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

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AimTo evaluate neuron-specific enolase (NSE) thresholds for prediction of neurological outcome after cardiac arrest and to analyze the influence of hemolysis and confounders. MethodsRetrospective 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). ResultsAmong 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. ConclusionsNSE 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 numberThe 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.”