Quantitative Monitoring and Control of Sedation and Pain in the ICU Environment

简介(申请人提供)：M.Brandon Westover博士是马萨诸塞州总医院(MGH)的执业神经学家和临床脑电图师，他的目标是成为一名独立研究员，在与危重患者的镇静和止痛相关的生物医学信号处理和药效学方面拥有专业知识。他的职业发展计划利用世界级环境的资源，汇聚了一支以波士顿马萨诸塞州总医院一家领先学术机构为中心的杰出调查团队。Westover博士已经获得了初步结果，证明了一项研究计划的可行性，该计划将药代动力学/药效学(PK/PD)建模与脑电和其他生理信号的实时自动处理相结合，对ICU患者的镇静和止痛进行定量监测和提供闭环控制。在埃默里·布朗博士、西德尼·卡什博士和帕特里克·珀登博士的指导下，Westover博士建议：1)确定脑电和其他生理信号的哪些特征与ICU患者的镇静和止痛水平有系统地相关；2)确定接受两种特定静脉镇静止痛药组合的ICU患者药效反应的全范围和变异性；以及3)研究将右美托咪啶和瑞芬太尼的群体水平PK/PD特征与关于个体疼痛水平和意识水平的实时生理反馈相结合的闭环给药系统可以实现比目前临床实践中更精确的镇静止痛控制。总体目标是了解如何客观和定量地监测ICU环境中的疼痛和镇静，并利用这种了解来减少目前普遍存在的由于镇静止痛药过量和不足而导致的发病率问题。该项目汇集了尖端技术和具有相关专业知识的团队，将为优化护理和改善范围广泛的ICU患者的结局开辟新的途径。这一明确的、以患者为导向的研究方案，与导师指导和结构化的教学课程相结合，将为韦斯特奥弗博士提供以下技能 在科学前沿的临床神经生理学研究中发展独立的职业生涯是必不可少的。

DESCRIPTION (provided by applicant): Dr. M. Brandon Westover is a practicing Neurologist and clinical electroencephalographer at Massachusetts General Hospital (MGH), whose goal is to become an independent investigator with expertise in biomedical signal processing and pharmacodynamics as they relate to sedation and analgesia in critically ill patients. His career development plan leverages the resources of a world-class environment by bringing together an out-standing team of investigators centered at a leading academic institution in Boston, Massachusetts General Hospital. Dr. Westover has already obtained preliminary results demonstrating the feasibility of a research plan that combines pharmacokinetic/pharmacodynamic (PK/PD) modeling with real-time automated processing of EEG and other physiological signals to quantitatively monitor and provide closed-loop control of sedation and analgesia in ICU patients. Under the mentorship of Dr. Emery Brown, and co-Mentors Dr. Sydney Cash and Dr. Patrick Purdon, Dr. Westover proposes: 1) To determine which features of the EEG and other physiological signals systematically relate with levels of sedation and analgesia in ICU patients, 2) To determine the full range and variability of pharmacodynamic responses in ICU patients receiving combinations of two specific intravenous sedative-analgesic medications, namely dexmedetomidine and remifentanil, and 3) To investigate whether a closed-loop drug delivery system, which integrates knowledge about population-level PK/PD characteristics of dexmedetomidine and remifentanil with real-time physiological feedback about an individual's level of pain and level of consciousness, can achieve more precise control of sedation-analgesia than is possible under current clinical practices. The overall goal is to develop an understanding of how to objectively and quantitatively monitor pain and sedation in the ICU setting, and to use this understanding to reduce the now pervasive problem of morbidity due to over- and under-dosing of sedative-analgesic drugs. Bringing together cutting-edge technology and a team with relevant expertise, this project will open new avenues for optimizing care and improving outcomes for a broad range of ICU patients. This well-defined patient-oriented research proposal, in concert with mentorship and a structured didactic curriculum, will provide Dr. Westover with the skills that are essential to develop an independent career in clinical neurophysiological research at the cutting edge of science.