Biomarkers associated with mortality in pediatric patients with cardiac arrest and acute respiratory distress syndrome

Aims: To identify plasma biomarkers associated with cardiac arrest in a cohort of children with acute respiratory distress syndrome (ARDS), and to assess the association of these biomarkers with mortality in children with cardiac arrest and ARDS (ARDS + CA). Methods: This was a secondary analysis of a single-center prospective cohort study of children with ARDS from 2014-2019 with 17 biomarkers measured. Clinical characteristics and biomarkers were compared between subjects with ARDS + CA and ARDS with univariate analysis. In a sub-cohort of ARDS + CA subjects, the association between biomarker levels and mortality was tested using 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). More arrests (69%) occurred out-of-hospital with a median CPR duration of 11 (IQR 5.5, 25) minutes. ARDS severity, PRISM III score, vasoactive-ionotropic score and extrapulmonary organ failures were worse in the ARDS + CA versus ARDS group. Eight biomarkers were elevated in the ARDS + CA versus ARDS cohort: sRAGE, nucleosomes, SP-D, CCL22, IL-6, HSP70, IL-8, and MIP-1b. sRAGE, SP-D, and CCL22 remained elevated when the cohorts were matched for illness severity. When controlling for severity of ARDS and cardiac arrest characteristics, sRAGE, IL-6 and granzyme B were associated with mortality in the ARDS + CA group. Conclusion: sRAGE, IL-6 and granzyme B were associated with cardiac arrest mortality when controlling for illness severity. sRAGE was consistently higher in the ARDS + CA cohort compared to ARDS and retained independent association with mortality.