(1054) Inflammatory Phenotypes in Pediatric Sepsis

Introduction: Hyper- and hypo-inflammatory patterns have been identified in adult and pediatric ARDS with different treatment responses and outcomes. It is unknown whether these biologic subgroups exist in pediatric sepsis. We hypothesized that clinical data together with biomarkers could identify hyper- and hypoinflammatory patterns with distinct outcomes in children with sepsis.

Methods: We conducted a secondary analysis of a previous observational study of 143 patients < 18 years old treated for sepsis in the intensive care unit at an academic children's hospital. Clinical data were obtained from the electronic health record. Plasma levels of ANG1, ANG2, CD163, ICAM1, IL6, IL8, IL18, MCP1, MIP1a, RANTES, sCD30, sRAGE, sTNFR1, Tie2, VCAM1 and VEGF were measured within 48 hours of ICU admission. We used latent class analysis (LCA) to identify data-driven phenotypes, without a predetermined number of groups. We compared clinical characteristics and hospital mortality using Wilcoxon rank sum and chi-square testing. To optimize clinical utility, a parsimonious model was developed using logistic regression to predict classification as determined by the full model.

Results: LCA showed a two-class model was optimal for our cohort. We identified a larger, hypoinflammatory phenotype and a smaller, hyperinflammatory phenotype. The hyperinflammatory group was characterized by higher levels of ANG2, CD163, ICAM1, IL6, IL8, MCP1, MIP1A, sCD30, sRAGE, sTNFRI, VCAM1, VEGF, creatinine and lactate. This hyperinflammatory group had lower platelet levels, lower absolute lymphocyte counts and higher mortality (15.6 % vs 4.5%, p= 0.03). Hospital length of stay, vasoactive inotrope score, PRISM-III score, PELOD score, and PCPC scores were significantly higher in the hyperinflammatory group. Parsimonious models that included only biomarkers IL6, sTNFR1, and VCAM1 or only the clinical variables of absolute lymphocyte count, platelet concentration, and serum creatinine provided the highest area under the receiver operating curves for phenotype classification (0.98 and 0.82, respectively).

Conclusions: As shown in previous ARDS studies, pediatric sepsis exhibits hyper- and hypo-inflammatory phenotypes with distinct outcomes. Further research is necessary to ascertain the practical implications of identifying these phenotypes.