Sleep Intervention During Acute Lung Injury

急性肺损伤期间的睡眠干预

• 批准号: 7740735
• 负责人: Sairam Parthasarathy
• 金额: $ 37.76万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740735
• 关键词: Acute; Acute Lung Injury; Adrenergic Agents; Adrenergic Agonists; Adult Respiratory Distress Syndrome; Analgesics; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Benzodiazepines; Brain; Catecholamines; Cell Culture Techniques; Cells; Cessation of life; Chronic; Clonidine; Critical Illness; Cross-Over Studies; Delirium; Dexmedetomidine; Double-Blind Method; Electroencephalography; Fentanyl; Functional disorder; Future; Goals; Immune system; Impaired health; In Vitro; Inflammation; Inflammatory; Infusion procedures; Interleukin-6; Intervention; Kale - dietary; Knowledge; Life; Lipopolysaccharides; Measures; Mechanical ventilation; Mediating; Memory; Methodology; Methods; Midazolam; Modeling; Narcotic Analgesics; Neurocognitive; Neurons; Pain; Pathogenesis; Pathway interactions; Patients; Pattern; Peripheral; Peripheral Blood Mononuclear Cell; Personal Satisfaction; Pharmaceutical Preparations; Play; Polysomnography; Post-Traumatic Stress Disorders; Production; Property; Psychologist; Quality of life; REM Sleep; Randomized; Rattus; Research; Research Personnel; Respiratory Failure; Role; Sedation procedure; Sepsis; Severities; Sleep; Sleep disturbances; Survivors; Sympathetic Nervous System; Syndrome; TNF gene; Therapeutic Intervention; Traumatic Stress Disorders; Wakefulness; adrenergic; base; cytokine; deprivation; experience; improved; in vivo; interleukin-10 receptor; lung injury; macrophage; member; mortality; neuropsychological; novel; programs; public health relevance; research study; respiratory; sedative; survivorship; tool

DESCRIPTION (provided by applicant): Critically ill patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) who receive mechanical ventilation can suffer from severe sleep disruption despite continuous sedative infusions. Sleep disruption, in turn, may activate the sympathetic nervous system and cause elevation of circulating inflammatory cytokines, which, in turn, may play a causative role in delirium and post-traumatic stress disorder through consolidation of unpleasant memories during awakenings from sleep. Currently, there is very little understanding of the inter-relationship between critical illness, sleep, and neuropsychological well-being, due to the lack of intervention-based trials that improve sleep during critical illness. The central purpose of this application is to study the short-term effects of sedation with sympatholysis (central 12 adrenergic agent) on sleep and inflammation in critically ill patients with ALI/ARDS. Sedation with sympatholysis will be achieved by a novel sleep-promoting agent with central 12 adrenergic properties. We will undertake sleep studies and measure circulating inflammatory cytokines that modulate sleep in patients with ALI/ARDS randomized to receive two different sedation strategies: central 12 adrenergic sedative-analgesic (dexmedetomidine) versus a conventional sedation strategy (midazolam and fentanyl) in a randomized, double blind, cross-over study. Specific Aim 1: To assess the short-term effect of an 12 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS. Specific Aim 2: To assess the short-term effect of an 12 adrenergic agent on sleep-modulating inflammatory cytokines in critically ill patients with ALI/ARDS. Specific aim 3: To determine the effect of 12 adrenergic agent on the in-vitro production of sleep-modulating inflammatory cytokines by peripheral blood mononuclear cells of patients with ALI/ARDS. Collectively, our study will identify the best sleep assessment tool in patients with ALI/ARDS and whether sleep disruption in such patients can be minimized. In the long-term, this program of research will identify sedation practices that are least associated with adverse short- and long-term consequences of critical illness, and thereby ultimately help improve quality of life of patients surviving critical illness. PUBLIC HEALTH RELEVANCE: During life support for respiratory failure, patients frequently awaken from sleep despite sedatives, and upon surviving may suffer from "flashback" of traumatic experiences that were memorized during awakenings from sleep (called 'PTSD'). There is little understanding of how such patients' sleep should be measured or improved. We will find the best sleep measurement tool and administer a new medication that improves sleep by soothing inflammation which may, in the future, improve the quality of life of patients.

描述（由申请人提供）：接受机械通气的急性肺损伤和急性呼吸窘迫综合征（ALI/ARDS）危重患者，尽管持续输注镇静剂，仍可能发生严重睡眠中断。睡眠中断，反过来，可能会激活交感神经系统，并导致循环炎性细胞因子的升高，这反过来可能会通过巩固不愉快的记忆从睡眠中醒来，在谵妄和创伤后应激障碍中发挥致病作用。目前，由于缺乏改善危重病期间睡眠的基于干预的试验，对危重病，睡眠和神经心理健康之间的相互关系了解甚少。本申请的主要目的是研究交感神经阻滞（中枢12肾上腺素能药物）镇静对ALI/ARDS重症患者睡眠和炎症的短期影响。具有中枢肾上腺素能特性的新型睡眠促进剂将实现交感神经松解的镇静作用。我们将在一项随机、双盲、交叉研究中进行睡眠研究并测量调节ALI/ARDS患者睡眠的循环炎性细胞因子，这些患者随机接受两种不同的镇静策略：中枢12肾上腺素能镇静镇痛药（右美托咪定）与常规镇静策略（咪达唑仑和芬太尼）。具体目标1：评估12肾上腺素能药物对急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）危重患者睡眠质量的短期影响。具体目标二：评估12肾上腺素能药物对急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）危重患者睡眠调节炎性细胞因子的短期影响。具体目标3：探讨12种肾上腺素能药物对急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）患者外周血单个核细胞（PBMC）分泌睡眠调节性炎性细胞因子的影响。总的来说，我们的研究将确定ALI/ARDS患者的最佳睡眠评估工具，以及这些患者的睡眠中断是否可以最小化。从长远来看，这项研究计划将确定与危重病的短期和长期不良后果相关性最小的镇静方法，从而最终帮助改善危重病患者的生活质量。公共卫生关系：在呼吸衰竭的生命支持期间，尽管使用镇静剂，患者仍经常从睡眠中醒来，并且在存活后可能遭受从睡眠中醒来期间记忆的创伤经历的“闪回”（称为“PTSD”）。人们对如何测量或改善这些患者的睡眠几乎没有了解。我们将找到最好的睡眠测量工具，并管理一种新的药物，通过缓解炎症来改善睡眠，这可能会在未来提高患者的生活质量。