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: 10393607
• 负责人: Hassan S. Dashti
• 金额: $ 16.37万
• 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/10393607
• 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) 环境不支持睡眠或维持术后昼夜节律 危重病人。影响因素之一是营养支持的常见做法 通过饲管过夜。睡眠和昼夜节律（我们的 24 小时内部时钟）对于 人类福祉。急性紊乱与炎症和心脏代谢紊乱有关，其中两种 已知会损害患者康复并导致在心脏外科 ICU 停留时间更长的重要因素。因此， 该研究的总体目标是通过确定是否 通过白天而不是隔夜喂食来提高睡眠质量并保持稳健的昼夜节律将 通过营养减轻心脏 ICU 患者术后炎症并改善心脏代谢特征 支持。我在一项自由生活的成人临床试验中的发现表明，血压和受损程度存在差异。 相对于生物晚上期间对葡萄糖挑战的响应的葡萄糖耐量 早晨。成为营养学和时间生物学或时间营养学交叉领域的研究人员， 领导“从实验室到临床”的转化精准营养研究项目，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临床转化 我在重症监护室的发现我假设隔夜营养支持会导致睡眠碎片化和迟钝 昼夜节律，因此代表了一种加剧炎症和心脏代谢的可修改机制 心脏病患者术后精神错乱。该假设将在三个具体目标中进行检验： 目标 1 [K99] 提出一项随机对照、交叉试验，对 60 名 ICU 患者进行肠内喂养，以检验这一假设 与夜间肠内营养相比，白天的睡眠碎片较少且更加稳定 24 小时昼夜节律。将使用非侵入性和状态客观评估睡眠和昼夜节律 最先进的技术，包括多导睡眠图、体动记录仪和体温。目标 2 [R00] 将测试 假设与夜间营养相比，白天的营养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组学调节昼夜节律并减少炎症。这将被测试 在目标 1（n=60；目标 2A）的临床试验和我正在进行的自由生活的补充交叉试验中 成人的普遍性（n=335 已完成；目标 2B）。目标 3 [R00] 将在临床试验中检验假设 从目标 1 可以看出，与隔夜肠内营养相比，白天肠内营养可减少炎症，并且 改善心脏代谢特征，包括血压和血糖。我的跨学科研究计划， 建议进行 ICU 临床试验实施和医学时间生物学方面的培训，以及独特的临床 能够使用最先进的表型分析设备的研究环境使我在年底前处于独特的地位 K99阶段过渡到独立研究员。这项研究还将提供框架 重新评估标准隔夜营养实践可能会影响美国每年 250,000 例入院病例。

项目成果

How Accurately Can We Recall the Timing of Food Intake? A Comparison of Food Times from Recall-Based Survey Questions and Daily Food Records.

我们能准确回忆起食物摄入的时间吗？基于回忆的调查问题和每日食物记录的食物时间比较。

• DOI: 10.1093/cdn/nzac002
• 发表时间: 2022-03
• 期刊: Current developments in nutrition
• 影响因子: 4.8
• 作者: Gioia SC;Guirette M;Chen A;Tucker C;Gray BE;Vetter C;Garaulet M;Scheer FAJL;Saxena R;Dashti HS
• 通讯作者: Dashti HS

Infusion timing and sleep habits of adults receiving home parenteral and enteral nutrition: A patient-oriented survey study.

接受家庭肠外和肠内营养的成人的输注时间和睡眠习惯：一项以患者为导向的调查研究。

• DOI: 10.1002/jpen.2446
• 发表时间: 2023
• 期刊: JPEN. Journal of parenteral and enteral nutrition
• 作者: Dashti,HassanS;Rhyner,JordanJ;Mogensen,KrisM;Godbole,Meghna;Saxena,Richa;Compher,Charlene;Winkler,MarionF
• 通讯作者: Winkler,MarionF

Sleep patterns of patients receiving home parenteral nutrition: A home-based observational study.

• DOI: 10.1002/jpen.2346
• 发表时间: 2022-09
• 期刊: JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
• 影响因子: 3.4
• 作者: Dashti, Hassan S.;Godbole, Meghna;Chen, Angela;Mogensen, Kris M.;Leong, Aaron;Burns, David L.;Winkler, Marion F.;Saxena, Richa;Compher, Charlene
• 通讯作者: Compher, Charlene