Respiratory Failure (see 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
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]
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
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
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
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
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
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
Decreased Oxygen Extraction Ratio
Etiology of Decreased Oxygen Extraction Ratio
Sepsis (see Sepsis, [[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 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
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
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
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)
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)
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
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
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)
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
Mechanism: per the simplified alveolar gas equation (above), increased arterial pCO2 (hypercapnia) results in an inverse decrease in arterial pO2 (hypoxemia)
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)
Right Ventricular Dysfunction Due to Right Ventricular infarct (see Coronary Artery Disease)
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)
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
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): acutely increased pulmonary artery pressure may result in new or exacerbated right to left shunt through a pre-existing PFO, etc
Worsened V/Q Mismatch (Above Levels Observed as Part of Normal Physiology)
Mechanism: worsening of V/Q mismatch, above the levels that are observed as part of normal human physiology
Etiology
Acute Pulmonary Embolism (Acute PE) (see Acute Pulmonary Embolism): while intrapulmonary shunt may be a contributor to hypoxemia in the setting of acute PE (typically with co-existent atelectasis), the major mechanism of hypoxemia in acute PE is V/Q mismatch
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
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
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]
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, [[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)
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
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]
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, [[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]
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
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 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]
