Prevalence of central sleep apnea among veterans and response rate to continuous positive airway pressure therapy.

Study Objectives: Sleep-disordered breathing (SDB) is common in the Veteran population. In this retrospective study, we investigated the prevalence of comorbid central and obstructive SDB and the response rate to PAP among Veterans. Methods: Veterans were screened from a single VA medical center who had polysomnography (PSG) study from 2017 to 2021 to ascertain the presence, severity, and type of SDB by measuring the apnea-hypopnea index (AHI) and central apnea index (CAI). Patients were excluded if they did not have complete studies (diagnostic and PAP titration studies). The inclusion criteria for these analyses were central sleep apnea (CSA) defined as AHI ≥ 10 events/hour and CAI ≥ 5 events/hour. Diagnostic "CSA only" was defined as AHI ≥ 10 events/hour and CAI ≥ 50% of AHI. "OSA only" was defined if AHI ≥ 10 events/hour and CAI < 5 events/hour. Comorbid central and obstructive sleep apnea (COSA) was defined if AHI ≥ 10 events/hour and CAI > 5 events/hour but < 50% of AHI. The responsiveness to PAP therapy was determined based on the CAI < 5 events/hour on the titration study. Results: A total of 90 patients met the inclusion criteria and from those 64 Veterans were found to have COSA (71%), 18 (20%) were CSA only, and 8 (9%) were OSA only. A total of 22 (24.4%) Veterans diagnosed with CSA or COSA were responsive to PAP therapy. Sixty days after treatment initiation, both responsive and nonresponsive groups had significant decreases in AHI and CAI (p < 0.05). Conclusions: Comorbid central and obstructive SDB is common among Veterans. The response to PAP therapy is suboptimal but improves over time.

International Consensus Statement on Obstructive Sleep Apnea.

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Tetraplegia is associated with increased hypoxic ventilatory response during nonrapid eye movement sleep.

People with cervical spinal cord injury (SCI) are likely to experience chronic intermittent hypoxia while sleeping. The physiological effects of intermittent hypoxia on the respiratory system during spontaneous sleep in individuals with chronic cervical SCI are unknown. We hypothesized that individuals with cervical SCI would demonstrate higher short- and long-term ventilatory responses to acute intermittent hypoxia (AIH) exposure than individuals with thoracic SCI during sleep. Twenty participants (10 with cervical SCI [9 male] and 10 with thoracic SCI [6 male]) underwent an AIH and sham protocol during sleep. During the AIH protocol, each participant experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2 ) and 40% carbon dioxide (CO2 ) to achieve an oxygen saturation of less than 90%. This was followed by two breaths of 100% oxygen (O2 ). Measurements were collected before, during, and 40 min after the AIH protocol to obtain ventilatory data. During the sham protocol, participants breathed room air for the same amount of time that elapsed during the AIH protocol and at approximately the same time of night. Hypoxic ventilatory response (HVR) during the AIH protocol was significantly higher in participants with cervical SCI than those with thoracic SCI. There was no significant difference in minute ventilation (V.E. ), tidal volume (V.T. ), or respiratory frequency (f) during the recovery period after AIH in cervical SCI compared to thoracic SCI groups. Individuals with cervical SCI demonstrated a significant short-term increase in HVR compared to thoracic SCI. However, there was no evidence of ventilatory long-term facilitation following AIH in either group.

Oxygen Therapy in Sleep-Disordered Breathing.

Sleep-disordered breathing (SDB) is highly prevalent in adults and leads to significant cardiovascular and neurologic sequelae. Intermittent hypoxia during sleep is a direct consequence of SDB. Administration of nocturnal supplemental oxygen (NSO) has been used as a therapeutic alternative to positive airway pressure (PAP) in SDB. NSO significantly improves oxygen saturation in OSA but is inferior to PAP in terms of reducing apnea severity and may prolong the duration of obstructive apneas. The effect of NSO on daytime sleepiness remains unclear, but NSO may improve physical function-related quality of life in OSA. Its effects on BP reduction remain inconclusive. The effects of NSO vs PAP in OSA with comorbid COPD (overlap syndrome) are unknown. NSO is effective in reducing central sleep apnea related to congestive heart failure; however, its impact on mortality and cardiovascular clinical outcomes are being investigated in an ongoing clinical trial. In conclusion, studies are inconclusive or limited regarding clinical outcomes with oxygen therapy compared with sham or PAP therapy in patients with OSA and overlap syndrome. Oxygen does mitigate central sleep apnea. This review examines the crucial knowledge gaps and suggests future research priorities to clarify the effects of optimal dose and duration of NSO, alone or in combination with PAP, on cardiovascular, sleep, and cognitive outcomes.

The Veterans Administration and Department of Defense clinical practice guidelines for the diagnosis and management of sleep disorders: what does this mean for the practice of sleep medicine?

None: In 2017 the Veterans Administration (VA) and Department of Defense (DOD) launched development of clinical practice guidelines (CPGs) for the diagnosis and treatment of sleep disorders, with the goal of informing and improving patient care. The guideline development process followed GRADE methodology, considering studies and systematic reviews published over the 10-year period prior to guideline development. A total of 41 recommendations were made,18 related to the diagnosis and treatment of obstructive sleep apnea (OSA) and 23 regarding chronic insomnia disorder. In contrast to other published guidelines, the VA DoD CPGs provide a comprehensive approach to diagnosis and management of the two most common sleep disorders, including a discussion of the sequencing of diagnostic approaches and treatment options. Regarding OSA, strong recommendations were made for follow-up evaluation after non-diagnostic home sleep apnea tests, positive airway pressure therapy as first-line treatment, and the incorporation of supportive, educational and behavioral interventions for patients at high risk for PAP therapy non-adherence due to comorbid conditions. Strong recommendations were also made for the use of cognitive-behavioral therapy for insomnia and against the use of kava (an herbal supplement) in the treatment of chronic insomnia disorder. These guidelines, while intended to directly inform care within VA and DOD, are broadly relevant to the practice of sleep medicine. The majority of scientific evidence was based on studies of non-military, non-veteran populations. The CPG is a major milestone for the VA and DOD in recognizing the importance of evidence-based treatments for sleep disorders in military personnel and veterans.

The Veterans Administration and Department of Defense clinical practice guidelines for the diagnosis and management of sleep disorders: what does this mean for the practice of sleep medicine?

In 2017 the Veterans Administration (VA) and Department of Defense (DOD) launched development of clinical practice guidelines (CPGs) for the diagnosis and treatment of sleep disorders, with the goal of informing and improving patient care. The guideline development process followed GRADE methodology, considering studies and systematic reviews published over the 10-year period prior to guideline development. A total of 41 recommendations were made,18 related to the diagnosis and treatment of obstructive sleep apnea (OSA) and 23 regarding chronic insomnia disorder. In contrast to other published guidelines, the VA DoD CPGs provide a comprehensive approach to diagnosis and management of the two most common sleep disorders, including a discussion of the sequencing of diagnostic approaches and treatment options. Regarding OSA, strong recommendations were made for follow-up evaluation after non-diagnostic home sleep apnea tests, positive airway pressure therapy as first-line treatment, and the incorporation of supportive, educational and behavioral interventions for patients at high risk for PAP therapy non-adherence due to comorbid conditions. Strong recommendations were also made for the use of cognitive-behavioral therapy for insomnia and against the use of kava (an herbal supplement) in the treatment of chronic insomnia disorder. These guidelines, while intended to directly inform care within VA and DOD, are broadly relevant to the practice of sleep medicine. The majority of scientific evidence was based on studies of non-military, non-veteran populations. The CPG is a major milestone for the VA and DOD in recognizing the importance of evidence-based treatments for sleep disorders in military personnel and veterans.

The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines

Description: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.

Effect of acetazolamide on susceptibility to central sleep apnea in chronic spinal cord injury.

Spinal cord injury (SCI) is an established risk factor for central sleep apnea. Acetazolamide (ACZ), a carbonic anhydrase inhibitor, has been shown to decrease the frequency of central apnea by inducing mild metabolic acidosis. We hypothesized that ACZ would decrease the propensity to develop hypocapnic central apnea and decrease the apneic threshold. We randomized 16 participants with sleep-disordered breathing (8 SCI and 8 able-bodied controls) to receive ACZ (500 mg twice a day for 3 days) or placebo with a 1-wk washout before crossing over to the other drug arm. Study nights included polysomnography and determination of the hypocapnic apneic threshold and CO2 reserve using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal Pco2 (PETCO2) before and after. Steady-state plant gain, the response of end-tidal Pco2 to changes in ventilation, was calculated from PETCO2 and V̇e ratio during stable sleep. Controller gain, the response of ventilatory drive to changes in end-tidal Pco2, was defined as the ratio of change in V̇e between control and hypopnea to the ΔCO2 during stable non-rapid eye movement sleep. Treatment with ACZ for three days resulted in widening of the CO2 reserve (-4.0 ± 1.2 vs. -3.0 ± 0.7 mmHg for able-bodied, -3.4 ± 1.9 vs. -2.2 ± 2.2 mmHg for SCI, P < 0.0001), and a corresponding decrease in the hypocapnic apnea threshold (28.3 ± 5.2 vs. 37.1 ± 5.6 mmHg for able-bodied, 29.9 ± 5.4 vs. 34.8 ± 6.9 mmHg for SCI, P < 0.0001), respectively. ACZ significantly reduced plant gain when compared with placebo (4.1 ± 1.7 vs. 5.4 ± 1.8 mmHg/L min for able-bodied, 4.1 ± 2.0 vs. 5.1 ± 1.7 mmHg·L-1·min for SCI, P < 0.01). Acetazolamide decreased apnea-hypopnea index (28.8 ± 22.9 vs. 39.3 ± 24.1 events/h; P = 0.05), central apnea index (0.6 ± 1.5 vs. 6.3 ± 13.1 events/h; P = 0.05), and oxyhemoglobin desaturation index (7.5 ± 8.3 vs. 19.2 ± 15.2 events/h; P = 0.01) compared with placebo. Our results suggest that treatment with ACZ decreases susceptibility to hypocapnic central apnea due to decreased plant gain. Acetazolamide may attenuate central sleep apnea and improve nocturnal oxygen saturation, but its clinical utility requires further investigation in a larger sample of patients.NEW & NOTEWORTHY Tetraplegia is a risk factor for central sleep-disordered breathing (SDB) and is associated with narrow CO2 reserve (a marker of susceptibility to central apnea). Treatment with high-dose acetazolamide for 3 days decreased susceptibility to hypocapnic central apnea and reduced the frequency of central respiratory events during sleep. Acetazolamide may play a therapeutic role in alleviating central SDB in patients with cervical spinal cord injury, but larger clinical trials are needed.

The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines.

Description: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. Methods: In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.

Correlates and consequences of central sleep apnea in a national sample of US veterans.

The prevalence and consequences of central sleep apnea (CSA) in adults are not well described. By utilizing the large Veterans Health Administration (VHA) national administrative databases, we sought to determine the incidence, clinical correlates, and impact of CSA on healthcare utilization in Veterans. Analysis of a retrospective cohort of patients with sleep disorders was performed from outpatient visits and inpatient admissions from fiscal years 2006 through 2012. The CSA group, defined by International Classification of Diseases-9, was compared with a comparison group. The number of newly diagnosed CSA cases increased fivefold during this timeframe; however, the prevalence was highly variable depending on the VHA site. The important predictors of CSA were male gender (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.94-2.76, p < 0.0001), heart failure (HF) (OR = 1.78, 95% CI: 1.64-1.92, p < 0.0001), atrial fibrillation (OR = 1.83, 95% CI: 1.69-2.00, p < 0.0001), pulmonary hypertension (OR = 1.38, 95% CI:1.19-1.59, p < 0.0001), stroke (OR = 1.65, 95% CI: 1.50-1.82, p < 0.0001), and chronic prescription opioid use (OR = 1.99, 95% CI: 1.87-2.13, p < 0.0001). Veterans with CSA were at an increased risk for hospital admissions related to cardiovascular disorders compared with the comparison group (incidence rate ratio [IRR] = 1.50, 95% CI: 1.16-1.95, p = 0.002). Additionally, the effect of prior HF on future admissions was greater in the CSA group (IRR: 4.78, 95% CI: 3.87-5.91, p < 0.0001) compared with the comparison group (IRR = 3.32, 95% CI: 3.18-3.47, p < 0.0001). Thus, CSA in veterans is associated with cardiovascular disorders, chronic prescription opioid use, and increased admissions related to the comorbid cardiovascular disorders. Furthermore, there is a need for standardization of diagnostics methods across the VHA to accurately diagnose CSA in high-risk populations.

Apnea in Older Adults.

Sleep-disordered breathing (SDB) is a highly prevalent chronic disease in older adults. A growing body of evidence demonstrates that SDB in older adults is linked to many adverse cardiovascular, neurocognitive, and metabolic sequelae. However, several unanswered questions remain regarding the diagnosis, consequences, and treatment of SDB in older adults. This review presents the current evidence pertaining to the management of SDB in older adults and identifies crucial gaps in knowledge that need further investigation.

Aging is associated with increased propensity for central apnea during NREM sleep.

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO2 reserve (-2.6 ± 0.4 vs. -4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min-1·mmHg-1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.

Sleep Disordered Breathing Caused by Chronic Opioid Use: Diverse Manifestations and Their Management.

Opioid-induced sleep disordered breathing presents a therapeutic predicament with the increasing incidence of prescription opioid use for noncancer chronic pain in the United States. Central sleep apnea with a Biot or cluster breathing pattern is characteristic of polysomnography studies; however, long-term clinical outcomes and the impact of therapy remain unknown. Novel ampakine-based therapies are being investigated. Randomized controlled trials with therapies that target the underlying pathophysiologic mechanisms of opioid-induced sleep disordered breathing are required.

Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for the diagnosis of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Academy of Sleep Medicine (AASM) guidelines on the evaluation and treatment of sleep-disordered breathing in adults. METHODS: The AASM commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use. In addition, the task force adopted foundational recommendations from prior guidelines as "good practice statements", that establish the basis for appropriate and effective diagnosis of OSA. The AASM Board of Directors approved the final recommendations. RECOMMENDATIONS: The following recommendations are intended as a guide for clinicians diagnosing OSA in adults. Under GRADE, a STRONG recommendation is one that clinicians should follow under most circumstances. A WEAK recommendation reflects a lower degree of certainty regarding the outcome and appropriateness of the patient-care strategy for all patients. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. Good Practice Statements: Diagnostic testing for OSA should be performed in conjunction with a comprehensive sleep evaluation and adequate follow-up. Polysomnography is the standard diagnostic test for the diagnosis of OSA in adult patients in whom there is a concern for OSA based on a comprehensive sleep evaluation.Recommendations: We recommend that clinical tools, questionnaires and prediction algorithms not be used to diagnose OSA in adults, in the absence of polysomnography or home sleep apnea testing. (STRONG). We recommend that polysomnography, or home sleep apnea testing with a technically adequate device, be used for the diagnosis of OSA in uncomplicated adult patients presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA. (STRONG). We recommend that if a single home sleep apnea test is negative, inconclusive, or technically inadequate, polysomnography be performed for the diagnosis of OSA. (STRONG). We recommend that polysomnography, rather than home sleep apnea testing, be used for the diagnosis of OSA in patients with significant cardiorespiratory disease, potential respiratory muscle weakness due to neuromuscular condition, awake hypoventilation or suspicion of sleep related hypoventilation, chronic opioid medication use, history of stroke or severe insomnia. (STRONG). We suggest that, if clinically appropriate, a split-night diagnostic protocol, rather than a full-night diagnostic protocol for polysomnography be used for the diagnosis of OSA. (WEAK). We suggest that when the initial polysomnogram is negative and clinical suspicion for OSA remains, a second polysomnogram be considered for the diagnosis of OSA. (WEAK).

Control of Ventilation in Health and Disease.

Control of ventilation occurs at different levels of the respiratory system through a negative feedback system that allows precise regulation of levels of arterial carbon dioxide and oxygen. Mechanisms for ventilatory instability leading to sleep-disordered breathing include changes in the genesis of respiratory rhythm and chemoresponsiveness to hypoxia and hypercapnia, cerebrovascular reactivity, abnormal chest wall and airway reflexes, and sleep state oscillations. One can potentially stabilize breathing during sleep and treat sleep-disordered breathing by identifying one or more of these pathophysiological mechanisms. This review describes the current concepts in ventilatory control that pertain to breathing instability during wakefulness and sleep, delineates potential avenues for alternative therapies to stabilize breathing during sleep, and proposes recommendations for future research.

Updated Adaptive Servo-Ventilation Recommendations for the 2012 AASM Guideline: "The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses".

ABSTRACT: An update of the 2012 systematic review and meta-analyses were performed and a modified-GRADE approach was used to update the recommendation for the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea syndrome (CSAS) related to congestive heart failure (CHF). Meta-analyses demonstrated an improvement in LVEF and a normalization of AHI in all patients. Analyses also demonstrated an increased risk of cardiac mortality in patients with an LVEF of ≤ 45% and moderate or severe CSA predominant sleep-disordered breathing. These data support a Standard level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF > 45% or mild CHF-related CSAS. The application of these recommendations is limited to the target patient populations; the ultimate judgment regarding propriety of any specific care must be made by the clinician.