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Hyperprocalcitonemia and Endothelial and Microcirculatory Dysfunction in Children With Sepsis and Septic Shock:
Briam Beltrán Hernandez1,2, Jaime Fernández-Sarmiento1,3, Hernando Mulett1,2,3
1Department of Pediatrics and Intensive Care, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia.
Insights
Children with sepsis and elevated procalcitonin (hyperprocalcitonemia) show signs of endothelial and microcirculatory dysfunction. This condition is linked to poorer clinical outcomes, suggesting microvascular integrity is a key therapeutic target.
Area of Science:
- Pediatric critical care medicine
- Sepsis research
- Microcirculation and endothelial function
Background:
- Sepsis and septic shock are critical conditions in children.
- Endothelial and microcirculatory dysfunction play a significant role in sepsis pathophysiology.
- The role of hyperprocalcitonemia in pediatric sepsis-related microvascular dysfunction requires further elucidation.
Purpose of the Study:
- To investigate the association between hyperprocalcitonemia and endothelial/microcirculatory dysfunction in pediatric sepsis.
- To determine the impact of hyperprocalcitonemia on clinical outcomes in children with sepsis and septic shock.
Main Methods:
- Prospective observational cohort study conducted in a tertiary pediatric intensive care unit (PICU).
- Included 230 children with sepsis/septic shock, measuring serum procalcitonin, microcirculation via sublingual videomicroscopy, and endothelial injury biomarkers (syndecan-1, angiopoietin-2, endocan).
- Hyperprocalcitonemia defined as procalcitonin > 2 ng/mL.
Main Results:
- 43.9% of patients presented with hyperprocalcitonemia.
- Hyperprocalcitonemia was associated with reduced capillary blood flow at 24 and 48 hours.
- Elevated syndecan-1 and angiopoietin-2 levels were observed in children with hyperprocalcitonemia at 24 hours.
- Hyperprocalcitonemia with severe dysfunction correlated with fluid overload, multiple organ dysfunction, and mortality.
Conclusions:
- Children with sepsis and hyperprocalcitonemia exhibit a distinct phenotype of endothelial and microvascular dysfunction.
- This phenotype is associated with adverse clinical outcomes, including increased mortality.
- Targeting microvascular integrity may offer a promising therapeutic strategy to improve outcomes in pediatric sepsis.
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 2 ng/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 (125.87 ng/mL [IQR, 49.56-224.30 ng/mL] vs. 107.71 ng/mL [IQR, 62.82-156.55 ng/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.
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