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.

项目摘要/摘要 败血症是一种威胁生命的器官功能障碍，占全球超过5000万例病例，是主要原因 死亡。通过抗生素疗法，呼吸机管理，血糖维持，红色血液的早期干预 当得到适当的支持时 诊断和正在进行的监控。值得注意的是，最新尚存的败血症运动指南（Sepsis-3）已有 确定的血液裂缝水平是化粪池冲击的关键生命体征，并承认早期管理 感染可以逆转乳酸酸中毒和休克状态。从诊断开始的每个小时的治疗延迟 抗生素疗法将败血性休克的死亡率增加7.6％。那就对文化引起了极大的兴趣 - 在早期败血症诊断，管理和预防抗生素的护理点上进行独立分析 过度使用。当前的临床文献突出了乳酸，葡萄糖，血细胞比容和氧饱和度早期 败血症诊断和正在进行的治疗监测的生物标志物，无论是流畅的复苏以应对 灌注不足；胰岛素输注以应对高血糖；挤满了血细胞输血以应对贫血； 或氧合疗法以应对电击。但是，符合SEPIS-3强制性及时违规和 由于各种分析前和分析挑战，其他分析测量值较差。值得注意的是，毛细管 基于条带的血糖监测设备是劳动密集型且错误的，而血气分析仪 可能已经成为贫血的患者的周转时间很长，并且浪费了大量的血液量。及时 了解4巨头关键分析物（葡萄糖，裂解，血细胞比容和SCVO2）的知识可以提示和 适当地施用抗生素疗法和支持干预措施，从而大大降低 发病率和死亡率。此形式是患者连接的自动化4 plex测量系统的基础 由Cascade Metrix（CMX）提出。 CMX自动多路复用分析仪（AutoPlexer）是一种患者附属系统，可及时，准确， 在自动乳酸，葡萄糖，血细胞比容和氧饱和度测量中的成本效益递送 使用经过验证的电化学和分光光度法的全血而无需任何护理人员样本 处理感染性血液或对患者的任何失血。 Autoplexer系统执行测量 用户定义的间隔或按需通过在传感器上拉出微量的血液以进行测量 然后在完全闭环，无肝素，消毒和 基于生物相容性管道的血液途径。在每个测量之前，系统执行自动 校准以确保高精度。已经进行了大鼠和猪模型的临床前研究 有助于验证自动葡萄糖测量原型的初步设计。意图 第一阶段的应用程序是进一步开发现有的体系结构，以允许“同时” GLU，LAC，HCT和 SCVO2测量使用单个血液样本，然后是临床前验证所得的自动旋转器 解决方案。