背景:目的是评估血浆中的神经胶质纤维酸性蛋白(GFAP)和总tau作为院外(OHCA)和院内心脏骤停(IHCA)后神经系统预后不良的预测因子,包括与神经丝光(NFL)和神经元特异性烯醇化酶(NSE)的比较。
方法:对2014-2018年瑞典三家医院重症监护病房(ICU)住院患者进行回顾性多中心观察研究。在入住ICU时采集血样,12h,和心脏骤停后48小时。不良的神经系统结局定义为心脏骤停后2-6个月的脑功能类别3-5。对血浆样本进行GFAP回顾性分析,tau,和NFL。在临床护理中分析血清NSE。用接受者工作特征曲线下面积(AUC)测试预后表现。
结果:在428名患者中,328是OHCA,100人是IHCA。入住ICU时,心脏骤停后12小时和48小时,GFAP预测OHCA后的神经系统结局,AUC(95%CI)为0.76(0.70-0.82),0.86(0.81-0.90)和0.91(0.87-0.96),IHCA后AUC(95%CI)0.77(0.66-0.87),0.83(0.74-0.92)和0.83(0.71-0.95)。在同一时间点,tau预测OHCA后的结果,AUC(95%CI)0.72(0.66-0.79),0.75(0.69-0.81),和0.93(0.89-0.96),IHCA后AUC(95%CI)为0.61(0.49-0.74),0.68(0.56-0.79),和0.77(0.65-0.90)。与最后一个时间点相比,在时间点之间添加生物标志物水平的变化并没有提高预测准确性。在一部分患者中,12小时和48小时的GFAP,以及在48小时的tau,在OHCA和IHCA治疗后48h(指南中建议的最早时间点NSE)提供与NSE相似的预测值.在OHCA和IHCA之后的所有时间点,NFL的预测性能与GFAP和tau相似或优于GFAP和tau。
结论:GFAP和tau是神经预后的有希望的生物标志物,在OHCA后48小时具有最高的预测性能,但不优于NFL。在心脏骤停后12小时,GFAP的预测能力可能足够高,可用于临床。
The purpose was to evaluate glial fibrillary acidic protein (GFAP) and total-tau in plasma as predictors of poor neurological outcome after out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA), including comparisons with neurofilament light (NFL) and neuron-specific enolase (NSE).
Retrospective multicentre observational study of patients admitted to an intensive care unit (ICU) in three hospitals in Sweden 2014-2018. Blood samples were collected at ICU admission, 12 h, and 48 h post-cardiac arrest. Poor neurological outcome was defined as Cerebral Performance Category 3-5 at 2-6 months after cardiac arrest. Plasma samples were retrospectively analysed for GFAP, tau, and NFL. Serum NSE was analysed in clinical care. Prognostic performances were tested with the area under the receiver operating characteristics curve (AUC).
Of the 428 included patients, 328 were OHCA, and 100 were IHCA. At ICU admission, 12 h and 48 h post-cardiac arrest, GFAP predicted neurological outcome after OHCA with AUC (95% CI) 0.76 (0.70-0.82), 0.86 (0.81-0.90) and 0.91 (0.87-0.96), and after IHCA with AUC (95% CI) 0.77 (0.66-0.87), 0.83 (0.74-0.92) and 0.83 (0.71-0.95). At the same time points, tau predicted outcome after OHCA with AUC (95% CI) 0.72 (0.66-0.79), 0.75 (0.69-0.81), and 0.93 (0.89-0.96) and after IHCA with AUC (95% CI) 0.61 (0.49-0.74), 0.68 (0.56-0.79), and 0.77 (0.65-0.90). Adding the change in biomarker levels between time points did not improve predictive accuracy compared to the last time point. In a subset of patients, GFAP at 12 h and 48 h, as well as tau at 48 h, offered similar predictive value as NSE at 48 h (the earliest time point NSE is recommended in guidelines) after both OHCA and IHCA. The predictive performance of NFL was similar or superior to GFAP and tau at all time points after OHCA and IHCA.
GFAP and tau are promising biomarkers for neuroprognostication, with the highest predictive performance at 48 h after OHCA, but not superior to NFL. The predictive ability of GFAP may be sufficiently high for clinical use at 12 h after cardiac arrest.