Crossing the apnoeic threshold: Causes and consequences

John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin, 1300 University Avenue, Rm. 4245 MSC, Madison, WI, USA.
Experimental Physiology (Impact Factor: 2.67). 02/2005; 90(1):13-24. DOI: 10.1113/expphysiol.2004.028985
Source: PubMed


This brief review addresses the characteristics, lability and the mechanisms underlying the hypocapnic-induced apnoeic threshold which is unmasked during NREM sleep. The role of carotid chemoreceptors as fast, sensitive detectors of dynamic changes in CO2 is emphasized and placed in historical context of the long-held debate over central vs. peripheral contributions to CO2 sensing and to apnoea. Finally, evidence is presented which points to a significant role for unstable, central respiratory motor output as a significant contributor to upper airway narrowing and obstruction during sleep.

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    • "Transient cessations in breathing rhythm (apneas), or in breath amplitude (hypopneas), sufficient to cause significant arterial hypercapnia and hypoxemiam activate a feedback circuit (loop gain) that is stable unless the PaCO 2 thresholds of apnoea and of eupnoea are very close: in this condition the loop gain becomes unstable and patients are predisposed to repetitive episodes of apnoea/hypopnea [54] [55] [56] [57] [58]. If breathing efforts persist, the SDB is classified as ''obstructive'' – OSA; in absence of brain stem respiratory motor output it is instead classified as ''central'' sleep apnea – CSA. "
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    ABSTRACT: Sleep disordered breathings (SDB) worsens the clinical prognosis of stroke patients. Continuous positive airway pressure (CPAP) is a promising effective treatment. Unfortunately, not all patients are compliant with CPAP, suggesting that it is not appropriate for all patients with obstructive sleep apnoea (OSA) after stroke. People with the highest likelihood of benefiting have to be identified. We present a classification of cases with stroke and SDB to be adopted in order to identify the best responders to CPAP treatment. We propose to classify patients in four subgroups: 1. patients who terminate the apnoea by arousing from sleep; these cases are those affected either by an anatomical or a functional obstruction of upper airways that may precede or are the consequence of stroke; 2. cases that alternate OSA to central sleep apnoea (CSA) cause of an altered loop gain; 3. cases in whom ischemic damages have altered the sleep microstructure (CAP); 4. cases that manifest a CSA as the direct consequence of stroke on the central neuronal drive to breath. So far, no study has investigated the consequences of stroke on sleep microstructure. In order to better elucidate these relationships, when reviewing the PSG tracings of stroke patients, the microstructure of sleep should be systematically analysed.
    Full-text · Article · Aug 2014 · Medical Hypotheses
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    • "Behavioral influences and neurocompensatory responses strongly inhibit apnea, even in the presence of marked decreases in PaCO2 during wakefulness, but this is not the case during sleep. Indeed, during sleep, all individuals are susceptible to breathing cessation when PaCO2 falls below a critical threshold known as the apnea threshold.13–15 The apnea threshold is usually 2–6 mmHg below the eucapnic sleeping PaCO2 level. "
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    ABSTRACT: Complex sleep apnea syndrome (CompSAS) is a distinct form of sleep-disordered breathing characterized as central sleep apnea (CSA), and presents in obstructive sleep apnea (OSA) patients during initial treatment with a continuous positive airway pressure (CPAP) device. The mechanisms of why CompSAS occurs are not well understood, though we have a high loop gain theory that may help to explain it. It is still controversial regarding the prevalence and the clinical significance of CompSAS. Patients with CompSAS have clinical features similar to OSA, but they do exhibit breathing patterns like CSA. In most CompSAS cases, CSA events during initial CPAP titration are transient and they may disappear after continued CPAP use for 4~8 weeks or even longer. However, the poor initial experience of CompSAS patients with CPAP may not be avoided, and nonadherence with continued therapy may often result. Treatment options like adaptive servo-ventilation are available now that may rapidly resolve the disorder and relieve the symptoms of this disease with the potential of increasing early adherence to therapy. But these approaches are associated with more expensive and complicated devices. In this review, the definition, potential plausible mechanisms, clinical characteristics, and treatment approaches of CompSAS will be summarized.
    Full-text · Article · Jul 2013 · Patient Preference and Adherence
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    • "More specifically, enhancement of peripheral and possibly central chemoreflex sensitivity , particularly during wakefulness (see Point A – Fig. 2), would likely induce profound hypocapnia, resulting in carbon dioxide levels that are significantly below the apneic threshold. This enhanced sensitivity, which might be coupled with a reduction in the carbon dioxide reserve [i.e. the difference between the carbon dioxide value that demarcates the apneic threshold and normal resting values – see Fig. 2 in (Dempsey, 2005) or Fig. 4 in (Mateika and Narwani, 2009) for additional clarification of carbon dioxide reserve if required], could ultimately result in a prolonged central and obstructive apnea during sleep because of the time required for carbon dioxide to build and exceed the apneic threshold . Alternatively, if respiratory muscle activity was enhanced by a mechanism that was independent of chemoreflex input (see Respiratory Plasticity for this discussion) and continued to persist in the presence of hypocapnia (Point B – Fig. 1), the development of a central apnea could be prevented. "
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    ABSTRACT: This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea.
    Full-text · Article · Apr 2013 · Respiratory Physiology & Neurobiology
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