Hypoxemia


Definitions

Respiratory Failure (see Respiratory Failure)

  • Definition
    • Respiratory Failure is Defined as the Occurrence of One or Both of the Following
      • Decreased pO2, as Predicted for the Patient’s Age (Hypoxemia)
      • Increased pCO2 (Hypercapnia) in the Setting of a Normal Serum Bicarbonate
        • A Normal Serum Bicarbonate is Specified Here Since a Primary Metabolic Alkalosis (with Increased Serum Bicarbonate) Would Be Expected to Result in a Normal Compensatory Increase in pCO2: this normal compensatory mechanism functions to maintain a normal serum pH and would not be considered “respiratory failure”

Hypoxemia (see Hypoxemia)

  • Definition
    • Hypoxemia is Defined a Decrease in Hemoglobin Oxygen Saturation (as Assessed by Pulse Oximetry: SaO2 or SpO2) or Decrease in Arterial pO2 (as Assessed by Arterial Blood Gas)
  • Note that a Patient May Be Hypoxemic, But Not Be Hypoxic
    • Example
      • A Young Hypoxemic Patient Can Significantly Increase Their Cardiac Output to Maintain Tissue Oxygen Delivery

Hypoxia (see Hypoxemia)

  • Definition
    • Hypoxia is Defined as a State of Impaired Tissue Oxygenation
  • Note that a Patient May Be Hypoxic, But Not Be Hypoxemic
    • Example
      • In Cyanide Intoxication, SaO2 Can Be Normal, But Tissues May Be Hypoxic (see Cyanide)

Anoxia

  • Definition
    • Anoxia is Defined as Complete Tissue Deprivation of Oxygen Supply

Hypercapnia (see Hypercapnia)

  • Definition
    • Hypercapnia is Defined as Increase in Arterial pCO2 (i.e. Increased Arterial Blood Partial Pressure of Carbon Dioxide) to >40 mm Hg

Acidemia

  • Definition
    • Acidemia is Defined as Decrease in Arterial pH < 7.40 (Due to Either Metabolic or Respiratory Acidosis)
  • Note that a Patient Can Be Acidemic without having a Respiratory Acidosis
    • Example
      • Metabolic Acidosis Can Produce Acidemia without the Presence of a Respiratory Acidosis

Alkalemia

  • Definition Alkalemia is Defined an Increase in Arterial pH to >7.40 (Due to Either Metabolic or Respiratory Alkalosis)

Acidosis

  • Definition
    • Acidosis is Defined as the Presence of an Acid-Producing Acid-Base Disturbance (with or without Concomitant Acidemia)
  • Clinical Scenarios in Which an Acidosis is Present, But in Which the pH is Not Acidemic
    • Presence of a Metabolic Acidosis May Not Necessarily Result in an Acidemic pH (pH <7.4), Since Respiratory Compensation (Hyperventilation) Occurs, Resulting in an Increase in the Serum pH
    • Presence of a (Chronic) Respiratory Acidosis May Not Necessarily Result in an Acidemic pH (pH <7.4), Since Metabolic Compensation (Renal Bicarbonate Retention) Generally Occurs Over a Period of Days, Resulting in an Increase in the Serum pH

Alkalosis

  • Definition
    • Alkalosis is Defined as the Presence of an Alkali-Producing Acid-Base Disturbance (with or without Concomitant Alkalemia)
  • Clinical Scenarios in Which an Alkalosis is Present, But in Which the pH is Not Alkalemic
    • Presence of a Metabolic Alkalosis May Not Necessarily Result in an Alkelemic pH (pH >7.4), Since Respiratory Compensation (Hypoventilation) Occurs Rapidly, Resulting in a Decrease in the Serum pH
    • Presence of a (Chronic) Respiratory Alkalosis May Not Necessarily Result in an Alkalemic pH (pH >7.4), Since Metabolic Compensation (Renal Bicarbonate Wasting) Generally Occurs Over a Period of Days, Resulting in a Decrease in the Serum pH

Respiratory Acidosis (see Respiratory Acidosis)

  • Definition
    • Respiratory Acidosis is Defined as a Disorder Which Results in Increase in Arterial pCO2 with an Associated Decrease in Arterial pH
  • Note that a Patient Can Have a Respiratory Acidosis without Being Significantly Acidemic
    • Example
      • Via Normal Compensatory Mechanisms, Chronic Respiratory Acidosis Induces Metabolic (Predominantly Renal) Compensation (with a Increase in Serum Bicarbonate Over Time), Culminating in Minimal Acidemia

Terms

  • PaO2: arterial pO2 (arterial oxygen tension)
    • Usually Referred to Simply as pO2
  • PAO2: alveolar PO2 (alveolar oxygen tension)
  • SpO2: pulse oximetry, as determined by peripheral pulse oximeter (see Pulse Oximetry)
  • SaO2: pulse oximetry, as determined by arterial blood gas co-oximeter (see Arterial Blood Gas)

Physiology of Gas Exchange and Oxygen Delivery

Oxygen Delivery and Consumption

General Comments

Arterial Oxygen Content Equation

Oxygen Delivery Equation

Oxygen Consumption Equation

Fick Equation

Oxygen Extraction Ratio

Oxygen Delivery/Oxygen Consumption Ratio (DO2/VO2 Ratio)

Oxygen Dissociation Curve

Sigmoidal Relationship Between Oxygen Saturation (SaO2) and pO2

Factors Which Shift Oxygen Dissociation Curve to the Left

Factors Which Shift Oxygen Dissociation Curve to the Right

Ventilation/Perfusion (V/Q) Relationships

Alveolar Gas Equation

Inverse Relationship Between Arterial pCO2 and pO2

Factors Accounting for the Presence of the Alveolar-Arterial (A-a) O2 Gradient (i.e. Why the A-a Gradient is Not Zero)

Etiology of Hypoxemia

Pseudohypoxemia

Processing Artifact

  • Mechanism
    • Arterial Blood Gas (ABG) Left at Room Temperature (Particularly with Severe Leukocytosis), Resulting in In Vitro Oxygen Consumption by White Blood Cells in the Sample
  • Diagnosis
  • Clinical
    • No Clinical Manifestations

Normal A-a Gradient Hypoxemia

Acute/Chronic Hypoventilation

  • Mechanism
    • Per the Simplified Alveolar Gas Equation (Above), Increased Arterial pCO2 (Hypercapnia) Results in an Inverse Decrease in Arterial pO2 (Hypoxemia)
  • Etiology

Decreased Inspired PO2 (PiO2)

  • Mechanism
    • Decreased PiO2 Results in Decreased Oxygen Delivery to the Alveoli (with Decreased Alveolar pO2)
    • PiO2 = FIO2 x (Patm – PH20)
      • Patm: atmospheric pressure
      • PH20: partial pressure of water (equal to 47 mm Hg at 37 degrees C)
  • Etiology
    • Fire in Enclosed Space
    • High Altitude (with Decreased Barometric Pressure)
      • Sea Level (0 ft): FIO2 = 21%, PIO2= 150, pATM = 760, pH2O = 47 (at 37 degree C)
      • Denver (5280 ft): FIO2 = 21%, PIO2= 125, pATM = 640, pH2O = 47 (at 37 degree C)
    • Inadvertent Administration of Low FIO2 During Mechanical Ventilation: due to circuit leak, clinician error, etc

Low Mixed Venous Oxygen Saturation

  • Mechanism
    • Blood Returns to the Right Side of the Heart in a Severely Deoxygenated State and Cardiopulmonary System is Incapable of Re-Oxygenating the Blood
    • Low Mixed Venous Oxygen Saturation Usually Only Results in Arterial Hypoxemia in the Setting of Coexistent Anemia, V/Q Mismatch, or Right-to-Left Shunt: these result in the impaired ability to re-oxygenate the blood
  • Etiology
    • Decreased Cardiac Output State/Cardiogenic Shock (see Cardiogenic Shock)
    • Increased Tissue Oxygen Extraction
      • Anxiety (see Anxiety)
      • Fever (see Fever)
      • Increased Work of Breathing

Elevated A-a Gradient Hypoxemia

Intrapulmonary Right-to-Left Shunt (see Intracardiac and Extracardiac Shunt)

  • Mechanism
    • Shunting of Unoxygenated Blood Through Lung, without Undergoing Oxygenation
    • Note that a Large Intrapulmonary Shunt Can Produce a Region of Near Zero V/Q Ratio
      • In This Respect, Intrapulmonary Shunt Really Represents the Most Extreme Form of V/Q Mismatch
    • Shunt is Classically Characterized by Poor Response of pO2 (or SaO2) to the Administration of Supplemental Oxygen
  • Quantification of Shunt Fraction: perform on 100% FIO2 for at least 20 min (to allow nitrogen washout)
    • Qs/Qt = (CcO2-CaO2) / (CcO2-CvO2)
      • PIO2 = FIO2 x pATM -> at sea level and on 100% FIO2, PIO2 = 760
      • PAO2 = PIO2 – (PCO2 x 1.25) -> at sea level and on 100% FIO2, PAO2 = 760 – (PCO2 x 1.25)
      • CcO2: end-capillary oxygen content = Hb x 1.39 + (0.003 x PAO2)
      • CaO2: arterial oxygen content = Hb x SaO2 x 1.39 + (0.003 x PaO2)
        • Use values from ABG
      • CvO2: mixed venous oxygen content = Hb x SvO2 x 1.39 + (0.003 x PvO2)
        • Use values from Swan-Ganz Catheter
    • Normal Shunt Fraction: <5%
      • This Accounts for the Normal Physiologic Degree of Anatomical Shunt Which Exists, Due to the Bronchial and Thebesian Circulations
  • Etiology
    • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)
      • Physiology: due to physiologic intrapulmonary shunt
    • Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism)
      • Epidemiology: case report of patient with platypnea-orthodeoxia due to bilateral lower lobe pulmonary emboli (South Med J, 2011) [MEDLINE]
      • Physiology: while intrapulmonary shunt may be a contributor to hypoxemia in the setting of acute pulmonary embolism (typically with coexistent atelectasis), the major mechanism of hypoxemia in acute pulmonary embolism is V/Q mismatch
    • Atelectasis (see Atelectasis)
      • Physiology: due to physiologic intrapulmonary shunt
    • Hepatopulmonary Syndrome (see Hepatopulmonary Syndrome)
      • Physiology: due to anatomic intrapulmonary shunt (which often increases with the patient in an upright position, resulting in orthodeoxia/platypnea)
    • Intralobar Pulmonary Sequestration (see Pulmonary Sequestration)
      • Epidemiology: one reported case of this resulting in an anatomic intrapulmonary shunt
    • Pneumonia
      • Physiology: due to physiologic intrapulmonary shunt
    • Pulmonary Arteriovenous Malformation (AVM) (see Pulmonary Arteriovenous Malformation (AVM)
      • Physiology: due to anatomic intrapulmonary shunt

Intracardiac Right-to-Left Shunt (see Intracardiac and Extracardiac Shunt)

  • Mechanism
    • Shunting of Unoxygenated Blood from the Right to the Left Side of the Heart, Bypassing the Pulmonary Vascular Bed
  • Etiology
    • Acute Pulmonary Embolism (Acute PE) with Right to Left Shunt (see Acute Pulmonary Embolism)
      • Physiology: acutely increased pulmonary artery pressure may result in new or exacerbated right to left shunt through a pre-existing PFO, etc
    • Atrial Septal Defect with Right to Left Shunt (see Atrial Septal Defect)
    • Patent Ductus Arteriosus with Right to Left Shunt (see Patent Ductus Arteriosus)
    • Patent Foramen Ovale with Right to Left Shunt (see Patent Foramen Ovale)
    • Tetralogy of Fallot with Right to Left Shunt (see Tetralogy of Fallot)
      • Physiology: ventricular septal defect + pulmonary artery stenosis
    • Ventricular Septal Defect (VSD) with Right to Left Shunt (see Ventricular Septal Defect)

Worsened V/Q Mismatch (Above Levels Observed as Part of Normal Physiology)

Diffusion Limitation

  • Mechanism
    • Limitation of Oxygen Exchange Across the Pulmonary Capillary Blood-Gas Barrier
      • Thickening of the Alveolar-Capillary Membrane (Associated with Interstitial Fibrosis, Cryptogenic Organizing Pneumonia, Acute Respiratory Distress Syndrome, Asbestos Exposure, etc) Results in Inadequate Red Blood Cell Transit Time in the Pulmonary Circulation, Not Allowing Adequate Equilibration of pO2 Between the Alveolar Gas and Pulmonary Capillary Blood
    • Note that Diffusion Limitation is Absent in Normal Subjects at Rest
  • Etiology
    • Heavy Exercise (Due to Increased Cardiac Output with Decreased Time Available for Oxygen Diffusion)
      • Resulting in Transient Pulmonary Interstitial Fluid Accumulation
      • Effect of Hypoxia
        • Humans Will Frequently Demonstrate Diffusion Limitation in Setting of Normoxia, But Almost All Will Demonstrate Diffusion Limitation in Setting of Hypoxia
      • Race Horses Develop Diffusion Limitation During Severe Exercise (Explaining the Common Practice of Administering Furosemide Prior to Races, with the Goal of Decreasing the Accumulation of High Cardiac Output-Associated Interstitial Pulmonary Edema)
    • Severe Interstitial Lung Disease with Exercise (see Interstitial Lung Disease)
      • Physiology: due to increased cardiac output with decreased time available for oxygen diffusion combined with thickening of the alveolar capillary membrane

Diagnosis

Pulse Oximetry (see Pulse Oximetry)

  • Hypoxemia

Arterial Blood Gas (ABG) (see Arterial Blood Gas)

  • Hypoxemia

Evaluation of Hypoxemia

Method #1: Using Calculation of the A-a Gradient

  • General Comments: this is the preferred method
  • Step 1: Calculate Alveolar PO2 Using the Simplified Alveolar Gas Equation
    • On Room Air at Sea Level: Alveolar PO2 (PAO2) = 150 – PCO2/0.8
      • Note: Arterial PaCO2 is Assumed to Be Nearly the Same as Alveolar PACO2 in this Equation
      • Respiratory Exchange Ratio (“R”) is Assumed to Be 0.8
        • Diet of Carbohydrate Alone -> R = 1.0
        • Diet of Fat Alone -> R = 0.7
        • Diet of Mixed Carbohydrates + Fats -> R = 0.8
  • Step 2: Use this Alveolar PO2 to then Calculate the A-a Gradient
    • A-a Gradient = Alveolar PO2 (PAO2) – Arterial PO2 (PaO2)
  • Step 3: Compare A-a Gradient to Age-Predicted A-a Gradient (multiple “rule of thumb” calculations are available, as follows, since there are no accepted reference values available for the age-corrected A-a gradient)
    • Predicted A-a Gradient = 0.43 x Age
    • Predicted A-a Gradient = 2.5 + (0.21 x Age)
    • Predicted A-a Gradient = (Age + 4)/4

Method #2: Using Age-Predicted PO2 (Determined from Experimental Data)

  • Compare Room Air PO2 to Predicted PO2 (Acta Physiol Scand, 1966) [MEDLINE]
    • Predicted Room Air PO2 (in a Normal Seated Adult Patient) = 104.2 – (0.27 x Age)

Clinical Manifestations

Clinical Manifestations of Hypoxemia

  • General Comments
    • Hypoxemia May Be Asymptomatic, Since Compensatory Mechanisms (Such as an Increase in Cardiac Output or an Increase in Hemoglobin) May Act to Maintain Tissue Oxygen Delivery and Avoid Hypoxic End-Organ Dysfunction
  • Cardiovascular Manifestations
    • Angina (see Coronary Artery Disease)
    • Arrhythmia
      • Atrial Fibrillation (AF) (see Atrial Fibrillation)
      • Atrial Flutter (see Atrial Flutter)
      • Ventricular Tachycardia (VT) (see Ventricular Tachycardia)
        • Sleep-Disordered Breathing is Associated with an Increased Risk of Nocturnal Ventricular Arrhythmias (Am J Respir Crit Care Med, 2006) [MEDLINE]
        • In Patients with Heart Failure and Sleep Apnea, Treatment with CPAP Eliminates Sleep-Disordered Breathing and Decreases Ventricular Irritability (Circulation, 2000) [MEDLINE]
      • Ventricular Fibrillation (AF) (see Ventricular Fibrillation)
    • Atrioventricular Heart Block
    • Congestive Heart Failure (CHF) (see Congestive Heart Failure)
    • Hypotension/Pulseless Electrical Activity (PEA) (see Hypotension and Pulseless Electrical Activity)
      • Due to Hypoxia-Induced Systemic Vasodilation (Which Attempts to Maintain Tissue Perfusion with Oxygen Delivery)
    • Prolonged QT Interval (see Torsade)
      • Hypoxemia Has Been Demonstrated to Prolong the QT Interval During Sleep in Patients with Coronary Artery Disease (CAD) (Chest, 1982) [MEDLINE]
      • Nocturnal Hypoxemia Has Been Demonstrated to Prolong the QT Interval in Patients with Chronic Obstructive Pulmonary Disease (COPD) (NEJM, 1982) [MEDLINE]
      • Acute Hypoxia Has Been Demonstrated to Prolong the QT Interval in Normal Subjects (Am J Cardiol, 2003) [MEDLINE]
      • Severe Obstructive Sleep Apnea Has Been Demonstrated to Prolong the QTc Interval in Patients with Congenital Long QT Syndrome (Independent of Age, Sex, BMI, Use of β-Blockers, and History of Syncope), Which is a Biomarker for Sudden Cardiac Death (Sleep, 2015) [MEDLINE] (see Obstructive Sleep Apnea)
        • Severity of Obstructive Sleep Apnea (as Represented by the Apnea-Hypoxia Index and Apnea Index During Sleep) is Directly Related to the Degree of QT Prolongation in This Population
        • The Obstructive Sleep Apnea-Related Increase in the QT May Be Mediated by Hypoxic Episodes (Typically Immediately Following the Apnea), Sympathetic Activation (During the Apnea), and/or Vagal Bradyarrhythmias (During the Apnea)
    • Sinus Tachycardia (see Sinus Tachycardia)
  • Neurologic Manifestations
  • Pulmonary Manifestations
  • Other Manifestations
    • Clubbing (see Clubbing): may occur with chronic hypoxemia
    • Cyanosis (see Cyanosis)
    • Polycythemia (see Polycythemia): may occur with chronic hypoxemia

Clinical Manifestations of Hypoxia

  • General Comments
    • Hypoxia is Always Symptomatic (Since it Reflects a State of Impaired Tissue Oxygenation) and is Typically Associated with Laboratory Manifestations of Lactic Acidosis
  • Cardiovascular Manifestations
    • Angina (see Coronary Artery Disease)
    • Arrhythmia
      • Atrial Fibrillation (AF) (see Atrial Fibrillation)
      • Atrial Flutter (see Atrial Flutter)
      • Ventricular Tachycardia (VT) (see Ventricular Tachycardia)
        • Sleep-Disordered Breathing is Associated with an Increased Risk of Nocturnal Ventricular Arrhythmias (Am J Respir Crit Care Med, 2006) [MEDLINE]
        • In Patients with Heart Failure and Sleep Apnea, Treatment with CPAP Eliminates Sleep-Disordered Breathing and Decreases Ventricular Irritability (Circulation, 2000) [MEDLINE]
      • Ventricular Fibrillation (AF) (see Ventricular Fibrillation)
    • Atrioventricular Heart Block
    • Congestive Heart Failure (CHF) (see Congestive Heart Failure)
    • Hypotension/Pulseless Electrical Activity (PAE) (see Hypotension and Pulseless Electrical Activity)
      • Due to Hypoxia-Induced Systemic Vasodilation (Which Attempts to Maintain Tissue Perfusion with Oxygen Delivery)
    • Prolonged QT Interval (see Torsade)
      • Hypoxemia Has Been Demonstrated to Prolong the QT Interval During Sleep in Patients with Coronary Artery Disease (CAD) (Chest, 1982) [MEDLINE]
      • Nocturnal Hypoxemia Has Been Demonstrated to Prolong the QT Interval in Patients with Chronic Obstructive Pulmonary Disease (COPD) (NEJM, 1982) [MEDLINE]
      • Severe Obstructive Sleep Apnea Has Been Demonstrated to Prolong the QTc Interval in Patients with Congenital Long QT Syndrome (Independent of Age, Sex, BMI, Use of β-Blockers, and History of Syncope), Which is a Biomarker for Sudden Cardiac Death (Sleep, 2015) [MEDLINE] (see Obstructive Sleep Apnea)
        • Severity of Obstructive Sleep Apnea (as Represented by the Apnea-Hypoxia Index and Apnea Index During Sleep) is Directly Related to the Degree of QT Prolongation in This Population
        • The Obstructive Sleep Apnea-Related Increase in the QT May Be Mediated by Hypoxic Episodes (Typically Immediately Following the Apnea), Sympathetic Activation (During the Apnea), and/or Vagal Bradyarrhythmias (During the Apnea)
      • Acute Hypoxia Has Been Demonstrated to Prolong the QT Interval in Normal Subjects (Am J Cardiol, 2003) [MEDLINE]
    • Sinus Tachycardia (see Sinus Tachycardia)
  • Neurologic Manifestations
  • Pulmonary Manifestations
  • Other Manifestations
    • Clubbing (see Clubbing): may occur with chronic hypoxemia
    • Cyanosis (see Cyanosis)
    • Polycythemia (see Polycythemia): may occur with chronic hypoxemia

Treatment of Hypoxemia

Supplemental Oxygen (see Oxygen)

  • See Oxygen

Noninvasive Positive-Pressure Ventilation (NIPPV) (see Noninvasive Positive-Pressure Ventilation)

  • See Noninvasive Positive-Pressure Ventilation

Invasive Mechanical Ventilation (see Invasive Mechanical Ventilation-General)

  • See Invasive Mechanical Ventilation-General

References

Pseudohypoxemia

General

Clinical Manifestations

Cardiovascular Manifestations

Treatment

General

High-Flow Nasal Cannula (see Oxygen)