Materiały źródłowe

• #1 Central Sleep Apnea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK578199/

  Central sleep apnea (CSA) is characterized by transient diminution or cessation of the respiratory rhythm generator located within the pontomedullary region of the brain. […] The pathophysiology of CSA can be variable due to its temporal relation with different comorbidities. Depending on the underlying medical condition, hypoventilation or hyperventilation with resultant hypocapnia below an apneic threshold is an integral mechanism that reinforces the evolution of central apnea. […] The enhanced chemosensitivity to arterial carbon dioxide levels during sleep results in overall increased loop gain, leading to ventilatory instability and CSA, especially in patients with HF. […] Regardless of the underlying condition or mechanism, once a cycle has started, it perpetuates the next one, resulting in repetitive episodes of hypoxia and irregular breathing, ultimately leading to upper airway narrowing.

• #2 Central Sleep Apnea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2287191/

  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. […] While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. […] The prevalence of CSA varies greatly between the various forms of CSA. […] However, as will be discussed, considerable overlap exists in the pathogenesis and pathophysiology of obstructive and central apnea, making this distinction somewhat difficult at times. […] The overlap between CSA and OSA suggests that common mechanistic traits are likely involved. […] Typically, CSA is considered to be the primary diagnosis when 50% of apneas are scored as central in origin (ie, 10 s cessation of breathing in the absence of respiratory effort); however, such thresholds are clearly arbitrary.

• #3 Central Sleep Apnea in Adults: An Interdisciplinary Approach to Diagnosis and Management—A Narrative Review

  https://www.mdpi.com/2077-0383/14/7/2369

  Central sleep apnea (CSA) is a heterogeneous group of sleep-related breathing disorders characterized by intermittent absence of respiratory effort during sleep. CSA results from impaired neurological signaling from the respiratory centers to the respiratory muscles, leading to airflow cessation for at least 10 s. […] This review outlines the pathophysiology of CSA, emphasizing ventilatory instability and brainstem dysfunction as key mechanisms. […] The mechanism of CSA production, unlike OSA (which presents respiratory effort), consists in the lack of transmission of nervous impulses from the respiratory centers to the respiratory muscles to trigger periodic breathing. […] Two major pathophysiological events cause CSA: (1) Ventilatory instability; (2) Depression of brainstem respiratory-centers or chemoreceptors.

• #4 Central Sleep Apnea

  https://ouci.dntb.gov.ua/en/works/4grdZEEE/

  Neurophysiologically, central apnea is due to a temporary failure in the pontomedullary pacemaker generating breathing rhythm. […] The mechanisms of central sleep apnea have been best studied in congestive heart failure and hypoxic conditions when there is increased CO2 sensitivity below eupnea resulting in lowering eupneic PCO2 below apneic threshold causing cessation of breathing until the PCO2 rises above the apneic threshold when breathing resumes. […] In many other disorders, the mechanism of central sleep apnea (CSA) remains to be investigated.

• #5 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis/print

  Central apneas are periods of absent airflow due to lack of respiratory effort. They occur when inhibitory input to the respiratory center of the brain exceeds excitatory input, which may occur during sleep because sleep abolishes wakefulness-related excitatory input. Recurrent central apneas are the hallmark feature of central sleep apnea (CSA), which is a heterogeneous group of disorders with varying etiologies and pathophysiologic mechanisms. […] In this topic review, the pathogenesis of central sleep apnea is discussed. […] Central apnea results if arterial PaCO2 is lowered below a highly sensitive „apneic threshold”. […] In patients who manifest central apneas, prolonged hyperventilation, prolonged hypoxia, or concomitant inhibitory factors offset the effects of STP and allow central apnea to occur when the PaCO2 is reduced below the apneic threshold. […] Central apnea occurs in cycles of apnea or hypopnea, alternating with hyperpnea.

• #6 Central Sleep Apnea and Periodic Breathing | Neupsy Key

  https://neupsykey.com/central-sleep-apnea-and-periodic-breathing/

  Central sleep apnea is a disorder characterized by recurrent episodes of apnea during sleep, resulting from temporary suspension of ventilatory effort. […] Such apneas generally result from the strong dependence of ventilation during sleep on the metabolic control system and, in particular, arterial PCO2. […] It is also becoming increasingly recognized that central apneas can occur during titration of continuous positive airway pressure (CPAP) in some persons (complex sleep apnea). […] The term central sleep apnea reflects several breathing patterns, all of which include pauses in inspiratory effort; it does not represent a single entity or result from a single cause. […] To understand central sleep apnea, the normal mechanisms controlling ventilation during wakefulness and sleep, and the pathologic influences on these mechanisms, must be understood.

• #7 Central Sleep Apnea Syndromes: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/304967-overview

  Knowledge of normal ventilatory control mechanisms is important for understanding the pathophysiology of central sleep apnea. Normal ventilation is tightly regulated to maintain levels of arterial oxygen (PaO2) and carbon dioxide (PaCO2) within narrow ranges. This is achieved by feedback loops that involve peripheral and central chemoreceptors, intrapulmonary vagal receptors, the respiratory control centers in the brain stem, and the respiratory muscles. […] Two types of pathophysiologic phenomena can cause central sleep apnea syndromes: 1) ventilatory instability or 2) depression of the brainstem respiratory centers or chemoreceptors. […] Ventilatory instability is the mechanism behind CSB-CSA, high-altitude periodic breathing, and probably primary central sleep apnea. […] The occurrence and perpetuation of ventilatory instability in the pathogenesis of central sleep apnea can be visualized in the context of loop gain, an engineering term that describes the overall gain of a system controlled by feedback loops.

• #8 Central Sleep Apnea in Adults: An Interdisciplinary Approach to Diagnosis and Management—A Narrative Review

  https://www.mdpi.com/2077-0383/14/7/2369

  Central sleep apnea (CSA) is a heterogeneous group of sleep-related breathing disorders characterized by intermittent absence of respiratory effort during sleep. CSA results from impaired neurological signaling from the respiratory centers to the respiratory muscles, leading to airflow cessation for at least 10 s. […] This review outlines the pathophysiology of CSA, emphasizing ventilatory instability and brainstem dysfunction as key mechanisms. […] The mechanism of CSA production, unlike OSA (which presents respiratory effort), consists in the lack of transmission of nervous impulses from the respiratory centers to the respiratory muscles to trigger periodic breathing. […] Two major pathophysiological events cause CSA: (1) Ventilatory instability; (2) Depression of brainstem respiratory-centers or chemoreceptors.

• #9 Central Sleep Apnea | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/141286

  The pathophysiology of CSA can be variable due to its temporal relation with different comorbidities. Depending on the underlying medical condition, hypoventilation or hyperventilation with resultant hypocapnia below an apneic threshold is an integral mechanism that reinforces the evolution of central apnea. Reduced ventilatory drive during NREM sleep can induce central apnea and hypopnea even in healthy individuals. The mechanism is complex, but studies have shown that central chemoreceptors and upper airway mechanics play important roles. In addition, ventilatory control can contribute to the resultant central apnea in a susceptible patient population, particularly patients with neuromuscular disorders (such as spinal cord injury) or chest wall abnormalities (such as kyphoscoliosis). The enhanced chemosensitivity to arterial carbon dioxide levels during sleep results in overall increased loop gain, leading to ventilatory instability and CSA, especially in patients with HF. Opioids and other medications with CNS sedating properties can suppress the respiratory rhythm generator located within the brainstem. Thus, the development of CSA can be attributed either to reduced central ventilatory motor output or high loop gain. Regardless of the underlying condition or mechanism, once a cycle has started, it perpetuates the next one, resulting in repetitive episodes of hypoxia and irregular breathing, ultimately leading to upper airway narrowing.

• #10 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis

  Central apneas are periods of absent airflow due to lack of respiratory effort. They occur when inhibitory input to the respiratory center of the brain exceeds excitatory input, which may occur during sleep because sleep abolishes wakefulness-related excitatory input. Recurrent central apneas are the hallmark feature of central sleep apnea (CSA), which is a heterogeneous group of disorders with varying etiologies and pathophysiologic mechanisms. […] In this topic review, the pathogenesis of central sleep apnea is discussed. […] Apneic threshold — Respiration during non-rapid eye movement (NREM) sleep is critically dependent on chemical influences, especially arterial carbon dioxide tension (PaCO2). Central apnea results if arterial PaCO2 is lowered below a highly sensitive „apneic threshold”.

• #11 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis/print

  Central apneas are periods of absent airflow due to lack of respiratory effort. They occur when inhibitory input to the respiratory center of the brain exceeds excitatory input, which may occur during sleep because sleep abolishes wakefulness-related excitatory input. Recurrent central apneas are the hallmark feature of central sleep apnea (CSA), which is a heterogeneous group of disorders with varying etiologies and pathophysiologic mechanisms. […] In this topic review, the pathogenesis of central sleep apnea is discussed. […] Central apnea results if arterial PaCO2 is lowered below a highly sensitive „apneic threshold”. […] In patients who manifest central apneas, prolonged hyperventilation, prolonged hypoxia, or concomitant inhibitory factors offset the effects of STP and allow central apnea to occur when the PaCO2 is reduced below the apneic threshold. […] Central apnea occurs in cycles of apnea or hypopnea, alternating with hyperpnea.

• #12 Central Sleep Apnea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2287191/

  The transition from wakefulness to sleep is an inherently unstable period in terms of cardiorespiratory control. […] In addition, several respiratory control mechanisms are down regulated at sleep onset. […] The apnea threshold is usually 2 to 6 mm Hg below the eucapnic sleeping Paco2 level. […] The resultant reduction in ventilation with progressive sleep is coupled with a gradual rise in Paco2 on the order of approximately 3 to 8 mm Hg, depending on the prevailing metabolic conditions. […] The rapid switch from sleep to wakefulness that occurs with arousal causes a sudden shift in the underlying homeostatic control of the cardiorespiratory system. […] The combination of a predisposition to sleep transition apnea and a low arousal threshold may be sufficient to facilitate a repetitive CSA cycle as the individual oscillates between wakefulness and sleep.

• #13 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis

  In patients who manifest central apneas, prolonged hyperventilation, prolonged hypoxia, or concomitant inhibitory factors offset the effects of STP and allow central apnea to occur when the PaCO2 is reduced below the apneic threshold. […] Central apnea occurs in cycles of apnea or hypopnea, alternating with hyperpnea.

• #14 Central Sleep Apnea Syndromes: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/304967-overview

  Knowledge of normal ventilatory control mechanisms is important for understanding the pathophysiology of central sleep apnea. Normal ventilation is tightly regulated to maintain levels of arterial oxygen (PaO2) and carbon dioxide (PaCO2) within narrow ranges. This is achieved by feedback loops that involve peripheral and central chemoreceptors, intrapulmonary vagal receptors, the respiratory control centers in the brain stem, and the respiratory muscles. […] Two types of pathophysiologic phenomena can cause central sleep apnea syndromes: 1) ventilatory instability or 2) depression of the brainstem respiratory centers or chemoreceptors. […] Ventilatory instability is the mechanism behind CSB-CSA, high-altitude periodic breathing, and probably primary central sleep apnea. […] The occurrence and perpetuation of ventilatory instability in the pathogenesis of central sleep apnea can be visualized in the context of loop gain, an engineering term that describes the overall gain of a system controlled by feedback loops.

• #15 Central Sleep Apnea Syndromes: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/304967-overview

  In the respiratory system, controller gain is manifested as chemoresponsiveness, whereas plant gain is the effectiveness of a given minute ventilation to eliminate carbon dioxide. […] The ventilatory system is at particular risk of instability when the resting PaCO2 approaches the PaCO2 apneic threshold. In the situation of either high controller gain or high plant gain in association with a low baseline PaCO2 close to the apneic threshold, a minor disruption in the system can give rise to a cyclic appearance of central apneas and hyperpneas. […] Central sleep apnea-hypoventilation syndromes such as those associated with narcotic use or brainstem lesions are due to disturbances of the central respiratory pattern center or peripheral chemoreceptors or both that may become more evident during sleep because of the suppression of wakefulness or behavior drive.

• #16

  https://link.springer.com/article/10.1007/s11910-022-01199-2

  The pathogenesis of central sleep apnea has a number of etiologies that also have varying underlying mechanisms, and broadly can be attributed to either inadequate ventilatory drive or a paradoxically excessive drive (elevated loop gain). […] The regulation of carbon dioxide in the body is a negative feedback control system that is attempting to keep the PaCO2 at roughly 40 mmHg. Major fluctuations in PaCO2 reflect a high gain on the system. […] The prototype for high loop gain is the clinical scenario of Cheyne-Stokes breathing (CSB) whereby individuals, commonly with congestive heart failure, have fluctuations in breathing as a function of CO2 fluctuations. […] Importantly, it should be recognized that CSA related to high loop gain is due to a hyperresponsive system associated with high respiratory drive, and not respiratory control failure leading to low drive.

• #17

  https://link.springer.com/article/10.1007/s11910-022-01199-2

  The pathogenesis of central sleep apnea has a number of etiologies that also have varying underlying mechanisms, and broadly can be attributed to either inadequate ventilatory drive or a paradoxically excessive drive (elevated loop gain). […] The regulation of carbon dioxide in the body is a negative feedback control system that is attempting to keep the PaCO2 at roughly 40 mmHg. Major fluctuations in PaCO2 reflect a high gain on the system. […] The prototype for high loop gain is the clinical scenario of Cheyne-Stokes breathing (CSB) whereby individuals, commonly with congestive heart failure, have fluctuations in breathing as a function of CO2 fluctuations. […] Importantly, it should be recognized that CSA related to high loop gain is due to a hyperresponsive system associated with high respiratory drive, and not respiratory control failure leading to low drive.

• #18 Central sleep apnea: misunderstood and mistreated! | F1000Research

  https://f1000research.com/articles/8-981

  The principal component of a high loop gain is an excessive chemosensitivity to CO2 both above and below the level of eupneic ventilation. […] The unmasking of these reflex mechanisms underlies a sleep-induced central apnea. However, the repeated cyclical occurrence of transient ventilatory undershoots (apneas/hypopneas) and overshoots requires that respiratory control system loop gain to be elevated. […] A common misconception particularly with reference to causes of periodic breathing in CHF is that a reduced steady-state PaCO2 will precipitate periodic breathing, presumably because the patients eupneic PaCO2 is moved closer to their apneic threshold. […] The key characteristics of CHF present an almost perfect storm to promote periodic breathing. […] The use of nocturnal supplemental O2 in the mildly hyperoxic range addresses the primary problem of excessive chemoreceptor sensitivity and has successfully reduced AHI and eliminated CIH in several descriptive studies using relatively small numbers of patients with CHF. […] The aim here is to treat sleep-induced hypoventilation and any associated increase in airway resistance and apneic and hypopneic events.

• #19 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis

  In patients who manifest central apneas, prolonged hyperventilation, prolonged hypoxia, or concomitant inhibitory factors offset the effects of STP and allow central apnea to occur when the PaCO2 is reduced below the apneic threshold. […] Central apnea occurs in cycles of apnea or hypopnea, alternating with hyperpnea.

• #20 Central sleep apnea – Wikipedia

  https://en.wikipedia.org/wiki/Central_sleep_apnea

  After the episode of apnea, breathing may be faster and/or more intense (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases, absorb more oxygen, and, when voluntary, enable a return to normal instinctive breathing patterns by restoring oxygen to the breathing muscles themselves.

• #21 Central Sleep Apnea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK578199/

  Central sleep apnea (CSA) is characterized by transient diminution or cessation of the respiratory rhythm generator located within the pontomedullary region of the brain. […] The pathophysiology of CSA can be variable due to its temporal relation with different comorbidities. Depending on the underlying medical condition, hypoventilation or hyperventilation with resultant hypocapnia below an apneic threshold is an integral mechanism that reinforces the evolution of central apnea. […] The enhanced chemosensitivity to arterial carbon dioxide levels during sleep results in overall increased loop gain, leading to ventilatory instability and CSA, especially in patients with HF. […] Regardless of the underlying condition or mechanism, once a cycle has started, it perpetuates the next one, resulting in repetitive episodes of hypoxia and irregular breathing, ultimately leading to upper airway narrowing.

• #22 Central Sleep Apnea | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/141286

  The pathophysiology of CSA can be variable due to its temporal relation with different comorbidities. Depending on the underlying medical condition, hypoventilation or hyperventilation with resultant hypocapnia below an apneic threshold is an integral mechanism that reinforces the evolution of central apnea. Reduced ventilatory drive during NREM sleep can induce central apnea and hypopnea even in healthy individuals. The mechanism is complex, but studies have shown that central chemoreceptors and upper airway mechanics play important roles. In addition, ventilatory control can contribute to the resultant central apnea in a susceptible patient population, particularly patients with neuromuscular disorders (such as spinal cord injury) or chest wall abnormalities (such as kyphoscoliosis). The enhanced chemosensitivity to arterial carbon dioxide levels during sleep results in overall increased loop gain, leading to ventilatory instability and CSA, especially in patients with HF. Opioids and other medications with CNS sedating properties can suppress the respiratory rhythm generator located within the brainstem. Thus, the development of CSA can be attributed either to reduced central ventilatory motor output or high loop gain. Regardless of the underlying condition or mechanism, once a cycle has started, it perpetuates the next one, resulting in repetitive episodes of hypoxia and irregular breathing, ultimately leading to upper airway narrowing.

• #23

  https://link.springer.com/article/10.1007/s11910-022-01199-2

  The pathogenesis of central sleep apnea has a number of etiologies that also have varying underlying mechanisms, and broadly can be attributed to either inadequate ventilatory drive or a paradoxically excessive drive (elevated loop gain). […] The regulation of carbon dioxide in the body is a negative feedback control system that is attempting to keep the PaCO2 at roughly 40 mmHg. Major fluctuations in PaCO2 reflect a high gain on the system. […] The prototype for high loop gain is the clinical scenario of Cheyne-Stokes breathing (CSB) whereby individuals, commonly with congestive heart failure, have fluctuations in breathing as a function of CO2 fluctuations. […] Importantly, it should be recognized that CSA related to high loop gain is due to a hyperresponsive system associated with high respiratory drive, and not respiratory control failure leading to low drive.

• #24 Identification and Treatment of Central Sleep Apnoea: Beyond SERVE-HF | CFR Journal

  https://www.cfrjournal.com/articles/identification-and-treatment-central-sleep-apnoea-beyond-serve-hf?language_content_entity=en

  Central sleep apnoea (CSA) occurs in a large proportion of HF patients. CSA has clear detrimental effects, resulting in intermittent hypoxia and sympathetic activation, and is associated with significant morbidity and mortality. […] Central sleep apnoea (CSA) occurs in approximately one-third of patients with HF and is associated with a significant increase in morbidity and mortality compared to HF patients without CSA. CSA results in intermittent hypoxia and activation of the reninangiotensin system, which contributes to worsening HF. […] CSA occurs in two primary forms, characterised by either CheyneStokes respiration or non-CheyneStokes respiration. In HF patients, the CheyneStokes respiratory pattern is much more common and has a characteristic oscillatory pattern of shallowdeepshallow breathing. CheyneStokes respiration results from a delay in the respiratory control centre in detecting and responding to changes in carbon dioxide levels in the blood. The full mechanism is complex and still not completely understood; however, a number of factors appear to play a role.

• #25 Central Sleep Apnea in Heart Failure | USC Journal

  https://www.uscjournal.com/articles/central-sleep-apnea-heart-failure?language_content_entity=en

  Central sleep apnea (CSA) is a manifestation of respiratory control instability in patients with heart failure. […] CSA worsens the prognosis of patients with systolic dysfunction. […] The mechanisms and prevalence of CSA in heart failure are briefly presented. […] The following discussion of the mechanism of CSA is brief and will focus on recent developments. […] Patients with heart failure have a pattern of chronic hyperventilation characterized by close proximity between their baseline sleep (eupneic) level of PaCO2 (steady-state level of ventilation) and their apnea threshold. […] The mechanism of this chronic hyperventilation in patients with heart failure is thought to be related to pulmonary interstitial congestion. […] Any slight increase in ventilation during sleep, as occurs with arousal or changes in sleep stage, will result in a drop in PaCO2 below the apnea threshold, precipitating apneic events.

• #26 Central Sleep Apnea in Heart Failure | USC Journal

  https://www.uscjournal.com/articles/central-sleep-apnea-heart-failure?language_content_entity=en

  Given the inertia in the respiratory control system, breathing does not resume until an excessive chemical stimulus (hypercapnea) has accumulated, producing an overshoot of ventilation that is likely to drop PaCO2 below the apnea threshold again and propagate periodic breathing and CSR. […] The role of increased filling pressure in the pathogenesis of SDB in patients with heart failure is intriguing and only minimally understood. […] Increased pulmonary vascular congestion is thought to contribute to hyperventilation and increased respiratory control instability, leading to CSA. […] Worsening of heart failure may therefore lead to both increased central and obstructive apneas. […] CSA is a manifestation of respiratory control instability in patients with severe systolic dysfunction.

• #27 Central sleep apnea | MedLink Neurology

  https://www.medlink.com/articles/central-sleep-apnea

  In nonhypercapnic central sleep apnea, PaCO2 is close to the apneic threshold of the ventilatory response to CO2, especially in NREM sleep. […] Hypercapnic central sleep apnea is seen in conditions affecting ventilation or respiratory drive, such as central nervous system disease, neuromuscular disease, medication, or abnormalities in respiratory mechanics. […] The mechanism of central sleep apnea differs based on the underlying etiology. […] Cheyne-Stokes respiration is characterized by episodes of central apneas alternating with hyperventilation and exhibiting a crescendo-decrescendo pattern. […] Delayed signaling between controller and plant due to circulatory delay from heart failure results in overcorrection of elevated PaCO2 with hyperventilation, resulting in apnea. […] In high-altitude central sleep apnea, hypoxemia due to high altitude increases respiratory drive, which results in hyperventilation and hypocapnia.

• #28 Central sleep apnea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/central-sleep-apnea/symptoms-causes/syc-20352109

  Central sleep apnea occurs because the brain doesn’t send proper signals to the muscles that control breathing. […] Central sleep apnea can be caused by a number of conditions that affect the ability of the brainstem to control breathing. […] The cause varies with the type of central sleep apnea you have. Types include: […] Cheyne-Stokes breathing. This type of central sleep apnea is most commonly associated with congestive heart failure or stroke. […] Drug-induced apnea. Taking certain medicines such as opioids can cause breathing to become irregular or stop completely for a short time. […] High-altitude periodic breathing. A Cheyne-Stokes breathing pattern can occur if you’re at a very high altitude. […] Treatment-emergent central sleep apnea. Some people with obstructive sleep apnea develop central sleep apnea while using continuous positive airway pressure (CPAP) for treatment. […] Medical condition-induced central sleep apnea. Several medical conditions, including end-stage kidney disease and stroke, may lead to central sleep apnea. […] Primary central sleep apnea, also known as idiopathic sleep apnea. The cause of this uncommon type of central sleep apnea is not known.

• #29 Central sleep apnea due to high-altitude periodic breathing | MedLink Neurology

  https://www.medlink.com/articles/central-sleep-apnea-due-to-high-altitude-periodic-breathing

  In central sleep apnea due to high-altitude periodic breathing, there is frequent arousal from N1, N2, and N3 sleep; the first two stages are more disrupted than the latter stage. […] Above 3000 meters, the sleep disturbance may be partially secondary to the discomfort caused by the headaches and nausea of acute mountain illness. […] Although hypoxia is the initiating stimulus, periodic breathing and the associated sleep disruption occur as a result of the interplay between hypoxia and the subsequent hypocapnic alkalosis. […] A recurrent cycle of alternating respiratory stimulation and inhibition occurs. […] Hypoxia stimulates increased ventilation, which causes improved oxygenation but leads to hypocapnic alkalosis and subsequent respiratory suppression. […] Neither hypoxia nor hypocapnia alone are sufficient to produce this syndrome, and symptoms can be blocked by administration of oxygen, carbon dioxide, or an inhibitor of carbonic anhydrase.

• #30 Central sleep apnoea—a clinical review – Muza – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4455/html

  If the PaCO2 falls below an individuals set value (apnoea threshold) a CSA will ensue. Ventilation will only resume after the PaCO2 has risen above that threshold. The sleeping PaCO2 is normally 2 to 8 mmHg above the wake level. The AT is usually 1 to 2 mmHg lower than the waking PaCO2. The important factor which determines the propensity to develop an apnoea is the difference between the individuals PaCO2 and the AT. The smaller the PaCO2-AT difference the more likely it is that a central apnoea will occur. It is important to note that an individuals PaCO2-AT difference is not fixed and can vary with ventilatory drive. […] The aetiology and pathogenesis of ICSA is still not clear. It is essentially a diagnosis of exclusion after excluding the known causes of CSA. […] These patents tend to have a high hypercapnic response and sleep state instability. Wake PaCO2 levels tend to be low. Arousals, usually non-respiratory related, cause a transient increase in ventilation and a consequent fall in PaCO2. Unlike Cheyne-Stokes there is no waxing and waning of ventilation.

• #31 Evaluation of the Impact of Body Position on Primary Central Sleep Apnea Syndrome | Archivos de Bronconeumología

  https://www.archbronconeumol.org/en-evaluation-impact-body-position-on-articulo-S0300289620300818

  Central sleep apnea syndrome (CSAS) is a clinical entity characterized by the temporary absence or diminution of respiratory drive coming from the respiratory center during sleep. Central sleep apnea (CSA) occurs in less than 5% of subjects admitted to sleep clinics. CSA could be primary (idiopathic) or secondary to medical conditions (e.g. heart failure, renal failure, cerebrovascular disease), high altitude, opioids, and drug use. Primary CSA is diagnosed by exclusion of any identifiable cardiac and neurologic cause in patients with CSA. Primary CSA seems to be driven by elevated chemosensitivity to PCO2. Circulation delay is defined as normal in these patients and is unlikely to contribute to CSA. […] In view of these findings, the purpose of the current study was to evaluate the impact of body position on primary central sleep apnea syndrome. Thereby, we also assessed the features of primary positional central sleep apnea (PCSA) and phenotypic approach to primary CSA.

• #32 Central sleep apnea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/central-sleep-apnea/symptoms-causes/syc-20352109

  Central sleep apnea occurs because the brain doesn’t send proper signals to the muscles that control breathing. […] Central sleep apnea can be caused by a number of conditions that affect the ability of the brainstem to control breathing. […] The cause varies with the type of central sleep apnea you have. Types include: […] Cheyne-Stokes breathing. This type of central sleep apnea is most commonly associated with congestive heart failure or stroke. […] Drug-induced apnea. Taking certain medicines such as opioids can cause breathing to become irregular or stop completely for a short time. […] High-altitude periodic breathing. A Cheyne-Stokes breathing pattern can occur if you’re at a very high altitude. […] Treatment-emergent central sleep apnea. Some people with obstructive sleep apnea develop central sleep apnea while using continuous positive airway pressure (CPAP) for treatment. […] Medical condition-induced central sleep apnea. Several medical conditions, including end-stage kidney disease and stroke, may lead to central sleep apnea. […] Primary central sleep apnea, also known as idiopathic sleep apnea. The cause of this uncommon type of central sleep apnea is not known.

• #33 Central sleep apnoea—a clinical review – Muza – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4455/html

  CSB patterns association with congestive heart failure is well known. […] Patients with CSB-CSA have a long circulation time. They tend to have relative daytime hypocapnia and the sleeping PaCO2-AT difference is small. The ventilatory drive is high due to a high sympathetic tone and stimulation of respiration from pulmonary congestion. […] Complex SA is identified by emergence or persistence of central apnoea upon exposure to CPAP treatment. PAP treatments eliminate the upper airway obstruction but do not correct the ventilatory control instability or the sleep state instability. […] The reasons for the emergence of central apnoeas remain obscure. It is likely that a high loop gain could be responsible for its persistence. […] Drugs in common use for pain control include morphine, fentanyl and methadone. Patients on high doses of these medications may have a slow sleeping respiratory rate. […] Treatment emergent central apnoeas are also common even if the diagnostic study might have shown mainly obstructive events.

• #34 Central Sleep Apnea | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/141286

  The pathophysiology of CSA can be variable due to its temporal relation with different comorbidities. Depending on the underlying medical condition, hypoventilation or hyperventilation with resultant hypocapnia below an apneic threshold is an integral mechanism that reinforces the evolution of central apnea. Reduced ventilatory drive during NREM sleep can induce central apnea and hypopnea even in healthy individuals. The mechanism is complex, but studies have shown that central chemoreceptors and upper airway mechanics play important roles. In addition, ventilatory control can contribute to the resultant central apnea in a susceptible patient population, particularly patients with neuromuscular disorders (such as spinal cord injury) or chest wall abnormalities (such as kyphoscoliosis). The enhanced chemosensitivity to arterial carbon dioxide levels during sleep results in overall increased loop gain, leading to ventilatory instability and CSA, especially in patients with HF. Opioids and other medications with CNS sedating properties can suppress the respiratory rhythm generator located within the brainstem. Thus, the development of CSA can be attributed either to reduced central ventilatory motor output or high loop gain. Regardless of the underlying condition or mechanism, once a cycle has started, it perpetuates the next one, resulting in repetitive episodes of hypoxia and irregular breathing, ultimately leading to upper airway narrowing.

• #35 Central sleep apnea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/central-sleep-apnea/symptoms-causes/syc-20352109

  Central sleep apnea occurs because the brain doesn’t send proper signals to the muscles that control breathing. […] Central sleep apnea can be caused by a number of conditions that affect the ability of the brainstem to control breathing. […] The cause varies with the type of central sleep apnea you have. Types include: […] Cheyne-Stokes breathing. This type of central sleep apnea is most commonly associated with congestive heart failure or stroke. […] Drug-induced apnea. Taking certain medicines such as opioids can cause breathing to become irregular or stop completely for a short time. […] High-altitude periodic breathing. A Cheyne-Stokes breathing pattern can occur if you’re at a very high altitude. […] Treatment-emergent central sleep apnea. Some people with obstructive sleep apnea develop central sleep apnea while using continuous positive airway pressure (CPAP) for treatment. […] Medical condition-induced central sleep apnea. Several medical conditions, including end-stage kidney disease and stroke, may lead to central sleep apnea. […] Primary central sleep apnea, also known as idiopathic sleep apnea. The cause of this uncommon type of central sleep apnea is not known.

• #36 Central Sleep Apnea and Periodic Breathing | Neupsy Key

  https://neupsykey.com/central-sleep-apnea-and-periodic-breathing/

  Central sleep apnea is a disorder characterized by recurrent episodes of apnea during sleep, resulting from temporary suspension of ventilatory effort. […] Such apneas generally result from the strong dependence of ventilation during sleep on the metabolic control system and, in particular, arterial PCO2. […] It is also becoming increasingly recognized that central apneas can occur during titration of continuous positive airway pressure (CPAP) in some persons (complex sleep apnea). […] The term central sleep apnea reflects several breathing patterns, all of which include pauses in inspiratory effort; it does not represent a single entity or result from a single cause. […] To understand central sleep apnea, the normal mechanisms controlling ventilation during wakefulness and sleep, and the pathologic influences on these mechanisms, must be understood.

• #37 Central sleep apnoea—a clinical review – Muza – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4455/html

  CSB patterns association with congestive heart failure is well known. […] Patients with CSB-CSA have a long circulation time. They tend to have relative daytime hypocapnia and the sleeping PaCO2-AT difference is small. The ventilatory drive is high due to a high sympathetic tone and stimulation of respiration from pulmonary congestion. […] Complex SA is identified by emergence or persistence of central apnoea upon exposure to CPAP treatment. PAP treatments eliminate the upper airway obstruction but do not correct the ventilatory control instability or the sleep state instability. […] The reasons for the emergence of central apnoeas remain obscure. It is likely that a high loop gain could be responsible for its persistence. […] Drugs in common use for pain control include morphine, fentanyl and methadone. Patients on high doses of these medications may have a slow sleeping respiratory rate. […] Treatment emergent central apnoeas are also common even if the diagnostic study might have shown mainly obstructive events.

• #38 Central Sleep Apnea Syndromes: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/304967-overview

  The mechanisms responsible for central sleep apnea and obstructive sleep apnea overlap, and patients with central apneas often have obstructive events. […] Thus, the susceptibility to upper airway collapse may determine whether central or obstructive apneas occur with cycling due to ventilatory instability.

• #39 Central Sleep Apnea | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/141286

  Central sleep apnea (CSA) is characterized by transient diminution or cessation of the respiratory rhythm generator located within the pontomedullary region of the brain. In general, CSA represents an array of sleep-disordered breathing (SDB) conditions due to the brief absence of ventilatory output during sleep. CSA manifests as a cyclical phenomenon/pattern during sleep; periods of apnea or hypopnea alternating with hyperpnea. Although there is a lack of effort during central events, it has been found that the upper airway narrows or nearly collapses during these events. Upper airway narrowing consistently occurs at the retropalatal level during induced hypocapnic central apnea and induced central hypopnea. […] Both hypoventilation and hyperventilation can result in central apneas, and each one acts through a distinct pathophysiological pathway. Thus, the degree of alveolar ventilation often serves as a basis for an alternate classification of CSA. Patients with heart failure are often hypocapnic during wakefulness and have an increased propensity to develop hyperventilation related CSA; however, hypoventilation related CSA commonly occur in neuromuscular diseases (amyotrophic lateral sclerosis, brainstem stroke), overuse of medications with side effects of central nervous system depression (opioids), cervical spinal cord injury and structural abnormalities affecting pulmonary dynamics (kyphoscoliosis).

• #40 Central Sleep Apnea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2287191/

  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. […] While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. […] The prevalence of CSA varies greatly between the various forms of CSA. […] However, as will be discussed, considerable overlap exists in the pathogenesis and pathophysiology of obstructive and central apnea, making this distinction somewhat difficult at times. […] The overlap between CSA and OSA suggests that common mechanistic traits are likely involved. […] Typically, CSA is considered to be the primary diagnosis when 50% of apneas are scored as central in origin (ie, 10 s cessation of breathing in the absence of respiratory effort); however, such thresholds are clearly arbitrary.

• #41 Central Sleep Apnea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2287191/

  The transition from wakefulness to sleep is an inherently unstable period in terms of cardiorespiratory control. […] In addition, several respiratory control mechanisms are down regulated at sleep onset. […] The apnea threshold is usually 2 to 6 mm Hg below the eucapnic sleeping Paco2 level. […] The resultant reduction in ventilation with progressive sleep is coupled with a gradual rise in Paco2 on the order of approximately 3 to 8 mm Hg, depending on the prevailing metabolic conditions. […] The rapid switch from sleep to wakefulness that occurs with arousal causes a sudden shift in the underlying homeostatic control of the cardiorespiratory system. […] The combination of a predisposition to sleep transition apnea and a low arousal threshold may be sufficient to facilitate a repetitive CSA cycle as the individual oscillates between wakefulness and sleep.

• #42 Central sleep apnoea—a clinical review – Muza – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/4455/html

  Central sleep apnoea (CSA) is characterised by recurrent apnoeas during sleep with no associated respiratory effort. It mostly results from withdrawal of the wakefulness drive in sleep leaving ventilation under metabolic control. A detailed physiological understanding of the control of breathing in wakefulness and sleep is essential to the understanding of CSA. It encompasses a diverse group of conditions with differing aetiologies and pathophysiology. […] Despite a lot of research into CSA in the past two decades the condition is still poorly understood and treatment is still suboptimal perhaps owing to its aetiological and pathophysiological diversity and heterogeneity. […] An understanding of the normal physiological changes in breathing between wake and NREM sleep is essential for the understanding of CSAs. Respiratory control is quite unstable during transition from wake to sleep and with further sleep stage transitions. There is usually a 2 to 8 mmHg rise in PaCO2 during NREM sleep. During NREM sleep ventilation is totally under metabolic control. The wakefulness drive is no longer operational, the hypercapnic and hypoxic drives are reduced and there is also increased upper airway resistance. […] Some doubt has been raised as to whether there is true loss of chemo-responsiveness and loss of drive and some have suggested that the changes in sleep might be mostly due to increased upper airway resistance.

• #43 Central Sleep Apnea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2287191/

  The transition from wakefulness to sleep is an inherently unstable period in terms of cardiorespiratory control. […] In addition, several respiratory control mechanisms are down regulated at sleep onset. […] The apnea threshold is usually 2 to 6 mm Hg below the eucapnic sleeping Paco2 level. […] The resultant reduction in ventilation with progressive sleep is coupled with a gradual rise in Paco2 on the order of approximately 3 to 8 mm Hg, depending on the prevailing metabolic conditions. […] The rapid switch from sleep to wakefulness that occurs with arousal causes a sudden shift in the underlying homeostatic control of the cardiorespiratory system. […] The combination of a predisposition to sleep transition apnea and a low arousal threshold may be sufficient to facilitate a repetitive CSA cycle as the individual oscillates between wakefulness and sleep.

• #44 Central Sleep Apnea

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2287191/

  The transition from wakefulness to sleep is an inherently unstable period in terms of cardiorespiratory control. […] In addition, several respiratory control mechanisms are down regulated at sleep onset. […] The apnea threshold is usually 2 to 6 mm Hg below the eucapnic sleeping Paco2 level. […] The resultant reduction in ventilation with progressive sleep is coupled with a gradual rise in Paco2 on the order of approximately 3 to 8 mm Hg, depending on the prevailing metabolic conditions. […] The rapid switch from sleep to wakefulness that occurs with arousal causes a sudden shift in the underlying homeostatic control of the cardiorespiratory system. […] The combination of a predisposition to sleep transition apnea and a low arousal threshold may be sufficient to facilitate a repetitive CSA cycle as the individual oscillates between wakefulness and sleep.

• #45 Central Sleep Apnea in Heart Failure | USC Journal

  https://www.uscjournal.com/articles/central-sleep-apnea-heart-failure?language_content_entity=en

  The recurrence of central respiratory events followed by a recovery phase induces a cyclical pattern of intermittent hypoxiareoxygenation. […] Following every apnea or hypopnea, the resulting hypoxia stimulates the chemoreceptors, which mediate an increase in sympathetic activity. […] This sympathetic activation produces peripheral vasoconstriction and a subsequent surge in blood pressure, increasing the afterload for a failing heart. […] The negative role of increased sympathetic tone is well established in heart failure. […] Sympathetic activation-mediated vasoconstriction may induce long-lasting structural changes in the resistance of microcirculatory vessels that contribute to the pathogenesis and persistence of hypertension. […] Hypoxia, as well as inducing systemic vasoconstriction, can induce pulmonary vasoconstriction and subsequently increase the right ventricular afterload.

• #46 Central Sleep Apnea in Heart Failure | USC Journal

  https://www.uscjournal.com/articles/central-sleep-apnea-heart-failure?language_content_entity=en

  The recurrence of central respiratory events followed by a recovery phase induces a cyclical pattern of intermittent hypoxiareoxygenation. […] Following every apnea or hypopnea, the resulting hypoxia stimulates the chemoreceptors, which mediate an increase in sympathetic activity. […] This sympathetic activation produces peripheral vasoconstriction and a subsequent surge in blood pressure, increasing the afterload for a failing heart. […] The negative role of increased sympathetic tone is well established in heart failure. […] Sympathetic activation-mediated vasoconstriction may induce long-lasting structural changes in the resistance of microcirculatory vessels that contribute to the pathogenesis and persistence of hypertension. […] Hypoxia, as well as inducing systemic vasoconstriction, can induce pulmonary vasoconstriction and subsequently increase the right ventricular afterload.

• #47 Central Sleep Apnea in Heart Failure | USC Journal

  https://www.uscjournal.com/articles/central-sleep-apnea-heart-failure?language_content_entity=en

  The impact of CSA on right ventricular function and load is another area that has not been evaluated in patients with existing systolic dysfunction and CSA. […] The mechanical perturbations associated with respiratory effort are less profound in CSA than OSA and probably have less severe implications for patients with heart failure. […] The sympathetic activation associated with CSA appears to be more important in mediating the cardiovascular effects of CSA than these less profound pressure changes. […] While CSA is associated with significant perturbations in the neuro-humoral system, its clinical impact on outcomes of patients with heart failure is incompletely understood. […] Several small studies have demonstrated a link between CSA and poor outcome in patients with heart failure, including an effect on mortality.

• #48 Central sleep apnea: misunderstood and mistreated! | F1000Research

  https://f1000research.com/articles/8-981

  Cyclical CSAs like their obstructive counterparts are pro-inflammatory with substantial long-term deleterious effects during wakefulness, including enhanced sympathetic vasomotor outflow and vascular endothelial dysfunction, neurocognitive deficits, and insulin insensitivity. […] The molecular basis for the highly inflammatory response to intermittent (as opposed to constant) hypoxemia has been explained by Semenza and Prabhakar as an upregulation of both pro- and anti-oxidant transcription factors, hypoxia-inducible factor (HIF) 1 and 2 in constant hypoxemia but a suppression of the anti-oxidant HIF 2 in intermittent hypoxemia. […] The transient cessation of the medullary respiratory pattern generator neurons requires an unmasking of a sensitized apneic threshold in NREM sleep, as induced by a transient ventilatory overshoot involving both mild to moderate hypocapnia plus augmented Vt values.

• #49 Central sleep apnea: misunderstood and mistreated! | F1000Research

  https://f1000research.com/articles/8-981

  Cyclical CSAs like their obstructive counterparts are pro-inflammatory with substantial long-term deleterious effects during wakefulness, including enhanced sympathetic vasomotor outflow and vascular endothelial dysfunction, neurocognitive deficits, and insulin insensitivity. […] The molecular basis for the highly inflammatory response to intermittent (as opposed to constant) hypoxemia has been explained by Semenza and Prabhakar as an upregulation of both pro- and anti-oxidant transcription factors, hypoxia-inducible factor (HIF) 1 and 2 in constant hypoxemia but a suppression of the anti-oxidant HIF 2 in intermittent hypoxemia. […] The transient cessation of the medullary respiratory pattern generator neurons requires an unmasking of a sensitized apneic threshold in NREM sleep, as induced by a transient ventilatory overshoot involving both mild to moderate hypocapnia plus augmented Vt values.

• #50 Central Sleep Apnea in Heart Failure | USC Journal

  https://www.uscjournal.com/articles/central-sleep-apnea-heart-failure?language_content_entity=en

  The severity of CSA is correlated with severity of the underlying systolic dysfunction. […] Optimal treatment of the heart failure is therefore of foremost importance in the management of CSA. […] The mechanism of effect of these medications may be mediated by decreased preload or improved cerebral perfusion and responsiveness at the level of the central chemoreceptors. […] Given the association between CSA and upper airway instability, and the salutary effects of CPAP on cardiac function, CPAP has been used for the treatment of CSA. […] These studies are promising but will require confirmation with an adequately powered randomized controlled trial.

• #51

  https://link.springer.com/article/10.1007/s11910-022-01199-2

  Some controversy exists regarding the importance of circulatory delay towards unstable breathing. […] In addition to CSB, some patients exhibit central apneas with fluctuating alertness, i.e., so-called state transition apneas. […] In some patients with hypercapnia, central apneas/hypopneas can occur during sleep. […] In rare congenital forms, CCHS (central congenital hypoventilation syndrome) can occur as a result of a mutation in the phox2b gene. […] Central sleep apnea is a heterogeneous and complex disease characterized by the temporary absence of ventilatory effort during sleep. In the majority of cases, it is a result of conditions leading to an elevated loop gain, sometimes driven by a robust ventilatory effort in response to perturbation.

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