Abstract

Introduction: The post-cardiac arrest state is comprised of an ischemic and reperfusion syndrome, with inflammation similar to sepsis and acute respiratory distress syndrome (ARDS). However, it is unknown whether cardiac arrest has a distinct inflammatory profile relative to these other critical illness syndromes. Using plasma biomarkers of systemic inflammation measured in children with ARDS, we aimed to evaluate identify unique biomarkers in a sub-cohort with cardiac arrest, and the association of these biomarkers with mortality. Methods: This was a retrospective single-center cohort study of 17 biomarkers prospectively collected from pediatric subjects with ARDS between 2014-2019. Biomarkers were drawn within 24 hours after both ARDS diagnosis and cardiac arrest. Clinical characteristics and biomarkers were compared between those with ARDS and those with ARDS and cardiac arrest (ARDS+CA) using nonparametric tests. In ARDS+CA subjects, associations of biomarkers with mortality were tested with univariate and bivariate logistic regression. Results: Biomarkers were measured in 333 subjects: 301 with ARDS (median age 5.3 years, 55.5% male) and 32 ARDS+CA (median age 8 years, 53.1% male). Majority of arrests (68.7%) were out-of-hospital with median 11 minutes of CPR. ARDS+CA subjects were more likely to be immunosuppressed and present after aspiration or drowning than the ARDS cohort. ARDS severity, PRISM III score, vasoactive-ionotropic score and extra-pulmonary organ failure were worse in the ARDS+CA group (p<0.05). Eight biomarkers were elevated in ARDS+CA compared to the ARDS cohort: sRAGE, nucleosomes, SP-D, CCL22, IL-6, HSP70, IL-8, and MIP-1b (p<0.05). In the ARDS+CA cohort, 3 biomarkers were associated with mortality when controlling for markers of disease and cardiac arrest severity: sRAGE (unadjusted odds ratio 3.48 [IQR 1.35, 8.99], p=0.010), IL-6 (OR 1.75 [1.13, 2.71], p=0.012) and granzyme B (OR 3.74 [1.46, 9.57], p=0.006). Conclusion: sRAGE, IL-6 and granzyme B were independently associated with mortality after pediatric cardiac arrest in ARDS. This exploratory work suggests that cardiac arrest may induce a distinct inflammatory state that differs from other critical illness syndromes and further investigation is needed.

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