Hypercapnia


Definitions

Hypercapnia

  • Definition
    • Hypercapnia is Defined as Increased Arterial pCO2 (i.e. Increased Arterial Blood Partial Pressure of Carbon Dioxide)

Acidemia

  • Definition
    • Acidemia is Defined as Decreased Arterial pH
  • 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

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

Etiology of Hypercapnia

Background

Determinants of Arterial pCO2

Terms and Assumptions

  • pCO2: arterial partial pressure of carbon dioxide
  • k: constant
  • VCO2: carbon dioxide production (normal = 90-130 L/min/m2)
    • Measured Using a Metabolic Cart (Which is Capable of Measuring Expired Carbon Dioxide)
  • VE: minute ventilation (respiratory rate x tidal volume)
  • VD/VT Ratio: dead space/tidal volume ratio

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%

Physiology

Simplified Alveolar Gas Equation (see also Hypoxemia)

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

Inverse Relationship Between Arterial pCO2 and pO2

Terms and Assumptions

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

Increased Carbon Dioxide (CO2) Production Normally Results in a Compensatory Increase in Alveolar Ventilation

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

Alveolar Ventilation is Inversely (But Not Linearly) Related to pCO2 (at Varying Levels of CO2 Production)

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)

Minute Ventilation (VE) is Inversely (But Not Linearly) Related to pCO2 (at Varying VD/VT Ratios)

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

Impact on Shunt Fraction on Arterial pO2 and pCO2

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

Diagnosis

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

Clinical Evaluation of Hypercapnia (see also Respiratory Failure)

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

Obstructive Pulmonary Function Tests (PFT’s)


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


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

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

Clinical Manifestations of Hypercapnia/Respiratory Acidosis (see Respiratory Acidosis)

Cardiopulmonary Manifestations

  • Acid-Base and Gas Exchange Abnormalities
  • Arrhythmias
  • Decreased Diaphragmatic Contractility
  • Decreased Myocardial Contractility
  • Decreased Renal Blood Flow
    • May Occur with pCO2 >150 mm Hg
  • Dyspnea (see Dyspnea)
    • Mechanisms
      • Hypercapnia-Associated Decreased Diaphragmatic Contractility
      • Hypercapnia-Associated Decreased Myocardial Contractility
      • 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
  • 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)

Treatment

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

Etiology

Physiology