Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immun
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RESEARCH
Open Access
Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immunoparalysis Katherine E. Bline1,2* , Melissa Moore-Clingenpeel1,3, Josey Hensley1, Lisa Steele1, Kristin Greathouse1, Larissa Anglim1, Lisa Hanson-Huber1, Jyotsna Nateri1, Jennifer A. Muszynski1,2, Octavio Ramilo1,4 and Mark W. Hall1,2
Abstract Background: Severe 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. Methods: Children 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 < 200 pg/ml being diagnostic of immunoparalysis. The primary outcome measure was number of days in 14 with MODS. Univariate and multivariable negative binomial regression models were used to examine associations between hydrocortisone use, immune function, and duration of MODS. Results: One 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 < 0.0001). Hydrocortisone use was associated with longer duration of MODS in children with immunoparalysis after adjusting for covariables (aRR 3.7 [1.8–7.9], 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). (Continued on next page)
* Correspondence: [email protected] 1 The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA 2 Division of Critical Care Medicine, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commo
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