Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immunoparalysis

BackgroundSevere critical illness-induced immune suppression, termed immunoparalysis, is associated with longer duration of organ dysfunction in septic children. mRNA studies have suggested differential benefit of hydrocortisone in septic children based on their immune phenotype, but this has not been shown using a functional readout of the immune response. This study represents a secondary analysis of a prospectively conducted immunophenotyping study of pediatric severe sepsis to test the hypothesis that hydrocortisone will be differentially associated with clinical outcomes in children with or without immunoparalysis.MethodsChildren with severe sepsis/septic shock underwent blood sampling within 48 h of sepsis onset. Immune function was measured by quantifying whole blood ex vivo LPS-induced TNFα production capacity, with a TNFα response ResultsOne hundred two children were enrolled (age 75 [6–160] months, 60% male). Thirty-one subjects received hydrocortisone and were more likely to be older (106 [52–184] vs 38 [3–153] months,p = 0.04), to have baseline immunocompromise (32 vs 8%,p = 0.006), to have higher PRISM III (13 [8–18] vs 7 [5–13],p = 0.0003) and vasoactive inotrope scores (20 [10–35] vs 10 [3–15],p = 0.0002) scores, and to have more MODS days (3 [1–9] vs 1 [0–3],p = 0.002). Thirty-three subjects had immunoparalysis (TNFα response 78 [52–141] vs 641 [418–1047] pg/ml,p p = 0.0006) whereas no association with MODS duration was seen in children without immunoparalysis (aRR 1.2 [0.6–2.3],p = 0.67).ConclusionHydrocortisone use was independently associated with longer duration of MODS in septic children with immunoparalysis but not in those with more robust immune function. Prospective clinical trials using a priori immunophenotyping are needed to understand optimal hydrocortisone strategies in this population.