Ing Caleb, Sun Ming, Olfson Mark, DiMaggio Charles J, Sun Lena S, Wall Melanie M, Li Guohua
From the Departments of Anesthesiology.
Epidemiology.
Anesth Analg. 2017 Dec;125(6):1988-1998. doi: 10.1213/ANE.0000000000002423.
Animals exposed to anesthetics during specific age periods of brain development experience neurotoxicity, with neurodevelopmental changes subsequently observed during adulthood. The corresponding vulnerable age in children, however, is unknown.
An observational cohort study was performed using a longitudinal dataset constructed by linking individual-level Medicaid claims from Texas and New York from 1999 to 2010. This dataset was evaluated to determine whether the timing of exposure to anesthesia ≤5 years of age for a single common procedure (pyloromyotomy, inguinal hernia, circumcision outside the perinatal period, or tonsillectomy and/or adenoidectomy) is associated with increased subsequent risk of diagnoses for any mental disorder, or specifically developmental delay (DD) such as reading and language disorders, and attention deficit hyperactivity disorder (ADHD). Exposure to anesthesia and surgery was evaluated in 11 separate age at exposure categories: ≤28 days old, >28 days and ≤6 months, >6 months and ≤1 year, and 6-month age intervals between >1 year old and ≤5 years old. For each exposed child, 5 children matched on propensity score calculated using sociodemographic and clinical covariates were selected for comparison. Cox proportional hazards models were used to measure the hazard ratio of a mental disorder diagnosis associated with exposure to surgery and anesthesia.
A total of 38,493 children with a single exposure and 192,465 propensity score-matched children unexposed before 5 years of age were included in the analysis. Increased risk of mental disorder diagnosis was observed at all ages at exposure with an overall hazard ratio of 1.26 (95% confidence interval [CI], 1.22-1.30), which did not vary significantly with the timing of exposure. Analysis of DD and ADHD showed similar results, with elevated hazard ratios distributed evenly across all ages, and overall hazard ratios of 1.26 (95% CI, 1.20-1.32) for DD and 1.31 (95% CI, 1.25-1.37) for ADHD.
Children who undergo minor surgery requiring anesthesia under age 5 have a small but statistically significant increased risk of mental disorder diagnoses and DD and ADHD diagnoses, but the timing of the surgical procedure does not alter the elevated risks. Based on these findings, there is little support for the concept of delaying a minor procedure to reduce long-term neurodevelopmental risks of anesthesia in children. In evaluating the influence of age at exposure, the types of procedures included may need to be considered, as some procedures are associated with specific comorbid conditions and are only performed at certain ages.
在大脑发育的特定年龄阶段接触麻醉剂的动物会经历神经毒性,随后在成年期会观察到神经发育变化。然而,儿童相应的易损年龄尚不清楚。
使用一个纵向数据集进行了一项观察性队列研究,该数据集通过链接1999年至2010年得克萨斯州和纽约州的个人医疗补助索赔构建而成。对该数据集进行评估,以确定在单个常见手术(幽门肌切开术、腹股沟疝、围产期外包皮环切术或扁桃体切除术和/或腺样体切除术)中5岁及以下接触麻醉剂的时间是否与随后任何精神障碍的诊断风险增加相关,或具体与发育迟缓(DD)如阅读和语言障碍以及注意力缺陷多动障碍(ADHD)相关。在11个不同的接触年龄类别中评估麻醉和手术暴露情况:≤28天、>28天且≤6个月、>6个月且≤1岁以及>1岁且≤5岁之间以6个月为间隔。对于每个暴露儿童,选择5名根据社会人口统计学和临床协变量计算的倾向得分匹配的儿童进行比较。使用Cox比例风险模型来衡量与手术和麻醉暴露相关的精神障碍诊断的风险比。
分析纳入了38493名单次暴露儿童和192465名5岁前未暴露的倾向得分匹配儿童。在所有暴露年龄均观察到精神障碍诊断风险增加,总体风险比为1.26(95%置信区间[CI],1.22 - 1.30),且未随暴露时间显著变化。对DD和ADHD的分析显示了类似结果,风险比升高在所有年龄均匀分布,DD的总体风险比为1.26(95%CI,1.20 - 1.32),ADHD的总体风险比为1.31(95%CI,1.25 - 1.37)。
5岁以下接受需要麻醉的小手术的儿童患精神障碍、DD和ADHD诊断的风险虽小但在统计学上有显著增加,但手术时间并不会改变升高的风险。基于这些发现,几乎没有证据支持推迟小手术以降低儿童麻醉长期神经发育风险这一概念。在评估暴露年龄的影响时,可能需要考虑所纳入手术的类型,因为一些手术与特定合并症相关且仅在特定年龄进行。