Respiratory failure is defined as inadequate gas exchange due to malfunction of one or more components of the respiratory system. There are two main types of acute respiratory failure: hypoxemic and hypercarbic. Hypoxemic respiratory failure is defined by arterial O₂ saturation <90% while receiving an increased inspired O₂ fraction. Acute hypoxemic respiratory failure can result from pneumonia, pulmonary edema (due to elevated pulmonary microvascular pressures in heart failure and intravascular volume overload, or with normal pulmonary microvascular pressures in acute respiratory distress syndrome [ARDS]), and alveolar hemorrhage. Hypoxemia results from ventilation-perfusion mismatch and intrapulmonary shunting. Lung injury in ARDS can be worsened by mechanical ventilation, and lower tidal volumes can reduce lung injury.

Hypercarbic respiratory failure is characterized by alveolar hypoventilation and respiratory acidosis. Hypercarbic respiratory failure results from decreased minute ventilation and/or increased physiologic dead space. Conditions associated with hypercarbic respiratory failure include neuromuscular diseases (e.g., myasthenia gravis), disease processes causing diminished respiratory drive (e.g., drug overdose, brainstem injury), and respiratory diseases associated with respiratory muscle fatigue (e.g., exacerbations of asthma and chronic obstructive pulmonary disease [COPD]). The primary therapeutic goal in hypercarbic respiratory failure is to reverse the underlying cause of respiratory failure. Noninvasive positive-pressure ventilation may be effective, especially in COPD exacerbations.

Two other types of respiratory failure are commonly considered: (1) perioperative respiratory failure related to lung atelectasis, which can be treated with physiotherapy, positional changes, and/or noninvasive positive-pressure ventilation; and (2) hypoperfusion of respiratory muscles related to shock, which typically improves with intubation and mechanical ventilation.