Effects of general vs. regional anesthesia on infant neurodevelopment and apnea

全身麻醉与区域麻醉对婴儿神经发育和呼吸暂停的影响

• 批准号: 8145555
• 负责人: David C Bellinger
• 金额: $ 40.13万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-21 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145555
• 关键词: 2 year old; Acute; Age; Americas; Anesthesia procedures; Anesthetics; Animal Model; Apnea; Area; Australia; Behavioral; Biological Models; Boston; Bradycardia; Brain; Breathing; Canada; Characteristics; Child; Clinical; Cognitive; Conduction Anesthesia; Confidence Intervals; Data; Development; Developmental Therapeutics Program; Dose; Drug usage; Enrollment; Equipment and supply inventories; Europe; Exposure to; Frequencies; Funding; Funding Opportunities; General Anesthesia; General anesthetic drugs; Goals; Health; Health Technology; Heart Rate; Hour; Infant; Inguinal Hernia; Interdisciplinary Study; International; Isoflurane; Language; Light; Linear Regressions; Logistic Regressions; Medical Research; Midazolam; Monitor; Motor; Neurologic Examination; Neurological status; New Zealand; Nitrous Oxide; Operative Surgical Procedures; Outcome; Oxygen; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Postoperative Period; Prospective Studies; Public Health; Randomized; Regression Analysis; Request for Applications; Research; Research Institute; Research Personnel; Risk; Safety; Side; Site; Technology Assessment; Therapeutic; Toddler; United Kingdom; United States; Vision Screening; Work; arm; awake; base; clinical research site; clinically significant; college; design; falls; hearing screening; infancy; inguinal herniorrhaphy; interdisciplinary collaboration; neonate; neurodevelopment; neuron loss; neurotoxic; patient oriented; programs; prospective; public health relevance; randomized trial; repaired; trial comparing

DESCRIPTION (provided by applicant): Each year large numbers of children undergo surgery involving 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., isoflurane, 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. The clinical implications of these data are controversial, however, because no prospective study has evaluated neurodevelopment in children after exposure to anesthetic agents in infancy. This application seeks funding for U.S. participation in an international, prospective, multi-site, randomized, controlled, equivalence trial comparing children's neurodevelopment following receipt of general or regional awake anesthesia. A total of 220 infants who undergo inguinal herniorrhaphy, a common surgery that can be performed using either form of anesthesia, will be enrolled at 9 sites in the USA over a 27-month period. Because a total of 24 patients have been enrolled during our pilot phase, an additional 196 patients will be enrolled during this project. An additional 440 infants will be enrolled at sites in Australia and the United Kingdom, for a total enrollment of 660. Funding has been obtained for the non-USA sites. The primary hypothesis is that neurodevelopmental outcomes at 2 years of age are equivalent in children who received general anesthesia or regional awake anesthesia. The primary endpoint will be the Cognitive score on the Bayley Scales of Infant and Toddler Development-3rd edition (BSID-III). Secondary endpoints include the Language and Motor Composite scores on the BSID-III, scores on the MacArthur-Bates Communicative Development Inventory, and neurologic status. The secondary hypothesis is that apnea rates in the first 12 post-operative hours are equivalent in the treatment groups. Multiple linear or logistic regression analysis, adjusting for potential confounders, will be used to estimate treatment group differences. The primary hypothesis of equivalence in Cognitive score at 2-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 are likely to have substantial public health implications. PUBLIC HEALTH RELEVANCE: If general anesthesia is neurotoxic to infants under conditions of clinical use, the public health implications would be substantial given the frequency with which such agents are used in infant surgery. If general and regional awake anesthesia result in neurodevelopmental outcomes that are equivalent, this would support the safety of general anesthetics as currently used.

描述（由申请人提供）：每年大量的儿童接受手术，涉及暴露于全身麻醉。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（例如异氟烷，咪达唑仑，一氧化二氮）增强了未成熟大脑的神经元细胞死亡，在某些研究的剂量低于要实现手术平面所需的剂量。但是，这些数据的临床意义是有争议的，因为在婴儿期暴露于麻醉药物后，没有前瞻性研究评估儿童的神经发育。该申请寻求资助美国参加国际，前瞻性，多站点，随机，受控的，等效试验，比较收到一般或区域清醒麻醉后儿童神经发育的比较。共有220名接受腹股沟疝的婴儿，这是一种可以使用两种麻醉的常见手术，将在27个月的时间内在美国的9个地点纳入美国的9个地点。由于在我们的试验阶段总共招募了24名患者，因此在此项目期间将增加196名患者。澳大利亚和英国的现场将再招募440名婴儿，总入学人数为660。主要的假设是，在接受全身麻醉或区域清醒麻醉的儿童中，2岁的神经发育结局等效。主要终点将是婴儿和蹒跚学步的发展3版（BSID-III）的Bayley量表上的认知评分。次要终点包括BSID-III上的语言和运动综合分数，MacArthur-Bates交流开发清单上的分数以及神经系统状况。次要假设是，在治疗组中，术后前12个小时的呼吸暂停率是等效的。对潜在混杂因素调整的多个线性或逻辑回归分析将用于估计治疗组差异。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，则将接受认知评分在2岁年龄段的认知评分的主要假设。鉴于在婴儿手术中广泛使用全身麻醉，结果可能会产生重大的公共卫生影响。 公共卫生相关性：如果在临床使用条件下进行全身麻醉对婴儿是神经毒性的，那么考虑到这种药物在婴儿手术中使用的频率，公共卫生的影响将是很大的。如果一般和区域清醒麻醉会导致同等的神经发育结果，这将支持当前使用的一般麻醉药的安全。