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    Acute Respiratory Distress Syndrome in Adults

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    Feb.05.2025

    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, aspiration of gastric contents, or 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 depending on disease severity and/or underlying cause
    • High mortality rate of up to 46%; survivors commonly have residual lung damage r1r2

    Pitfalls

    • Early stages can be difficult to differentiate from cardiogenic pulmonary edema, possibly resulting in delay of critical interventions r3
    • 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 r4r5

    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: r1r6
      • 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 (fraction of inspired oxygen) 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:
      • Three categories of acute respiratory distress syndrome are based on degree of hypoxemia, as shown by the PaO₂ to FiO₂ (fraction of inspired oxygen) ratio r1r6
        • Mild: 200 mm Hg less than PaO₂:FiO₂ less than or equal to 300 mm Hg
        • Moderate: 100 mm Hg less than PaO₂:FiO₂ less than or equal to 200 mm Hg
        • Severe: PaO₂:FiO₂ less than or equal to 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 r1r6

    Diagnosis

    Clinical Presentation

    History

    • Recent known clinical insult (usually within 3 days and nearly always within 7 days) of new or worsening respiratory symptoms r1c1c2c3
      • 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 initially being mild; 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 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 c16c17c18
    • Evaluate carefully for the following:
      • 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 c19c20c21c22c23c24
      • Signs of underlying infection, including pneumonia (egophony, rales, dullness to percussion), lymphadenopathy, and septic emboli of the skin c25c26c27c28

    Causes and Risk Factors

    Causes

    • Direct alveolar injury
      • Pneumonia c29
      • Aspiration of gastric contents c30
      • Near drowning c31
      • Noxious inhalation (eg, chlorine, high oxygen) c32c33c34
      • Fat, amniotic fluid, or air emboli c35c36
      • Vaping-related injury r7c37
    • Indirect alveolar injury
      • Sepsis (nonpulmonary origin) c38
      • Trauma c39
      • Multiple blood transfusions c40
      • Drug reaction (eg, nitrofurantoin, amiodarone, anticancer drugs) or overdose (eg, opiates) c41c42c43c44
      • 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 r8c48c49c50
    • In vaping-related pulmonary disease, most patients are aged 18 to 34 years r4c51
    Sex
    • Among trauma patients, females are at increased risk r9c52c53
    Ethnicity/race
    • Mortality rates are higher for Black people than for White people in broad epidemiologic studies r10c54c55
    • When limited to national (United States) trauma data r11
      • 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 r12c59
    • 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 r1c61
      • Chest radiography is the initial diagnostic evaluation r1c62
      • CT is not routine but is often obtained for more detail c63
      • Early stages can be difficult to differentiate from cardiogenic pulmonary edema based on history and physical examination, possibly resulting in delay of critical interventions; additional evaluation with transthoracic echocardiography may be helpful

    Laboratory

    • Arterial blood gas measurement r1c64
      • Indicated for diagnosis and ongoing monitoring of all patients in whom the syndrome is suspected
      • Findings include the following:
        • Varying degrees of hypoxemia
        • Earliest finding is respiratory alkalosis; with progression, respiratory acidosis with hypercapnia
        • Widened alveolar-arterial gradient
    • Routine laboratory tests include CBC, blood chemistries, serum lactate level, and coagulation studies; in addition, the following laboratory tests are typically obtained: c65c66c67
      • Brain natriuretic peptide or N-terminal pro–brain natriuretic peptide level (to distinguish cardiogenic from noncardiogenic pulmonary edema) c68c69
        • Result below 100 pg/mL has high specificity (approximately 95%) for acute respiratory distress syndrome; however, higher levels do not exclude the diagnosis r13
      • Sputum Gram stain and culture c70c71
      • Serum amylase or lipase level if acute pancreatitis is suspected c72c73
      • Consider COVID-19 testing for patients who are at risk r6

    Imaging

    • Chest radiography c74
      • 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 c75
      • 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 r1c76
      • 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 c77
      • 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 r13r14
    • Viral or bacterial pneumonitis c78c79
      • Clinical indicators
        • Upper respiratory symptoms may precede illness
        • Fever is likely
      • Differentiating features
        • History, physical examination, and diagnostic test findings will not meet Berlin definitionr1
        • 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) c80c81c82c83
      • 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 and 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 definitionr1
        • CT scan may suggest diagnosis
        • Lung tissue biopsy confirms diagnosis
    • Acute interstitial pneumonitis c84d1
      • 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 c85d2
      • 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 definitionr1
        • Bronchoalveolar lavage may reveal malignant cells
    • Diffuse alveolar hemorrhage c86
      • 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% r15
    • 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 r16
      • Urine output of more than 0.5 mL/kg r16
      • Adequate cardiac output r16
    • 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
      • Most patients are managed with invasive mechanical ventilation (via an endotracheal tube or tracheostomy) using higher PEEP and a lung-protective strategy of low tidal volumes and airway pressures to mitigate ventilator-induced lung injury r17r18r19
      • Prone positioning improves mortality in severe cases and should be used as an upfront management strategy rather than as a rescue effort r17r20r21r22
      • Combination of low tidal volumes with more than 12 hours/day of prone ventilation is associated with the greatest reduction in mortality in moderate-to-severe acute respiratory distress syndrome r23
      • Minority of patients may be managed with noninvasive ventilation (eg, high-flow oxygen via nasal cannula [humidified oxygen with flow rates 20 L/minute or greater]) or CPAP or BPAP ventilation via mask or helmet r16r24r25
      • Venovenous extracorporeal membrane oxygenation is commonly used as rescue therapy for patients with refractory hypoxemia r18
        • Consider in patients with severe acute respiratory distress syndrome and hypoxemia (PaO₂:FiO₂ less than 80 mm Hg) or severe hypercapnic respiratory failure (pH less than 7.25 with a PaCO₂ of 60 mm Hg or greater) that is refractory to optimal conventional management (including a trial of prone positioning and neuromuscular blockade) r26r27
        • Improved oxygenation, but limited data on effect on mortality; one study reported a significantly lower 28-day mortality compared with lung-protective ventilation r18r20
        • Increased risk for futility of extracorporeal membrane oxygenation if irreversible cause of respiratory failure, mechanical ventilation longer than 7 days, older age, immunosuppression, multi-organ failure, contraindication to anticoagulation, chronic medical condition with life expectancy less than 1 year, CNS hemorrhage, or irreversible CNS pathology r17
    • Fluid management
      • Fluid management strategies to optimize oxygenation and maintain effective tissue perfusion include use of IV crystalloids, vasopressors (eg, norepinephrine), inotropes (eg, dobutamine), and diuretics (eg, furosemide)
      • Conservative fluid management compared with liberal fluid management results in more ventilator-free days and fewer days in the ICU r28r29
        • 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) r29
        • 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 routinely be used r30
    • Pharmacological therapies
      • Corticosteroids
        • May be associated increased risk of harm when initiated more than 14 days after initiation of mechanical ventilation r17
        • Administer corticosteroids if indicated for treatment of underlying condition (eg, COVID-19, septic shock, community acquired pneumonia, or steroid-responsive conditions)
          • Corticosteroid therapy has been reported in many cases to be useful in vaping-related lung injury r31
          • Consider discontinuation at time of extubation for patients that improve rapidly r17
        • Role for corticosteroids in other patients with acute respiratory distress syndrome is controversial and use is variable
          • Systematic reviews and meta-analyses show treatment with corticosteroids may reduce mortality and shorten the duration of mechanical ventilation r32r33
          • Optimal regimen and dosage has not been established; however, methylprednisolone is commonly used r34
          • Do not use corticosteroids for acute respiratory distress syndrome caused by influenza as may be associated with increased mortality in this subset of patients r33
        • Monitor closely for adverse steroid-related effects r17
      • Convalescent plasma within 5 days of initiating mechanical ventilation reduces mortality r26
        • Effect was primarily reported in patients receiving therapy within 48 hours of starting mechanical ventilation
      • Inhaled pulmonary vasodilators r35
        • Inhaled nitric oxide or prostaglandins are not routinely indicated
        • May improve oxygenation transiently in patients with severe hypoxemia; however, have not been shown to reduce morbidity or mortality r36
    • Supportive therapies
      • Sedatives r37
        • Typically administered for patient comfort and safety
        • Guidelines recommend using either dexmedetomidine or propofol to achieve light levels of sedation in adults receiving mechanical ventilation and continuous sedation r37
      • Neuromuscular blockade
        • Addition of neuromuscular blockade during mechanical ventilation is a recommended strategy for early severe acute respiratory distress syndrome (less than 48 hours of mechanical ventilation with PaO₂:FiO₂ equal to or less than 100) r17r38
          • Benefits of neuromuscular blockade include reduced patient–ventilator dyssynchrony, reduced work of breathing, and reduced accumulation of alveolar fluid r39
          • However, administration of neuromuscular blocking agents for longer than 48 hours is associated with later neuromuscular weakness and requires deeper sedation, which can have negative consequences (eg, delirium, coma, long-term cognitive impairment)r37r39
          • Reduced mortality compared with deep sedation, but no mortality benefit compared with light sedation r17r39
          • Either bolus dosing or continuous infusion is acceptable; consider cessation after 48 hours (earlier for patients who rapidly improve) r33
      • Other supportive care, including nutrition and prophylaxis of expected medical complications (eg, deep venous thrombosis, stress ulcers) r40

    Drug therapy

    • Pharmaceutical interventions should aim to do the following:
      • Treat root causes (eg, antibiotics for bacterial pneumoniar41) c87
      • If indicated, maintain blood pressure and effective tissue perfusion and oxygenation (eg, vasopressors, inotropes, diuretics) c88c89c90

    Nondrug and supportive care

    Prone positioning c91

    • 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 r11r21r22r42
      • May be especially helpful in subpopulation of patients who are already receiving low-tidal-volume ventilation without improvement r17r23
      • Outcomes are best when used in combination with low-tidal-volume ventilation (6 mL/kg) and neuromuscular blockade r17r22r23
      • Prone position is maintained for at least 12 hours/day r17
      • 2024 American Thoracic Society clinical practice guidelines recommend prone positioning for more than 12 hours/day in severe acute respiratory distress syndrome r17
      • Prone positioning has been reported in up to 76% of COVID-19 patients receiving mechanical ventilation, improving oxygenation in approximately 80% r43c92
        • 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 r44
      • 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 r17r22
    • Indication
      • Patients with severe acute respiratory distress syndrome who do not improve with lung-protective ventilator strategies

    Careful fluid management c93

    • 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) r28r29
    • Evidence-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 r45
      • Details of management used in research studies (including a protocol algorithm)r46 are available from the NIH National Heart, Lung, and Blood Institute ARDS Networkr45
      • Conservative fluid management results in enhanced oxygenation, more ventilator-free days, and fewer days in the ICU compared with liberal fluid management; may also have mortality benefit r28

    Other supportive care

    • Nutritional support r47c94
      • 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 r48
      • 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 r49
    • Gastrointestinal bleeding prophylaxis for patients receiving mechanical ventilation r50r51
    Procedures
    Conventional mechanical ventilation using lung-protective strategy c95
    General explanation
    • Lung-protective strategies include low-tidal-volume ventilation and/or low-pressure ventilation c96c97
      • Decreased mortality at 28 days, but evidence is insufficient regarding long-term morbidity and quality of life after protective strategy versus conventional strategy r19
      • 2024 American Thoracic Society 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) r17
      • Cochrane Review found insufficient evidence to confirm or refute any advantage with low-tidal-volume ventilation compared with low-pressure ventilation r52
      • Low-tidal-volume ventilation
        • Tidal volume of approximately 6 mL/kg (predicted body weight) is considered low volume compared with usual 8 to 15 mL/kg r53
          • Ultra-low tidal volumes (target of approximately 4 mL/kg) does not provide additional benefit r54
        • Predicted body weight is approximately 20% lower than measured body weight and is calculated as follows:
          • Males (in kg): 50 + 0.91 (height in cm minus 152.4 cm) r55
          • Females (in kg): 45.5 + 0.91 (height in cm minus 152.4 cm) r55
        • 6-mL/kg volume is recommended by international guidelines for management of patients who develop acute respiratory distress syndrome due to sepsis r53
        • 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 r15r56
        • Mechanical ventilation goals in acute respiratory distress syndrome.From Przybysz TM et al: Early treatment of severe acute respiratory distress syndrome. Emerg Med Clin North Am. 34(1):1-14, 2016, Table 7
          Tidal volume4-6 mL/kg of ideal body weight
          Plateau pressureIdeally less than 30 cm H₂O but lower may be better
          pH, respiratory rate, minute ventilationDepends on patient comorbidities but pH of 7.2 is widely accepted as acceptable permissive hypercapnia; lower may also be acceptable
          PEEPUnknown; higher may be better for severe ARDS
          FiO₂Unknown; titration based on PEEP to FiO₂ table is appropriate
      • Low-pressure ventilation r19
        • Plateau pressure 30 cm H₂O or less r19
    • Other evidence-based ventilation strategies
      • Use PEEP to improve oxygenation and prevent atelectasis r57c98
        • Set PEEP for at least 5 cm H₂O; higher may be better r57
          • Optimal strategy is unknown; options include oxygenation-based titration, titration to maximize compliance, or titration to maximal safe plateau pressure
          • Adverse clinical responses include worsening of oxygenation, dead space, compliance, and/or hemodynamics; require re-evaluation of PEEP level
          • Improves oxygenation; however, there is no clear mortality benefit of higher PEEP r58
          • No significant increase in the risk of barotrauma with higher PEEP r58
          • 2024 American Thoracic Society clinical practice guidelines recommend higher PEEP in patients with moderate or severe acute respiratory distress syndrome (PaO₂:FiO₂ less than or equal to 200) r17r22
      • Consider using recruitment maneuvers to keep all alveoli open (or to open previously collapsed alveoli) in refractory hypoxemia r57
        • 2024 American Thoracic Society clinical practice guidelines recommend recruitment maneuvers in patients with moderate or severe acute respiratory distress syndrome (PaO₂:FiO₂ less than or equal to 200) and discourage prolonged recruitment maneuvers r17r22
        • 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 r55
      • Sedation to improve mechanical ventilation tolerance and decrease oxygen requirements r55
    • 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 settingsr59 and a guide to troubleshooting problems in ventilated patients for nonintensivistsr60
      • NIH ARDS Network ventilator protocol r15c99
        • Calculate predicted body weight
          • Males (in kg) = 50 + 2.3 (height in inches minus 60 inches) r15
          • Females (in kg) = 45.5 + 2.3 (height in inches minus 60 inches) r15
        • Select any ventilator mode
        • Set ventilator settings to achieve initial tidal volume of 8 mL/kg predicted body weight r15
          • Reduce by 1 mL/kg at intervals of 2 hours or less until tidal volume equals 6 mL/kg predicted body weight r15
        • Set initial rate to approximate baseline minute ventilation (not greater than 35 breaths per minute) r15
        • Adjust tidal volume and respiratory rate to achieve pH and plateau pressure goals
        • Plateau pressure goal is 30 cm H₂O or less r15
          • 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) r15
          • 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 r15
          • 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) r15
        • Oxygenation goal is PaO₂ of 55 to 80 mm Hg or SpO₂ of 88% to 95% r15
          • 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)r62 and another found a restrictive oxygenation strategy (target PaO₂ 55 to 70 mm Hg; SpO₂ 88 to 92%) could be potentially harmful r61
          • Use a minimum PEEP of 5 cm H₂O r15
          • Consider use of incremental FiO₂/PEEP combinations to achieve goal using ARDS Network table of combinationsr15
    Indication
    • Acute respiratory distress syndrome of any severity classification
    Complications
    • Hypercapnic respiratory acidosis may develop in some patients

    Comorbidities c100

    • 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 r38
      • 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: r63
        • Higher PEEP with broad variation is used in COVID-19 patients
        • Higher FiO₂ (fraction of inspired oxygen) 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 r64
      • Refer to published guidelines for management recommendations specific for COVID-19 r64r65
        • Anticoagulation is recommended for hospitalized, nonpregnant adults with COVID-19 who are receiving supplemental oxygen r18

    Monitoring

    • Continuously monitor blood pressure, pulse oximetry, temperature, and respiratory rate (from ventilator) c101c102c103
    • Frequently monitor arterial blood gas c104
    • Central venous pressure monitoring is not mandatory but can assist with fluid management; pulmonary artery catheter is not indicated c105

    Complications and Prognosis

    Complications

    • Common complications that occur in an ICU setting include the following:
      • Ventilator-induced lung injury, especially pulmonary edema c106c107
      • Ventilator-associated barotrauma (eg, pneumothorax, subcutaneous edema) c108c109c110
      • Ventilator-associated pneumonia r6c111
      • Catheter-related infections c112
      • Poor nutrition and loss of muscle mass c113c114
      • Deep vein thrombosis c115
      • Gastrointestinal bleeding c116
      • Delirium r66c117
    • Pulmonary fibrosis develops in roughly two-thirds of patients with acute respiratory distress syndrome; patient may become increasingly reliant on persistent mechanical ventilation r67c118
    • Cognitive impairment (post-intensive care syndrome) is common (70%-100% at hospital discharge, 46%-80% at 1 year, and 20% at 5 years) r18r68r69c119
    • Depression and posttraumatic stress disorder are common r69c120c121
    • Long-term physical disability and neuromuscular weakness r18r68c122c123

    Prognosis

    • No specific biomarker is considered predictive of outcome r53
    • Mortality outside of a clinical trial setting remains high and relatively unchanged since the original consensus definition was developed in 1994 r18r70
      • 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 r55

    Screening and Prevention

    Prevention c124

    • No evidence exists for effective preventive measures specific to this syndrome; however, practices likely to decrease risk include: r71
      • Primary prevention of nosocomial pneumonia
      • Primary prevention of aspiration c125
      • Appropriate antibiotic use
      • Restrictive use of blood transfusions c126
      • Avoid vaping and e-cigarette use r4c127c128d5
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