Non-Human Primate Model for Developing Closed-Loop Anesthesia Delivery Systems

用于开发闭环麻醉输送系统的非人类灵长类动物模型

• 批准号: 10610946
• 负责人: EMERY N BROWN
• 金额: $ 39.37万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10610946
• 关键词: Algorithms; Anesthesia procedures; Anesthesiology; Anesthetics; Animal Model; Animals; Artificial Intelligence; Behavior; Blood Pressure; Brain; Breathing; COVID-19 patient; Caring; Central Nervous System; Circulation; Computer Assisted; Computers; Data; Development; Dexmedetomidine; Dose; Elderly; Electroencephalography; Ensure; Fostering; Foundations; General Anesthesia; Health; Heart Rate; Hour; Human; Hypotension; Infusion procedures; Intelligence; Intensive Care Units; Left; Manuals; Medicine; Modeling; Modernization; Molecular Target; Monitor; Morbidity - disease rate; Nausea; Operating Rooms; Operative Surgical Procedures; Oxygen; Pain management; Patient Care; Patient Monitoring; Patients; Persons; Pharmaceutical Preparations; Physiologic Monitoring; Physiological; Propofol; Provider; Pump; Real-Time Systems; Research; Research Design; Research Project Grants; Safety; Sedation procedure; Specific qualifier value; Syringes; System; Temperature; Testing; Time; Unconscious State; antinociception; brain dysfunction; control theory; experience; improved; model design; neural; neural circuit; neurophysiology; nonhuman primate; patient safety; pharmacodynamic model; pharmacokinetics and pharmacodynamics; post-operative cognitive dysfunction; sensor; side effect; signal processing; vigilance

ABSTRACT/PROJECT SUMMARY Continuous monitoring of physiological state (oxygenation, breathing, circulation) is a standard practice for all patients receiving general anesthesia and sedation. Anesthetics produce their primary effects of unconsciousness and antinociception by acting on molecular targets and neural circuits in the brain and central nervous system. Nevertheless, continuous monitoring of brain function is not a practice requirement. It is no surprise that brain dysfunction following general anesthesia is highly prevalent, particularly among the elderly. Similarly, COVID 19 patients who can be anesthetized for weeks in the intensive care unit, are often left with profound brain dysfunction following termination of ventilatory support. Many years of research have shown that the level of unconsciousness of a patient receiving general anesthesia can be reliably tracked using real-time processing of electroencephalogram (EEG) recordings. In recent years, dramatic advances have been made in sensors, actuators, artificial intelligence and control theory algorithms. A highly plausible solution is the development of closed loop anesthesia delivery (CLAD) systems that determine in real time from the EEG the patient’s level of unconsciousness and precisely control an anesthetic infusion to maintain the level at an appropriate target. The Federal Drug Administration (FDA) readily acknowledges the significant enhancement to patient care that CLAD systems can provide. To date, no system has been approved for human use due to a lack of appropriate animal models to test adequately the reliability and robustness of these systems. Therefore the research design of this project will be to conduct in non-human primates neurophysiological recordings (EEG, local field potentials and neural spiking activity) while simultaneously administering anesthetics using a computer-controlled syringe pump as the animals execute a behavior task to characterize level of unconsciousness. The data will be analyzed by combining pharmacokinetics and pharmacodynamic modeling, modern control theory and statistical signal processing approaches to develop and test real-time CLAD systems. The specific aims of this research project are to develop and test in a non-human primate model, CLAD systems for real-time control of unconsciousness using the anesthetics: propofol, dexmedetomidine, and propofol and dexmedetomidine administered simultaneously. The broad long-term objectives are to: establish a non-human primate model paradigm for development and testing of CLAD systems; and make the use of CLAD systems a standard for intelligent brain state monitoring and precise second-to-second drug dosing in anesthesiology. The health relatedness impact of the research will be a new paradigm for computer-assisted vigilance of brain state and computer-assisted dosing of anesthetic agents. Such systems should enhance patient safety by reducing provider errors and by fostering significant decreases in anesthesia-associate brain dysfunction as well as other anesthesia-related morbidities (inadequate pain control, hypotension, nausea) commonly experienced by the millions of patients who each year receive anesthesia care in operating rooms and intensive care units.

摘要/项目摘要 持续监测生理状态（氧合、呼吸、循环）是所有人的标准做法 接受全身麻醉和镇静的患者产生其主要作用。 通过作用于大脑和中枢的分子靶标和神经回路来实现无意识和预感 然而，持续监测大脑功能并不是实践的要求。 令人惊讶的是，全身麻醉后脑功能障碍非常普遍，尤其是在老年人中。 同样，可以在重症监护病房麻醉数周的 COVID-19 患者通常会被留下 多年的研究表明，通气支持终止后会出现严重的脑功能障碍。 可以实时可靠地跟踪接受全身麻醉的患者的意识丧失程度 近年来，脑电图（EEG）记录的处理取得了巨大的进步。 传感器、执行器、人工智能和控制理论算法是一个非常合理的解决方案。 开发闭环麻醉输送 (CLAD) 系统，该系统根据脑电图实时确定 患者的意识不清程度并精确控制麻醉剂输注以将其维持在 联邦药物管理局 (FDA) 欣然承认这一显着增强。 迄今为止，由于 CLAD 系统可以提供的患者护理，还没有任何系统被批准用于人类使用。 缺乏适当的动物模型来充分测试这些系统的可靠性和稳健性。 该项目的研究设计将在非人类灵长类动物中进行神经生理学记录（脑电图， 局部场电位和神经尖峰活动），同时使用麻醉剂进行麻醉 当动物执行行为任务时，计算机控制注射泵来表征 将通过结合药代动力学和药效学模型来分析数据， 现代控制理论和统计信号处理方法来开发和测试实时 CLAD 系统。 该研究项目的具体目标是在非人类灵长类动物模型中开发和测试 CLAD 系统 使用麻醉剂实时控制意识丧失：异丙酚、右美托咪定和异丙酚 同时给予右美托咪定的广泛长期目标是：建立非人类。 用于开发和测试 CLAD 系统的灵长类动物模型范例；并使 CLAD 系统的使用成为可能 麻醉学中智能大脑状态监测和精确的每秒药物剂量的标准。 该研究的健康相关性影响将成为计算机辅助大脑状态警戒的新范式 麻醉剂的计算机辅助给药系统应通过减少麻醉剂的用量来提高患者的安全性。 提供者的错误并通过促进麻醉相关的脑功能障碍以及其他 麻醉相关疾病（疼痛控制不足、低血压、恶心）通常是患者所经历的 每年有数百万患者在手术室和重症监护室接受麻醉护理。

项目成果

Closed-loop control of anesthetic state in nonhuman primates.

非人类灵长类动物麻醉状态的闭环控制。

• 发表时间: 2023-10
• 作者: Chakravarty, Sourish;Donoghue, Jacob;Waite, Ayan S.;Mahnke, Meredith;Garwood, Indie C.;Gallo, Sebastian;Miller, Earl K.;Brown, Emery N.
• 通讯作者: Brown, Emery N.