Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE-BioLINCC)

<u>**Data Access NOTE **</u> Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions.

<u>**Objectives**</u> The primary aim of the RESTORE clinical trial was to determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol would experience fewer days of mechanical ventilation than participants receiving usual care.

<u>**Background**</u> Ensuring the safety and comfort of critically ill infants and children supported by mechanical ventilation is integral to the practice of pediatric critical care. Although sedation therapy benefits young participants who cannot understand the imperative nature of invasive life-sustaining therapies, sedative use is also associated with untoward adverse effects. Specifically, opioids and benzodiazepines commonly used for pediatric sedation may impair bedside neurological assessment, depress spontaneous ventilation, and prolong mechanical ventilation. Over time, drug tolerance develops, which may precipitate iatrogenic withdrawal syndrome when sedation therapy is no longer necessary.

Numerous studies in adult critical care support a minimal yet effective approach to sedation management. Sedation goals for mechanically ventilated adults have shifted from an unresponsive state to a calm, easily aroused, readily evaluated participant. Studies in adult participants evaluating targeted sedation, daily interruption and/or titration of sedation, pairing of spontaneous awakening with breathing, and no sedation have reported improved clinical outcomes, including decreased length of mechanical ventilation when compared with usual care.

In contrast, few data inform sedation practices in pediatric critical care, and international studies describe significant practice variation. Given unique biobehavioral differences, knowledge generated in adult critical care may not translate to the care of critically ill children. The RESTORE study was conducted to test the effect of a nurse-implemented, goal-directed sedation protocol on clinical outcomes in pediatric participants with acute respiratory failure.

<u>**Participants**</u> There was a total of 2,449 participants (mean age: 4.7 years; range: 2 weeks to 17 years).

<u>**Design**</u> The RESTORE study was a cluster randomized clinical trial conducted in 31 US PICUs. Intervention PICUs (17 sites; 1,225 participants) used a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; 1,224 participants) managed sedation per usual care. The primary outcome variable was duration of mechanical ventilation.

<u>**Conclusions**</u> Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relationship among wakefulness, pain, and agitation ([JAMA 2015; 313(4):379-89](https://pubmed.ncbi.nlm.nih.gov/25602358/)).