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

神經元特異性烯醇化酶(NSE)預測心髒驟停和目標溫度管理後不良預後：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：心髒驟停後的預後預測對決定是否繼續重症監護非常重要。神經元特異性烯醇化酶(NSE)是一種容易測量的、獨立於觀察者的預後標誌物。最近的研究對目標溫度管理後的預後價值產生了矛盾的結果。

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).

研究設計方法：本研究分析了德國、奧地利和意大利五家醫院非創傷性院內及院外心髒驟停患者3天後血清神經元特異性烯醇化酶濃度及預後情況。患者在33°C低溫治療24小時，在出院時評估腦功能分類級別。對神經元特異性烯醇化酶大於90μg/L、神經元特異性烯醇化酶低於17μg/L(正常上限)的預後差的患者進行回顧性分析。

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.

測量和主要結果：神經元特異性烯醇化酶血清濃度大於90μg / L預測大腦功能分類4 – 5級，陽性預測值為99%，假陽性率為0.5%，敏感度為48%。3例神經元特異性烯醇化酶大於90μg且腦功能分類1～2級的患者均有神經元特異性烯醇化酶升高的混雜因素。神經元特異性烯醇化酶血清濃度小於或等於17μg/L，排除腦功能4～5級的陰性預測值為92%。14例神經元特異性烯醇化酶低於或等於17μg/L死亡的患者中，其死因並非缺氧缺血性腦病，而是另有其他原因。預測預後不良的特異性和敏感性與年齡、性別和初始水平無關，但與院內心髒驟停患者相比，院外心髒驟停更高。

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.

結論：血清高濃度神經元特異性烯醇化酶是一項可預測ICU出院不良結局可靠的指標。與院內心髒驟停患者相比，院外心髒驟停的預測準確度不同，效果更好。該試驗的“現場”數據表明，90μg/L作為一個閾值，在可接受的靈敏度上幾乎沒有假陽性。但是神經元特異性烯醇化酶升高的混雜因素應積極考慮：神經元特異性烯醇化酶也是腫瘤、急性腦疾病和溶血的預測指標。我們強烈建議常規測量溶血定量，而神經元特異性烯醇化酶血清濃度小於或等於17μg/L不能預測不相容的缺氧缺血性腦病蘇醒。

翻譯：張雅芝

審校：曹廣慧