The effect of triazolam on arousal and respiration in central sleep apnea patients

It was hypothesized that triazolam might decrease central apneas associated with arousal periods in patients with central sleep apnea by hastening the onset of consolidated sleep. Five male patients, diagnosed as having central sleep apnea on a screening night, participated in a double-blind randomized crossover study of the effect of placebo, 0.125 mg triazolam, and 0.25 mg triazolam on sleep, respiration, and daytime function. Results indicated that the medication increased total sleep and decreased central apnea index and number of brief arousals. Improved sleep quality was reflected in improved daytime psychomotor performance and alertness. These data, if replicated, imply that benzodiazepine use may be beneficial in patients with central sleep apnea.     

Effect of infant sleeping position on sleep spindles

Sleep spindles play an active role in inducing and maintaining sleep and may affect arousal by blocking the transmission of external stimuli through the thalamus to the cortex. Previously we have demonstrated that sleeping in the prone position impairs arousal in infants at 2-3 months of age, but not at 5-6 months. We aimed to examine if sleeping position and postnatal age affected duration and/or density of sleep spindles. Twenty-one healthy term infants were studied using daytime polysomnography at 2-3 months and 16 were again studied at 5-6 months. Infants slept both prone and supine at each study. The mean duration of non-rapid eye movement (NREM) sleep was not different between the two studies in either position. At 2-3 months both spindle density (P < 0.001) and proportion of NREM sleep (P < 0.025) with spindles were significantly greater in the supine than in the prone position. At 5-6 months spindle duration was longer in the supine than in the prone position (P < 0.03). Spindle density in the supine position was not different between the two studies, however, when infants slept prone, it was significantly increased at 5-6 months compared with 2-3 months (P < 0.001). Arousal threshold was not correlated with either spindle density or percentage of NREM sleep with spindles in either position at either study. In this study spindle density and the percentage time spent with spindles were not well correlated with infant arousability, and hence may not be able to be used as markers of depressed arousal responses in infants.     

Idiopathic central sleep apnea during REM sleep

Idiopathic central sleep apnea during rapid eye movement (REM) sleep is an extremely rare condition and only two cases have been reported so far. We present the case of a male patient who presented with chronic insomnia. Blood gas analysis during wakefulness suggested the presence of hypocapnia. Polysomnographic examination revealed central sleep apnea occurring predominantly during REM sleep. The patient responded well to continuous positive airway pressure (CPAP) at a pressure of 6 cmH₂O as well as to acetazolamide therapy.     

Sleep apnea and body position during sleep

In patients with obstructive sleep apnea, it is believed that body position influences apnea frequency. Sleeping in the lateral decubitus position often results in significantly fewer apneas, and some have recommended sleeping on the side as the major treatment intervention. Previous studies, although calculating apnea-hypopnea index (AHI) for supine and lateral decubitus positions, have not taken sleep stage into account. To examine the effect of both sleep stage and body position on apnea duration (AD) and frequency, we determined AHI and AD in all spontaneous body positions during rapid eye movement (REM) and non-REM (NREM) sleep by reviewing videotapes and polysomnograms from 11 overnight studies of 7 obese patients with severe sleep apnea. Consistent with previous work, AD was significantly longer in REM then in NREM (32.5 +/- 2.3 s versus 23.5 +/- 1.9 s; p less than 0.05). This difference persisted when adjusting for body position. AHI was greater on the back than on the sides (84.4 +/- 4.9/h versus 73.6 +/- 7.5/h, p less than 0.05), but after accounting for sleep stage, this difference remained only for NREM (103 +/- 4.8/h versus 80.3 +/- 9.2/h, p less than 0.05) and not for REM (83.6 +/- 5.3/h versus 71.1 +/- 4.2/h, p NS). Although reduced, AHI on the sides still remained clinically very high. Body position changed frequently throughout the night, but some patients spent little or no time on their back. We conclude that AD is longer in REM than NREM, regardless of position, and AHI is higher on the back only in NREM. As AHI remains very high on the sides, favoring the lateral decubitus position may not be as beneficial as previously thought in very obese patients. Less obese patients are more likely to benefit by position changes.     

Body position and obstructive sleep apnea in children

STUDY OBJECTIVES: In adults, sleep apnea is worse when the patient is in the supine position. However, the relationship between sleep position and obstructive apnea in children is unknown. The objective of this study was to evaluate the relationship between obstructive apnea and body position during sleep in children. DESIGN: Retrospective analysis of the relationship between body position and obstructive apnea in obese and non-obese children. SETTING: Tertiary care pediatric sleep center. PATIENTS: Otherwise healthy children, aged 1-10 years, undergoing polysomnography for suspected obstructive sleep apnea syndrome. Obese and non-obese children were evaluated separately. INTERVENTIONS: Retrospective review of the relationship between sleep position and obstructive apnea during polysomnography. MEASUREMENTS AND RESULTS: Eighty polysomnograms from 56 non-obese and 24 obese children were analyzed. Body position was determined by a sensor during polysomnography, and confirmed by review of videotapes. Children had a lower obstructive apnea hypopnea index when supine vs. prone, and shorter apneas when supine then when on their side. There was no difference in apnea duration between the supine and prone positions. Obese and non-obese children showed similar positional changes. CONCLUSIONS: Children with obstructive sleep apnea, in contrast to adults, breathe best when in the supine position.     

Treatment of central sleep apnea in heart failure

Recent studies show that central sleep apnea occur in about 40% of patients with heart failure and systolic dysfunction. The pathophysiological consequences of central sleep apnea may contribute to morbidity and mortality of heart failure. Three treatment modalities, oxygen, continuous positive airway pressure and theophylline have been shown to decrease periodic breathing modestly with considerable improvement in arterial oxyhemoglobin desaturation, and variable effects on sleep characteristics. However, long-term effects of central sleep apnea and its treatment on the natural history of heart failure remain to be determined.     

Classification algorithms for predicting sleepiness and sleep apnea severity

Identifying predictors of subjective sleepiness and severity of sleep apnea are important yet challenging goals in sleep medicine. Classification algorithms may provide insights, especially when large data sets are available. We analyzed polysomnography and clinical features available from the Sleep Heart Health Study. The Epworth Sleepiness Scale and the apnea-hypopnea index were the targets of three classifiers: k-nearest neighbor, naive Bayes and support vector machine algorithms. Classification was based on up to 26 features including demographics, polysomnogram, and electrocardiogram (spectrogram). Naive Bayes was best for predicting abnormal Epworth class (0-10 versus 11-24), although prediction was weak: polysomnogram features had 16.7% sensitivity and 88.8% specificity; spectrogram features had 5.3% sensitivity and 96.5% specificity. The support vector machine performed similarly to naive Bayes for predicting sleep apnea class (0-5 versus >5): 59.0% sensitivity and 74.5% specificity using clinical features and 43.4% sensitivity and 83.5% specificity using spectrographic features compared with the naive Bayes classifier, which had 57.5% sensitivity and 73.7% specificity (clinical), and 39.0% sensitivity and 82.7% specificity (spectrogram). Mutual information analysis confirmed the minimal dependency of the Epworth score on any feature, while the apnea-hypopnea index showed modest dependency on body mass index, arousal index, oxygenation and spectrogram features. Apnea classification was modestly accurate, using either clinical or spectrogram features, and showed lower sensitivity and higher specificity than common sleep apnea screening tools. Thus, clinical prediction of sleep apnea may be feasible with easily obtained demographic and electrocardiographic analysis, but the utility of the Epworth is questioned by its minimal relation to clinical, electrocardiographic, or polysomnographic features.     

Metrics of sleep apnea severity: beyond the apnea-hypopnea index

Obstructive sleep apnea (OSA) is thought to affect almost 1 billion people worldwide. OSA has well established cardiovascular and neurocognitive sequelae, although the optimal metric to assess its severity and/or potential response to therapy remains unclear. The apnea-hypopnea index (AHI) is well established; thus, we review its history and predictive value in various different clinical contexts. Although the AHI is often criticized for its limitations, it remains the best studied metric of OSA severity, albeit imperfect. We further review the potential value of alternative metrics including hypoxic burden, arousal intensity, odds ratio product, and cardiopulmonary coupling. We conclude with possible future directions to capture clinically meaningful OSA endophenotypes including the use of genetics, blood biomarkers, machine/deep learning and wearable technologies. Further research in OSA should be directed towards providing diagnostic and prognostic information to make the OSA diagnosis more accessible and to improving prognostic information regarding OSA consequences, in order to guide patient care and to help in the design of future clinical trials.     

Association between atrial fibrillation and central sleep apnea

BACKGROUND: We previously described an association between atrial fibrillation and central sleep apnea in a group of patients with congestive heart failure. We hypothesized that the prevalence of atrial fibrillation might also be increased in patients with central sleep apnea in the absence of other cardiac disease. METHODS AND RESULTS: We compared the prevalence of atrial fibrillation in a series of 60 consecutive patients with idiopathic central sleep apnea (apnea-hypopnea index > 10 events per hour, > 50% central events) with that in 60 patients with obstructive sleep apnea (apnea-hypopnea index > 10, > 50% obstructive events) and 60 patients without sleep apnea (apnea-hypopnea index < 10), matched for age, sex, and body mass index. Subjects with a history of congestive heart failure, coronary artery disease, or stroke were excluded from the study. The prevalence of atrial fibrillation among patients with idiopathic central sleep apnea was found to be significantly higher than the prevalence among patients with obstructive sleep apnea or no sleep apnea (27%, 1.7%, and 3.3%, respectively, P < .001). However, hypertension was most common and oxygen desaturation most extreme among patients with obstructive sleep apnea. CONCLUSIONS: We conclude that there is a markedly increased prevalence of atrial fibrillation among patients with idiopathic central sleep apnea in the absence of congestive heart failure. Moreover, the high prevalence of atrial fibrillation among patients with idiopathic central sleep apnea is not explainable by the presence of hypertension or nocturnal oxygen desaturation, since both of these were more strongly associated with obstructive sleep apnea.     

Cheyne-Stokes breathing and systemic arterial pressure periodic pattern during sleep in central alveolar hypoventilation

This report refers to a 51 year old man with the clinical features of central alveolar hypoventilation (CAH). Polysomnographic recordings showed periodic breathing and central apnoeas associated with abnormal oscillations of systemic arterial pressure and heart rate during all sleep stages. Oxygen administration during sleep reduced hypoxia, while the periodic breathing and arterial pressure oscillations persisted. The authors suggest that an impairment of the brain structures that play a role in homeostatic adjustment of autonomic functions in connection with the sleep-wake cycle, is responsible for the unusual sleep-related disturbances shown by this patient.     

Surgical treatment of the sleep apnea syndrome reduces associated major depression

Prior small and retrospective studies have indicated that obstructive sleep apnea (OSA) disease-related psychiatric morbidity might be reversed by correcting the sleep-related breathing disorder. To evaluate the effect of surgical intervention (uvulopalatopharyngoplasty, UPPP) on associated psychiatric morbidity we prospectively evaluated a large cohort (n = 53) of OSA patients before and after UPPP. Surgical intervention resulted in a significant reduction of depressive disorder (p < .001) in parallel with improvement of the sleep disorder. Our results show that sleep disturbance and reduced daytime alertness may be at least one of the factors behind depressive symptoms in OSA. This study was supported by grants from the Swedish Medical Research Council (Grant No. 9892), the Swedish Heart and Lung Foundation, Inga-Britt and Arne Lundbergs Research Foundation, Skandia Insurance Company, The Swedish Medical Society, and Gothenburg University Research Foundation. Nils-Gunnar Pehrsson and Andreas Hagelin are gratefully acknowledged for skillful statistical assistance.     

Effects of age and sleeping position on arousal from sleep in preterm infants

STUDY OBJECTIVES: Preterm infants are at increased risk of sudden infant death syndrome (SIDS). We investigated whether the prone sleeping position impaired arousal from sleep in healthy preterm infants and whether this impairment was related to cardiorespiratory variables, temperature or postnatal age. DESIGN: Longitudinal SETTING/PARTICIPANTS: 14 healthy preterm infants (mean 32 +/- 0.4 weeks) were studied using daytime polysomnography on 4 occasions: 36-38 weeks postconception age, 2 to 3 weeks postterm, 2 to 3 months postterm, and 5 to 6 months postterm. Interventions: N/A. MEASUREMENTS: Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both AS and QS when infants slept prone at 36 to 38 weeks postconception age and 2 to 3 months postterm but not at 2 to 3 weeks or 5 to 6 months postterm. These increases were independent of any sleep position-related changes in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation or heart rate. CONCLUSIONS: At the age when the risk of SIDS is highest, the prone position significantly impairs arousal from both active sleep and quiet sleep in healthy infants born prematurely. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory parameters or body temperature. Decreased arousability from sleep in the prone position may explain its role as a risk factor for SIDS.     

Nocturnal oximetry parameters as predictors of sleep apnea severity in resource-limited settings

Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9–9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19–1.51); and OR 4.10, 95% CI 2.06–8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842–0.964] versus 0.745 [95% CI 0.668–0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available.     

Nocturnal nasal obstruction is frequent and reduces sleep quality in patients with obstructive sleep apnea

The prevalence and consequences of nasal obstruction in untreated obstructive sleep apnea patients are not known. The study objectives were to investigate the frequency of subjective and objective nasal obstruction in untreated sleep apnea patients and the associations with sleep and quality of life. Patients in the Icelandic Sleep Apnea Cohort were subjected to a type 3 sleep study, answered questionnaires and had their nasal dimensions measured by acoustic rhinometry. In total, 810 patients participated (including 153 females), aged 54.5 ± 10.6 years [mean ± standard deviation (SD)] with an apnea/hypopnea index 44.7 ± 20.7 h^?1. Nocturnal nasal obstruction (greater than or equal to three times per week) was reported by 35% of the patients. These patients had smaller nasal dimensions measured by the minimum cross‐sectional area within the smaller nasal valve (0.42 ± 0.17 versus 0.45 ± 0.16 cm², P = 0.013), reported more daytime sleepiness (Epworth Sleepiness Scale score 12.5 ± 4.9 versus 10.8 ± 5.0; P < 0.001) and slightly lower mental quality of life than patients without nocturnal nasal obstruction. Nocturnal nasal obstruction is reported in one‐third of the sleep apnea patients and they are more likely to suffer from daytime sleepiness and slightly reduced quality of life than other sleep apnea patients.     

Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea

Collapsibility of the upper airways has been identified as an important pathogenic factor in obstructive sleep apnea (OSA). Objective measures of collapsibility are pharyngeal critical pressure (Pcrit) and resistance of the upstream segment (Rus). To systematically determine the effects of sleep stage and body position we investigated 16 male subjects suffering from OSA. We compared the measures in light sleep, slow-wave sleep, REM sleep and supine vs. lateral positions. The pressure-flow relationship of the upper airways has been evaluated by simultaneous readings of maximal inspiratory airflow (Vimax) and nasal pressure (p-nCPAP). With two-factor repeated measures ANOVA on those 7 patients which had all 6 situations we found a significant influence of body position on Pcrit (p<0.05) whereas there was no significant influence of sleep stage and no significant interaction between body position and sleep stage. When comparing the body positions Pcrit was higher in the supine than in the lateral positions. During light sleep Pcrit decreased from 0.6 +/- 0.8 cm H2O (supine) to -2.2 +/- 3.6 cm H2O (lateral) (p<0.01), during slow-wave sleep Pcrit decreased from 0.3 +/- 1.4 cm H2O (supine) to -1.7 +/- 2.6 (lateral) (p<0.05) and during REM sleep it decreased from 1.2 +/- 1.5 cm H2O to -2.0 +/- 2.2 cm H2O (p<0.05). Changes in Rus revealed no body position nor sleep-stage dependence. Comparing the different body positions Rus was only significantly higher in the lateral position during REM sleep (p<0.05). The results indicate that collapsibility of the upper airways is not mediated by sleep stages but is strongly influenced by body position. As a consequence lower nCPAP pressure is needed during lateral positions compared to supine positions.     

Polysomnography with an epiglottic pressure catheter does not alter obstructive sleep apnea severity or sleep efficiency

Pharyngeal and oesophageal manometry is used clinically and in research to quantify respiratory effort, upper‐airway mechanics and the pathophysiological contributors to obstructive sleep apnea. However, the effects of this equipment on respiratory events and sleep in obstructive sleep apnea are unclear. As part of a clinical trial (ANZCTRN12613001106729), data from 28 participants who successfully completed a physiology night with an epiglottic catheter and nasal mask followed by a standard in‐laboratory polysomnography were compared. The apnea–hypopnea index was not different during the physiology night versus standard polysomnography (22 ± 14 versus 23 ± 13 events per hr, p = 0.71). Key sleep parameters were also not different compared between conditions, including sleep efficiency (79 ± 13 versus 81 ± 11%, p = 0.31) and the arousal index (26 ± 11 versus 27 ± 11 arousals per hr, p = 0.83). There were, however, sleep stage distribution changes between nights with less N3 and rapid eye movement sleep and more N1 on the physiology night, with no difference in N2 (53 ± 15 versus 48 ± 9, p = 0.08). However, these changes did not increase next‐day sleepiness. These findings indicate that while minor sleep stage distribution changes do occur towards lighter sleep, epiglottic manometry does not alter obstructive sleep apnea severity or sleep efficiency. Thus, epiglottic manometry can be used clinically and to collect detailed physiological information for research without major sleep disruption.