Abstract Body: Background: Progressive post-cardiac arrest syndrome (PCAS) ensues within seconds of an out-of-hospital cardiac arrest (OHCA) and results in damage over days, yet longitudinal changes in blood biomarkers during PCAS are poorly understood. We characterize novel biomarkers at early time points after return of spontaneous circulation (ROSC) and determine associations with survival.

Methods: Blood plasma samples from OHCA patients were collected at 1, 6, 24, 48, 72 hours and 7 days after ROSC. Samples were analyzed using a Meso Scale Diagnostics 40-plex assay which included proinflammatory, cytokine, chemokine, angiogenesis, and vascular injury panels. The data distribution was heavily skewed, requiring log-transformation. Biomarkers were compared between survivors and non-survivors at each follow-up time point using a two-sample t-test. Mixed-effect and Generalized Estimation Equation models were used to examine the association between biomarkers and survival and assess trends over time.

Results: Thirty-three patients were included, of which 54% (N=18) were males, the mean age was 57 (+/-15) years, and 54% (N=18) survived to discharge. Six out of the 40 biomarkers had a statistically significant difference in biomarker levels between survivors and non-survivors at one or more time points. At the 1-hour, macrophage derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) were significantly higher in survivors. At 6-hour, interleukin-13 (IL-13) was the only pro-inflammatory biomarker that was significantly higher in non-survivors. At 24-hour, pro-inflammatory biomarkers interleukin-12p70 (IL-12p70) and IL-13 were higher in non-survivors, whereas vascular endothelial growth factor A (VEGF-A) was significantly higher in survivors. At 48-hours, VEGF-A was also significantly higher in survivors. At 72 hours, interleukin-8 was the only biomarker with significantly higher levels in non-survivors. Overall, IL-12p70, IL-13, and MDC levels decreased over time (p=0.02, p=0.003, p=0.01, respectively) for both survivors and non-survivors. Survivors had a lower average level for IL-12p70 (p=0.03) and for IL-13 (p=0.04), but higher average level for MDC (p=0.01) than non-survivors at discharge.

Conclusion: This pilot investigation extends prior biomarker work by highlighting new biomarkers, their longitudinal changes during PCAS, and their relation to survival. Future analysis will explore differences in biomarkers for neurological outcomes after OHCA.