The GAS trial: neurocognitive outcomes 5 years after infant anesthesia

GAS 试验：婴儿麻醉 5 年后的神经认知结果

• 批准号: 9146375
• 负责人: David C Bellinger
• 金额: $ 21.84万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-18 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9146375
• 关键词: 5 year old; Academic achievement; Accounting; Adaptive Behaviors; Address; Age; Anesthesia procedures; Anesthetics; Animal Model; Attention; Australia; Behavior; Brain; Canada; Child; Childhood; Clinical; Cohort Studies; Conduction Anesthesia; Confidence Intervals; Data; Development; Developmental Delay Disorders; Dose; Enrollment; Etiology; Europe; Exposure to; Frequencies; Funding; General Anesthesia; General anesthetic drugs; Gold; Health; Human; Infant; Inguinal Hernia; Intelligence; International; Isoflurane; Italy; Language; Lead; Learning; Light; Memory; Midazolam; Necrosis; Netherlands; Neurocognitive; Neurologic Examination; Neurons; New Zealand; Nitrous Oxide; North America; Nursery Schools; Observational Study; Operative Surgical Procedures; Outcome; Participant; Primates; Propofol; Public Health; Randomized; Randomized Controlled Trials; Regression Analysis; Risk; Safety; Schedule; Sedation procedure; Side; Site; Social Perception; Testing; Toddler; United Kingdom; Vision Screening; Visuospatial; awake; clinical research site; design; executive function; follow-up; hearing screening; infancy; inguinal herniorrhaphy; neonate; neurodevelopment; neuron loss; neurotoxic; neurotoxicity; patient population; prospective; randomized trial; repaired; research study; sedative; sevoflurane; skills; treatment group; trial comparing; visual motor

 DESCRIPTION (provided by applicant): Each year millions of infants and toddlers undergo surgery that involves exposure to general anesthesia. Whether such exposure increases a child's neurodevelopmental risk has never been established. Studies in animal models provide compelling evidence that commonly used agents (e.g., sevoflurane, isoflurane, propofol, midazolam, nitrous oxide) enhance neuronal cell death in the immature brain, in some studies at doses lower than those required to achieve a surgical plane of anesthesia. Some retrospective cohort studies in children have shown that early exposure to general anesthesia, even a single short exposure, is associated with later learning difficulties. The clinical implications of these data are controversial, however, because none of the studies used the gold standard design of a randomized trial to evaluate neurodevelopment in children after exposure to anesthetic agents in infancy, thus limiting the inferences that can be drawn about causality. This application seeks funding for USA sites to complete the GAS study, an ongoing international, prospective, multi-site, randomized, controlled, equivalence trial comparing children's neurodevelopment following receipt of general or regional awake anesthesia. A total of 149 infants who underwent inguinal herniorrhaphy, a common surgery that can be performed using either form of anesthesia, were enrolled at 10 sites in the USA. An additional 573 infants were enrolled at sites in Australia/New Zealand, the United Kingdom, Canada, Italy and the Netherlands, for a total enrollment of 722. Enrollment was completed in January 2013. The primary hypothesis is that neurodevelopmental outcomes at 5 years of age are equivalent in children who received general anesthesia or regional awake anesthesia. The primary endpoint is the Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence. Secondary endpoints include test scores that assess specific domains, including attention/executive function, verbal/language skills, memory and learning, social perception, visuomotor integration, sensorimotor skills, academic achievement, behavior, and adaptive skills. The primary hypothesis of equivalence in Full Scale IQ at 5-years of age will be accepted if the 2-sided 95% confidence interval of the adjusted treatment group difference in means lies within -5 and +5 points. In light of the widespread use of general anesthesia in infant surgery, the results will have substantial public health implications, either supporting the safety of general anesthesia or indicating the need to consider alternative sedation strategies in this patient population.

 描述（由适用提供）：每年数以百万计的婴儿和幼儿涉及暴露于全身麻醉的情况。这种暴露是否会增加儿童的神经发育风险。动物模型中的研究提供了令人信服的证据，表明常见的药物（例如，七氟烷，异氟烷，提案，咪达唑仑，氧化二氮）可以增强未成熟大脑中神经元细胞死亡的研究，在某些剂量的剂量低于相于获得麻醉外科平面所需的剂量。一些儿童的回顾性队列研究表明，早期暴露于全身麻醉，即使是一次短期暴露也与后来的学习困难有关。但是，这些数据的临床意义是有争议的，因为没有一项研究使用随机试验的黄金标准设计来评估婴儿期发生麻醉剂后儿童的神经发育，因此限制了可以对休闲性得出的推论。该申请为美国站点寻求资金来完成GAS研究，这是一项正在进行的国际，前瞻性，多站点，随机，受控的，等效试验，比较了收到一般或区域清醒麻醉后儿童神经发育的比较。共有149名接受腹股沟疝的婴儿，这是一种可以使用任何一种麻醉形式进行的常见手术，在美国的10个部位都纳入了。在澳大利亚/新西兰，英国，加拿大，意大利和荷兰的现场又招募了573名婴儿，总入学人数为722。2013年1月，入学率是在2013年1月完成的。主要假设是神经开发年龄在5年内接受了5岁以上的儿童。主要终点是Wechsler学前班和智力初级规模上的全尺度智商。次要终点包括测试分数，即评估特定领域，包括注意/执行功能，口头/语言技能，记忆和学习，社会知觉，视觉运动整合，感觉运动技能，学术成就，行为和适应性技能。如果调整后的治疗组差异的2侧95％置信区间在-5和+5点以内，则将接受全尺度智商的等价智商为5岁的主要假设。鉴于在婴儿手术中使用全身麻醉的宽度，结果将具有很大的公共卫生影响，要么支持全身麻醉的安全，要么表明需要考虑该患者人群中的替代镇静策略。