van Hoorn Camille E, Hoeks Sanne E, Essink Heleen, Tibboel Dick, de Graaff Jurgen C
Department of Anesthesia, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
Department of Pediatric Surgery and Intensive Care, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
Paediatr Anaesth. 2019 Feb;29(2):125-136. doi: 10.1111/pan.13553. Epub 2019 Jan 15.
Recent experimental studies suggest that currently used anesthetics have neurotoxic effects on young animals. Clinical studies are increasingly publishing about the effects of anesthesia on the long-term outcome, providing contradictory results. The selective alpha-2 adrenergic receptor agonist dexmedetomidine has been suggested as an alternative nontoxic sedative agent.
The aim of this systematic review was to assess the potential neuroprotective and neurobehavioral effects of dexmedetomidine in young animals and children.
Systematic searches separately for preclinical and clinical studies were performed in Medline Ovid and Embase on February 14, 2018.
The initial search found preclinical (n = 661) and clinical (n = 240) studies. A total of 20 preclinical studies were included. None of the clinical studies met the predefined eligibility criteria. Histologic injury by dexmedetomidine was evaluated in 11 studies, and was confirmed in three of these studies (caspase-3 activation or apoptosis). Decrease of injury caused by another anesthetic was evaluated in 16 studies and confirmed in 13 of these. Neurobehavioral tests were performed in seven out of the 20 studies. Of these seven rodent studies, three studies tested the effects of dexmedetomidine alone on neurobehavioral outcome in animals (younger than P21). All three studies found no negative effect of dexmedetomidine on the outcome. In six studies, outcome was evaluated when dexmedetomidine was administered following another anesthetic. Dexmedetomidine was found to lessen the negative effects of the anesthetic.
In animals, dexmedetomidine was found not to induce histologic injury and to show a beneficial effect when administered with another anesthetic. No clinical results on the long-term effects in children have been identified yet.
最近的实验研究表明，目前使用的麻醉剂对幼龄动物具有神经毒性作用。关于麻醉对长期预后影响的临床研究越来越多，但结果相互矛盾。选择性α-2肾上腺素能受体激动剂右美托咪定被认为是一种替代性的无毒镇静剂。
本系统评价的目的是评估右美托咪定对幼龄动物和儿童的潜在神经保护和神经行为学效应。
2018年2月14日在Medline Ovid和Embase中分别对临床前和临床研究进行系统检索。
初步检索发现临床前研究（n = 661项）和临床研究（n = 240项）。共纳入20项临床前研究。没有一项临床研究符合预先设定的纳入标准。11项研究评估了右美托咪定引起的组织学损伤，其中3项研究得到证实（半胱天冬酶-3激活或凋亡）。16项研究评估了右美托咪定对另一种麻醉剂所致损伤的减轻作用，其中13项得到证实。20项研究中有7项进行了神经行为学测试。在这7项啮齿动物研究中，3项研究单独测试了右美托咪定对动物（出生后21天以内）神经行为学结局的影响。所有3项研究均未发现右美托咪定对结局有负面影响。在6项研究中，在给予另一种麻醉剂后再给予右美托咪定，评估其结局。发现右美托咪定可减轻麻醉剂的负面影响。
在动物中，发现右美托咪定不会引起组织学损伤，并且与另一种麻醉剂联用时显示出有益作用。目前尚未发现关于其对儿童长期影响的临床结果。
