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.

重症监护室（ICU）环境不支持睡眠或保留术后昼夜节律 重病患者。在促成因素中，要管理营养支持的常见实践 通过喂食管过夜。睡眠和昼夜节律，我们的24小时内钟，对于 人类的福祉。急性灾害与感染和心脏代谢演变有关，两种 已知的重要因素会损害患者康复并导致在心脏手术ICU中更长的住宿。那， 该研究的总体目的是通过确定是否是否确定是否是否 增强睡眠质量并通过白天而不是过夜饲料来保留稳健的昼夜节律 减轻炎症并改善营养术后心脏ICU患者的心脏代谢特征 支持。我来自自由生活的成人临床试验的发现，表明血压差异和受损 响应于在生物夜进行的葡萄糖挑战响应的葡萄糖耐受性相对于 早晨。成为营养与计时生物学或计时核病学交集的研究人员， 领导“基准对床”翻译精度营养研究计划，该计划直接测试 从健康受试者到患者人群的发现，逻辑下一步是评估 我在ICU中的发现。我假设隔夜营养支持会导致睡眠碎片和蓝色 昼夜节律，因此代表可修改的机制加剧注射和心脏代谢 术后心脏患者的进化。该假设将以三个特定目的进行检验：目标1 [K99]提出了60名ICU患者的随机控制，分频试验，以检验假设 与隔夜肠营养相比 24小时昼夜节律。睡眠和昼夜节律将使用非侵入性和状态 - ART技术，包括多肌术，行动摄影和体温。 AIM 2 [R00]将测试 假设白天与过夜营养相比与稳健的基因表达信号有关 昼夜节律通过非侵入性血单核细胞转录组学减少了炎症。这将进行测试 在AIM 1（n = 60; aim 2a）的临床试验中，在我正在进行的完整杂交试验中 成年人的推广性（n = 335； AIM 2B）。 AIM 3 [R00]将在临床试验中检验假设 与过夜的肠内营养相比，白天的AIM 1与注射量减少有关 改善了心脏代谢谱，包括血压和葡萄糖。我的跨学科研究计划， ICU临床试验实施和医学年度生物学的拟议培训以及独特的临床 在访问最先进的表型设备的研究环境之前 转向独立研究人员的K99阶段。这项研究还将为 重新评估标准的隔夜营养实践，可能每年在美国影响25万个住院。