Sepsis impacts 1.7 million Americans annually, leading to 270,000 deaths and $62 billion in costs. Most of the sepsis treatment follows the Surviving Sepsis Campaign (SSC) guidelines, consisting of early antibiotics, liberal fluid resuscitation, and vasopressor use in persistent hypotension. However, the fundamental assumption that sepsis universally results in high capillary leak leading to hypovolemia that benefits from aggressive fluid resuscitation, has been refuted by multiple publications suggesting improved outcomes with the administration of less or even no fluid. In fact, other studies have shown that even very restrictive fluid resuscitation might benefit septic shock. Despite these findings, U.S.-based treatment guidelines and CMS requirements are a weight-based fluid administration for all patients, irrespective of actual intravascular fluid status. Thus, there is a significant unmet need for clinically validated sepsis fluid management strategies based on precise, objective assessment of circulating BV. Daxorâs BVA-100, provides 98% accurate quantitative measurement of total blood volume, plasma volume, and red blood cell volume, which it then compares to validated patient-specific norms to provide an accurate measure of intravascular blood volume composition and derangement. A prospective randomized controlled trial (RCT) evaluated the impact of BVA in critically ill surgical patients (n=100) with septic shock, severe sepsis, severe respiratory failure, and/or cardiovascular collapse. In this study access to BVA resulted in a change in treatment in 44% of the time to patients randomized to the BV group and would have resulted in a treatment change in 61% of the patients in the control group. Additionally, the control group received red blood cell transfusions 1.5 ± 2 days later that the BVA group, at which time the abnormality became clinically evident. The preliminary work presented supports Daxorâs hypotheses that (1) sepsis patients are highly heterogeneous with respect to BV and RBCV status implying that (2) standard care decongestion strategies for treating such patients would benefit from BVA as a uniquely precise, objective diagnostic measure of intravascular BV and RBCV derangement. Here, Daxor hypothesizes that fluid management guided by direct quantification of BV status represents a potential paradigm shift in clinical practice, which to date has been based on surrogate markers that lack GS sensitivity and specificity. Transitioning this initial success to clinical acceptance requires the development of a validated, protolyzed methodology for the implementation of BVA, as well as a clinical decision-support system (CDSS) translating BVA results into actionable treatment decisions. The proposed Phase I supports the development of the Sepsis FLO (Sepsis FLuid Optimizer), a CDSS designed to precisely guide BV diagnosis and treatment in sepsis patients. This will be achieved through 1) the development of an alpha prototype through user-centered design; 2) the validation of three functional prototypes through formative usability testing; and 3) the development of a functional beta prototype. In Phase II, the Sepsis- FLO will be further validated in a RCT powered to assess improvements of clinical outcomes versus usual care.
Public Health Relevance Statement: NARRATIVE Sepsis is present in up to 50% of hospitalizations that culminate in death, leading to 270,000 deaths and $62 billion in costs in the United States annually. U.S.-based treatment guidelines and CMS requirements are a weight-based fluid administration for all patients, irrespective of actual intravascular fluid status, despite sepsis patients being highly heterogeneous with respect to blood volume and red blood cell volume statuses. The purpose of this Phase I SBIR project is to develop an evidence-based decision support tool integrating gold standard blood volume assessments into sepsis care.
Project Terms: 21+ years old; Adult Human; adulthood; Adult; Affect; Antibiotic Agents; Antibiotic Drugs; Miscellaneous Antibiotic; Antibiotics; Blood Volume; Blood capillaries; capillary; comorbidity; co-morbid; co-morbidity; Control Groups; Critical Illness; Critically Ill; Cessation of life; Death; Diagnosis; Erythrocytes; Blood erythrocyte; Erythrocytic; Marrow erythrocyte; Red Blood Cells; Red Cell; blood corpuscles; Health Personnel; Health Care Providers; Healthcare Providers; Healthcare worker; health care personnel; health care worker; health provider; health workforce; healthcare personnel; medical personnel; treatment provider; Hematocrit procedure; Hct; Hematocrit; Packed Erythrocyte Volume; Packed Red-Cell Volume; hemodynamics; Hemoglobin; Hospitalization; Hospital Admission; Hospitals; Hypotension; Low Blood Pressure; Vascular Hypotensive Disorder; Marketing; Methods; Methodology; Patients; Blood Plasma Volume; Plasma Volume; Publications; Scientific Publication; Recommendation; Resuscitation; Role; social role; Sensitivity and Specificity; Septic Shock; Signs and Symptoms; Diagnostic Findings; Technology; Testing; Time; Translating; United States; Vasoconstrictor Agents; Vasoactive Agonists; Vasoconstrictor Drugs; Vasoconstrictors; Vasopressor Agents; vasopressor; Weight; weights; Work; Dilution Techniques; Dilution Technics; Measures; Red Blood Cell Transfusion; Erythrocyte Transfusion; surrogate bio-markers; surrogate biomarkers; Surrogate Markers; Caring; Electrical Impedance; Impedance; electric impedance; Guidelines; improved; Clinical; Phase; Evaluation; Measurement; randomized control trial; Randomized, Controlled Trials; fluid; liquid; Liquid substance; tool; Diagnostic; Knowledge; Techniques; System; Clinical Decision Support Systems; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Hypovolemia; American; Cell Volumes; experience; success; Familiarity; technological innovation; Positioning Attribute; Position; Hypovolemics; Chest; Thorace; Thoracic; Thorax; Airway failure; Respiratory Failure; Data; Iatrogenesis; iatrogenic; iatrogenically; iatrogenicity; Randomized; randomisation; randomization; randomly assigned; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Tracer; Development; developmental; cost; designing; design; blood infection; bloodstream infection; Sepsis; mistreatment; maltreatment; Outcome; prospective; user-friendly; user centered design; usability; commercial application; prototype; commercialization; evidence base; standard treatment; standard care; care as usual; usual care; treatment as usual; bio-markers; biologic marker; biomarker; Biological Markers; clinical practice; Randomization trial; randomized trial; hypoperfusion; cardiovascular collapse; support tools; improved outcome; sepsis patients; septic patients; treatment guidelines; first in man; first-in-h
