-
F1000Research 2019Central sleep apnea is prevalent in patients with heart failure, healthy individuals at high altitudes, and chronic opiate users and in the initiation of "mixed" (that... (Review)
Review
Central sleep apnea is prevalent in patients with heart failure, healthy individuals at high altitudes, and chronic opiate users and in the initiation of "mixed" (that is, central plus obstructive apneas). This brief review focuses on (a) the causes of repetitive, cyclical central apneas as mediated primarily through enhanced sensitivities in the respiratory control system and (b) treatment of central sleep apnea through modification of key components of neurochemical control as opposed to the current universal use of positive airway pressure.
Topics: Altitude; Analgesics, Opioid; Heart Failure; Humans; Prevalence; Respiratory System; Sleep Apnea, Central; Sleep Apnea, Obstructive
PubMed: 31297185
DOI: 10.12688/f1000research.18358.1 -
Chest Feb 2007Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas... (Review)
Review
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.
Topics: Humans; Respiration; Sleep; Sleep Apnea, Central
PubMed: 17296668
DOI: 10.1378/chest.06.2287 -
Cleveland Clinic Journal of Medicine Sep 2019The normal sleep-wake cycle is characterized by diurnal variations in blood pressure, heart rate, and cardiac events. Sleep apnea disrupts the normal sleep-heart... (Review)
Review
The normal sleep-wake cycle is characterized by diurnal variations in blood pressure, heart rate, and cardiac events. Sleep apnea disrupts the normal sleep-heart interaction, and the pathophysiology varies for obstructive sleep apnea (OSA) and central sleep apnea (CSA). Associations exist between sleep-disordered breathing (which encompasses both OSA and CSA) and heart failure, atrial fibrillation, stroke, coronary artery disease, and cardiovascular mortality. Treatment options include positive airway pressure as well as adaptive servo-ventilation and phrenic nerve stimulation for CSA. Treatment improves blood pressure, quality of life, and sleepiness, the last particularly in those at risk for cardiovascular disease. Results from clinical trials are not definitive in terms of hard cardiovascular outcomes.
Topics: Blood Pressure; Cardiovascular Diseases; Circadian Rhythm; Continuous Positive Airway Pressure; Heart; Heart Rate; Humans; Sleep; Sleep Apnea, Central; Sleep Apnea, Obstructive
PubMed: 31509499
DOI: 10.3949/ccjm.86.s1.03 -
Sleep Mar 2023Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. In some conditions, such as heart failure,... (Review)
Review
Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. 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 "apneic threshold". 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-feedback 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 "loop gain" (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.
Topics: Humans; Sleep Apnea, Central; Hypocapnia; Respiration; Sleep; Heart Failure
PubMed: 35551411
DOI: 10.1093/sleep/zsac113 -
Chest Dec 2020Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights.
RESEARCH QUESTION
How efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose?
STUDY DESIGN AND METHODS
We queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods.
RESULTS
We included 28 studies (13 OSA/15 CSA; N = 542; N = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by -0.7 effect sizes (95% CI, -0.83 to -0.58; I = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, -44.7 to -31.3) or 13.8/h (95% CI, -16.3 to -11.4; AHI = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE).
INTERPRETATION
Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic treatment of patients with sleep apnea.
CLINICAL TRIAL REGISTRATION
PROSPERO (CRD42019147504).
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Humans; Sleep Apnea, Central; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 32768459
DOI: 10.1016/j.chest.2020.06.078 -
The European Respiratory Journal Jan 2021Sleep-related breathing disorders (SBDs) include obstructive apnoea, central apnoea and sleep-related hypoventilation. These nocturnal events have the potential to... (Review)
Review
Sleep-related breathing disorders (SBDs) include obstructive apnoea, central apnoea and sleep-related hypoventilation. These nocturnal events have the potential to increase pulmonary arterial pressure (PAP) during sleep but also in the waking state. "Pure" obstructive sleep apnoea syndrome (OSAS) is responsible for a small increase in PAP whose clinical impact has not been demonstrated. By contrast, in obesity hypoventilation syndrome (OHS) or overlap syndrome (the association of chronic obstructive pulmonary disease (COPD) with obstructive sleep apnoea (OSA)), nocturnal respiratory events contribute to the development of pulmonary hypertension (PH), which is often severe. In the latter circumstances, treatment of SBDs is essential in order to improve pulmonary haemodynamics.Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are at risk of developing SBDs. Obstructive and central apnoea, as well as a worsening of ventilation-perfusion mismatch, can be observed during sleep. There should be a strong suspicion of SBDs in such a patient population; however, the precise indications for sleep studies and the type of recording remain to be specified. The diagnosis of OSAS in patients with PAH or CTEPH should encourage treatment with continuous positive airway pressure (CPAP). The presence of isolated nocturnal hypoxaemia should also prompt the initiation of long-term oxygen therapy. These treatments are likely to avoid worsening of PH; however, it is prudent not to treat central apnoea and Cheyne-Stokes respiration (CSR) with adaptive servo-ventilation in patients with chronic right-heart failure because of a potential risk of serious adverse effects from such treatment.In this review we will consider the current knowledge of the consequences of SBDs on pulmonary haemodynamics in patients with and without chronic respiratory disease (group 3 of the clinical classification of PH) and the effect of treatments of respiratory events during sleep on PH. The prevalence and consequences of SBDs in PAH and CTEPH (groups 1 and 4 of the clinical classification of PH, respectively), as well as therapeutic options, will also be discussed.
Topics: Cheyne-Stokes Respiration; Continuous Positive Airway Pressure; Humans; Hypertension, Pulmonary; Sleep; Sleep Apnea, Central
PubMed: 32747397
DOI: 10.1183/13993003.02258-2020 -
The American Journal of Cardiology Jan 2021The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was... (Randomized Controlled Trial)
Randomized Controlled Trial
The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was assessed by single-night polysomnography (PSG) in 54 PICM patients within 1 month after left ventricular lead implantation (with biventricular stimulation still not activated). CSA was diagnosed in half of patients (n = 27). Patients with moderate or severe CSA were randomized to cardiac resynchronization therapy (CRT) versus right ventricular pacing (RVP) in a double-blinded cross-over design and re-scheduled for a follow-up PSG within 3 to 5 months. After crossing-over of stimulation mode another PSG was conducted 3 to 5 months later. CRT led to a significant increase in left ventricular ejection fraction and significant reduction in left ventricular end systolic volumes and N-terminal pro brain natriuretic peptide plasma levels, whereas no significant effects were observed with ongoing RVP. CSA was significantly improved after 3.9 (3.2 to 4.4) months of CRT: apnea-hypopnea index decreased from 39.1 (32.1 to 54.0) events per hour at baseline to 22.2/h (10.9 to 36.7) by CRT (p <0.001). Central apnea index decreased from 27.1/h (17.7 to 36.1) at baseline to 6.8/h (1.1 to 14.4) after CRT activation (p <0.001). Ongoing RVP yielded only a minor improvement in apnea-hypopnea index and central apnea index. Pre-existent CSA did not affect structural response rate and had no impact on mid-term follow-up (median 2.8 years). In conclusion, CSA is highly prevalent in patients with PICM. CRT upgrading significantly improves CSA leading to a similar outcome in PICM patients without pre-existent CSA.
Topics: Aged; Cardiac Pacing, Artificial; Cardiomyopathies; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Polysomnography; Prospective Studies; Sleep Apnea, Central; Stroke Volume; Ventricular Function, Left
PubMed: 33002463
DOI: 10.1016/j.amjcard.2020.09.027 -
Sleep Sep 2023
Topics: Humans; Sleep Apnea, Central; Sleep Apnea, Obstructive; Positive-Pressure Respiration
PubMed: 37436100
DOI: 10.1093/sleep/zsad189 -
Orphanet Journal of Rare Diseases Sep 2020Congenital Central Hypoventilation Syndrome (CCHS) is a rare condition characterized by an alveolar hypoventilation due to a deficient autonomic central control of... (Review)
Review
BACKGROUND
Congenital Central Hypoventilation Syndrome (CCHS) is a rare condition characterized by an alveolar hypoventilation due to a deficient autonomic central control of ventilation and a global autonomic dysfunction. Paired-like homeobox 2B (PHOX2B) mutations are found in most of the patients with CCHS. In recent years, the condition has evolved from a life-threatening neonatal onset disorder to include broader and milder clinical presentations, affecting children, adults and families. Genes other than PHOX2B have been found responsible for CCHS in rare cases and there are as yet other unknown genes that may account for the disease. At present, management relies on lifelong ventilatory support and close follow up of dysautonomic progression. BODY: This paper provides a state-of-the-art comprehensive description of CCHS and of the components of diagnostic evaluation and multi-disciplinary management, as well as considerations for future research.
CONCLUSION
Awareness and knowledge of the diagnosis and management of this rare disease should be brought to a large health community including adult physicians and health carers.
Topics: Adult; Child; Homeodomain Proteins; Humans; Hypoventilation; Mutation; Sleep Apnea, Central; Transcription Factors
PubMed: 32958024
DOI: 10.1186/s13023-020-01460-2 -
Current Neurology and Neuroscience... Jul 2022The purpose of this article is to review the recent literature on central apnea. Sleep disordered breathing (SDB) is characterized by apneas (cessation in breathing),... (Review)
Review
PURPOSE
The purpose of this article is to review the recent literature on central apnea. Sleep disordered breathing (SDB) is characterized by apneas (cessation in breathing), and hypopneas (reductions in breathing), that occur during sleep. Central sleep apnea (CSA) is sleep disordered breathing in which there is an absence or diminution of respiratory effort during breathing disturbances while asleep. In obstructive sleep apnea (OSA), on the other hand, there is an absence of flow despite ongoing ventilatory effort.
RECENT FINDINGS
Central sleep apnea is a heterogeneous disease with multiple clinical manifestations. OSA is by far the more common condition; however, CSA is highly prevalent among certain patient groups. Complex sleep apnea (CompSA) is defined as the occurrence/emergence of CSA upon treatment of OSA. Similarly, there is considerable overlap between CSA and OSA in pathogenesis as well as impacts. Thus, understanding sleep disordered breathing is important for many practicing clinicians.
Topics: Humans; Sleep; Sleep Apnea Syndromes; Sleep Apnea, Central; Sleep Apnea, Obstructive
PubMed: 35588042
DOI: 10.1007/s11910-022-01199-2