Respiratory Failure-Part 2


Acute Ventilatory Failure

  • Acute Ventilatory Failure Exists when pCO2 Increases Enough Above the Patient’s Baseline pCO2 to Produce a Clinically Significant Decrease in pH (i.e. Acidemia)
    • Note that the Absolute pCO2 Value Alone Does Not Necessarily Indicate the Presence of Acute Ventilatory Failure (as Increased pCO2 Values Can Also Be Observed as Part of Physiologic Respiratory Compensation in Metabolic Alkalosis and in Chronic Hypoventilation)
    • The Normal Physiologic Response to Hypercapnia is Renal Reabsorption of Bicarbonate (a Process Which Usually Takes a Period of Days)
  • Pre-Existing Chronic Hypoventilation
    • In the Special Clinical Context of a Patient with Pre-Existing Chronic Hypercapnia (Chronic Hypoventilation), the Rise in pCO2 Above the Patient’s Baseline Must Be Large Enough to Produce a Clinically Significant Decrease in pH to Be Considered Concomitant Acute Ventilatory Failure
    • In Some Patients with Pre-Existing Chronic Hypoventilation (with Chronically Elevated Serum Bicarbonate), an Acute Decrease in the Serum Bicarbonate (Due to an Unrelated Metabolic Acidosis) May Be Sufficient to Produce Acidemia without Technically Being Due to Concomitant Acute Ventilatory Failure
      • In Such Cases, the Clinical Context of the Combined Acid-Base Disturbance is Crucial to Correctly Interpret the Respiratory Component
      • Example: 50 y/o Morbidly Obese Male with Prior History of Obstructive Sleep Apnea (OSA) and Associated Chronic Hypoventilation (Baseline ABG: ph 7.40, pCO2 60 and Serum Bicarbonate: 36), Now Presents with Superimposed Diabetic Ketoacidosis (Current ABG: pH 7.22, pCO2 60, Serum Bicarbonate: 24)
        • In This Example, without a Prior ABG (Indicating the Presence of Chronic Hypoventilation), the Patient Might Be Mistakenly Interpreted to Have Acute Ventilatory Failure



  • Arterial Blood Gas (ABG) (see Arterial Blood Gas)
    • Arterial Blood Gas is an Essential Diagnostic Procedure in Respiratory Failure, as it Provides Information Regarding the Arterial pH, Arterial pCO2, Arterial pO2, and the Serum Bicarbonate
  • Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)
    • Pulmonary Function Tests are Useful to Diagnose Underlying Obstructive and Restrictive Lung Disease
  • Pulse Oximetry (see Pulse Oximetry)
    • Pulse Oximetry Only Measures Oxygen Saturation and Does Not Provide the pH and pCO2 (the Latter Two of Which are Required to Diagnose Acidemia and Hypercapnia)
  • End-Tidal Carbon Dioxide (Capnography) (see Capnography)
    • Capnography May Be Used to Diagnose Hypercapnia
  • Transcutaneous Carbon Dioxide
    • Transcutaneous Carbon Dioxide Measurement May Be Used to Diagnose Hypercapnia
  • Chest X-Ray (see Chest X-Ray)
    • Chest X-Ray is Standardly Used to Diagnose Underlying Lung Disease
  • Chest CT (see Chest Computed Tomography)
    • Chest CT is Standardly Used to Diagnose Underlying Lung Disease
  • Thyroid Function Tests (TFT’s) (see Thyroid Function Tests)
    • Thyroid Function Tests areUseful to Diagnose Both Hypothyroidism and Hyperthyroidism (see Hypothyroidism)

Diagnosis of Chronic Type II-Hypoxemic, Hypercapnic Respiratory Failure

  • Chemosensitivity Disorders
    • ABG: normal A-a gradient
    • PFT’s: normal spirometry and lung volumes (usually), normal MIP+MEP
  • Neuromuscular Disease
    • ABG: normal A-a gradient
    • PFT’s: restriction, decreased MIP+MEP
  • Upper Airway/Lower Airway/Chest Wall Disease
    • ABG: increased A-a gradient
    • PFT’s: restriction or obstruction, normal MIP+MEP

Clinical Manifestations

Practical Daily Assessment of Respiratory Failure

Acute Type II-Hypoxemic, Hypercapnic Respiratory Failure

Upper Airway/Proximal Tracheal Airway Obstruction

  • Characteristics of Upper Airway/Tracheal Obstruction
    • Role of Airway Diameter: progressive/gradual airway obstruction can be tolerated until upper airway/tracheal diameter reaches approximately 5-6 mm
    • Role of the Location of Airway Obstruction: impacts whether inspiratory and/or expiratory flows are more adversely affected by the obstructing lesion
      • Variable Extrathoracic Upper Airway Obstruction: adversely affects predominantly inspiratory flow (as inspiratory negative intraluminal pressures exacerbate the inspiratory airway narrowing, while expiratory positive intraluminal pressures splints the obstruction open)
        • Example: vocal cord paralysis -> inspiratory stridor with no expiratory obstruction
      • Variable Intrathoracic Upper Airway Obstruction: adversely affects predominantly expiratory flow (as inspiratory negative pressures decrease the inspiratory airway narrowing, while expiratory positive intrapleural pressures exacerbate the airway obstruction)
        • Example: tracheomalacia -> expiratory worsening of airway obstruction
      • Fixed Upper Airway Obstruction: adversely affects both inspiratory and espiratory flows
    • Complication by Negative Pressure Pulmonary Edema: negative pressure pulmonary edema may occur in cases with critical, acute upper airway obstruction (such as laryngospasm)

Clinical Manifestations of Inspiratory Muscle Fatigue

  • Patients with Acute Respiratory Failure Typically Progress Through a Defined Sequence of Clinical Stages (Am J Med, 1982) [MEDLINE]
    • Study Involved 12 Postextubation Patients with Intact Ventilatory Drive, But Decreased Ventilatory Output
    • 6 of the Patients Manifested EMG Evidence of Inspiratory Muscle Fatigue
    • Importantly, the Stages were of Variable Duration and Some Patients Skipped Some Stages Altogether
    • Main Conclusion is that Respiratory Arrest is Typically Heralded by Preceding Clinical Events

Clinical Manifestation of Hypoxemia (see Hypoxemia)

  • General Comments
    • Hypoxemia May Be Asymptomatic, Since Compensatory Mechanisms (Such as Increase in Cardiac Output, Increase in Hemoglobin) May Act to Maintain Tissue Oxygen Delivery and Avoid Hypoxic End-Organ Dysfunction
    • In Contrast, Hypoxia is Defined as a State of Impaired Tissue Oxygenation and is Always Symptomatic (See Definition Above)
  • 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
    • 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
  • Pulmonary Manifestations
  • Other Manifestations
    • Clubbing (see Clubbing): may occur with chronic hypoxemia
    • Cyanosis (see Cyanosis)
    • Polycythemia (see Polycythemia): may occur with chronic hypoxemia

Clinical Manifestations of Hypercapnia

  • General Comments
    • Normal (Normocapnic) Patients Generally Do Not Develop Altered Mental Status Until the pCO2 Exceeds 75-80 mm Hg
    • Chronically Hypercapnic Patients Do Not Develop Altered Mental Status Until the pCO2 Exceeds 90-100 mm Hg
  • Mild-Moderate Hypercapnia (Which Develops Gradually)
    • Anxiety (see Anxiety)
    • Decreased Alveolar pO2
    • Dyspnea (see Dyspnea)
      • Mechanisms
        • Hypercapnia-Associated Decreased Diaphragmatic Contractility: this decrease in diaphragmatic contractility may contribute further to the development of respiratory failure
        • Hypercapnia-Associated Decreased Myocardial Contractility
        • Hypercapnia-Associated with Acidemia (with Stimulation of Central and Peripheral Chemoreceptors)
        • Hypercapnia-Induced Increase in Respiratory Drive
    • Excessive Daytime Somnolence (see Excessive Daytime Somnolence)
    • Headache (see Headache)
    • Respiratory Acidosis (see Respiratory Acidosis)
  • Moderate (or Rapidly Developing) Hypercapnia
    • Both Stimulated and Depressed Cardiovascular System
      • Via Competing Effects to Decrease Systemic Vascular Resistance (SVR), Increase Cardiac Output (CO), etc
      • Hypercapnia Usually Results in Pulmonary Hypertension and an Increase in Cardiac Output (CO) Though
    • Confusion/Delirium (see Delirium)
    • Depression (see Depression)
    • Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)
      • Hypercapnia Causes Cerebral Vasodilation with Increased Cerebral Blood Flow
    • Obtundation/Coma (“CO2 Narcosis”) (see Obtundation/Coma)
      • Acute Hypercapnia Initially Causes Increased Respiratory Drive with Hyperventilation (Anesthesiology, 1960) [MEDLINE] (NEJM, 1984) [MEDLINE]
        • Subsequently, There is Development of Decreased Respiratory Drive, Leading to Worsening Hypercapnia with Depressed Mental Status (“CO2 Narcosis”)
        • These Later Effects are Mediated Via Increased Brain Glutamine, Increased Brain γ-Aminobutyric Acid (GABA), Decreased Brain Glutamate, and Decreased Brain Aspartate
    • Paranoia (see Paranoia)
    • Rightward Shift of the Oxyhemoglobin Dissociation Curve (Due to Hypercapnia and/or Acidemia): this results in increased oxygen release at the tissues (Bohr Effect)
      • Decreased Hemoglobin Affinity for Oxygen in the Lungs (with Decreased Oxygen Loading) and Increased Oxygen Unloading at the Tissues (Bohr Effect)
  • Severe Hypercapnia
    • Altered Action of Pharmacologic Agents
      • Due to Intracellular Acidosis, Not Due to the Hypercapnia Itself
    • Anesthesia
      • Observed with pCO2 >200 mm Hg
    • Asterixis (see Asterixis)
    • Decreased Renal Blood Flow
      • Observed with pCO2 >150 mm Hg
    • Leakage of Intracellular Potassium
      • Observed with pCO2 >150 mm Hg
    • Increased Intracranial Pressure (ICP) with Papilledema (see Increased Intracranial Pressure)
      • 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)
    • Myoclonus (see Myoclonus)
    • Peripheral Venodilation with Hypotension (see Hypotension)
    • Seizures (see Seizures)

Clinical Recognition of Respiratory Failure

  • Clinicians are Generally Poor at Recognizing the Clinical Signs of Respiratory Failure
    • In a Study of Clinical Assessment of Patients Requiring CPR, Physicians were Poor at Recognizing a Lack of Respiratory Effort (Ann Emerg Med, 1999) [MEDLINE]
      • Approximately 89.7% of Emergency Personnel Accurately Recognized Failure of Respiratory Effort
      • Approximately 84.5% of Physicians Accurately Recognized Failure of Respiratory Effort
      • Approximately 78.4% of Medical Students Accurately Recognized Failure of Respiratory Effort
    • In a Study of Automated Graphical Assessment of Respiratory Activity During Endoscopy, Visual Recognition of Changes Respiratory Activity (Which Might Precede the Development of Hypoxemia) was Poor (Gastrointest Endosc, 2002) [MEDLINE]
      • Capnography was an Excellent Indicator of Respiratory Rate, as Compared to Auscultation (r = 0.967, p < 0.001)
      • Fifty Four Episodes of Apnea or Disordered Respiration Occurred in 28 Patients (Mean Duration: 70.8 sec)
      • Only 50% of the Apnea or Disordered Respiration Episodes were Detected by Pulse Oximetry and None were Detected by Visual Assessment (p < 0.0010)

Chronic Type II-Hypoxemic, Hypercapnic Respiratory Failure

  • Consequences of Hypoventilation-Associated Sleep-Disordered Breathing
    • Morning Headache: due to cerebral vasodilation
    • Sleep Disruption: due to cerebral vasodilation
    • Daytime Somnolence: due to cerebral vasodilation
    • Confusion: due to cerebral vasodilation
    • Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension)
  • Consequences of Hypoventilation-Associated Hypercapnia
    • Metabolic Compensation: elevated bicarbonate
  • Consequences of Hypoventilation-Associated Hypoxemia


Site of Care

  • Criteria for Intensive Care Unit Admission in Patients with Respiratory Failure: no established guidelines exist
    • Need for Endotracheal Intubation/Mechanical Ventilation: this is the only criterion which mandates ICU admission
    • Altered Mental Status
    • Neuromuscular Disease (Particularly with Vital Capacity <1L)
    • Severe Acidosis (pH < 7.25)
    • Hemodynamic Instability
    • Need for Active Titration of Supplemental Oxygen
    • Need for Close Monitoring of Noninvasive Positive-Pressure Ventilation (NIPPV)
  • Carefully Selected Patients with Respiratory Failure May Be Cared for Outside of the Intensive Care Unit (For Example, on Stepdown Units
    • Patients with Do Not Resuscitate (DNR) Status Who Require Palliative Noninvasive Positive-Pressure Ventilation

Supplemental Oxygen Therapy (see Oxygen)


  • First Priority is to Ensure Adequate Oxygenation
  • However, Provider Should Judiciously Use Supplemental Oxygen in Patients with Type II-Hypoxemic, Hypercapnic Respiratory Failure: generally titrated to achieve SpO2 90-94%
    • Risk Factors for Oxygen-Induced Worsening of Hypercapnia in Chronically Hypercapnic Patients with COPD (Am J Med, 1978) [MEDLINE]
      • History of Baseline Hypercapnia with/without Oxygen Administration
      • Low Initial pH (<7.33) and/or Low Arterial pO2
    • Mechanisms by Which Supplemental Oxygen May Worsen Hypercapnia
      • Hyperoxia Blunts Hypoxic Respiratory Drive (Lancet, 1977) [MEDLINE]
      • Hyperoxia Causes Oxygen-Induced Bronchodilation in Poorly-Perfused Lung Units, Worsening V/Q Mismatch and Increasing Physiologic Dead Space
      • Haldane Effect Oxyhemoglobin Binds Carbon Dioxide Less Avidly than Deoxyhemoglobin, Increasing Blood Carbon Dioxide Levels
    • Examples of Patients in Whom Supplemental Oxygen Should Be Used Judiciously
      • Chronic Obstructive Pulmonary Disease (COPD) with Chronic Hypercapnia (i.e. Chronic Hypoventilation) (see Chronic Obstructive Pulmonary Disease)
      • Neuromuscular Disease with Chronic Hypercapnia (Mayo Clin Proc, 1995) [MEDLINE]

Oxygen Delivery Methods

  • Nasal Cannula (NC)
  • High-Flow Nasal Cannula (HFNC)
  • Ventimask
  • Rebreather Mask
  • Non-Rebreather Mask
  • Transtracheal Catheter
  • Noninvasive Mechanical Ventilation (NIPPV) (see Noninvasive Mechanical Ventilation)
  • Bag-Valve-Mask Ventilation (see Airway Management)
    • May Be Used Temporarily for Hypoxemia and/or Hypercapnia, Typically Prior to Endotracheal Intubation with Invasive Mechanical Ventilation
  • Endotracheal Intubation with Invasive Mechanical Ventilation

Management of Pharmacologic Respiratory System Depressants

  • Discontinuation of General Anesthesia (see General Anesthesia)
  • Discontinuation of Opiates (see Opiates)
  • Discontinuation of Sedatives
  • Reversal of Opiates (see Opiates)
    • Opiate Agents (Selected)
    • Reversal Agentes
  • Reversal of Paralytic Agents
  • Reversal of Benzodiazepines
    • Benzodiazepines (Selected) (see Benzodiazepines)
    • Reversal Agents
    • Specific Treatment of Patients with Respiratory Depressant Intoxication
      • Specific Antidote to Intoxication
      • Gastric Decontamination Techniques: may be used in select sedative overdoses (and generally only in an intubated patient, where the risk of aspiration has been minimized

Treat Other Underlying Etiology (if Present)


  • Myasthenia Gravis (see Myasthenia Gravis)
    • Corticosteroids, Plasmapheresis, and Intravenous Immunoglobulin (IVIG) (see Myasthenia Gravis)
  • Severe Hypokalemia (see Hypokalemia)
    • Potassium Replacement: in patients who require significant replacement over a shorter period of time, central venous catheter (CVC) may be required

Respiratory Stimulants

  • General Comments
    • These Agents Have No Proven Benefit in the Management of Acute/Chronic Type II-Hypoxemic, Hypercapnic Respiratory Failure: no longer recommended
  • Agents

Heliox (see Heliox)

Bag-Valve-Mask Ventilation (see Airway Management)

  • Indications
    • Temporary Ventilation While Preparing for Endotracheal Intubation with Invasive Mechanical Ventilation
    • Temporary Ventilation While Treating an Etiology Which is Expected to Rapidly Resolve (Such as Opiate Intoxication)

Noninvasive Positive-Pressure Ventilation (NIPPV) (see Noninvasive Positive-Pressure Ventilation)

  • Clinical Indications (Selected)

Endotracheal Intubation with Invasive Mechanical Ventilation (see Airway Management, Endotracheal Intubation, and Mechanical Ventilation-General)

Prone Ventilation

Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO) (see Venovenous Extracorporeal Membrane Oxygenation)

Management of Specific Disorders

  • Specific Management of Hypothyroidism (see Hypothyroidism)
    • Hormone Replacement
    • Evaluation/Treatment of Concomitant Sleep-Disordered Breathing/Obstructive Sleep Apnea (OSA)
    • Evaluation/Treatment of Concomitant Congestive Heart Failure (CHF): if present
  • Specific Management of Obesity-Hypoventilation Syndrome (see Obesity Hypoventilation Syndrome)
    • Evaluation/Treatment of Concomitant Sleep-Disordered Breathing/Obstructive Sleep Apnea (OSA): if present
      • In Retrospective Study of 54 Morbidly Obese Patients (Mean BMI: 44), 87% of Whom Had Concomitant OSA, Chronic Nocturnal Nasal NIPPV Improved Gas Exchange, Dyspnea, and Sleepiness (Chest, 2005) [MEDLINE]
    • Evaluation/Treatment of Concomitant Congestive Heart Failure (CHF): if present
    • Weight Loss
  • Management of Chest Trauma
    • In Subset of Chest Trauma Patients with Persistent Hypoxemia, NIPPV Has Been Demonstrated to Decrease the Need for Intubation and Shorten Hospital Length of Stay (Chest, 2010) [MEDLINE]