Department of Anaesthesiology, UZ Leuven, Department of Cardiovascular Sciences, Group Biomedical Sciences, KU Leuven, Leuven, Belgium.
Department of Obstetrics and Gynaecology, UZ Leuven, Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU Leuven, Leuven, Belgium.
J Clin Anesth. 2023 May;85:111050. doi: 10.1016/j.jclinane.2022.111050. Epub 2023 Jan 12.
Anaesthesia is required in 0.4-1% of pregnant women, and prolonged and repeated exposures to anaesthesia may be required. It is unknown whether these exposures may result in foetal neurotoxicity in humans. As sheep have a gestation comparable to that of humans, the objective of this study was to analyse the neurodevelopmental outcome of ovine foetuses that had been exposed in utero to repeated and prolonged anaesthesia.
Randomized controlled preclinical study.
Anaesthesia for non-obstetric surgery during pregnancy.
Twenty-four healthy pregnant Swifter ewes.
The ewes were randomized to no anaesthesia exposure (control-group), single exposure (at gestational age 68-70 days), or repeated exposure (at gestational age 68-70 days and 96-98 days) to 2.5 h of sevoflurane anaesthesia and maternal laparotomy. All lambs were delivered at approximately term gestation (gestational age: 140-143 days).
The primary outcome was neuron density in the frontal cortex 24 h after birth for the control-group versus the repeated-exposure-group. Key secondary outcome was the time needed to achieve the milestone of standing. Secondary outcomes included other neurobehavioural assessments (e.g., motoric milestones) and histological parameters quantified in multiple brain regions (neuron density, total cell density, proliferation, inflammation, synaptogenesis, astrocytes and myelination).
Neuron density in the frontal cortex did not differ between groups (mean ± standard deviation: control-group: 403 ± 39, single-exposure group: 436 ± 23 and repeated-exposure-group: 403 ± 40 neurons/mm, control-group versus repeated-exposure-group: p = 0.986, control-group versus single-exposure-group: p = 0.097). No significant difference was observed for the time needed to achieve the milestone of standing. Only very limited differences were observed for other histological outcome parameters and neurobehavioural assessments.
There is no evidence for foetal neuronal injury or neurobehavioural impairments after a cumulative duration of 5 h repetitive prenatal anaesthesia in sheep.
孕妇中需要麻醉的比例为 0.4-1%，且可能需要长时间重复接触麻醉。目前尚不清楚这些接触是否会导致人类胎儿神经毒性。由于绵羊的妊娠期与人类相似，因此本研究的目的是分析宫内反复长时间暴露于麻醉下的绵羊胎儿的神经发育结果。
随机对照临床前研究。
妊娠期间非产科手术的麻醉。
24 只健康妊娠的斯威夫特母羊。
母羊随机分为无麻醉暴露（对照组）、单次暴露（妊娠 68-70 天）或重复暴露（妊娠 68-70 天和 96-98 天），接受 2.5 小时七氟醚麻醉和母亲剖腹术。所有羔羊均在接近足月时分娩（妊娠龄：140-143 天）。
主要结局是出生后 24 小时对照组与重复暴露组的额皮质神经元密度。关键次要结局是达到站立里程碑所需的时间。次要结局包括其他神经行为评估（例如运动里程碑）和多个脑区的组织学参数（神经元密度、总细胞密度、增殖、炎症、突触发生、星形胶质细胞和髓鞘形成）。
额皮质神经元密度在各组之间无差异（平均值±标准差：对照组：403±39，单次暴露组：436±23，重复暴露组：403±40 个神经元/mm，对照组与重复暴露组：p=0.986，对照组与单次暴露组：p=0.097）。达到站立里程碑所需的时间无显著差异。其他组织学结果参数和神经行为评估仅观察到非常有限的差异。
在绵羊中，累计 5 小时重复产前麻醉后，没有证据表明胎儿神经元损伤或神经行为障碍。
