A Multiplex Analyzer for Sepsis Management

用于脓毒症管理的多重分析仪

• 批准号: 10483277
• 负责人: Kislaya Kunjan
• 金额: $ 34.99万
• 依托单位: CASCADE METRIX, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483277
• 关键词: Acute; Admission activity; Adult; Anemia; Antibiotic Therapy; Antibiotics; Architecture; Award; Biosensor; Blood; Blood Cells; Blood Glucose; Blood Volume; Blood capillaries; Blood specimen; Calibration; Caregivers; Catheters; Cause of Death; Cells; Clinical; Clinical Trials; Complement; Computer software; Cost Savings; Critical Care; Culture-independent methods; Data; Development; Devices; Diagnosis; Diagnostic; Early Diagnosis; Early Intervention; Electrochemistry; Electrodes; Ensure; Erythrocyte Transfusion; Evaluation; Family suidae; Film; Functional disorder; Funding; Glucose; Guidelines; Health Care Costs; Healthcare Systems; Hematocrit procedure; Hemorrhage; Heparin; Hospital Mortality; Hour; Hyperglycemia; Infection; Infusion procedures; Inpatients; Insulin; Intervention; Knowledge; Lactic Acidosis; Life; Liquid substance; Literature; Maintenance; Measurement; Microfluidics; Modification; Monitor; Morbidity - disease rate; Neonatal; Organ; Outcome; Oxygen; Oxygen saturation measurement; Pathway interactions; Patients; Performance; Peripheral; Phase; Population; Prevention; Privatization; Production; Protocols documentation; Rattus; Resuscitation; Risk; Saline; Sampling; Secondary to; Sepsis; Septic Shock; Shock; Source; Spectrophotometry; System; Technology; Testing; Therapeutic; Thick; Time; Transfusion; Validation; Venous; Ventilator; Whole Blood; Work; base; biomaterial compatibility; blood gas analyzer; commercialization; cost efficient; design; diabetic; early detection biomarkers; glucose monitor; glucose sensor; hypoperfusion; infection management; interest; monitoring device; mortality; novel; point of care; porcine model; pre-clinical; preclinical study; preclinical trial; prototype; sensor; validation studies; wasting

PROJECT SUMMARY/ABSTRACT Sepsis, a life-threatening organ dysfunction accounts for over 50 million cases globally and is the leading cause of death. Early intervention via antibiotic therapy, ventilator management, blood glucose maintenance, red blood cell transfusions, and fluid resuscitative strategies reduce mortality from sepsis when supported by appropriate diagnostics and ongoing monitoring. Notably, the latest Surviving Sepsis Campaign guidelines (Sepsis-3) has established blood lactate levels as a key vital sign for septic shock and acknowledged that early management of infection can reverse lactic acidosis and shock status. Every hour of delay in treatment from the time of diagnosis to antibiotic therapy increases mortality of septic shock by 7.6%. Thus, there has been great interest in culture- independent analysis at the point of care for early sepsis diagnosis, management, and prevention of antibiotic overuse. Current clinical literature has highlighted lactate, glucose, hematocrit, and oxygen saturation as early biomarkers of sepsis diagnosis and ongoing monitoring of therapy, be it fluid resuscitations to deal with hypoperfusion; insulin infusion to deal with hyperglycemia; packed blood cell transfusions to deal with anemia; or oxygenation therapies to deal with shock. However, compliance with the Sepsis-3 mandated timely lactate and other analytical measurements is poor due to various pre-analytical and analytical challenges. Notably, capillary blood glucose monitoring devices based on strips are labor intensive and erroneous, while blood gas analyzers have long turnaround times and waste substantial blood volume in patients who may already be anemic. Timely knowledge of the big 4 critical analytes (glucose, lactate, hematocrit and ScvO2) can allow prompt and appropriate administration of antibiotic therapy and supporting interventions thereby significantly reducing morbidity and mortality. This forms the basis of the patient-attached automated 4-plex measurement system proposed by Cascade Metrix (CMX). The CMX Automated Multiplex Analyzer (AutoPlexer) is a patient-attached system that enables timely, accurate, and cost-efficient delivery of automated lactate, glucose, hematocrit and oxygen saturation measurements in whole blood using proven electrochemistry and spectrophotometry without the need for any caregiver sample handling of infectious blood or any blood loss to the patient. The AutoPlexer system performs measurements at user-defined intervals or on-demand by pulling micro-volumes of blood across the sensors for measurement followed by a safe return of the blood using saline in a completely closed-loop, heparin-free, sterilized and biocompatible tubing-based blood pathway. Prior to each measurement, the system performs an automatic calibration to ensure high accuracy. A pilot pre-clinical study in rat and swine models has been performed which helped validate the preliminary design of the prototype for automated glucose measurements. The intent of this Phase I application is to further develop the existing architecture to allow for “simultaneous” glu, lac, hct and ScvO2 measurements using a single blood sample followed by preclinical validation of the resulting AutoPlexer solution.

项目概要/摘要 脓毒症是一种危及生命的器官功能障碍，全球有超过 5000 万例病例，是导致脓毒症的主要原因 死亡。通过抗生素治疗、呼吸机管理、血糖维持、红血球进行早期干预 在适当的支持下，细胞输血和液体复苏策略可降低脓毒症死亡率 诊断和持续监测。值得注意的是，最新的“拯救败血症运动”指南 (Sepsis-3) 已 将血乳酸水平确定为感染性休克的关键生命体征，并承认早期管理 感染可逆转乳酸性酸中毒和休克状态。自诊断之日起每延迟治疗一小时 抗生素治疗会使感染性休克的死亡率增加 7.6%。于是，人们对文化产生了极大的兴趣—— 脓毒症早期诊断、管理和抗生素预防的护理点独立分析 过度使用。目前的临床文献尽早强调了乳酸、葡萄糖、血细胞比容和氧饱和度 脓毒症诊断的生物标志物和治疗的持续监测，无论是液体复苏还是要处理 灌注不足；输注胰岛素以应对高血糖；浓缩血细胞输注治疗贫血； 或氧合疗法来应对休克。然而，遵守 Sepsis-3 要求及时乳酸和 由于各种预分析和分析挑战，其他分析测量效果较差。值得注意的是，毛细管 基于试纸的血糖监测设备是劳动密集型的并且存在错误，而血气分析仪 周转时间长，并且会浪费可能已经贫血的患者的大量血容量。及时 了解四大关键分析物（葡萄糖、乳酸、血细胞比容和 ScvO2）可以帮助您快速、准确地了解 适当施用抗生素治疗和支持干预措施，从而显着减少 发病率和死亡率。这构成了患者附着的自动 4 重测量系统的基础 由 Cascade Metrix (CMX) 提出。 CMX 自动多重分析仪 (AutoPlexer) 是一种附在患者身上的系统，可实现及时、准确、 以及经济有效地提供自动乳酸、葡萄糖、血细胞比容和氧饱和度测量 使用经过验证的电化学和分光光度法测定全血，无需任何护理人员样本 处理感染性血液或患者的任何失血。 AutoPlexer 系统执行测量 用户定义的时间间隔或按需通过传感器抽取微量血液进行测量 然后使用生理盐水在完全闭环、无肝素、无菌且安全的环境中安全返回血液。 基于生物相容性管道的血液通路。每次测量之前，系统会自动执行 校准以确保高精度。已在大鼠和猪模型中进行了一项试点临床前研究， 帮助验证自动葡萄糖测量原型的初步设计。这样做的意图 第一阶段的应用是进一步开发现有的架构，以允许“同时”进行 glu、lac、hct 和 使用单一血液样本进行 ScvO2 测量，然后对所得 AutoPlexer 进行临床前验证 解决方案。