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

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.