Real-time Continuous Intravenous Drug Monitor for Closed-Loop Anesthesia Delivery

用于闭环麻醉输送的实时连续静脉药物监测

• 批准号: 8981998
• 负责人: Brian Scott Ferguson
• 金额: $ 22.03万
• 依托单位: APTITUDE MEDICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-05 至 2017-02-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8981998
• 关键词: Address; Affect; Affinity; Algorithms; American; Anesthesia procedures; Anesthesiology; Anesthetics; Animals; Automobile Driving; Binding; Biofeedback; Biological Assay; Biological Models; Biometry; Biosensor; Blood; Capital; Chronic; Clinical; Clinical Chemistry; Clinical Research; Collaborations; Complex; Computer Systems; Data; Detection; Devices; Diabetes Mellitus; Dose; Doxorubicin; Drug Delivery Systems; Drug Monitoring; Drug usage; Elderly; Electrodes; Ensure; Feedback; General Anesthesia; General anesthetic drugs; Goals; Gold; Hand; Hospitals; Human; Infant; Infusion procedures; Intravenous; Intravenous Anesthetics; Investments; Letters; Life; Ligands; Marketing; Measurement; Measures; Medicine; Methodist Church; Methods; Microfluidic Microchips; Microfluidics; Modeling; Monitor; National Institute of General Medical Sciences; Nucleic Acids; Obesity; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Output; Patient Self-Report; Patients; Performance; Pharmaceutical Preparations; Phase; Physician Executives; Plasma; Population; Propofol; Protocols documentation; Publishing; Reagent; Regimen; Relative (related person); Resolution; Risk; Safety; Sampling; Science; Sedation procedure; Serum; Site; Specificity; Staging; Stimulus; Stretching; System; Systemic disease; Technology; Testing; Therapeutic; Time; Translating; Translational Research; United States Food and Drug Administration; Weight; Whole Blood; Work; aptamer; awake; base; commercialization; design; detector; experience; hazard; human subject; improved; in vivo; industry partner; innovation; meetings; mortality; older patient; particle; patient population; pharmacokinetic model; prevent; prototype; public health relevance; response; screening; sensor; stem; temporal measurement

 DESCRIPTION (provided by applicant): Anesthesiology is the leading field of medicine in addressing safety, but it still has a long way to go. Despite significant decreases in anesthesia-related mortality, crucial factors remain that pose real hazards to the 21 million Americans that receive general anesthesia each year, and According to the NIGMS, "general anesthetics are still among the most dangerous drugs used by doctors, particularly for elderly patients and those with certain chronic, systemic diseases, such as diabetes." It is now clear that the manner in which anesthesia is delivered has a profound impact on safety. Yet, there given a patient population with highly diverse and changing pharmacological differences, practitioners of anesthesia have no direct means of knowing the precise drug plasma levels in the patient at any given time. Thus, there is no direct measure of how to tailor dosing to achieve optimal safety. Such a capability would have a transformative impact, driving the practice of anesthesia to an exacting science that will improve the safety and outcomes of patients. Target controlled infusion systems exist which can automatically adjust doses. However, these are based on a prediction of the plasma drug concentration, by extrapolating from a small model population of healthy patients, leading to major safety concerns, and an absence of FDA clearance. Direct measurement of intravenous concentrations is required to manage these risks and gain market approval. Thus, we propose to develop the first system that directly measures and precisely controls intravenous anesthetic drug concentrations continuously in real-time. We present a disposable system that exploits an aptamer sensor in a microfluidic device that prevents degradation from unmodified whole blood and maintains drift-free quantification with sub-minute time resolution, and nanomolar sensitivity. The completion of Phase I Aims will deliver a proof of concept system, which affirms our ability to measure and control plasma propofol levels in real time in live rabbits, as verified by gold standard LC-MS/MS methods. We will also determine if our feedback-controlled propofol infusion can reduce excursions from a desired depth of sedation versus standard sedation protocol as tested by response to physical stimuli. In Phase II, we will include human subjects to validate our potential to accurately measure propofol levels in humans. We will deliver design improvements and performance metrics, ready for clinical study. We expect to follow on with private capital or strategic investment from a partner company to proceed through clinical stage and FDA clearance via collaboration with industry partners.

 描述(申请人提供)：麻醉学是解决安全性的医学的领先领域，但它仍然有很长的路要走。尽管与麻醉相关的死亡率显著下降，但关键因素仍然对每年接受全身麻醉的2100万美国人构成真正的危险，根据NIGMS的说法，“全身麻醉剂仍然是医生使用的最危险的药物之一，特别是对老年患者和那些患有某些慢性系统性疾病的人，如糖尿病。”现在很明显，麻醉的方式对安全性有深远的影响。然而，由于患者群体具有高度多样化和不断变化的药理差异，麻醉从业者无法直接了解患者在任何给定时间的准确血药浓度。因此，没有直接的措施来衡量如何调整剂量以实现最佳安全性。这种能力将产生革命性的影响，推动麻醉实践成为一门严格的科学，将提高患者的安全性和结果。靶控输液系统可以自动调整剂量。然而，这些都是基于对血浆药物浓度的预测，通过从一小部分健康患者的模型人群进行外推，导致了主要的安全问题，并且没有FDA的批准。为了管理这些风险并获得市场批准，需要直接测量静脉注射浓度。因此，我们建议开发第一个直接测量和实时连续精确控制静脉麻醉药物浓度的系统。我们提出了一种一次性系统，该系统利用微流控设备中的适体传感器来防止未经修改的全血的降解，并保持亚分钟时间分辨率和纳摩尔灵敏度的无漂移定量。第一阶段目标的完成将提供一个概念验证系统，它确认了我们有能力实时测量和控制活体兔的异丙酚血浆浓度，这一能力得到了金标准LC-MS/MS方法的验证。我们还将确定我们的反馈控制异丙酚输注是否可以减少对物理刺激的反应测试的标准镇静药物的镇静深度的漂移。在第二阶段，我们将包括人体受试者，以验证我们准确测量人类异丙酚水平的潜力。我们将提供设计改进和性能指标，为临床研究做好准备。我们希望从合作伙伴公司获得私人资本或战略投资，通过与行业合作伙伴的合作，继续通过临床阶段和FDA的批准。