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Novel serum biomarkers for predicting neurological outcomes in postcardiac arrest patients treated with targeted temperature management

Critical Care：用于预测心脏骤停患者接受目标温度管理（TTM）的神经系统预后的新型血清生物标志物

【编者注】

OHCA复苏后昏迷患者行TTM治疗，用何种标志物预测神经功能远期预后？都可以。本研究采用了传统标志物，如神经元特异性烯醇化酶（NSE）和S100钙结合蛋白（S-100B），以及新的生物标志物，包括tau蛋白、神经丝轻链（NFL）、胶质纤维酸性蛋白（GFAP）和泛素C端水解酶-L1 （UCH-L1）。结果提示几种生物标志物都有良好的神经功能预测能力，并进行了较好的外部验证。
 

Objective

To determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM).

探讨新型血清生物标志物在目标温度管理（TTM）治疗院外心脏骤停（OHCA）患者应用的临床可行性。
 

Methods

This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron‑specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA.

本研究是一项前瞻性观察性研究，纳入行TTM治疗的OHCA患者。应用SIMOA免疫分析法，我们在自主循环恢复（ROSC）后0、24、48和72小时，检测了传统的生物标志物神经元特异性烯醇化酶（NSE）和S100钙结合蛋白（S-100B），以及新的生物标志物，包括tau蛋白、神经丝轻链（NFL）、胶质纤维酸性蛋白（GFAP）和泛素C端水解酶-L1 （UCH-L1）。主要结局是OHCA后6个月较差的神经系统预后。

Results

A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9-89.6) in predicting poor neurological outcomes while maintaining 100% specificity.

2018年8月至2020年5月共纳入100例患者，其中46例患者在OHCA后6个月有良好的神经转归。所有传统和新型血清生物标志物都有能力区分良好和不良神经结局组(p < 0.001)。新型血清生物标志物曲线下面积在心脏骤停（CA）后72小时最高（Tau为0.906, NFL为0.946, GFAP为0.875, UCH-L1为0.935）。CA后72 h的NFL对预测不良神经功能预后的敏感性最高（77.1%，95% CI 59.9-89.6），特异性为100%。

Novel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.

新型血清生物标志物可靠地预测了在生命支持治疗时接受TTM治疗的OHCA患者的不良神经系统预后，其截断值在两个大型现有研究（TTM研究和COMACARE亚组）进行了外部验证。新生物标志物的预测能力在CA后72 h时最高。