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A6015 - An Evaluation of Plasma RIPK3 Levels in Patients with a Concern for Sepsis in the Emergency Department
Author Block: E. Schenck1, S. Rotter2, E. J. Finkelzstein1, W. J. Ford3, J. K. Lessing3, J. E. Arbo3, I. I. Siempos1, A. M. K. Choi2; 1Medicine Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, United States, 2Medicine, Weill Cornell Medicine, New York, NY, United States, 3Medicine Division of Emergency Medicine and Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, United States.
Introduction: Necroptosis is a form of programmed immunologically active cell death that is important in the activation and perpetuation of the innate immune response in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3). We have previously demonstrated that RIPK3 is elevated in human critical illness in several large ICU cohorts. However, there is limited evidence regarding the role of extracellular RIPK3 in patients who present to the emergency department. We explored the association between plasma levels of RIPK3, mortality, and organ failure in patients admitted to the emergency department with a concern for sepsis. Methods: Plasma RIPK3 levels were measured in the first 37 patients prospectively enrolled in a cohort of a tertiary academic medical center in New York City. Patients were selected by a concern for sepsis as defined by the presence of greater than 2 SIRS criteria with a documented clinical suspicion for an infection. Blood samples were collected within four hours of arrival to the emergency department. RIPK3 concentrations among patients were compared with prospectively collected phenotypic and outcomes data. Results: The patients in this cohort had a mean age of 62, 23 (62%) were male, 10 (27%) had diabetes, and 14 (38%) had leukemia. 6 (14%) patients were judged to have a potentially terminal condition by an investigator at enrollment. The median Mortality in Emergency Department Sepsis score was 6 (interquartile range 3-8) and the median qSOFA score was 1 (interquartile rage 1-2). After admission to the hospital 11 (29%) of patients were admitted to the ICU. In the ICU 6 (14 %) were treated with mechanical ventilation and 6 (14%) vasopressor therapy. RIPK3 levels in the plasma were higher in patients who died at 28 days compared to those who survived (p=0.04). Additional associations with baseline severity of organ dysfunction and clinically important outcomes were explored. Conclusions: Our findings suggest elevated levels of RIPK3 in the plasma of patients in the emergency department are associated with important outcomes and upfront organ failure. These findings suggest that RIPK3 may be playing a role in acute illness evaluated in the emergency department.