Acute Respiratory Distress Syndrome (ARDS)-Part 1


History

In 1967, Ashbaugh Introduced the Term “Respiratory Distress Syndrome” to Describe a Clinical Syndrome with Defined Features

  • Acute Onset of Tachypnea (see Tachypnea)
  • Decreased Lung Compliance
  • Diffuse Pulmonary Infiltrates
  • High Short-Term Adult Mortality Rates
  • Hypoxemia (see Hypoxemia)

Epidemiology

Prevalence

  • LUNG SAFE Global Observational Study of ARDS in 50 Countries (JAMA, 2016) [MEDLINE]
    • Epidemiology
      • Approximately 10.4% of ICU Admissions Met ARDS Criteria
      • Approximately 23.4% of Mechanically Ventilated Patients Met ARDS Criteria
    • Clinical
      • Clinical Recognition of ARDS Ranged from 51.3% in Mild ARDS to 78.5% in Severe ARDS
    • Therapy
      • Less Than 66% of the Patients Received Tidal Volume <8 mL/kg
      • Proning was Used in Only 16.3% of Patients with Severe ARDS
    • Hospital Mortality Rates
      • Mild ARDS: 34.9%
      • Moderate ARDS: 40.3%
      • Severe ARDS: 46.1%
    • Conclusions
      • ARDS Recognition and Management Has Room for Potential Clinical Improvement

Cost

  • Systematic Review of the Costs of ARDS (Chest, 2021) [MEDLINE]: n = 49,483 (from 22 studies)
    • Mean Inpatient Costs Ranged from $8,476 (2021 US Dollars) to $547,974 (2021 US Dollars) and were Highest in Publications of Lower Quality and in American Health Systems and were Associated with Trauma Cohorts
    • Mean Outpatient Costs were Highest in Publications with Higher Readmission Rates, Longer Durations of Follow-Up, and in American Health Systems

Risk Factors

Prediction of Acute Respiratory Distress Syndrome Using Clinical Factors

  • Lung Injury Prediction Score (LIPS) Study (Am J Respir Crit Care Med, 2011) [MEDLINE]: multicenter observational cohort study (n = 5,584 patients at risk)
    • Acute Lung Injury Occurred at a Median of 2 Days in 6.8% of Patients
    • Acute Lung Injury Can Be Predicted Early in the Course of Illness Using Clinical Parameters
      • Aspiration: LIPS points +2 pts
      • High-Risk Surgery (add 1.5 pts if emergency surgery)
        • Aortic/Vascular: +3.5 pts
        • Cardiac: +2.5 pts
        • Acute Abdomen: +2 pts
        • Orthopedic Spine: +1 pt
      • High-Risk Trauma
        • Traumatic Brain Injury: +2 pts
        • Smoke Inhalation: +2 pts
        • Near Drowning: +2 pts
        • Lung Contusion: +1.5 pts
        • Multiple Fractures: +1.5 pts
      • Pneumonia: +1.5 pts
      • Shock: +2 pts
      • Sepsis: +1 pt
      • Negative Risk Modifiers (Decrease the Risk of Acute Lung Injury)
        • Diabetes Mellitus: -1 pt (only if sepsis)
        • Note: Diabetes Mellitus is the Only Risk factor Which Decreases the Risk of Developing ARDS
      • Positive Risk Modifiers (Increase the Risk of Acute Lung Injury)
        • FIO2 >35%: +2 pts
        • pH <7.35: +1.5 pts
        • Tachypnea with RR >30: +1.5 pts
        • Alcohol Abuse: +1 pts
        • Obesity with BMI >30: +1 pt
        • Hypoalbuminemia: +1 pt
        • Chemotherapy: +1 pt
        • SpO2 <95%: +1 pt
    • Scoring
      • Over 4 points (Optimal Cutoff Point in the Study Based on the Area Under the Curve Analysis): 69% sensitivity and 78% specificity for the prediction of development of ARDS

Prediction of Acute Respiratory Distress Syndrome Using Clinical Factors Present in the Emergency Department

  • Emergency Department Lung Injury Prediction Score Study (EDLIPS)/LIPS-1 Study (Int J Emerg Med, 2012) [MEDLINE]
    • Incidence of Acute Lung Injury was 7%
    • EDLIPS (Obtained Early in ED Course) Discriminated Patients Who Developed Acute Lung Injury Better than APACHE II Scoring and Similar to Original LIPS Score

Age

  • Prospective Multicenter Observational Cohort Study of Hospitalized Patients at Risk of Developing ARDS (from 3/09-8/09) (J Intensive Care Med, 2019) [MEDLINE]: n = 5,584 (22 hospitals)
    • Approximately 6.8% of the Patients Developed ARDS
    • After Adjusting for Severity of Illness and the Risk of ARDS Development Attributable to Other Factors, Older Adult Patients Had a Lower Incidence of ARDS, as Compared to Younger Patients (Odds Ratio: 0.28, 95% Confidence Interval: 0.18-0.42)

Corticosteroids (see Corticosteroids)

  • Retrospective Study Examining the Effect of Preadmission Oral Corticosteroid on the Risk of Development of Acute Respiratory Distress Syndrome in ICU Patients with Sepsis (Crit Care Med, 2017) [MEDLINE]: n = 1080
    • Preadmission Oral Corticosteroid Use Decreases the Risk of Early Acute Respiratory Distress Syndrome (Within 96 hrs of ICU Admission) in ICU Patients with Sepsis (35%), as Compared to Patients Who Had Not Received Preadmission Corticosteroids (42%)
    • Higher Corticosteroid Doses (Prednisone 30 qday) were Associated with Lower Risk of ARDS (Odds Ratio 0.53) than were Lower Corticosteroid Doses (Prednisone 5 mg qday)
    • Preadmission Oral Corticosteroid Use Did Not Impact the In-Hospital Mortality Rate, ICU Length of Stay, or Ventilator-Free Days

Etiology

Infection

General

  • Sepsis (see Sepsis)
    • Epidemiology
      • Sepsis is the Most Common Etiology of ARDS
    • Risk Factors for the Development of Sepsis-Associated ARDS
      • Acute Abdomen (Ann Intensive Care, 2017) [MEDLINE]
      • Acute Pancreatitis (Ann Intensive Care, 2017) [MEDLINE]
      • Alcohol Abuse (Crit Care Med, 2003) [MEDLINE] and (Crit Care Med, 2008) [MEDLINE]
        • Ethanol May Decrease Glutathione Concentrations in the Epithelial Lining Fluid, Increasing the Risk of Oxidative iInjury to the Lung
      • Delayed Antibiotics (Crit Care Med, 2008) [MEDLINE]
      • Delayed Goal-Directed Resuscitation (Crit Care Med, 2008) [MEDLINE]
      • Diabetes Mellitus (Crit Care Med, 2008) [MEDLINE]
      • Higher APACHE II Score (Ann Intensive Care, 2017) [MEDLINE]
      • Higher Intravenous Fluid Resuscitation within the First 6 hrs (Ann Intensive Care, 2017) [MEDLINE]
        • In Stratified Analysis, the Total Fluid Infused within the First 6 hrs was a Risk Factor in the Non-Shock Group, But Not in the Shock Group
      • Increased Baseline Respiratory Rate (Crit Care Med, 2008) [MEDLINE]
      • Older Age (Ann Intensive Care, 2017) [MEDLINE]
      • Pneumonia as the Site of Infection (Ann Intensive Care, 2017) [MEDLINE]
      • Recent Chemotherapy (Crit Care Med, 2008) [MEDLINE]
      • Shock (Ann Intensive Care, 2017) [MEDLINE]
      • Transfusion (Crit Care Med, 2008) [MEDLINE]

Viral Pneumonia

Bacterial Pneumonia

Fungal Pneumonia

Parasitic Pneumonia

Aspiration

Trauma/Surgery

  • Burns (see Burns)
  • Blast Injury
    • Explosion
    • Lightning
  • Fat Embolism (see Fat Embolism)
  • Head Trauma/Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)
  • Pulmonary Contusion (see Pulmonary Contusion)
  • Surgery
    • Systematic Review/Meta-Analysis of Morbidity/Mortality in Post-Operative Acute Lung Injury (Lancet Respir Med, 2014) [MEDLINE]
      • Incidence of Acute Lung Injury was Similar Following Both Thoracic and Abdominal Surgery
      • Risk Factors for Post-Operative Acute Lung Injury
        • Higher American Society of Anesthesiology (ASA) Score
        • Higher Prevalence of Pre-Existing Sepsis or Pneumonia
        • Older Age
        • Receipt of Blood Transfusions
        • Receipt of High Tidal Volume Ventilation and/or Low PEEP During Surgery
      • Post-Operative Acute Lung Injury Increased ICU Length of Stay and Hospital Length of Stay
      • Overall Attributable Mortality Rate for Post-Operative Acute Lung Injury: 19%
        • Attributable Mortality Rate for Post-Operative Acute Lung Injury Following Thoracic Surgery: 26.5%
        • Attributable Mortality Rate for Post-Operative Acute Lung Injury Following Abdominal Surgery: 12.2%
      • Risk of In-Hospital Mortality was Independent of the Ventilation Strategy
  • Other Trauma

Mechanical Pulmonary Edema

Hemodynamic Disturbance

Hematologic Disorder

Neurogenic Pulmonary Edema (see Neurogenic Pulmonary Edema)

Rheumatologic Disease

Lung Transplant Rejection/Dysfunction (see Lung Transplant Rejection)

Drug

Toxin

  • Acetic Acid Inhalation (see Acetic Acid)
    • Inhalational Exposure
  • Acetic Anhydride Inhalation (see Acetic Anhydride)
    • Inhalational Exposure
  • Acrolein Inhalation (see Acrolein)
    • Inhalational Exposure
  • Acute Beryllium Exposure (see Beryllium)
    • Inhalational Exposure
  • Amitrole Inhalation (see Amitrole)
    • Inhalational Exposure
  • Ammonia Inhalation (see Ammonia)
    • Inhalational Exposure
  • Bromine/Methyl Bromide Inhalation (see Bromine-Methyl Bromide)
    • Inhalational Exposures
      • Bromine Liquid (Readily Vaporizes): used in chemical synthesis and water purification
      • Methyl Bromide Gas (Bromomethane): used as industrial fumigant
  • Carboxyhemoglobinemia (see Carboxyhemoglobinemia)
    • Inhalational Exposure
  • Chlorine Inhalation (see Chlorine)
    • Inhalational Exposure
  • Chloropicrin Gas Inhalation (see Chloropicrin Gas)
    • Inhalational Exposures
      • Chemical Manufacturing
      • Fumigant
      • World War I Wartime Exposure
  • Chromic Acid Inhalation (see Chromic Acid)
    • Inhalational Exposures: used in electroplating
  • Contaminated Rapeseed Oil (see Contaminated Rapeseed Oil)
  • Copper Dust/Fume Inhalation (see Copper)
    • Inhalational Exposure
  • Cyanide Intoxication (see Cyanide)
    • Dermal, Ingestion, and Inhalational Exposures
      • Fire/Smoke Inhalation (see Smoke Inhalation): smoke inhalation is the most common etiology of cyanide intoxication in industrialized countries
      • Industrial Exposure: jewelry electroplating, plastic and rubber manufacturing, metal extraction during mining, photography, hair removal from hides, rodent pesticide and fumigant use
      • Medical Administration: amygdalin (laetrile), nitroprusside (nipride)
      • Dietary Ingestion: Rosaceae family seeds
      • Other: during illicit synthesis of phencyclidine, as a result of terrorist attack, ingestion of acetonitrile nail polish remover, tobacco abuse
  • Diazomethane Inhalation (see Diazomethane)
    • Inhalational Exposure
  • Diborane Gas Inhalation (see Diborane Gas)
    • Inhalational Exposure During Microelectronics Manufacturing
  • Dinitrogen Tetroxide Inhalation (see Dinitrogen Tetroxide)
    • Inhalational Exposure to Rocket Propellant
  • Ethylene Oxide Gas Inhalation (see Ethylene Oxide Gas)
    • Inhalational Exposure During Medical Disinfection and Sterilization
  • Formic Acid Inhalation (see Formic Acid)
    • Inhalational (Aerosol, Vapor) Exposures
      • Leather Tanning
      • Limescale Remover
      • Rubber Manufacturing
      • Textile Industry
      • Toilet Bowl Cleaner
      • Treatment of Livestock Feed: due to to its antibacterial properties
  • Glyphosate Ingestion (see Glyphosate
    • Ingestion Exposure to Herbicide (Roundup, etc)
  • Heavy Metal Fume Inhalation
  • Hydrocarbons (see Hydrocarbons)
    • Ingestion/Aspiration Exposure
  • Hydrofluoric Acid Inhalation (see Hydrofluoric Acid)
    • Inhalational Exposure
  • Hydrogen Sulfide Gas Inhalation (see Hydrogen Sulfide Gas)
    • Inhalational Exposure
  • Isopropanol Intoxication (see Isopropanol)
  • Lycoperdonosis (see Lycoperdonosis)
    • Inhalational Exposure to Puffball Mushroom (Lycoperdon) Spore, Resulting in Allergic Bronchioloalveolitis
  • Methamphetamine Intoxication (see Methamphetamine)
  • Methyl Isocyanate Inhalation (see Methyl Isocyanate)
    • Inhalational Exposure
  • Methyl Isothiocyanate Inhalation (see Methyl Isothiocyanate)
    • Inhalational Exposure
  • Nickel Carbonyl Inhalation (see Nickel Carbonyl)
    • Inhalational Exposure
  • Nitric Acid Inhalation (see Nitric Acid)
    • Inhalational Exposure
  • Nitrogen Dioxide Inhalation (see Nitrogen Dioxide)
    • Inhalational Exposure
  • Nitrogen Mustard Gas Inhalation (see Nitrogen Mustard Gas)
    • Inhalational Exposure
  • Osmium Tetroxide Inhalation (see Osmium Tetroxide)
    • Inhalational Exposure
  • Ozone Inhalation (see Ozone)
    • Inhalational Exposure (Welding/Water Treatment/Pulp Paper Bleaching)
  • Palytoxin (see Palytoxin)
    • Epidemiology
      • Palytoxin Rarely is Associated with ARDS
    • Inhalational Exposure to Microalgae (Ostreopsis Ovate, Ostreopsis Siamensis), Corals, and Sea Anemones
  • Paraquat Intoxication (see Paraquat)
    • Ingestion Exposure
  • Phosgene Gas Inhalation (see Phosgene Gas)
    • Inhalational Exposure
  • Phosphine Gas Inhalation (see Phosphine Gas)
    • Inhalational Exposure
  • Polytetrafluoroethylene (PTFE, Teflon) Inhalation (see Polytetrafluoroethylene)
    • Inhalational Exposure
  • Rattlesnake Bite (see Rattlesnake Bite)
  • Smoke Inhalation (see Smoke Inhalation)
    • Inhalational Exposure to Fire (Especially in an Enclosed Space)
  • Sodium Azide Inhalation (see Sodium Azide)
    • Inhalational Exposure (Automobile Airbag Deployment)
  • Sulfur Dioxide Inhalation (see Sulfur Dioxide
    • Inhalational Exposure
  • Sulfuric Acid Inhalation (see Sulfuric Acid)
    • Inhalational Exposure
  • Sulfur Mustard Gas Inhalation (see Sulfur Mustard Gas)
    • Inhalational Exposure
  • Tear Gas Inhalation (see Tear Gas)
    • Inhalational Exposure to Tear Gas Used by Police/Military for Crowd Control
  • White Phosphorus Inhalation (see White Phosphorus)
    • Inhalational Exposure to Firework/Incendiary Explosion
  • Zinc Chloride Gas Inhalation (see Zinc Chloride Gas)
    • Inhalational Exposure to Smoke Bomb

Other

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 is 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 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 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 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 (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 ARDS

  • Timing: within 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 due to cardiac origin or fluid overload
    • Objective Assessment (Echocardiogram, Swan, etc): required in the absence of risk factors for ARDS
  • Oxygenation: 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

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

Aspirin (see Acetylsalicylic Acid

  • LIPS-A (Phase 2b) Trial of Aspirin to Prevent ARDS in Patients Presenting to the ED Who are At-Risk for 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 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 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 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

General

Epidemiology

Etiology

Infection

Hematologic Disorder

Other

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