KIDS KETAMINE

儿童氯胺酮

• 批准号: 7603389
• 负责人: JOHN W. NEWCOMER
• 金额: $ 0.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603389
• 关键词: Adrenergic Agonists; Adverse effects; Analysis of Variance; Anesthetics; Area; Behavioral; Brain; Child; Cholinergic Agents; Clinical; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Depth; Dissociation; Dose; Double-Blind Method; Effectiveness; Emergency Situation; Funding; Future; Glutamate Receptor; Glutamates; Grant; Human; Individual; Institution; Ketamine; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neuro-Oncological Ventral Antigen 2; Prevention; Prevention strategy; Psyche structure; Range; Reaction; Research; Research Personnel; Resources; Risk; Safety; Schizophrenia; Sedation procedure; Source; Symptoms; Testing; United States Food and Drug Administration; United States National Institutes of Health; Ventilatory Depression; age group; cholinergic; cognitive function; prevent; randomized placebo controlled trial; research study

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 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 choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression. However, emergence reactions are an important adverse effect of ketamine, characterized by transient changes in cognitive function, dissociation and mild schizophrenia-like symptoms. These 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. 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 study is a double-blind, placebo-controlled, randomized trial to test the safety and effectiveness of dexamedetomidine, an FDA approved alpha-2 adrenergic agonist, in preventing ketamine-induced mental symptoms in children. Primary analyses will evaluate effects of the prevention treatment on clinical and cognitive variables using ANOVA. These experiments are relevant to future prevention trials for individuals at risk for schizophrenia, and to preventing adverse effects of NMDA antagonist anesthetic agents.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的长期目标有两个方面：1）使紧急程序镇静安全，有效，对儿童心理无创伤，2）开发预防精神分裂症的药理学策略。 氯胺酮，FDA批准的麻醉剂，正在成为儿童紧急镇静的选择，因为它会导致深度镇静，呼吸抑制最小。 然而，苏醒反应是氯胺酮的重要不良反应，其特征为认知功能的一过性变化、分离和轻度精神分裂症样症状。 氯胺酮和其他N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂可剂量依赖性诱导这些效应。 NMDA受体功能减退可以解除大脑关键区域的兴奋性（胆碱能/多巴胺能）投射，这已经被提出来解释精神分裂症的关键特征。 阻断兴奋性递质过度释放的几种治疗方法也被证明可以预防氯胺酮诱导的NMDA受体功能减退对人类认知和行为的影响。 然而，这种预防策略尚未在儿童中进行评估。 儿童目前接受临床治疗的NMDA拮抗剂，氯胺酮，这一年龄组是一个重要的目标，旨在预防精神分裂症的药理学策略。 本研究是一项双盲、安慰剂对照、随机试验，旨在检测FDA批准的α-2肾上腺素能激动剂dexamedetomidine在预防儿童氯胺酮诱导的精神症状方面的安全性和有效性。 主要分析将使用ANOVA评价预防治疗对临床和认知变量的影响。 这些实验与未来针对精神分裂症高危人群的预防试验以及预防NMDA拮抗剂麻醉剂的不良反应相关。