Study protocol for a two-center test of a nurse-implemented chronotherapeutic restoring bundle in critically ill children: RESTORE Resilience (R(2))

Often, pediatric intensive care environments are not conducive to healing the sick. Critically ill children experience disruptions in their circadian rhythms, which can contribute to delayed recovery and poor outcomes. We aim to test the hypothesis that children managed via RESTORE Resilience (R(2)), a nurse-implemented chronotherapeutic bundle, will experience restorative circadian rhythms compared to children receiving usual care. In this two-phased, prospective cohort study, two separate pediatric intensive care units in the United Sates will enroll a total of 20 baseline subjects followed by 40 intervention subjects, 6 months to less than 18 years of age, requiring invasive mechanical ventilation. During the intervention phase, we will implement the R(2) bundle, which includes: (1) a focused effort to replicate the child's pre-hospitalization daily routine, (2) cycled day-night lighting and sound modulation, (3) minimal yet effective sedation (RESTORE), (4) nighttime fasting with bolus enteral daytime feedings, (5) early progressive mobility (PICU Up!), (6) continuity in nursing care, and (7) parent diaries. Our primary outcome is circadian activity ratio post-extubation. We hypothesize that children receiving R(2) will experience restored circadian rhythms as evidenced by decreased nighttime activity while in the PICU. Our exploratory outcomes include salivary melatonin levels; electroencephalogram (EEG) slow-wave activity; R(2) feasibility, adherence, and system barriers; levels of patient comfort; exposure to sedative medications; time to physiological stability; and parent perception of being well cared for. This paper describes the design, rationale, and implementation of R(2). CLINICALTRIALS.GOV IDENTIFIER: NCT04695392.