Circulating Histones and Severity of Illness in Children with Sepsis: A Prospective Observational Study

Objectives: To measure circulating histone H3 levels in children with severe sepsis and explore its relationship with severity of illness and organ failures. Methods: Children aged 3 mo to 12 y with severe sepsis admitted to pediatric intensive care unit (PICU) were prospectively studied. Healthy controls were enrolled from the outpatient department for comparison. Levels of H3 histones were measured on day 1 and day 3. Results: Thirty-seven patients and 14 controls with median (IQR) age 5 (0.67, 8) and 5 (3, 7) y, respectively were enrolled. Common diagnoses included severe pneumonia (n = 9), staphylococcal sepsis (n = 6), and seasonal tropical infections (n = 4). Two-third (n = 26, 70%) had septic shock. One third (35%) had an unfavorable outcome; 11 died and 2 discontinued care. Median (IQR) H3 levels were not statistically different among patients with sepsis and controls [0.84 (0.62, 1.13) vs. 0.72 (0.52, 0.87) ng/mL; p = 0.10]. There was no significant change in H3 between day 1 and day 3 [0.84 (0.62, 1.13) vs 0.74 (0.5, 0.98) ng/mL; p = 0.22]. Children with thrombocytopenia (n = 27) showed a trend towards higher H3 compared to those without thrombocytopenia (n = 10) [0.9 vs. 0.67 ng/mL; p = 0.06]. However, H3 levels were not elevated in patients with cardiovascular dysfunction, those needing renal-replacement therapy, or unfavorable outcomes. Conclusion: The present data provides early evidence that in children hospitalized with severe sepsis, histone H3 is not elevated as compared to healthy controls. H3 levels during initial days of sepsis requiring PICU admission were not different with regards to severity of illness, organ dysfunction, and clinical outcome. There was a trend towards elevated H3 in children with thrombocytopenia, which needs further evaluation.