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.

在美国，阿片类药物过量死亡仍然是一个主要的公共卫生问题。现在已经认识到手术和 术后疼痛是持续使用阿片类药物使用和依赖性的主要因素。管理不足 术中伤害感受可导致术后疼痛增加，这可能导致阿片类药物增加 利用，慢性疼痛，阿片类药物依赖和阿片类药物滥用。在此围手术期间，一个重大挑战 是患者要么是无意识的（在手术室），要么镇静（在麻醉后护理中） 单位），无法报告其疼痛水平。在这些情况下，麻醉师和护士只能猜测 阿片类药物对患者的需求，因为他们无能实时测量阿片类药物的作用。一个 如果存在实时测量阿片类药物的作用，则可以使麻醉师和护士得以实现 精确滴定阿片类药物，可以显着改善术后疼痛管理和随后的率 阿片类药物的利用，依赖性和过量。在过去的两年中 阿片类药物的时间生物标志物，可用于提供阿片类药物的更精确滴定和药物 发现应用程序。在这个项目中，我们建议研究该生物标志物的基础机制 并开发进一步的转化科学，以支持该生物标志物的临床应用。