• Bradley S Podd, Russell K Banks, Ron Reeder, Russell Telford, Richard Holubkov, Joseph Carcillo, Robert A Berg, David Wessel, Murray M Pollack, Kathleen Meert, Mark Hall, Christopher Newth, John C Lin, Allan Doctor, Tom Shanley, Tim Cornell, Rick E Harrison, Athena F Zuppa, Katherine Sward, J Michael Dean, Adrienne G Randolph, and on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
• Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Children's Hospital of Pittsburgh, Center for Critical Care Nephrology and Clinical Research Investigation and Systems Modeling of Acute Illness Center, University of Pittsburgh, Pittsburgh, PA.
• Crit. Care Med. 2023 Dec 1; 51 (12): 176617761766-1776.

ObjectivesSepsis-associated immune suppression correlates with poor outcomes. Adult trials are evaluating immune support therapies. Limited data exist to support consideration of immunomodulation in pediatric sepsis. We tested the hypothesis that early, persistent lymphopenia predicts worse outcomes in pediatric severe sepsis.DesignObservational cohort comparing children with severe sepsis and early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 d between study days 0-5) to children without. The composite outcome was prolonged multiple organ dysfunction syndrome (MODS, organ dysfunction beyond day 7) or PICU mortality.SettingNine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017.PatientsChildren with severe sepsis and indwelling arterial and/or central venous catheters.InterventionsBlood sampling and clinical data analysis.Measurements And Main ResultsAmong 401 pediatric patients with severe sepsis, 152 (38%) had persistent lymphopenia. These patients were older, had higher illness severity, and were more likely to have underlying comorbidities including solid organ transplant or malignancy. Persistent lymphopenia was associated with the composite outcome prolonged MODS or PICU mortality (66/152, 43% vs 45/249, 18%; p < 0.01) and its components prolonged MODS (59/152 [39%] vs 43/249 [17%]), and PICU mortality (32/152, 21% vs 12/249, 5%; p < 0.01) versus children without. After adjusting for baseline factors at enrollment, the presence of persistent lymphopenia was associated with an odds ratio of 2.98 (95% CI [1.85-4.02]; p < 0.01) for the composite outcome. Lymphocyte count trajectories showed that patients with persistent lymphopenia generally did not recover lymphocyte counts during the study, had lower nadir whole blood tumor necrosis factor-α response to lipopolysaccharide stimulation, and higher maximal inflammatory markers (C-reactive protein and ferritin) during days 0-3 ( p < 0.01).ConclusionsChildren with severe sepsis and persistent lymphopenia are at risk of prolonged MODS or PICU mortality. This evidence supports testing therapies for pediatric severe sepsis patients risk-stratified by early, persistent lymphopenia.Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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