Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study

Abstract

BackgroundThe prediction of neurological outcome in comatose patients after cardiac arrest has major ethical and socioeconomic implications. The purpose of this study was to assess the capability of serum neuron-specific enolase (NSE), a biomarker of hypoxic brain damage, to predict death or vegetative state in comatose cardiac-arrest survivors.MethodsWe conducted a prospective observational cohort study in one university hospital and one general hospital Intensive Care Unit (ICU). All consecutive patients who suffered cardiac arrest and were subsequently admitted from June 2007 to February 2009 were considered for inclusion in the study. Patients who died or awoke within the first 48 hours of admission were excluded from the analysis. Patients were followed for 3 months or until death after cardiopulmonary resuscitation. The Cerebral Performance Categories scale (CPC) was used as the outcome measure; a CPC of 4-5 was regarded as a poor outcome, and a CPC of 1-3 a good outcome. Measurement of serum NSE was performed at 24 h and at 72 h after the time of cardiac arrest using an enzyme immunoassay. Clinicians were blinded to NSE results.ResultsNinety-seven patients were included. All patients were actively supported during the first days following cardiac arrest. Sixty-five patients (67%) underwent cooling after resuscitation. At 3 months 72 (74%) patients had a poor outcome (CPC 4-5) and 25 (26%) a good outcome (CPC 1-3). The median and Interquartile Range [IQR] levels of NSE at 24 h and at 72 h were significantly higher in patients with poor outcomes: NSE at 24 h: 59.4 ng/mL [37-106] versus 28.8 ng/mL [18-41] (p < 0.0001); and NSE at 72 h: 129.5 ng/mL [40-247] versus 15.7 ng/mL [12-19] (p < 0.0001). The Receiver Operator Characteristics (ROC) curve for poor outcome for the highest observed NSE value for each patient determined a cut-off value for NSE of 97 ng/mL to predict a poor neurological outcome with a specificity of 100% [95% CI = 87-100] and a sensitivity of 49% [95% CI = 37-60]. However, an approach based on a combination of SSEPs, NSE and clinical-EEG tests allowed to increase the number of patients (63/72 (88%)) identified as having a poor outcome and for whom intensive treatment could be regarded as futile.ConclusionNSE levels measured early in the course of patient care for those who remained comatose after cardiac arrest were significantly higher in patients with outcomes of death or vegetative state. In addition, we provide a cut-off value for NSE (> 97 ng/mL) with 100% positive predictive value of poor outcome. Nevertheless, for decisions concerning the continuation of treatment in this setting, we emphasize that an approach based on a combination of SSEPs, NSE and clinical EEG would be more accurate for identifying patients with a poor neurological outcome.

Early Multimodal Outcome Prediction After Cardiac Arrest in Patients Treated With Hypothermia*

“…The predictive performance of NSE in our cohort (ROC area of 0.72 for poor outcome and mortality at 33 μg/L; slightly less for mortality at 75 μg/L, which offers 100% specificity) appears somewhat lower than reported by other groups: 0.85 (cutoff 26 μg/L) (32), 0.84 (cutoff 26 μg/L) (33), 0.82 (cutoff 80 μg/L) (7), and 0.86 (cutoff 97 μg/L) (8). This probably reflects differences in patients' cohorts and laboratory assays (14,17).…”

“…An analysis on 34 patients in coma 4.5 days after CA showed that serum biomarkers correlate with other prognostic variables, but SSEP recordings were not performed in four of them (18). In 65 subjects undergoing TH, seven did not have EEG, and an unspecified number lacked SSEP (8). A multicenter study on 390 patients pointed out that NSE and motor scores should be applied with caution in this setting; EEG was not described, the majority of patients lacked brainstem reflexes analysis, and SSEPs were performed in part during hypothermia (7).…”

“…To prevent hemolysis and false-positive test results, samples were handled manually and measured with an automated immunofluorescent assay (Thermo Scientific Brahms NSE Kryptor Immunoassay). In the vast majority of patients, at least one probe was collected at 48 hours, and for the present analysis, we considered the peak value, exploring cutoffs at 33 μg/L (17) and higher, to reach a 100% specificity for poor outcome (7)(8)(9).…”

“…Several recent studies have shown that TH and the related pharmacological sedation may influence some prognosticators commonly used in this setting as compared with patients not undergoing hypothermia. Particularly, motor response may recover over a longer time frame, and serum biomarkers such as neuron-specific enolase (NSE) can display cutoff levels for poor outcome considerably higher than previously thought (4)(5)(6)(7)(8)(9)(10). In contrast, electrophysiological investigations with electroencephalography (EEG), particularly focusing on continuous patterns and background reactivity during and after TH (11)(12)(13), and somatosensory-evoked potentials (SSEPs) (7) seem to provide greater prognostic accuracy in this setting.…”

Correlation between initial serum levels of lactate after return of spontaneous circulation and survival and neurological outcomes in patients who undergo therapeutic hypothermia after cardiac arrest

“…However, no single effective method for the prediction of outcome has been found. Several biological markers, such as the S-100B protein and neuron-specific enolase, have been demonstrated to be useful, and electroencephalography and neuroimaging, including brain computed tomography and magnetic resonance imaging, have been used by physicians to predict neurological outcomes [4][5][6][7][8][9][10][11][12] . However, these methods require serial check-ups and longer times to determine results.…”