Chest
Volume 131, Issue 2, February 2007, Pages 595-607
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Postgraduate Education Corner: Contemporary Reviews in Sleep Medicine
Central Sleep Apnea: Pathophysiology and Treatment

https://doi.org/10.1378/chest.06.2287Get rights and content

Abstract

Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime breathing disturbances can lead to important comorbidity and increased risk of adverse cardiovascular outcomes. There are several manifestations of CSA, including high altitude-induced periodic breathing, idiopathic CSA, narcotic-induced central apnea, obesity hypoventilation syndrome, and Cheyne-Stokes breathing. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. This brief review summarizes the underlying physiology and modulating components influencing ventilatory control in CSA, describes the etiology of each of the various forms of CSA, and examines the key factors that may exacerbate apnea severity. The clinical implications of improved CSA pathophysiology knowledge and the potential for novel therapeutic treatment approaches are also discussed.

Section snippets

Chemical Control of Breathing

Chemoreceptor inputs (medullary neurons responding to CO2via shifts in H+concentration and peripherally at the carotid body via Pao2and Paco2) play a key role in modulating ventilation. The ventilatory output to a given change in Pao2or Paco2(“chemosensitivity”) can vary greatly between individuals and with disease status. Highly sensitive chemoresponses can place an individual at risk for unstable breathing patterns because these individuals “overrespond” to small changes in chemical stimuli.

Other Important Components That Regulate Breathing

In addition to chemical control, there are several other important homeostatic feedback mechanisms that regulate ventilation to maintain gas exchange within tightly controlled limits. Afferent information from Golgi tendon organs and muscle spindles from the chest wall and respiratory muscles also play an important role in regulating the rate and depth of breathing. During wakefulness nonrespiratory behavioral influences are also capable of modulating ventilatory activity. Examples include

Transition to Sleep

The transition from wakefulness to sleep is an inherently unstable period in terms of cardiorespiratory control.12, 13With sleep onset, there is a loss of the wakefulness stimulus and behavioral influences.14In addition, several respiratory control mechanisms are down regulated at sleep onset. Upper airway (UA) dilator and respiratory pump muscle tone is reduced, and there is an accompanying increase in UA resistance leading to a reduction in ventilation for a given level of drive.15, 16

Manifestations of CSA

CSA syndromes can be broadly classified into two groups according to the wakefulness CO2levels (hypercapnic vs nonhypercapnic), although the prevailing abnormalities in these two groups can be quite disparate.31These underlying physiologic differences contribute to the varying CSA etiologies.

Hypoxia

While deviations in chemosensitivity from normality may contribute to the pathophysiology of the various forms of CSA, there is evidence to suggest that the depressive effects of hypoxia may further increase disease severity. The different forms of CSA result in varied magnitude and duration of hypoxia, which are likely important determinants for the possible development of hypoxia-induced depressive effects. ICSA and CSB are characterized by intermittent hypoxia during sleep, while OHS is

Therapeutic Interventions

Given the range of pathophysiologic factors contributing to the varied forms of CSA (summarized schematically inFig 5), treatment approaches also vary considerably. Gradual dose reduction of opioid medication may improve high-dose narcotic-induced CSA (Fig 2,bottom,B). Weight loss is likely to lead to improvement of SDB in patients with OHS.46In practice, both these goals may be difficult to achieve. However, surgical weight loss may be an effective alternative option for morbidly obese

Summary

In summary, CSA encompasses a wide range of distinct yet interrelated forms of unstable breathing that can lead to substantial comorbidity and increased risk of adverse cardiovascular outcomes. The underlying pathophysiology and the prevalence of the various forms of CSA varies greatly. Given the range of pathophysiologic factors contributing to the varied forms of CSA, treatment approaches also vary considerably. NIV remains a major treatment approach for many patients. While short-term

Acknowledgments

The authors are grateful to Dr. Nick Antic and Dr. Rajeev Ratnavadivel of the Adelaide Institute for Sleep Health for providing polysomnography examples of narcotic-induced CSA and CSB, respectively.

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    Dr. Eckert is a recipient of the Thoracic Society of Australia and New Zealand/Allen and Hanbury's respiratory research fellowship. Dr. Jordan is supported by a grant from the American Heart Association. Dr. Malhotra is funded by National Institute of Aging, Beeson Award (from 2004 to 2008), “Aging Influence on the Development of Sleep Apnea” (AG024837–01), National Institutes of Health (from 2004 to 2008), “Sleep Apnea and Obesity: Cardiovascular Risk Assessment” (RO1-HL73146–01), and National Institutes of Health, Specialized Center of Research Project 1.

    Drs. Eckert, Jordan, and Merchia have no conflict of interest to declare in relation to the subject matter contained within this review article. Dr. Malhotra is a consultant for Respironics, Restore Medical, and Inspiration Medication), receiving < $20,000 per year from each of these companies. He has received an unrestricted research grant from Respironics for $100,000 to study the cardiovascular complications of sleep apnea. He has received an industry grant from Restore Medical for $100,000 to develop a computational model of the upper airway.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml

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