Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest,Intensive Care Medicine

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Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest
Intensive Care Medicine ( IF 27.1 ) Pub Date : 2021-08-21 , DOI: 10.1007/s00134-021-06481-4
Marion Moseby-Knappe ₁ , Niklas Mattsson-Carlgren _{1,

2,

3} , Pascal Stammet ₄ , Sofia Backman ₅ , Kaj Blennow _{6,

7} , Josef Dankiewicz ₈ , Hans Friberg ₉ , Christian Hassager _{10,

11} , Janneke Horn ₁₂ , Jesper Kjaergaard ₁₃ , Gisela Lilja ₁ , Christian Rylander ₁₄ , Susann Ullén ₁₅ , Johan Undén _{16,

17} , Erik Westhall ₅ , Matt P Wise ₁₈ , Henrik Zetterberg _{6,

7,

19,

20,

21} , Niklas Nielsen ₂₂ , Tobias Cronberg ₁

Affiliation

Department of Clinical Sciences Lund, Neurology, Skåne University Hospital, Lund University, Getingevägen 4, 222 41, Lund, Sweden.
Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
Medical and Health Department, National Fire and Rescue Corps, Luxembourg, Luxembourg.
Department of Clinical Sciences Lund, Clinical Neurophysiology, Skåne University Hospital, Lund University, Lund, Sweden.
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Clinical Sciences Lund, Cardiology, Skåne University Hospital, Lund University, Lund, Sweden.
Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Skåne University Hospital, Lund University, Malmö, Sweden.
Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Intensive Care, Amsterdam Neuroscience, Amsterdam UMC, Location Academic Medical Center, Amsterdam, The Netherlands.
Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska Academy, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
Clinical Studies Sweden-Forum South, Skane University Hospital, Lund, Sweden.
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Department of Operation and Intensive Care, Lund University, Hallands Hospital Halmstad, Halland, Sweden.
Adult Critical Care, University Hospital of Wales, Cardiff, UK.
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
UK Dementia Research Institute at UCL, London, UK.
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Helsingborg Hospital, Lund University, Lund, Sweden.

Purpose

The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines.

Methods

Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months.

Results

Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome.

Conclusion

Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.

中文翻译：

脑损伤的血清标志物可以预测院外心脏骤停后良好的神经系统结果

目的

大多数心脏骤停（CA）后失去知觉的患者不符合可能预后不良的指导标准，他们的预后被认为是“不确定的”。我们比较了血液中的脑损伤标志物，以预测良好的结果，并根据指南的建议识别不良结果的假阳性预测。

方法

在院外心脏骤停 (TTM) 试验后的目标温度管理中，对逮捕后 24、48 和 72 小时前瞻性收集的血清样本进行回顾性分析。分析了临床可用的标记物神经元特异性烯醇化酶 (NSE) 和 S100B，以及新型标记物神经丝轻链 (NFL)、总 tau、泛素羧基末端水解酶 L1 (UCH-L1) 和胶质纤维酸性蛋白 (GFAP)。使用参考实验室指定或文献定义的先验临界值的正常水平来预测 6 个月时的良好结果（无至中度残疾，脑功能类别量表 1-2）。

结果

其中包括七百一十七名患者。正常的 NFL、tau 和 GFAP 具有最高的敏感性（97.2-98% 预后不良的患者血清水平异常）和 NPV（正常水平预示 87-95% 患者的良好预后）。正常的 S100B 和 NSE 预测良好的结果，NPV 为 76-82.2%。正常 NSE 正确识别出 67/190 (35.3%) 的患者，其中 67/190 (35.3%) 的患者在指南归类为“不确定结果”的患者中具有良好的结果。尽管生物标志物正常，但五名具有单一病理预后结果的患者却取得了良好的结果。