The impact of overnight nutrition support on sleep and circadian rhythm disruption in the ICU

夜间营养支持对 ICU 睡眠和昼夜节律紊乱的影响

• 批准号: 10215183
• 负责人: Hassan S. Dashti
• 金额: $ 16.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-16 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215183
• 关键词: Acute; Adult; Affect; American; Arousal; Attenuated; Biological; Biological Assay; Biological Clocks; Biological Markers; Blood Glucose; Blood Pressure; Body Temperature; C-reactive protein; Cardiac; Chronobiology; Circadian Rhythms; Clinical; Clinical Nutrition; Clinical Research; Clinical Trials; Computerized Medical Record; Conflict (Psychology); Critical Care; Critical Illness; Cross-Over Trials; Data; Delirium; Devices; Dietitian; Dimensions; Disease; Eating; Enteral Feeding; Enteral Nutrition; Environment; Evaluation; Feeds; Food; Gene Expression Profile; Genomic medicine; Glucose; Goals; Health; Hospitalization; Hour; Human; Impairment; Inflammation; Inflammatory; Intensive Care Units; Interdisciplinary Study; Interleukin-6; Intervention; Intravenous; Light; Measures; Mediating; Mediation; Medical; Monitor; Morbidity - disease rate; Noise; Nutritional Study; OGTT; Operative Surgical Procedures; Oral; Outcome; Parenteral Nutrition; Participant; Pathway interactions; Patient Care; Patients; Personal Satisfaction; Phase; Phenotype; Physiological; Polysomnography; Positioning Attribute; Postoperative Period; Randomized; Recovery; Research Personnel; Risk; Serum; Sleep; Sleep Fragmentations; Societies; Strategic Planning; Surgical Intensive Care; TNF gene; Technology; Temperature; Testing; Time; Training; Transcript; United States National Institutes of Health; actigraphy; bench to bedside; cardiac intensive care unit; cardiometabolism; circadian; circadian pacemaker; clinical care; clinical translation; clinical trial implementation; factor A; feeding; human subject; impaired glucose tolerance; improved; monocyte; novel; nutrition; patient population; precision nutrition; preservation; prevent; programs; response; sleep quality; transcriptomics

Intensive care unit (ICU) environments do not support sleep or preserve circadian rhythms of postoperative critically ill patients. Among the contributing factors is the common practice of administering nutrition support through feeding tubes overnight. Sleep and circadian rhythms, our 24-hour internal clock, are essential to human well-being. Acute disturbances are associated with inflammation and cardiometabolic derangements, two important factors known to impair patient recovery and contribute to longer stays at cardiac surgical ICUs. Thus, the overall objective of the study is to examine a novel dimension of clinical nutrition by determining whether enhancing sleep quality and preserving robust circadian rhythms through daytime instead of overnight feeds will attenuate inflammation and improve cardiometabolic profiles of postoperative cardiac ICU patients on nutrition support. My findings from a free-living adults clinical trial indicate differences in blood pressure and impaired glucose tolerance in response to a glucose challenge administered during the biological evening relative to the morning. To be a researcher at the intersection of nutrition and chronobiology, or chrono-nutrition, leading a “bench-to-bedside” translational precision nutrition research program, which directly tests discoveries from healthy subjects into patient populations, a logical next step is to evaluate clinical translation of my findings in an ICU. I hypothesize that overnight nutrition support results in fragmented sleep and blunted circadian rhythms and thus represent a modifiable mechanism exacerbating inflammation and cardiometabolic derangements in postoperative cardiac patients. This hypothesis will be tested in three specific aims: Aim 1 [K99] proposes a randomized-controlled, crossover trial of 60 ICU patients on enteral feeds to test the hypothesis that daytime compared to overnight enteral nutrition is associated with less fragmented sleep and more robust 24hr circadian rhythms. Sleep and circadian rhythms will be assessed objectively using non-invasive and state- of-the-art technologies including polysomnography, actigraphy and body temperature. Aim 2 [R00] will test the hypothesis that daytime compared to overnight nutrition is associated with gene expression signatures of robust circadian rhythms and reduced inflammation via noninvasive blood monocyte transcriptomics. This will be tested in the clinical trial from Aim 1 (n=60; Aim 2A) and in my ongoing complementary cross-over trial of free-living adults for generalizability (n=335 completed; Aim 2B). Aim 3 [R00] will test the hypothesis in the clinical trial from Aim 1 that daytime compared to overnight enteral nutrition is associated with reduced inflammation and improved cardiometabolic profiles, including blood pressure and glucose. My interdisciplinary research plan, proposed training in ICU clinical trials implementation and medical chronobiology, along with a unique clinical research environment with access to state-of-the-art phenotyping devices uniquely position me by the end of the K99 phase to transition to an independent researcher. This study will also provide the framework to reevaluate standard overnight nutrition practice likely affecting 250,000 hospital admissions annually in the US.

重症监护病房(ICU)环境不支持术后睡眠或维持昼夜节律 危重病人。造成这种情况的原因之一是实施营养支持的普遍做法。 通过饲养管过夜。睡眠和昼夜节律，也就是我们的24小时生物钟，对 人类的福祉。急性紊乱与炎症和心脏代谢紊乱有关，有两个 已知的影响患者康复和在心脏外科ICU停留时间更长的重要因素。因此， 这项研究的总体目标是通过确定临床营养的新维度 提高睡眠质量，并在白天保持强劲的昼夜节律，而不是过夜进食 心脏ICU术后患者的营养抗炎及改善心脏代谢的研究 支持。我在一项自由生活的成年人临床试验中的发现表明，血压和受损程度存在差异。 在生物之夜给予葡萄糖挑战时的葡萄糖耐量与 早上。成为营养学和时间生物学或时间营养学的交叉点的研究人员， 领导一个“从工作台到床边”的翻译精准营养研究项目，该项目直接测试 从健康受试者到患者群体的发现，合乎逻辑的下一步是评估 我在重症监护室的发现。我假设通宵营养支持会导致睡眠分散和迟钝 昼夜节律，因此代表了一种可改变的机制，加剧了炎症和心脏代谢 心脏术后患者的精神错乱。这一假设将在三个具体目标中得到检验：目标1 [K99]提出了一项针对60名接受肠道喂养的ICU患者的随机对照交叉试验，以检验这一假设 与过夜的肠内营养相比，白天的营养与更少的零碎睡眠和更健康的睡眠有关 24小时昼夜节律。睡眠和昼夜节律将使用非侵入性和状态- 最先进的技术，包括多导睡眠图、动作图和体温。Aim 2[R00]将测试 假设白天营养与过夜营养相比与强健的基因表达特征有关 通过非侵入性血液单核细胞转录物来实现昼夜节律和减少炎症。这将会被测试 在来自目标1(n=60；目标2A)的临床试验中，以及我正在进行的自由生活的补充交叉试验中 成人推广(n=335人已完成；目标2B)。目标3[R00]将在临床试验中检验这一假设 根据目标1，与过夜的肠内营养相比，白天的肠内营养与减少炎症和 改善心脏代谢状况，包括血压和血糖。我的跨学科研究计划， 在ICU临床试验实施和医学时间生物学方面的拟议培训，以及独特的临床 能够使用最先进的表型设备的研究环境使我在 K99阶段过渡到独立研究人员。这项研究还将提供框架，以 重新评估标准的过夜营养做法，可能会影响美国每年25万入院人数。