MD Nexus

Acute Respiratory Distress Syndrome (ARDS)-Part 2

Physiology

Factors Which Promote or Exacerbate Acute Respiratory Distress Syndrome (ARDS)

  • High Tidal Volume (VT)
  • Plateau Pressure >30 cm H2O
  • High Respiratory Rate: due to high frequency of stretch
  • High Rate of Stretch: due to rapid lung inflation

Monocyte Activation

  • Substudy of LIPS-A Trial Examining Monocyte Activation in ARDS (Am J Respir Crit Care Med, 2018) [MEDLINE]
    • Biomarkers of Intravascular Monocyte Activation in At-Risk patients were Associated with the Development of ARDS

Ventilator-Induced Lung Injury (VILI)

  • Marini and Gattinoni Have Described the Progression of Ventilator-Induced Lung Injury (VILI) as a “Shrinking of the Baby Lung”, Whereby in Lungs Subjected to Low Tidal Volume Ventilation, Tissue Moves from the Open to the Atelectatic Compartment, a Process Called the “VILI Vortex” (Crit Care, 2022) [MEDLINE]
    • By Way of Background, the Lung in Acute Respiratory Distress Syndrome (ARDS) is Composed of Two Distinct, Gravitationally-Separated Compartments
      • Dependent Lung Regions Consisting of Atelectatic and/or Edematous Airspaces
      • Normally Inflated Lung Tissue in Less Dependent Regions (Comprising the So-Called “Baby Lung”)
    • This Concept Led to the Hypothesis that Ventilating ARDS Patients Using Low Tidal Volumes (as is the Current Standard Practice) Would Protect the Baby Lung from Volutrauma Caused by Overdistension, While Simultaneously Allowing the Atelectatic Compartment to Rest and Potentially Recover
    • This Concept Also Assumed that an Appropriate Amount of Positive End-Expiratory Pressure (PEEP) (as is Also the Current Standard Practice), Based on Oxygenation, Could Avoid the Development of Atelectrauma
  • Some Have Suggested that Time-Controlled Adaptive Ventilation (TCAV) Using Airway Pressure Release Ventilation (APRV) May Enhance Lung Protection by Stabilizing Alveoli and Progressively Reopening Recalcitrant Atelectatic Lung Regions (Crit Care, 2022) [MEDLINE]
    • The TCAV Method to Set APRV Uses the Following
      • The Ratchet Approach Combined with an Extended Inspiratory Duration Necessary to Recruit Alveoli
      • A Brief Expiratory Duration to Brake the Derecruitment of Rapidly Collapsing Alveoli

Pathology

Pathologic Stages of Acute Respiratory Distress Syndrome (ARDS)

  • Early Exudative Stage (Characterized by Diffuse Alveolar Damage): first 7-10 days
    • Diffuse Alveolar Damage is a Nonspecific Reaction to Lung Injury by a Number of Insults (see Diffuse Alveolar Damage)
      • Diffuse Alveolar Damage is Characterized by Interstitial Edema, Acute/Chronic Inflammation, Type II Cell Hyperplasia, and Hyaline Membrane Formation
    • In Patients with Confirmed ARDS by the Berlin Definition, Approximately 45% Had Diffuse Alveolar Damage on Autopsy (Am J Respir Crit Care Med, 2013) [MEDLINE]
  • Fibroproliferative Stage: lasts 14-21 days
    • Resolution of Pulmonary Edema
    • Type II Alveolar Cell Proliferation
    • Squamous Metaplasia
    • Interstitial Infiltration by Myofibroblasts
    • Early Collagen Deposition
  • Fibrotic Stage
    • Destruction of Normal Lung Architecture
    • Variable Degree of Fibrosis
    • Cyst Formation

Diagnosis

History and Physical Exam Elements Which Should Be Explored in the Patient

  • Cardiac Disease (Which May Suggest Cardiogenic Pulmonary Edema)
    • Chest Pain
    • Dyspnea
    • History of Congestive Heart Failure (CHF)
    • History of Coronary Artery Disease (CAD)
    • Orthopnea (see Orthopnea)
    • Peripheral Edema (see Peripheral Edema)
    • Weight Gain (see Weight Gain)
  • Dermatologic Disease
  • Gastrointestinal/Hepatic Disease
  • Hematologic Disease
  • Infectious Disease
    • Animal Exposures
    • Fever (see Fever)
    • History of Recent Dental Procedures
    • History of Recent Travel (Especially Foreign Travel)
    • History of Tick Exposure (Example: Hiking, Camping, etc)
    • History of Unusual Food Ingestion (Example: Unpasteurized Milk Products, etc)
    • Sick Contacts
  • Malignancy
  • Pulmonary Disease
    • Abnormal Lung Sounds (Crackles, Wheezing, Egophony, etc)
    • Cough/Sputum Production (see Cough)
    • Dyspnea (see Dyspnea)
    • Hemoptysis (see Hemoptysis)
    • History of Choking/Aspiration (see Aspiration Pneumonia)
    • History of Lung Disease (Asthma, Bronchiectasis, Chronic Obstructive Pulmonary Disease)
    • Hypoxemia (see Hypoxemia)
  • Reproductive Disease
    • Abdominal Pain
    • History of Pelvic Inflammatory Disease
    • Pregnancy or Recent Vaginal Delivery/C-Section
    • Vaginal Discharge
  • Rheumatologic Disease
  • Surgery/Trauma
    • Burns (see Burns)
    • Recent Surgery
    • Trauma
  • Medication Use
    • Change in Prescribed Medications
    • New Prescribed Medications
  • Illicit Drug Use
  • Toxin Exposure

Standard Blood Testing

  • Arterial Blood Gas (ABG) (see Arterial Blood Gas)
    • Standardly Utilized to Assess for Hypoxemia and Hypercapnia
      • Arterial Blood Gas is Especially Useful in Patients in Whom SpO2 May Not Correlate Well with the Arterial pO2 (i.e. Patients in Whom the Oxygen-Hemoglobin Dissociation Curve May Be Shifted Either Left or Right, Creating an Unexpected Disparity Between the SpO2 and Arterial pO2)
  • Complete Blood Count (CBC) (see Complete Blood Count)
  • Serum Chemistry with Liver Function Tests (LFT’s) (see Serum Chemistry and Liver Function Tests)
    • Standardly Utilized to Evaluate for Electrolyte Disturbance, Acid-Base Disturbance Abnormality, Abnormal Hepatic Function, and Abnormal Renal Function
  • Serum Amylase and Lipase (see Serum Amylase and Serum Lipase)
    • Serum Amylase and Lipase are Useful to Evaluate for Acute Pancreatitis in a Patient with Abdominal Pain
  • Coagulation Tests
  • Serum Lactate (see Serum Lactate
    • Serum Lactate is Standardly Utilized to Evaluate for Sepsis
      • Since Sepsis is the Most Common Etiology of ARDS

Infectious Workup

Blood Culture (see Blood Culture)

  • Useful to Rule Out an Infectious Etiology of ARDS

Sputum Culture (see Sputum Culture)

  • Useful to Rule Out Pneumonia an Etiology of ARDS

Bronchoscopy (see Bronchoscopy)

  • Indications
    • Diagnose Aspiration Pneumonia (see Aspiration Pneumonia): food material in the airways may suggest aspiration as the etiology
    • Diagnose Lipoid Pneumonia (see Lipoid Pneumonia): lipid-laden macrophages may suggest the diagnosis (although lung biopsy is usually required ton confirm the diagnosis)
    • Diagnose Uncommon (or Less Easily Diagnosed) Infectious Etiologies
    • Diagnose Malignancy
    • Diagnose Eosinophilic Pneumonias
    • Diagnose Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage)
  • Clinical Efficacy
    • Bacterial Pneumonia May Be Diagnosed by Bronchoscopy Even When it is Not Suspected Clinically
      • Autopsy Study Demonstrated Presence of Bacterial Pneumonia in 58% of ARDS Cases, While Only 20% of These Cases were Clinically Suspected Antemortem (Chest. 1981) [MEDLINE]

Lung Biopsy (see Video-Assisted Thoracoscopic Lung Biopsy)

  • May Be Useful in Cases Where Other Diagnostic Testing Has Been Negative/Inconclusive (and Patient is Clinically Worsening or Not Improving)
  • Clinical Efficacy
    • Open Lung Biopsy Can Be Performed Safely in Select Patients with ARDS and Often Reveals an Unsuspected Diagnosis, Leading to an Alteration in Therapy (Chest, 2004) [MEDLINE]: unsuspected diagnoses in the study included infection (n = 8), alveolar hemorrhage (n = 5), and bronchiolitis obliterans organizing pneumonia (n = 5)
    • Diffuse Alveolar Damage is Present in Most Patients with Unresolving ARDS and its Frequency is the Same Regardless of the Stage of ARDS (Mild, Moderate, Severe) (Intensive Care Med, 2015) [MEDLINE]: authors concluded that steroid therapy is not recommended
    • Meta-Analysis of Utility of Open Lung Biopsy in ARDS Demonstrated that Biopsy Revleaed a Wide Range of Diagnoses and was Associated with a Change in Therapy in 78% of Cases (Ann Am Thorac Soc, 2015) [MEDLINE]
      • The Most Common Diagnoses were “Fibrosis/Pneumonitis” (n = 155, 25%; 95% CI: 14-37%) and Infection (n = 113, 20%; 95% CI: 15-27%): viruses were the most common infectious agents (accounted for 50% of infectious cases)
      • Diffuse Alveolar Damage was Present in Only 16% of Specimens
      • Procedure-Related Complications Occurred in 29% of Patients: most commonly persistent air leak

Thoracentesis (see Thoracentesis)

  • Useful to Establish an Infectious Etiology of ARDS (When a Pleural Effusion is Present)

Urinalysis with Urine Culture (see Urinalysis and Urine Culture)

  • Useful to Rule Out Urinary Tract Infection as an Etiology of ARDS

Wound Culture

  • Useful to Establish an Infectious Etiology of ARDS (When a Wound is Present)

GenMark ePlex Respiratory Pathogen Panel (see GenMark ePlex Respiratory Pathogen Panel)

Urinary Legionella Antigen (see Urinary Legionella Antigen)

  • Useful to Evaluate ARDS When Pneumonia is the Inciting Etiology

Urinary Pneumococcal Antigen (see Urinary Pneumococcal Antigen)

  • Useful to Evaluate ARDS When Pneumonia is the Inciting Etiology

Urinary Histoplasma Antigen (see Urinary Histoplasma Antigen)

  • Useful to Evaluate ARDS When Pneumonia is the Inciting Etiology

Human Immunodeficiency Virus (HIV) Test (see Human Immunodeficiency Virus)

  • Useful When HIV is a Diagnostic Consideration

Hantavirus Serology (see Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome)

  • Useful When Hantavirus Infection is a Diagnostic Consideration as the Etiology of ARDS

Leptospirosis Serology (see Leptospirosis)

  • Useful When Leptospirosis is a Diagnostic Consideration as the Etiology of ARDS

Respiratory Specimen Testing with rRT-PCR For Middle East Respiratory Syndrome Coronavirus

Severe Acute Respiratory Syndrome Serology and RT-PCR

Coccidioidomycosis Serology (see Coccidioidomycosis Serology)

  • Useful When Coccidioidomycosis is a Diagnostic Consideration as the Etiology of ARDS (see Coccidioidomycosis)

Lung Imaging

Lung Imaging Modalities

  • Chest X-Ray (CXR) (see Chest X-Ray)
    • Presence of Bilateral Pulmonary Infiltrates is Required for the Diagnosis of ARDS
    • Dependent Atelectasis May Be Present
  • Chest Computed Tomography (CT) (see Chest Computed Tomography)
    • Presence of Bilateral Pulmonary Infiltrates is Required for the Diagnosis of ARDS
    • Dependent Atelectasis May Be Present
    • Chest CT Findings Correlate with Prone Positioning Oxygenation Response
      • In a Study of Moderate-Severe ARDS (n = 96), a Greater Difference in the Extent of Consolidation Along the Dependent-Independent Axis (i.e. Median Dorsal-Ventral Difference) on Chest CT Scan was Associated with Subsequent Prone Positioning Oxygenation Response, But Not with the 60-Day Mortality Rate (BMC Pulm Med, 2022) [MEDLINE]
        • High Total Ground Glass Opacity Scores (≥15) were Associated an Increased 60-Day Mortality Rate (Odds Ratio 4.07; 95% Confidence Interval: 1.39-11.89; p = 0.010)
  • Computed Tomography (CT) Pulmonary Artery Angiogram (see Computed Tomography Pulmonary Artery Angiogram)
    • Occasionally Useful to Exclude Acute Pulmonary Embolism (May Mimic ARDS in Some Cases)
  • Thoracic Ultrasound (see Thoracic Ultrasound)
    • May Be Useful to Evaluate for Pleural Effusion, B-Lines (Which are Believed to Represent Thickened Interlobular Septae), etc

Clinical Efficacy

  • Study of Interobserver Variability in the Radiographic Diagnosis of Acute Respiratory Distress Syndrome (ARDS) (Chest, 1999) [MEDLINE]
    • The Radiographic Criterion used in the Current AECC Definition for ALI/ARDS Showed High Interobserver Variability when Applied by Expert iInvestigators in the Fields of Mechanical Ventilation and ARDS
  • Study of Comparative Accuracy of Chest X-Ray vs Chest CT in the Diagnosis of Acute Respiratory Distress Syndrome (ARDS) (J Crit Care, 2013) [MEDLINE]
    • Chest X-Ray (as Compared to Chest CT)
      • Sensitivity: 73%
      • Specificity: 70%
      • Positive Predictive Value: 88%
      • Negative Predictive Value: 47%
    • Female Sex was Associated with Higher Sensitivity and Lower Specificity
  • Retrospective, Observational Study of Chest CT in Diagnosing Acute Respiratory Distress Syndrome (ARDS) (Respir Care, 2016) [MEDLINE]
    • In Patients with ARDS, the Most Common Pathologic Findings of the Lung Parenchyma were Consolidation (94.1% of Cases) and Ground-Glass Infiltrates (85.3% of Cases)
      • Other CT Scan Findings
        • Pleural Effusions (80.4%)
        • Mediastinal Lymphadenopathy (66.7%)
        • Signs of Right Ventricular Strain and Pulmonary Hypertension (53.9%)
        • Pericardial Effusion (37.3%)
        • Subcutaneous Emphysema (12.3%)
        • Pneumothorax (11.8%)
        • Pneumomediastinum (7.4%)
        • Pulmonary Embolism (2.5%)
    • Results of Chest CT Scans Led to Changes in Management in 26.5% of ARDS Cases
  • Study of Chest X-Ray Diagnosis of Acute Respiratory Distress Syndrome (ARDS) (Crit Care Med, 2018) [MEDLINE]: n = 463
    • Radiographic Criteria for Acute Respiratory Distress Syndrome Have Been Criticized for Poor Reliability
    • Only 56% of Observers Correctly Identified ARDS on Chest X-Ray Studies
    • An Educational Intervention Did Not Improve the Rate of Successful Identification (58%)
    • Overall Agreement Between Raters was 0.296 for the Educational intervention Group and 0.272 for the Control Group (p < 0.001)

Other Imaging

  • Abdominal/Pelvic CT (see Abdominal-Pelvic Computed Tomography)
    • May Be Useful to Evaluate Abdominal Pain in the Setting of ARDS: especially for diagnoses such as abdominal abscess, acute pancreatitis, etc

Specific Testing to Rule Out the Alternative Diagnosis of Cardiogenic Pulmonary Edema (see Cardiogenic Pulmonary Edema)

  • General Comments
    • Some of the Same Etiologies Which Cause ARDS (Such as Sepsis) May Also Cause Cardiomyopathy (Eur Heart J, 2012) [MEDLINE]
  • Electrocardiogram (EKG) (see Electrocardiogram)
    • Often Useful to Rule Out Cardiac Etiology of Cardiogenic Pulmonary Edema
  • Serum Brain Natriuretic Peptide (BNP) (see Serum Brain Natriuretic Peptide)
    • Often Useful to Rule Out Cardiac Etiology of Cardiogenic Pulmonary Edema: however, it is probably not useful in isolation
    • Prospective Study of BNP in Sepsis (Crit Care Med, 2006) [MEDLINE]
      • In patients with Severe Sepsis/Septic Shock, BNP and N-Terminal Pro-BNP Values are Highly Elevated and (Despite Significant Hemodynamic Differences) Comparable with Those Found in Acute Heart Failure Patients
    • Prospective Cohort Study of Diagnostic Value of BNP in Critically Ill Patients with Pulmonary Edema (Crit Care, 2008) [MEDLINE]: n= 54
      • BNP Level Drawn within 48 hrs of ICU Admission Do Not Reliably Distinguish ARDS from Cardiogenic Pulmonary Edema, Do Not Correlate with Invasive Hemodynamics, and Daily Measurements Do Not Track Predictably with Volume Status
      • BNP<100 pg/mL Identified ARDS with Sensitivity of 27%/Specificity of 95%
  • Serum Troponin (see Serum Troponin)
    • Often Useful to Rule Out Cardiac Etiology of Cardiogenic Pulmonary Edema
  • Echocardiogram (see Echocardiogram)
    • Often Useful to Rule Out Cardiac Etiology of Cardiogenic Pulmonary Edema
  • Swan-Ganz Catheter (see Swan-Ganz Catheter)
    • May Be Useful in Select Cases to Rule Out Cardiac Etiology (of Cardiogenic Pulmonary Edema)
    • Clinical Efficacy
      • Study of Pulmonary Capillary Wedge Pressure in Acute Respiratory Distress Syndrome (Intensive Care Med, 2002) [MEDLINE]
        • Median PCWP was 16.6 mm Hg in ARDS Patients
        • Patients Who Met Standard Criteria for ARDS Were More Likely to Have a High PCWP
        • PCWP >18 mm Hg was a Strong Predictor of Mortality in ARDS Patients (After Correction of Baseline Differences)
      • Study of Swan-Ganz Catheter to Guide Treatment of Acute Respiratory Distress Syndrome (N Engl J Med, 2006) [MEDLINE]
        • Swan-Ganz Catheter-Guided Therapy Did Not Improve Mortality Rate or Organ Function, But was Associated with More Complications than Central Venous Catheter-Guided Therapy
      • Study of Swan-Ganz Catheter in Shock and ARDS (JAMA, 2003) [MEDLINE]
        • Early Use of Swan-Ganz Catheter Did Not Improve Morbidity or Mortality in Patients with Shock and/or ARDS
    • Recommendations (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
      • Swan-Ganz Catheter is Not Routinely Recommended in the Management of Sepsis-Associated ARDS (Strong Recommendation, High Quality of Evidence)
  • FloTrac (see FloTrac)

Specific Testing to Rule Out the Alternative Diagnosis of Venous Thromboembolism (see Deep Venous Thrombosis and Acute Pulmonary Embolism)

Other

Clinical: Berlin Definition of Acute Respiratory Distress Syndrome (ARDS) (JAMA, 2012) [MEDLINE]

Criteria for the Diagnosis of Acute Respiratory Distress Syndrome (ARDS)

  • Timing
    • Within 7 Days (1 Week) of a Known Clinical Insult or Worsening Respiratory Symptoms
  • Chest Imaging
    • Bilateral Pulmonary Infiltrates (on Chest X-Ray or Chest CT) Which are Not Fully Explained by Effusions, Lobar/Lung Collapse, or Lung Nodules
  • Origin of Edema Not of Cardiac Origin or Due to Fluid Overload
    • Objective Assessment (Echocardiogram, Swan, etc): required in the absence of risk factors for ARDS
  • Oxygenation Criteria (Using pO2/FIO2 Ratio (pO2 in mm Hg, FIO2 in Decimal)
    • General Comments
      • In Cases Where ABG Cannot Be Obtained, Nonlinear Imputation of PaO2/FIO2 from the SpO2/FIO2 Ratio Could Alternatively Be Used (Crit Care Med, 2017) [MEDLINE]
    • Mild ARDS: pO2/FIO2 ratio 200-300 with PEEP/CPAP ≥5 cm H20
    • Moderate ARDS: pO2/FIO2 ratio 100-200 with PEEP/CPAP ≥5 cm H20
    • Severe ARDS: pO2/FIO2 ratio ≤100 with PEEP/CPAP ≥5 cm H20

Critiques of the Berlin Definition (Crit Care, 2022) [MEDLINE]

  • Berlin Definition Timing Criteria are Problematic
    • The Use of a 7 Day Latency from a Known Clinical Insult is Arbitrary and is Not Evidence-Based
      • For Example, the Onset of Respiratory Failure in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2, COVID 2019) is Typically 8-12 Days After the First Symptoms (Crit Care, 2020) [MEDLINE]
  • Berlin Definition Chest Imaging Criteria are Problematic
    • Study of Chest X-Ray Diagnosis of Acute Respiratory Distress Syndrome (Crit Care Med, 2018) [MEDLINE]: n = 463
      • Radiographic Criteria for Acute Respiratory Distress Syndrome Have Been Criticized for Poor Reliability
      • Only 56% of Observers Correctly Identified ARDS on Chest X-Ray Studies
      • An Educational Intervention Did Not Improve the Rate of Successful Identification (58%)
      • Overall Agreement Between Raters was 0.296 for the Educational intervention Group and 0.272 for the Control Group (p < 0.001)
  • Berlin Definition Oxygenation Criteria are Problematic
    • pO2 has a Curvilinear Relationship with FIO2 (Am Rev Respir Dis, 1977) [MEDLINE] (Clin Chest Med, 1982) [MEDLINE]
      • pO2/FIO2 Ratio Varies with the Degree of Ventilation/Perfusion Mismatch and Intrapulmonary Shunt
      • In Patients with ARDS and a Fixed Degree of Intrapulmonary Shunt, Changes in FIO2 Cause the pO2/FIO2 Ratio to Fluctuate Unpredictably by >100 mm Hg (Crit Care Med, 1997) [MEDLINE]

Clinical: Proposed Revised Definition of Acute Respiratory Distress Syndrome (ARDS) (Am J Respir Crit Care Med, 2024) [MEDLINE]

Criteria Which Apply to All Acute Respiratory Distress Syndrome (ARDS) Categories

Risk Factors and Origin of Edema

  • Precipitated by an Acute Predisposing Risk Factor (Such as Pneumonia, Non-Pulmonary Infection, Trauma, Transfusion, Aspiration, or Shock)
    • Pulmonary Edema is Not Exclusively or Primarily Attributable to Cardiogenic Pulmonary Edema/Fluid Overload and Hypoxemia/Gas Exchange Abnormalities are Not Primarily Attributable to Atelectasis
    • However, Acute Respiratory Distress Syndrome (ARDS) Can Be Diagnosed in the Presence of These Conditions if a Predisposing Risk Factor for Acute Respiratory Distress Syndrome (ARDS) is Also Present

Timing

  • Acute Onset or Worsening of Hypoxemic Respiratory Failure within 1 Week of the Estimated Onset of the Predisposing Risk Factor (or New or Worsening Respiratory Symptoms)
    • This Recognizes that the Onset May Be More Indolent for Some Insults (Such as COVID-19, etc)

Chest Imaging

  • Bilateral Opacities on Chest Radiography and Computed Tomography or Bilateral B Lines and/or Consolidations on Thoracic Ultrasound (Not Fully Explained by Pleural Effusions, Atelectasis, or Nodules/Masses)

Criteria Which Apply to Specific Acute Respiratory Distress Syndrome (ARDS) Categories

Non-Intubated Acute Respiratory Distress Syndrome (ARDS)

  • General Comments
    • Estimated FIO2 = Ambient FIO2 (0.21) + 0.03 x O2 Flow Rate (in L/min)
    • Blood Gas and Oximetry Measurements Should Be Made When the Patient is at Rest and ≥30 min After Changes in Position, FIO2, and/or Flow Rate
    • For Pulse Oximetry
      • Ensure an Adequate Waveform and Oximeter Placement
      • SpO2/FIO2 Ratio is Not Valid for SpO2 >97%
      • Pulse Oximetry is Not Recommended for Diagnosis of Acute Respiratory Distress Syndrome (ARDS) if a Hemoglobin Abnormality (Methemoglobinemia, Carboxyhemoglobinemia, etc) is Suspected
  • pO2/FIO2 Ratio ≤300 on High-Flow Nasal Cannula with a Minimum Flow Rate of ≥30 L/min or Noninvasive Positive-Pressure Ventilation (NIPPV) (on Either Bilevel Positive Airway Pressure or Continuous Positive Airway Pressure) with a Minimum of 5 cm H2O of End-Expiratory Pressure
    • Alternate: Oxygen Saturation as Measured by Pulse Oximetry SpO2/FIO2 ≤315 (if Oxygen Saturation as Measured by Pulse Oximetry is ≤97%) on High-Flow Nasal Cannula with a Minimum Flow Rate of ≥30 L/min or Noninvasive Positive-Pressure Ventilation (NIPPV) (on Either Bilevel Positive Airway Pressure or Continuous Positive Airway Pressure) with a Minimum of 5 cm H2O of End-Expiratory Pressure

Intubated Acute Respiratory Distress Syndrome (ARDS)

  • General Comments
    • All Severity Categories Require a Minimum PEEP of 5 cm H2O
    • Patients May Move from One Category to Another During Their Disease Course
    • Blood Gas and Oximetry Measurements Should Be Made When the Patient is at Rest and ≥30 min After Changes in Position, FIO2, and/or Flow Rate
    • For Pulse Oximetry
      • Ensure an Adequate Waveform and Oximeter Placement
      • SpO2/FIO2 Ratio is Not Valid for SpO2 >97%
      • Pulse Oximetry is Not Recommended for Diagnosis of Acute Respiratory Distress Syndrome (ARDS) if a Hemoglobin Abnormality (Methemoglobinemia, Carboxyhemoglobinemia, etc) is Suspected
  • Mild: pO2/FIO2 Ratio >200 and ≤300
    • Alternate: Pulse Oximetry SpO2/FIO2 >235 and ≤315 (if Pulse Oximetry Oxygen Saturation is ≤97%)
  • Moderate: pO2/FIO2 Ratio >100 and ≤200
    • Alternate: Pulse Oximetry SpO2/FIO2 >148 and ≤235 (if Pulse Oximetry Oxygen Saturation is ≤97%)
  • Severe: pO2/FIO2 Ratio ≤100
    • Alternate: Pulse Oximetry SpO2/FIO2 ≤148 (if Pulse Oximetry Oxygen Saturation is ≤97%)

Modified Definition for Resource-Limited Settings

  • General Comments
    • Modified Oxygenation Criteria Can Be Applied in Settings in Which Arterial Blood Gas and/or High-Flow Nasal Cannula, Noninvasive Positive-Pressure Ventilation (NIPPV), and Mechanical Ventilation are Not Routinely Available
    • Blood Gas and Oximetry Measurements Should Be Made When the Patient is at Rest and ≥30 min After Changes in Position, FIO2, and/or Flow Rate
    • For Pulse Oximetry
      • Ensure an Adequate Waveform and Oximeter Placement
      • SpO2/FIO2 Ratio is Not Valid for SpO2 >97%
      • Pulse Oximetry is Not Recommended for Diagnosis of Acute Respiratory Distress Syndrome (ARDS) if a Hemoglobin Abnormality (Methemoglobinemia, Carboxyhemoglobinemia, etc) is Suspected
  • SpO2/FIO2 Ratio ≤315 (if Pulse Oximetry Oxygen Saturation is ≤97%)
    • Neither Positive End-Expiratory Pressure Nor a Minimum Oxygen Flow Rate is Required for the Diagnosis in Resource-Limited Settings

Clinical: Practical Daily Assessment of Respiratory Failure

Clinical Manifestations

Cardiovascular Manifestations

Gastrointestinal Manifestations

Hematologic Manifestations

  • Coagulopathy (see Coagulopathy
    • Epidemiology
      • While Coagulopathy May Occur in ARDS, Disseminated Intravascular Coagulation (DIC) is Uncommon, Except When Sepsis or Malignancy is Present
    • Clinical
      • Elevated Partial Thromboplastin Time (PTT)
      • Elevated Prothrombin Time (PT)
  • Elevated Plasma D-Dimer (see Elevated Plasma D-Dimer)
    • Epidemiology
      • Variably Present
  • Leukocytosis with/without Bandemia (see Leukocytosis)
    • Epidemiology
      • Variably Present
  • Leukopenia (see Leukopenia)
    • Epidemiology
      • Variably Present

Pulmonary Manifestations

Bilateral Pulmonary Infiltrates

  • Epidemiology
    • By Definition, Bilateral Pulmonary Infiltrates are a Required Diagnostic Feature of ARDS
    • Radiographic Pulmonary Infiltrates Generally Appear Between 6-72 hrs Following an Inciting Event
  • Physiology
    • Alveolar Filling Process
  • Diagnosis
    • Decreased Lung Compliance: static and dynamic compliance can be measured on the ventilator
    • Increased Dead Space/Tidal Volume (VD/VT) Ratio
    • Chest X-Ray (see Chest X-Ray)
      • Alveolar Infiltrates (with/without Dependent Atelectasis)
      • Atelectasis: may also be present
    • Chest CT (see Chest Computed Tomography)
      • Alveolar Filling/Consolidation
      • Ground-Glass Infiltrates
      • Atelectasis: may also be present
  • Clinical
    • Cough (see Cough)
    • Crackles
    • Cyanosis (see Cyanosis): may occur in severe cases
    • Dyspnea (see Dyspnea)
    • Increased A-a Gradient Hypoxemia (see Hypoxemia)
      • Epidemiology
        • Type I-Hypoxemic Respiratory Failure: most commonly observed
        • Type II-Hypoxemic, Hypercapnic Respiratory Failure: may be observed in cases with severe ARDS (and usually requires mechanical ventilation)
    • Respiratory Alkalosis (see Respiratory Alkalosis)
    • Tachypnea (see Tachypnea)

Bronchospasm (see Obstructive Lung Disease)

  • Epidemiology
    • Variably Present
  • Clinical
    • Increased Peak Inspiratory Pressure-Plateau Pressure Difference (>5 cm H2O) on Ventilator
    • Wheezing (see Wheezing)

Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage)

  • Epidemiology
    • While Low-Grade Diffuse Alveolar Hemorrhage May Occur in Some Cases of ARDS, the Presence of Significant Hemoptysis Requires that Diffuse Alveolar Hemorrhage is Ruled Out as a Primary Disorder
  • Diagnosis
    • Bronchoscopy (see Bronchoscopy): routinely used to evaluate hemoptysis in the setting of ARDS
  • Clinical

Pulmonary Hypertension (see Pulmonary Hypertension)

  • Physiology
    • Hypercapnia-Induced Pulmonary Vasoconstriction (see Hypercapnia) (J Appl Physiol, 2003) [MEDLINE]
      • Hypercapnic Vasoconstriction May Be Responsive to Nitric Oxide
      • When Associated with High PEEP in the Setting of ARDS, Hypercapnic Vasoconstriction May Result in RV Dysfunction (Intensive Care Med, 2009) [MEDLINE]
    • Hypoxemia-Induced Pulmonary Vasoconstriction (see Hypoxemia)
      • Hypoxic Vasoconstriction is Enhanced by Acidosis

Other Manifestations

  • Fever (see Fever)
    • Presence of Fever (or Hypothermia) is Associated with Delayed Liberation from Mechanical Ventilation
      • Analysis of Prospective Cohort Study Evaluating the Impact of Fever on Ventilator Weaning in Patients with Acute Respiratory Distress Syndrome (Ann Am Thorac Soc, 2013) [MEDLINE]: n = 450 (from 13 ICU’s at 4 hospitals in Baltimore, Maryland)
        • Only 12% of Patients were Normothermic During the First 3 Days After Onset of Acute Respiratory Distress Syndrome
        • Fever was Associated with Delayed Liberation from Mechanical Ventilation
        • During the First Week Post-Acute Respiratory Distress Syndrome, Each Additional Day of Fever Resulted in a 33% Reduction in the Likelihood of Successful Ventilator Liberation (95% Confidence Interval for Adjusted Hazard Ratio, 0.57-0.78; P<0.001
        • Hypothermia was Associated with Delayed Liberation from Mechanical Ventilation and Increased Mortality Rate
        • Hypothermia was Independently Associated with Decreased Ventilator-Free Days (Hypothermia During Each of the First 3 Days: Reduction of 5.58 Days, 95% CI: -9.04 to -2.13; P = 0.002)
        • Hypothermia was Independently Associated with Increased Mortality (Hypothermia During Each of the First 3 Days: Relative Risk, 1.68; 95% CI: 1.06-2.66; P = 0.03)

Complications

Infectious Complications

  • Central Line-Associated Blood Stream Infection (CLABSI) (see Central Venous Catheter)
    • Epidemiology
      • May Occur as a Complication When a Central Venous Catheter Has Been Previously Placed as a Component of Either Sepsis or ARDS Therapy
  • Sepsis (see Sepsis)
    • Epidemiology
      • May Occur as a Complication in a Critically Ill Patient with Portals for Entry (Endotracheal Tube, Central Venous Catheter, etc)

Gastrointestinal Complications

  • Clostridium Difficile Colitis (see Clostridium Difficile)
    • Epidemiology
      • May Occur as a Complication When Antibiotics Have Been Previously Utilized in the Treatment of ARDS
  • Impaired Nutrition
    • Epidemiology
      • May Occur as a Complication in a Critically Ill Patient

Vascular Complications

  • Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis)
    • Epidemiology
      • May Occur as a Complication in an Immobilized, Critically Ill Patient

Neurologic Complications

  • Delirium (see Delirium)
    • Epidemiology
      • Delirium is a Common Complication in Critical Illness (Both as a Component of the Primary Disease Process and as a Result of Treatments Such as Sedation, etc)
        • BRAIN-ICU Study (NEJM, 2013) [MEDLINE]: in a study of patients with respiratory failure or shock in the medical or surgical intensive care unit (n = 821), 74% of cases had delirium
  • Intensive Care Unit (ICU)-Acquired Weakness (see Intensive Care Unit-Acquired Weakness)
    • Epidemiology
      • Generalized Weakness is a Common Complication of Critical Illness with Prolonged Immobilization
        • Study of Vasoactive Medications in Mechanically-Ventilated Patients (Chest, 2018) [MEDLINE]: in mechanically-ventilated patients, the use of vasoactive medications was associated with an increased risk of ICU-acquired weakness
  • Sleep Disturbance
    • Epidemiology
      • May Occur as a Complication in a Critically Ill Patient

Pulmonary Complications Associated with the Use of Invasive Mechanical Ventilation (see Invasive Mechanical Ventilation-Adverse Effects and Complications)

Renal Complications

  • Acute Kidney Injury (AKI) (see Acute Kidney Injury)
    • Epidemiology
      • AKI Occurs in Approximately 68% of ARDS Patients (After ARDS Onset) (Ann Intensive Care, 2019) [MEDLINE]
    • Retrospective Study of Risk Factors for the Development of AKI in Patients with ARDS (Ann Intensive Care, 2019) [MEDLINE]: n = 357
      • Approximately 24.6% of Patients had Stage I AKI, 27% had stage II AKI, and 48.4% had Stage III AKI
      • Median Time of AKI Onset for Stage I AKI was 2 Days (Interquartile Range: 1.5–5.5), While Stage II and III AKI was 4 Days
      • Risk Factors
        • Acidosis (on Day 1 of ARDS): subdistribution hazard ratio per 0.1 units decrease was 1.18 (95% CI: 1.05–1.32)
        • Age: subdistribution hazard ratio 1.01 (95% CI: 1.00–1.02)
        • Higher Severity of Illness (SOFA Score): subdistribution hazard ratio 1.16 (95% CI: 1.12–1.21)
        • History of Diabetes Mellitus (see Diabetes Mellitus): subdistribution hazard ratio 1.42 (95% CI: 1.07–1.89)

Prevention

General Comments

  • Prevention of Acute Respiratory Distress Syndrome (ARDS) is an Important Clinical Goal, Since the Radiographic Identification of the Findings of Acute Respiratory Distress Syndrome (ARDS) is Generally Unreliable (Crit Care Med, 2018) [MEDLINE]

Aspirin (see Acetylsalicylic Acid)

  • LIPS-A (Phase 2b) Trial of Aspirin to Prevent Acute Respiratory Distress Syndrome (ARDS) in Patients Presenting to the ED Who are At-Risk for Acute Respiratory Distress Syndrome (ARDS) (JAMA, 2016) [MEDLINE]
    • Aspirin Administered to At-Risk Patients in the Emergency Department Had No Clinical Benefit in the Prevention of ARDS at 7 Days

Low Tidal Volume Ventilation

  • IMPROVE Trial of Low Tidal Volume Ventilation in Abdominal Surgery Patients at Risk for Acute Respiratory Distress Syndrome (ARDS) (N Engl J Med, 2013) [MEDLINE]
    • As Compared with Nonprotective Mechanical vVentilation, the Lung Protective Ventilation in Intermediate/High-Risk Patients Undergoing Major Abdominal Surgery was Associated with Improved Clinical Outcomes and Decreased Health Care Utilization
  • Meta-Analysis of Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome (ARDS) (Intensive Care Med, 2014) [MEDLINE]
    • Use of Lower Tidal Volumes in Patients without ARDS at the Onset of Mechanical Ventilation Could Be Associated with a Shorter Duration of Ventilation
    • Use of Lower Tidal Volumes Seems No to Affect Sedation or Analgesia Needs, But This Must Be Confirmed in a Robust, Well-Powered Randomized Controlled Trial
  • Meta-Analysis of Efficacy of Intraoperative Low Tidal Volume Ventilation in Preventing Postoperative Pulmonary Complications (Ann Surg, 2016) [MEDLINE]: n = 1054 (16 studies)
    • Intraoperative Low Tidal Volume Ventilation in Conjunction with PEEP and Recruitment Maneuvers Improved Clinical Pulmonary Outcomes (Atelectasis, Lung Infection, Acute Lung Injury) and Decreased Hospital Length of Stay in Otherwise Healthy Patients Undergoing General Surgery
  • PReVENT Trial Comparing Low (7 mL/kg PBW) vs Intermediate (9 mL/kg PBW) Tidal Volume Ventilation in ICU Patients at Risk for Acute Respiratory Distress Syndrome (ARDS) (JAMA, 2018) [MEDLINE]: n = 961 (6 centers)
    • Study Design
      • The Majority of Patients were Randomized within 1 hr of Start of Mechanical Ventilation
      • Only Patients Who were Not Expected to Be Extubated within 24 hrs of Randomization were Included in the Trial
      • Low Tidal Volume Group Used Higher Tidal Volume (7 mL/kg PBW) than in Other Similar Studies (Which Generally Used 6 mL/kg PBW), Because Pressure Support was Used More Frequently in this Group
        • By Day 1, 58% of Patients in the Low Tidal Volume Group were Receiving Pressure Support Ventilation (Which Allowed Large Spontaneous Tidal Volumes if the Patients were on Minimal Ventilatory Support)
        • On Day 1, 59% of Patient in the Low Tidal Volume Group Received a Tidal Volume >6 mL/kg PBW and 14% of Patients Received a Tidal Volume >9.5 mL/kg PBW
        • On Days 1 and 2, Respectively, Estimates Suggest that Only 25% and 25% of Patients in the Intermediate Tidal Volume Group Received Tidal Volumes >10 mL/kg PBW
    • In ICU Patients without ARDS, There was No Difference Between Low Tidal Volume Ventilation Strategy (7 mL/kg PBW) and Intermediate Tidal Volume Ventilation Strategy (9 mL/kg PBW), in Terms of Ventilator-Free Days at Day 28
    • In ICU Patients without ARDS, There was No Difference Between Low Tidal Volume Ventilation Strategy (7 mL/kg PBW) and Intermediate Tidal Volume Ventilation Strategy (9 mL/kg PBW), in Terms of ICU Length of Stay, Hospital Length of Stay, 90-Day Mortality, Incidence of ARDS, Incidence of Pneumonia, Incidence of Severe Atelectasis, and Incidence of Pneumothorax
    • Possible Explanations for Lack of Effect of the Low Tidal Volume Ventilation Strategy
      • The Low Tidal Volume Ventilation Strategy was Associated with Respiratory Acidosis, Which Might Have Influenced the Duration of Ventilation
      • Driving Pressure in the Intermediate Volume Ventilation Strategy was Still within a Protective Range for Patients without ARDS
    • Critique
      • Some Experts Have Suggested that the PReVENT Trial Demonstrates that a Negative Trial May Be the Result of Inadequate Separation Between Interventions

References

Physiology

Diagnosis

General

Chest X-Ray (see Chest X-Ray)

Chest Computed Tomography (CT) (see Chest Computed Tomography)

Echocardiogram (see Echocardiogram)

Swan-Ganz (Pulmonary Artery) Catheter (see Swan-Ganz Catheter)

Serum Brain Natriuretic Peptide (BNP) (see Serum Brain Natriuretic Peptide)

Bronchoscopy (see Bronchoscopy)

Lung Biopsy

Clinical Manifestations

General

Intensive Care Unit (ICU)-Acquired Weakness

Ventilator-Induced Lung Injury (VILI)/Barotrauma

Pulmonary Hypertension (see Pulmonary Hypertension)

Other

Complications

Prevention