Respiratory Failure (see Respiratory Failure)

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

Hypoxemia (see Hypoxemia)

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

Hypoxia (see Hypoxemia)

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

Anoxia

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

Hypercapnia (see Hypercapnia)

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

Acidemia

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

Alkalemia

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

Acidosis

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

Alkalosis

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

Respiratory Acidosis (see Respiratory Acidosis)

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

Terms

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

Specific Etiologies of Hypercapnia

• Respiratory Compensation for Metabolic Alkalosis (see Metabolic Alkalosis)
  • Mechanism
    • Elevated pH Results in Hypoventilation with a Compensatory Increase in pCO2
      • However, the Degree of Hypoventilation is Limited by the Hypoxic Respiratory Drive to Breathe
    • The Predicted Compensatory Increase in pCO2 in Response to a Primary Metabolic Alkalosis Obeys the Acid-Base Rules (see Acid-Base Physiology)
      • Expect an Increase of 7 in pCO2 for Each Increase of 10 in the HCO3
      • Expected pCO2 = (bicarb x 0.7) + 21 + 1.5
    • Clinical Pearls
      • ALL Cases of Subacute or Chronic Hypercapnia are Accompanied by Elevated Serum Bicarbonate (on Serum Chemistry or Arterial Blood Gas)
      • Presence of Elevated Serum Carbon Dioxide Should Raise the Suspicion for Presence of Either a Primary Metabolic Alkalosis OR a Primary Respiratory Acidosis with Compensatory Metabolic Alkalosis
      • One Would Order an Arterial Blood Gas to Differentiate These Conditions
• Increased Carbon Dioxide Production (VCO2)
  • Occurs with Overfeeding (Generally with Tube Feedings or Total Parenteral Nutrition)
  • Increased Carbon Dioxide Production Only Results in Hypercapnia When Alveolar Ventilation (VE) is Inadequate (ie: in the Presence of Significant Lung Disease, Such as Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome, etc)
• Acute Hypoventilation with Acutely Decreased Minute Ventilation (VE) (see Respiratory Failure)
• Chronic Hypoventilation with Chronically Decreased Minute Ventilation (VE) (see Respiratory Failure)
• Increased Dead Space Ventilation with Increased VD/VT Ratio
  • Hypercapnia Only Occurs When the VD/VT Ratio Exceeds 50%

Terms and Assumptions

• PAO2: alveolar partial pressure of oxygen (PO2 or alveolar oxygen tension)
• Respiratory Exchange Ratio: 0.8
• Arterial PaCO2 (pCO2) is Assumed to Be Nearly the Same as Alveolar PACO2 in This Equation
• FIO2 is Assumed to Be Room Air (21% FIO2)
• Altitude is Assumed to Be Sea Level

Terms and Assumptions

• A-a Gradient Remains the Same (in this Case, A-a Gradient = 10)
• Respiratory Exchange Ratio: 0.8

At a Constant Alveolar (Minute) Ventilation, Increased Carbon Dioxide (CO2) Production Should Theoretically Increase the pCO2

• In a Normal Patient
  • Increased Carbon Dioxide (CO2) Production Results in an Increase in Alveolar (Minute) Ventilation, Decreasing the pCO2 Back to a Normal Level (i.e. Approximately 40 mm Hg)
• In a Patient with Moderate-Severe Lung Disease
  • Patient May Be Unable to Increase Their Alveolar (Minute) Ventilation to Compensate for the Increased Carbon Dioxide (CO2) Production
  • Therefor, pCO2 May Increase, Possibly Resulting in Respiratory Failure

Clinical Examples

• In a Patient with Acute/Chronic Hypocapnia: assuming a constant CO2 production (VCO2), a significant increase in minute ventilation (VE) must be present to maintain the low pCO2
  • Example: DKA patient with pH 7.40 and pCO2 30 must maintain a significanty increased VE to maintain the pCO2 at that level -> despite a normal pH, rapid respiratory failure can occur if, for any reason, patient cannot maintain that high VE
• In a Patient with Acute/Chronic Hypercapnia: assuming a constant CO2 production (VCO2), a relatively small decrease in VE can produce a significant increase in pCO2
  • Example: chronically hypercapnic COPD with pCO2 60 can experience a significant increase in pCO2 with even a small decrease in VE (due to minimal sedation, etc)

Terms and Assumptions

• Graph Assumes a Constant Carbon Dioxide Production (VCO2) of 200 ml/min
• VCO2 = VA x (PaCO2/PB)
• VE = VA x 1.21/(1-VD/VT)

Key Points

• VD/VT Ratio Determines How Efficiently the Lungs Excrete Carbon Dioxide (CO2) Per Breath (i.e How “Sick” the Lungs Are)
  • Low VD/VT Ratio = More Efficient Carbon Dioxide (CO2) Excretion Per Breath
  • High VD/VT Ratio = Less Efficient Carbon Dioxide (CO2) Excretion Per Breath
• At a Low VD/VT Ratio (Healthy Lungs), a Relatively Low Minute Ventilation (VE) is Required to Maintain pCO2 Constant at 40 mm Hg
• At a High VD/VT Ratio (“Sick Lungs”), a High Minute Ventilation (VE) is Required to Maintain pCO2 Constant at 40 mm Hg
  • If This Level of Increased Minute Ventilation Cannot Be Maintained, the Patient Will Develop Hypercapnic Respiratory Failure

Key Points

• pO2 Decreases Linearly and Inversely with Increasing Shunt Fraction
  • The Higher the Degree of Shunt, the Lower the pO2
• In Contrast, pCO2 Remains Relatively Constant Over a Wide Range of Shunt Fractions
  • pCO2 Only Increases After the Shunt Fraction Exceeds 50%
    • For This Reason, Shunt Does Not Typically Result in Hypercapnia

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

• Required for the Diagnosis of Hypercapnia/Respiratory Acidosis (see Respiratory Acidosis)

Normal/Unchanged Alveolar-Arterial (A-a) Gradient

Obstructive Pulmonary Function Tests (PFT’s)

• Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
  • Hypercapnia in COPD is Multifactorial (Due to Hypoventilation, V/Q Mismatch, etc)

Restrictive Pulmonary Function Tests (PFT’s) + Normal Maximal Inspiratory Pressure (MIP)

• Obesity Hypoventilation Syndrome (OHS) (see Obesity Hypoventilation Syndrome)
• Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea)
• Primary Idiopathic Alveolar Hypoventilation Syndrome (Ondine’s Curse) (see Primary Idiopathic Alveolar Hypoventilation Syndrome)
• Brainstem Disease
• Pharmacologic Central Respiratory Depressants
  • Opiates (see Opiates)
  • Barbiturates (see Barbiturates)
  • Benzodiazepines (see Benzodiazepines)
  • Propofol (Diprivan) (see Propofol)

Restrictive Pulmonary Function Tests (PFT’s) + Decreased Maximal Inspiratory Pressure (MIP)

• Chest Wall Disease
  • Kyphoscoliosis (see Kyphoscoliosis)
• Motor Neuron Disease
  • Amyotrophic Lateral Sclerosis (ALS) (see Amyotrophic Lateral Sclerosis)
• Neuromuscular Junction Disease
  • Myasthenia Gravis (see Myasthenia Gravis)
• Myopathy (see Myopathy)
  • Duchenne Muscular Dystrophy (see Duchenne Muscular Dystrophy)
• Peripheral Neuropathy (see Peripheral Neuropathy)
  • Guillain-Barre Syndrome (see Guillain-Barre Syndrome)

Increased Alveolar-Arterial (A-a) Gradient

Normal VCO2 (Normal Carbon Dioxide Production)

• V/Q Mismatch (V/Q Ratio >1, Dead Space Ventilation)
  • Hypercapnia Only Occurs When VD/VT Ratio is >50%
• Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
  • Hypercapnia in COPD is Multifactorial (Due to Hypoventilation, V/Q Mismatch, etc)

Increased VCO2 (Increased Carbon Dioxide Production)

• General Comments
  • These Conditions Usually Cause Hypercapnia Only in the Setting of Underlying Lung Disease (with Impairment in Carbon Dioxide Excretion)
• Hypermetabolism
• Overfeeding: especially wtih excessive carbohydrate, whch generates more carbon dioxide per calorie than do fats
• Organic Acidosis

Cardiopulmonary Manifestations

• Acid-Base and Gas Exchange Abnormalities
  • Decreased Alveolar pO2 (see Hypoxemia)
  • Respiratory Acidosis (see Respiratory Acidosis)
• Arrhythmias
• Decreased Diaphragmatic Contractility
  • May Result in Respiratory Failure (see Respiratory Failure)
• Decreased Myocardial Contractility
  • May Result in Congestive Heart Failure (CHF) (see Congestive Heart Failure)
• Decreased Renal Blood Flow
  • May Occur with pCO2 >150 mm Hg
• Dyspnea (see Dyspnea)
  • Mechanisms
    • Hypercapnia-Associated Decreased Diaphragmatic Contractility
      • May Result in Respiratory Failure (see Respiratory Failure)
    • Hypercapnia-Associated Decreased Myocardial Contractility
      • May Result in Congestive Heart Failure (CHF) (see Congestive Heart Failure)
    • Hypercapnia-Associated Acidemia, Resulting in Stimulation of Central and Peripheral Chemoreceptors
    • Hypercapnia-Induced Increase in Respiratory Drive (Early), Then Decreased Respiratory Drive (Later)
• Early Increased Respiratory Drive, Later Decreased Respiratory Drive
• Leakage of Intracellular Potassium
  • May Occur with pCO2 >150 mm Hg
• Peripheral Venodilation with Hypotension (see Hypotension)
  • May Occur with Severe Hypercapnia
• Rightward Shift of the Oxyhemoglobin Dissociation Curve (Due to Hypercapnia and/or Acidemia)
  • Decreased Hemoglobin Affinity for Oxygen in the Lungs (with Decreased Oxygen Loading) and Increased Oxygen Unloading at the Tissues (Bohr Effect)

Neurologic Manifestations

• Altered Mental Status (see Altered Mental Status)
  • Confusion (see Confusion)
    • May Occur with Moderate (or Rapidly Developing) Hypercapnia
  • Delirium (see Delirium)
    • May Occur with Moderate (or Rapidly Developing) Hypercapnia
  • Obtundation/Coma (“CO2 Narcosis”) (see Obtundation/Coma)
    • Acute Hypercapnia Initially Increases the Respiratory Drive (with Associated Hyperventilation) (Anesthesiology, 1960) [MEDLINE] (NEJM, 1984) [MEDLINE]
    • Later, Acute Hypercapnia Decreases the Respiratory Drive, Leading to Worsening Hypercapnia with Depressed Mental Status (“CO2 Narcosis”)
    • Normal (Normocapnic) Patients Generally Do Not Develop Altered Mental Status Until the pCO2 Exceeds 75-80 mm Hg
    • Chronically Hypercapnic Patients Generally Do Not Develop Altered Mental Status Until the pCO2 Exceeds 90-100 mm Hg
      • These Later Effects are Mediated Via Increased Brain Glutamine, Increased Brain γ-Aminobutyric Acid (GABA), Decreased Brain Glutamate, and Decreased Brain Aspartate
• Anesthesia (see Anesthesia)
  • May Occur with pCO2 >200 mm Hg
• Anxiety (see Anxiety)
  • May Occur with Mild-Moderate Hypercapnia (Which Develops Gradually
• Asterixis (see Asterixis)
  • May Occur with Severe Hypercapnia
• Depression (see Depression)
  • May Occur with Moderate (or Rapidly Developing) Hypercapnia
• Excessive Daytime Somnolence (see Excessive Daytime Somnolence)
  • May Occur with Mild-Moderate Hypercapnia (Which Develops Gradually
• Headache (see Headache)
  • May Occur with Mild-Moderate Hypercapnia (Which Develops Gradually
• Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure) (Anesthesiology, 1960) [MEDLINE] (NEJM, 1984) [MEDLINE]
  • Hypercapnia Causes Cerebral Vasodilation with Increased Cerebral Blood Flow
    • The Increased Cerebral Blood Flow May Undesirably Potentiate Neurologic Injury in Traumatic Brain injury (TBI), etc (see Traumatic Brain injury)
  • Papilledema May Occur with Severe Hypercapnia (see Papilledema)
• Myoclonus (see Myoclonus)
  • May Occur with Severe Hypercapnia
• Paranoia (see Paranoia)
  • May Occur with Moderate (or Rapidly Developing) Hypercapnia
• Seizures (see Seizures)
  • May Occur with Severe Hypercapnia

Manifestations Due to the Acidosis Itself

• Altered Action of Pharmacologic Agents
  • Intracellular Acidosis Potentiates the Effect of Neuromuscular Junction Antagonists (Cisatracurium, Rocuronium, etc) (see Neuromuscular Junction Antagonists)
• Cardiovascular Instability/Cardiac Arrest (see Cardiac Arrest)
• Central Nervous System Depression
• Decreased Calcium Binding to Albumin (with Increase Serum Ionized Calcium Levels) (see Hypercalcemia)
• Hyperkalemia Due to Extracellular Shift of Potassium (see Hyperkalemia)
• Hypotension/Pulseless Electrical Activity (PEA) (see Hypotension and Pulseless Electrical Activity)
  • Due to Decreased Systemic Vascular Resistance (SVR)