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Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia Barynia Backeljauw BS , Cincinnati Childrens Hospital Medical Center 儿童期是敏感的神经发育阶段,由于麻醉 药能够强烈的兴奋或抑制神经传递,因此 麻醉药能够干扰神经网络发育,导致长期 功能障碍。 在动物幼体实验中发现,麻醉后会出现神 经元缺失和长期的学习、记忆损伤等神经 认知功能受损的情况 前言 由于小儿特殊的生理和心理特点,麻醉 是否会对其脑功能有所影响、麻醉药是 否影响其发育等一直以来都是麻醉科、 儿科和神经科医生普遍关注的问题。虽 然进行了大量的研究,许多问题尚未清 楚。 Background Anesthetics induce widespread cell death, permanent neuronal deletion, and abstract neurocognitive impairment in immature animals, raising substantial concerns about similar effects occurring in young children. Background Epidemiologic studies have been unable to sufficiently address this concern, in part due to reliance on group-administered achievement tests, inability to assess brain structure, and limited control for confounders. Methods We compared healthy participants of a language development study at age 5 to 18 years who had undergone surgery with anesthesia before 4 years of age (n = 53) with unexposed peers (n = 53) who were matched for age, gender, handedness, and socioeconomic status. Neurocognitive assessments included the Oral and Written Language Scales and the Wechsler Intelligence Scales (WAIS) or WISC, as appropriate for age. Brain structural comparisons were conducted by using T1-weighted MRI scans. 方法 Results Average test scores were within population norms, regardless of surgical history. However, compared with control subjects, previously exposed children scored significantly lower in listening comprehension and performance IQ. 智力 听力理解能力 Results Exposure did not lead to gross elimination of gray matter in regions previously identified as vulnerable in animals. Decreased performance IQ and language comprehension, however, were associated with lower gray matter density in the occipital cortex and cerebellum. Conclusions The present findings suggest that general anesthesia for a surgical procedure in early childhood may be associated with long-term diminution of language abilities and cognition, as well as regional volumetric alterations in brain structure. Conclusions Although causation remains unresolved, these findings nonetheless warrant additional research into the phenomenons mechanism and mitigating strategies. 为什么成年人和儿童早期接受麻醉后的 影响差异很大? 动物研究发现,未完全成熟的小脑神经 元易受麻醉药物影响,而小脑结构的损 害可能与较低的IQ相关。 讨论 动物实验证明:全麻药物可诱发神经 细胞凋亡,最终导致神经系统功能损 害 动物研究发现,未完全成熟的小脑神经 元易受麻醉药物影响,而小脑结构的损 害可能与较低的IQ相关。 全麻药触发啮齿类动物发育期大脑的神 经细胞凋亡,并致成年期的神经功能缺 陷,在人类发育期大脑全麻药是否也能 导致相似的神经毒性? 临床上没有足够临床资料和流行病学证 据;麻醉后人脑神经元凋亡的组织学证 据也无法获得(在实践上和道德上是不 可能的) Wilder等和Kallman等回顾性研究认 为4岁前接受麻醉药,使用一种以上全 麻药和长时间暴露是导致学习能力减退 的危险因素,其中2岁前暴露风险较大 并不能排除这些神经认知功能方面的异 常是由围手术期因素导致的,例如疼 痛、炎症反应或一些遗传相关的因素。 未能区分手术和麻醉各自本身的影响 ,也不能排除需要手术的患儿原发疾病 更易发生学习能力减退的可能 目前并没有排除这些因素的干扰。 讨论-混杂因素 分析发现,对于本研究中绝大多数接受 麻醉的孩子,各项量表的评分不仅在正 常范围内,甚至有的还高于总体人群平 均水平。 因此,如果将这些孩子与总体人群比较 ,则显示麻醉并没有上述不良影响。 讨论-统计学 Our study has several limitations. The MRI data used in this study are between 8 and 11 years old. More contemporary imaging techniques might provide better resolution and improved sensitivity to subtle brain volumetric differences. Furthermore, the timing between the surgical procedure and the MRI scan and neurocognitive assessment varied from less than 2 to 15 years after surgery, which could have limited the extent of the detectable changes due to brain plasticity and repair. The studys sample size was relatively small, and the time interval since the original study made adequate follow-up difficult. Moreover, study participants were volunteered by their parents for the initial language assessment study, which could affect generalizability of the results to a broader population but did not influence the comparisons between the 2 study groups, which were drawn from the same cohort. As typical for surgery in infants and toddlers, many children in our study underwent surgery for chronic ear infections, which could potentially have influenced language development due to hearing impairment Concerns for neurobehavioral disorders and abnormalities in brain function caused by environmental chemical exposure during early brain development have recently been extended to anesthetics and sedatives, which are administered to millions of young children worldwide.1,16 Many surgical procedures early in life treat life-threatening conditions, avert serious health complications, or improve quality of life and therefore cannot be easily postponed or avoided. Neurotoxic effects of all commonly used anesthetics and sedatives have now been found in a wide variety of animal species, and postexposure learning impairments have been documented in rodents and nonhuman primates.8,17 Accordingly, the present study assessed the effects of early childhood anesthesia for surgery on long-term cognitive function and brain structure by comparing previously exposed children, whose anesthesia records were reviewed, versus matched unexposed control subjects to limit confounding of cognitive performance and structural assessmen 对麻醉的神经毒性的临床研究 临床试验 探讨麻醉药物是否引起小儿的认知功能障碍和学习记 忆力减退 1、Anesthesiology杂志2009,回顾性研究文章,认 为4岁以
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