4.6 Article

Elevated Plasma Angiopoietin-2 Levels Are Associated With Fluid Overload, Organ Dysfunction, and Mortality in Human Septic Shock

期刊

CRITICAL CARE MEDICINE
卷 44, 期 11, 页码 2018-2027

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0000000000001853

关键词

acute kidney injury; angiopoietin-2; fluid overload; organ dysfunction; septic shock

资金

  1. Canadian Institutes of Health Research [MCT 44152]
  2. Providence Health Care Research Scholarship
  3. Canadian Institutes of Health Research
  4. Ferring Pharmaceutical
  5. AKPA
  6. Cubist by Merck
  7. Grifols
  8. Leading Biosciences
  9. La Jolla Pharmaceuticals
  10. Cytovale

向作者/读者索取更多资源

Objectives: Angiopoietins modulate endothelial permeability via endothelial cell junctions. Angiopoietin-2 blocks the angiopoietin-1/Tie-2 interaction that stabilizes these junctions, and elevated plasma angiopoietin-2 levels are associated with vascular leakage. We hypothesized that plasma angiopoietin-1 and angiopoietin-2 levels are associated with indirect markers of increased vascular permeability, organ dysfunction, mortality, and plasma proinflammatory cytokine levels in human septic shock. Design: Multicenter observational cohort study derived from a randomized controlled trial (Vasopressin and Septic Shock Trial of vasopressin versus norepinephrine in septic shock). Setting: ICUs of hospitals in Canada, Australia, and the United States. Patients: Three hundred forty-one patients in the randomized, controlled Vasopressin and Septic Shock Trial trial of vasopressin versus norepinephrine in septic shock. Interventions: None. Measurement and Main Results: We measured plasma levels of angiopoietin-1 and angiopoietin-2 at study baseline and determined their association with percent fluid overload and acute organ dysfunction and generated a receiver operating characteristic curve for plasma angiopoietin-2 levels versus acute kidney injury. We also determined the association of angiopoietin-1 and angiopoietin-2 levels with hemodynamics, mortality, and plasma cytokine levels. Plasma angiopoietin-2 levels were directly associated with percent fluid overload at baseline (r(s) = 0.18; p = 0.0008) and at 6 hours (r(s) = 0.13; p = 0.023), but not at 24 hours (r(s) = 0.041; p = 0.46). Plasma angiopoietin-2 levels were associated with the development of hepatic (p < 0.0001) and coagulation (p < 0.0001) dysfunction and acute kidney injury (p < 0.0001). Receiver operating characteristic curve had an area under the curve of 0.73 for acute kidney injury. angiopoietin-2 levels were also inversely associated with days alive (r = -0.24; p = 0.010) and positively associated with increased 7-day (log-rank trend chi-square = 5.9; p = 0.015) and 28-day (log-rank chi square = 4.9; p = 0.027) mortality. A threshold of angiopoietin-2 levels above the first quartile (> 5,807 pg/mL) was observed to be associated with increased mortality risk, which aligns with prior studies. Plasma angiopoietin-2 levels were positively associated with plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6 at baseline (r(s) = 0.39; p < 0.0001 and r(s) = 0.51; p < 0.0001) and at 24 hours (r(s) = 0.29; p < 0.0001 and r(s) = 0.41; p < 0.0001). Conclusions: Increased plasma angiopoietin-2 levels are associated with increased fluid overload, hepatic and coagulation dysfunction, acute kidney injury, mortality, and plasma cytokines in human septic shock. angiopoietin-2 activation may increase vascular leakage leading to increased fluid requirements, organ dysfunction, and death from septic shock.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据