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  • Acute-on-chronic respiratory failure (ACRF) occurs when often minor, although commonly multiple, insults cause acute deterioration in a patient with chronic respiratory insufficiency and is associated with a significant morbidity and mortality burden.

  • ACRF is usually seen in patients known to have severe chronic obstructive pulmonary disease or interstitial lung disease, including idiopathic pulmonary fibrosis, but occasionally it manifests as cryptic respiratory failure or postoperative ventilator dependence in a patient with no known lung disease.

  • The wide variety of causes of ACRF may be compartmentalized into causes of incremental load, diminished neuromuscular competence, or depressed drive, superimposed on a limited ventilatory reserve.

  • Intrinsic positive end-expiratory pressure (PEEPi) is a central contributor to the excess work of breathing in patients with ACRF.

  • The most important therapeutic interventions are administration of oxygen, bronchodilators, and corticosteroids, heated high-flow nasal cannula oxygen, and noninvasive positive-pressure ventilation (NPPV). NPPV can be used in most patients to avoid intubation and has been shown to improve survival.

  • The decision to intubate a patient with ACRF benefits from clinical judgment and a bedside presence. Hypotension, delirium, and severe alkalemia commonly complicate the immediate peri-intubation course, but they are usually avoidable. However, delaying intubation when NPPV is ineffective may worsen outcomes.

  • Ventilator settings should mimic the patient’s breathing pattern with a modest respiratory rate (eg, 20/min) and small tidal volume (eg, 450 mL); some PEEP (eg, 5 cm H2O) should be added.

  • Prevention of complications such as gastrointestinal hemorrhage, venous thrombosis, and nosocomial infection is a crucial component of the care plan.

  • The key to liberating the patient from the ventilator is to increase neuromuscular competence while reducing respiratory system load. Early mobilization and cautious supplemental enteral nutrition can play a key role.

  • In selected patients, extubation to NPPV despite failed spontaneous breathing trials reduces ventilator and ICU days and further improves survival.


Chronic lung disease (CLD)-related mortality remains persistently high and was the third leading cause of age-adjusted mortality globally in 2017: ∼545 million people had a chronic respiratory disease, an increase of ∼40% compared with 1990.1 Chronic obstructive pulmonary disease (COPD) accounts for more than half of global CLD-related mortality. Globally, COPD was the third leading cause of death after ischemic heart disease and stroke in 2019, accounting for ∼40 deaths per 100,000 population.2 In the United States, encouraging epidemiological trends have been reported over the last decade for chronic lower respiratory disorder-related mortality, now the fourth most common cause of age-adjusted mortality behind cardiovascular diseases, neoplasms, and trauma.3 As a lagging indicator of declining tobacco-use, age-adjusted COPD mortality declined from 73 per 100,000 in 2004 to 67.4 per 100,000 of the United States population in 2019, accounting for ∼6.7% of recorded death in the year prior to the COVID-19. However, a concerning increasing mortality rate was reported among female African-Americans, pointing to important disparities in exposure risk, ...

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