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In some conditions, such as heart failure, central apneic events are due to transient inhibition of ventilatory motor output during sleep, owing to the overlapping influences of sleep and hypocapnia. Specifically, the sleep state is associated with removal of wakefulness drive to breathe; thus, rendering ventilatory motor output dependent on the metabolic ventilatory control system, principally PaCO2. Accordingly, central apnea occurs when PaCO2 is reduced below the \u201capneic threshold\u201d. Our understanding of the pathophysiology of central sleep apnea has evolved appreciably over the past decade; accordingly, in disorders such as heart failure, central apnea is viewed as a form of breathing instability, manifesting as recurrent cycles of apnea\/hypopnea, alternating with hyperpnea. In other words, ventilatory control operates as a negative\u2014feedback closed-loop system to maintain homeostasis of blood gas tensions within a relatively narrow physiologic range, principally PaCO2. Therefore, many authors have adopted the engineering concept of \u201cloop gain\u201d (LG) as a measure of ventilatory instability and susceptibility to central apnea. Increased LG promotes breathing instabilities in a number of medical disorders. In some other conditions, such as with use of opioids, central apnea occurs due to inhibition of rhythm generation within the brainstem. This review will address the pathogenesis, pathophysiologic classification, and the multitude of clinical conditions that are associated with central apnea, and highlight areas of uncertainty.<\/jats:p>","DOI":"10.1093\/sleep\/zsac113","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T15:18:58Z","timestamp":1652368738000},"source":"Crossref","is-referenced-by-count":94,"title":["Central sleep apnea: pathophysiologic classification"],"prefix":"10.1093","volume":"46","author":[{"given":"Shahrokh","family":"Javaheri","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Sleep Medicine, Bethesda North Hospital , Cincinnati, OH , USA"},{"name":"Division of Pulmonary Critical Care and Sleep Medicine, University of Cincinnati , Cincinnati, OH , USA"},{"name":"Division of Cardiology, Department of Medicine, Ohio State University , Columbus, OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Safwan","family":"Badr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liborio Tranchida, MD, Endowed Professor of Medicine, Wayne State University School of Medicine, University Health Center , Detroit, MI , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"issue":"3","key":"2023030906592242500_","first-page":"813","article-title":"Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation","volume":"55","author":"Skatrud","year":"1983","journal-title":"J Appl Physiol Respir Environ Exerc Physiol."},{"issue":"1","key":"2023030906592242500_","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s13665-019-0221-z","article-title":"Central sleep apnea: a brief review","volume":"8","author":"Badr","year":"2019","journal-title":"Curr Pulmonol 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