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

简介（由申请人提供）：M. Brandon Westover博士是马萨诸塞州总医院（MGH）的一名执业神经科医生和临床脑电图学家，他的目标是成为一名在生物医学信号处理和药效学方面具有专业知识的独立研究者，因为它们与危重患者的镇静和镇痛有关。他的职业发展计划利用了世界一流环境的资源，在波士顿马萨诸塞州总医院的领先学术机构汇集了一支杰出的研究团队。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，该研究计划将药代动力学/药效学（PK/PD）建模与脑电图和其他生理信号的实时自动处理相结合，定量监测ICU患者的镇静和镇痛并提供闭环控制。在Emery Brown博士、联合导师Sydney Cash博士和Patrick Purdon博士的指导下，Westover博士提出：1)确定哪些脑电图特征和其他生理信号与ICU患者镇静镇痛水平有系统的关系；2)确定ICU患者联合使用右美托咪定和瑞芬太尼两种特定静脉镇静镇痛药物时的药效学反应的全范围和变异性；3)研究闭环给药系统是否该系统将右美托咪定和瑞芬太尼在人群水平的PK/PD特征与个体疼痛水平和意识水平的实时生理反馈相结合，可以实现比目前临床实践更精确的镇静镇痛控制。总体目标是了解如何在ICU环境中客观定量地监测疼痛和镇静，并利用这种理解来减少目前普遍存在的因镇静镇痛药物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广泛的ICU患者的预后开辟新的途径。这个明确的以患者为导向的研究计划，配合指导和结构化的教学课程，将为韦斯特弗博士提供以下技能

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.