The impact of central sleep apnea in patients receiving medications for opioid use disorder

中枢性睡眠呼吸暂停对接受阿片类药物使用障碍药物治疗的患者的影响

• 批准号: 10783888
• 负责人: Sanjay R Patel
• 金额: $ 106.45万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10783888
• 关键词: Acetazolamide; Acute; Address; Adult; Adverse effects; American; Anxiety; Arousal; Automobile Driving; Autonomic Dysfunction; Autonomic nervous system; Blood; Brain Stem; Breathing; Buprenorphine; Central Sleep Apnea; Chemoreceptors; Chronic; Clinical; Clinical Treatment; Data; Dropout; Drowsiness; Enrollment; Epidemic; Equilibrium; Feedback; Geographic Locations; High Prevalence; Home; Hypoxemia; Individual; Intervention; Knowledge; Measures; Mediating; Mental Depression; Methadone; Morbidity - disease rate; Nervous System Physiology; Opioid; Outcome; Oxygen; Pathogenesis; Pathway interactions; Patients; Peripheral; Persons; Pharmaceutical Preparations; Phenotype; Physiological; Placebos; Play; Polysomnography; Population; Population Control; Protocols documentation; Relapse; Risk; Role; Secondary to; Site; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Fragmentations; Sleeplessness; Testing; Time; Treatment outcome; Virus Diseases; Work; adverse outcome; circadian; clinically significant; cohort; common symptom; drug craving; drug relapse; effective therapy; emotional distress; improved; improved outcome; improvement on sleep; medication for opioid use disorder; mortality; novel; opioid mortality; opioid use; opioid use disorder; overdose death; public health emergency; randomized trial; response; retention rate; sleep difficulty; sleep quality; treatment program; ventilation

ABSTRACT Opioid use disorder has reached epidemic proportions in the US causing substantial mortality and morbidity. While medication treatment for opioid use disorder (MOUD) can improve clinical outcomes, relapse rates remain high. In addition, common medications used for MOUD such as methadone and buprenorphine have been found to cause central sleep apnea (CSA) in as many as 30% of patients receiving treatment. Given the high prevalence of sleep complaints in patients on MOUD and evidence that CSA causes sleep fragmentation and intermittent hypoxemia that have been associated with adverse clinical consequences in other forms of sleep- disordered breathing, there is an urgent need to better understand whether CSA caused by MOUD has an adverse effect on clinical outcomes and the mechanistic pathways implicated. Preliminary data suggest CSA may lead to sympathetic activation and nocturnal arousal which in turn exacerbate emotional distress and drug craving that can then increase risk of drug relapse and reduce treatment retention. In this proposal, we will use home sleep apnea testing to identify a cohort of patients receiving MOUD therapy with CSA and a control population without any sleep-disordered breathing, confirm CSA status with polysomnography, and assess differences in sleep, autonomic nervous system function, nocturnal arousal, anxiety, depression, and drug craving. We will also assess longitudinally the risk of drug lapses and treatment retention rates over six months in the two groups. This work will establish whether CSA is associated with worse outcomes among patients receiving MOUD therapy and the extent to which sympathetic activation and nocturnal arousal play roles in mediating this effect. In addition, we will conduct a short-term randomized trial of acetazolamide versus placebo in 40 patients receiving MOUD therapy with CSA to evaluate the impact of treating CSA on improving sleep quality, restoring autonomic balance, and reducing nocturnal arousal, emotional distress, and drug craving. Results from this proposal will advance understanding of the impact of CSA among patients receiving MOUD therapy and help establish the role of sympathetic activation and nocturnal arousal in mediating the adverse effects of this increasingly common form of sleep-disordered breathing. Our findings will advance understanding of the potential importance of identifying and treating CSA in patients receiving MOUD as a means to improve clinical outcomes. Our work will also help identify potential interventions to limit the adverse impact of CSA in this population.

抽象的 阿片类药物使用障碍在美国已达到流行病的程度，造成大量死亡率和发病率。 虽然阿片类药物使用障碍 (MOUD) 的药物治疗可以改善临床结果，但复发率仍然存在 高的。此外，还发现了用于 MOUD 的常用药物，例如美沙酮和丁丙诺啡 多达 30% 的接受治疗的患者会出现中枢性睡眠呼吸暂停 (CSA)。鉴于高 MOUD 患者睡眠抱怨的患病率以及 CSA 导致睡眠碎片化的证据 间歇性低氧血症与其他形式的睡眠中的不良临床后果有关 呼吸紊乱，迫切需要更好地了解 MOUD 引起的 CSA 是否具有 对临床结果和所涉及的机制途径产生不利影响。初步数据表明CSA 可能导致交感神经激活和夜间兴奋，进而加剧情绪困扰和药物 渴望会增加药物复发的风险并减少治疗保留。 在本提案中，我们将使用家庭睡眠呼吸暂停测试来识别一组接受 MOUD 治疗的患者 具有 CSA 和没有任何睡眠呼吸障碍的对照人群，确认 CSA 状态 多导睡眠图，并评估睡眠、自主神经系统功能、夜间觉醒的差异， 焦虑、抑郁和毒瘾。我们还将纵向评估药物失效和治疗的风险 两组在六个月内的保留率。这项工作将确定 CSA 是否与更糟糕的症状有关 接受 MOUD 治疗的患者的结果以及交感神经激活和夜间活动的程度 唤醒在调节这种效应中发挥着作用。此外，我们还将进行一项短期随机试验 对 40 名接受 MOUD 联合 CSA 治疗的患者进行乙酰唑胺与安慰剂对比，以评估治疗效果 CSA 改善睡眠质量、恢复植物神经平衡、减少夜间觉醒、情绪激动 痛苦和对毒品的渴望。 该提案的结果将促进对 CSA 对接受 MOUD 的患者影响的了解 治疗并帮助确定交感神经激活和夜间唤醒在介导不良反应中的作用 这种日益常见的睡眠呼吸障碍的影响。我们的发现将促进理解 认识到在接受 MOUD 的患者中识别和治疗 CSA 作为改善病情的一种手段具有潜在的重要性 临床结果。我们的工作还将有助于确定潜在的干预措施，以限制 CSA 对 这个人口。