KIDS KETAMINE

儿童氯胺酮

• 批准号: 7377258
• 负责人: JOHN W. NEWCOMER
• 金额: $ 0.54万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377258
• 关键词: KIDS; KETAMINE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-range objectives of this collaborative research are twofold: 1) to make emergency procedural sedation safe, effective, and psychologically atraumatic for children, and 2) to develop pharmacological strategies for preventing schizophrenia. Ketamine, an FDA approved anesthetic agent, is becoming the sedative/analgesic of choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression in comparison to other available agents. However, emergence reactions are an important adverse effect of ketamine, characterized by transient changes in cognitive function, dissociation and mild schizophrenia-like symptoms. These cognitive and behavioral effects are dose-dependently induced by ketamine and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor. NMDA receptor hypofunction can disinhibit excitatory (cholinergic/glutamatergic) projections in key areas of the brain, and this has been proposed to explain key features of schizophrenia. Several treatments that block excessive excitatory transmitter release have also been shown to prevent cognitive and behavioral effects of ketamine-induced NMDA receptor hypofunction in humans. Alpha-2 adrenergic agonists, which can presynaptically inhibit acetylcholine release, can prevent mild ketamine-induced behavioral and cognitive symptoms in healthy human adults. However, this prevention strategy has not been evaluated in children. Children currently receive clinically-indicated treatment with the NMDA antagonist, ketamine, and this age group is an important target for pharmacological strategies aimed at the prevention of schizophrenia. This application proposes a double-blind, placebo-controlled, randomized trial to test the safety and effectiveness of dexmedetomidine, an FDA approved alpha-2 adrenergic agonist, in preventing ketamine-induced mental symptoms in children. Planned primary analyses will evaluate effects of the hyposthesized prevention treatment on clinical and cognitive variables using ANOVA. The proposed experiments are relevant to future prevention trials for individuals at risk for schizophrenia, and to preventing adverse effects of NMDA antagonist anesthetic agents (ketamine, nitrous oxide).

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。这项合作研究的长期目标有两个：1）使紧急程序镇静对儿童安全、有效且不会造成心理创伤；2）制定预防精神分裂症的药理学策略。氯胺酮是 FDA 批准的麻醉剂，正成为儿童紧急镇静的首选镇静/镇痛剂，因为与其他可用药物相比，它能产生深度镇静，且呼吸抑制最小。然而，苏醒反应是氯胺酮的一个重要不良反应，其特征是认知功能的短暂改变、解离和轻度精神分裂症样症状。这些认知和行为影响是由氯胺酮和其他 N-甲基-D-天冬氨酸 (NMDA) 谷氨酸受体拮抗剂引起的剂量依赖性。 NMDA 受体功能减退可以抑制大脑关键区域的兴奋性（胆碱能/谷氨酸）投射，这被认为可以解释精神分裂症的关键特征。一些阻止过度兴奋性递质释放的治疗方法也被证明可以预防氯胺酮引起的人类 NMDA 受体功能低下的认知和行为影响。 Alpha-2 肾上腺素能激动剂可以在突触前抑制乙酰胆碱的释放，可以预防健康成年人由氯胺酮引起的轻度行为和认知症状。然而，这种预防策略尚未在儿童中进行评估。目前，儿童接受 NMDA 拮抗剂氯胺酮的临床适应症治疗，该年龄组是旨在预防精神分裂症的药物策略的重要目标。本申请提出了一项双盲、安慰剂对照、随机试验，以测试右美托咪定（FDA 批准的 α-2 肾上腺素能激动剂）预防氯胺酮引起的儿童精神症状的安全性和有效性。计划的初步分析将使用方差分析评估假设的预防治疗对临床和认知变量的影响。拟议的实验与未来针对有精神分裂症风险的个体的预防试验以及预防 NMDA 拮抗剂麻醉剂（氯胺酮、一氧化二氮）的不良反应相关。