Temporal analysis of nitric oxide as potential sepsis biomarker

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DESCRIPTION (provided by applicant): Sepsis is the leading cause of death in non-cardiac Intensive Care Units (ICUs) and the 10th leading cause of death in the U.S. Due to extended hospital stays, expensive treatment protocols, and significant morbidity, $17 billion/year is currently spent treating sepsis (roughly $50,000 per incidence). Prompt detection and action are critical for successful diagnosis and treatment outcomes. Early diagnosis of sepsis has been shown to increase patient survival via appropriate treatment and decrease hospital stays/costs. Unfortunately, current methods of diagnosing sepsis are non-ideal as they rely on the detection of symptoms (e.g., fever, shortness of breath, irregular heart rate) that only become evident after the infection has progressed to dangerous levels (late stages). The goal of this project is t develop new analytical methodology that will allow for the measurement of physiologically relevant nitric oxide and nitrosothiols concentrations in drawn blood to facilitate earlier intervention. Although previous literature clearly shows significant elevations in both nitric oxid and nitrosothiol levels (>10x basal) in blood due to sepsis, the real-time variations in these analytes both before the onset and during the progression of early sepsis are unknown. Our hypothesis is that these analytes change well before the clinical signs of sepsis based on the body's immune response to pathogens that lead to sepsis. Indeed, immune cells (e.g., macrophages) release nitric oxide in response to bacteria, with increasing magnitude according to bacteria burden. As such, we believe that the measurement of nitric oxide and nitrosothiols in blood represents a new paradigm for sepsis screening based on their rate of change. Through the proposed studies we will develop novel, miniturizable sensing platforms capable of measuring nitric oxide and nitrosothiol in small blood volumes. The temporal changes of these analytes will then be evaluated in an appropriate animal (porcine) model of sepsis to determine their predictive value. PUBLIC HEALTH RELEVANCE: Sepsis is the leading cause of death in non-cardiac Intensive Care Units (ICUs) and the 10th leading cause of death in the U.S. overall. Prompt detection of sepsis and early intervention are critical to saving lives of the critically ill. The objective of his project is to determine how nitric oxide and nitrosothiol concentrations in blood vary temporally in early sepsis. In turn, this knowledge could lead to a significant breakthrough in current sepsis screening methods. To achieve our goals, novel analytical sensor methodology will be developed and implemented in a standardized swine model of sepsis.