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Early, Persistent Lymphopenia Is Associated With Prolonged Multiple Organ Failure and Mortality in Septic Children
Bradley S Podd1,2, Russell K Banks3, Ron Reeder3
1Division 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.
Insights
Early, persistent lymphopenia in pediatric severe sepsis is linked to worse outcomes, including prolonged organ dysfunction or death. This finding supports targeted immune therapies for at-risk children.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Sepsis research
Background:
- Sepsis-associated immune suppression is a known factor in poor outcomes.
- Adult studies are exploring immune support therapies for sepsis.
- Data on immunomodulation in pediatric sepsis is limited.
Purpose of the Study:
- To investigate the association between early, persistent lymphopenia and outcomes in pediatric severe sepsis.
- To test the hypothesis that lymphopenia predicts worse outcomes in this population.
Main Methods:
- An observational cohort study was conducted in nine PICUs.
- Patients with severe sepsis were categorized based on early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 days between study days 0-5).
- The composite outcome assessed was prolonged multiple organ dysfunction syndrome (MODS) or PICU mortality.
Main Results:
- 38% of 401 pediatric severe sepsis patients had persistent lymphopenia.
- Persistent lymphopenia was associated with a significantly higher risk of prolonged MODS or PICU mortality (43% vs. 18%).
- Patients with lymphopenia showed impaired TNF-α response and elevated inflammatory markers.
Conclusions:
- Early, persistent lymphopenia in pediatric severe sepsis identifies patients at high risk for prolonged MODS or PICU mortality.
- This risk stratification supports the investigation of immunomodulatory therapies in this patient group.
- Further research is warranted to develop targeted treatments for pediatric sepsis based on immune status.
Objectives:
Sepsis-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.
Design:
Observational 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.
Setting:
Nine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017.
Patients:
Children with severe sepsis and indwelling arterial and/or central venous catheters.
Interventions:
Blood sampling and clinical data analysis.
Measurements And Main Results:
Among 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).
Conclusions:
Children 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.
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