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 对物理状态的连续监测（氧合，呼吸，循环）是所有人的标准练习 接受全身麻醉和镇静的患者。麻醉剂产生其主要影响 通过作用于大脑和中央的分子靶标和神经回路，无意识和反伤害感受 神经系统。然而，对大脑功能的持续监测不是实践要求。是没有 令人惊讶的是，全身麻醉后的大脑功能障碍非常普遍，尤其是在古老的中。 同样，在重症监护病房中可以麻醉数周的19例COVID患者通常会留下 通风支持终止后，大脑功能障碍深刻。多年的研究表明 可以使用实时跟踪接受全身麻醉的患者的无意识水平 脑电图（EEG）记录的处理。近年来，已经取得了巨大的进步 传感器，执行器，人工智能和控制理论算法。高度合理的解决方案是 开发闭环麻醉输送（CLAD）系统，这些系统从脑电图实时确定 患者的无意识水平并精确控制麻醉输注，以维持水平 适当的目标。联邦药物管理局（FDA）很容易地承认重大增强 为患者护理，外壳系统可以提供。迄今为止，由于A 缺乏适当的动物模型来适当测试这些系统的可靠性和鲁棒性。所以 该项目的研究设计将是在非人类隐私神经生理记录中进行（EEG， 局部现场电位和神经尖峰活动）同时使用A 当动物执行行为任务时，计算机控制的注射器泵以表征 无意识。将通过结合药代动力学和药效学建模来分析数据， 现代控制理论和统计信号处理方法，用于开发和测试实时外壳系统。 该研究项目的具体目的是在非人类的私人模型中开发和测试。 使用麻醉剂实时控制无意识：提案群，右美托咪定和提案fol和提案。 右美托咪定简单地施用。广泛的长期目标是：建立非人类 灵长类动物模型范式用于开发和测试外壳系统；并使用clad系统 麻醉学中智能大脑状态监测和精确的二次药物剂量的标准。这 该研究的健康相关性影响将是针对计算机辅助警惕大脑状态的新范式 和计算机辅助的麻醉剂给药。这样的系统应通过减少来提高患者的安全 提供者错误并通过促进麻醉促进脑功能障碍以及其他方面的大幅下降。 与麻醉相关的病毒性（疼痛控制不足，低血压，恶心）通常经历 每年数以百万计的患者在手术室和重症监护病房接受麻醉护理。

项目成果

Closed-loop control of anesthetic state in nonhuman primates.

• DOI: 10.1093/pnasnexus/pgad293
• 发表时间: 2023-10
• 期刊: PNAS NEXUS
• 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.