Reestablishing Sleep and Circadian Alignment in Medically Critically Ill Patients via a Mechanistic Randomized Controlled Trial of an ICU Sleep Chronobundle (ReAlign-ICU)

项目摘要 一种循证治疗，同时解决重症监护病房（ICU）的睡眠和昼夜节律 我们迫切需要中断（SCD）。这种治疗是必要的，因为进入ICU的患者在 急性SCD直接导致不良结局的风险较高。它在健康对照组中得到了很好的建立 急性SCD与代谢、认知 心血管、呼吸、骨骼肌和免疫功能障碍。睡眠和昼夜节律正常化 改善这些功能障碍。在ICU中，睡眠和昼夜节律过程不能分开， 可能存在SCD的几个重叠域（例如，睡眠持续时间、定时、架构和连续性， 以及昼夜节律排列和幅度）。因此，睡眠和昼夜节律促进的捆绑方法保持了 大多数有望逆转SCD，使更广泛的生理中断正常化，并改善ICU的结果。 到目前为止，ICU睡眠促进捆绑在记录改善睡眠方面取得的成功有限， Bundle通常忽略了昼夜节律中断和基于昼夜节律的睡眠促进策略。这是一 临界间隙将昼夜节律原则转化为ICU睡眠促进至关重要，因为 生物和时钟时间允许随后的行为策略调度，例如，调度睡眠 在生物夜间促进，以改善睡眠时间和质量。此外，昼夜节律调整 更广泛的生理意义和相关潜力，以改善各种器官的功能 系统，例如，在生物日期间安排饮食以改善葡萄糖耐量。调查以 迄今为止，尚未测试多方面干预的效果，包括促进昼夜节律 通过光和非光授时器的排列和通过非药物策略的过夜睡眠（睡眠 chronobundle）。这个项目的总体目标是测试睡眠时间束，包括白天， 明亮的光线，有时间限制的白天喂养，增加白天的流动性，促进夜间睡眠 减轻ICU SCD。一项机械随机对照试验将用于检验我们的中心假设， 睡眠时间束将（1）使生物和时钟昼夜对齐;（2）重叠行为（例如，睡眠和饮食） 正确地与生物时间段;因此（3）改善ICU中的睡眠和代谢过程。我们 由于睡眠和葡萄糖代谢指标与危重疾病的高度相关性， 项目目标包括：（1）通过以下方式确定睡眠时间束对昼夜节律调整的影响： 尿液6-硫酸氧褪黑激素的采样;（2）确定睡眠时间束对过夜的影响。 使用便携式多导睡眠描记仪进行睡眠;（3）确定睡眠时间束对血糖的影响 通过持续葡萄糖监测的耐受性。最终，这项工作将提供ICU的机械见解 SCD和形成的研究，可以测试的睡眠时间束ICU的结果的影响的基础。

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, for example, scheduling sleep promotion during the biologic night to improve sleep duration and quality. In addition, circadian alignment has broader physiologic implications and related potential to improve function across a wide variety of organ systems, for example, scheduling eating during the biologic day to improve glucose tolerance. 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. We are focusing on sleep and glucose metabolism metrics because of their high relevance to critical illness. 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.