Abstract Sat702: Increasing Biomarkers of Systemic Inflammation after Pediatric Cardiac Arrest are Associated with Hospital Mortality: A Preliminary Report from a Prospective Cohort Study

Abstract

Introduction: Post-cardiac arrest syndrome (PCAS) includes a sepsis-like inflammatory state. Best characterized in adults, elevated levels of plasma biomarkers including interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF) receptor 2 are associated with mortality. In contrast, post-cardiac arrest inflammation has not been well studied in children, and its impact on post-arrest survival and outcomes remains unknown. Aims: We aimed to understand the association of several blood-based biomarkers with hospital mortality and the association of the change in biomarkers measured over time with mortality. Hypothesis: We hypothesized the increase in inflammatory biomarkers measurements over time will be associated with hospital mortality, suggesting an inflamed PCAS state. Methods: We enrolled children < 18 years old after in- and out-of-hospital cardiac arrest cared for in our center’s intensive care units. Blood samples were collected at 2 timepoints: (T1) 24±12 hours, and (T2) 72-120 hours after cardiac arrest. Eighteen biomarkers associated with systemic and myocardial inflammation were measured with a custom-built multiplex ELISA (Figure 1). In these preliminary analyses, p<0.1 was deemed significant. Results: Among 64 subjects (of a planned 200), 23 had blood samples analyzed at T1, and 25 at T2. Median age was 28 months (IQR 7 months-8 years), with 38 (59%) having out-of-hospital arrest. On univariate comparison, no biomarkers at T1 were associated with hospital mortality, but 3 biomarkers at T2 were associated with mortality: MMP9 was lower (p = 0.02), and ST2 (p=0.05) and IL-8 (p=0.01) were higher in non-survivors compared to survivors. With mixed effects modeling, accounting for inter-subject correlation, the association between repeated biomarker measures and mortality was different in non-survivors compared to survivors for 3 biomarkers: increase in IL-6 (p=0.06), IL-17 (p=0.02), and a decrease in RANTES (p=0.09) (Figure 1). Conclusions: This preliminary report suggests several inflammatory biomarkers are associated with post-cardiac arrest hospital mortality, particularly three whose change over time were associated with mortality: an increase in pro-inflammatory IL-6 and IL-17, and a decrease in chemokine RANTES (CCL5). Further evaluations are warranted to assess the associations of these biomarkers with clinical parameters over time.