Confounders for prognostic accuracy of neuron-specific enolase after cardiac arrest: A retrospective cohort study

Constanze Czimmeck; Martin Kenda; Noelle Aalberts; Christian Endisch; Christoph J Ploner; Christian Storm; Jens Nee; Kaspar J Streitberger; Christoph Leithner

doi:10.1016/j.resuscitation.2023.109964

Confounders for prognostic accuracy of neuron-specific enolase after cardiac arrest: A retrospective cohort study

Resuscitation. 2023 Nov:192:109964. doi: 10.1016/j.resuscitation.2023.109964. Epub 2023 Sep 6.

Authors

Constanze Czimmeck¹, Martin Kenda², Noelle Aalberts³, Christian Endisch³, Christoph J Ploner³, Christian Storm⁴, Jens Nee⁵, Kaspar J Streitberger³, Christoph Leithner³

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department of Neurology and Experimental Neurology, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: constanze.czimmeck@charite.de.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department of Neurology and Experimental Neurology, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Digital Clinician Scientist Program, Charitéplatz 1, 10117 Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department of Neurology and Experimental Neurology, Augustenburger Platz 1, 13353 Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department of Nephrology and Medical Intensive Care, Charitéplatz 1, 10117 Berlin, Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department of Nephrology and Medical Intensive Care, Circulatory Arrest Center of Excellence Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

PMID: 37683997
DOI: 10.1016/j.resuscitation.2023.109964

Abstract

Aim: To evaluate neuron-specific enolase (NSE) thresholds for prediction of neurological outcome after cardiac arrest and to analyze the influence of hemolysis and confounders.

Methods: Retrospective analysis from a cardiac arrest registry. Determination of NSE serum concentration and hemolysis-index (h-index) 48-96 hours after cardiac arrest. Evaluation of neurological outcome using the Cerebral Performance Category score (CPC) at hospital discharge. Separate analyses considering CPC 1-3 and CPC 1-2 as good neurological outcome. Analysis of specificity and sensitivity for poor and good neurological outcome prediction with and without exclusion of hemolytic samples (h-index larger than 50).

Results: Among 356 survivors three days after cardiac arrest, hemolysis was detected in 28 samples (7.9%). At a threshold of 60 µg/L, NSE predicted poor neurological outcome (CPC 4-5) in all samples with a specificity of 92% (86-95%) and sensitivity of 73% (66-79%). In non-hemolytic samples, specificity was 94% (89-97%) and sensitivity 70% (62-76%). At a threshold of 100 µg/L, specificity was 98% (95-100%, all samples) and 99% (95-100%, non-hemolytic samples), and sensitivity 58% (51-65%) and 55% (47-63%), respectively. Possible confounders for elevated NSE in patients with good neurological outcome were ECMO, malignancies, blood transfusions and acute brain diseases. Nine patients with NSE below 17 µg/L had CPC 5, all had plausible death causes other than hypoxic-ischemic encephalopathy.

Conclusions: NSE concentrations higher than 100 µg/L predicted poor neurological outcome with high specificity. An NSE less than 17 µg/L indicated absence of severe hypoxic-ischemic encephalopathy. Hemolysis and other confounders need to be considered.

Institutional protocol number: The local ethics committee (board name: Ethikkommission der Charité) approved this study by the number: EA2/066/23, approval date: 28th June 2023, study title "'ROSC' - Resuscitation Outcome Study."

Keywords: Cardiac Arrest; Hypoxic-ischemic encephalopathy; Neurological outcome; Neuron-specific enolase; Prognostication.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Heart Arrest* / therapy
Hemolysis
Humans
Hypoxia-Ischemia, Brain*
Out-of-Hospital Cardiac Arrest* / therapy
Phosphopyruvate Hydratase
Prognosis
Prospective Studies
Retrospective Studies

Substances

Biomarkers
Phosphopyruvate Hydratase
ENO2 protein, human