Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

OBJECTIVE

Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC).

DESIGN

Prospective observational study of children < 5 years old. Patients were classified as non-systemic inflammatory response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock.

SETTING

Tertiary care pediatric hospitals.

PATIENTS

Critically ill children.

INTERVENTIONS

None.

MEASUREMENTS

Plasma angpt-1 and -2 levels were measured with enzyme-linked immunoassays. Expression of angpt-2 in endothelial cells was assessed with quantitative polymerase chain reaction. Permeability changes in cultured HDMECs were assessed with transendothelial electrical resistance measurements.

RESULTS

Angpt-1 levels were significantly higher in younger children compared with levels found in previous study of older children across disease severity (all P < 0.001). Angpt-2 was significantly higher in this cohort with severe sepsis/septic shock compared with children without SIRS and SIRS/sepsis (all P < 0.003). Angpt-2/1 ratio was also elevated in children with severe sepsis/septic shock but an order of magnitude less than older children (P < 0.02, P = 0.002). Angpt-1 and -2 did not affect basal HDMEC permeability or modulate leak in isolation or in the presence of tumor necrosis factor (TNF).

CONCLUSIONS

Angpt-2 levels and the angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal HDMEC permeability alone or modulates TNF induced capillary leak.