title: 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-1 and angiopoietin-2, play opposing roles in capillary stabilization in patients with sepsis. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angiopoietin-2/1 ratios when compared with nonseptic PICU patients over a 7-day period.
  
  
  METHODS
  Prospective observational study. Patients were classified within 24 hours of admission into non-systemic inflammatory response syndrome, systemic inflammatory response syndrome/sepsis, or severe sepsis/shock. Plasma levels of angiopoietin-1 and angiopoietin-2 were measured via enzyme-linked immunosorbent assay. The angiopoietin-2/1 ratio was graphically plotted and determined whether patients fell into "constant" or "variable" patterns.
  
  
  METHODS
  Tertiary care center PICU.
  
  
  METHODS
  Critically ill pediatric patients with varying sepsis severity.
  
  
  METHODS
  None.
  
  
  RESULTS
  Forty-five patients were enrolled (nine non-systemic inflammatory response syndrome, 19 systemic inflammatory response syndrome/sepsis, and 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 angiopoietin-2 levels and angiopoietin-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 systemic inflammatory response syndrome/sepsis and 82% of severe sepsis/shock had variable angiopoietin-2/1 ratio patterns compared with none in the control group (p < 0.001).
  
  
  CONCLUSIONS
  Pediatric patients with severe sepsis and septic shock possess significantly elevated angiopoietin-2/1 ratios during their first 3 days of illness, which peak at day 2 of illness. A subset of these patients demonstrated variable angiopoietin-2/1 ratio patterns.
authors.affiliation: 1Department of Pediatrics, Division of Critical Care Medicine, Yale University School of Medicine, New Haven, CT. 2Yale Center for Analytic Sciences, Yale University School of Medicine and School of Public Health, New Haven, CT. 3Pediatric Intensive Care Unit, Yale-New Haven Children's Hospital, New Haven, CT. 4Department of Pediatrics, Division of Perinatal Medicine, Department of Obstetrics/Gynecology/Reproductive Sciences, Yale University School of Medicine, New Haven, CT.
authors.forename: John S
authors.initials: JS
authors.lastname: Giuliano
authors.forename: Kevin
authors.initials: K
authors.lastname: Tran
authors.forename: Fang-Yong
authors.initials: FY
authors.lastname: Li
authors.forename: Veronika
authors.initials: V
authors.lastname: Shabanova
authors.forename: Joana A
authors.initials: JA
authors.lastname: Tala
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
mesh_terms: D000293:Adolescent; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015278:Intensive Care Units, Pediatric; D007902:Length of Stay; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000382:microbiology; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000382:microbiology; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000382:microbiology; D013997:Time Factors
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers