Developing and Evaluating a Personalized Approach to Initial Fluid Resuscitation in Patients with Hospital-Onset Sepsis

PROJECT SUMMARY Candidate’s Long-Term Career Goal: Dr. Elizabeth Munroe’s career goal is to become an independent physician-scientist leading novel clinical trials to improve the early management of critically ill patients. Clinical Problem to be Addressed: Intravenous fluids are a core component of sepsis management. Yet, administering both too much and too little fluid can cause harm, and the optimal fluid volume to prescribe is often unclear. Traditional clinical trials miss the critical window of initial fluid resuscitation and use one-size-fits- all approaches to fluid resuscitation. Furthermore, like most sepsis research, fluid trials have largely excluded patients who develop sepsis in the hospital (hospital-onset sepsis), an important and distinct population that experiences two-times higher mortality than patients with community-onset sepsis. Specific Aims: In this K23 proposal, Dr. Munroe aims to 1) understand the impact of initial fluid volume on outcomes in patients with hospital-onset sepsis through an electronic health record (EHR)-based cohort study, 2) develop a personalized, physiology (stroke volume) guided approach to initial fluid resuscitation for patients with hospital-onset sepsis, and 3) conduct a pilot pragmatic clinical trial comparing personalized, stroke volume guided initial fluid resuscitation vs usual care during rapid response evaluations. Candidate Background: Dr. Munroe is a clinical instructor in Pulmonary and Critical Care at the University of Michigan and current NHLBI NRSA F32 awardee. She will be promoted to Assistant Professor, not contingent on the outcome of this application. She is recognized as a rising star in the field of sepsis, with 6 first-author publications, 8 conference presentations, and 5 national invited lectures. Career Development Plan: Through this project, Dr. Munroe will build on her expertise in sepsis management and health services research to gain expertise in 1) EHR-data extraction, 2) implementation science-based intervention design and evaluation, and 3) pragmatic clinical trial design, execution, and analysis. Her 5-year training plan carefully pairs her training and research aims and is further supported by curated coursework and career development activities that will position her for successful transition to independence. Mentors: Dr. Munroe’s primary mentor, Dr. Hallie Prescott, is a sepsis expert who has mentored 5 clinician- scientists on K-series/career development awards. Dr. Munroe and Dr. Prescott have an excellent track record of success, working together since 2020. Dr. Munroe will receive complementary support from co-mentors: Dr. Michael Sjoding (EHR-based data science), Dr. Stephanie Parks Taylor (implementation science), and Dr. Robert Hyzy (clinical trials), as well a national advisory team with deep expertise in pragmatic clinical trials. Deliverables: Completing these aims will advance our understanding of fluid resuscitation in hospital-onset sepsis, generate preliminary data to compete for R-series awards for follow-up trials, and uniquely position Dr. Munroe to lead novel clinical trials of early interventions in critical care.