Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients

神经元特异性烯醇化酶(NSE)预测心脏骤停和目标温度管理后不良预后：1053例多中心研究

Objective

Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management.

目的：心脏骤停后的预后预测对决定是否继续重症监护非常重要。神经元特异性烯醇化酶(NSE)是一种容易测量的、独立于观察者的预后标志物。最近的研究对目标温度管理后的预后价值产生了矛盾的结果。

Design, Setting, and Patients

We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 μg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 μg/L (upper limit of normal).

研究设计方法：本研究分析了德国、奥地利和意大利五家医院非创伤性院内及院外心脏骤停患者3天后血清神经元特异性烯醇化酶浓度及预后情况。患者在33°C低温治疗24小时，在出院时评估脑功能分类级别。对神经元特异性烯醇化酶大于90μg/L、神经元特异性烯醇化酶低于17μg/L(正常上限)的预后差的患者进行回顾性分析。

Measurements and Main Results

A neuron-specific enolase serum concentration greater than 90 μg/L predicted Cerebral Performance Category 4–5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 μg/L and Cerebral Performance Category 1–2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 μg/L excluded Cerebral Performance Category 4–5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 μg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients.

测量和主要结果：神经元特异性烯醇化酶血清浓度大于90μg / L预测大脑功能分类4 – 5级，阳性预测值为99%，假阳性率为0.5%，敏感度为48%。3例神经元特异性烯醇化酶大于90μg且脑功能分类1～2级的患者均有神经元特异性烯醇化酶升高的混杂因素。神经元特异性烯醇化酶血清浓度小于或等于17μg/L，排除脑功能4～5级的阴性预测值为92%。14例神经元特异性烯醇化酶低于或等于17μg/L死亡的患者中，其死因并非缺氧缺血性脑病，而是另有其他原因。预测预后不良的特异性和敏感性与年龄、性别和初始水平无关，但与院内心脏骤停患者相比，院外心脏骤停更高。

Conclusion

High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our “in-the-field” data indicate 90 μg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase–producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 μg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

结论：血清高浓度神经元特异性烯醇化酶是一项可预测ICU出院不良结局可靠的指标。与院内心脏骤停患者相比，院外心脏骤停的预测准确度不同，效果更好。该试验的“现场”数据表明，90μg/L作为一个阈值，在可接受的灵敏度上几乎没有假阳性。但是神经元特异性烯醇化酶升高的混杂因素应积极考虑：神经元特异性烯醇化酶也是肿瘤、急性脑疾病和溶血的预测指标。我们强烈建议常规测量溶血定量，而神经元特异性烯醇化酶血清浓度小于或等于17μg/L不能预测不相容的缺氧缺血性脑病苏醒。

翻译：张雅芝

审校：曹广慧