Olsen Emily A, Brambrink Ansgar M
aDepartment of Anesthesiology and Perioperative Medicine bDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon, USA.
Curr Opin Anaesthesiol. 2013 Oct;26(5):535-42. doi: 10.1097/01.aco.0000433061.59939.b7.
Every year, millions of children undergo anesthesia. Emerging evidence from experimental in-vitro and in-vivo models supports a role for neuropathologic injury and neurobehavioral deficits at older age after early exposure to various anesthetic regimens. Clinical studies have sought to identify a phenotype of developmental anesthesia neurotoxicity in humans, but the current evidence is limited to data from retrospective studies with their associated confounders. Experimental models have been used to further define the injury and to help identify potential mechanisms of this neurotoxicity.
A recent clinical trial from an Australian birth cohort suggests a single anesthesia exposure as a neonate or infant may increase the risk for language and abstract reasoning deficits later in life, though residual data confounders may remain. Several ongoing clinical trials like Mayo Safety in Kids, Pediatric Anesthesia NeuroDevelopment Assessment, and General Anesthesia and Apoptosis Study will likely offer more clear answers in the future. In the interim, experimental models have described roles for neuroinflammation, mitochondrial damage from reactive oxygen species, and the presence of several neuronal morphology changes from anesthesia exposure. Additionally, several potential neuroprotective agents and strategies have been tested in the laboratory.
Whether anesthesia-associated neurotoxicity affects the developing human brain and whether this leads to clinically measurable deficits remains unclear.
每年,数以百万计的儿童接受麻醉。来自体外和体内实验模型的新证据支持早期接触各种麻醉方案会导致老年时神经病理损伤和神经行为缺陷。临床研究试图确定人类发育性麻醉神经毒性的表型,但目前的证据仅限于来自回顾性研究及其相关混杂因素的数据。实验模型已被用于进一步定义损伤并帮助确定这种神经毒性的潜在机制。
澳大利亚一个出生队列的近期一项临床试验表明,新生儿或婴儿期单次接触麻醉可能会增加日后出现语言和抽象推理缺陷的风险,不过可能仍存在残留数据混杂因素。梅奥儿童安全研究、儿科麻醉神经发育评估以及全身麻醉与细胞凋亡研究等几项正在进行的临床试验未来可能会给出更明确的答案。在此期间,实验模型描述了神经炎症、活性氧导致的线粒体损伤以及麻醉暴露引起的几种神经元形态变化所起的作用。此外,几种潜在的神经保护剂和策略已在实验室进行了测试。
麻醉相关神经毒性是否会影响发育中的人类大脑以及这是否会导致临床上可测量的缺陷仍不清楚。