Critical Care Medicine UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States; Children's Neuroscience Institute, University of Pittsburgh, Pittsburgh, PA, United States.
Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States.
Resuscitation. 2021 Oct;167:307-316. doi: 10.1016/j.resuscitation.2021.07.007. Epub 2021 Jul 14.
We hypothesized that serum biomarkers of inflammation including chemokine, cytokine, pituitary hormones, and growth factors following cardiac arrest in children would independently associate with 6-month neurologic outcome.
In this prospective observational single center study of children with in-hospital and out-of-hospital cardiac arrest surviving to intensive care unit admission, serum was obtained twice per 24 h period between 0 h and 96 h and once at approximately 196 h post-cardiac arrest. Inflammatory mediators, hormones, and growth factors were analyzed by Luminex Multiplex Bead Immunoassay. We recorded demographics, resuscitation characteristics, and Pediatric Cerebral Performance Category (PCPC) at 6 months. We analyzed the association and area under the curve (AUC) of biomarker levels with favorable (PCPC 1-3) or unfavorable (PCPC 4-6, or >1 increase from baseline) outcome.
Forty-two children (50% female; median age of 2.5 [IQR: 0.4-10.2]) were enrolled and 18 (42%) died prior to 6-month follow up. Receiver operator curves for initial levels of ciliary neurotrophic factor (CNTF, AUC 0.84, 95% CI 0.73-0.96, p < 0.001) and interleukin (IL-17, AUC 0.84, 95% CI 0.73-0.97, p < 0.001) best classified favorable versus unfavorable 6-month outcome. In multivariable analysis, initial levels of CNTF and IL-17 remained associated with 6-month PCPC. Peak levels of interferon-γ-inducible protein 10 (IP-10), CNTF, and hepatocyte growth factor (HGF) were also independently associated with outcome.
Increased serum concentrations of CNTF and IL-17 associated with unfavorable 6-month neurologic outcome of children surviving cardiac arrest. Further investigation of the prognostic utility and roles of CNTF and IL-17 in the pathophysiology of post-cardiac arrest syndrome are warranted. This project is registered with clinicaltrials.gov (NCT00797680) as "Duration of Hypothermia for Neuroprotection after Pediatric Cardiac Arrest: A Randomized, Controlled Trial".
我们假设，儿童心脏骤停后血清炎症标志物（趋化因子、细胞因子、垂体激素和生长因子）将与 6 个月时的神经功能结局独立相关。
本研究为前瞻性观察性单中心研究，纳入了院内和院外心脏骤停并存活至重症监护病房的患儿。在心脏骤停后 0 小时至 96 小时内，每 24 小时采集 2 次血清，在心脏骤停后约 196 小时采集 1 次。采用 Luminex 多重珠免疫分析法定量分析炎症介质、激素和生长因子。我们记录了患儿的人口统计学、复苏特征和儿科脑功能预后分类（PCPC）。我们分析了生物标志物水平与结局（PCPC 1-3 为有利结局，PCPC 4-6 或较基线升高 1 级为不利结局）的相关性和曲线下面积（AUC）。
共纳入 42 名患儿（50%为女性，中位年龄为 2.5 岁[IQR：0.4-10.2]），其中 18 名（42%）在 6 个月随访前死亡。初始睫状神经营养因子（CNTF，AUC 0.84，95%CI 0.73-0.96，p<0.001）和白细胞介素（IL）-17 水平的受试者工作特征曲线可最佳区分 6 个月时的有利与不利结局。多变量分析显示，初始 CNTF 和 IL-17 水平与 6 个月时的 PCPC 相关。干扰素-γ诱导蛋白 10（IP-10）、CNTF 和肝细胞生长因子（HGF）的峰值水平也与结局独立相关。
血清 CNTF 和 IL-17 浓度升高与儿童心脏骤停后 6 个月时不良神经结局相关。进一步研究 CNTF 和 IL-17 在心脏骤停后综合征病理生理学中的预后作用非常必要。本研究在 clinicaltrials.gov 注册（NCT00797680），题为“儿科心脏骤停后神经保护的低温持续时间：一项随机对照试验”。
