Restore Resilience in Critically Ill Children

Acute Respiratory Distress Syndrome Clinical Trial

— R2  

Official title:

Restore Resilience in Critically Ill Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04695392
• Other study ID #: 828061
• Status: Completed
• Phase: N/A
• Start date: September 5, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Other:
• R2 Bundle
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.

Locations

Country	Name	City	State
United States	Johns Hopkins University - Charlotte Bloomberg Children's Center	Baltimore	Maryland
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Pennsylvania	Boston Children's Hospital, Children's Hospital of Philadelphia, Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (18)

Aitken LM, Rattray J, Hull A, Kenardy JA, Le Brocque R, Ullman AJ. The use of diaries in psychological recovery from intensive care. Crit Care. 2013 Dec 18;17(6):253. doi: 10.1186/cc13164. — View Citation

Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry BL, Revell VL. Measuring melatonin in humans. J Clin Sleep Med. 2008 Feb 15;4(1):66-9. — View Citation

Curley MA, Harris SK, Fraser KA, Johnson RA, Arnold JH. State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med. 2006 Mar;7(2):107-14. doi: 10.1097/01.PCC.0000200955.40962.38. — View Citation

Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med. 2008 Nov;9(6):573-80. doi: 10.1097/PCC.0b013e31818c8328. — View Citation

Gehlbach BK, Chapotot F, Leproult R, Whitmore H, Poston J, Pohlman M, Miller A, Pohlman AS, Nedeltcheva A, Jacobsen JH, Hall JB, Van Cauter E. Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation. Sleep. 2012 Aug 1;35(8):1105-14. doi: 10.5665/sleep.1998. — View Citation

Hopkins RO, Choong K, Zebuhr CA, Kudchadkar SR. Transforming PICU Culture to Facilitate Early Rehabilitation. J Pediatr Intensive Care. 2015 Dec;4(4):204-211. doi: 10.1055/s-0035-1563547. — View Citation

Hu RF, Jiang XY, Hegadoren KM, Zhang YH. Effects of earplugs and eye masks combined with relaxing music on sleep, melatonin and cortisol levels in ICU patients: a randomized controlled trial. Crit Care. 2015 Mar 27;19(1):115. doi: 10.1186/s13054-015-0855-3. — View Citation

Huang HW, Zheng BL, Jiang L, Lin ZT, Zhang GB, Shen L, Xi XM. Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation? Crit Care. 2015 Mar 19;19(1):124. doi: 10.1186/s13054-015-0842-8. — View Citation

Jones C, Backman C, Capuzzo M, Egerod I, Flaatten H, Granja C, Rylander C, Griffiths RD; RACHEL group. Intensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial. Crit Care. 2010;14(5):R168. doi: 10.1186/cc9260. Epub 2010 Sep 15. — View Citation

Kamdar BB, Knauert MP, Jones SF, Parsons EC, Parthasarathy S, Pisani MA; Sleep in the ICU (SLEEPii) Task Force. Perceptions and Practices Regarding Sleep in the Intensive Care Unit. A Survey of 1,223 Critical Care Providers. Ann Am Thorac Soc. 2016 Aug;13(8):1370-7. doi: 10.1513/AnnalsATS.201601-087OC. — View Citation

Kamdar BB, Niessen T, Colantuoni E, King LM, Neufeld KJ, Bienvenu OJ, Rowden AM, Collop NA, Needham DM. Delirium transitions in the medical ICU: exploring the role of sleep quality and other factors. Crit Care Med. 2015 Jan;43(1):135-141. doi: 10.1097/CCM.0000000000000610. — View Citation

Kamdar BB, Yang J, King LM, Neufeld KJ, Bienvenu OJ, Rowden AM, Brower RG, Collop NA, Needham DM. Developing, implementing, and evaluating a multifaceted quality improvement intervention to promote sleep in an ICU. Am J Med Qual. 2014 Nov-Dec;29(6):546-54. doi: 10.1177/1062860613509684. Epub 2013 Nov 22. — View Citation

Kudchadkar SR, Aljohani OA, Punjabi NM. Sleep of critically ill children in the pediatric intensive care unit: a systematic review. Sleep Med Rev. 2014 Apr;18(2):103-10. doi: 10.1016/j.smrv.2013.02.002. Epub 2013 May 21. — View Citation

Kudchadkar SR, Yaster M, Punjabi AN, Quan SF, Goodwin JL, Easley RB, Punjabi NM. Temporal Characteristics of the Sleep EEG Power Spectrum in Critically Ill Children. J Clin Sleep Med. 2015 Dec 15;11(12):1449-54. doi: 10.5664/jcsm.5286. — View Citation

Oyarzun F. [Perception of a person's face and the process of personalization-depersonalization]. Actas Luso Esp Neurol Psiquiatr Cienc Afines. 1985 Mar-Apr;13(2):74-6. No abstract available. Spanish. — View Citation

Pollack MM, Holubkov R, Funai T, Berger JT, Clark AE, Meert K, Berg RA, Carcillo J, Wessel DL, Moler F, Dalton H, Newth CJ, Shanley T, Harrison RE, Doctor A, Jenkins TL, Tamburro R, Dean JM; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment. Crit Care Med. 2015 Aug;43(8):1699-709. doi: 10.1097/CCM.0000000000001081. — View Citation

Pollack MM, Holubkov R, Funai T, Clark A, Berger JT, Meert K, Newth CJ, Shanley T, Moler F, Carcillo J, Berg RA, Dalton H, Wessel DL, Harrison RE, Doctor A, Dean JM, Jenkins TL; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Pediatric intensive care outcomes: development of new morbidities during pediatric critical care. Pediatr Crit Care Med. 2014 Nov;15(9):821-7. doi: 10.1097/PCC.0000000000000250. — View Citation

Wieczorek B, Burke C, Al-Harbi A, Kudchadkar SR. Early mobilization in the pediatric intensive care unit: a systematic review. J Pediatr Intensive Care. 2015;2015(4):129-170. doi: 10.1055/s-0035-1563386. Epub 2015 Sep 3. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DARE (Daytime Activity Ratio Estimate), Post Extubation	DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.	From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days
Secondary	Delta Between Average Nighttime and Average Daytime Salivary Melatonin Levels	Delta between average nighttime (19:00 to 06:59) and average daytime (07:00 to 18:59) salivary melatonin levels	Day 5 of PICU hospitalization
Secondary	Percentage of Study Days Where Light and Sound Were Modulated	Percentage of study days where light and sound were modulated to reflect day-night variation in light and sound levels; 0 = no study days where light and sound were modulated; 100% = light and sound modulated on all study days	From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Secondary	Percentage of Study Days Where the Patient Not Fed Enterally After Bedtime	Percentage of study days where the patient was not fed enterally after bedtime	From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Secondary	Continuity in Nursing Care	Continuity in Nursing Care Index (CINC) defined as (N nurses/N shifts)*100. Score range 0-100, lower scores are better.	From date of enrollment until the date of PICU discharge, assessed for up to 28 days
Secondary	Pain Free Days	Percentage of PICU days where pain was assessed (0-10 pain scale) without pain (Pain score <4)	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	Agitation Free Days	Percentage of PICU days without agitation (Agitation = State Behavioral Scale [SBS; range -3 to +2] >/= 1)	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	Delirium Free Days	Percentage of PICU days, where delirium was assessed, without delirium (using the CAPD, pCAM-ICU or psCAM-ICU; cut score determined by instrument)	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	Iatrogenic Withdrawal Syndrome (IWS) Free Days	Percentage of PICU days without IWS (Withdrawal Assessment Tool - version 1 [WAT-1]; range of scores 0-12 where no IWS = WAT-1 < 3)	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	Peak Daily Dose of All Opioid Sedative Agents	Highest daily mg/kg dose of all opioid sedative agents	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	Cumulative Dose of All Opioid Sedative Agents	Total PICU mg/kg dose of all opioid sedative agents received	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	Total PICU Days of Opioid Sedation	Total number of PICU days exposed to opioid sedation	From date of PICU admission until the date of PICU discharge, assessed for up to 28 days
Secondary	PICU Length of Stay	Time between the start and stop of PICU care	From date and time of PICU admission until the date and time of PICU discharge
Secondary	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 indicate a better match	On the date of PICU discharge, assessed once within an average of 2 weeks post PICU admission
Secondary	DARE (Daytime Activity Ratio Estimate), Acute Phase	DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.	From study enrollment to endotracheal extubation