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

重症监护病房(ICU)环境不支持术后危重病人的睡眠或维持昼夜节律。造成这种情况的原因之一是通宵通过饲养管进行营养支持的做法。睡眠和昼夜节律，也就是我们的24小时生物钟，对人类的幸福至关重要。急性紊乱与炎症和心脏代谢紊乱有关，这两个已知的重要因素会损害患者的康复，并导致在心脏外科ICU停留的时间更长。因此，这项研究的总体目标是通过确定提高睡眠质量和通过白天而不是过夜喂养来保持强劲的昼夜节律是否可以减轻炎症并改善接受营养支持的术后心脏ICU患者的心脏代谢状况，来检验临床营养的新维度。在接受家庭外营养支持的患者中，我们观察到睡眠中断主要是由于难以维持睡眠所致。我们还发现，在自由生活的成年人中，在生物晚上相对于早上进行葡萄糖挑战时，血压和糖耐量受损的反应存在差异。作为一名营养学和时间生物学交叉点的研究人员，我领导着一个“从工作台到床边”的翻译精确营养研究项目，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在ICU评估我的发现的临床翻译。我假设过夜营养支持会导致睡眠破碎和昼夜节律迟钝，从而代表了一种可改变的机制，加剧了心脏术后患者的炎症和心脏代谢紊乱。这一假设将在三个具体目标中进行检验：目标1建议对60名接受肠内营养的ICU患者进行随机对照交叉试验，以检验以下假设：与隔夜肠内营养相比，白天与夜间肠内营养相比，睡眠碎片更少，24小时昼夜节律更强劲(NCT04737200)。睡眠和昼夜节律将使用非侵入性和最先进的技术进行客观评估。目的2将验证这一假说，即与夜间营养相比，白天营养与代谢产物的变化有关，代谢产物通过血浆代谢组学参与与昼夜节律和炎症相关的通路。这将在目标1的临床试验(n=60)和针对自由生活的成年人的全面补充交叉试验(n=366；NCT02997319)中进行测试。Aim 3将在Aim 1的临床试验中验证这一假设，即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有关，包括血压和血糖。拟议的AIMS将为在R00阶段提交关于精确营养的竞争性R01赠款提供充足的数据，这是一个与NIH优先事项一致的研究领域。这项研究还将提供框架，以重新评估标准的过夜营养做法，可能影响美国每年25万住院人数。

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.