Rise in Angiopoietin-2 Following Neonatal Cardiac Surgery Is Associated With Adverse Clinical Outcomes.
Journal
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
ISSN: 1529-7535
Titre abrégé: Pediatr Crit Care Med
Pays: United States
ID NLM: 100954653
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
24
7
2020
medline:
7
1
2021
entrez:
24
7
2020
Statut:
ppublish
Résumé
Neonatal cardiac surgery for congenital cardiac defects is associated with significant morbidity and mortality, and there is a need for early identification of patients at highest risk of adverse outcomes. Because vascular endothelial injury mediates damage across organ systems, we measured serum biomarkers of endothelial injury in neonates following cardiopulmonary bypass and examined their associations with short-term outcomes. Prospective cohort study. Pediatric cardiac ICU. Thirty neonates less than 2 weeks old undergoing repair of congenital cardiac defects with cardiopulmonary bypass. None. Biomarkers of endothelial integrity, angiopoietin-1 and angiopoietin-2, were measured preoperatively and at 24 hours postoperatively. A composite adverse outcome was defined as any of the following: stroke, need for renal replacement therapy, extracorporeal membrane oxygenation support, cardiac arrest, or death. Associations of biomarkers with adverse outcomes were examined using Wilcoxon rank-sum test. There was an increase in angiopoietin-2 from preoperatively to 24 hours postoperatively (p < 0.0001) and a decrease in angiopoietin-1 from preoperatively to 24 hours postoperatively (p < 0.0001). Patients with greater rise in angiopoietin-2 from preoperatively to 24 hours postoperatively had greater risk of composite adverse outcome (p = 0.04). They had a trend toward higher Vasoactive-Inotropic Score (p = 0.06) and a higher prevalence of low cardiac output syndrome (p = 0.06). Twenty-four hour postoperative angiopoietin-2 level was associated with the composite adverse outcome (p = 0.03). The rise in angiopoietin-2 level from preoperatively to 24 hours postoperatively directly correlated with cardiopulmonary bypass duration (r = 0.47; p = 0.01). In neonatal cardiac surgery, longer duration of cardiopulmonary bypass is directly associated with greater endothelial injury as measured by increased serum levels of angiopoietin-2. Angiopoietin-2 levels 24 hours postoperatively were significantly associated with a composite adverse outcome. Postoperative angiopoietin-2 level may serve as an early indicator of patients in need of closer monitoring and protective intervention. Further research into endothelial protective strategies is warranted.
Identifiants
pubmed: 32701748
doi: 10.1097/PCC.0000000000002479
pii: 00130478-202009000-00053
doi:
Substances chimiques
Angiopoietin-2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e827-e833Références
Gaies M, Pasquali SK, Donohue JE, et al. Seminal postoperative complications and mode of death after pediatric cardiac surgical procedures. Ann Thorac Surg 2016; 102:628–635
Cines DB, Pollak ES, Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91:3527–3561
Carcillo JA, Podd B, Aneja R, et al. Pathophysiology of pediatric multiple organ dysfunction syndrome. Pediatr Crit Care Med 2017; 18:S32–S45
Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996; 87:1171–1180
Davis S, Aldrich TH, Jones PF, et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 1996; 87:1161–1169
Wong AL, Haroon ZA, Werner S, et al. Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues. Circ Res 1997; 81:567–574
Thurston G, Rudge JS, Ioffe E, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000; 6:460–463
Mammoto T, Parikh SM, Mammoto A, et al. Angiopoietin-1 requires p190 RhoGAP to protect against vascular leakage in vivo. J Biol Chem 2007; 282:23910–23918
Fiedler U, Scharpfenecker M, Koidl S, et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 2004; 103:4150–4156
Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997; 277:55–60
Parikh SM. The angiopoietin-tie2 signaling axis in systemic inflammation. J Am Soc Nephrol 2017; 28:1973–1982
Kümpers P, Lukasz A, David S, et al. Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients. Crit Care 2008; 12:R147
Siner JM, Bhandari V, Engle KM, et al. Elevated serum angiopoietin 2 levels are associated with increased mortality in sepsis. Shock 2009; 31:348–353
Russell MW, Chung WK, Kaltman JR, et al. Advances in the understanding of the genetic determinants of congenital heart disease and their impact on clinical outcomes. J Am Heart Assoc 2018; 7:e006906
Gaies MG, Gurney JG, Yen AH, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 2010; 11:234–238
Giuliano JS Jr, Lahni PM, Bigham MT, et al. Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypass. Intensive Care Med 2008; 34:1851–1857
Clajus C, Lukasz A, David S, et al. Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass. Cytokine 2012; 60:352–359
Adams PS, Vargas D, Baust T, et al. Associations of perioperative renal oximetry via near-infrared spectroscopy, urinary biomarkers, and postoperative acute kidney injury in infants after congenital heart surgery: Should creatinine continue to be the gold standard? Pediatr Crit Care Med 2019; 20:27–37
Basu RK, Wang Y, Wong HR, et al. Incorporation of biomarkers with the renal angina index for prediction of severe AKI in critically ill children. Clin J Am Soc Nephrol 2014; 9:654–662
Hazle MA, Gajarski RJ, Yu S, et al. Fluid overload in infants following congenital heart surgery. Pediatr Crit Care Med 2013; 14:44–49
Tikkanen AU, Nathan M, Sleeper LA, et al. Predictors of postoperative rehabilitation therapy following congenital heart surgery. J Am Heart Assoc 2018; 7:e008094
Salis S, Mazzanti VV, Merli G, et al. Cardiopulmonary bypass duration is an independent predictor of morbidity and mortality after cardiac surgery. J Cardiothorac Vasc Anesth 2008; 22:814–822
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101:1644–1655
Watson RS, Crow SS, Hartman ME, et al. Epidemiology and outcomes of pediatric multiple organ dysfunction syndrome. Pediatr Crit Care Med 2017; 18:S4–S16
Upperman JS, Lacroix J, Curley MAQ, et al. Specific etiologies associated with the multiple organ dysfunction syndrome in children: Part 1. Pediatr Crit Care Med 2017; 18(3_Suppl Suppl 1):S50–S57