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

描述（由申请人提供）：Dr. M.布兰登Westover是一个执业神经学家和临床脑电图在马萨诸塞州总医院（MGH），其目标是成为一个独立的研究者，在生物医学信号处理和药效学的专业知识，因为它们涉及到危重病人的镇静和镇痛。他的职业发展计划利用世界一流环境的资源，汇集了一支以波士顿领先学术机构马萨诸塞州总医院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EEG和其他生理信号的实时自动处理相结合，以定量监测并提供ICU患者镇静和镇痛的闭环控制。在埃默里·布朗博士、共同导师悉尼·卡什博士和帕特里克·珀登博士的指导下，韦斯特弗博士提出：1）确定EEG和其他生理信号的哪些特征与ICU患者的镇静和镇痛水平系统地相关，2）确定接受两种特定静脉内镇静-镇痛药物组合的ICU患者的药效学反应的全范围和可变性，即右美托咪啶和瑞芬太尼，以及3）研究闭环药物递送系统是否可以实现比在当前临床实践下可能的更精确的镇静-镇痛控制，所述闭环药物递送系统将关于右美托咪啶和瑞芬太尼的群体水平PK/PD特征的知识与关于个体的疼痛水平和意识水平的实时生理反馈整合。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问题，由于过度和剂量不足的镇静镇痛药物的发病率。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。这个明确的以病人为导向的研究计划，与导师制和结构化的教学课程相结合，将为Westover博士提供 在科学的前沿发展临床神经生理学研究的独立职业生涯至关重要。

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.