Sedation Strategy and Cognitive Outcome after Critical Illness in Early Childhood

儿童早期危重疾病后的镇静策略和认知结果

• 批准号: 8579491
• 负责人: Martha AQ Curley
• 金额: $ 66.32万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8579491
• 关键词: Acute respiratory failure; Admission activity; Affect; Age; Animals; Attention; Barbiturates; Behavior; Benzodiazepines; Biologic Characteristic; Brain; Caring; Child; Child Support; Childhood; Clinical Data; Clinical Trials Design; Cognition; Cognitive; Combination Medication; Control Groups; Critical Care; Critical Illness; Critically ill children; Data; Development; Dose; Enrollment; Ensure; Environment; Environmental Risk Factor; Evaluation; Exposure to; Family; Goals; Hospitals; Hour; Human; Impairment; Infant; Intervention; Ketamine; Language; Learning; Long-Term Effects; Lung; Mechanical ventilation; Memory; Memory impairment; Motor Skills; Neurocognitive; Opioid; Outcome; Patients; Pediatric Intensive Care Units; Pharmaceutical Preparations; Population; Process; Propofol; Protocols documentation; Quality of life; Randomized; Randomized Controlled Trials; Residual state; Respiratory Failure; Risk; Safety; Sedation procedure; Severities; Severity of illness; Siblings; Site; Societies; Staging; Testing; Titrations; Variant; Visuospatial; age related; aged; alpha 2 agonist; barbituric acid salt; cognitive function; drug testing; early childhood; executive function; neurocognitive test; neuron apoptosis; processing speed; public health relevance; randomized trial; sedative; skills; synaptogenesis

DESCRIPTION (provided by applicant): Ensuring the safety and comfort of the more than 100,000 critically ill infants and young children supported on mechanical ventilation in the US each year is integral to the practice of pediatric critical care. Humane care of these young patients requires the use of sedating medications, most commonly combinations of opioids and benzodiazepines. Unfortunately, sedative use also carries risk. Animal studies found that even transient administration of benzodiazepines and other sedatives during periods of developmental synaptogenesis caused widespread neuronal apoptosis and residual learning and memory deficits. Sedation is administered for days to weeks to >90% of acutely-ill, ventilated infants and children. Thus, a commonly used treatment in critically ill young children may itself have detrimental, age-dependent long-term effects. An opportunity to increase the understanding of the long-term cognitive effects of sedation during critical illness in children ha been provided by the cluster randomized, controlled trial of a sedation protocol, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), U01 HL086622, PI Curley, 31 sites, n=2,816. This trial will determine if the trial's sedation protocol used at intervention sites can decrease the duration of mechanical ventilation and sedative exposure among children with acute respiratory failure due to a primary pulmonary process. Control sites continue usual sedation practice. We are collecting detailed data on doses and durations of sedative medications, in-hospital course, and post-discharge quality of life. Testing neurocognitive outcomes was beyond the scope of the initial trial design. However, given evolving concerns about the long-lasting neurocognitive effects of some sedatives, understanding these outcomes is now crucial in this population, regardless of the protocol's short-term effects. The purpose of this study is to determine the relationships between sedative exposure during pediatric critical illness and long-term neurocognitive outcomes. We will assess multiple domains of neurocognitive function 3 years post-discharge in 500 RESTORE subjects with normal baseline cognitive function aged 2 weeks to eight years at pediatric intensive care unit admission. In addition, we will study 310 matched, healthy siblings of RESTORE subjects to provide data on an unexposed group with similar baseline biological characteristics and environment. Our goal is to increase our understanding of the relationships between sedative exposure and long-term neurocognitive outcomes in infants and young children.

描述(申请人提供)：确保美国每年100,000多名接受机械通风支持的危重婴儿和幼儿的安全和舒适是儿科危重护理实践不可或缺的一部分。对这些年轻患者的人道护理需要使用镇静药物，最常见的是阿片类药物和苯二氮卓类药物的组合。不幸的是，使用镇静剂也有风险。动物研究发现，在发育突触发生期间，即使是短暂地给予苯二氮类药物和其他镇静剂，也会导致广泛的神经元凋亡和残留的学习和记忆缺陷。90%的急病、呼吸困难的婴儿和儿童需要几天到几周的镇静剂。因此，危重儿童常用的治疗方法本身可能会产生有害的、与年龄相关的长期影响。一项镇静方案的群组随机对照试验，呼吸衰竭镇静滴定的随机评估(RESTORE)，U01 HL086622，Pi Curley，31个站点，n=2,816提供了增加对危重疾病期间儿童镇静的长期认知影响的理解的机会。这项试验将确定该试验在干预地点使用的镇静方案是否可以减少因原发肺过程而导致急性呼吸衰竭的儿童的机械通气和镇静药物暴露的时间。控制点继续通常的镇静做法。我们正在收集有关镇静药物的剂量和持续时间、住院疗程和出院后生活质量的详细数据。测试神经认知结果超出了最初试验设计的范围。然而，考虑到对一些镇静剂的长期神经认知影响的不断发展的担忧，了解这些结果在这一人群中现在是至关重要的，无论该方案的短期影响如何。这项研究的目的是确定儿科危重疾病期间镇静剂暴露与长期神经认知结果之间的关系。我们将评估500名在儿科重症监护病房入院时基线认知功能正常、年龄在2周至8岁之间的恢复者出院3年后的多个神经认知功能领域。此外，我们将研究恢复受试者的310个匹配的、健康的兄弟姐妹，以提供具有相似基线生物学特征和环境的未暴露组的数据。我们的目标是增加我们对镇静剂暴露和婴儿和幼儿长期神经认知结果之间关系的理解。