Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea

Ramelteon is a selective MT₁/MT₂-receptor agonist indicated for insomnia treatment. Because it has no depressant effects on the nervous system, it is not expected to affect the control of breathing. The potential effects of ramelteon on apneic and hypopneic events and arterial oxygen saturation (SaO₂) in individuals with obstructive sleep apnea were assessed. In this double-blind, randomized, crossover study, 26 adults with mild to moderate obstructive sleep apnea received ramelteon 16 mg and placebo for one night each, with a 5- to 12-day washout period between treatments. Treatments were administered 30 min before habitual bedtime. Respiratory effort was monitored using respiratory inductance plethysmography, SaO₂ was measured by pulse oximetry, and sleep onset and duration were measured by polysomnography and post-sleep questionnaire. Post-sleep questionnaire also measured next-day residual effects. The primary measure was apnea–hypopnea index. Apnea–hypopnea index was similar in ramelteon and placebo groups (11.4 vs 11.1, respectively; CI = −2.1, 2.6, P = 0.812). Ramelteon had no effect on the number of central, obstructive, or mixed apnea episodes. No significant differences were observed in SaO₂ for the entire night between ramelteon and placebo (95.1 vs 94.7%; P = 0.070). Ramelteon did not meaningfully affect sleep when evaluated by polysomnography and post-sleep questionnaire. Compared with placebo, ramelteon had no significant effect on next-day residual effects. Adverse events were reported by three subjects in the ramelteon group: headache (n = 2) and urinary tract infection (n = 1). No adverse events were reported with placebo. Ramelteon was well-tolerated and, as expected, did not worsen sleep apnea when administered to subjects with mild to moderate obstructive sleep apnea.     

Pro-atherogenic cytokine profile of patients with suspected obstructive sleep apnea

Purpose

Systemic inflammation is important in the pathogenesis of cardiovascular disease (CVD). We sought to characterize the systemic inflammatory profile associated with obstructive sleep apnea (OSA).

Methods

Adult patients referred for suspected OSA at the University of British Columbia Hospital Sleep Disorders Program were recruited for our study. Patients using HMG CoA inhibitors or a history of CVD were excluded. Fasting serum samples were obtained the morning after their diagnostic polysomnograms. Samples were tested for the following circulating inflammatory mediators: interferon gamma; interleukins 1B, 6, and 8; intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1); and leptin using a multiplex Luminex System.

Results

There were 176 patients; 68% were male, mean age?=?50?±?(SD) 11 years, mean apnea/hyponea index (AHI)?=?22.9?±?22/h, mean desaturation (i.e. % of sleep time spent below an oxyhemoglobin saturation of 90%)?=?5.4%?±?15, and mean body mass index (BMI)?=?32.2?±?8 kg/m². In univariate analyses, only leptin, sVCAM-1, and sICAM-1 were significantly associated with indices of OSA severity (i.e. AHI and/or desaturation). In multivariate linear regression analyses that controlled for BMI, gender, age, and current smoking; desaturation persisted as a significant independent predictor for elevated sVCAM-1 and leptin.

Conclusions

We did not find significant associations between OSA and markers of activated innate immunity (IL-1B, 6, and 8). However, OSA severity was independently associated with serum levels of sVCAM-1 and leptin; these may represent mechanisms involved in the pathogenesis of OSA-related CVD.     

阻塞性睡眠呼吸暂停综合征患者的心率变异性研究

目的:观察阻塞性睡眠呼吸暂停综合征(OSAS)患者心率变异性(HRV)的变化。方法:健康对照组46名,轻度OSAS患者83名及中重度OSAS患者78名分别行24小时动态心电图和多导睡眠图监测。比较睡眠呼吸暂停指数、睡眠结构对HRV的影响。结果:OSAS患者与正常人比较,日间HRV无明显差异,夜间HRV明显降低(P<0.05～<0.01)。中重度OSAS组的HRV低于轻度OSAS组的(P<0.05～<0.01),其非快速动眼睡眠(NREM)的Ⅲ～Ⅳ期和快速动眼睡眠(REM)时间占总睡眠时间的比率(7.36％和11.32％)显著低于其他各组,呼吸暂停一低通气指数与Ⅲ～Ⅳ期和REM期睡眠呈负相关。结论:阻塞性睡眠呼吸暂停综合征患者迷走神经功能受损,HRV与呼吸暂停严重程度和睡眠结构破坏显著相关(r=-0.344,-0.326)。     

阻塞性睡眠呼吸暂停患者血清瘦素水平的研究

目的　探讨瘦素在阻塞性睡眠呼吸暂停综合征 (OSAS)患者体内的变化。方法　选择年龄及体重指数 (BMI)差异无显著性的OSAS患者 5 8例和单纯肥胖者 2 1例 ,用多导睡眠呼吸监测仪进行监测 ,用放射免疫法测定所有对象的血清瘦素。结果　 (1)无论男性还是女性 ,OSAS患者瘦素水平 [(6 1± 1 7) μg/L ,(19 5± 9 9) μg/L]平均高于单纯肥胖者 [(4 5± 1 7) μg/L ,(10 5± 2 4) μg/L](P <0 0 1,P <0 0 5 )。 (2 )单纯肥胖者及OSAS患者血清瘦素水平分别与BMI呈显著正相关 (r=0 5 9,P <0 0 1;r=0 6 4,P <0 0 1) ,同时OSAS患者血清瘦素水平分别与呼吸暂停及低通气指数 (AHI) (r=0 47,P <0 0 1)和颈围 (r=0 6 4,P <0 0 1)也有明显的正相关。结论　OSAS患者血清瘦素水平比单纯肥胖者更高 ,除了肥胖、颈围宽外 ,OSAS本身也是引起瘦素水平升高的原因。     

男性阻塞性睡眠呼吸暂停综合征患者性激素研究

目的探讨男性阻塞性睡眠呼吸暂停综合征患者(OSAHS)是否存在性激素的异常及性激素与多导睡眠监测(PSG)指标的关系。方法研究79名确诊OSAHS患者及12名非OSAHS患者作为对照组的资料。观察指标包括整晚睡眠监测及性激素六项水平。结果 1.非OSAHS组与OSAHS组的睾酮有统计学差异(P<0.01),且OSAHS组的睾酮降低;其余五项激素差异不具有统计学意义。2.睾酮的变化与腹围等相关。结论男性阻塞性睡眠呼吸暂停综合征患者存在性激素水平的差异,且其变化与呼吸暂停低通气指数(AHI)严重程度无关,与肥胖度有关。     

Depressive symptoms in patients with obstructive sleep apnea/hypopnea syndrome

Objective

The objective of this study was to determine the frequency of depressive symptoms in Peruvian patients with obstructive sleep apnea/hypopnea (OSAH) and the association between the presence of depressive symptoms and OSAH severity.

Methods

Physical examination, Beck Depression Inventory (BDI), and Epworth Sleepiness Scale (ESS) were applied, and a polysomnography test was performed.

Results

Data on 312 patients, 12 % females, 46.1?±?11.7 years of age, were analyzed. BDI and ESS scores were 8.3?±?5.7 and 9.8?±?5.5, respectively. A total of 244 (78 %) patients had OSAH: 27 % of the cases were mild, 23 % were moderate, and 50 % were severe. Eighteen percent of the population had depression. A univariate analysis found a relationship between depressive symptoms and OSAH, as well as with some polysomnographic variables related to OSAH severity. The association between depression and OSAH was not significant in the multivariate analysis.

Conclusions

No association was found between depressive symptoms and OSAH.     

Usefulness of cephalometry in sparing polysomnography of patients with suspected obstructive sleep apnea

The aim of this investigation was to evaluate the contribution of cephalometry to a statistical model integrating clinical, physical, and oximetric variables, to reduce demands for polysomnographies. Two hundred and twenty-five consecutive patients that had been referred to the sleep clinic for suspected obstructive sleep apnea (OSA) were studied. The clinical assessment of all patients consisted of a sleep related questionnaire, the Epworth sleepiness scale, and a physical examination. In addition, they all underwent spirometry, cephalometry, and a full polysomnography. The clinical variables related with OSA were questions concerning witnessing of apneas by bed partners, intensity of snoring, a history of hypertension, and nocturia. A significant relation was also found with score on the Epworth scale, sex, age, body mass index, neck and waist circumferences, total number and frequency of oxygen desaturations, and the lowest oxygen saturation value. Significant cephalometric measurements were: the linear distance from gonion to gnathion, from the hyoid bone to the mandibular plane, and from the posterior nasal spine to the tip of the soft palate, and the thickness of the uvula as well. A statistical model was built to estimate a patient’s probability of having OSA based on clinical variables, physical examination, pulse oximetry, and cephalometry. The validation of this model demonstrated a remarkable ability in reducing the number of polysomnographic studies. We conclude that cephalometry combined with clinical variables, physical examination, and nocturnal oximetry is useful in the diagnosis of OSA and enables the sparing of a considerable number of polysomnographies.     

Prediction of obstructive sleep apnea in patients presenting to a tertiary care center

The objective of this prospective observational clinical study is to derive and validate a diagnostic model for prediction of obstructive sleep apnea (OSA) in subjects presenting with non-sleep-related complaints in a tertiary care center in north India. We included 102 subjects (group I, range 31–70 years) presenting to the hospital with non-sleep-related complaints. None of the subjects had any significant comorbid illness such as respiratory or congestive cardiac failure. All subjects underwent detailed evaluation including polysomnography (PSG). Various parameters were compared between the cases (apnea–hypopnea index, AHI ≥15/h) and controls (AHI <15/h). Using multivariate logistic regression analysis, a diagnostic model for prediction of OSA was derived. Subsequently, using similar selection criteria, 104 subjects (group II, range 32–68 years) were included for validation of the newly derived diagnostic model. Body mass index [BMI; OR (95% CI), 1.14(1.1–1.2)], male gender 5.0(1.4–27.1), relative-reported snoring index (SI) 2.8(1.7–5.0), and choking index (ChI) 8.1(1.4–46.5) were significant, independent predictors of OSA. Diagnostic model was computed as where, gender: 0=female, 1=male and SI, ChI, BMI are actual values. The diagnostic model had an area under the receiver operator characteristics curve of 89.6%. A cutoff of 4.3 for the score was associated with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 91.3, 68.5, 70.5, and 92.3%, respectively. Misclassification rate with the application of the diagnostic model on group II subjects was 13.5% (14/104). Sensitivity, specificity, PPV, and NPV of the model for predicting OSA in this group were 82, 90.7, 89.1, and 84.5%, respectively. BMI, male gender, SI, and ChI are independent predictors of OSA. Diagnostic model derived from these parameters is useful for predicting presence of OSA and screening subjects for PSG.     

阻塞性睡眠呼吸暂停对非酒精性脂肪性肝病的影响

阻塞性睡眠呼吸暂停(OSA)引起机体长期处于慢性间歇性缺氧可导致多系统、多器官病变,严重者可发生心源性猝死。除合并呼吸、心脑血管、内分泌代谢等疾病外,OSA与消化系统疾病中的非酒精性脂肪性肝病(NAFLD)也有密切关联。简述了OSA和NAFLD的现状,叙述了OSA对NAFLD的影响,归纳了OSA影响NAFLD的机制,提出通过探索OSA影响NAFLD的可能机制,从OSA角度为NAFLD寻找新的潜在防治靶点,对延缓、甚至阻断NAFLD进展具有重要意义。     

肝硬化合并呼吸睡眠暂停32例分析

目的发现晚期肝硬化会出现呼吸睡眠暂停。方法32例肝硬化患者应用携带式多频道睡眠记录仪进行夜间呼吸暂停,其中Child—Pugh分级A级8例、B级10例、C级14例。结果肝硬化出现呼吸睡眠暂停,C组10例（占71．4％）明显高于A组1例（占12．5％）和B组4例（占40％）。结论肝硬化进入晚期阶段,会出现睡眠呼吸暂停。     

Therapy and clinical symptoms in patients with obstructive sleep apnea in Japan]

To investigate the long-term outcome of therapy and clinical symptoms of patients with OSAS (obstructive sleep apnea syndrome) in Japan, we studied 34 patients with OSAS who had been diagnosed by standard polysomnography more than one years (36.0 +/- 19.7 months: mean +/- SD) previously. They were 53.8 +/- 10.5 years old, body mass index was 27.8 +/- 5.2 kg/m2, and AHI (apnea & hypopnea index) was 50.0 +/- 24.2/h. The subjects had achieved weight loss (p less than 0.01), but had regained their initial weight at our follow-up. Eleven patients with OSAS were initially candidates for NCPAP (nasal continuous positive airway pressure), but only 5 patients used it for a prolonged time. The other 6 patients with OSAS could not use NCPAP because they did not wish to purchase a NCPAP instrument. One of 5 patients who used NCPAP for a long time died from lung cancer; thus, 4 patients used NCPAP continuously. Ten patients were commenced on ACZ (acetazolamide); however, only 5 patients took it continuously. ACZ resulted in some improvements in the sleep parameters (AHI index, desaturation time below SaO2 90%), but apnea & hypopnea duration and the difference in transcutaneous PCO2 between wake and sleep were not significantly improved by ACZ administration. ACZ was not as effective as NCPAP. Almost 60% of patients with OSAS had excessive daytime sleepiness. Hypertension was detected in about 60% of patients. Nine of 25 patients who had an automobile license had had more than one automobile accident. Nine patients who had had more than one automobile accident showed AHI greater than or equal to 30 in our study.(ABSTRACT TRUNCATED AT 250 WORDS)     

阻塞性睡眠呼吸暂停综合征不同压力滴定方法及其比较

阻塞性睡眠呼吸暂停综合征(OSAS)是一种常见的睡眠疾病,目前首选治疗方法仍然是经鼻无创持续气道正压通气技术.压力滴定的目的是为气道正压治疗确定最佳治疗压力,是决定治疗效果和治疗依从性的关键.本文就气道正压治疗压力滴定技术与方法进行了系统复习.     

阻塞性睡眠呼吸暂停综合征患者清醒状态时肺动脉高压形成的危险因素分析

目的探讨阻塞性睡眠呼吸暂停综合征(OSAS)患者清醒状态时肺动脉高压形成的相关危险因素。方法15例OSAS患者,右颈内静脉置SwanGanz导管测肺动脉压(PAP),同步行多导睡眠图监测,测肺通气功能[用力呼吸容积(FVC)占预计值的百分比,第1秒钟用力呼吸容积(FEV1.0)占预计值的百分比]、呼吸驱动[低氧通气反应以Δ口腔内阻断压(P0.1)/Δ脉搏血氧饱和度(SpO2)来表示;高碳酸通气反应以ΔP0.1/Δ呼气末CO2分压(PETCO2)来表示]、Hb等指标,行血气分析,对所测指标行多因素相关分析、多元逐步回归分析。结果(1)15例OSAS患者清醒状态时的PAP为(20.39±11.04)mmHg(1mmHg=0.133kPa),睡眠时平均最大PAP为(37.93±19.20)mmHg;其中8例PAP正常,7例PAP升高(PAP≥20mmHg);与PAP正常者相比,PAP升高者的体重指数(BMI)、PaCO2、Hb增高,而FVC占预计值的百分比、PaO2降低。(2)清醒状态时平均PAP与睡眠中平均最大PAP(β=0.35,标准误为0.10,R2=0.89,P=0.006)、PaCO2(β=0.72,标准误为0.27,R2=0.94,P=0.022)关系最为密切;而PaCO2、PaO2、BMI、快动眼睡眠的ΔPAP/ΔSpO2是与睡眠中平均最大PAP关系最密切的因素,并建立回归方程:y'=-152.70+1.92PaCO2+1.37BMI+0.67PaO2+16.29快动眼睡眠的ΔPAP/ΔSpO2。结论OSAS患者PAP升高与呼吸暂停引起的日间CO2升高和低氧、FVC、BMI、快动眼睡眠的低氧等有关,与暂停指数未表现明显关系。     

Perioperative treatment of patients with obstructive sleep apnea

PURPOSE OF REVIEW: Obstructive sleep apnea is a common disorder. Despite reports of its role as a risk factor for postoperative morbidity and mortality, only a few investigators have examined the optimal treatment of patients during this vulnerable period. Recognition of obstructive sleep apnea during conscious sedation or in the perioperative period is important to prevent the occurrence of adverse outcomes. This review discusses the influence of sedative, anesthetic, and analgesic agents and other factors during the perioperative period on patients with obstructive sleep apnea. The aim of this article is to emphasize the importance of recognizing and appropriately treating surgical patients with obstructive sleep apnea. RECENT FINDINGS: Sedative, analgesic, and anesthetic agents used perioperatively play a major role in the development of sleep-disordered breathing during the postoperative period. Postoperative apneic episodes frequently occur even after surgery remote from the upper airway. Sleep apnea predisposes patients to a greater than normal risk for postsurgical complications. Adequate screening of patients preoperatively and initiation of continuous positive airway pressure therapy perioperatively could prevent serious complications, including hypoxemia, arrhythmias, myocardial infarction, and respiratory arrest. SUMMARY: Obstructive sleep apnea places a significant proportion of surgical patients at increased risk of perioperative complications. Obstructive sleep apnea can be induced, unmasked, or exacerbated by the effects of sedative, analgesic, and anesthetic agents regardless of the site of surgery. The role of sleep apnea as a risk factor for development of postoperative complications needs greater emphasis. Increased awareness of the risk posed by an obstructed upper airway and appropriate management are important to optimize the perioperative care of patients with obstructive sleep apnea.     

阻塞性睡眠呼吸暂停对动态血压影响的研究

目的　探讨阻塞性睡眠呼吸暂停 (OSA)夜间低氧血症对动态血压变化的影响。方法　选择阻塞性睡眠呼吸暂停综合征 (OSAS)患者 60例和正常对照组 2 0例进行多导睡眠图检查和 2 4h血压监测。结果　轻度OSAS患者的动态血压及其昼夜节律的改变与正常对照组相比无显著性差异 ;中度OSAS患者的nMDP及血压昼夜节律与正常对照组相比已有显著性差异 ;而重度OSAS组的动态血压改变则更加明显 ,2 4hMDP、2 4hMAP、dMSP、dMDP、dMAP、nMSP、nMDP、nMAP均明显高于对照组 ,其中 2 4hMDP、dMDP、dMAP、nMSP、nMDP与轻、中度组比较有显著性差异 ,同时夜间血压下降节律紊乱 ,昼夜血压差值减小。OSAS患者 2 4hMDP、dMDP、nMSP、nMDP、nMAP与睡眠呼吸暂停低通气指数 (AHI)呈显著正相关 ,而 2 4hMSP、2 4hMAP、nMSP、nMAP、ΔSBP、ΔDBP与睡眠中经皮血氧饱和度(SpO2 )降低大于 0 0 4的总次数、SpO2 低于 0 90的时间均呈正相关 ,而与睡眠中SpO2 最低值、SpO2 平均值呈负相关。结论　OSAS患者各期血压的平均水平与AHI、呼吸暂停持续时间及SpO2 降低的程度显著相关 ,OSAS的病情越重 ,这种血压变化及昼夜节律改变越显著