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: 10791953
• 负责人: Hassan S. Dashti
• 金额: $ 24.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10791953
• 关键词: impact; overnight; nutrition; support; sleep

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. In patients supported with home parenteral nutrition, we observed disrupted sleep largely driven by difficulty maintaining sleep. We also found differences in blood pressure and impaired glucose tolerance in response to a glucose challenge administered during the biological evening relative to the morning in free-living adults. To be a researcher at the intersection of nutrition and chronobiology 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 the 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 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 (NCT04737200). Sleep and circadian rhythms will be assessed objectively using non-invasive and state-of-the-art technologies. Aim 2 will test the hypothesis that daytime compared to overnight nutrition is associated with changes in metabolites involved in pathways related to circadian rhythms and inflammation via plasma metabolomics. This will be tested in the clinical trial from Aim 1 (n=60) and in a completed, complementary cross-over trial of free-living adults for generalizability (n=366; NCT02997319). Aim 3 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. The proposed aims will provide ample data for a competitive R01 grant submission during the R00 phase on precision nutrition, an area of research aligned with the priorities of the NIH. 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危重患者的昼夜节律，其中一个影响因素是通过夜间喂食管提供营养支持的常见做法。睡眠和昼夜节律，即我们的 24 小时生物钟。急性紊乱与炎症和心脏代谢紊乱有关，这两个因素会损害患者的康复并导致患者在心脏外科 ICU 的住院时间延长。该研究旨在探讨临床营养的一个新维度，通过确定通过白天而不是夜间喂养来提高睡眠质量和保持稳健的昼夜节律是否会减轻炎症并改善接受家庭肠外营养支持的术后心脏病 ICU 患者的心脏代谢状况。营养方面，我们观察到，睡眠障碍很大程度上是由睡眠困难引起的，我们还发现，相对于早晨，自由生活的成年人对血糖挑战的反应存在血压和糖耐量受损的差异。这营养学和时间生物学的交叉点领导了一个“从实验室到临床”的转化精准营养研究项目，该项目直接测试健康受试者的发现到患者群体中，合乎逻辑的下一步是评估我的研究结果在一夜之间在 ICU 中的临床转化。营养支持会导致睡眠碎片化和昼夜节律迟钝，因此代表了一种可改变的机制，加剧了术后心脏病患者的炎症和心脏代谢紊乱。该假设将在三个具体目标中进行检验：目标 1 提出。一项对 60 名 ICU 患者进行肠内营养的随机对照交叉试验，旨在检验这样的假设：与夜间肠内营养相比，白天与较少的零碎睡眠和更稳健的 24 小时昼夜节律相关（NCT04737200）将使用客观评估睡眠和昼夜节律。目标 2 将检验以下假设：与夜间营养相比，白天的营养与途径中代谢物的变化有关。通过血浆代谢组学与昼夜节律和炎症相关，这将在目标 1 (n=60) 的临床试验和自由生活成年人的完整补充交叉试验中进行测试，以验证其普遍性。目标 3 将检验目标 1 临床试验中的假设，即与隔夜肠内营养相比，日间肠内营养与减少炎症和改善心脏代谢特征相关，包括血压和血压。拟议的目标将为精准营养 R00 阶段的竞争性 R01 拨款申请提供充足的数据，该研究领域与 NIH 的优先事项一致。这项研究还将提供重新评估标准隔夜营养实践的框架。美国每年可能会影响 25 万人入院。