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”
- Respiratory Failure is Defined as the Occurrence of One or Both of the Following
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
- Example
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)
- Example
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
- Example
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
- Example
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
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
- PAO2 = [FIO2 x (Patm – PH2O)] – (pCO2/R)
- PAO2 = [FIO2 x (760 – 47)] – (pCO2/0.8)
- Terms
- PAO2: alveolar PO2 (alveolar oxygen tension)
- FIO2: fraction of inspired gas which is oxygen
- Patm: atmospheric pressure
- PH2O: saturated water vapor pressure
- pCO2: arterial partial pressure of CO2
- R: respiratory quotient
Simplified Alveolar Gas Equation
- Terms
- PAO2: alveolar PO2 (alveolar oxygen tension)
- Assumptions
- FIO2: room air
- Altitude: sea level
- Note: arterial PaCO2 (pCO2) is assumed to be nearly the same as alveolar PACO2 in this equation
- Respiratory Exchange Ratio (RER) = 0.8 (Reflecting a Balanced Diet)
- Oxidation of a Molecule of Carbohydrate -> RER = 1.0
- Oxidation of a Molecule of Fatty Acid -> RER = 0.7
Inverse Relationship Between Arterial pCO2 and pO2
- Assumptions
- A-a gradient remains the same (in this case, A-a gradient = 10)
- Respiratory Exchange Ratio (RER) = 0.8 (Reflecting a Balanced Diet)
- Oxidation of a Molecule of Carbohydrate -> RER = 1.0
- Oxidation of a Molecule of Fatty Acid -> RER = 0.7
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 1.0)
- 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
- Venous Blood from Bronchial Circulation Drains into the Pulmonary Veins
- 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
2,3-Bisphosphoglycerate (2,3-BPG)
General Concepts
- Human Red Blood Cells Normally Have Levels of 2,3-Bisphosphoglycerate (2,3-BPG) Which are 1000x Higher than the Levels Present in Other Cells and Approximately Match the Molar Level of the Hemoglobin Tetramer (NEJM, 2022) [MEDLINE]
- 2,3-Bisphosphoglycerate (2,3-BPG) is an Intermediate in the Glycolytic Pathway Which Binds to Dexoyhemoglobin and Functions to Lower its Affinity for Oxygen
- When Hemoglobin is Exposed to Increasing Oxygen Pressure, the Presence of 2,3-BPG Lowers the Fractional Oxygen Saturation, Shifting the Oxygen-Hemoglobin Dissociation Curve to the Right
Anemia Increases Red Blood Cell 2,3-BPG Levels
- Nearly All Patients with Anemia (Regardless of Etiology) Have Increased 2,3-BPG Levels
- This Increased 2,3-BPG Shifts the Oxygen-Hemoglobin Dissociation Curve to the Right, Enhancing Oxygen Delivery
- For Example, an Anemia-Associated Increase in 2,3-BPG Might Increase from 20% of the Oxygen Unloaded to 30% of the Oxygen Unloaded
- This Enhanced Oxygen Unloading Partially Compensates for the Decrease in Red Cell Mass Which is Seen in the Setting of Anemia
- This Increased 2,3-BPG Shifts the Oxygen-Hemoglobin Dissociation Curve to the Right, Enhancing Oxygen Delivery
Oxygen-Hemoglobin Dissociation Curve
Sigmoidal Relationship Between Oxygen Saturation (SaO2) and pO2
- Sigmoidal Shape of the Oxygen-Hemoglobin 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-Hemoglobin 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 (Resulting in a Decrease in Arterial pO2), Hemoglobin Loading with Oxygen 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 Can Extract a Relatively Large Amount of Oxygen from Hemoglobin with a Small Decrease in Arterial pO2
Factors Which Shift the Oxygen-Hemoglobin 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)
- Carboxyhemoglobinemia (see Carboxyhemoglobinemia)
- Alkalemia (Increased Serum pH) (see Metabolic Alkalosis)
- Includes the Administration of Sodium Bicarbonate (see Sodium Bicarbonate)
- 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
- Etiology of Decreased 2,3-BPG
- Hexokinase Deficiency (see Hexokinase Deficiency)
- Hypophosphatemia (see Hypophosphatemia) (NEJM, 1971) [MEDLINE]
- Septic Shock (see Sepsis)
- Decreased Red Blood Cell Mean Corpuscular Hemoglobin Concentration (MCHC)
- Hypocapnia (see Hypocapnia)
- Hypothermia (see Hypothermia)
Factors Which Shift the Oxygen-Hemoglobin 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
- Sickle Cell Disease (see Sickle Cell Disease)
- 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 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
- Etiology of Increased 2,3-BPG
- States of Decreased Tissue Oxygen Delivery
- Anemia (see Anemia)
- Congestive Heart Failure (see Heart Failure)
- Chronic Lung Disease
- Hypoxemia
- States of Increased Glycolytic Pathway Activity
- Hyperthyroidism (see Hyperthyroidism)
- Pyruvate Kinase Deficiency (see Pyruvate Kinase Deficiency)
- States of Decreased Tissue Oxygen Delivery
- 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
Oxygen Delivery and Consumption
General Comments
- Cardiopulmonary Function is Designed to Facilitate the Delivery of Adequate Oxygen to Meet the Demands of Peripheral Tissues
- Determinants of Adequate Oxygenation at the Tissue Level
- Oxygen Delivery (in mL O2/min)
- Tissue Oxygen Consumption (in mL O2/min)
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 the Setting of Severe Anemia
- The Constant 0.0031 in the Arterial Oxygen Content Equation is the Solubility Coefficient of Oxygen at Body Temperature
- 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]
- 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 the Setting of Severe Anemia
- Arterial Oxygen Content = [(1.34 x Hb x 10 x SaO2) + (pO2 x 0.0031 x 10)]
- Constant 1.34 mL O2/g Hb: approximately 1.34 ml of O2 is carried per g of Hb
- While the Normal Oxygen Carrying Capacity is 1.39 ml O2 per g of Hb, the Presence of Abnormal Hemoglobins (Such as Carboxyhemoglobin and Methemoglobin) Decreases this Value to 1.34 ml O2 per g of Hb
- Hemoglobin (Hb): in g/dL
- 10 dL/1L: corrects the units from dL to L
- Arterial Oxygen Saturation (SaO2): as a decimal
- pO2: in mm Hg
- Constant 0.0031 mL O2/L/mm Hg: solubility coefficient of oxygen at body temperature
- 10 dL/1L: corrects the units from dL to L
- Normal Arterial Oxygen Content: approximately 200 mL O2/L (or 20 mL O2/dL)
- Note: 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
- Constant 1.34 mL O2/g Hb: approximately 1.34 ml of O2 is carried per g of Hb
- Simplified Arterial Oxygen Content Equation Omitting the Relatively Minor Contribution of the pO2 Term: this is justified, since the amount of dissolved oxygen represents <1% of the arterial oxygen content
- Arterial Oxygen Content = [1.34 x Hb x 10 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
- Note that the Hemoglobin Concentration Significantly Impacts the Oxygen Delivery
- Example: with a Hb of 20 ml/dl, the oxygen content is twice as much as the oxygen content with a Hb of 10 ml/dl, even though the oxygen saturation and PO2 are the same in both samples
- Using a Train Analogy
- Oxygen Delivery = [Arterial Oxygen Content] x CO
- Oxygen Delivery = [(1.34 x Hb x 10 x SaO2)] x CO
- Constant 1.34 mL O2/g Hb: approximately 1.34 ml of O2 is carried per g of Hb
- While the Normal Oxygen Carrying Capacity is 1.39 ml O2 per g of Hb, the Presence of Abnormal Hemoglobins (Such as Carboxyhemoglobin and Methemoglobin) Decreases this Value to 1.34 ml O2 per g of Hb
- Hemoglobin (Hb): in g/dL
- 10 dL/1L: corrects the units from dL to L
- Arterial Oxygen Saturation (SaO2): as a decimal
- Thermodilution-Measured Cardiac Output from Swan-Ganz Catheter (CO): in L/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
- Constant 1.34 mL O2/g Hb: approximately 1.34 ml of O2 is carried per g of Hb
Oxygen Consumption Equation
- Oxygen Consumption = [1.34 x Hb x 10 x (SaO2-SvO2)] x CO
- Oxygen Consumption: in mL/min
- Constant 1.34 mL O2/g Hb: approximately 1.34 ml of O2 is carried per g of Hb
- While the Normal Oxygen Carrying Capacity is 1.39 ml O2 per g of Hb, the Presence of Abnormal Hemoglobins (Such as Carboxyhemoglobin and Methemoglobin) Decreases this Value to 1.34 ml O2 per g of Hb
- Hemoglobin (Hb): in g/dL
- 10 dL/1L: corrects the units from dL to L
- Arterial Oxygen Saturation (SaO2): as a decimal
- Venous Oxygen Saturation (SvO2): as a decimal
- Thermodilution-Measured Cardiac Output from Swan-Ganz Catheter (CO): in L/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
- Etiology of Increased Oxygen Consumption
- Catecholamine Release or Administration
- Exercise
- Sepsis (see Sepsis)
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/[(1.34 Hb x 10 x SaO2) – (1.34 x Hb x 10 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
- Constant 1.34 mL O2/g Hb: approximately 1.34 ml of O2 is carried per g of Hb
- While the Normal Oxygen Carrying Capacity is 1.39 ml O2 per g of Hb, the Presence of Abnormal Hemoglobins (Such as Carboxyhemoglobin and Methemoglobin) Decreases this Value to 1.34 ml O2 per g of Hb
- Hemoglobin (Hb): in g/dL
- 10 dL/1L: corrects the units from dL to L
- 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)
- Increased Oxygen Extraction Ratio
- Etiology of Increased Oxygen Extraction Ratio
- Low Cardiac Output State
- Cardiogenic Shock
- Hypovolemic Shock
- Low Cardiac Output State
- Etiology of Increased Oxygen Extraction Ratio
- Decreased Oxygen Extraction Ratio
- 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
- Etiology of Decreased Oxygen Extraction Ratio
- 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 Delivery/Oxygen Consumption Ratio (DO2/VO2 Ratio)
- Normal Oxygen Delivery/Oxygen Consumption Ratio
- Homeostatic Mechanisms Normally Maintain an Oxygen Delivery/Consumption Ratio of 5:1
- Consequently, in the Normal Resting Adult, Only 20% of the Delivered Oxygen is Utilized for Metabolism, Leaving 80% in the Venous Blood
- During States of Increased Oxygen Consumption (Catecholamine Release/Administration, Exercise, Sepsis, etc), Oxygen Delivery is Increased to Maintain the Oxygen Delivery/Consumption Ratio of 5:1
- Decreased Oxygen Delivery/Oxygen Consumption Ratio
- When the Oxygen Delivery/Oxygen Consumption Ratio Decreases Below 2:1 (i.e. 50% Extraction), There is Inadequate Oxygen to Maintain Oxygen-Dependent (Aerobic) Metabolism, Resulting in Switching to Anaerobic Metabolism, Resulting in Lactic Acidosis
- Anaerobic Metabolism is Tolerated for a Few Hours at Most, and if it Persists, Cardiovascular and Metabolic Collapse May Occur
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
- Arterial Blood Gas (ABG) (see Arterial Blood Gas)
- Decreased pO2
- Arterial Blood Gas (ABG) (see Arterial Blood Gas)
- 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
- Acute Hypoventilation (see Respiratory Failure)
- Chronic Hypoventilation (see Respiratory Failure)
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 Conditions Result in an Impaired Ability to Re-Oxygenate the Blood
- Etiology
- Decreased Cardiac Output State/Cardiogenic Shock (see Cardiogenic Shock)
- Right Ventricular Dysfunction Due to Right Ventricular infarct (see Coronary Artery Disease)
- Acute Cor Pulmonale Due to Acute Pulmonary Embolism (see Acute Pulmonary Embolism)
- Tamponade (see Tamponade): unclear why this results in decreased mixed venous oxygen saturation
- Increased Tissue Oxygen Extraction
- Decreased Cardiac Output State/Cardiogenic Shock (see Cardiogenic Shock)
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
- Physiology
- 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 the Development of 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
- Epidemiology
- Atelectasis (see Atelectasis)
- Physiology
- Due to Physiologic Intrapulmonary Shunt
- Physiology
- 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)
- Physiology
- Intralobar Pulmonary Sequestration (see Pulmonary Sequestration)
- Epidemiology
- One Reported Case of This Resulting in an Anatomic Intrapulmonary Shunt
- Epidemiology
- Pneumonia
- Physiology
- Due to Physiologic Intrapulmonary Shunt
- Clinical
- Community-Acquired Pneumonia (see Community-Acquired Pneumonia)
- Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP) (see Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia)
- Physiology
- Pulmonary Arteriovenous Malformation (AVM) (see Pulmonary Arteriovenous Malformation (AVM))
- Physiology
- Due to Anatomic Intrapulmonary Shunt
- Physiology
- Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)
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
- Physiology
- 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 and Pulmonary Artery Stenosis
- Physiology
- Ventricular Septal Defect (VSD) with Right-to-Left Shunt (see Ventricular Septal Defect)
- Acute Pulmonary Embolism (Acute PE) with Right-to-Left Shunt (see Acute Pulmonary Embolism)
Worsened V/Q Mismatch (Above Levels Observed as Part of Normal Physiology)
- Mechanism
- Worsening of V/Q Mismatch, Above the Levels Which are Observed as Part of Normal Human Physiology
- Etiology
- Acute Pulmonary Embolism (Acute PE) (see Acute Pulmonary Embolism)
- Physiology
- While Intrapulmonary Shunt May Be a Contributor to the Development of 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
- Physiology
- Atelectasis (see Atelectasis)
- Hemodialysis-Associated Hypoxemia (see Hemodialysis)
- Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)
- Leukostasis (see Leukostasis)
- Obstructive Lung Disease (see Obstructive Lung Disease)
- Clinical
- Asthma (see Asthma)
- Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
- Clinical
- Pneumonia
- Clinical
- Community-Acquired Pneumonia (see Community-Acquired Pneumonia)
- Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP) (see Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia)
- Clinical
- Pulmonary Vascular Disease (see Pulmonary Hypertension)
- Acute Pulmonary Embolism (Acute PE) (see Acute Pulmonary Embolism)
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
- Limitation of Oxygen Exchange Across the Pulmonary Capillary Blood-Gas Barrier
- 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
- Physiology
- Heavy Exercise (Due to Increased Cardiac Output with Decreased Time Available for Oxygen Diffusion)
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
- On Room Air at Sea Level: Alveolar PO2 (PAO2) = 150 – PCO2/0.8
- 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
- First Degree Atrioventricular Block (see First Degree Atrioventricular Block)
- Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I)
- Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II)
- Third Degree Atrioventricular Block (see Third Degree Atrioventricular 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
- Altered Mental Status
- Confusion/Delirium (see Delirium)
- Lethargy/Obtundation (see Obtundation-Coma)
- Anxiety (see Anxiety)
- Dizziness (see Dizziness)
- Headache (see Headache)
- Hypoxemia-Induced Cerebral Vasodilation with Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)
- This May Potentiate Neurologic Injury in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)
- Irritability/Restlessness
- Altered Mental Status
- Pulmonary Manifestations
- Dyspnea (see Dyspnea)
- Pulmonary Vasoconstriction with Worsening of Pulmonary Hypertension (see Pulmonary Hypertension)
- Hypoxic Pulmonary Vasoconstriction is Further Enhanced by Acidosis (see Metabolic Acidosis-General)
- 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
- First Degree Atrioventricular Block (see First Degree Atrioventricular Block)
- Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I)
- Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II)
- Third Degree Atrioventricular Block (see Third Degree Atrioventricular 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
- Altered Mental Status
- Confusion/Delirium (see Delirium)
- Lethargy/Obtundation (see Obtundation-Coma)
- Anxiety (see Anxiety)
- Dizziness (see Dizziness)
- Headache (see Headache)
- Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)
- Due to Hypoxemia-Induced Cerebral Vasodilation
- This May Potentiate Neurologic Injury in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)
- Irritability/Restlessness
- Altered Mental Status
- Pulmonary Manifestations
- Dyspnea (see Dyspnea)
- Pulmonary Vasoconstriction with Worsening of Pulmonary Hypertension (see Pulmonary Hypertension)
- Hypoxic Pulmonary Vasoconstriction is Further Enhanced by Acidosis (see Metabolic Acidosis-General)
- 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
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]
Physiology
- Intracellular organic phosphates as regulators of oxygen release by haemoglobin. Nature. 1969 Feb 15;221(5181):618-22. doi: 10.1038/221618a0 [MEDLINE]
- Oxygen-hemoglobulin dissociation curves: effect of inherited enzyme defects of the red cell. Science. 1969 Aug 8;165(3893):601-2. doi: 10.1126/science.165.3893.601 [MEDLINE]
- The role of the left-shifted or right-shifted oxygen-hemoglobin equilibrium curve. Ann Intern Med. 1971 Jan;74(1):44-6. doi: 10.7326/0003-4819-74-1-44 [MEDLINE]
- Acute lung injury. Assessment of tissue oxygenation. Crit Care Clin. 1986;2(3):537 [MEDLINE]
- Lactate levels as predictors of the relationship between oxygen delivery and consumption in ARDS. Chest. 1990;98(4):959 [MEDLINE]
- Effects of catecholamines on oxygen consumption and oxygen delivery in critically ill patients. Chest. 1991;100(6):1676 [MEDLINE]
- Measurement of hemoglobin saturation by oxygen in children and adolescents with sickle cell disease. Pediatr Pulmonol. 1999;28(6):423 [MEDLINE]
- Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction. Circ Heart Fail. 2015 Mar;8(2):286-94 [MEDLINE]
- Oxygen Delivery in the Treatment of Anemia. N Engl J Med. 2022 Dec 22;387(25):2362-2365. doi: 10.1056/NEJMra2212266 [MEDLINE]
Etiology
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]
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]