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Updated: Apr 20, 2026

A Model to Simulate Clinically Relevant Hypoxia in Humans
Published on: December 22, 2016
Hypoventilation syndromes
Amanda J Piper1, Brendon J Yee
1Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown; Woolcock Institute of Medical Research, University of Sydney, NSW, Australia.
Abstract:
In patients with impaired inspiratory muscle function or altered respiratory system mechanics, an imbalance between load and capacity can arise. The ventilatory control system normally compensates for this by increasing drive to maintain adequate alveolar ventilation levels, thereby keeping arterial CO2 within its normal range. To reduce work of breathing, a pattern of reduced tidal volume and increased respiratory rate occurs. This pattern itself may eventually reduce effective ventilation by increasing dead space ventilation. However, the impact of sleep on breathing and its role in the development of diurnal respiratory failure is often overlooked in this process. Sleep not only reduces respiratory drive, but also diminishes chemoresponsiveness to hypoxia and hypercapnia creating an environment where significant alterations in oxygenation and CO2 can occur. Acute increases in CO2 load especially during rapid eye movement sleep can initiate the process of bicarbonate retention which further depresses ventilatory responsiveness to CO2. Treatment of hypoventilation needs to be directed toward factors underlying its development. Nocturnal noninvasive positive pressure therapy is the most widely used and reliable strategy currently available to manage hypoventilation syndromes. Although this may not consistently alter respiratory muscle strength or the mechanical properties of the respiratory system, it does appear to reset chemosensitivity by reducing bicarbonate, resulting in a more appropriate ventilatory response to CO2 during wakefulness. Not only is diurnal hypoventilation reduced with noninvasive ventilation, but quality of life, functional capacity and survival are also improved. However, close attention to how therapy is set up and used are key factors in achieving clinical benefits.
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