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.

项目总结/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，是导致死亡的主要原因。 死亡之通过抗生素治疗、呼吸机管理、血糖维持、红细胞计数进行早期干预 细胞输注和液体复苏策略可降低败血症的死亡率， 诊断和持续监测。值得注意的是，最新的败血症生存运动指南（败血症-3） 确立了血乳酸水平是感染性休克的关键生命体征，并承认 感染可以逆转乳酸酸中毒和休克状态。从确诊开始每延误一小时的治疗 抗生素治疗使感染性休克的死亡率增加7.6%。因此，人们对文化产生了极大的兴趣- 在早期脓毒症诊断、管理和抗生素预防的护理点进行独立分析 过度使用目前的临床文献强调乳酸、葡萄糖、红细胞压积和氧饱和度作为早期诊断指标。 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， 低灌注;胰岛素输注以处理高血糖;浓缩血细胞输注以处理贫血; 或氧合疗法来应对休克。然而，遵守脓毒症-3要求及时乳酸和 由于各种预分析和分析挑战，其他分析测量很差。值得注意的是， 基于条带的血糖监测设备是劳动密集型的并且是错误的，而血气分析仪 在可能已经贫血的患者中具有长的周转时间并且浪费大量的血液体积。及时 了解4大关键分析物（葡萄糖、乳酸盐、红细胞压积和ScvO 2）， 适当的抗生素治疗和支持干预，从而显着减少 发病率和死亡率。这构成了患者连接的自动化4重测量系统的基础 由Cascade Meetings（CMX）提出。 CMX自动多路复用分析仪（AutoPlexer）是一种与患者连接的系统，能够及时、准确、 并且具有成本效益地提供自动化乳酸盐、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检测全血，无需任何护理人员样本 处理感染性血液或患者失血。AutoPlexer系统在以下条件下进行测量： 用户定义的间隔或按需通过将微量血液拉过传感器进行测量 然后使用生理盐水在完全闭环、无肝素、无菌和无菌的环境中安全回输血液， 生物相容的基于管道的血液通路。在每次测量之前，系统执行自动 校准以确保高精度。已经在大鼠和猪模型中进行了初步临床前研究， 帮助验证自动血糖测量原型的初步设计。这样做的目的是 第一阶段的应用是进一步发展现有的架构，以允许“同时”glu，lac，hct和 使用单个血液样本进行ScvO 2测量，然后对所得AutoPlexer进行临床前验证 溶液