Respiratory Failure

General Principles


  • Hypoxemic (type 1) respiratory failure: Occurs when normal gas exchange is seriously impaired, causing hypoxemia (arterial oxygen tension [PaO2] <60 mm Hg or arterial oxygen saturation [SaO2] <90%). Usually associated with tachypnea and hypocapnia; however, progression can lead to hypercapnia as well. Acute respiratory distress syndrome (ARDS) is an important form of hypoxemic respiratory failure caused by acute lung injury. The common end result is disruption of the alveolocapillary membrane, leading to increased vascular permeability and accumulation of inflammatory cells and protein-rich fluid within the alveolar space.
    • The ARDS Definition Task Force defined ARDS as follows1:
      • Onset within 1 week of a known clinical insult or new or worsening respiratory symptoms;
      • Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules;
      • Respiratory failure not fully explained by cardiac failure or volume overload; and
      • Impaired oxygenation with low PaO2 to fraction of inspired oxygen (FIO2) ratio (PaO2/FIO2 ≤300 mm Hg).
    • The severity of ARDS is stratified based on PaO2/FIO2.
      • Mild: 200 <PaO2/FIO2 ≤300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cm H2O
      • Moderate: 100 <PaO2/FIO2 ≤200 mm Hg with PEEP ≥5 cm H2O
      • Severe: PaO2/FIO2 ≤100 mm Hg with PEEP ≥5 cm H2O
  • Hypercapnic (type 2) respiratory failure: Occurs with acute elevation of carbon dioxide (arterial carbon dioxide tension [PaCO2] >45 mm Hg), producing a respiratory acidosis (pH <7.35).
  • Postoperative (type 3) respiratory failure: Occurs when patients develop atelectasis from pain or the use of sedatives postoperatively. In reality, this is a subset of type 1 or 2 respiratory failure; however, as this is so common, it is often classified as its own type of respiratory failure.
  • Respiratory failure from shock (type 4): Respiratory failure where the metabolic demands of the patient are too high for the respiratory system to compensate for (e.g., from sepsis or fever). Patients are often intubated in the process of resuscitation to off-load the respiratory system and decrease oxygen consumption.
  • Mixed respiratory failure: Most commonly, respiratory failure is due to multiple pathophysiologic processes that can lead to both hypercarbia and hypoxemia.


  • Hypoxemic respiratory failure (type 1): Usually is the result of the lung’s reduced ability to deliver oxygen across the alveolocapillary membrane. The severity of gas exchange impairment is determined by calculating the P(A–a) O2 gradient (A-a gradient) using the alveolar gas equation:Descriptive text is not available for this imagewhere FIO2 = the fraction of inspired oxygen, PATM = atmospheric pressure, Descriptive text is not available for this image = water vapor pressure, and R = the respiratory quotient. Hypoxemia is caused by one of the following five mechanisms:
    • Ventilation–perfusion (V/Q) mismatch: Occurs when perfusion does not compensate for a change in ventilation or vice versa (e.g., emphysema, pneumonia, pulmonary edema, pulmonary embolism). V/Q mismatch leads to an elevated A-a gradient. Administration of supplemental oxygen increases PaO2 (of note, supplemental oxygen paradoxically worsens V/Q mismatching in emphysema via reversing hypoxic vasoconstriction of pulmonary capillaries supplying poorly ventilated alveoli).
    • Shunt: Occurs when mixed venous blood bypasses lung units and enters systemic arterial circulation without receiving oxygenation. Shunts can be congenital (e.g., intracardiac shunt) or acquired (atelectasis, hepatopulmonary syndrome). Shunt leads to an elevated A-a gradient. In pure shunt, administration of supplemental oxygen does not increase PaO2. See Table 8-1 for different causes of shunt.
    • Diffusion abnormality: Occurs owing to abnormalities of the interstitium wherein the time it takes for gas equilibration is longer than the red blood cell transit time through the pulmonary capillaries (e.g., pulmonary fibrosis, pulmonary hypertension). Diffusion abnormalities lead to an elevated A-a gradient. Administration of supplemental oxygen increases PaO2.
    • Hypoventilation: Occurs owing to a decrease in minute ventilation that results in an increase in PaCO2 (see the causes of hypercapnia under “Hypercapnic respiratory failure [type 2]”) and displacement of oxygen. The A-a gradient is normal. Primary treatment is directed at correcting the cause of hypoventilation. Administration of supplemental oxygen increases PaO2.
    • Low inspired oxygen: Occurs owing to a low partial pressure of inspired oxygen (e.g., high-altitude travel). A-a gradient is normal. Administration of supplemental oxygen increases PaO2.
  • Hypercapnic respiratory failure (type 2): Primarily occurs owing to ventilatory failure, resulting in an elevated PaCO2 >45 mm Hg:Descriptive text is not available for this imagewhere CO2 = CO2 production, VA = alveolar ventilation, VE = expired total ventilation, and VD = dead space ventilation. The cause of hypercapnia is generally failure of one of the following components of the respiratory system:
    • Disorders of the central nervous system: An impaired respiratory drive causes a decreased respiratory rate (“won’t breathe”); e.g., opiate overdose, central apnea/hypoventilation, metabolic alkalosis, central nervous system (CNS) infection.
    • Disorders of anterior horn cells, peripheral nervous system, or muscles: Neuromuscular failure or muscle weakness causes decreased tidal volume (“can’t breathe”); e.g., Guillain–Barré syndrome, myasthenia gravis, amyotrophic lateral sclerosis, muscular dystrophies, myopathies.
    • Disorders of the thoracic cavity: Anatomic abnormality causes decreased tidal volume; e.g., kyphoscoliosis, morbid obesity, pleural effusions, abdominal distention, diaphragmatic injury.
    • Disorders of the airway or lung parenchyma: Lung pathology causes increased dead space; e.g., asthma, chronic obstructive pulmonary disease (COPD), severe ARDS.
    • Hypermetabolic states can cause increased CO2 production and lead to ­hypercapnia; e.g., sepsis, seizure, thyrotoxicosis, serotonin syndrome.
Table 8-1: Causes of Shunt
Pulmonary Shunts
WaterCardiogenic pulmonary edema
Acute myocardial infarction
Systolic or diastolic left ventricular failure
Mitral regurgitation or stenosis
Noncardiogenic pulmonary edema
Primary acute respiratory distress syndrome
Inhalational injury
Near drowning
Secondary acute respiratory distress syndrome
Reperfusion injury
Upper airway obstruction pulmonary edema
Neurogenic pulmonary edema
High-altitude pulmonary edema
BloodDiffuse alveolar hemorrhage
AtelectasisPleural effusion with atelectasis
Mucous plugging with lobar collapse
Cardiac shuntsPatent foramen ovale
Atrial septal defect
Ventricular septal defect
Vascular shuntsArteriovenous malformation

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