Andropoulos Dean B
Texas Children's Hospital, and Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA.
Fetal Diagn Ther. 2018;43(1):1-11. doi: 10.1159/000475928. Epub 2017 Jun 7.
The potential for commonly used anesthetics and sedatives to cause neuroapoptosis and other neurodegenerative changes in the developing mammalian brain has become evident in animal studies over the past 15 years. This concern has led to a number of retrospective studies in human infants and young children, and some of these studies observed an association between exposure to general anesthesia as an infant, and later neurobehavioral problems in childhood. This association is particularly evident for prolonged or repeated exposures. Because of the significant growth of fetal interventions requiring sedation and analgesia for the fetus, or because of maternal anesthetic effects, this concern about anesthetic neurotoxicity is relevant for the fetus. The potential for anesthetic neurotoxicity is the most important clinical and research problem in the field of pediatric anesthesiology. This review will first briefly summarize the rapid brain growth and development in the fetus and neonate. Next, animal model data of anesthetic neurotoxicity in the fetus and neonate will be presented, followed by a review of recent human clinical anesthetic neurotoxicity trials. Finally, the rationale for studying dexmedetomidine as a potential neuroprotectant agent in anesthetic neurotoxicity will be reviewed along with study design for two human clinical trials involving dexmedetomidine.
在过去15年的动物研究中，常用麻醉剂和镇静剂在发育中的哺乳动物大脑中引发神经细胞凋亡及其他神经退行性变化的可能性已变得明显。这种担忧促使人们对人类婴幼儿进行了多项回顾性研究，其中一些研究发现婴儿期接受全身麻醉与后期儿童期神经行为问题之间存在关联。这种关联在长时间或反复接触的情况下尤为明显。由于需要对胎儿进行镇静和镇痛的胎儿干预措施显著增加，或者由于母体麻醉作用，这种对麻醉剂神经毒性的担忧与胎儿相关。麻醉剂神经毒性的可能性是小儿麻醉学领域最重要的临床和研究问题。本综述将首先简要总结胎儿和新生儿大脑的快速生长和发育情况。接下来将呈现胎儿和新生儿麻醉剂神经毒性的动物模型数据，随后回顾近期人类临床麻醉剂神经毒性试验。最后，将回顾研究右美托咪定作为麻醉剂神经毒性潜在神经保护剂的理论依据，以及两项涉及右美托咪定的人类临床试验的研究设计。
