We propose the ?Normalizing vasopressor dose to standardize vasopressors practice in septic shock? study to improve the standardization and knowledge of vasopressors during septic shock through the development of a novel measure of vasopressor dose normalized to blood pressure response and through characterization of vasopressor practice patterns. Sepsis is a common, life-threatening, dysregulated response to infection. Septic shock is the most severe form of sepsis where circulatory and metabolic failure results in case fatality approaching 50%. Vasopressor medications operationalize septic shock (septic shock is defined as hypotension and hyperlactatemia requiring vasopressors to maintain organ perfusion) and vasopressor choices have important implications for septic shock outcomes. Despite the importance of vasopressors in the definition and management of septic shock, numerous knowledge gaps regarding vasopressor dosing and the choice and timing of second vasopressors exist. These vasopressor knowledge gaps prevent standardization of clinical practice and septic shock trials that hinder progress in improving vasopressor use in septic shock. Simple measures that normalize dose to response have led to improved standardization and understanding of disease severity in other critical care syndromes (e.g. PaO2/FiO2 in Acute Respiratory Distress Syndrome) but no such measure exists in septic shock. We propose two necessary foundational steps to improve the evaluation and use of vasopressors in septic shock using high-resolution critical care electronic health record data: 1) develop and validate a measure of vasopressor dose normalized to blood pressure response with strong predictive validity for septic shock mortality and 2) leverage hospital variation in vasopressor dosing to determine the optimal timing of second vasopressor initiation when norepinephrine alone is inadequate. Completion of this proposal will result in better understanding of the relationship between vasopressor dose, blood pressure response and septic shock mortality, and develop novel tools for both clinicians and clinical trialists to improve and standardize care. The rich collaborative environment at Boston University School of Medicine and the individually-tailored gradated training plan outlined in this proposal are ideally suited to support Dr. Bosch in accomplishing the study aims and to prepare him to apply for Mentored Career Development funding with the ultimate goal of becoming a physician-scientist specializing in cardiovascular critical care data science.
Septic shock is a life-threatening response to infection where inadequate tissue perfusion leads to low blood pressure. However, the defining feature of septic shock treatment, the use of vasopressor medication to increase blood pressure, is understudied and unstandardized. The goal of this proposed research is to develop and validate a novel measure of vasopressor dose with prognostic significance, and to characterize variation in vasopressor use between hospitals; two fundamental steps towards standardizing and improving vasopressor use in clinical care and randomized trials.
