Acute Respiratory Distress Syndrome (ARDS)

Overview

Definition

Acute respiratory distress syndrome is a clinical syndrome (not a pathological diagnosis) characterized by a sudden onset of hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome and bilateral pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema without cardiac failure Cardiac failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Heart Failure.

The underlying mechanism of ARDS is diffuse alveolar damage (DAD):

• Also the histological correlate
• Indicates damage to the endothelial and alveolar epithelial cells
• Associated with inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and the development of hyaline membranes lining the inner alveolar walls

Acute respiratory distress syndrome is clinically diagnosed using the Berlin diagnostic criteria.

Epidemiology

• ARDS is the most common cause of non-cardiogenic pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema. 
• Approximately 140,000 to 160,000 cases of ARDS are reported in the United States each year.
  • Decline in numbers from earlier estimates (~190,000), likely due to improvements in sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock management, mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing strategies, and broader preventive care
  • COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). temporarily increased cases, but post-pandemic data stabilized the rates again.
• ≥ 20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are mechanically ventilated meet the criteria for ARDS
• Mortality Mortality All deaths reported in a given population. Measures of Health Status rate: 27%–43%

Etiology

Acute respiratory distress syndrome results from clinical disorders that affect the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy either directly or indirectly.

Direct lung injury:

• Bacterial pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia (e.g., Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae)
• Viral pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia (e.g., influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza, SARS-CoV-2 [ COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). ])
• Aspiration of gastric contents
• Pulmonary contusion Pulmonary Contusion Flail Chest
• Near-drowning incidents
• Toxic inhalation injury
• Lung transplant

Indirect lung injury:

• Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock (most common cause)
• Severe trauma:
  • Multiple bone fractures Bone fractures Breaks in bones. Bones: Remodeling and Healing
  • Flail chest Flail chest Flail chest is a life-threatening traumatic injury that occurs when 3 or more contiguous ribs are fractured in 2 or more different locations. Patients present with chest pain, tachypnea, hypoxia, and paradoxical chest wall movement. Flail Chest
  • Head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma
  • Burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns
• Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
• Multiple transfusions ( transfusion-related acute lung injury Transfusion-related acute lung injury A rare but serious transfusion-related reaction in which fluid builds up in the lungs unrelated to excessively high infusion rate and/or volume (transfusion-associated circulatory overload). Signs of transfusion-related acute lung injury include pulmonary secretions; hypotension; fever; dyspnea; tachypnea; tachycardia; and cyanosis. Transfusion Reactions (TRALI))
• Drug overdose
• Postcardiopulmonary bypass
• Hematopoietic stem cell transplant
• Fat embolism Fat embolism Blocking of a blood vessel by fat deposits in the circulation. It is often seen after fractures of large bones or after administration of corticosteroids. Nonthrombotic Embolism and amniotic fluid embolism Amniotic Fluid Embolism Blocking of maternal circulation by amniotic fluid that is forced into uterine veins by strong uterine contraction near the end of pregnancy. It is characterized by the sudden onset of severe respiratory distress and hypotension that can lead to maternal death. Complications during Childbirth

Risk of ARDS:

• Increases in a patient with multiple predisposing clinical conditions
• 25% in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe trauma, which increases to 56% if there is associated sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
• Other risk factors:
  • Alcohol-abuse disorder
  • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity

Pathophysiology

Acute respiratory distress syndrome begins with an initial injury to the pneumocytes and pulmonary endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology, which starts a chain reaction of increasing inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and pulmonary damage that can have an uneven/patchy distribution.

Exudative phase Exudative Phase Hypertensive Retinopathy

• Starts within 6–72 hours after an eliciting risk factor
• Progresses rapidly
• Lasts about 7 days
• Destruction of alveolar epithelial cells/ type 1 Type 1 Spinal Muscular Atrophy pneumocytes (type 2 pneumocytes are more resistant to damage, but both are damaged) and capillary endothelial cells, producing numerous effects:
  • Damage to the alveolar capillary membrane → endothelial cell membranes become leaky → protein-rich fluid exits into the interstitial and alveolar spaces
  • Release of pro-inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response → leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology are recruited to the interstitia and alveoli
  • Inactivation of the surfactant (which helps keep alveoli open)
  • Fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis precipitates, plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, necrotic debris, and dysfunctional surfactant form the “hyaline membranes” that line the inner alveolar walls (glassy/waxy appearance).
  • Loss of surfactant also results in a large increase in the surface tension of alveoli, leading to:
    • Alveolar instability
    • Atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis
• Effects on lung function:
  • “Stiff lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy” → reduced lung compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology
  • Reduced diffusing capacity, shortness of breath Shortness of breath Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, and hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome
  • Intrapulmonary shunting results from alveolar microvascular occlusion.
  • Reduction of pulmonary arterial blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure to the ventilated portions of the lung
  • Pulmonary dead space Dead space That part of the respiratory tract or the air within the respiratory tract that does not exchange oxygen and carbon dioxide with pulmonary capillary blood. Ventilation: Mechanics of Breathing is increased, ultimately leading to hypercapnia Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. Neonatal Respiratory Distress Syndrome in addition to hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome.

Proliferative phase Proliferative phase Menstrual Cycle

• Usually lasts 7–21 days
• Many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship recover within 3–4 weeks after the initial lung injury.
• Beginning stage of lung repair and resolution of pathophysiological changes (reparative process)
• Alveolar epithelial cells begin proliferating along the alveolar basement membranes.
• New pulmonary surfactant is produced.

Fibrotic phase

• Inflammatory exudates are converted into variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables quantities of alveolar duct and interstitial fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans.
• Intimal fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of pulmonary vessels leads to progressive vascular occlusion and pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension.
• Emphysema-like changes develop in some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, consequently requiring supplemental oxygen Supplemental Oxygen Respiratory Failure.

Clinical Presentation

Vitals

• Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
• Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever may/may not be present
• Hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome despite supplemental oxygen Supplemental Oxygen Respiratory Failure

Physical exam

• Diffuse rales Rales Respiratory Syncytial Virus/crackles
• Labored breathing
• Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
• Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination

Exam findings not consistent with ARDS

• Cardiac exam:
  • S3 S3 Heart Sounds or S4 gallop S4 gallop Heart Sounds
  • New or changed murmur
• Jugular venous distension Jugular Venous Distension Cardiovascular Examination ( JVD JVD Cardiovascular Examination)
• Lower extremity pitting edema Pitting edema Edema caused by excess fluid without excess colloid. Leaves “pits” due to fluid displacement when pressure is applied to the area Edema

Diagnosis

Berlin diagnostic criteria of ARDS

• Acute onset (within 1 week)
• Diffuse bilateral infiltrates on chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests
• No evidence of left heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) or fluid overload
• Partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of O₂/fraction of inspired O₂ (PaO₂/FiO₂) < 300 mm Hg:
  • Mild ARDS: 201–300 mm Hg
  • Moderate ARDS: 101–200 mm Hg
  • Severe ARDS: ≤ 100 mm Hg
• Diagnosis requires the presence of a known clinical risk factor (e.g., pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, trauma, sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock), OR hydrostatic edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema is ruled out via imaging (e.g. echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA)) when a risk factor is absent.
• 2024 clinical definition of ARDS update:
  • Includes both intubated and nonintubated patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (such as those requiring high-flow nasal oxygen)
  • PaO2/ FiO2 FiO2 percentage of oxygen delivered directly to the patient Invasive Mechanical Ventilation ratio is still used but SpO2/ FiO2 FiO2 percentage of oxygen delivered directly to the patient Invasive Mechanical Ventilation ratio is a valid alternative to identify hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome (SpO2/ FiO2 FiO2 percentage of oxygen delivered directly to the patient Invasive Mechanical Ventilation ≤ 315 mmHg if the SpO2 is ≤ 97% while on high-flow oxygen or noninvasive ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing).
  • Includes ultrasound as an imaging modality especially in resource-limited settings
• Significance of 2024 update:
  • Previous Berlin Definition limited ARDS diagnosis to intubated patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with PEEP PEEP Pressure remaining in the distal airways of the patient at the end of expiration Invasive Mechanical Ventilation ≥ 5 cm H₂O.
  • Additions made broaden the criteria and enhance early detection.

Laboratory tests

• BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation levels < 100 pg/mL favors ARDS (higher levels neither confirm heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) nor exclude ARDS).
• Arterial blood gas Arterial blood gas Respiratory Alkalosis (ABG):
  • Hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome
  • Acute respiratory alkalosis Acute respiratory alkalosis Respiratory Alkalosis may be present initially.
  • Respiratory acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis can occur with severe ARDS.
• Alveolar-arterial (A-a) gradient widening:
  • A-a gradient measures the difference between alveolar oxygen concentration and arterial oxygen.
  • Calculated using the following factors: age, atmospheric pressure Atmospheric pressure The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. Ventilation: Mechanics of Breathing, FiO₂, arterial O₂ and CO₂ in blood gas

Imaging

• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • ARDS: bilateral pulmonary infiltrates
  • Findings more consistent with cardiogenic pulmonary edema Cardiogenic Pulmonary Edema Pulmonary Edema:
    • Pulmonary venous congestion
    • Cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
  • Finding more consistent with pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia: consolidation Consolidation Pulmonary Function Tests
• CT scan:
  • Not necessary, but gives more pulmonary details
  • ARDS: widespread patchy airspace opacities that are more apparent in the dependent lung zones
  • ARDS excluded by the following findings:
    • Pericardial effusion Pericardial effusion Fluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
    • Cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
    • Cavitation Cavitation Imaging of the Lungs and Pleura
• Lung ultrasound:
  • B lines with smooth pleural morphology are suggestive of cardiogenic pulmonary edema Cardiogenic Pulmonary Edema Pulmonary Edema.
  • B lines with uneven pleural line may indicate ARDS.
• Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA):
  • Helps distinguish cardiac dysfunction if the clinical presentation is unclear
  • Findings more consistent with a cardiogenic cause:
    • Reduced left ventricular ejection fraction Ejection fraction Cardiac Cycle 
    • Elevated right-side filling pressure 
    • Severe aortic or mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy dysfunction

Additional tests

• Certain tests are conducted to evaluate the suspected etiology and/or rule out other conditions:
  • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) and cardiac enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes in acute coronary syndrome
  • Lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion in pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
  • Microbiological studies (e.g., cultures) in sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock/infectious etiology
• Non-pulmonary imaging in cases of trauma ( brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy imaging) or abdominal etiology, such as peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury or pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis (abdominal CT)
• Bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia:
  • If etiology is unclear 
  • Specimens can be obtained for cytological and biochemical evaluation.
• Right heart catheterization:
  • Not performed routinely 
  • Helps in determining fluid status
  • Pulmonary-artery capillary wedge pressure:
    • Normal left ventricular (LV) function implies a non-cardiogenic cause.
    • High pulmonary-artery capillary wedge pressure (≥ 18 mm Hg) implies a cardiogenic cause.
• Lung biopsy Lung Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis:
  • Invasive and rarely needed
  • Performed if it will guide therapeutic management

Management

Treatment

Almost all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are managed in the ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus

• Correct the underlying causes:
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
  • Trauma
  • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
• Fluid management is difficult:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock require a large fluid volume to maintain their BP.
  • Fluid restriction helps reduce left atrial filling pressure and improves oxygenation.
  • For balance, diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication can facilitate fluid restriction/removal
• Supplemental oxygen Supplemental Oxygen Respiratory Failure:
  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship require a high FiO_2.
  • Delivered via high-flow nasal cannula Nasal Cannula Respiratory Failure, face mask, or by intubation Intubation Peritonsillar Abscess (mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing)
• Mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing:
  • Almost all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will require intubation Intubation Peritonsillar Abscess and mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing. 
  • Low tidal volumes (4–8 mL/kg of predicted body weight)
  • Plateau Plateau Cardiac Physiology pressure < 30 cm H₂O
  • Positive end-expiratory pressure Positive end-expiratory pressure Pressure remaining in the distal airways of the patient at the end of expiration Invasive Mechanical Ventilation ( PEEP PEEP Pressure remaining in the distal airways of the patient at the end of expiration Invasive Mechanical Ventilation):
    • 5–20 cm H₂O (start at minimum PEEP PEEP Pressure remaining in the distal airways of the patient at the end of expiration Invasive Mechanical Ventilation for given FiO₂)
    • Opens the collapsed alveoli
    • Minimizes FiO₂ and maximizes PaO₂
  • Prone position has shown benefit.
• ECMO:
  • Last resort or rescue therapy
  • An option if respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure is potentially reversible
  • Most common complication: bleeding
• Pharmacological therapies:
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
    • Given if the patient is with non-ARDS indications
    • Early (within 14 days) in the course of persistent and moderate-to-severe ARDS
    • COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). ARDS 
  • Neuromuscular blockade Neuromuscular Blockade The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction (neural conduction) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. Aminoglycosides to promote ventilator synchrony during paralysis:
    • Preferred use early in the course of the disease ( first 48 hours) and ideally, should not be used for > 48 hours
    • Reevaluate use daily.
  • Pulmonary vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger Disease) (e.g., inhaled nitrous oxide Nitrous oxide Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. Inhaled Anesthetics) may be harmful and worsen renal function even if oxygenation is temporarily improved.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

Acute respiratory distress syndrome is a serious condition that is usually associated with high mortality Mortality All deaths reported in a given population. Measures of Health Status and morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status.

Several risk factors have been identified that can estimate the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas in a patient with ARDS:

• Advanced age (higher mortality Mortality All deaths reported in a given population. Measures of Health Status rate)
• Preexisting organ dysfunction from chronic diseases:
  • Chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
  • CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
  • Immunosuppression
• Direct lung injuries result in twice the number of mortalities compared to indirect causes of lung injury.

The majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship recover most of their lung function, but will take months.

Long-term complications:

• Many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will develop lung fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, whereas some may require long-term mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing and oxygen supply. 
• Others: cognitive dysfunction (in 30%–55%), psychiatric illness (e.g., depression), reduced exercise endurance with muscle weakness

Differential Diagnosis

• Cardiogenic pulmonary edema Cardiogenic Pulmonary Edema Pulmonary Edema: a condition caused by excess fluid in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, resulting from cardiac failure Cardiac failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Heart Failure. Cardiogenic etiology is suggested by an S3 S3 Heart Sounds or S4 gallop S4 gallop Heart Sounds, elevated jugular venous pressure Jugular Venous Pressure Portal Hypertension, and lower extremity edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema with typical chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests findings (pulmonary venous congestion, cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly, pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion, response to diuresis). Management of cardiogenic pulmonary edema Cardiogenic Pulmonary Edema Pulmonary Edema involves diuresis.
• Diffuse alveolar hemorrhage: a condition resulting from injury to the arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology, venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology, or capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology. Diffuse alveolar hemorrhage is associated with multiple diseases (e.g., Goodpasture syndrome Goodpasture Syndrome Goodpasture syndrome, also known as anti-glomerular basement membrane (GBM) disease, is an autoimmune disease characterized by circulating antibodies directed against glomerular and alveolar basement membranes. Affected individuals present with symptoms of rapidly progressive glomerulonephritis and alveolar hemorrhage. Goodpasture Syndrome). Hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis is usually present. Diffuse alveolar hemorrhage may present with sudden-onset respiratory distress, like ARDS. Diagnosis is by chest CT and bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia with bronchoalveolar lavage Bronchoalveolar lavage Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. Pulmonary Fibrosis (BAL), which shows fresh RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology and hemosiderin-laden macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation.
• Acute interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7 (Hamman-Rich syndrome): a fulminant form of diffuse lung injury that mimics ARDS. The onset of acute interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7 is acute, and the symptoms include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, cough, and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Acute interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7 may be a subset of idiopathic Idiopathic Dermatomyositis ARDS but without a known risk factor. Diagnosis is by lung biopsy Lung Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis, which shows diffuse damage to the alveoli.
• Acute exacerbation of idiopathic Idiopathic Dermatomyositis pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans: a condition similar to ARDS that presents with diffuse alveolar damage and acute interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7, but with a worse prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas. Acute exacerbation of idiopathic Idiopathic Dermatomyositis pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans can occur in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with previously undiagnosed interstitial lung disease. Diagnosis is made by comparing previous radiographic and CT images, and by lung biopsy Lung Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis.