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
基本信息
- 批准号:10735115
- 负责人:
- 金额:$ 53.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAdoptedAdultAnesthesia proceduresAnestheticsAttenuatedBiological MarkersBrainBrain InjuriesBrain IschemiaCardiopulmonary ResuscitationCaringCause of DeathCerebrovascular CirculationCerebrumCirculationComaDexmedetomidineElectroencephalographyElectrophysiology (science)EncephalopathiesExclusionFemaleGeneticGuidelinesHeart ArrestHospitalsHyperemiaHypothalamic structureInfusion proceduresIntravenous infusion proceduresKetamineKnowledgeMetabolicMetabolismMethodsMusNervous System TraumaNeurological outcomeNeuronsOutcomePatientsPhysiologicalPreventionPropofolPublishingRecoveryRoleSedation procedureSleepSlow-Wave SleepSurvival RateTemperatureTestingWithdrawing Carecerebrovascularimprovedinnovationmalenatural hypothermianeuralneurological recoveryneurophysiologyneuroprotectionpoor sleeppreventsleep qualitytoolvirtual
项目摘要
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.
尽管心肺复苏技术取得了进步,但心脏骤停(CA)仍然是导致死亡的主要原因。
(CPR) 方法,只有 10-20% 的成年 CA 受害者能存活到出院,主要是神经损伤。
最初恢复自主循环的患者的死亡原因和停止治疗的原因
尽管轻度低温已被广泛采用来改善 CA 后的神经功能恢复。
ROSC,最近的证据反驳了其功效,导致制定了不建议低温治疗的新指南
因为无论温度管理如何,大多数昏迷的 CA 后患者都会服用镇静剂,
镇静对 CA 后神经功能恢复的确切影响尚不清楚,不包括 CA 后患者的研究。
表明镇静会导致睡眠质量非常差,因此大力推动 ICU 中尽量减少镇静。
另一方面,CA 后镇静可能发挥神经保护作用。
CA 后脑病的共同特征并与不良结果相关,镇静可能会恢复正常。
CA 后通过同时调节能量需求和脑血流量 (CBF) 来调节脑代谢。
需要进行研究来阐明镇静对 CA 后神经功能恢复的作用。
脑电图 (EEG) 广泛用于 CA 后神经预测。
ROSC 后早期用异丙酚诱导脑电图慢波活动与良好的神经功能相关
CA 后患者的结果 下丘脑中的麻醉激活神经元 (AAN) 被多种激活。
类麻醉剂产生慢三角振荡,但生理作用为慢波。
在最近发表的与这一提议相关的研究中,振荡,尤其是缺血后的大脑,是未知的。
我们观察了低温 (33°C) 治疗小鼠中镇静对 CA 后结果的影响。
与CA后不镇静的低温相比,静脉输液镇静的低温
丙泊酚或右美托咪定(DEX)减轻脑充血,诱导较高的慢波脑电图功率
在新的初步研究中,ROSC 后,雄性和雌性小鼠的神经系统结果和存活率均得到改善。
研究表明,CA 后注射氯胺酮镇静未能提高生存率,而化学遗传学激活
ROSC 后的 AAN 会诱导慢波睡眠,并倾向于提高小鼠的存活率。
我们研究发现,CA 后低温镇静可通过促进 CA 后的神经功能恢复来改善
电生理恢复和预防脑血管功能和代谢失调。
为了解决这个假设,具体来说,我们建议确定异丙酚或 CA 后镇静的效果
正常体温期间右美托咪定,以表征 CA 后氯胺酮镇静对
神经系统结果,并阐明慢波振荡在 CA 后神经保护作用中的作用
虽然大多数 CA 后患者都使用镇静剂,但镇静剂对神经系统结果的影响在很大程度上仍然存在。
未知。拟议的研究将填补知识空白并寻求优化 CA 后护理中的镇静。
项目成果
期刊论文数量(0)
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FUMITO ICHINOSE其他文献
FUMITO ICHINOSE的其他文献
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{{ truncateString('FUMITO ICHINOSE', 18)}}的其他基金
Role of sulfide catabolism in ischemic brain injury
硫化物分解代谢在缺血性脑损伤中的作用
- 批准号:
10378758 - 财政年份:2019
- 资助金额:
$ 53.34万 - 项目类别:
Role of sulfide catabolism in ischemic brain injury
硫化物分解代谢在缺血性脑损伤中的作用
- 批准号:
10588192 - 财政年份:2019
- 资助金额:
$ 53.34万 - 项目类别:
IMPACT OF HYDROGEN SULFIDE ON OUTCOME OF CARDIAC ARREST AND CARDIOPULMONARY RESUS
硫化氢对心脏骤停和心肺复苏结果的影响
- 批准号:
8463026 - 财政年份:2010
- 资助金额:
$ 53.34万 - 项目类别:
IMPACT OF HYDROGEN SULFIDE ON OUTCOME OF CARDIAC ARREST AND CARDIOPULMONARY RESUS
硫化氢对心脏骤停和心肺复苏结果的影响
- 批准号:
8055816 - 财政年份:2010
- 资助金额:
$ 53.34万 - 项目类别:
IMPACT OF HYDROGEN SULFIDE ON OUTCOME OF CARDIAC ARREST AND CARDIOPULMONARY RESUS
硫化氢对心脏骤停和心肺复苏结果的影响
- 批准号:
8236893 - 财政年份:2010
- 资助金额:
$ 53.34万 - 项目类别:
IMPACT OF HYDROGEN SULFIDE ON OUTCOME OF CARDIAC ARREST AND CARDIOPULMONARY RESUS
硫化氢对心脏骤停和心肺复苏结果的影响
- 批准号:
8645697 - 财政年份:2010
- 资助金额:
$ 53.34万 - 项目类别:
IMPACT OF HYDROGEN SULFIDE ON OUTCOME OF CARDIAC ARREST AND CARDIOPULMONARY RESUS
硫化氢对心脏骤停和心肺复苏结果的影响
- 批准号:
7862033 - 财政年份:2010
- 资助金额:
$ 53.34万 - 项目类别:
Impact of nitric oxide synthase on myocardial dysfunction of sepsis
一氧化氮合酶对脓毒症心肌功能障碍的影响
- 批准号:
7186477 - 财政年份:2007
- 资助金额:
$ 53.34万 - 项目类别:
Impact of nitric oxide synthase on myocardial dysfunction of sepsis
一氧化氮合酶对脓毒症心肌功能障碍的影响
- 批准号:
7805407 - 财政年份:2007
- 资助金额:
$ 53.34万 - 项目类别:
Impact of nitric oxide synthase on myocardial dysfunction of sepsis
一氧化氮合酶对脓毒症心肌功能障碍的影响
- 批准号:
7618495 - 财政年份:2007
- 资助金额:
$ 53.34万 - 项目类别:
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