Hypoxemia

Definitions

  • Respiratory Failure: defined as the occurrence of one or both 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: decreased hemoglobin saturation (as assessed by pulse oximetry: SaO2 or SpO2) or decreased arterial pO2 (as assessed by arterial blood gas)
    • In Specific Clinical Circumstances, a Patient May Be Hypoxemic, But Not Be Hypoxic
      • Example: a young hypoxemic patient can significantly increase cardiac output to maintain tissue oxygen delivery
  • Hypoxia: state of impaired tissue oxygenation
    • In Specific Clinical Circumstances, 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: compelete tissue deprivation of oxygen supply
  • Hypercapnia (see Hypercapnia): increased arterial pCO2
  • Acidemia: acidic serum pH (due to either metabolic or respiratory acidosis)
  • Alkalemia: alkaline serum pH (due to either metabolic or respiratory alkalosis)
  • Acidosis: presence of 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: presence of 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
  • 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

  • Purpose of Cardiopulmonary Function: delivery of adequate oxygen to meet the demands of peripheral tissues
  • Determinants of Adequate Oxygenation at the Tissue Level
    • Amount of Oxygen Delivery
    • Rate of Tissue Oxygen Consumption

Arterial Oxygen Content Equation

  • Most of the Oxygen Which Diffuses from the Alveolus into the Blood is Bound by Hemoglobin
    • The Amount of Oxygen Dissolved in Plasma is Generally Small Relative to the Amount of Oxygen Bound to Hemoglobin, But Becomes Significant at Very High pO2 (as in a Hyperbaric Chamber) or in Severe Anemia
      • The Constant 0.0031 in the Arterial Oxygen Content Represents the Amount of Oxygen Dissolved in the Plasma
      • Because this Amount is Relatively Small, the pO2 Term is Commonly Omitted from the Arterial Oxygen Content Equation (as We Do Below)
    • Under Normal Conditions, Complete Oxygenation of the Blood Occurs in 0.25 sec (This is Approximately One Third of the Total Time that the Blood is in Contact with the Alveolar-Capillary Membrane)
      • This Rapid Diffusion Normally Allows the System to Sufficiently Compensate for Any Impairment in Oxygen Diffusion
    • In Dyshemoglobinemias (Such as Sickle Cell Disease, etc), the Arterial Oxygen Content is Calculated with the Same Equation as Below, Although the Saturations (and Therefore, the Oxygen Content) Will Be Different for a Specific pO2 (Pediatr Pulmonol, 1999) [MEDLINE]
  • Arterial Oxygen Content = [Hb x 13.4 x SaO2 x (0.0031 x pO2)]
    • Hemoglobin (Hb): in g/dL
    • Constant 13.4: accounts for the fact that 1.34 ml of O2 is carried per g of Hb (13.4 is used in the equation to correct the units from dL to L)
    • Arterial Oxygen Saturation (SaO2): as a decimal
    • pO2: in mm Hg
    • Normal Arterial Oxygen Content: approximately 200 mL O2/L (or 20 mL/dL)
      • This Equation Will Yield the Arterial Oxygen Content in mL O2/L, Which Allows the Arterial Oxygen Content Value to Be Plugged into the Oxygen Delivery Equation Below without Unit Conversion
  • Arterial Oxygen Content (Simplified Equation Omitting the pO2 Term) = [Hb x 13.4 x SaO2]

Oxygen Delivery Equation

  • Definition: rate at which oxygen is transported from the lungs to the tissues
    • Using a Train Analogy
      • Hb = number of boxcars
      • SaO2= how full the boxcars are
      • CO = how fast the train is going
  • Oxygen Delivery = [Arterial Oxygen Content] x CO
  • Oxygen Delivery = [Hb x 13.4 x SaO2] x CO
    • Hemoglobin (Hb): in g/dL
    • Arterial Oxygen Saturation (SaO2): as a decimal
    • Thermodilution-Measured Cardiac Output from Swan-Ganz Catheter (CO): in liters per min
    • Normal Oxygen Delivery (Using Cardiac Output = CO): approximately 1000 mL O2/min
      • Normal Oxygen Delivery (Using Cardiac Index = CI): approximately 550-650 mL/min/m2

Oxygen Consumption Equation

  • Oxygen Consumption = [Hb x 13.4 x (SaO2-SvO2)] x CO
    • Oxygen Consumption: in mL/min
    • Hemoglobin (Hb): in g/dL
    • Arterial Oxygen Saturation (SaO2): as a decimal
    • Venous Oxygen Saturation (SvO2): as a decimal
    • Thermodilution-Measured Cardiac Output from Swan-Ganz Catheter (CO): in liters per min
    • Normal Oxygen Consumption (Using Cardiac Output = CO): approximately 250 mL O2/min
      • Normal Oxygen Consumption (Using Cardiac Index = CI): approximately 110-130 mL/min/m2

Fick Equation

  • Fick Cardiac Output = Oxygen Consumption/(10 x Arteriovenous O2 Difference)
  • Fick Cardiac Output = Oxygen Consumption/(10 x Arterial Oxygen Content – Venous Oxygen Content)
  • Fick Cardiac Output = 250/[(Hb x 13.4 x SaO2) – (Hb x 13.4 x SvO2)]
    • Oxygen Consumption: this equation assumes the oxygen consumption is approximately 250 mL/min (or determined by respirometry or a nomogram)
    • Arteriovenous O2 Difference: in mL O2/dL
    • Hemoglobin (Hb): in g/dL
    • Arterial Oxygen Saturation (SaO2): as a decimal
    • Venous Oxygen Saturation (SaO2): as a decimal

Oxygen Extraction Ratio

  • Oxygen Extraction Ratio = (Arterial Oxygen Content – Venous Oxygen Content)/Arterial Oxygen Content
    • Normal Oxygen Extraction Ratio: approximately 0.25-0.30 (interpretation: only 25-30% of oxygen delivered is taken up by tissues)
  • Etiology of Increased Oxygen Extraction Ratio
    • Low Cardiac Output State
      • Cardiogenic Shock
      • Hypovolemic Shock
  • Etiology of Decreased Oxygen Extraction Ratio
    • Sepsis (see Sepsis): due to peripheral shunting and decreased tissue extraction
    • Hepatopulmonary Syndrome (see Hepatopulmonary Syndrome): due to high CO + low SVR state seen in cirrhosis
  • During States of Increased Metabolic Demand (Exercise, Pregnancy,etc), Oxygenation Consumption Increases Because More Oxygen is Required to Maintain Aerobic Cellular Metabolism
    • This is Achieved by Increasing Both Oxygen Delivery and Oxygen Extraction (Crit Care Clin, 1986) [MEDLINE] (Chest, 1990) [MEDLINE]
    • Oxygen Consumption is Disproportionately Impacted by the Increased Oxygen Extraction, with the Increased Oxygen Delivery Contributing a Small Amount (Chest, 1991) [MEDLINE]
    • Enhanced Oxygen Extraction Appears to Be Mediated at the Capillary Level (Crit Care Clin, 1986) [MEDLINE]
  • Dysregulation of Peripheral Oxygen Extraction Has Been Observed in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF), Leading to Impaired Functional Capacity (Circ Heart Fail, 2015) [MEDLINE]

Oxygen Dissociation Curve

Sigmoidal Relationship Between Oxygen Saturation (SaO2) and pO2

  • Sigmoidal Shape of Oxygen Dissociation Curve is a Result of Cooperative Binding of Oxygen Molecules to the 4 Binding Sites on Hemoglobin
    • Cooperative Binding: the characteristic of hemoglobin to demonstrate an enhanced ability to bind an oxygen molecule after a subunit has already bound an oxygen molecule
    • Consequences of the Sigmoidal Shape of the Oxygen Dissociation Curve
      • With pO2 >60 mmg Hg (Right Flat Portion of the Curve): a large increase in pO2 results in a small increase in SaO2
      • With pO2 <60 mm Hg (Left Steep Portion of the Curve): a small decrease in pO2 results in a large decrease in SaO2
    • Oxygen Loading: occurs in the lungs over the flat portion of curve
      • Due to the Flat Slope in this Region of the Curve, Even if the Alveolar pO2 Decreases Somewhat (Resulting in a Decrease in Arterial pO2), the Hemoglobin Oxygen Saturation Will Be Minimally Affected
    • Oxygen Unloading: occurs at the tissues over the steep portion of curve
      • Due to the Steep Slope of this Region of the Curve, Peripheral Tissues Extract a Relatively Large Amount of Oxygen (Resulting in Decreased Oxygen Saturation) with a Small Decrease in Arterial pO2

Factors Which Shift Oxygen Dissociation Curve to the Left

  • General Comments
    • Shift of the Oxygen-Hemoglobin Dissociation Curve to the Left Increases Hemoglobin Affinity for Oxygen and Decreases Oxygen Delivery to Tissues
  • Abnormal Hemoglobin
    • Carboxyhemoglobinemia (see Carboxyhemoglobinemia)
      • Hemoglobin Binds to Carbon Monoxide 200–250x More Avidly than Oxygen
      • Arterial pO2 Remains Normal, But Tissue Hypoxia Occurs
    • Fetal Hemoglobin
      • Fetal Hemoglobin (Which is Composed of Two Alpha and Two Gamma Chains) Has a Higher Affinity for Oxygen than Normal Hemoglobin A (Which is Composed of Two Alpha and Two Beta Chains)
    • Hemoglobin Variants with Decreased Hemoglobin Affinity for 2,3-BPG
      • Hb Rahere (lys82thr)
      • Hb Helsinki (lys82met)
      • Hb Providence (lys82asn—>asp)
    • Hemoglobin Variants with Increased Hemoglobin Affinity for Oxygen
      • Hemoglobin Chesapeake: oxygen affinity studies revealed a whole blood p50 of 19 mmHg (normal: 26 mmHg), normal Bohr effect (increase in oxygen affinity with elevations in pH), and normal 2,3-BPG binding
      • Hemoglobin Montefiore
      • Hemoglobin Heathrow (HBB phe103leu)
    • Methemoglobinemia (see Methemoglobinemia)
      • In Methemoglobinemia, the Iron Center Has Been Oxidized from the Normal +2 Oxidation State to the +3 State
      • Ferric Hemes of Methemoglobin are Unable to Bind Oxygen and Therefore, Result in a “Functional Anemia” with Decreased Oxygen Delivery to Tissues
        • While the Ferric Heme is Unable to Bind Oxygen, the Remaining Three Ferrous Hemes in the Hemoglobin Tetramer Have Increased Avidity for Oxygen, Resulting in Impaired Oxygen Unloading at the Tissues
      • Tissue Hypoxia Occurs
    • Hemoglobin H (Alpha Thalassemia Intermedia) (see Thalassemias)
  • Alkalemia (Increased Serum pH) (see Metabolic Alkalosis)
  • Decreased Red Blood Cell 2,3-Bisphosphoglycerate (2,3-BPG) (Previously Called 2,3-Diphosphoglycerate or 2,3-DPG)
    • The Polyanion, 2,3-BPG is Normally Present within Red Blood Cells and is Formed as a Product of the Glycolytic Pathway
    • 2,3-BPG Binds to Deoxyhemoglobin, Decreasing the Affinity of Hemoglobin for Oxygen
    • Decreased 2,3-BPG Results in a Leftward Shift of the Hemoglobin Dissociation Curve, Increased Hemoglobin Affinity for Oxygen, and Decreased Oxygen Delivery to Tissues
  • Decreased Red Blood Cell Mean Corpuscular Hemoglobin Concentration (MCHC)
  • Hypocapnia (see Hypocapnia)
  • Hypothermia (see Hypothermia)

Factors Which Shift Oxygen Dissociation Curve to the Right

  • General Comments
    • Shift of the Oxygen-Hemoglobin Dissociation Curve to the Right Decreases Hemoglobin Affinity for Oxygen and Increases Oxygen Delivery to the Tissues (Bohr Effect)
    • Rightward Shift of the Curve is Advantageous During Exercise, Respiratory Distress, or Prolonged Hypoxia
  • Abnormal Hemoglobin
    • Sulfhemoglobinemia (see Sulfhemoglobinemia)
      • Sulfhemoglobin Has Iron in the Ferric State, as Well as a Sulfur Atom Incorporated into the Hemoglobin, Resulting in Impaired Oxygen Carriage
      • However, Counteracting that, Sulfhemoglobin Also Results in a Rightward Shift of the Hemoglobin by Decreasing the Oxygen Affinity of the Remaining Unaffected Hemoglobin, Resulting in Enhanced Oxygen Unloading at the Tissues
      • Although a Patient with Sulfhemoglobinemia May Have a Similar Percentage of Hemoglobin Affected as a Patient with Methemoglobinemia, They are Generally Less Clinically Symptomatic Due to the Counteracting Effect on the Oxygen-Hemoglobin Dissociation Curve
      • Unlike Methemoglobinemia, Sulfhemoglobin Cannot Be Converted Back to Normal Hemoglobin Using Methylene Blue
        • Although Packed Red Blood Cell Transfusion May Be Useful in Some Cases, Sulfhemoglobin is Only Removed from the Affected Red Blood Cells with Elimination of the Red Blood Cell After Their Normal Lifespan of 120 Days
  • Acidemia (Decreased Serum pH) (see Metabolic Acidosis-General)
  • Exercise
  • Hypercapnia (see Hypercapnia)
  • Hyperthermia/Fever (see Fever)
  • Increased Red Blood Cell 2,3-Bisphosphoglycerate (2,3-BPG) (Previously Called 2,3-Diphosphoglycerate or 2,3-DPG)
    • The Polyanion, 2,3-BPG is Normally Present within Red Blood Cells and is Formed as a Product of the Glycolytic Pathway
      • 2,3-BPG is Increased During States of Decreased Tissue Oxygen Delivery (Hypoxemia, Congestive Heart Failure, Chronic Lung Disease, Anemia, etc) or Increased Glycolytic Pathway Activity (Hyperthyroidism)
    • 2,3-BPG Binds to Deoxyhemoglobin, Decreasing the Affinity of Hemoglobin for Oxygen
    • Increased 2,3-BPG Results in a Rightward Shift of the Hemoglobin Dissociation Curve, Decreased Hemoglobin Affinity for Oxygen, and Increased Oxygen Delivery to Tissues
  • Increased Red Blood Cell Mean Corpuscular Hemoglobin Concentration (MCHC)
  • Propanolol (see Propanolol)
  • Myo-Inositol Trispyrophosphate (ITPP) (Also Known as OXY111A)
    • ITPP is a Medication Which Causes Allosteric Modulation of Red Blood Cell Hemoglobin and was Developed to Decrease Tissue Hypoxia

Ventilation/Perfusion (V/Q) Relationships

  • V/Q Matching is Normally Heterogeneous Throughout Various Lung Regions
    • Higher V/Q Ratios are Present in the Lung Apices, as Compared to the Bases
    • The Normal Overall V/Q Ratio of the Lungs is About 0.8: not 1, as one would ideally predict
    • There is Normally a Small Amount of V/Q Mismatch as Part of Normal Human Physiology
  • In Pathologic States, Extreme V/Q Relationships May Occur
    • V/Q = 0: in effect, there is perfusion without ventilation -> termed “shunt”
    • V/Q = Infinity: in effect, there is ventilation without associated perfusion -> termed “dead space”

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)

  • Small Amount of Physiologic V/Q Mismatch is Normally Present: overall V/Q of the lungs is about 0.8 (not 1)
    • V/Q Mismatch Increases with Age, Requiring Age-Correction of the Expected A-a Gradient
  • Small Amount of Anatomic Shunt is Normally Present: in normal health, the following two sources represent about 2% of the normal cardiac output and account for about 33% of the normal A-a gradient observed
    • Venous Blood from Bronchial Circulation Drains into the Pulmonary Veins: bronchial circulation provides blood supply to the conducting zone airways
    • Venous Blood from Coronary Circulation Drains Through the Thebesian Veins into the Left Ventricle

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: 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 that exists, due to the bronchial and Thebesian circulations)
  • Etiology
    • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome): 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): due to physiologic intrapulmonary shunt
    • Hepatopulmonary Syndrome (see Hepatopulmonary Syndrome): 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): one reported case of this resulting in an anatomic intrapulmonary shunt
    • Pneumonia: due to physiologic intrapulmonary shunt
    • Pulmonary Arteriovenous Malformation (AVM) (see Pulmonary Arteriovenous Malformation (AVM): 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

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, ARDS, 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: diffusion limitation is absent in normal subjects at rest
  • Etiology
    • Heavy Exercise: due to increased cardiac outut with decreased time available for oxygen diffusion
      • With resulting transient pulmonary interstitial fluid accumulation
      • Effect of Hypoxia: humans will freqently 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): due to increased cardiac outut 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

General Comments

  • Hypoxemia May Be Asymptomatic: in contrast, hypoxia reflects end-organ compromise due to inadequate tissue oxygenation and is always symptomatic (see above)

Hypoxemia

Hypoxia

Cardiovascular Manifestations

  • Angina (see Chest Pain)
  • Arrhythmia
  • Atrioventricular Heart Blocks
  • Congestive Heart Failure (CHF) (see Congestive Heart Failure)
  • Prolonged QT (see Torsade)
    • Physiology
      • Acute Hypoxia Has Been Demonstrated to Prolong the QT Interval in Normal Subjects (Am J Cardiol, 2003) [MEDLINE]
      • Nocturnal Hypoxemia Has Been Demonstrated to Prolong the QT Interval in Patients with Chronic Obstructive Pulmonary Disease (COPD) (NEJM, 1982) [MEDLINE]
      • Hypoxemia Has Been Demonstrated to Prolong the QT Interval During Sleep in Patients with Coronary Artery Disease (CAD) (Chest, 1982) [MEDLINE]
      • 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]
      • 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

Treatment of Hypoxemia

Oxygen (see Oxygen)

Nasal Cannula (NC)

  • xxx

High-Flow Nasal Cannula (HFNC)

  • Technique
    • Heated Circuit
    • Humidification
  • Clinical Effects/Advantages
    • Ability to Deliver Higher FIO2
    • Decreased Anatomic Dead Space, Due to Flushing of the Posterior Pharynx (NEJM, 2015) [MEDLINE]
    • Development of a Modest Amount of CPAP
    • Turbulent Flow in Posterior Pharynx, Facilitating Better Gas Mixing
  • Contraindications
    • Hypercapnic Respiratory Failure
    • Mid-Maxillary Facial Trauma
    • Suspected Pneumothorax
  • French/Belgian FLORALI Randomized Study Comparing High-Flow Nasal Cannula Oxygen with Standard Oxygen and Non-Invasive Ventilation in Hypoxemic, Non-Hypercapnic Respiratory Failure (NEJM, 2015) [MEDLINE]: n = 313
    • Patient Population Consisted of Patients with pO2/FIO2 Ratio <300
      • Approximately 66% of Patients Had CAP
      • Approximately 10% of Patients Had HAP
    • Despite a Trend, There was No Statistically Significant Difference in Intubation Rates (Primary Outcome) Between the HFNC (38%), Standard Oxygen (47%), and NIPPV (50%) Groups (p = 0.18)
    • HFNC Group Had a Significantly Higher Number of Ventilator-Free Days at Day 28, as Compared to Standard Oxygen and NIPPV
    • HFNC Decreased the Hazard Ratio for 90-Day Mortality, as Compared to Standard Oxygen and NIPPV
    • In Post-Hoc Analysis in the Subset of Patients with pO2/FiO2 Ratio ≤200, HFNC Group Had Significantly Decreased the Intubation Rate, as Compared to Standard Oxygen and NIPPV
    • HFNC Increased Patient Comfort and Decreased Dyspnea, as Compared to Standard Oxygen and NIPPV
    • Criticism of Study: the noninvasive ventilation group was unconventionally ventilated with 9 ml/kg PBW, possibly increasing lung injury in this group
  • Spanish Trial of High-Flow Nasal Cannula vs Conventional Oxygen Therapy in Extubated Patients at Low Risk of Reintubation (JAMA, 2016) [MEDLINE]: multicenter randomized trial in Spain
    • In Extubated Patients at Low Risk of Reintubation, High-Flow Nasal Cannula Decreased the Risk of Reintubation within 72 hrs, as Compared to Conventional Oxygen Therapy

Ventimask

  • xxx

Non-Rebreather Mask

  • xxx

Mechanical Ventilation (see Mechanical Ventilation-General)

  • xxx

References

Pseudohypoxemia

  • Pseudohypoxemia secondary to leukemia and thrombocytosis. N Engl J Med. 1979 Aug 16;301(7):361-3 [MEDLINE]
  • Spurious hypoxemia. Crit Care Med. 2005 Aug;33(8):1854-6 [MEDLINE]

General

  • The continuous inhalation of oxygen in cases of pneumonia otherwise fatal, and in other diseases. Boston Med J 1890;123:481-5
  • The alveolar-arterial oxygen difference: its size and components in normal man. Acta Physiol Scand. 1966 May;67(1):10-20 [MEDLINE]
  • Alterations of red-cell glycolytic intermediates and oxygen transport as a consequence of hypophosphatemia in patients receiving intravenous hyperalimentation. N Engl J Med. 1971;285(14):763 [MEDLINE]
  • Hypoxemia in acute pulmonary embolism. Chest. 1985;88(6):829-836 [MEDLINE]
  • Mechanism of exercise-induced hypoxemia in horses. Journal of Applied Physiology March 1989 vol. 66 no. 3 1227-1233 [MEDLINE]
  • The contribution of intrapulmonary shunts to the alveolar-to-arterial oxygen difference during exercise is very small. J Physiol 586.9 (2008) pp 2381-2391 [MEDLINE]
  • Intracardiac shunt with hypoxemia caused by right ventricular dysfunction following pericardiocentesis. Can J Cardiol. 2008 September; 24(9): e60-e62 [MEDLINE]
  • Hypoxia and cardiac arrhythmias in breath-hold divers during voluntary immersed breath-holds. Eur J Appl Physiol. 2009 Mar;105(5):673-8. doi: 10.1007/s00421-008-0945-x. Epub 2008 Nov 26 [MEDLINE]
  • Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit Care. 2010;14(5):R169 [MEDLINE]
  • Platypnea-orthodeoxia: bilateral lower-lobe pulmonary emboli and review of associated pathophysiology and management. South Med J. 2011 Mar;104(3):215-21. doi: 10.1097/SMJ.0b013e31820bfb54 [MEDLINE]

Clinical Manifestations

Cardiovascular Manifestations

  • Nocturnal hypoxemia and associated electrocardiographic changes in patients with chronic obstructive airways disease. N Engl J Med 1982;306:125–30 [MEDLINE]
  • Disordered breathing and hypoxia during sleep in coronary artery disease. Chest 1982;82:548–52 [MEDLINE]
  • Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation 2000;101:392–7 [MEDLINE]
  • Effect of acute hypoxia on QT rate dependence and corrected QT interval in healthy subjects. Am J Cardiol. 2003 Apr 1;91(7):916-9 [MEDLINE]
  • Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol. 2006 Jan 17;47(2):362-7 [MEDLINE]
  • Obstructive Sleep Apnea in Patients with Congenital Long QT Syndrome: Implications for Increased Risk of Sudden Cardiac Death. Sleep. 2015 Jul 1;38(7):1113-9. doi: 10.5665/sleep.4824 [MEDLINE]

Treatment

General

  • Nasal high-flow versus Venturi mask oxygen therapy after extubation: effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med 2014;190:282-8
  • Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia 2015;70:323-9 [MEDLINE]

High-Flow Nasal Cannula (see Oxygen)

  • High-flow nasal cannula oxygen therapy during hypoxemic respiratory failure. Respir Care. 2012 Oct;57(10):1696-8 [MEDLINE]
  • High flow nasal oxygen in acute respiratory failure. Minerva Anestesiol. 2012 Jul;78(7):836-41. Epub 2012 Apr 24 [MEDLINE]
  • High-flow oxygen administration by nasal cannula for adult and perinatal patients. Respir Care 2013;58:98-122
  • Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med. 2013 Feb;39(2):247-57. doi: 10.1007/s00134-012-2743-5. Epub 2012 Nov 10 [MEDLINE]
  • High-flow oxygen administration by nasal cannula for adult and perinatal patients. Respir Care 2013;58:98-122
  • High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014 Apr;59(4):485-90. doi: 10.4187/respcare.02397. Epub 2013 Sep 17 [MEDLINE]
  • FLORALI Study. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015. DOI: 10.1056/NEJMoa1503326 [MEDLINE]
  • Saving lives with high-flow nasal oxygen. N Engl J Med. 2015 Jun 4;372(23):2225-6. doi: 10.1056/NEJMe1504852. Epub 2015 May 17 [MEDLINE]
  • Use of high-flow nasal cannula oxygen therapy to prevent desaturation during tracheal intubation of intensive care patients with mild-to-moderate hypoxemia. Crit Care Med. 2015;43:574–583 [MEDLINE]
  • Heated humidified high-flow nasal oxygen in adults: mechanisms of action and clinical implications. Chest. 2015;148(1):253–261 [MEDLINE]
  • Use of high-flow nasal cannula oxygen therapy in subjects with ARDS: a 1-year observational study. Respir Care. 2015;60:162–169 [MEDLINE]
  • Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial. JAMA. 2016;315(13):1354 [MEDLINE]
  • High-flow nasal cannula oxygen therapy in adults. J Intensive Care. 2015 Mar 31;3(1):15. doi: 10.1186/s40560-015-0084-5. eCollection 2015 [MEDLINE]
  • Noninvasive respiratory support for acute respiratory failure-high flow nasal cannula oxygen or non-invasive ventilation? J Thorac Dis. 2015 Jul;7(7):1092-7. doi: 10.3978/j.issn.2072-1439.2015.07.18 [MEDLINE]
  • Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial. JAMA. 2016;315(13):1354 [MEDLINE]