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: 8859881
• 负责人: Martha AQ Curley
• 金额: $ 61.04万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8859881
• 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; Health; 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; 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（由申请人提供）：确保美国每年有超过10万名危重婴儿和幼儿依靠机械通气的安全和舒适，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，即使在发育突触发生期间短暂使用苯二氮卓类药物和其他镇静剂，也会引起广泛的神经元凋亡和残余的学习和记忆缺陷。90%的危重、需要呼吸通气的婴儿和儿童需要服用镇静剂数天至数周。因此，一种通常用于危重幼儿的治疗方法本身可能具有有害的、与年龄相关的长期影响。一项镇静方案的集群随机对照试验提供了一个机会，以增加对危重疾病期间镇静对儿童长期认知影响的理解。《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。该试验将确定在干预点使用的镇静方案是否可以减少因原发性肺疾病引起的急性呼吸衰竭儿童机械通气和镇静暴露的持续时间。对照组继续常规镇静治疗。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，考虑到对某些镇静剂的长期神经认知影响的不断发展的担忧，了解这些结果现在在这一人群中至关重要，无论该方案的短期影响如何。本研究的目的是确定小儿危重疾病期间镇静暴露与长期神经认知结果之间的关系。我们将对500名在儿童重症监护病房入院时基线认知功能正常（2周至8岁）的RESTORE患者出院3年后的多个神经认知功能领域进行评估。此外，我们将研究310名RESTORE受试者匹配的健康兄弟姐妹，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暴露与婴幼儿长期神经认知结果之间关系的理解。