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

重症监护室（ICU）环境不支持睡眠或维持术后患者的昼夜节律。 危重病人。其中一个促成因素是管理营养支持的常见做法 通过喂食管睡眠和昼夜节律，我们24小时的内部时钟，是必不可少的， 人类福祉。急性紊乱与炎症和心脏代谢紊乱有关， 已知影响患者恢复并导致在心脏外科ICU停留时间延长的重要因素。因此，在本发明中， 这项研究的总体目标是通过确定是否 提高睡眠质量，在白天而不是夜间进食时保持强健的昼夜节律， 减轻炎症和改善心脏术后ICU患者的心脏代谢特征 支持.我从一个自由生活的成人临床试验中的发现表明， 响应于相对于所述葡萄糖耐受性的所述生物学夜晚期间施用的葡萄糖激发的葡萄糖耐受性。 早上要成为一名研究营养学和时间生物学，或时间营养学的研究人员， 领导一个“从实验室到床边”的转化精确营养研究计划， 从健康受试者到患者人群的发现，合乎逻辑的下一步是评估 我在重症监护室的发现我推测，夜间营养支持导致睡眠碎片和迟钝， 昼夜节律，因此代表了一种可改变的机制， 心脏术后患者的紊乱。这一假设将在三个具体目标中得到检验： [K99]提出了一个随机对照，交叉试验的60名ICU病人的肠内喂养，以检验这一假设 白天与夜间肠内营养相比， 24小时昼夜节律。睡眠和昼夜节律将使用非侵入性和状态- 最先进的技术，包括多导睡眠描记术、体动描记术和体温。目标2 [R 00]将测试 假设白天与夜间营养相比， 昼夜节律和减少炎症通过非侵入性血液单核细胞转录组学。这将受到考验 在Aim 1的临床试验（n=60; Aim 2A）和我正在进行的自由生活补充交叉试验中， 成人的普遍性（n=335完成;目标2B）。目的3 [R 00]将在临床试验中检验假设 根据目标1，与过夜肠内营养相比，日间肠内营养与炎症减少有关， 改善心脏代谢特征，包括血压和血糖。我的跨学科研究计划， 建议在ICU临床试验实施和医学时间生物学的培训，沿着独特的临床 研究环境与访问国家的最先进的表型设备独特的位置我年底 K99阶段过渡到独立研究员。这项研究还将提供框架， 重新评估标准的夜间营养实践可能会影响美国每年25万例住院患者。

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.