Restore Resilience in Critically Ill Children

Study Overview
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Brief Summary
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The study design will allow investigators to describe usual care in each PICU and identify the facilitating and restraining factors impacting the implementation of R2 at each PICU. The purpose of this pilot study is to improve the care, environment, daily routine and sleep patterns of children in the PICU. The goal of this study is to learn what can be improved to support a critically ill child's healing and circadian rhythms.

Detailed Description
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Hospitals should do the sick no harm. That noted, modern day pediatric intensive care units (PICUs) are not healing milieus. Immediately upon admission to the PICU, the child's daily routine and sleep patterns are replaced by a well-intended but not patient-centered PICU routine. The interprofessional investigative team believes that PICU care and environments can be modulated to sustain a young child's circadian rhythm (CR) and support their physiological resilience and capacity to heal. The first step in this program of research is to pilot-test RESTORE resilience (R2), a 7-item individualized bundle that we hypothesize will restore CR in critically ill children using a pre-posttest design. Two separate PICUs will each enroll 10 baseline subjects followed by 20 intervention subjects, 6 months to 18 years of age, who are intubated and mechanically ventilated for acute respiratory failure. Specifically, as soon as possible after PICU admission, parents will be interviewed to create an individualized chronotherapeutic bundle to include (1) focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods), (2) cycled day-night lighting and modulation of sound to match the child's routine, (3) minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE), (4) night fasting with bolus enteral daytime feedings, (5) early, developmentally-appropriate, progressive exercise and mobility (PICU Up!), (6) continuity in nursing care, and (7) parent diaries. The overall objective of this study is to pilot-test an intervention that can be implemented in any PICU that will improve sleep-wake patterns with restoration/maintenance of circadian rhythms in critically ill children with acute respiratory failure. Results of this pilot study will be used to inform the design of an adequately powered multicenter randomized trial of R2.

Official Title
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Restore Resilience in Critically Ill Children

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Other: R2 Bundle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PICU admission at one of the study sites in which elements of R2 are typically but sporadically implemented Transferred to the PICU from another hospital unit/ward with ≤4 nights in the hospital (≤2 nights in PICU) Between the ages 6 months and 18 years at the time of enrollment (has not had their 18th birthday) Intubated and mechanically ventilated for acute airway or parenchymal disease within last 48 hours Expected to be intubated for more than 12 hours past enrollment Parent/Guardian providing consent, provides primary care for subject Exclusion Criteria: A baseline cognitive dysfunction, measured by the Pediatric Cerebral Performance Category (PCPC ≥4) A history of an uncontrolled seizure disorder (seizure within past 3 months), cerebral hypertension, neuromuscular respiratory failure, ventilator dependence (excluding BiPAP or CPAP at night) A history of inability to tolerate bolus enteral feeds (full J-Tube fed patients) The presence of any of the following within 24 hours of admission: Modal pain scores greater than 4 Persistent hypotension/hypertension unresponsive to standard therapies Use of High Frequency Oscillatory Ventilation or Extracorporeal Membrane Oxygenation Administered melatonin within the past week Has an active do-not-resuscitate plan

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective Cohort Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>R2 Bundle | Other: R2 Bundle<br>* During the intervention phase subjects will receive R2. Focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods), Cycled day-night lighting and modulation of sound to match the child's routine, Minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE), Night fasting with bolus enteral daytime feedings, Early, developmentally-appropriate, progressive exercise and mobility (PICU Up!), Continuity in nursing care, and Parent diaries.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in circadian activity ratio (CAR) - Acute Phase | CAR = Daytime activity/total 24-hr actigraphy activity | From study enrollment to immediately after endotracheal extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Melatonin levels | Salivary melatonin levels | 8 samples over 24 hours on Days 2 and 5 of PICU hospitalization | 
| Slow-wave EEG activity | Proportion of slow-wave EEG activity during endotracheal intubation | First 72 hours of PICU hospitalization | 
| Daily R2 bundle feasibility | Proportion of the seven R2 elements implemented per day per enrolled subject | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Daily R2 bundle adherence | Proportion of daily feeding and sleep activities that match the subject's preadmission routine | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Daily R2 bundle system barriers | Daily survey of non-patient related factors that prevented R2 bundle implementation | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Pain free days | Proportion of PICU days without pain (Pain score > 3) | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Agitation free days | Proportion of PICU days without agitation (SBS > 0) | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Delirium free days | Proportion of PICU days without delirium (Cornell Assessment for Pediatric Delirium positive) | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Iatrogenic withdrawal syndrome free days | Proportion of PICU days without IWS (WAT-1 > 2) | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Peak daily dose of all sedative agents | Highest daily mg/kg dose of all sedative agents | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Cumulative dose of all sedative agents | Total PICU mg/kg dose of all sedative agents received | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Total PICU days of sedation | Total number of PICU days exposed to sedatives | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Time to physiological stability | Time between the start and stop of vasoactive medications, mechanical ventilation, PICU care | From date of enrollment until the date of PICU discharge, assessed for up to 2 months | 
| Parent perception of being well-cared-for | Percent match on the 7-item family-centered care scale (FCCS); range from 0-100% match; where higher scores are better | On the date of PICU discharge, assessed once within an average of 2 weeks post PICU admission | 
| Change in circadian activity ratio (CAR) - Recovery | CAR = Daytime activity/total 24-hr actigraphy activity | From immediately after endotracheal extubation to immediately after PICU discharge |