Role of Sedation in the Post-Cardiac Arrest Neurological Recovery

镇静在心脏骤停后神经恢复中的作用

• 批准号: 10735115
• 负责人: FUMITO ICHINOSE
• 金额: $ 53.34万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735115
• 关键词: Address; Adopted; Adult; Anesthesia procedures; Anesthetics; Attenuated; Biological Markers; Brain; Brain Injuries; Brain Ischemia; Cardiopulmonary Resuscitation; Caring; Cause of Death; Cerebrovascular Circulation; Cerebrum; Circulation; Coma; Dexmedetomidine; Electroencephalography; Electrophysiology (science); Encephalopathies; Exclusion; Female; Genetic; Guidelines; Heart Arrest; Hospitals; Hyperemia; Hypothalamic structure; Infusion procedures; Intravenous infusion procedures; Ketamine; Knowledge; Metabolic; Metabolism; Methods; Mus; Nervous System Trauma; Neurological outcome; Neurons; Outcome; Patients; Physiological; Prevention; Propofol; Publishing; Recovery; Role; Sedation procedure; Sleep; Slow-Wave Sleep; Survival Rate; Temperature; Testing; Withdrawing Care; cerebrovascular; improved; innovation; male; natural hypothermia; neural; neurological recovery; neurophysiology; neuroprotection; poor sleep; prevent; sleep quality; tool; virtual

Sudden cardiac arrest (CA) is a leading cause of death. Despite advances in cardiopulmonary resuscitation (CPR) methods, only 10-20% of adult CA victims survive to hospital discharge. Neurologic injury is the main cause of death and reason to withdraw care in patients who initially achieve return of spontaneous circulation (ROSC) after CA. Although mild hypothermia has been widely adopted to improve neurologic recovery after ROSC, recent evidence refuted its efficacy leading to a new guideline that does not recommend hypothermia any longer. Because majority of comatose post-CA patients are sedated regardless of temperature management, precise impact of sedation on post-CA neurologic recovery is unknown. Studies excluding post-CA patients suggest that sedation provides very poor sleep quality, leading to a significant push to minimize sedation in ICU. On the other hand, post-CA sedation may exert neuroprotective effects. Cerebrovascular dysregulation is a common feature of post-CA encephalopathy and associated with poor outcomes. Sedation may normalize cerebral metabolism by concurrently modulating energy demand and cerebral blood flow (CBF) after CA. Further studies are needed to elucidate the role of sedation on neurologic recovery after CA. Quantitative electroencephalogram (EEG) is widely used for post-CA neuroprognostication. Recent studies showed that induction of slow-wave activities on EEG by propofol early after ROSC is associated with favorable neurologic outcomes in post-CA patients. Anesthesia-activated neurons (AANs) in hypothalamus are activated by diverse classes of anesthetic agents to produce slow-delta oscillations. However, physiological role of slow-wave oscillation, especially in post-ischemic brain, is unknown. In recently published studies related to this proposal, we evaluated the effects of sedation on outcomes after CA in hypothermia (33°C)-treated mice. We observed that, compared to hypothermia without sedation after CA, hypothermia with sedation with an intravenous infusion of propofol or dexmedetomidine (DEX) attenuated cerebral hyperemia, induced higher slow wave EEG power after ROSC, and improved neurological outcomes and survival in male and female mice. In new preliminary studies, post-CA sedation with ketamine infusion failed to improve survival, whereas chemogenetic activation of AANs after ROSC induced slow wave sleep and tended to improve survival rates in mice. Based on these results, we hypothesize that post-CA sedation during hypothermia improves neurological recovery after CA by promoting electrophysiological recovery and preventing dysregulation of cerebrovascular function and metabolism. To address this hypothesis, specifically, we propose to determine the effects of post-CA sedation with propofol or dexmedetomidine during normothermia, to characterize the effects of post-CA sedation with ketamine on neurologic outcomes, and to elucidate the role of slow-wave oscillation in the neuroprotective effects of post-CA sedation. While most post-CA patients are sedated, how sedation alters neurologic outcomes remains largely unknown. The proposed studies will fill the knowledge gap and seek to optimize sedation in post-CA care.

心脏骤停（CA）是死亡的主要原因。尽管心肺复苏进展 （CPR）方法，只有10％至20％的成年CA受害者出院。神经损伤是主要的 死亡原因和理由撤回最初获得赞助循环返回的患者的护理原因 （ROSC）大约之后。尽管温和的体温过低已被广泛采用，以改善 ROSC，最近的证据驳斥了其有效性，导致了不建议体温过低的新指南 再过。由于大多数昏迷后CA患者被镇静了，无论温度管理如何 镇静对CA后神经系统恢复的精确影响尚不清楚。不包括后CA患者的研究 表明镇静剂提供的睡眠质量非常低，从而大大推动了ICU中的镇静作用。 另一方面，CA后镇静剂可能会执行神经保护作用。脑血管失调是 CA后脑病的共同特征，并且与不良结局有关。镇静可能正常 通过同时调节能量需求和脑血流（CBF），大脑代谢。更远 需要进行研究来阐明镇静作用在大约之后神经系统恢复中的作用。定量 脑电图（EEG）被广泛用于CA后神经proptostication。最近的研究表明 ROSC提早提前对脑电图的慢波活动诱导与有利的神经系统相关 后CA患者的结果。下丘脑中麻醉的神经元（AAN）被多种激活 麻醉剂类别以产生缓慢的振荡。但是，慢波的身体角色 振荡，尤其是在缺血后大脑中，尚不清楚。在最近发表的与该提案有关的研究中 我们评估了镇静对体温过低（33°C）治疗的小鼠CA后结局的影响。我们观察到 与CA后没有镇静的体温过低相比，静脉输注的镇静体内症状 提案或右美托汀（DEX）减弱脑充血，诱导较高的慢波脑电图 在ROSC之后，改善了雄性和雌性小鼠的神经系统结局和生存。在新的初步中 研究，氯胺酮输注后CA镇静作用未能提高生存率，而化学遗传激活 ROSC诱导慢波睡眠后的AAS倾向于提高小鼠的存活率。基于这些结果， 我们假设在体温过低期间CA后CA镇静作用通过促进CA后改善了神经系统恢复 电生理恢复并防止脑血管功能和代谢失调。到 具体来说，我们建议通过提案类似或 在Normothotermia期间的右美托胺，以表征氯胺酮后CA镇静的影响 神经系统结局，并阐明慢波振荡在CA后神经保护作用中的作用 镇静。虽然大多数CA后患者都被镇静了，但镇静如何改变神经系统效果 未知。拟议的研究将填补知识差距，并寻求优化CA后护理中的镇静剂。