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/)).

**数据获取须知** 请参阅下文的“授权访问”章节，了解本次dbGaP数据集的获取方式与其他dbGaP数据集的差异。

**研究目标** RESTORE临床试验的主要目的为评估：采用护士执行的目标导向镇静方案进行管理的危重症儿童，其机械通气时长是否短于接受常规护理的受试者。

**研究背景** 保障接受机械通气支持的危重症婴幼儿的安全与舒适，是儿科重症监护临床实践的核心组成部分。尽管镇静治疗可使无法理解有创生命支持治疗强制性要求的年轻受试者获益，但镇静药物的使用也可能引发不良事件。具体而言，儿科镇静常用的阿片类药物与苯二氮䓬类药物，可能损害床旁神经功能评估、抑制自主呼吸并延长机械通气时长。长期用药还会产生药物耐受，当无需继续镇静治疗时，可能诱发医源性戒断综合征。

诸多成人重症监护领域的研究证实，采用最小有效方案进行镇静管理可改善患者结局。机械通气成人患者的镇静目标已从“无反应状态”转变为“安静、易于唤醒、便于评估”的状态。针对成人受试者的目标镇静、每日中断镇静及/或镇静药物滴定、自主觉醒与呼吸配合、无需镇静等相关研究显示，相较于常规护理，这些方案可改善临床结局，包括缩短机械通气时长。

相较而言，儿科重症监护领域的镇静实践相关数据较为匮乏，且国际研究显示其临床实践存在显著差异。由于儿童存在独特的生物行为学差异，成人重症监护领域的研究结论未必能直接推广至危重症儿童的诊疗中。本RESTORE研究旨在评估护士执行的目标导向镇静方案对急性呼吸衰竭儿科患者临床结局的影响。

**研究对象** 本研究共纳入2449名受试者，平均年龄4.7岁，年龄范围为2周至17岁。

**研究设计** RESTORE研究为一项集群随机临床试验，共在美国31家儿科重症监护病房（Pediatric Intensive Care Unit, PICU）开展。干预组PICU（17家机构，1225名受试者）所采用的方案涵盖目标镇静、觉醒评估、拔管准备评估、每8小时一次的镇静药物调整以及镇静减停流程；对照组PICU（14家机构，1224名受试者）则采用常规镇静管理方案。本研究的主要结局指标为机械通气时长。

**研究结论** 针对因急性呼吸衰竭接受机械通气的儿童，采用镇静方案相较于常规护理并未缩短机械通气时长。对次要结局的探索性分析显示，觉醒状态、疼痛与躁动之间存在复杂关联（[JAMA 2015; 313(4):379-89](https://pubmed.ncbi.nlm.nih.gov/25602358/))。