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 (cardiogenic or noncardiogenic), and alveolar hemorrhage. Hypoxemia results from ventilation-perfusion mismatch and intrapulmonary shunting.

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]). In acute hypercarbic respiratory failure, PaCO2 is typically >50 mmHg. With acute-on-chronic respiratory failure, as is often seen with COPD exacerbations, considerably higher PaCO2 values may be observed. The degree of respiratory acidosis, the pt’s mental status, and the pt’s degree of respiratory distress are better indicators of the need for mechanical ventilation than a specific PaCO2 level in acute-on-chronic respiratory failure. Two other types of respiratory failure are commonly considered: (1) perioperative respiratory failure related to atelectasis, and (2) hypoperfusion of respiratory muscles related to shock.


Respiratory failure often requires treatment with mechanical ventilation to decrease the work of breathing and reverse severe hypoxemia and respiratory acidosis. There are two general classes of mechanical ventilation: noninvasive ventilation (NIV) and conventional mechanical ventilation. NIV, administered through a tightly fitting nasal or facial mask, is widely used in acute-on-chronic respiratory failure related to COPD exacerbations. NIV typically involves a preset positive pressure applied during inspiration and a lower pressure applied during expiration; it is associated with fewer complications such as nosocomial pneumonia than conventional mechanical ventilation through an endotracheal tube. However, NIV is contraindicated in cardiopulmonary arrest, severe encephalopathy, severe GI hemorrhage, hemodynamic instability, unstable coronary artery disease, facial surgery or trauma, upper airway obstruction, inability to protect the airway, and inability to clear secretions.

Most pts with acute respiratory failure require conventional mechanical ventilation via a cuffed endotracheal tube. The goal of mechanical ventilation is to optimize oxygenation while avoiding ventilator-induced lung injury. Various modes of conventional mechanical ventilation are commonly used; different modes are characterized by a trigger (what the ventilator senses to initiate a machine-delivered breath), a cycle (what determines the end of inspiration), and limiting factors (operator-specified values for key parameters that are monitored by the ventilator and not allowed to be exceeded). Three of the common modes of mechanical ventilation are described below; additional information is provided in Table 15-1.

Ventilator ModeIndependent Variables (Set by User)Dependent Variables (Monitored by User)Trigger/Cycle LimitAdvantagesDisadvantages


Tidal volume

Ventilator rate

Level of PEEP

Inspiratory flow pattern

Peak inspiratory flow Pressure limit

Peak airway pressure

Minute ventilation

Plateau pressure

Mean airway pressure

I/E ratio

Pt effort


Pressure limit

Timer backup

Pt-vent synchrony

Pt controls minute ventilation

Not useful for weaning

Potential for dangerous respiratory alkalosis due to hyperventilation

Barotrauma risk

SIMVSame as for ACMVSame as for ACMVSame as for ACMV

Timer backup is useful for weaning

Comfort from spontaneous breaths

Potential dyssynchrony


Inspiratory pressure level PEEP pressure limit

Tidal volume

Respiratory rate

Minute ventilation


Inspiratory flow Pressure limit

Assures synchrony

Good for weaning

No timer backup; may result in hypoventilation

Inspiratory and expiratory pressure levels


Tidal volume

Respiratory rate

I/E ratio

Minute ventilation


Pressure limit Inspiratory flowPt control

Discomfort and bruising from mask

Leaks are common Hypoventilation risk

Abbreviations: ACMV, assist-control mandatory ventilation; I/E, inspiration/expiration; FIO2, inspired O2; NIV, noninvasive ventilation; PEEP, positive end-expiratory pressure; PSV, pressure-support ventilation; SIMV, synchronized intermittent mandatory ventilation.
  • Assist-control ventilation: The trigger for a machine-delivered breath is the pt’s inspiratory effort, which causes a synchronized breath to be delivered. If no effort is detected over a prespecified time interval, a timer-triggered machine breath is delivered. Assist-control is volume-cycled with an operator-determined tidal volume. Limiting factors include the minimum respiratory rate, which is specified by the operator; pt efforts can lead to higher respiratory rates. Other limiting factors include the airway pressure limit, which is also set by the operator. Because the pt will receive a full tidal breath with each inspiratory effort, tachypnea due to nonrespiratory factors, such as pain, can lead to respiratory alkalosis. In pts with airflow obstruction (e.g., asthma or COPD), auto-PEEP (positive end-expiratory pressure) can develop.
  • Synchronized intermittent mandatory ventilation (SIMV): As with assist-control, SIMV is volume-cycled, with similar limiting factors. As with assist-control, the trigger for a machine-delivered breath can be either pt effort or a specified time interval. However, if the pt’s next inspiratory effort occurs before the time interval for another mandatory breath has elapsed, only their spontaneous respiratory effort (without machine support) is delivered. Thus, the number of machine-delivered breaths is limited in SIMV, allowing pts to exercise their inspiratory muscles between assisted breaths.
  • Pressure-support ventilation (PSV): PSV is triggered by the pt’s inspiratory effort. The cycle of PSV is determined by the inspiratory flow rate. Because a specific respiratory rate is not provided, this mode of ventilation may be combined with SIMV to ensure that an adequate respiratory rate is achieved in pts with respiratory depression.

Other modes of ventilation may be appropriate in specific clinical situations; for example, pressure-control ventilation is helpful to regulate airway pressures in pts with barotrauma or in the postoperative period from thoracic surgery.


General care of mechanically ventilated pts is reviewed in Chap. 4, along with weaning from mechanical ventilation. A cuffed endotracheal tube is often used to provide positive pressure ventilation with conditioned gas. A protective ventilation approach is generally recommended, including the following elements: (1) target tidal volume of ~6 mL/kg of ideal body weight; (2) avoid plateau pressures >30 cm H2O; (3) use the lowest fraction of inspired oxygen (FIO2) to maintain arterial oxygen saturation ≥90%; and (4) apply PEEP to maintain alveolar patency while avoiding overdistention. This approach may result in a permissible degree of hypercapnia. After an endotracheal tube has been in place for an extended period of time, tracheostomy should be considered, primarily to improve pt comfort, reduce needs for sedative medications, and provide a more secure airway. No absolute time frame for tracheostomy placement exists, but pts who are likely to require mechanical ventilatory support for >2 weeks should be considered for a tracheostomy.

A variety of complications can result from mechanical ventilation. Barotrauma—overdistention and damage of lung tissue—can cause pneumomediastinum, subcutaneous emphysema, and pneumothorax. Ventilator-related pneumothorax typically requires treatment with tube thoracostomy. Ventilator-associated pneumonia is a major complication in intubated pts; common pathogens include Pseudomonas aeruginosa and other gram-negative bacilli, as well as Staphylococcus aureus.

For a more detailed discussion

For a more detailed discussion, see Celli BR: Mechanical Ventilatory Support, Chap. 323, p. 1740; and Kress JP, Hall JB: Approach to the Patient with Critical Illness, Chap. 321, p. 1729, in HPIM-19.

Respiratory Failure is a sample topic from the Harrison's Manual of Medicine.

To view other topics, please or purchase a subscription.

Harrison’s Manual of Medicine 19th edition provides 600+ internal medicine topics in a rapid-access format. Download Harrison’s App to iPhone, iPad, and Android smartphone and tablet. Learn more.


TY - ELEC T1 - Respiratory Failure ID - 623068 PB - Harrison's Manual of Medicine UR - ER -