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.
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.
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predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn.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.
方法:本研究是一项对接受TTM的OHCA患者进行的前瞻性观察性研究。我们测量了传统的生物标志物,神经元特异性烯醇化酶和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末端水解酶-L1(UCH-L1),在通过SIMOA免疫测定鉴定的自发循环恢复后0、24、48和72小时。主要结果是OHCA后6个月的神经学结果较差。
结果:从2018年8月至2020年5月,本研究共纳入100例患者。在纳入的患者中,46例患者在OHCA后6个月有良好的神经系统预后。所有常规和新的血清生物标志物都能够区分好的和差的神经学结果组(p<0.001)。新的血清生物标志物的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小时的NFL敏感度最高(77.1%,95%CI59.9-89.6)在维持100%特异性的同时预测不良神经系统预后。
结论:新的血清生物标志物可靠地预测了接受TTM治疗的OHCA患者在未停止维持生命治疗时的不良神经系统预后。在我们的研究中,对两项大型现有研究(TTM和COMACARE子研究)的截止值进行了外部验证。新生物标志物的预测能力在CA后72小时最高。