Identification of Sleep Medicine and Anesthesia Core Topics for Anesthesia Residency: A Modified Delphi Technique Survey.

BACKGROUND: Sleep disorders affect up to 25% of the general population and are associated with increased risk of adverse perioperative events. The key sleep medicine topics that are most important for the practice of anesthesiology have not been well-defined. The objective of this study was to determine the high-priority sleep medicine topics that should be included in the education of anesthesia residents based on the insight of experts in the fields of anesthesia and sleep medicine. METHODS: We conducted a prospective cross-sectional survey of experts in the fields of sleep medicine and anesthesia based on the Delphi technique to establish consensus on the sleep medicine topics that should be incorporated into anesthesia residency curricula. Consensus for inclusion of a topic was defined as >80% of all experts selecting "agree" or "strongly agree" on a 5-point Likert scale. Responses to the survey questions were analyzed with descriptive statistical methods and presented as percentages or weighted mean values with standard deviations (SD) for Likert scale data. RESULTS: The topics that were found to have 100% agreement among experts were the influence of opioids and anesthetics on control of breathing and upper airway obstruction; potential interactions of wake-promoting/hypnotic medications with anesthetic agents; effects of sleep and anesthesia on upper airway patency; and anesthetic management of sleep apnea. Less than 80% agreement was found for topics on the anesthetic implications of other sleep disorders and future pathways in sleep medicine and anesthesia. CONCLUSIONS: We identify key topics of sleep medicine that can be included in the future design of anesthesia residency training curricula.

The Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study: design, rationale, and methods.

PURPOSE: The goal of the Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study is to develop a prognostic model for cardiovascular outcomes, based on physiologic variables-related to breathing, sleep architecture, and oxygenation-measured during polysomnography in US veterans. METHODS: The DREAM study is a multi-site, retrospective observational cohort study conducted at three Veterans Affairs (VA) centers (West Haven, CT; Indianapolis, IN; Cleveland, OH). Veterans undergoing polysomnography between January 1, 2000 and December 31, 2004 were included based on referral for evaluation of sleep-disordered breathing, documented history and physical prior to sleep testing, and ≥2-h sleep monitoring. Demographic, anthropomorphic, medical, medication, and social history factors were recorded. Measures to determine sleep apnea, sleep architecture, and oxygenation were recorded from polysomnography. VA Patient Treatment File, VA-Medicare Data, Vista Computerized Patient Record System, and VA Vital Status File were reviewed on dates subsequent to polysomnography, ranging from 0.06 to 8.8 years (5.5 ± 1.3 years; mean ± SD). RESULTS: The study population includes 1840 predominantly male, middle-aged veterans. As designed, the main primary outcome is the composite endpoint of acute coronary syndrome, stroke, transient ischemic attack, or death. Secondary outcomes include incidents of neoplasm, congestive heart failure, cardiac arrhythmia, diabetes, depression, and post-traumatic stress disorder. Laboratory outcomes include measures of glycemic control, cholesterol, and kidney function. (Actual results are pending.) CONCLUSIONS: This manuscript provides the rationale for the inclusion of veterans in a study to determine the association between physiologic sleep measures and cardiovascular outcomes and specifically the development of a corresponding outcome-based prognostic model.

Severe obstructive sleep apnea increases mortality in patients with ischemic heart disease and myocardial injury.

OBJECTIVES: We hypothesized that obstructive sleep apnea(OSA) has a dose-dependent impact on mortality in those with ischemic heart disease or previous myocardial injury. METHODS: We performed a retrospective cohort study of 281 consecutive OSA patients with a history of myocardial injury as determined by elevated troponin levels or with known existing ischemic heart disease. We compared survival between those with severe OSA [apnea­hypopneaindex (AHI) ≥30] and those with mild to moderate OSA(AHI >5 and <30). RESULTS: Of the 281 patients (mean age 65 years, mean BMI34, 98% male, 58% with diabetes), 151 patients had mild moderate OSA and 130 had severe OSA. During a mean follow-up of 4.1 years, there were significantly greater deaths in the severe OSA group compared to the mild moderate OSA group [53 deaths (41%) vs. 44 deaths(29%), respectively, p00.04]. The adjusted hazard ratio for mortality with severe OSA was 1.72 (95% confidence interval1.01­2.91, p00.04). CONCLUSIONS: The severity of obstructive sleep apnea is associated with increased risk of death, and risk stratification based on OSA severity is relevant even in the diseased cardiac patient.

The use of continuous positive airway pressure in COPD-OSA overlap syndrome: A systematic review.

BACKGROUND: The co-occurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), known as COPD-OSA overlap syndrome, increases morbidity and mortality. The effectiveness of continuous positive airway pressure (CPAP) therapy, a commonly used treatment for OSA, in this patient population remains uncertain. Therefore, we conducted a systematic review to evaluate the efficacy of CPAP therapy in improving clinical outcomes. METHODS: We conducted a comprehensive systematic review to identify studies that evaluated the impact of CPAP therapy on COPD exacerbation, hospitalization, and mortality in patients with COPD-OSA overlap syndrome. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Statement and assessed the quality of each study using the Newcastle-Ottawa quality scale. RESULTS: From the initial 3184 articles identified, we reviewed 365 and included five in the systematic review. Our findings revealed that CPAP therapy improved clinical outcomes, including COPD exacerbation, COPD related hospitalization, and mortality in patients with COPD-OSA overlap syndrome. However, the definition of COPD and OSA varied across studies, and the definition of CPAP usage was not consistent. CONCLUSION: Our systematic review suggests that CPAP therapy is effective in improving outcomes in patients with COPD-OSA overlap syndrome. Nonetheless, further research is required to establish the efficacy of CPAP therapy by standardizing the definition of COPD, OSA, and CPAP usage.

Society of Anesthesia and Sleep Medicine and the Society for Obstetric Anesthesia and Perinatology Consensus Guideline on the Screening, Diagnosis, and Treatment of Obstructive Sleep Apnea in Pregnancy.

The Society of Anesthesia and Sleep Medicine and the Society for Obstetric Anesthesia and Perinatology tasked an expert group to review existing evidence and to generate recommendations on the screening, diagnosis, and treatment of patients with obstructive sleep apnea during pregnancy. These recommendations are based on a systematic review of the available scientific evidence and expert opinion when scientific evidence is lacking. This guideline may not be appropriate for all clinical situations and patients, and physicians must decide whether these recommendations are appropriate for their patients on an individual basis. We recognize that not all pregnant people may identify as women. However, data on non-cisgendered pregnant patients are lacking, and many published studies use gender-binary terms; therefore, depending on the study referenced, we may refer to pregnant individuals as women. This guideline may inform the creation of clinical protocols by individual institutions that consider the unique considerations of their patient populations and the available resources.

Recent cannabis use and nightly sleep duration in adults: a population analysis of the NHANES from 2005 to 2018.

BACKGROUND: While popularly consumed for its perceived benefits as a sleeping aid, the impact of cannabis on sleep-wake regulation in clinical studies is inconclusive. The purpose of this study was to determine the relationship between cannabis use and nightly sleep duration in a nationally representative dataset. METHODS: A cross-sectional analysis of adults was undertaken using the National Health and Nutrition Examination Survey data from 2005 to 2018. Respondents were dichotomized as recent users or non-users if they had used or not used cannabis in the past 30 days, respectively. The primary outcome was nightly sleep duration, categorized as short (<6 hours), optimal (6-9 hours), and long (>9 hours). Multinomial logistic regression was used to adjust for sociodemographic and health-related covariates, and survey sample weights were used in modeling. RESULTS: From a sample representing approximately 146 million adults in the USA, 14.5% reported recent cannabis use. In an adjusted analysis, recent users were more likely than non-users to report both short sleep (OR 1.34, 95% CI 1.12 to 1.59, p<0.001) and long sleep (OR 1.56, 95% CI 1.25 to 1.96, p<0.001). Heavy users (≥20 of the past 30 days) were even more likely to be at the extremes of nightly sleep duration. DISCUSSION: Recent cannabis use was associated with the extremes of nightly sleep duration in a nationally representative sample of adults, with suggestions of a dose-response relationship. Our findings highlight the need to further characterize the sleep health of regular cannabis users in the population.

Impact of Sex on Sleep Disorders Across the Lifespan.

Sleep throughout a woman's life impacts her quality of life and medical comorbidities. The prevalence of sleep symptoms and disorders varies throughout a woman's life in association with the reproductive milestones of pregnancy and menopause. Studies have failed to identify a clear sex predominance of sleep disorders in childhood and adolescence. Sleep disturbances in pregnancy are common and may be associated with increased risk for adverse maternal outcomes. Menopause is associated with sleep disruption owing to increased rates of sleep-disordered breathing, development of insomnia owing to vasomotor symptoms and hormonal changes, circadian derangements, and changes in sleep architecture.

Optimal NIV Medicare Access Promotion: Patients With Hypoventilation Syndromes: A Technical Expert Panel Report From the American College of Chest Physicians, the American Association for Respiratory Care, the American Academy of Sleep Medicine, and the American Thoracic Society.

The existing coverage criteria for home noninvasive ventilation (NIV) do not recognize the diversity of hypoventilation syndromes and advances in technologies. This document summarizes the work of the hypoventilation syndromes Technical Expert Panel working group. The most pressing current coverage barriers identified were: (1) overreliance on arterial blood gases (particularly during sleep); (2) need to perform testing on prescribed oxygen; (3) requiring a sleep study to rule out OSA as the cause of sustained hypoxemia; (4) need for spirometry; (5) need to show bilevel positive airway pressure (BPAP) without a backup rate failure to qualify for BPAP spontaneous/timed; and (6) qualifying hospitalized patients for home NIV therapy at the time of discharge. Critical evidence support for changes to current policies includes randomized controlled trial evidence and clinical practice guidelines. To decrease morbidity and mortality by achieving timely access to NIV for patients with hypoventilation, particularly those with obesity hypoventilation syndrome, we make the following key suggestions: (1) given the significant technological advances, we advise acceptance of surrogate noninvasive end-tidal and transcutaneous Pco2 and venous blood gases in lieu of arterial blood gases; (2) not requiring Pco2 measures while on prescribed oxygen; (3) not requiring a sleep study to avoid delays in care in patients being discharged from the hospital; (4) remove spirometry as a requirement; and (5) not requiring BPAP without a backup rate failure to approve BPAP spontaneous/timed. The overarching goal of the Technical Expert Panel is to establish pathways that improve clinicians' management capability to provide Medicare beneficiaries access to appropriate home NIV therapy. Adoption of these proposed suggestions would result in the right device, for the right type of patient with hypoventilation syndromes, at the right time.

The use of telemedicine for the diagnosis and treatment of sleep disorders: an American Academy of Sleep Medicine update.

NONE: The COVID-19 pandemic led to widespread use of telemedicine and highlighted its importance in improving access to sleep care and advocating for sleep health. This update incorporates the lessons learned from such widespread utilization of telehealth to build on the American Academy of Sleep Medicine's 2015 position paper on the use of telemedicine for diagnosing and treating sleep disorders. Important key factors in this update include an emphasis on quality and value, privacy and safety, health advocacy through sleep telemedicine, and future directions.

A neutrophil activation signature predicts critical illness and mortality in COVID-19.

Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.

Sex differences in obstructive sleep apnea phenotypes, the multi-ethnic study of atherosclerosis.

STUDY OBJECTIVES: The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea-hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes. METHODS: Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI. RESULTS: The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%-10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P. CONCLUSIONS: There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.

Circulating markers of angiogenesis and endotheliopathy in COVID-19.

Increase in thrombotic and microvascular complications is emerging to be a key feature of patients with critical illness associated with COVID-19 infection. While endotheliopathy is thought to be a key factor of COVID-19-associated coagulopathy, markers indicative of this process that are prognostic of disease severity have not been well-established in this patient population. Using plasma profiling of patients with COVID-19, we identified circulating markers that segregated with disease severity: markers of angiogenesis (VEGF-A, PDGF-AA and PDGF-AB/BB) were elevated in hospitalized patients with non-critical COVID-19 infection, while markers of endothelial injury (angiopoietin-2, FLT-3L, PAI-1) were elevated in patients with critical COVID-19 infection. In survival analysis, elevated markers of endothelial injury (angiopoietin-2, follistatin, PAI-1) were strongly predictive of in-hospital mortality. Our findings demonstrate that non-critical and critical phases of COVID-19 disease may be driven by distinct mechanisms involving key aspects of endothelial cell function, and identify drivers of COVID-19 pathogenesis and potential targets for future therapies.

A neutrophil activation signature predicts critical illness and mortality in COVID-19.

Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of over 3,300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, HGF, IL-8, and G-CSF, as the strongest predictors of critical illness. Neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, we define an essential role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular neutrophil markers that distinguish patients at risk of future clinical decompensation.

Sleep in Women Across the Life Span.

There are many ways in which women experience sleep differently from men. Women contending with distinct sleep challenges respond differently to sleep disorders, as well as sleep deprivation and deficiency, and face particular health outcomes as a result of poor sleep. Idiosyncrasies, including changes that occur with the biological life cycles of menstruation, pregnancy, and menopause, make the understanding of sleep in women an important topic to study. Each phase of a woman's life, from childhood to menopause, increases the risk of sleep disturbance in unique ways that may require distinct management. Indeed, new research is unraveling novel aspects of sleep pathology in women and the fundamental role that sex hormones play in influencing sleep regulation and arousals and possibly outcomes of sleep conditions. Moreover, studies indicate that during times of hormonal change, women are at an increased risk for sleep disturbances such as poor sleep quality and sleep deprivation, as well as sleep disorders such as OSA, restless legs syndrome, and insomnia. This article reviews sleep changes in female subjects from neonatal life to menopause.

Servo-Ventilation Therapy for Sleep-Disordered Breathing.

As seen in this CME online activity (available at http://journal.cme.chestnet.org/sv-sleep-disorder), central sleep apnea (CSA) is associated with increased mortality in patients with heart failure (HF), and it has been thought that treatment of CSA may improve underlying HF. Positive airway pressure therapy, specifically auto-servoventilation (ASV), can not only suppress abnormal breathing patterns but has been reported to improve cardiac function in HF patients with CSA. In patients with HF and with CSA unsuppressed with CPAP, newer ASV use has been associated with significant CSA improvement; in addition, several studies have reported efficacy of ASV in the treatment of underlying cardiac dysfunction in HF patients with CSA. However, results from the large randomized Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo-Ventilation in Patients with Heart Failure (SERVE-HF) trial (Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. New Engl J Med. 2015;373[12]:1095-1105) showed no significant effect on the primary end point in patients with stable HF with reduced ejection fraction and predominantly CSA, but all-cause and cardiovascular mortality were both increased in the ASV arm. These results are surprising and inconsistent with earlier smaller studies reporting positive surrogate outcomes, and they require additional study and resolution. However, until this is done, there is an urgent educational need for review of the approved labeling and validated clinical use of ASV within the medical community. The purpose of this educational activity is to review the appropriate use of ASV for the treatment of sleep-disordered breathing, including Cheyne-Stokes respiration, treatment-emergent central apnea, and opioid-induced periodic breathing. Emphasis will be placed on proper patient and therapy selection, especially in patients with HF.

Varying Hypopnea Definitions Affect Obstructive Sleep Apnea Severity Classification and Association With Cardiovascular Disease.

STUDY OBJECTIVES: To compare clinical features and cardiovascular risks in patients with obstructive sleep apnea (OSA) based on ≥ 3% desaturation or arousal, and ≥ 4% desaturation hypopnea criteria. METHODS: This is a cross-sectional analysis of 1,400 veterans who underwent polysomnography for suspected sleep-disordered breathing. Hypopneas were scored using ≥ 4% desaturation criteria per the American Academy of Sleep Medicine (AASM) 2007 guidelines, then re-scored using ≥ 3% desaturation or arousal criteria per AASM 2012 guidelines. The effect on OSA disease categorization by these two different definitions were compared and correlated with symptoms and cardiovascular associations using unadjusted and adjusted logistic regression. RESULTS: The application of the ≥ 3% desaturation or arousal definition of hypopnea captured an additional 175 OSA diagnoses (12.5%). This newly diagnosed OSA group (OSAnew) was symptomatic with daytime sleepiness similarly to those in whom OSA had been diagnosed based on ≥ 4% desaturation criteria (OSA4%). The OSAnew group was more obese and more likely to be male than those without OSA based on either criterion (No-OSA). However, the OSAnew group was younger, less obese, more likely female, and had a lesser smoking history compared to the OSA4% group. Those with any severity of OSA4% had an increased adjusted odds ratio for arrhythmias (odds ratio = 1.95 [95% confidence interval 1.37-2.78], P = .0155). The more inclusive hypopnea definition (ie, ≥ 3% desaturation or arousal) resulted in recategorization of OSA diagnosis and severity, and attenuated the increased odds ratio for arrhythmias observed in mild and moderate OSA4%. However, severe OSA based on ≥ 3% desaturation or arousals (OSA3%/Ar) remained a significant risk factor for arrhythmias. OSA based on any definition was not associated with ischemic heart disease or heart failure. CONCLUSIONS: The most current AASM criteria for hypopnea identify a unique group of patients who are sleepy, but who are not at increased risk for cardiovascular disease. Though the different hypopnea definitions result in recategorization of OSA severity, severe disease whether defined by ≥ 3% desaturation/arousals or ≥ 4% desaturation remains predictive of cardiac arrhythmias. COMMENTARY: A commentary on this article appears in this issue on page 1971.

Diagnosing and Treating Sleep Apnea in Patients With Acute Cerebrovascular Disease.

Background Obstructive sleep apnea ( OSA ) is common among patients with acute ischemic stroke and transient ischemic attack. We evaluated whether continuous positive airway pressure for OSA among patients with recent ischemic stroke or transient ischemic attack improved clinical outcomes. Methods and Results This randomized controlled trial among patients with ischemic stroke/transient ischemic attack compared 2 strategies (standard or enhanced) for the diagnosis and treatment of OSA versus usual care over 1 year. Primary outcomes were National Institutes of Health Stroke Scale and modified Rankin Scale scores. Among 252 patients (84, control; 86, standard; 82, enhanced), OSA prevalence was as follows: control, 69%; standard, 74%; and enhanced, 80%. Continuous positive airway pressure use occurred on average 50% of nights and was similar among standard (3.9±2.1 mean hours/nights used) and enhanced (4.3±2.4 hours/nights used; P=0.46) patients. In intention-to-treat analyses, changes in National Institutes of Health Stroke Scale and modified Rankin Scale scores were similar across groups. In as-treated analyses among patients with OSA, increasing continuous positive airway pressure use was associated with improved National Institutes of Health Stroke Scale score (no/poor, -0.6±2.9; some, -0.9±1.4; good, -0.3±1.0; P=0.0064) and improved modified Rankin Scale score (no/poor, -0.3±1.5; some, -0.4±1.0; good, -0.9±1.2; P=0.0237). In shift analyses among patients with OSA, 59% of intervention patients had best neurological symptom severity (National Institutes of Health Stroke Scale score, 0-1) versus 38% of controls ( P=0.038); absolute risk reduction was 21% (number needed to treat, 4.8). Conclusions Although changes in neurological functioning and functional status were similar across the groups in the intention-to-treat analyses, continuous positive airway pressure use was associated with improved neurological functioning among patients with acute ischemic stroke/transient ischemic attack with OSA . Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT 01446913.