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Hyperprocalcitonemia and Endothelial and Microcirculatory Dysfunction in Children With Sepsis and Septic Shock: Single-Center Observational Cohort Study in Colombia, 2021–2024
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Beltrán Hernández, Briam
Fernández-Sarmiento, Jaime
Mullet, Hernando
Niño Ariza, Maria Carolina
Aguirre Gutierrez, Valeria
Cárdenas, Carolina
Cardona, María Paula
Bernal Sierra, Tatiana
Cabezas Rosas, Marisol
Garzón Angel, Lina
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2025-06-25
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OBJECTIVES: To evaluate the association between hyperprocalcitonemia and endothelial and microcirculatory dysfunction in children with sepsis and septic shock and clinical outcomes. DESIGN: A prospective observational cohort study, 2021–2024. SETTING: A tertiary PICU with 15 medical-surgical beds in a university hospital. PATIENTS: We included children with sepsis and/or septic shock who had serum procalcitonin measured at admission, 24 hours, and 48 hours, simultaneously with microcirculatory assessment using sublingual videomicroscopy and biomarkers of endothelial injury (syndecan-1, angiopoietin-2, and endocan). Hyperprocalcitonemia was defined as procalcitonin greater than 2ng/mL. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 230 patients, 43.9% (101/230) had hyperprocalcitonemia at PICU admission. After adjusting for confounders, children with hyperprocalcitonemia, compared with those with normal procalcitonin, had higher adjusted odds ratio (aOR [95% CI]) of reduced capillary blood flow at 24 hours (aOR, 1.35 [95% CI, 1.08–1.72]) and 48 hours (aOR, 1.14 [95%CI, 1.04–1.24]) after admission. At 24 hours, children with hyperprocalcitonemia compared with those without hyperprocalcitonemia had higher median (interquartile range [IQR]) syndecan-1 levels (125.87ng/mL [IQR, 49.56–224.30ng/mL] vs. 107.71ng/mL [IQR, 62.82–156.55ng/mL], respectively; p < 0.01) and greater odds of angiopoietin-2 elevation (aOR, 2.28 [95% CI, 1.08–5.17]; p = 0.042). Hyperprocalcitonemia with severe endothelial/microcirculatory dysfunction was associated with fluid overload greater than 10% (aOR, 2.01 [95% CI, 1.06– 3.80]; p = 0.033), multiple organ dysfunction (aOR, 1.87 [95% CI, 1.01–3.57]; p = 0.041), and mortality (aOR, 1.66 [95% CI, 1.06–2.61]; p = 0.022). We failed to identify differences in capillary density (4–6 µm), angiopoietin-2, or Endocan between children with and without hyperprocalcitonemia at PICU admission. CONCLUSIONS: Children with sepsis and septic shock with hyperprocalcitonemia represent a phenotype characterized by endothelial and microvascular dysfunction, which is associated with worse clinical outcomes. Our study suggests that preserving microvascular integrity may be a therapeutic target to reduce microcirculatory damage and improve outcomes.
Abstract
OBJECTIVES: To evaluate the association between hyperprocalcitonemia and endothelial and microcirculatory dysfunction in children with sepsis and septic shock and clinical outcomes. DESIGN: A prospective observational cohort study, 2021–2024. SETTING: A tertiary PICU with 15 medical-surgical beds in a university hospital. PATIENTS: We included children with sepsis and/or septic shock who had serum procalcitonin measured at admission, 24 hours, and 48 hours, simultaneously with microcirculatory assessment using sublingual videomicroscopy and biomarkers of endothelial injury (syndecan-1, angiopoietin-2, and endocan). Hyperprocalcitonemia was defined as procalcitonin greater than 2ng/mL. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 230 patients, 43.9% (101/230) had hyperprocalcitonemia at PICU admission. After adjusting for confounders, children with hyperprocalcitonemia, compared with those with normal procalcitonin, had higher adjusted odds ratio (aOR [95% CI]) of reduced capillary blood flow at 24 hours (aOR, 1.35 [95% CI, 1.08–1.72]) and 48 hours (aOR, 1.14 [95%CI, 1.04–1.24]) after admission. At 24 hours, children with hyperprocalcitonemia compared with those without hyperprocalcitonemia had higher median (interquartile range [IQR]) syndecan-1 levels (125.87ng/mL [IQR, 49.56–224.30ng/mL] vs. 107.71ng/mL [IQR, 62.82–156.55ng/mL], respectively; p < 0.01) and greater odds of angiopoietin-2 elevation (aOR, 2.28 [95% CI, 1.08–5.17]; p = 0.042). Hyperprocalcitonemia with severe endothelial/microcirculatory dysfunction was associated with fluid overload greater than 10% (aOR, 2.01 [95% CI, 1.06– 3.80]; p = 0.033), multiple organ dysfunction (aOR, 1.87 [95% CI, 1.01–3.57]; p = 0.041), and mortality (aOR, 1.66 [95% CI, 1.06–2.61]; p = 0.022). We failed to identify differences in capillary density (4–6 µm), angiopoietin-2, or Endocan between children with and without hyperprocalcitonemia at PICU admission. CONCLUSIONS: Children with sepsis and septic shock with hyperprocalcitonemia represent a phenotype characterized by endothelial and microvascular dysfunction, which is associated with worse clinical outcomes. Our study suggests that preserving microvascular integrity may be a therapeutic target to reduce microcirculatory damage and improve outcomes.
Palabras clave
Endothelium , Extracellular matrix , Outcomes , Proteoglycans , Sepsis , Vascular permeability
Keywords
Endothelium , Extracellular matrix , Outcomes , Proteoglycans , Sepsis , Vascular permeability
