Pharmacotherapy of obstructive sleep apnea

Introduction: Obstructive sleep apnea syndrome is a common public health problem in the general population. The important health-related consequences of obstructive sleep apnea include cardiovascular disorders, such as myocardial infarction and hypertension, stroke, sudden death and difficult blood sugar control related to diabetes mellitus. The current main treatment options include body weight loss, continuous positive airway pressure, oral appliances and surgical treatment. The effects of pharmacotherapy on sleep apnea continue to be controversial and supplemental only. Current medications for sleep apnea mainly act through reducing risk factors, treating predisposing endocrine disorders, improving residual sleepiness post management and controlling associated hypertension and metabolic disorders.

Areas covered: This article discusses the pharmacotherapy of sleep apnea, including ventilatory stimulants, serotoninergic and REM sleep suppressant agents, acetylcholinesterase inhibitors, medications for predisposing endocrine disorders, stimulants, associated sleep apnea health problems and sleep apnea patient anesthetic precaution. Weight loss is not a direct pharmacological approach and is only briefly mentioned.

Expert opinion: At present, there is no appropriate pharmacological treatment for obstructive sleep apnea. There are adjunct treatments such as anti-allergy treatment, and, if residual sleepiness is present, nonamphetaminic stimulants can help. Usage of these stimulants will, however, produce negative effects in an anticipated rate of about 10% of subjects taking these medications.     

Pharmacotherapy of obstructive sleep apnea

INTRODUCTION: Obstructive sleep apnea syndrome is a common public health problem in the general population. The important health-related consequences of obstructive sleep apnea include cardiovascular disorders, such as myocardial infarction and hypertension, stroke, sudden death and difficult blood sugar control related to diabetes mellitus. The current main treatment options include body weight loss, continuous positive airway pressure, oral appliances and surgical treatment. The effects of pharmacotherapy on sleep apnea continue to be controversial and supplemental only. Current medications for sleep apnea mainly act through reducing risk factors, treating predisposing endocrine disorders, improving residual sleepiness post management and controlling associated hypertension and metabolic disorders. AREAS COVERED: This article discusses the pharmacotherapy of sleep apnea, including ventilatory stimulants, serotoninergic and REM sleep suppressant agents, acetylcholinesterase inhibitors, medications for predisposing endocrine disorders, stimulants, associated sleep apnea health problems and sleep apnea patient anesthetic precaution. Weight loss is not a direct pharmacological approach and is only briefly mentioned. EXPERT OPINION: At present, there is no appropriate pharmacological treatment for obstructive sleep apnea. There are adjunct treatments such as anti-allergy treatment, and, if residual sleepiness is present, nonamphetaminic stimulants can help. Usage of these stimulants will, however, produce negative effects in an anticipated rate of about 10% of subjects taking these medications.     

难治性高血压与阻塞性睡眠呼吸暂停综合征

越来越多的证据证实难治性高血压（RH）与阻塞性睡眠呼吸暂停综合征（OSAS）之间的联系。近年研究发现,OSAS与交感神经活动亢进密切相关。提高对OSAS的认识,应成为所有高血压患者系统治疗中的一个重要环节。本文综述与OSAS相关RH的流行病学及发病机制。     

阻塞性睡眠呼吸暂停综合征患者心脏自主神经调节功能改变与心律失常的关系

目的探讨阻塞性睡眠呼吸暂停综合征(OSAS)患者心脏自主神经调节功能改变与心律失常的关系。方法 118例主诉打鼾患者经多导睡眠呼吸监测仪(PSG)行整夜睡眠监测,并同步监测24-h动态心电图。根据呼吸暂停低通气指数(AHI)将118例患者分为重度OSAS组(A组,46例,AHI>40)、轻中度OSAS组(B组,45例,5≤AHI≤40)和单纯鼾症组(C组,27例,AHI<5)。结果 A组时域指标SDNN、SDANN指数均显著低于B组和C组,心率变异性频域指标LF显著高于B组和C组(P<0.05)。相关分析显示,氧减指数(ODI)、血氧低于90%的时间比(T90)、最低血氧饱和度(LSaO2)与SDNN、SDANN指数和LF显著相关(P<0.05)。A组心律失常发生率为71.7%,明显高于B组的48.9%和C组的29.6%(P<0.05)。结论 OSAS患者心率变异性变化与间歇低氧血症相关,心脏自主神经调节功能改变可能是OSAS导致心律失常的重要机制之一。     

Pharmacological treatment of obstructive sleep apnea

Obstructive sleep apnea (OSA) is a growing public health hazard fueled by the obesity epidemic and an aging population. Untreated sleep apnea can result in significant consequences both in the short-term and long-term. We need to educate the public to recognize the symptoms of sleep apnea and to publicize that effective treatments are available. Positive airway pressure therapy remains the gold standard currently in treating OSA. Alternative treatments include an oral appliance or surgical options. This paper discusses the pharmacologic treatment of sleep apnea: goals include medications to address the ventilatory control of breathing, treat co-morbid diseases, treat associated health problems/complaints, address special issues, such as anesthetic precautions, and propose future targets.     

The pharmacotherapeutic management of obstructive sleep apnea

ABSTRACT

Introduction: Obstructive sleep apneas are a frequent clinical condition in which there are momentary interruptions or reductions in breathing activity. To date, the gold standard therapy is the use of Continous Positive Airway Pressure (CPAP). But, due to the relatevely high frequency of poor compliant patients, there is the need to research possible pharmacological treatments for obstructive apnea (OSA).

Areas covered: A recent study divided OSA into four major phenotypes. With this characterization in hand, the authors have reviewed the pharmacological treatments present to date according to the different phenotypes in which they could be used. Afterwards, they analyzed the efficacy of different medicaments for the therapy of the residual (despite CPAP treatment) excessive day-time sleepiness (EDS) that often afflicts OSA’ patients.

Expert opinion: Different drug classes have been evaluated, with some positive results. However, there is still the need to better define treatment strategies for every single phenotype. This underlines the importance to avoid considering the pathology like a single entity without any differences between each single form. The authors are concerned about the risk that, treating only EDS, patients could reduce their compliance to CPAP, thus not reducing the cardiovascular risk associated with OSA.     

阻塞性睡眠呼吸暂停综合征与高血压关系研究

目的探讨阻塞性睡眠呼吸暂停综合征（OSAS）与高血压的相关性。方法回顾性分析124例OSAS伴高血压患者的临床资料,并按低氧血症的程度分为三组,监测夜间7h的多导睡眠图,比较各组睡前、醒后血压变化。结果124例OSAS合并高血压临床表现：打鼾124例（100．0％）,白天嗜睡74例（59．7％）,夜间憋醒49例（39．5％）,夜间呼吸暂停39例（31．5％）,醒后憋闷26例（21．0％）,晨起头痛19例（15．3％）。OSAS合并高血压患者中,轻、中、重度低氧血症组间睡前血压、醒后血压变化差异有统计学意义（P〈0．05）。结论低氧血症与高血压有明显相关。     

阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与脑卒中的关系

阻塞性睡眠呼吸暂停低通气综合征与脑卒中关系密切。近年来国内外大量流行病学研究表明,阻塞性睡眠呼吸暂停低通气综合征(OSAHS)可显著增加脑卒中发生和死亡的风险,被认为是脑卒中发生的独立危险因素。呼吸暂停和低通气、低氧血症、高碳酸血症、血流动力学改变、脑血管自动调节功能紊乱及血液流变学改变是患者发生脑卒中的主要机制。本文综述阻塞性睡眠呼吸暂停低通气综合征与脑卒中的关系及其防治。     

主动脉夹层与阻塞性睡眠呼吸暂停综合征相关性研究进展

主动脉夹层是一种十分凶险的心血管疾病,尚无确定的发病机制.阻塞性睡眠呼吸暂停综合征是最常见的睡眠呼吸暂停综合征,与主动脉夹层的发生有重要的联系.笔者查阅近年来大量相关文献报道,对主动脉夹层与阻塞性睡眠呼吸暂停综合征相关性进行综述,以期为主动脉夹层临床预防和治疗提供理论基础.     

阻塞性睡眠呼吸暂停低通气综合征相关因素分析

目的探讨阻塞性睡眠呼吸暂停低通气综合征（OSAHS）的相关因素。方法对我科2010年1月至2011年12月所有诊断为OSAHS的580例患者根据OSAHS的严重程度分为轻度组（180例）、中度组（290例）、重度组（110例）,比较BMI、呼吸暂停低通气指数（AHI）和夜间最低血氧饱和度等指标。结果重度组SAHS患者呼吸暂停低通气指数、平均血氧饱和度、夜间最低血氧饱和度高于轻度及中度组,组间差异均有统计学意义[分别为（67±20）7欠／h比（15±4）、（29±2）次／h,（86±3）％比（93±1）、（91±2）％,（69±2）％比（85±1）、（91±3）％,均P〈0．05]。结论OSAHS的发病因素有很多,肥胖、高血压等均为OSAHS的危险因素。     

手术治疗儿童阻塞性睡眠呼吸暂停综合征87例分析

目的探讨儿童阻塞性睡眠呼吸暂停综合征（OSAHS）的手术方法及疗效。方法对通过询问病史、常规及特殊体格检查确诊为OSAHS的患儿,根据病因采取相应的手术治疗,以解除患儿呼吸道阻塞。结果87例患儿治愈62例,占71.3%,好转25例,占28.7%,有效率100%。结论儿童OSAHS与成人在病因及诊断和治疗方法上都不尽相同,有一定的特殊性。儿童OSAHS在治疗上以手术解除上呼吸道阻塞为主,辅以微波治疗及正压通气等,预后良好。注意儿童OSAHS围手术期的治疗,可以避免发生严重的并发症。     

非肥胖型阻塞性睡眠呼吸暂停综合征的呼吸障碍特点

目的分析非肥胖型阻塞性睡眠呼吸暂停综合征（OSAS）的呼吸障碍特点。方法我院2007年3月至2008年2月确诊的136例OSAS患者中体质指数≤25的患者36例为非肥胖组,另选择年龄、性别相匹配的36例肥胖型OSAS患者作为肥胖组。比较2组睡眠呼吸障碍的指标。结果非肥胖型OSAS患者的呼吸暂停指数、夜间缺氧时间少于肥胖型OSAS患者,夜间最低血氧饱和度高于肥胖型OSAS患者,差异有统计学意义（P〈0．05）。2组的平均呼吸暂停时间差异无统计学意义（P〉0．05）,非肥胖组中混合性呼吸暂停占的比例较大。病情严重度方面,非肥胖型OSAS以中度和轻度为主,肥胖型OSAS以重度为主。结论非肥胖型OSAS患者相对于同龄、同性别的肥胖型OSAS患者睡眠呼吸障碍程度较轻,混合性呼吸暂停占的比例较大,推测非肥胖型OSAS发病机制可能与中枢驱动和上气道的神经调节有关。     

阻塞性睡眠呼吸暂停综合征围术期麻醉管理

目的探讨阻塞性睡眠呼吸暂停综合征(OSAS)的围术期麻醉管理方法。方法OSAS患者86例均采用全身麻醉方法,术前根据Malampati试验评估分Ⅰ～Ⅳ级,Ⅰ～Ⅱ级视为插管条件良好,Ⅲ～Ⅳ级视为插管条件不佳,采用不同的诱导方法、气管插管方法、术中及术后处理。结果Ⅰ～Ⅱ级48例全部采用经鼻快速诱导插管,Ⅲ～Ⅳ级中经鼻盲探插管23例,经鼻纤维支气管镜导引插管14例,气管切开1例。术后0.5h内拔管38例,带气管导管回病房48例,出现严重气道阻塞1例,立即再次气管插管。结论合理气道评估和插管方式的选择及合并症的合理处理有助于麻醉安全,防止重大并发症发生。     

The effects of transdermal scopolamine on autonomic nervous activity during sleep

We studied the effect of transdermally applied scopolamine (scopolamine-TTS) on autonomic nervous activity during sleep. The double-blind, randomized, crossover study was carried out in six healthy male volunteers by applying 1.5 mg scopolamine-TTS or placebo patch on the retroauricular skin and by monitoring heart rate, cardiac ballistogram, respiration and body movements by using electrocardiogram and static charge sensitive bed.Scopolamine did not decrease the time the subjects desired to sleep (516 min after TTS, 511 min after placebo) or the number of body movements of 3–5 s duration the subjects spontaneously performed during sleep (47 after TTS, 58 after placebo). No adverse effects of scopolamine were reported spontaneously. Scopolamine-TTS slowed the mean heart rate during quiet sleep from 53.2 to 44.9 beats · min^–1, and increased the duration of bradycardia in response to body movements (MIB-reflex) from 12.5 to 14.7 s with a significant difference between scopolamine and placebo effects. The bradycardias were not associated with disturbances in cardiorespiratory or central nervous system functions. The cardiac vagomimetic action of scopolamine-TTS could be explained by low plasma drug concentrations (175 pg/ml) primarily blocking only neuronal inhibitory prejunctional muscarinic receptors which regulate acetylcholine release from the autonomic ganglia and parasympathetic nerve-endings.Because of the central role of acetylcholine in the physiological regulation of sleep, the effect of scopolamine-TTS on sleep merits further investigations.     

阻塞性睡眠呼吸暂停与非酒精性脂肪性肝病的关系研究

目的：探讨阻塞性睡眠呼吸暂停（ OSA）与非酒精性脂肪性肝病（ NAFLD）的关系。方法141例进行多导睡眠监测的患者为研究对象,根据监测结果分为阻塞性睡眠呼吸暂停低通气综合征（ OSAHS）组和非OSAHS组,均进行肝脏B超检查。比较两组间一般临床资料和实验室检查结果、呼吸暂停低通气指数（ AHI）指数与NAFLD发病率关系以及最低血氧饱和度（ LSaO2）与肝酶指标的相关性并分析原因。结果诊断为OSAHS者83例,其他58例纳入非OSAHS组。 OSAHS组的性别、年龄、血压、血脂、糖尿病、体质指数（ BMI ）和天冬氨酸氨基转移酶（ AST ）,与非OSAHS组比较差异无统计学意义（ P＞0.05）,但丙氨酸氨基转移酶（ALT）、稳态模型胰岛素抵抗（HOMA-IR）指数和NAFLD发病率较非OSAHS组显著增高（P＜0.01）。 AHI指数增加与NAFLD发病率相关。在OSAHS组中,LSaO2与ALT呈负相关,而与AST无相关性。结论 OSA患者易于发生NAFLD,可能与胰岛素抵抗和夜间间歇性低氧有关。     

阻塞性睡眠呼吸暂停综合征并发心力衰竭的综合治疗分析

目的探讨阻塞性睡眠呼吸暂停综合征（OSAS）并发心力衰竭的综合疗法。方法通过社区登记、医院临床体检及辅助检查确诊的148例OSAS并发心力衰竭患者根据病情分成轻度组（62例）、中度组（48例）、重度组（38例）,对3组患者均采用内科保守治疗及外科手术治疗的综合治疗方式,比较3组患者的临床疗效及治疗前后心功能、血氧饱和度（SaO2）的变化。结果治疗后3组患者收缩压、舒张压、呼吸暂停低通气指数（AHI）、左室射血分数（LVEF）、最长低通气时间、SaO2均明显好转,与治疗前比较,差异有统计学意义（P〈0．05）;治疗后3组间AHI、最长低通气时间、SaO：差异有统计学意义（P〈0．05）,且两两组间比较差异有统计学意义（P〈0．05）,AHI、最长低通气时间、SaO2的改善情况随病情的加重而减弱。轻度组治愈率为51．61％、总有效率为95．16％。中度组治愈率为35．42％％、总有效率为89．58％,重度组治愈率为28．95％、总有效率为78．95％,3组疗效比较差异有统计学意义（x^2=8．659,P〈0．05）。结论OSAS并发心力衰竭的综合治疗效果良好,患者心功能、阻塞性睡眠呼吸暂停改善明显。     

Effect of sedative-hypnotics,anesthetics and analgesics on sleep architecture in obstructive sleep apnea

The perioperative care of obstructive sleep apnea (OSA) patients is currently receiving much attention due to an increased risk for complications. It is established that postoperative changes in sleep architecture occur and this may have pathophysiological implications for OSA patients. Upper airway muscle activity decreases during rapid eye movement sleep (REMS). Severe OSA patients exhibit exaggerated chemoreceptor-driven ventilation during non-rapid eye movement sleep (NREMS), which leads to central and obstructive apnea. This article critically reviewed the literature relevant to preoperative screening for OSA, prevalence of OSA in surgical populations and changes in postoperative sleep architecture relevant to OSA patients. In particular, we addressed three questions in regard to the effects of sedative-hypnotics, anesthetics and analgesics on sleep architecture, the underlying mechanisms and the relevance to OSA. Indeed, these classes of drugs alter sleep architecture, which likely significantly contributes to abnormal postoperative sleep architecture, exacerbation of OSA and postoperative complications.     

阻塞性睡眠呼吸暂停低通气综合征患者睡眠结构分析

目的分析不同严重程度阻塞性睡眠呼吸暂停低通气综合征（OSAnS）患者的睡眠结构特点。方法选择确诊为OSAHS的成年患者168例为观察组,并选取同期与其条件相当的单纯鼾症者136例作为对照组。采用多导睡眠监测仪（PSG）对所有入选者进行整夜监测,对比分析不同严重程度OSAHS患者以及单纯鼾症者夜间睡眠结构情况。结果OSAHS患者组与单纯鼾症组相比,睡眠时间与睡眠效率差异无统计学意义（P〉0．05）,而睡眠I期所占比例升高,睡眠Ⅱ期、SWS相和REM相所占比例显著降低（均P〈0．05）。睡眠结构紊乱在重度分级中（AHI≥40）差异更显著。结论OSAHS患者的浅睡眠比单纯鼾症者明显增加,而深睡眠和快动眼睡眠比单纯鼾症者明显减少;随着OSAHS病情分级的加重,对睡眠结构紊乱的影响也更加明显。