阻塞性与中枢性睡眠呼吸暂停事件的鉴别

睡眠呼吸暂停是一种有严重危害的常见病,可导致白天嗜睡、患者生活质量下降等,是心脑血管病变的独立危险因素.合理治疗这一疾病对于减少交通事故的发生,降低心脑血管疾病的发病率及病死率均有重大意义.睡眠呼吸暂停可分为阻塞性睡眠呼吸暂停(OSA)和中枢性睡眠呼吸暂停(CSA).由于二者病因及发病机制不同,治疗方法也有很大差异,正确区分OSA与CSA具有重要临床价值.     

Relationship of arousals from sleep to sympathetic nervous system activity and BP in obstructive sleep apnea.

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) patients have a high frequency of arousals. We hypothesized that arousals significantly influence tonic sympathetic nervous system function. DESIGN: We examined the association of 11 variables measuring sympathetic activity, including plasma norepinephrine (NE), urinary NE, and BP measurements, with movement and cortical arousals. PATIENTS: Sixty-seven subjects with various degrees of hypertension and OSA were evaluated. All patients were free from antihypertensive medications. RESULTS: The age (range, 35 to 60 years), weight (range, 100 to 150% of ideal body weight), and diet of the subjects were similar. The movement arousal index was correlated with daytime baseline plasma NE (BNE), daytime urine NE, mean daytime diastolic BP, and systolic BP during rapid eye movement sleep (r = 0.39 to 0.53; p < or = 0.002). Cortical arousals did not correlate with any of the variables. A multiple regression procedure was performed to examine how well movement arousals predicted those variables with significant correlations. The respiratory disturbance index (RDI) and nighttime pulse oxyhemoglobin saturation were included in the regression equation due to their close association with movement arousals. Movement arousals independently predicted BNE (t [48] = 2.06; p < 0.05). No other variable independently predicted any of the measurements of sympathetic activity. CONCLUSIONS: These findings suggest that movement arousals may influence daytime sympathetic tone independently of RDI and nighttime saturation.     

Role of arousals in the pathogenesis of obstructive sleep apnea

Arousal is believed to be needed for upper airway opening in obstructive hypopneas-apneas, without compelling evidence to support this notion. The association may be incidental. I studied the temporal relation between arousal and opening and impact of arousal on flow response at opening in 82 patients (apnea-hypopnea index, 46 +/- 35/hour). Obstructive apneas-hypopneas were induced by dial-down of continuous positive airway pressure. Obstructions and hypopneas occurred in 44 and 56% of dial-downs, respectively. When arousal occurred (83% of dial-downs), the temporal relation between arousal and opening was inconsistent between and within patients. Frequency of opening without or before arousal increased with milder obstructions (p < 10(-9)) and with delta power of EEG (p < 10(-6)). Time of opening was unaffected by whether arousal occurred before or after opening (18.0 +/- 9.8 vs. 18.1 +/- 10.5 seconds). Flow response was already excessive when opening occurred without or before arousal (180 +/- 148% of initial flow decline) and was considerably higher when arousal occurred (267 +/- 154%, p < 10(-10)). Flow undershoot after first ventilatory response was greater if arousal occurred (p < 0.01). It is concluded that arousals are incidental events that occur when thresholds for arousal and for arousal-independent opening are close. They are not needed to initiate opening or to obtain adequate flow and they likely increase the severity of the disorder by promoting greater ventilatory instability.     

A shift from central and mixed sleep apnea to obstructive sleep apnea resulting from low-flow oxygen

Low-flow oxygen decreases the frequency of the 3 types of apnea (central, mixed, and obstructive) in patients with predominantly obstructive sleep apnea. The decrease in frequency appears to be accompanied by a shift in apnea distribution, consisting of a decrease in the proportion of central and mixed apneas and an increase in that of obstructive apneas. To determine whether this shift represents a greater inhibitory effect on central and mixed apneas or an increased tendency toward obstructive apneas, we administered low-flow oxygen during sleep to 9 patients who demonstrated predominantly central and mixed sleep apnea (51 +/- 33% and 33 +/- 21% of apneic events, respectively, mean +/- SD) and had resting, room air, oxygen tensions of 83 +/- 11 mmHg. During non-REM sleep, oxygen increased the baseline oxyhemoglobin saturation while reducing the average peak fall in oxyhemoglobin saturation during each apneic event. Oxygen reduced the overall apnea frequency from 66 +/- 7.8 (mean +/- SE) to 43.0 +/- 10.7 episodes per hour (p less than 0.02). Central and mixed apneas decreased markedly from 31.4 +/- 0.6 to 6.4 +/- 4.3 episodes per hour (p less than 0.02) and from 20.9 +/- 5.0 to 4.9 +/- 1.5 episodes per hour (p less than 0.02), respectively. However, obstructive apnea frequency more than doubled from 13.9 +/- 7.0 to 32.1 +/- 9.2 episodes per hour (p less than 0.02). We conclude that in these patients oxygen tension altered both the frequency and distribution of sleep-induced apnea, with a lower oxygen tension increasing the frequency of central and mixed apneas and a higher oxygen tension increasing the frequency of obstructive apneas.(ABSTRACT TRUNCATED AT 250 WORDS)     

The appearance of central sleep apnea after treatment of obstructive sleep apnea

Patients with a primary diagnosis of obstructive sleep apnea frequently demonstrate central sleep apnea that emerges during treatment with CPAP. Although a number of mechanisms for this finding have been hypothesized, the pathophysiology is not definitively known. Controversy exists as to whether the concomitant appearance of the two phenomena represents a distinct meaningful entity. Regardless, the coincidence of these diseases may have important clinical implications. Herein, we review the proposed mechanisms for obstructive sleep apnea complicated by central sleep apnea. Future research is needed to elucidate the relative importance and susceptibility to intervention of the various pathophysiologic mechanisms responsible for this phenomenon, and whether a treatment approach distinct from that of pure obstructive apnea is justified.From the Emory University School of Medicine (Drs Hoffman and Schulman), Atlanta, GA.Correspondence to: David A. Schulman, MD, MPH, FCCP, Emory University School of Medicine, 615 Michael St, Ste 205, Atlanta, GA 30322; e-mail: daschul@emory.eduFinancial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.     

Mechanisms and management of central sleep apnea

Central sleep apnea is not a single disease but represents the final pathway in a large group of heterogeneous disorders. Control of normal breathing during sleep relies upon finely coordinated anatomical and physiological mechanisms and their destabilization leads to central apnea. The causes of central sleep apnea can be classified into 4 groups: neurologic disorders, periodic breathing, upper airway abnormalities, and idiopathic syndromes. Clinical features result from the interaction between the underlying disorder and control of respiration. Two different prototypes emerge: patients who are hypercapnic (central hypoventilation and/or impaired respiratory mechanics) and those who are eucapnic or hypocapnic (periodic breathing and idiopathic hyperventilation). The causes and severity of apnea can be determined by clinical assessment, pulmonary function testing, and overnight polysomnography. Further management involves specific treatment of the underlying condition and reducing the sequelae of recurrent apneas during sleep, namely cardiorespiratory dysfunction and sleep disruption. This review outlines an approach to the management of central sleep apnea based upon an understanding of its pathophysiology.     

Pathogenesis of obstructive and central sleep apnea

Considerable progress has been made over the last several decades in our understanding of the pathophysiology of both central and obstructive sleep apnea. Central sleep apnea, in its various forms, is generally the product of an unstable ventilatory control system (high loop gain) with increased controller gain (high hypercapnic responsiveness) generally being the cause. High plant gain can contribute under certain circumstances (hypercapnic patients). On the other hand, obstructive sleep apnea can develop as the result of a variety of physiologic characteristics. The combinations of these may vary considerably between patients. Most obstructive apnea patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake, but not asleep. However, individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be. These include: (1) upper airway anatomy, (2) the ability of upper airway dilator muscles to respond to rising intrapharyngeal negative pressure and increasing Co(2) during sleep, (3) arousal threshold in response to respiratory stimulation, and (4) loop gain (ventilatory control instability). As a result, patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.     

中枢性睡眠呼吸暂停的原因及临床基本特征

中枢性睡眠呼吸暂停(CSA)是一类以睡眠期间呼吸努力消失所致呼吸暂停为主要特征的睡眠呼吸障碍.相对于阻塞性呼吸暂停,虽然其发生率更低且常不被了解,但引起CSA的因素众多,分类也较复杂,临床意义各异.本文就不同原因所致CSA及基本特征进行了介绍.     

Effect of sleep position on sleep apnea and parafunctional activity

Parafunctional activity (toothgrinding, toothclenching and bruxism) is a common problem which may lead to masticatory muscle and temporomandibular joint pain, and may result from sleep arousal or disturbances. Sleep apnea is another common sleep disorder which results in disrupted sleep architecture and frequent arousals. Because sleep apnea leads to sleep arousals, and because sleep arousals are thought to result in increased parafunctional activity, we undertook the present study to determine the relationship between sleep apnea and parafunctional activity. We were also interested in assessing the effects of sleep posture on sleep disordered breathing and parafunctional activity. We prospectively studied 24 patients who were referred to the clinical sleep apnea laboratory for study. They underwent standard nocturnal polysomnographic examination; in addition, masticatory activity was measured with a masseter electromyogram. Patients slept in the supine and lateral decubitus positions. Nocturnal clenching was slightly higher in patients with sleep apnea than those without (12.2 vs 7.6 clenches/hr, p = 0.18), and there was a correlation between the clench index (CI) and apnea plus hypopnea index (A + HI) by linear regression (r = 0.49, p less than 0.05). There were significant falls in both the A + HI (64.4 +/- 28.8 vs 36.5 +/- 36.7, p = 0.02) and CI (12.5 +/- 12.1 vs 7.0 +/- 8.6, p = 0.04) in the lateral decubitus vs supine sleeping positions. We conclude that there is an association between obstructive sleep apnea and parafunctional activity, that sleep position affects the incidence of both sleep disordered breathing and parafunctional activity, and that analysis of apneas and hypopneas in both supine and lateral decubitus sleeping positions may be helpful.     

Regulation of respiration during sleep in congenital central sleep apnea

We report on 2 children aged 13 and 14 months with congenital central alveolar sleep apnea which showed depression of respiratory drive during sleep resulting from dysfunction of central chemoreceptors. Hypoventilation was found to be more severe during NREM sleep (minimum of alveolar ventilation in stages 3/4) than during REM sleep. During NREM sleep arousal responses to hypoxia proved to be an important factor in influencing the level of alveolar ventilation and in preventing fatal asphyxia.     

Recurrence of sleep apnea syndrome following tracheostomy. A shift from obstructive to central apnea

This report describes an unusual case of severe obstructive sleep apnea and alveolar hypoventilation leading to hypersomnolence and cor pulmonale, which were corrected by tracheostomy. Four years later, after a 22.5-kg weight gain, nocturnal apneas of similar frequency, duration, and depth of desaturation reappeared but were totally central in origin. The central apneas were eliminated with home nocturnal positive-pressure ventilation via cuffed tracheostomy tube. Each time the patient's apneas were corrected (obstructive: tracheostomy; central: mechanical ventilation), daytime alveolar hypoventilation disappeared rapidly. Yearly right heart catheterizations and radionuclide ejection fractions documented pulmonary hypertension and right heart failure, with resolution following tracheostomy and recurrence after appearance of central apneas. The changes in hemodynamic status corresponded to the patient's weight, presence of apnea, daytime alveolar hypoventilation, and treatment of nocturnal oxyhemoglobin desaturation. This case illustrates the theory of a common etiology of both central and obstructive apnea through abnormal respiratory controller gain and points to several roles obesity may play in apnea.     

阻塞性睡眠呼吸暂停患者残余嗜睡与中枢性睡眠呼吸暂停事件的相关性

目的 探讨阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSAS)患者连续气道正压通气(continuous positive airway pressure,CPAP)治疗后残余嗜睡与中枢性睡眠呼吸暂停(central sleep apnea,CSA)事件的相关性以及匹配伺服通气(adaptive Bervo-ventilation,ASV)对CSA相关残余嗜睡的影响. 方法 选择正规使用CPAP治疗且排除其他嗜睡相关疾病的中、重度OSAS患者50例,分为残余嗜睡组(26例)和无残余嗜睡的对照组(24例).2组患者均先后接受自动CPAP治疗1个月和ASV治疗1周.分别比较2组患者治疗前、自动CPAP治疗时及ASV治疗时睡眠期的中枢性睡眠呼吸暂停指数(central sleep apnea index,CSAI),微觉醒指数(micro-arousal index,MAI)等多导睡眠监测参数及白天Epworth嗜睡评分(ESS),采用酶联免疫吸附试验测定肿瘤坏死因子a(tumor necrosis factor-a,TNF-a).两组间比较采用t检验,组内比较使用单因素方差分析,组内3个阶段两两比较采用q检验,两变量相关分析采用Pearson相关检验. 结果 治疗前2组呼吸暂停低通气指数(apnea hypoapnea index,AHI)、MAI、最低SpO2、ESS评分及血浆TNF-a水平组间比较差异没有统计学意义(t值分别为0.630、1.223、0.691、0.764和0.192,均P>0.05),但残余嗜睡组患者的CSAJ(14.39±4.21)次/h显著高于对照组[(8.58±5.75)次/h,t=4.097,P＜0.05].自动CPAP治疗1个月时2组的AHI、CSM、MAI和ESS评分均明显低于治疗前(g值为0.87～112.55,均P.＜0.05),但残余嗜睡组CSAI、MAI及ESS评分明显高于对照组[CSM:(7.19±1.75)次/h,(3.37±1.04)次/h,t=9.473,P＜O.05;MAI:(9.00±1.95)次/h,(2.36 4-0.66)次/h,f=14.385,P＜0.05;ESS:(9.54 4-0.51)分,(5.42±1.32)分,t=2.857,P＜0.05].ASV治疗时残余嗜睡组与对照组的CSAI、MAI及白天ESS评分均进一步下降,尤以残余嗜睡组的下降更为明显.此外残余嗜睡组内血浆TNF-a水平与治疗前(17.2±3.3)残余嗜睡,μg/L相比,自动CPAP治疗时(16.5 4-3.6)μg/L无明显下降(q值为11.696,P>0.05),但在ASV治疗时(12.6±3.4)μg/L与治疗前相比显著降低(q值为11.696,P＜0.05).血浆TNF-a水平与ESS评分呈显著正线性相关(r=0.503,P＜0.01),与MAI亦呈显著正相关(r=0.545,P＜0.01). 结论 经自动CPAP治疗后OSAS患者的残余嗜睡与治疗前、中存在的CSA事件频率有关.ASV在显著降低CSAI的同时也明显改善了提示ASV可有效治疗OSAS患者的残余嗜睡.TNF-a也与残余嗜睡患者的嗜睡程度相关,可能参与了残余嗜睡的发生.     

Differences in pharyngeal properties between snorers with predominantly central sleep apnea and those without sleep apnea

The underlying cause of idiopathic central sleep apnea syndrome is not well understood. We therefore examined the possibility that patients with idiopathic central sleep apnea may have abnormalities of upper airway mechanics that might contribute to the pathogenesis of central apneas. The acoustic reflection technique was used to assess pharyngeal size, lung volume dependence, and pharyngeal "compliance" in 8 patients with idiopathic central sleep apnea, all of whom were snorers, and in 8 weight-matched, snoring control subjects with normal sleep studies. Patients with central sleep apnea when compared with control subjects exhibited markedly increased specific pharyngeal "compliance" (0.12 +/- 0.05 versus 0.03 +/- 0.01 cm H2O-1; p less than 0.001), increased change in pharyngeal area from FRC to RV (0.8 +/- 0.5 versus 0.03 +/- 0.3 cm2; p less than 0.05), and a larger pharyngeal area at FRC (4.7 +/- 0.9 versus 3.8 +/- 0.8 cm2; p less than 0.03). We conclude that increased pharyngeal "compliance" and lung volume dependence may play a role in the etiology of central apneas in this syndrome.     

Reversal of central sleep apnea using nasal CPAP

Based on the theory that obstructive (OSA) and central (CSA) sleep apneas share common pathophysiologic mechanisms, we attempted to treat eight patients with predominantly CSA by continuous positive airway pressure (CPAP). All patients exhibited repetitive episodes of CSA and mixed sleep apneas (MSA) in the supine position with a mean duration of 23.7 +/- 0.7 s and 34.5 +/- 1.3 s, respectively. The pattern of apnea changed when the subject lay in the lateral position. Five patients were observed to develop OSA in the lateral position with a mean duration of 27.2 +/- 1.5 s, while the other three patients snored continuously. High levels of CPAP (range 9.0 to 16.5 cm H2O) prevented all CSA and MSA and resulted in quiet breathing in all eight patients. Intermediate levels of CPAP produced firstly MSA, then purely OSA and/or continuous snoring. Low levels of nasal CPAP also prevented OSA and snoring occurring in the lateral posture in all subjects (range 2.0 to 8.3 cm H2O). Three patients are currently on home CPAP therapy for a range of four to 36 months. We conclude that upper airway collapse in the supine posture has a key role in the induction of CSA. We suggest that a reflex inhibition of respiration through activation of supraglottic mucosal receptors during passive oropharyngeal airway closure caused CSA in these patients.     

The effect of esophageal acid volume on arousals from sleep and acid clearance

To assess the effect of different volumes of acid infused into the esophagus, seven normal volunteers were studied in the waking and sleep state. All subjects were studied for three nights in the sleep laboratory, which included complete polysomnographic monitoring and esophageal pH recording. Multiple infusions of either 5, 15, or 25 ml of 0.1 N HCL were administered each night. Similar infusions were also accomplished in the waking state. The results showed a significant (p less than 0.05) decrease in the arousal from sleep with 25-ml vs 5-ml infusions. During sleep, the latency to the first swallow was significantly (p less than .05) shorter with the 25-ml infusion when compared with that of the 5-ml infusion. While awake, the infusion volume did not affect the latency to the first swallow. The acid clearance times were not significantly altered by the different volumes infused. It is concluded that the larger volumes of acid in the esophagus create an afferent "warning" signal to the central nervous system to produce a rapid arousal from sleep along with a shortened interval to the first swallow. These responses rapidly empty the larger acid volumes from the esophagus.     

Cycle length identifies obstructive sleep apnea and central sleep apnea in heart failure with reduced ejection fraction

Aim

To clarify whether unmasking of central sleep apnea during continuous positive airway pressure (CPAP) initiation can be identified from initial diagnostic polysomnography (PSG) in patients with heart failure with reduced ejection fraction (HFREF) and obstructive sleep apnea (OSA)

Materials and methods

Forty-three consecutive patients with obstructive sleep apnea and central sleep apnea (OSA/CSA) in HFREF were matched with 43 HFREF patients with OSA and successful CPAP initiation. Obstructive apneas during diagnostic PSG were then analyzed for cycle length (CL), ventilation length (VL), apnea length (AL), time to peak ventilation (TTPV), and circulatory delay (CD). We calculated duty ratio (DR) as the ratio of VL/CL and mathematic loop gain (LG).

Results

While AL was similar, CL, VL, TTPV, CD, and DR was significantly longer in patients with OSA/CSA compared to those with OSA, and LG was significantly higher. Receiver operator curves identified optimal cutoff values of 50.2 s for CL (area under the curve (AUC) 0.85, 29.2 s for VL (AUC 0.92), 11.5 s for TTPV (AUC 0.82), 26.4 s for CD (AUC 0.79), and 3.96 (AUC 0.78)) respectively for LG to identify OSA/CSA.

Conclusion

OSA/CSA in HFREF can be identified by longer CL, VL, TTPV, and CD from obstructive events in initial diagnostic PSG. The underlying mechanisms seem to be the presence of an increased LG.

     

中枢性睡眠呼吸暂停与心力衰竭研究新进展

心力衰竭(HF)患者常合并睡眠呼吸紊乱。目前有研究认为阻塞性睡眠呼吸暂停可促进HF的发生、发展,OSA引起的心功能恶化继而导致OSA向中枢性睡眠呼吸暂停(CSA)转变。并且,CSA也可认为是心功能加重到一定程度的代偿表现,然而这种代偿只在短期内有效,长期来看可能是有害的。目前CSA与HF的发病机制不明,但近些年来相关研究有了许多新的进展。本文就CSA与HF发病率、临床特点、分型、病理机制及治疗方面进行综述。