Characterizing brain dynamic biomarkers of fentanyl using intracranial and high-density electroencephalogram in humans

使用人类颅内高密度脑电图表征芬太尼的大脑动态生物标志物

• 批准号: 10501397
• 负责人: Patrick L. Purdon
• 金额: $ 74.33万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10501397
• 关键词: Acute; Adjuvant; Anesthesia procedures; Anesthetics; Attenuated; Basic Science; Behavioral; Biological Markers; Brain; Caring; Chronic; Clinical; Clinical Research; Data; Dependence; Development; Dopamine Antagonists; Electroencephalogram; Electroencephalography; Fentanyl; Formulation; Frequencies; Funding; General Anesthesia; Human; Intensive Care; Knowledge; Laboratories; Lead; Measures; Methods; Monitor; Names; National Institute of Drug Abuse; Nociception; Nurses; Operating Rooms; Operative Surgical Procedures; Opiate Addiction; Opioid; Opioid Analgesics; Overdose; Pain; Pain management; Patients; Perioperative; Pharmaceutical Preparations; Physiological; Play; Postoperative Pain; Property; Public Health; Reporting; Research Project Grants; Rewards; Role; Sedation procedure; Time; Titrations; Translational Research; Unconscious State; Ventilatory Depression; base; behavior measurement; chronic pain; clinical application; clinical translation; density; drug development; drug discovery; improved; individual patient; neurophysiology; novel; novel therapeutics; opioid abuse; opioid epidemic; opioid mortality; opioid sparing; opioid use; overdose death; prescription opioid; source localization; surgical pain; temporal measurement; tool

Opioid overdose deaths remain a major public health problem in the US. It is now recognized that surgery and post-operative pain are major contributors to persistent opioid use and dependence. Inadequate management of intraoperative nociception can lead to increased post-operative pain, which can lead to increased opioid utilization, chronic pain, opioid dependence, and opioid abuse. In this perioperative setting a major challenge is that patients are either unconscious (in the operating room) or heavily sedated (in the post-anesthesia care unit) and cannot report their pain levels. In these scenarios, anesthesiologists and nurses can only guess the opioid requirements for their patients, as they have no means to measure opioid drug effects in real-time. A real-time measurement of opioid drug effects, if it existed, would allow anesthesiologists and nurses to precisely titrate opioids and could significantly improve post-operative pain management and subsequent rates of opioid utilization, dependence, and overdose. Over the past two years my laboratory has developed a real- time biomarker for opioid drugs that could be used to provide more precise titration of opioid drugs and for drug discovery applications. In this project we propose to investigate the mechanisms underlying this biomarker and develop further translational science to support clinical application of this biomarker.

阿片类药物过量死亡仍然是美国的一个主要公共卫生问题。现在人们认识到手术和 术后疼痛是阿片类药物持续使用和依赖的主要原因。管理不足 术中伤害感受的增加会导致术后疼痛增加，从而导致阿片类药物增加 使用、慢性疼痛、阿片类药物依赖和阿片类药物滥用。在这种围手术期环境中，一个重大挑战 患者要么失去知觉（在手术室），要么处于严重镇静状态（在麻醉后护理中） 单位）并且无法报告他们的疼痛程度。在这些情况下，麻醉师和护士只能猜测 患者对阿片类药物的需求，因为他们无法实时测量阿片类药物的效果。一个 实时测量阿片类药物的作用（如果存在）将使麻醉师和护士能够 精确滴定阿片类药物，可以显着改善术后疼痛管理和后续发生率 阿片类药物的使用、依赖和过量。在过去的两年里，我的实验室开发了一种真正的 阿片类药物的时间生物标志物，可用于提供更精确的阿片类药物滴定和药物滴定 发现应用程序。在这个项目中，我们建议研究该生物标志物背后的机制 并进一步发展转化科学以支持该生物标志物的临床应用。