A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure
A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure
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DOI：
10.1097/pcc.0000000000002105
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发表时间：
2019-12-01
影响因子：
4.1
通讯作者：
Dean, J. Michael
中科院分区：
文献类型：
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作者：
Carcillo, Joseph A.;Berg, Robert A.;Dean, J. Michael
目的：正在进行的成人脓毒症临床试验正在评估针对三种炎症表型的治疗方法，包括 1) 免疫麻痹相关，2) 血栓性微血管病驱动的血小板减少症相关，以及 3) 序贯性肝衰竭相关的多器官衰竭。这三种表型尚未在儿科多中心环境中进行评估。我们检验了以下假设：这些表型与儿童脓毒症中巨噬细胞活化综合征和死亡率增加相关。设计：前瞻性严重败血症队列研究，将患有多器官衰竭和任何这些表型的儿童与患有多器官衰竭但没有这些表型的儿童和患有单器官衰竭的儿童进行比较。地点：尤尼斯·肯尼迪·施赖弗国家儿童健康与人类发展研究所儿科重症监护协作研究网络中的九个 PICU。患者：患有严重败血症并留置动脉或中心静脉导管的儿童。干预措施：临床数据收集和每周两次血液采样，直至 PICU 第 28 天或出院。测量和主要结果：在纳入的 401 例严重脓毒症病例中，112 例 (28%) 出现单器官衰竭（0% 巨噬细胞激活综合征 0/112；< 1% 死亡率 1/112），而 289 例 (72%) 出现多器官衰竭（9% 巨噬细胞激活综合征 24/289；15% 死亡率 43/289）。患有多器官和表型的儿童的总体死亡率较高（24/101 vs 20/300；相对风险，3.56；95% CI，2.06-6.17）。与188名不具有这些炎症表型的多器官衰竭患者相比，101名具有这些表型的多器官衰竭患者的巨噬细胞活化综合征（19% vs 3%；相对风险，7.07；95% CI，2.72-18.38）和死亡率（24% vs 10%；相对风险，2.35；95% CI，2.35；95% CI，2.72-18.38）和死亡率均增加。 1.35-4.08）。结论：这三种炎症表型与儿童脓毒症引起的多器官衰竭的巨噬细胞活化综合征和死亡率增加相关。这项研究为规划针对儿童这些炎症表型的多中心临床试验提供了动力和必要的基线数据。
Objectives: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis. Design: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure. Setting: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Patients: Children with severe sepsis and indwelling arterial or central venous catheters. Interventions: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge. Measurements and Main Results: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08). Conclusions: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.