Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul.
Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Br J Anaesth. 2021 May;126(5):1009-1021. doi: 10.1016/j.bja.2021.01.033. Epub 2021 Mar 12.
Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating therapy in a sevoflurane dose-sparing approach.
Neonatal rats were randomised to 6 h of sevoflurane 2.5%, sevoflurane 1% with or without three injections of dexmedetomidine every 2 h (resulting in 2.5, 5, 10, 25, 37.5, or 50 μg kg h), or fasting in room air. Heart rate, oxygen saturation, level of hypnosis, and response to pain were measured during exposure. Neuronal cell death was quantified histologically after exposure.
Sevoflurane at 2.5% was more injurious than at 1% in the hippocampal cornu ammonis (CA)1 and CA2/3 subfields; ventral posterior and lateral dorsal thalamic nuclei; prefrontal, retrosplenial, and somatosensory cortices; and subiculum. Although sevoflurane 1% did not provide complete anaesthesia, supplementation with dexmedetomidine dose dependently increased depth of anaesthesia and diminished responses to pain. The combination of sevoflurane 1% and dexmedetomidine did not reliably reduce neuronal apoptosis relative to an equianaesthetic dose of sevoflurane 2.5%.
A sub-anaesthetic dose of sevoflurane combined with dexmedetomidine achieved a level of anaesthesia comparable with that of sevoflurane 2.5%. Similar levels of anaesthesia caused comparable programmed cell death in several developing brain regions. Depth of anaesthesia may be an important factor when comparing the neurotoxic effects of different anaesthetic regimens.
在新生动物中，长时间接触所有常规使用的全身麻醉药物后会出现结构脑异常，这引起了人们对每年数百万例接受手术的儿童中发生类似影响的极大关注。将全身麻醉与非损伤性镇静剂结合使用可能提供一种更安全的麻醉技术。我们在七氟醚剂量节约方法中测试了右美托咪定作为缓解治疗的作用。
将新生大鼠随机分为 6 小时七氟醚 2.5%组、七氟醚 1%组和七氟醚 1%组加或不加每 2 小时三次右美托咪定注射（分别产生 2.5、5、10、25、37.5 或 50μg/kg/h 的剂量），或在室内空气中禁食。暴露期间测量心率、氧饱和度、催眠水平和对疼痛的反应。暴露后通过组织学量化神经元细胞死亡。
与七氟醚 1%相比，2.5%的七氟醚在海马角（CA）1 和 CA2/3 亚区、腹后和外侧背丘脑核、前额叶、后扣带回和体感皮质以及下托中造成更严重的损伤；虽然七氟醚 1%不能提供完全的麻醉，但右美托咪定的补充剂量依赖性地增加了麻醉深度，并减少了对疼痛的反应。与等效麻醉剂量的七氟醚 2.5%相比，七氟醚 1%与右美托咪定的联合使用并不能可靠地减少神经元细胞凋亡。
七氟醚亚麻醉剂量联合右美托咪定可达到与七氟醚 2.5%相当的麻醉水平。在几个发育中的脑区，相似水平的麻醉引起了相似的程序性细胞死亡。在比较不同麻醉方案的神经毒性作用时，麻醉深度可能是一个重要因素。
