Hyperpnea (see Hyperpnea)

• Definition
  • Hyperpnea is Defined as an Increase in Tidal Volume with or without an Increase in Respiratory Rate

Tachypnea (see Tachypnea)

• Definition
  • Tachypnea is Defined as an Increase in Respiratory Rate

Hypocapnia (see Hypocapnia)

• Definition
  • Hypocapnia is Defined as Decrease in Arterial pCO2 (i.e. Decreased Arterial Blood Partial Pressure of Carbon Dioxide) to <40 mm Hg

Alkalemia

• Definition
  • Alkalemia is Defined as Increase in the Arterial pH to >7.40
• Note that a Patient Can Be Alkalemic without Having a Respiratory Alkalosis
  • Example
    • Metabolic Alkalosis Can Produce Alkalemia without the Presence of a Respiratory Alkalosis

Respiratory Alkalosis (see Respiratory Alkalosis)

• Definition
  • Respiratory Alkalosis is Defined as an Acid-Base Disorder Characterized by a Decrease in Arterial pCO2 with an Associated Increase in Arterial pH (at Least Initially)
• Note that a Patient Can Have a Respiratory Alkalosis without Being Alkalemic
  • Example
    • Due to Normal Compensatory Mechanisms, Chronic Respiratory Alkalosis Induces Metabolic (Predominantly Renal) Compensation (with a Progressive Decrease in Serum Bicarbonate Over Time), Culminating in Only Minimal/Absent Alkalemia

Cardiovascular Disease-Induced Hyperventilation

Congestive Heart Failure (CHF) (see Congestive Heart Failure)

• Physiology
  • Pulmonary Congestion, Resulting in Stimulation of Pulmonary Vascular and Interstitial Receptors, Increasing Respiratory Drive
  • Low Cardiac Output and Hypotension, Resulting in Stimulation of Arterial Baroreceptors -> Increasing Respiratory Drive
  • “Stagnant Hypoxia” of Carotid Body Chemoreceptors, Resulting in Increased Respiratory Drive

Hypotension (see Hypotension)

• Physiology
  • Pulmonary Congestion, Resulting in Stimulation of Pulmonary Vascular and Interstitial Receptors, Increasing Respiratory Drive
  • Low Cardiac Output and Hypotension, Resulting in Stimulation of Arterial Baroreceptors -> Increasing Respiratory Drive
  • “Stagnant Hypoxia” of Carotid Body Chemoreceptors, Resulting in Increased Respiratory Drive

Fever/Sepsis-Induced Hyperventilation (see Fever and Sepsis)

Physiology

• Fever-Related Stimulation of Hypothalamus or Carotid Bodies
  • Occurs Independent of Hypotension and Metabolic Rate

Clinical

• Respiratory Alkalosis May Occur Early Prior to the Onset of Fever and Hypotension

Hypoxemia-Induced Hyperventilation

High Altitude (see Chronic Mountain Sickness)

• Physiology
  • Hypoxemia-Induced Stimulation of Peripheral Chemoreceptors in the Carotid Bodies
    • However, the Degree of Hypoxemia-Induced Increase in Minute Ventilation is Modulated by Co-Existing pCO2 and pH, Mechanics of the Lung and Chest Wall, Genetic Factors, and the Overall Duration of Hypoxemia
    • The Increase in Minute Ventilation (VE) in Response to Decrease in pO2 is Non-Linear
      • The Most Pronounced Response is Observed with pO2 <60 mm Hg
    • The Increase in Minute Ventilation (VE) in Response to Decreased SaO2 is Relatively Linear
• Clinical
  • On Mount Everest (Where pO2 is 27 mm Hg), the pCO2 is Decreased to 7.5 mm Hg (J Appl Physiol Respir Environ Exerc Physiol, 1983) [MEDLINE]

Intracardiac Shunt (see Intracardiac and Extracardiac Shunt)

• Physiology
  • Hypoxemia-Induced Stimulation of Peripheral Chemoreceptors in the Carotid Bodies
    • However, the Degree of Hypoxemia-Induced Increase in Minute Ventilation is Modulated by Co-Existing pCO2 and pH, Mechanics of the Lung and Chest Wall, Genetic Factors, and the Overall Duration of Hypoxemia
    • The Increase in Minute Ventilation (VE) in Response to Decrease in pO2 is Non-Linear
      • The Most Pronounced Response is Observed with pO2 <60 mm Hg
    • The Increase in Minute Ventilation (VE) in Response to Decreased SaO2 is Relatively Linear

Pulmonary Disease (of Any Etiology Resulting in Hypoxemia)

• Physiology
  • Hypoxemia-Induced Stimulation of Peripheral Chemoreceptors in the Carotid Bodies
    • However, the Degree of Hypoxemia-Induced Increase in Minute Ventilation is Modulated by Co-Existing pCO2 and pH, Mechanics of the Lung and Chest Wall, Genetic Factors, and the Overall Duration of Hypoxemia
    • The Increase in Minute Ventilation (VE) in Response to Decrease in pO2 is Non-Linear
      • The Most Pronounced Response is Observed with pO2 <60 mm Hg
    • The Increase in Minute Ventilation (VE) in Response to Decreased SaO2 is Relatively Linear

Metabolic Disorder-Induced Hyperventilation

Acidosis (i.e. Acidemia of Any Etiology) (see Metabolic Acidosis-Elevated Anion Gap and Metabolic Acidosis-Normal Anion Gap)

• Physiology
  • Stimulation of Peripheral and Central Chemoreceptors (and Increased Sensitivity of Peripheral Chemoreceptors to Hypoxia), Resulting in Increased Respiratory Drive

Hyperthyroidism (see Hyperthyroidism)

• Physiology
  • Due to increased ventilatory chemoreflexes

Liver Disease

• Etiology
  • Acute Hepatic Failure (see Acute Hepatic Failure)
  • Cirrhosis (see Cirrhosis)
• Physiology
  • Sympathetic Overactivity, Increased Serum Progesterone and Vasoactive Intestinal Peptide (VIP), Increased Brain Ammonia and Glutamine, and Hypoxemia from the Formation of Small Intrapulmonary Shunts (ie: Hepatopulmonary Syndrome), All Resulting in Increased Respiratory Drive (Int J Cardiol, 2012) [MEDLINE]
• Clinical
  • Severity of Respiratory Alkalosis Correlates with the Degree of Hepatic Insufficiency

Severe Anemia (see Anemia)

• Physiology
  • Decreased Oxygen Delivery

Neurologic/Psychogenic Disorder-Induced Hyperventilation

Anxiety/Panic Disorder (see Anxiety)

• Epidemiology
  • Hyperventilation is a Common Clinical Feature in Panic Attacks

Brainstem Tumor

• Physiology
  • Lactic Acidosis by Malignant Cells in Midbrain, Resulting in Increased Respiratory Drive

Central Nervous System Infection

• Etiology
  • Encephalitis (see Encephalitis)
  • Meningitis (see Meningitis)
• Physiology
  • Involvement of Midbrain or Hypothalamus, Resulting in Increased Respiratory Drive

Intracerebral Hemorrhage (see Intracerebral Hemorrhage)

• Physiology
  • Red Blood Cell Glycolysis and Acidosis in the Cerebrospinal Fluid, Resulting in Increased Respiratory Drive

Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)

• Physiology
  • Impairment of Inhibition of the Cortex on the Brainstem Respiratory Center

Psychogenic Hyperventilation

• Physiology
  • Anxiety/Stress
    • Supported by the Fact that This Type of Hyperventilation Decreases During Sleep

Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)

• Physiology
  • Involvement of Midbrain or Hypothalamus, Resulting in Increased Respiratory Drive

Withdrawal

• Delirium Tremens (DT’s) (see Ethanol)

Pain-Induced Hyperventilation

Physiology

• Adrenergic Stimulation of Peripheral and Central Chemoreceptors

Pregnancy-Induced Hyperventilation (and Luteal Phase of Menstrual Cycle)-Induced Hyperventilation (see Pregnancy)

Physiology

• Progesterone and Other Hormone Stimulation of the Medullary Respiratory Center

Pulmonary Disease-Induced Hyperventilation

Asthma (see Asthma)

• Physiology
  • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
  • Stimulation of Chest Wall Receptors (in Asthma, Pulmonary Fibrosis, and Chest Wall Disease), Resulting in Increased Respiratory Drive (and Dyspnea)

Cardiogenic Pulmonary Edema (see Cardiogenic Pulmonary Edema)

• Physiology
  • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Chest Wall Disease

• Etiology
  • Fibrothorax (see Fibrothorax)
  • Kyphoscoliosis (see Kyphoscoliosis)
  • Pectus Excavatum (see Pectus Excavatum)
• Physiology
  • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
  • Stimulation of Chest Wall Receptors (in Asthma, Pulmonary Fibrosis, and Chest Wall Disease), Resulting in Increased Respiratory Drive (and Dyspnea)

Community-Acquired Pneumonia (CAP)/Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia (VAP) (see Community-Acquired Pneumonia and Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia)

• Physiology
  • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)

• Epidemiology
  • Respiratory Alkalosis is Common
• Etiology
  • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis)
    • Physiology
      • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
      • Stimulation of Chest Wall Receptors (in Asthma, Pulmonary Fibrosis, and Chest Wall Disease), Resulting in Increased Respiratory Drive (and Dyspnea)

Pneumothorax (see Pneumothorax)

• Physiology
  • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Pulmonary Vascular Disease

• Etiology
  • Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism)
    • Physiology
      • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
  • Pulmonary Hypertension (see Pulmonary Hypertension)
    • Physiology
      • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Drug-Induced Hyperventilation

Beta-2 Adrenergic Receptor Agonists (see β2-Adrenergic Receptor Agonists)

• Physiology
  • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive

Doxapram (Dopram, Stimulex Respiram) (see Doxapram)

• Physiology
  • Doxapram Stimulates Carotid Body Chemoreceptors (in the Carotid Arteries), Resulting in Stimulation of the Brainstem Respiratory Center
• Clinical
  • Intravenous Respiratory Stimulant
  • Increases Respiratory Rate and Tidal Volume

Methylxanthines

• Physiology
  • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive
• Agents
  • Aminophylline (see Aminophylline)
  • Caffeine (see Caffeine)
  • Pentoxifylline (Trental) (see Pentoxifylline)
  • Theobromine (see Theobromine)
  • Theophylline (see Theophylline)

Progesterone (see Progesterone)

• Physiology
  • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive
• Clinical
  • Progesterone Increases Ventilation and Lowers the Arterial pCO2 by as Much as 5–10 mm Hg

Salicylate Intoxication (see Salicylates)

• Epidemiology
  • Salicylates are the Most Common Etiology of Drug-Induced Respiratory Alkalosis
• Physiology
  • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive
  • With Salicylates, Secondary Metabolic Acidosis Can Also Drive Respiration

General Comments

• Clinical Manifestations in Acute Respiratory Alkalosis are More Common Than in Metabolic Alkalosis (see Metabolic Alkalosis)
  • Respiratory Alkalosis Probably Causes a Larger Change in Intracellular and Brain pH than Does Metabolic Alkalosis
    • Acute Respiratory Alkalosis Results in a Rapid Shift in Arterial pCO2, Which is Almost Immediately Transmitted Throughout the Total Body Water (Including the Intracellular Fluid Compartment, the Brain, and the Cerebrospinal Fluid)
      • This Accounts for the Characteristic Symptoms of Paresthesias, Carpopedal Spasm, and Lightheadedness Observed in Acute Respiratory Alkalosis
    • Metabolic Alkalosis-Associated Alterations in Blood Bicarbonate Cause Slower and Less Marked pH Changes within the Intracellular Fluid Compartment and Across the Blood-Brain Barrier

Cardiovascular Manifestations

Arrhythmias

• Epidemiology
  • Hypocapnia has Been Linked to the Development of Arrhythmias, Both in Critically Ill Patients and in Patients with Panic Disorder
• Physiology
  • Arrhythmias are Likely Mediated by Alkalemia-Mediated Electrophysiologic Effects on the Cardiac Conduction System (J Thorac Cardiovasc Surg, 1966) [MEDLINE]
  • May Also Be Mediated to Myocardial Ischemia (Although Specific Direct Myocardial Effects May Occur)
• Treatment
  • Arrhythmias are More Resistant to Pharmacologic Treatment in the Setting of Alkalemia

Decreased Oxygen Delivery to Tissues (see Hemodynamics and Hypoxemia)

• Mechanisms
  • Leftward Shift of the Oxyhemoglobin Dissociation Curve (see Hypoxemia)
    • Decreases the Ability of Hemoglobin to Release Oxygen at the Tissue Level
  • Hypocapnia Results in Vasoconstriction and Decreased Perfusion of the Brain, Heart, and Peripheral Tissues
    • In Vitro Studies Indicate that Alkalemia is the Critical Determinant of Vascular Smooth Muscle Tone
      • This Similarly Occurs in the Setting of Metabolic Alkalosis (see Metabolic Alkalosis)
• Clinical
  • Lactic Acidosis (see Lactic Acidosis)

Myocardial Ischemia (see Coronary Artery Disease)

• Physiology
  • Coronary Artery Vasospasm
  • Decreased Myocardial Oxygen Supply
    • Decreased Coronary Artery and Collateral Artery Blood Flow
    • Increased Coronary Vascular Resistance
    • Increased Risk of Coronary Artery Spasm
    • Increased Coronary Microvascular Leakage
    • Increased Platelet Count and Aggregation
  • Increased Myocardial Oxygen Demand
    • Increased Oxygen Extraction
    • Increased (and Later Decreased) Contractility
    • Increased Intracellular Calcium Concentration
    • Increased Systemic Vascular Resistance (SVR)
  • Myocardial Ischemia
  • Reperfusion Injury
    • Rapid Correction of Severe Hypocapnia Causes Vasodilation in Ischemic Areas
• Diagnosis
  • Ischemic Electrocardiographic Changes (see Electrocardiogram)
• Clinical
  • Chest Pain (see Chest Pain)
  • Syncope (see Syncope)

Palpitations (see Palpitations)

• Epidemiology
  • Palpitations May Occur in the Setting of Hyperventilation/Hypocapnia (Lancet, 1998) [MEDLINE]

Dermatologic Manifestations

Diaphoresis (see Diaphoresis)

• Epidemiology
  • XXXXX

Neurologic Manifestations

Carpopedal Spasm (see Carpopedal Spasm)

• Epidemiology
  • May Occur in the Setting of Hyperventilation/Hypocapnia

Confusion (see Delirium)

• Epidemiology
  • May Occur in the Setting of Hyperventilation/Hypocapnia

Dizziness/Lightheadedness (see Dizziness)

• Epidemiology
  • May Occur in the Setting of Hyperventilation/Hypocapnia

Muscle Cramps (see Muscle Cramps)

• Physiology
  • Muscle Cramps May Occur in the Setting of Hypocapnia (Lancet, 1998) [MEDLINE]

Neonatal Brain Injury

• Physiology
  • Cerebral Infarction
  • Cystic Periventricular Leukomalacia
  • Multicystic Encephalomalacia
  • Pontosubicular Necrosis
  • Reactive Hyperemia and Hemorrhage

Neuromuscular Irritability (see Myoclonus)

• Epidemiology
  • May Occur in the Setting of Hyperventilation/Hypocapnia

Paresthesias (see Paresthesias)

• Physiology
  • Paresthesias May Occur in the Setting of Hypocapnia (Lancet, 1998) [MEDLINE]
• Clinical
  • Paresthesias of the Extremities and Circumoral Area

Poorer Outcome in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)

• Epidemiology
  • In Traumatic Brain Injury, Prophylactic Hyperventilation is Associated with Worse Outcome (and is Therefore, Not Recommended)
• Physiology
  • Decreased Cerebral Oxygenation
  • Although Hyperventilation May Transiently Decrease Intracranial Pressure, it May Do so at the Expense of Cerebral Perfusion
  • Additionally, Hypocapnia May Exacerbate Secondary Brain Injury, Because Increased Cerebral Vascular Reactivity and Vasoconstriction Can Result in Decreased Regional Cerebral Blood Flow
  • Reperfusion Injury
    • Rapid Correction of Severe Hypocapnia Causes Vasodilation in Ischemic Areas

Poorer Outcome in Acute Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)

• Epidemiology
  • In Ischemic Cerebrovascular Accident, Prophylactic Hyperventilation is Associated with Worse Outcome (and is Therefore, Not Recommended)
• Physiology
  • Any Beneficial Effects of Hypocapnia on Intracranial Pressure are Likely Outweighed by the Effects of a Decreased Oxygen Supply (Due to Decreased Cerebral Perfusion)
  • Reperfusion Injury
    • Rapid Correction of Severe Hypocapnia Causes Vasodilation in Ischemic Areas

Postoperative Psychomotor Dysfunction

• Epidemiology
  • Acute Hypocapnia is Common During General Anesthesia
  • Otherwise Healthy Patients Who are Subjected to Hypocapnia During General Anesthesia Have Been Found to Have Impaired Psychomotor Function for Up to 6 Days
    • Such Effects are Especially Pronounced in Older Patients
• Clinical
  • Effects are Generally Reversible

Seizures (see Seizures)

• Epidemiology
  • Seizures May Occur in the Setting of Hypocapnia (Lancet, 1998)[MEDLINE]
• Physiology
  • Increased Neuronal Excitability, Seizure Activity, and Anaerobic Metabolism
  • Hypocapnic Potentiation of Seizure Activity, in Addition to Increasing Oxygen Demand, Augments Production of the Cytotoxic Excitatory Amino Acids Associated with Seizures
  • Hypocapnia May Also Induce Increased Neuronal Dopamine, Which May Increase the Risk of Seizures

Tetany (see Tetany)

• Epidemiology
  • Respiratory Alkalosis Can Cause Tetany Alone or Act Synergistically with Hypocalcemia to Cause Tetany (see Hypocalcemia)

Pulmonary Manifestations

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

• Physiology
  • Increased Pulmonary Capillary Permeability, Parenchymal Injury, and Depletion of Lamellar Bodies
    • These Effects are All Ameliorated by the Administration of Supplemental Carbon Dioxide
  • Hypocapnia Decreases Lung Compliance in Humans (Possibly Due to Effects on Surfactant Function)
  • Alveolar Hypocapnia Attenuates Hypoxic Pulmonary Vasoconstriction, Worsening Intrapulmonary Shunt and Systemic Oxygenation

Bronchospasm (see Bronchospasm)

• Physiology
  • Airway Hypocapnia Increases Airway Resistance by Inducing Bronchospasm and Increasing Airway Microvascular Permeability

Decreased Oxygen Delivery to Tissues (see Hemodynamics and Hypoxemia)

• Mechanisms
  • Leftward Shift of the Oxyhemoglobin Dissociation Curve (see Hypoxemia)
    • Decreases the Ability of Hemoglobin to Release Oxygen at the Tissue Level
  • Hypocapnia Results in Vasoconstriction and Decreased Perfusion of the Brain, Heart, and Peripheral Circulation
    • In Vitro Studies Indicate that Alkalemia is the Critical Determinant of Vascular Smooth Muscle Tone
      • This Similarly Occurs in the Setting of Metabolic Alkalosis (see Metabolic Alkalosis)
• Clinical
  • Lactic Acidosis (see Lactic Acidosis)

Renal Manifestations

Decreased Ionized Calcium (see Hypocalcemia)

• Physiology
  • XXXXX

Hypokalemia (see Hypokalemia)

• Physiology
  • XXXXX

Hypophosphatemia (see Hypophosphatemia)

• Physiology
  • XXXXX