Int J Med Sci 2019; 16(2):318-323. doi:10.7150/ijms.27731 This issue

Research Paper

Systemic Angiopoietin-1/2 Dysregulation in Pediatric Sepsis and Septic Shock

Elliot Melendez1✉, Jane E. Whitney2, Jackson S. Norton3, Melanie Silverman3, Susanna Harju-Baker4, Carmen Mikacenic4, Mark M. Wurfel4, W. Conrad Liles4

1. Division of Pediatric Critical Care, John Hopkins All Children's Hospital, St. Petersburg, FL
2. Division of Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA
3. Division of Medicine Critical Care, Boston Children's Hospital, Boston, MA
4. Department of Medicine, University of Washington, Seattle, WA

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Melendez E, Whitney JE, Norton JS, Silverman M, Harju-Baker S, Mikacenic C, Wurfel MM, Liles WC. Systemic Angiopoietin-1/2 Dysregulation in Pediatric Sepsis and Septic Shock. Int J Med Sci 2019; 16(2):318-323. doi:10.7150/ijms.27731. Available from

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Background: Angiopoietin-1 and -2 are vascular growth factors that exert opposing effects on endothelial activation and dysfunction. The aim of this study was to assess the association of these biomarkers with outcomes in children with sepsis.

Methods: Biomarkers were assayed from the blood collected in an emergency department prior to any intervention. Predictor variables were Ang-1 and Ang-2 levels and the Ang-2/Ang-1 ratio. Outcomes included mortality, length of time on vasopressors, and ICU and hospital lengths of stay. The Pediatric RISk of Mortality III Score was calculated. A vasoactive inotrope score was calculated every 12 hours.

Results: Forty-five children with sepsis and 49 with septic shock were analyzed. The median Ang-2 was higher in septic shock. The Ang-2/Ang-1 ratio was approximately 2-fold greater in those with septic shock. The Ang-2/Ang-1 ratio was associated with higher doses of vasoactive agents at 12 hours and longer ICU length of stay. In septic shock, for every 0.35 unit increase in the Ang-2/Ang-1 ratio, the PRISM III score increased by 1.

Conclusions: The Ang-2/Ang-1 ratio was higher in children with septic shock. Ang-2/Ang-1 was associated with higher vasoactive agents, longer ICU length of stay, and correlated with the severity of illness score.

Keywords: Angiopoietin, Pediatric, Sepsis, Septic Shock, Outcome, Biomarker