Turner Ashley D, Sullivan Travis, Drury Kurt, Hall Trevor A, Williams Cydni N, Guilliams Kristin P, Murphy Sarah, Iqbal O'Meara A M
Division of Pediatric Critical Care, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States.
Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
Front Behav Neurosci. 2021 Aug 16;15:713668. doi: 10.3389/fnbeh.2021.713668. eCollection 2021.
In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately "reverse translate" critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care.
在人们对手术麻醉后潜在的神经发育影响表示担忧之际，越来越多的人意识到，危重症期间需要镇静的儿童易患统称为儿科重症监护后综合征（PICS-p）的神经功能障碍。与接受择期手术的健康儿童不同，危重症儿童面临过度的神经应激或损伤，需要单独考虑。尽管人们已经认识到PICS-p，但出院后评估的技术和时间不一致仍然是理解镇静在后期认知功能障碍中具体作用的重大障碍。尽管如此，现有考虑到镇痛和镇静的儿科研究一致将镇静剂和阿片类镇痛药的暴露确定为住院谵妄和出院后神经后遗症的危险因素。动物模型的临床观察结果表明存在神经炎症、神经元死亡增加、髓鞘形成异常以及突触可塑性和神经传递改变。此外，重症监护镇静还会导致睡眠中断，这是急性疾病和出院后恢复期间一个重要但被忽视的变量。由于镇痛和镇静可能是可调节的，了解其潜在机制可能会改变镇静策略以改善预后。为了在这方面取得进展，前瞻性临床研究将受益于数据集和核心结局评估（包括睡眠质量）的一致性。分析还应考虑广泛的诊断、该人群的异质性以及年龄队列中神经发育的动态性质。许多相关的临床前证据是在婴儿期健康动物相对短暂的麻醉暴露中进行研究的，并不适用于危重症儿童。因此，需要更准确地“反向转化”危重症模式以及镇痛和镇静对神经病理学和功能结局影响的互补动物模型。本综述探讨了镇静剂的相互作用以及危重症儿童的神经易损性与生存和功能结局的关系，这是儿科重症监护的下一个前沿领域。
