The Temporal Kinetics of Circulating Angiopoietin Levels in Children With Sepsis

Abstract

Objective Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin (angpt)-1 and angpt-2, play opposing roles in capillary stabilization in septic patients, respectively. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angpt-2/1 ratios when compared to non-septic pediatric intensive care unit (PICU) patients over a 7-day period. Design Prospective, observational study. Patients were classified within 24h of admission into: non-systemic inflammatory response syndrome (non-SIRS), SIRS/sepsis, or severe sepsis/shock. Plasma levels of angpt-1 and angpt-2 were measured via ELISA. The angpt-2/1 ratio was graphically plotted and determined whether patients fell into ‘constant’ or ‘variable’ patterns. Setting Tertiary care center PICU. Patients Critically ill pediatric patients with varying sepsis severity. Interventions None Measurements and Main Results Forty five patients were enrolled (n=9 non-SIRS, n=19 SIRS/sepsis, and n=17 severe sepsis/shock). Gender, age, weight, comorbidities and PICU length of stay were not significantly different between the groups. Admission pediatric risk stratification scores and net fluid ins/outs were significantly elevated in the severe sepsis/shock group when compared (all p<0.05). Admission angpt-2 levels and angpt-2/1 ratios were significantly different in the severe sepsis/shock group when all groups were compared (both p<0.05). Additionally, the latter were significantly elevated in the severe sepsis/shock group at multiple time points (all p≤0.05) with the peak occurring on day 2 of illness. In a separate analysis, 32% of SIRS/sepsis and 82% of severe sepsis/shock had ‘variable’ angpt-2/1 ratio patterns compared to none in the control group (p<0.001). Conclusions Pediatric patients with severe sepsis and septic shock possess significantly elevated angpt-2/1 ratios during their first 3 days of illness which peak at day 2 of illness. A subset of these patients demonstrated ‘variable’ angpt-2/1 ratio patterns.

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

“…A number of trials investigate the value of an Ang-1/-2 ratio in predicting outcome of septic patients. This ratio was significantly elevated in children with severe sepsis and septic shock compared to control patients with or without SIRS or sepsis during the first 3 d on pediatric ICU [121] . Similarly, using Canonical Correlation Analysis, Wang et al [122] identified a strong correlation between the combination of Ang-1, Ang-2, bicarbonate and disease severity or outcome of sepsis in children.…”

Endothelial Cell Function and Dysfunction in Critically Ill Children

“…Levels of soluble EC adhesion molecules post-CPB have been associated with nonspecific neutrophil activation and impaired regulation of inflammation. 63 -69 Collectively, these studies show decreased levels of all Giuliano et al 51 Observational study of 45 children ranging from healthy control subjects to patients with septic shock Admission and peak levels of ANGPT2 and ANGP2/ANGPT1 ratios were elevated in children with severe sepsis and septic shock compared with children with SIRS or control children Wang et al 52 Observational study of 45 children ranging from healthy control subjects to patients with septic shock ANGPT1, ANGPT2, and serum bicarbonate demonstrated the strongest correlation with sepsis severity Wong et al 53 Temporal extension of sepsis biomarkers from 225 children with septic shock…”

The Role of Angiopoietine-2 in the Diagnosis and Prognosis of Sepsis

“…In the current study, the values of ANG-2 in the control group were higher (6.0 ng/ mL), probably due to the fact that patients with infections, but without sepsis, were included in this group. Nevertheless, the statistically significant difference in ANG-2, between the two groups, proves that this biomarker can be useful for assessment of severity of infection in agreement with other stufies [12][13][14].…”