Personalized vasopressor therapy in patients with septic shock

PROJECT SUMMARY/ABSTRACT
Septic shock has a mortality rate above 40%, and is treated with supportive care including vasopressors. Yet,
evidence shows vasopressor treatment response and clinician practices are heterogeneous. The key factors
mediating this heterogeneity are unknown. This research project investigates the role of patient-specific factors
in treatment response to initial and adjunctive vasopressor therapy in patients with septic shock. We seek to
develop accurate, individualized tools to predict the heterogeneity of response to a variety of vasopressors in
individual septic shock patients and implement these tools into bedside practice. Our preliminary data show early
initiation of adjunctive vasopressin is associated with lower mortality, and individual patient and treatment
characteristics are associated with vasopressin responsiveness. Therefore, we propose the novel hypothesis
that clinically translatable models are capable of predicting early vasopressor treatment response and will
optimize initial and adjunctive vasopressor therapy to improve clinical outcomes. This hypothesis will be tested
through three interrelated, but independent specific aims: (1) to apply machine learning techniques to predict
initial vasopressor therapy response; (2) to develop a decision model for optimizing adjunctive
vasopressor therapy outcomes; and (3) to identify determinants of successful vasopressor prediction
model clinical translation. Our proposal is innovative in concept because it is the first to use cutting-edge data
science methods to develop prediction models for initial and adjunctive vasopressor treatment effects. The
proposed research is significant because it has the potential to decrease mortality in septic shock patients by
developing and implementing personalized vasopressor treatment approaches. Cleveland Clinic is the ideal
environment to complete the proposed research due to the high volume (>6,000 yearly) of clinically and socio-
demographically diverse sepsis patients, integrated multi-professional treatment and research teams, extensive
informatics infrastructure, large cohesive health-system with a shared electronic health record, and history of
successful evidence translation into improved care delivery. As a critical care clinical pharmacist, Dr. Bauer is
uniquely positioned to develop and implement innovative vasopressor treatment strategies through knowledge
of the combined influences of medication pharmacology and pharmacodynamics, patient comorbidities, and
disease pathophysiology on treatment effects. With the mentorship of Dr. Vidula Vachharajani and other
internationally-recognized experts, Dr. Bauer will pursue training goals to enhance his understanding of applied
clinical translational science, clinical prediction modeling, implementation science, and research leadership.
Pursuit of these aims and training goals through the K08 Career Development Award mechanism will facilitate
achievement of Dr. Bauer’s long-term goal of becoming an independent clinician-scientist who improves the
health and outcomes of patients with septic shock through the optimized utilization of vasopressor therapies.

Grant Number: 5K08GM147806-04
NIH Institute/Center: NIH
Principal Investigator: SETH BAUER