Wiberg Sebastian, Hassager Christian, Stammet Pascal, Winther-Jensen Matilde, Thomsen Jakob Hartvig, Erlinge David, Wanscher Michael, Nielsen Niklas, Pellis Tommaso, Åneman Anders, Friberg Hans, Hovdenes Jan, Horn Janneke, Wetterslev Jørn, Bro-Jeppesen John, Wise Matthew P, Kuiper Michael, Cronberg Tobias, Gasche Yvan, Devaux Yvan, Kjaergaard Jesper
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Anaesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
PLoS One. 2017 Jan 18;12(1):e0168894. doi: 10.1371/journal.pone.0168894. eCollection 2017.
Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population.
This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5.
A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58-0.84 versus 0.83).
NSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials. While combinations of serial NSE measurements may provide an increase in overall prognostic information, it is unclear whether actual clinical prognostication with low false-positive rates is improved by application of serial measurements in persistently unconscious patients. The findings of this study should be confirmed in another prospective cohort.
NCT01020916.
神经功能预后的预测是心脏骤停后护理的关键部分，对于目标温度管理（TTM）复温后仍处于昏迷和/或镇静状态的患者进行预测仍然很困难。当前指南建议，对于院外心脏骤停（OHCA）后入院的患者，使用生物标志物神经元特异性烯醇化酶（NSE）的系列测量结果，并结合其他预后预测指标。本研究旨在调查NSE预测OHCA后第三天仍未苏醒患者不良预后的能力。此外，本研究还旨在调查，与该人群48小时时单次测量NSE相比，系列测量NSE是否能提供更多的预后信息。
本研究是TTM试验的事后亚研究，将OHCA患者随机分为33°C或36°C的TTM疗程。患者来自参与TTM试验生物样本库亚研究的地点。在自主循环恢复（ROSC）后24、48和72小时测量NSE，并在180天后结束随访。主要终点是神经功能不良或死亡，由脑功能分类评分（CPC评分）3至5定义。
共有685例（73%）患者参与了本研究。在OHCA后第三天，63例（9%）患者死亡，473例（69%）患者未苏醒。在这些患者中，48小时时单次测量NSE预测不良预后的受试者工作特征曲线下面积（AUC）为0.83。所有三次NSE测量结果相结合得出的AUC最高（0.88，p = 0.0002）。与48小时时单次测量相比（AUC为0.58 - 0.84对0.83），系列NSE测量的易于应用的组合并未显著改善预测效果。
对于接受TTM的持续昏迷患者，NSE是OHCA后不良预后的有力预测指标，并且在临床试验中NSE是一个有前景的预后替代标志物。虽然系列NSE测量结果的组合可能会增加总体预后信息，但尚不清楚在持续昏迷患者中应用系列测量是否能改善实际临床预后且假阳性率较低。本研究结果应在另一项前瞻性队列研究中得到证实。
NCT01020916。
