Reestablishing Sleep and Circadian Alignment in Medically Critically Ill Patients via a Mechanistic Randomized Controlled Trial of an ICU Sleep Chronobundle (ReAlign-ICU) - PROJECT SUMMARY An evidence-based treatment that simultaneously addresses intensive care unit (ICU) sleep and circadian disruption (SCD) is desperately needed. Such treatment is needed because patients admitted to the ICU are at high risk for adverse outcomes resulting directly from acute SCD. It is well established among healthy controls that acute SCD is associated with immediate negative consequences such as metabolic, cognitive, cardiovascular, respiratory, skeletal muscle, and immune dysfunction. Normalization of sleep and circadian processes improves these dysfunctions. In the ICU, sleep and circadian processes cannot be segregated, and there are likely several overlapping domains of SCD (e.g., sleep duration, timing, architecture, and continuity, and circadian alignment and amplitude). Thus, a bundled approach to sleep and circadian promotion holds the most promise for reversing SCD, normalizing broader physiologic disruptions, and improving ICU outcomes. To date, ICU sleep promotion bundles have had limited success in documenting improved sleep, and sleep bundles have commonly ignored circadian disruption and circadian-based sleep promotion strategies. This is a critical gap. Translation of circadian principles to ICU sleep promotion is essential because alignment between biologic and clock time allows for subsequent strategic scheduling of behaviors such as sleeping and eating. In addition, circadian alignment has broader physiologic implications and related potential to improve function across a wide variety of organ systems. Investigations to date have not tested the effect of a multifaceted intervention that includes promotion of both circadian alignment via photic and nonphotic zeitgebers and overnight sleep via non-pharmacologic strategies (sleep chronobundle). The overall objective of this project is to test whether a sleep chronobundle, including daytime bright light, time-restricted daytime feeding, increased daytime mobility, and overnight sleep promotion mitigates ICU SCD. A mechanistic randomized controlled trial will be used to test our central hypotheses that a sleep chronobundle will (1) align biologic and clock day-night; (2) overlap behaviors (e.g., sleeping and eating) correctly with biologic time periods; and therefore (3) improve sleep and metabolic processes in the ICU. Project aims include (1) Establishing the effect of the sleep chronobundle on circadian alignment via sampling of urine 6-sulfatoxymelatonin; (2) Determining the impact of the sleep chronobundle on overnight sleep using portable polysomnography; and (3) Defining the impact of the sleep chronobundle on glucose tolerance via continuous glucose monitoring. Ultimately, this work will provide mechanistic insights into ICU SCD and form the basis of studies that can test the impact of the sleep chronobundle on ICU outcomes. This project includes Prof Xavier Drouot as a consultant. Prof Drouot has unparalleled expertise in interpretation of PSG in critically ill patients. His expertise cannot be replicated, and, as such, he is a tremendous asset to this project. He has committed to interpreting all data from the portable PSG measures. His expertise will improve the rigor and reproducibility of the project data and, in turn, contribute to the development of sleep and circadian interventions that are predicted to directly benefit critically ill patients in the United States immediately following the conclusion of this project.
