Impact of Prolonged Perioperative Sedation on Infant Brain

围手术期长期镇静对婴儿大脑的影响

• 批准号: 10645492
• 负责人: DUSICA BAJIC
• 金额: $ 28.26万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645492
• 关键词: 1 year old; Address; Age; Age Months; Amygdaloid structure; Anesthesia procedures; Anisotropy; Award; Basal Ganglia; Brain; Brain region; Characteristics; Chest; Child; Childhood; Clinical; Clinical Data; Collaborations; Complex; Congenital Abnormality; Corpus Callosum; Critical Care; Critical Illness; Data; Data Collection; Dependence; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Drug Modulation; Early identification; Esophageal Atresia; Evaluation; Exhibits; Exposure to; Extracorporeal Circulation; Foundations; Future; Gestational Age; Goals; Growth; Human; Incidence; Infant; Infant Care; Knowledge; Lead; Life; Liquid substance; Longitudinal cohort study; Magnetic Resonance Imaging; Manuscripts; Maps; Measures; Mission; National Institute of Child Health and Human Development; National Institute of Drug Abuse; Neonatal; Neurocognitive; Neurologic Effect; Neurotransmitters; Nociception; Operative Surgical Procedures; Opioid; Outcome; Outcome Study; Pain; Pathway interactions; Pediatric Radiologist; Perioperative; Perioperative Care; Pharmaceutical Preparations; Physical Dependence; Play; Postoperative Period; Premature Infant; Publications; Reporting; Research; Risk; Role; Scanning; Sedation procedure; Sensory; Shapes; Site; Socioeconomic Status; Specificity; Structure; Techniques; Thalamic structure; Time; Toddler; United States; age related; brain abnormalities; brain magnetic resonance imaging; brain size; brain volume; clinical care; cohort; disability; experience; gastrointestinal; gray matter; high risk infant; human old age (65+); improved; infancy; innovation; international center; medical complication; neonate; neurobehavioral; neurodevelopment; neuroimaging; neuroprotection; novel; opiate tolerance; opioid exposure; pain processing; postnatal; premature; prevent; prognostic indicator; prospective; recruit; repaired; sex; tool; tractography; white matter

ABSTRACT Prolonged sedation treatment is currently considered standard practice in the safe and compassionate care of critically ill neonates and infants despite leading to opioid tolerance and a high incidence (35-57%) of physical dependence. A unique cohort of infants with congenital long-gap esophageal atresia (EA) undergoes complex perioperative critical care necessitating extraordinarily prolonged sedation (on the scale of weeks). Although our group recently reported decreased brain size and delayed brain growth in term-born infants following long-gap EA repair with prolonged postoperative sedation, there is a fundamental gap in our knowledge of (i) underlying mechanisms and (ii) long-term neurodevelopmental outcomes. Guided by strong preliminary data, this proposal will address 3 key gaps in our knowledge: (1) timing of brain findings (pre vs. during perioperative repair); (2) regional specificity (gray vs. white matter) of (mal)adaptations; as well as (3) infant brain and clinical correlates to early neurodevelopmental outcomes at 1-year of age. The study will employ structural MRI techniques to address these aims. Selected term-born and premature infants with short-gap (brief pain/sedation treatment) and long-gap EA (prolonged sedation treatment) will be scanned twice (AIM 1): before (as neonates), and after complex perioperative critical care (at 4(±1) months of age). Early neurodevelopmental outcomes will be evaluated using standard approaches (AIM 2). The findings will inform (I) mechanisms of brain (mal)adaptations associated with delayed vs. abnormal brain development in infants exposed to prolonged sedation; (II) identify early diagnostic and prognostic indicators for longitudinal neurocognitive correlates; and (III) inform future development of neonatal/infant therapies to mitigate the neurological effects in vulnerable infants exposed to prolonged sedation. Our application aligns with the goals of the National Institute of Child Health and Human Development (NICHD) and National Institute of Drug Abuse (NIDA) to improve the lives of children throughout all stages of development. We established the feasibility serving critical data collection, and we assembled an interdisciplinary team of experts for its successful completion. This research is innovative in that it encompasses a selected group of term-born infants exposed to prolonged sedation associated with dependence to drugs of sedation; novel in that it will investigate underlying mechanisms and neurodevelopmental impact of complex thoracic non-cardiac critical care; and significant in that it is expected to evolve pediatric critical care by developing novel adjunct therapies for age-specific pain and sedation treatment in the United States and the world.

抽象的 长期镇静治疗目前被认为是安全和富有同情心的护理的标准做法 尽管导致阿片类药物耐受并且身体不适发生率很高（35-57%），但危重新生儿和婴儿 依赖性。一群患有先天性长间隙食管闭锁（EA）的独特婴儿经历了复杂的治疗 围手术期重症监护需要极长时间的镇静（数周）。虽然我们的 研究小组最近报告称，足月出生的婴儿在长间隔后大脑尺寸减小，大脑生长延迟 EA 修复需要长时间术后镇静，我们对以下方面的认识存在根本差距：(i) 机制和（ii）长期神经发育结果。 在强有力的初步数据的指导下，该提案将解决我们知识中的 3 个关键差距：(1) 大脑的时序 结果（术前与围手术期修复期间）； (2)（不良）适应的区域特异性（灰质与白质）； (3) 婴儿大脑和临床与 1 岁时早期神经发育结果相关。这 研究将采用结构核磁共振技术来实现这些目标。选定的足月出生婴儿和早产儿 将扫描短间隙（短暂疼痛/镇静治疗）和长间隙 EA（长时间镇静治疗） 两次 (AIM 1)：在复杂的围手术期重症监护之前（新生儿时）和之后（4(±1) 月龄时）。早期的 将使用标准方法（AIM 2）评估神经发育结果。 研究结果将告知（I）与延迟与异常大脑相关的大脑（不良）适应机制 长期服用镇静剂的婴儿的发育； (II) 确定早期诊断和预后指标 纵向神经认知相关性； (III) 为新生儿/婴儿疗法的未来发展提供信息，以减轻 长期镇静对脆弱婴儿的神经系统影响。我们的应用程序与目标一致 国家儿童健康和人类发展研究所 (NICHD) 和国家药物滥用研究所 (NIDA) 改善儿童各个发展阶段的生活。我们确定了可行性 服务于关键数据收集，我们组建了一个跨学科的专家团队，以确保其成功 完成。这项研究的创新之处在于它涵盖了一组选定的足月出生婴儿 与镇静药物依赖相关的长期镇静；新颖之处在于它将调查潜在的 复杂胸部非心脏重症监护的机制和神经发育影响；并显着于 预计通过开发针对特定年龄疼痛的新型辅助疗法来发展儿科重症监护 美国和世界各地的镇静治疗。