild acute respiratory distress syndrome is associated with 34.9% mortality ^r2
- Moderate disease is associated with 40.3% mortality ^r2
- Severe disease is associated with 46.1% mortality ^r2
- Highest risk of death is when sepsis is the underlying cause; trauma-related cases have a lower mortality rate than those unrelated to trauma ^r48

Screening and Prevention

Screening ^c128

Prevention ^c129

No evidence exists for effective preventive measures specific to this syndrome; however, practices likely to decrease risk include: ^r62
- Primary prevention of nosocomial pneumonia
- Primary prevention of aspiration ^c130
- Appropriate antibiotic use
- Restrictive use of blood transfusions ^c131
- Avoid vaping and e-cigarette use ^r7^c132^c133^d5
  - If continuing e-cigarette use or vaping
    - Do not use devices purchased from sources other than authorized retailers
    - Do not modify devices or use devices modified in any manner not intended by the manufacturer
    - Only use substances sold by an authorized manufacturer
    - Do not use products that contain THC (tetrahydrocannabinol)

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Acute Respiratory Distress Syndrome in Adults

Synopsis

Key Points

Urgent Action

Pitfalls

Terminology

Clinical Clarification

Classification

Diagnosis

Clinical Presentation

History

Physical examination

Causes and Risk Factors

Causes

Risk factors and/or associations

Age

Sex

Ethnicity/race

Other risk factors/associations

Diagnostic Procedures

Primary diagnostic tools

Laboratory

Imaging

Differential Diagnosis

Most common

Treatment

Goals

Disposition

Admission criteria

Criteria for ICU admission

Recommendations for specialist referral

Treatment Options

Drug therapy

Nondrug and supportive care

Procedures

Conventional mechanical ventilation using lung-protective strategy c99

Comorbidities c104

Special populations

Monitoring

Complications and Prognosis

Complications

Prognosis

Screening and Prevention

Screening c128

Prevention c129

Conventional mechanical ventilation using lung-protective strategy ^c99

Comorbidities ^c104

Screening ^c128

Prevention ^c129