Recent Developments in Oral Appliance Therapy of Sleep Disordered Breathing

Oral appliances are increasingly gaining a place in the treatment of sleep disordered breathing caused by upper airway obstruction. This review of publications since 1995 documents substantial progress in the scientific basis for this therapy. Imaging by several techniques has shown that mandibular advancing oral appliances open the airway in awake and anaesthetized subjects, creating the presumption that this effect is maintained in sleep. Three controlled cross-over treatment trials have shown that patients consistently prefer oral appliance over continuous positive airway pressure therapy, especially when the treatment effect is strong. Appliance design and use indicates a preference for adjustable mandibular advancing appliances. Complications of therapy appear to be infrequent, but evidence for safety of long-term use is still limited. Oral appliance therapy can be an effective therapy for sleep disorders caused by upper airway obstruction. Considering the accumulated evidence, it is no longer tenable to label oral appliance therapy an experimentalÕ procedure.     

Little Effect of Ordinary Antihypertensive Therapy on Nocturnal High Blood Pressure in Patients with Sleep Disordered Breathing

The antihypertensive effects of four different antihypertensive medications (β-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM).Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM.Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD ± 14) mm Hg with atenolol, 7 (SD ± 10) mm Hg with isradipine SRO, 3 mm Hg (SD ± 14) with HCTZ, and 6 (SD ± 15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50.Negative correlation was observed between the apnea time and the mean systolic 24-h (r = −0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = −0.590, P = NS).Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.     

Sleep Disordered Breathing in Patients with Heart Failure: Pathophysiology and Management

Sleep disordered breathing (SDB) is common in heart failure patients across the range of ejection fractions and is associated with adverse prognosis. Although effective pharmacologic and device-based treatment of heart failure may reduce the frequency or severity of SDB, heart failure treatment alone may not be adequate to restore normal breathing during sleep. Continuous positive airway pressure (CPAP) is the major treatment for SDB in heart failure, especially if obstructive rather than central sleep apnea (CSA) predominates. Adequate suppression of CSA by PAP is associated with a heart transplant-free survival benefit, although randomized trials are ongoing. Bilevel PAP (BPAP) may be as effective as CPAP in treating SDB and may be preferable over CPAP in patients who experience expiratory pressure discomfort. Adaptive (or auto) servo-ventilation (ASV), which adjusts the PAP depending on the patient’s airflow or tidal volume, may be useful in congestive heart failure patients if CPAP is ineffective. Other therapies that have been proposed for SDB in congestive heart failure include nocturnal oxygen, CO₂ administration (by adding dead space), theophylline, and acetazolamide; most of which have not been systematically studied in outcome-based prospective randomized trials.     

Management of Sleep Disordered Breathing in Patients with Heart Failure

Purpose of Review

This paper reviews treatment options for sleep disordered breathing (SDB) in patients with heart failure. We sought to identify therapies for SDB with the best evidence for long-term use in patients with heart failure and to minimize uncertainties in clinical practice by examining frequently discussed questions: what is the role of continuous positive airway pressure (CPAP) in patients with heart failure? Is adaptive servo-ventilation (ASV) safe in patients with heart failure? To what extent is SDB a modifiable risk factor?

Recent Findings

Consistent evidence has demonstrated that the development of SDB in patients with heart failure is a poor prognostic indicator and a risk factor for cardiovascular mortality. However, despite numerous available interventions for obstructive sleep apnea and central sleep apnea, it remains unclear what effect these therapies have on patients with heart failure. To date, all major randomized clinical trials have failed to demonstrate a survival benefit with SDB therapy and one major study investigating the use of adaptive servo-ventilation demonstrated harm.

Summary

Significant questions persist regarding the management of SDB in patients with heart failure. Until appropriately powered trials identify a treatment modality that increases cardiovascular survival in patients with SDB and heart failure, a patient’s heart failure management should remain the priority of medical care.

     

Sleep Disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease

Sleep-related disordered breathing (SDB) and its influence on desaturation were examined in stable COPD patients with waking SpO₂ > 90%. With respiratory inductance plethysmography, thoracic-abdominal respiratory movements for all events with more than 4% desaturation were analyzed in 26 patients. Types of SDB were confirmed by full polysomnography. Irregular breathing induced desaturation, while stable respiration continued during some desaturation events. Three types of altered ventilation were observed: hypoventilation, paradoxical movement and periodic breathing. An unusual type of paradoxical movement, with normal airflow despite progressive desaturation, was observed in REM sleep. Patients were divided into desaturation (15 patients) and non-desaturation (11 patients) groups. Daytime arterial blood gas, lung function values, and 6-min walking distance did not differ. Awake, mode, maximum and minimum nocturnal SpO₂ were lower in the desaturation group. SDB-induced desaturation events in the desaturation group were more frequent (9.2 ± 3.5 vs. 1.8 ± 2.2 times), a greater SpO₂ decrease (11.4 ± 7.1% vs. 5.2 ± 2.1%) and longer duration (73.2 ± 34.8 vs. 18.8 ± 39.0 min). Patterns of SDB in the desaturation group were hypoventilation (74.4 ± 23.4%), paradoxical movement (10.2 ± 14.5%), periodic breathing (12.1 ± 18.3%) and unclassified (5.8 ± 11.2%). These results reveal that lower SpO₂ and SDB influence nocturnal desaturation in stable COPD patients.     

Arrhythmia Risk Associated with Sleep Disordered Breathing in Chronic Heart Failure

The intersecting relationships of sleep disordered breathing (SDB), arrhythmogenic risk and chronic heart failure (HF) are complex and most likely multi-directional and synergistic. Autonomic dysfunction is a common pathophysiological feature of each of these entities. Intermittent hypoxia, hypercapnia, mechanical cardiac influences due to upper airway obstruction and rostral fluid shifts are SDB-specific mechanisms which may trigger, perpetuate and exacerbate HF and arrhythmogenesis. Specific pathophysiological mechanisms will vary according to the predominance of central as compared to obstructive sleep apnea. The risk of cardiac arrhythmias and HF attributable to SDB may be considerable given the high prevalence of SDB and its likely physiologic burden. The current review focuses on the data, which have accrued elucidating the specific contributory mechanisms of SDB in cardiac arrhythmias and HF, highlighting the clinical relevance and effects of standard SDB treatment on these outcomes, and describing the role of novel therapeutics.     

Association of Migraine and Sleep-Related Breathing Disorder: A Population-Based Cohort Study

In this nationwide population-based cohort study, we aimed to evaluate the effects of sleep-related breathing disorders (SBD) on migraine development.Patients ages 20 years or more and diagnosed with SBD between 2000 and 2009 were evaluated as the SBD cohort (n = 3411), and compared with comparison cohort (n = 13,644). The adjusted hazard ratio (aHR) for developing migraine was calculated in both cohorts by multivariate Cox proportional hazards model.The cumulative incidence of migraine was significantly higher in the SBD cohort than in the comparison cohort. In the SBD cohort, the overall aHR for developing migraine was 2.43 (95% confidence interval [CI] = 1.72–3.44). The risk of developing migraine was higher in men (aHR 2.71) than in women (aHR 2.29) with SBD. When stratifying by age, we observed increased incidence of migraine in patients ages 20 to 44 years and 45 to 64 years, with a higher aHR of 2.51 (95% CI = 1.47–4.30) and 2.68 (95% CI = 1.63–4.43), respectively. The risk of developing migraine in the patients with SBD with or without comorbidity exhibited nonsignificant differences. After stratifying by the use of hypnotics, the aHR for developing migraine was 2.39 in the patients with hypnotics use and 3.58 in the patients without hypnotics use.Our findings indicate increased risk of developing migraine in adults, but not elderly ones, with SBD.     

Chronic Sleep Complaints in Premenopausal Women and Their Association with Sleep-Disordered Breathing

Background  In clinical practice, we have found that premenopausal women have delayed diagnosis of sleep-disordered breathing (SDB). Methods  During a 4-year period, we systematically collected the clinical and polysomnographic variables for all women referred for sleep complaints using preestablished questionnaires, scales, clinical grid, polygraphic montage, and scoring criteria. The variables collected on premenopausal SDB women were analyzed and compared to those of postmenopausal women within 5 years of menopause. Results  Of 977 women, 316 were premenopausal with SDB. Complaints of chronic insomnia and sleepwalking were the most common reasons for referral, had been present for a mean of 6.4 ± 5.4 years, and had lead to unsuccessful symptomatic treatment. The normal-weight premenopausal SDB group had anatomically small upper airways, while those with body mass index (BMI) ≥ 25 kg/m² complained more frequently of snoring and daytime sleepiness and their clinical presentation was closer to those of the postmenopausal SDB comparison group. Premenopausal women often had a low apnea-hypopnea index (AHI), but there was a discrepancy between the low AHI and the amount of continuous positive airway pressure (CPAP) needed to control the SDB, and there was a need for higher pressures in overweight premenopausal SDB women (mean 9.1 ± 1.9 and 10.1 ± 2.6 cmH₂O). Conclusion  Normal-weight premenopausal SDB women often present with atypical sleep complaints of chronic insomnia and parasomnias. Clinical attention paid to craniofacial features and use of specific scales such as Mallampati help with the suspicion of the presence of SDB, and a low AHI is unrelated to the positive clinical impact of nasal CPAP treatment.     

nCPAP 对中重度阻塞性睡眠呼吸暂停低通气综合征患者心肌供血的影响

目的 观察中重度阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与心肌供血的关系,探讨经鼻持续气道内正压通气(nCPAP)治疗对中重度OSAHS患者心肌供血的影响.方法 将明确诊断为中重度OSAHS患者中随机分为持续nCPAP治疗1年以上的长期治疗组(n=32 例),短期治疗组(n=30 例)及对照组(n=31 例).治疗前三组的临床基本特征差异无统计学意义(P＞0.05).分别对治疗后的三组患者进行24h动态心电图和睡眠呼吸监测,观察呼吸睡眠暂停-低通气事件、心肌缺血负荷,同时实时观察呼吸暂停-低通气事件和血氧饱和度下降与心肌缺血的关系.结果 对照组中13 例(41.94%)夜间出现心肌缺血发作,心肌缺血负荷为(59.12±7.18)mm·min / h.其与呼吸暂停- 低通气累计持续时间及累计次数呈正相关(r=0.816、0.749,P＜0.01).随着血氧饱和度下降幅度增加,心肌缺血发作次数也增多,差异有显著统计学意义(P＜0.01).长期治疗组患者经1年的nCPAP 治疗后夜间心肌缺血发生例数(6.25%、41.94%)及心肌缺血负荷[(1.32±0.78)mm·min / h、(59.12±17.18)mm·min / h],与对照组相比均明显减少,差异有显著统计学意义(P＜0.01),与短期治疗组比较差异无明显统计学意义(P＞0.05).在短期组中,仅3 例(10.00%)夜间出现心肌缺血发作,心肌缺血负荷为(2.42±1.43)mm·min / h,与对照组比较,心肌缺血程度减少,差异有显著统计学意义(P＜0.01).结论 夜间心肌缺血在中重度OSAHS患者中较多见,且与呼吸暂停- 低通气持续时间、发生次数及血氧饱和度下降幅度有关.无论长期还是短期的nCPAP 治疗都能明显减少中重度OSAHS 患者夜间心肌缺血的发生例数.     

阿罗洛尔降压疗效和对睡眠呼吸障碍的影响

目的：阿罗洛尔的抗高血压疗效和对睡眠呼吸状况的影响。方法：随机、单盲、自身对照法。２０例原发性高血压患者在治疗前后分别接受多导睡眠仪和动态血压等监测。结果：患者服药４周，收缩压从２１．７±２．０ｋＰａ（１６３±１５ｍｍＨｇ）降至１８．９±２．５ｋＰａ（１４２±１９ｍｍＨｇ）（Ｐ＝０．０００，ｎ＝２０），舒张压从１３．５±０．９ｋＰａ（１０１±７ｍｍＨｇ）降至１１．７±０．９ｋＰａ（８８±７ｍｍＨｇ）（Ｐ＝０．０００，ｎ＝２０）。合并睡眠呼吸暂停者治疗后呼吸紊乱指数从２４．６０降至１３．１６（Ｐ＜０．０５，ｎ＝５）。超声心动图结果提示患者心功能状态有显著改善。心率无明显下降，治疗后血浆高密度脂蛋白胆固醇增加，血浆肾素浓度降低。结论：阿罗洛尔有较好的降压疗效，可以减轻睡眠呼吸暂停患者的睡眠呼吸障碍，改善心功能，对代谢无不良影响     

Sleep Related Breathing Disorders Are Common Contributing Factors to the Production of Essential Hypertension But Are Neglected, Underdiagnosed, and Undertreated

There is now strong evidence from animal studies and, in humans, from epidemiological studies as well as from retrospective and prospective intervention studies, that obstructive sleep apnea (OSA) can cause persistent hypertension not only during sleep but during waking hours as well. There is also some evidence that habitual snoring alone, even without OSA, can do the same. Many of the hitherto unexplained epidemiological, clinical, biochemical, hematological, and physiological abnormalities seen in essential hypertension (EH) could be explained by the accompanying sleep related breathing disorders (SRBD). Many cases of resistant hypertension are probably due to SRBD. Recent studies show that SRBD are extremely common in EH but that the vast majority of patients with these sleep disorders are being missed by physicians who are treating the accompanying hypertension, even when the patients already have blatant symptoms of OSA. Recent investigations have shown that the probable reason for this underdiagnosis of OSA is lack of physician knowledge about the condition. This lack of knowledge is prevalent not only among family physicians, but among hypertension specialists and researchers in the field of hypertension as well. OSA is a common, easily diagnosed, and eminently treatable condition that is associated not only with disturbed sleep, loud snoring and excessive daytime sleepiness (which greatly increases the risk of traffic accidents), but also with hypertension, especially resistant hypertension, a broad range of cardiovascular problems, decreased sexual functioning, memory deficits, difficulty concentrating, and changes in personality and mood. It deserves much more attention by physicians treating hypertension than it is currently getting.