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

重症监护病房（ICU）环境不支持睡眠或维持术后患者的昼夜节律

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.