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新生儿心脏手术后血管生成素-2水平升高与不良临床结局相关。

Rise in Angiopoietin-2 Following Neonatal Cardiac Surgery Is Associated With Adverse Clinical Outcomes.

机构信息

Department of Pediatrics, Division of Cardiology, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI.

Department of Anesthesiology, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI.

出版信息

Pediatr Crit Care Med. 2020 Sep;21(9):e827-e833. doi: 10.1097/PCC.0000000000002479.

DOI:10.1097/PCC.0000000000002479
PMID:32701748
Abstract

OBJECTIVES

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.

DESIGN

Prospective cohort study.

SETTING

Pediatric cardiac ICU.

PATIENTS

Thirty neonates less than 2 weeks old undergoing repair of congenital cardiac defects with cardiopulmonary bypass.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

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).

CONCLUSIONS

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.

摘要

目的

新生儿心脏手术治疗先天性心脏缺陷与较高的发病率和死亡率相关,因此需要早期识别出有发生不良预后风险的高危患者。由于血管内皮损伤介导了多个器官系统的损伤,我们测量了体外循环后新生儿的血清内皮损伤生物标志物,并研究了它们与短期结局的相关性。

设计

前瞻性队列研究。

地点

儿科心脏重症监护病房。

患者

30 名年龄小于 2 周且需行心脏修补术的先天性心脏缺陷新生儿。

干预措施

无。

测量指标和主要结果

于术前和术后 24 小时测量内皮完整性的生物标志物,即血管生成素-1 和血管生成素-2。复合不良结局定义为以下任意一项:脑卒中、需要肾脏替代治疗、体外膜肺氧合支持、心脏骤停或死亡。采用 Wilcoxon 秩和检验分析生物标志物与不良结局的相关性。与术前相比,术后 24 小时血管生成素-2显著增加(p<0.0001),而血管生成素-1则显著减少(p<0.0001)。与术前相比,术后 24 小时血管生成素-2水平升高幅度更大的患者发生复合不良结局的风险更高(p=0.04)。这些患者的血管活性-正性肌力药物评分(p=0.06)更高,且低心排血量综合征的发生率更高(p=0.06)。术后 24 小时血管生成素-2水平与复合不良结局相关(p=0.03)。与术前相比,术后 24 小时血管生成素-2水平升高幅度与体外循环持续时间直接相关(r=0.47,p=0.01)。

结论

在新生儿心脏手术中,体外循环时间延长与血清血管生成素-2水平升高导致的更大内皮损伤直接相关。术后 24 小时血管生成素-2水平与复合不良结局显著相关。术后血管生成素-2水平可能是需要更密切监测和保护干预的患者的早期指标。需要进一步研究内皮保护策略。

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