Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management

This study investigated the prognostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). The study included 85 comatose adult patients with OHCA who underwent TTM between May 2018 and December 2020. Serum NGAL and neuron-specific enolase (NSE) were measured at 24-h intervals until 72 h after return of spontaneous circulation (ROSC). The primary outcome was neurological status at 3 months after OHCA. Forty-nine patients (57.6%) had a poor neurological outcome; NGAL levels at all time points measured were significantly higher in these patients than in those with a good outcome (p<0.01). NGAL showed lower maximal sensitivity (95% CI) under a false-positive rate of 0% for the primary outcome compared with NSE (18.2% [95% CI 8.2-32.7] vs. 66.7% [95% CI 50.5-80.4]). Combination of NGAL with NSE at 48 h showed the highest sensitivity (69.1% [95% CI 52.9-82.4]) and had the highest AUC (0.91 [95% CI 0.81-0.96]) for a poor outcome. The prognostic performance of NGAL alone was inadequate at all time points. However, NGAL obtained at 24 and 48 h after ROSC showed improved sensitivity when combined with NSE. NGAL should be considered as an additional biomarker to improve accuracy for prognostication in these patients.

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Impact of low and high partial pressure of carbon dioxide on neuron-specific enolase derived from serum and cerebrospinal fluid in patients who underwent targeted temperature management after out-of-hospital cardiac arrest: A retrospective study

Resuscitation ◽

10.1016/j.resuscitation.2020.05.050 ◽

2020 ◽

Vol 153 ◽

pp. 79-87

Author(s):

Changshin Kang ◽

Yong Nam In ◽

Jung Soo Park ◽

Yeonho You ◽

Jin Hong Min ◽

...

Keyword(s):

Carbon Dioxide ◽

Cerebrospinal Fluid ◽

Cardiac Arrest ◽

Retrospective Study ◽

Partial Pressure ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management ◽

High Partial Pressure ◽

Hospital Cardiac Arrest

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Head computed tomography for prognostication of poor outcome in comatose patients after cardiac arrest and targeted temperature management

Resuscitation ◽

10.1016/j.resuscitation.2017.06.027 ◽

2017 ◽

Vol 119 ◽

pp. 89-94 ◽

Cited By ~ 28

Author(s):

Marion Moseby-Knappe ◽

Tommaso Pellis ◽

Irina Dragancea ◽

Hans Friberg ◽

Niklas Nielsen ◽

...

Keyword(s):

Computed Tomography ◽

Cardiac Arrest ◽

Targeted Temperature Management ◽

Temperature Management ◽

Poor Outcome ◽

Head Computed Tomography

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Arterial blood pressure during targeted temperature management after out-of-hospital cardiac arrest and association with brain injury and long-term cognitive function

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872619860804 ◽

2019 ◽

Vol 9 (4_suppl) ◽

pp. S122-S130 ◽

Cited By ~ 4

Author(s):

Johannes Grand ◽

Gisela Lilja ◽

Jesper Kjaergaard ◽

John Bro-Jeppesen ◽

Hans Friberg ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Cognitive Function ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management ◽

Impaired Cognitive Function ◽

Hospital Cardiac Arrest

Objectives: During targeted temperature management after out-of-hospital cardiac arrest infusion of vasoactive drugs is often needed to ensure cerebral perfusion pressure. This study investigated mean arterial pressure after out-of-hospital cardiac arrest and the association with brain injury and long-term cognitive function. Methods: Post-hoc analysis of patients surviving at least 48 hours in the biobank substudy of the targeted temperature management trial with available blood pressure data. Patients were stratified in three groups according to mean arterial pressure during targeted temperature management (4–28 hours after admission; <70 mmHg, 70–80 mmHg, >80 mmHg). A biomarker of brain injury, neuron-specific enolase, was measured and impaired cognitive function was defined as a mini-mental state examination score below 27 in 6-month survivors. Results: Of the 657 patients included in the present analysis, 154 (23%) had mean arterial pressure less than 70 mmHg, 288 (44%) had mean arterial pressure between 70 and 80 mmHg and 215 (33%) had mean arterial pressure greater than 80 mmHg. There were no statistically significant differences in survival ( P=0.35) or neuron-specific enolase levels ( P=0.12) between the groups. The level of target temperature did not statistically significantly interact with mean arterial pressure regarding neuron-specific enolase ( Pinteraction_MAP*TTM=0.58). In the subgroup of survivors with impaired cognitive function ( n=132) (35%) mean arterial pressure during targeted temperature management was significantly higher ( Pgroup=0.03). Conclusions: In a large cohort of comatose out-of-hospital cardiac arrest patients, low mean arterial pressure during targeted temperature management was not associated with higher neuron-specific enolase regardless of the level of target temperature (33°C or 36°C for 24 hours). In survivors with impaired cognitive function, mean arterial pressure during targeted temperature management was significantly higher.

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Prognostic Abilities of Serial Neuron-Specific Enolase and Lactate and their Combination in Cardiac Arrest Survivors During Targeted Temperature Management

Journal of Clinical Medicine ◽

10.3390/jcm9010159 ◽

2020 ◽

Vol 9 (1) ◽

pp. 159 ◽

Cited By ~ 1

Author(s):

Seung Mok Ryoo ◽

Youn-Jung Kim ◽

Chang Hwan Sohn ◽

Shin Ahn ◽

Dong Woo Seo ◽

...

Keyword(s):

Cardiac Arrest ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management ◽

Prognostic Information ◽

Neurological Outcomes ◽

Poor Neurological Outcome ◽

Serial Serum ◽

Lactate Levels ◽

Hospital Cardiac Arrest

This study aimed to determine the prognostic ability of serial neuron-specific enolase (NSE) and lactate in cardiac arrest survivors treated with targeted temperature management (TTM) and to investigate whether a combination of NSE and lactate could increase prognostic information. This observational, retrospective, cohort study was conducted between January 2013 and December 2018; data were extracted from an out-of-hospital cardiac arrest registry. We collected serial serum NSE and lactate levels during TTM. The primary endpoint was poor neurological outcome at 28 days from cardiac arrest. Of all 160 included patients, 98 (61.3%) had poor neurological outcomes. Areas under the curves (AUCs) for NSE were 0.797, 0.871, and 0.843 at 24, 48, and 72 h, respectively (all p < 0.05). AUCs for lactate were 0.669, 0.578, 0.634, and 0.620 at 0, 24, 48, and 72 h, respectively (all p < 0.05). Although the combination of initial lactate and NSE at 48 h yielded the highest discovered AUC (0.877) it was not statistically different from that for the 48 h NSE alone (p = 0.692). During the TTM, NSE at 48 h from cardiac arrest was the most robust prognostic marker in comatose cardiac arrest survivors. However, a combination of the 48 h NSE with lactate did not increase the prognostic information.

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Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2015.03.538 ◽

2015 ◽

Vol 65 (19) ◽

pp. 2104-2114 ◽

Cited By ~ 142

Author(s):

Pascal Stammet ◽

Olivier Collignon ◽

Christian Hassager ◽

Matthew P. Wise ◽

Jan Hovdenes ◽

...

Keyword(s):

Cardiac Arrest ◽

Neurological Outcome ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management ◽

Poor Neurological Outcome ◽

Hospital Cardiac Arrest

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Neuron-specific enolase and S-100b in prolonged targeted temperature management after cardiac arrest: A randomised study

Resuscitation ◽

10.1016/j.resuscitation.2017.11.052 ◽

2018 ◽

Vol 122 ◽

pp. 79-86 ◽

Cited By ~ 22

Author(s):

Christophe Henri Valdemar Duez ◽

Anders Morten Grejs ◽

Anni Nørgaard Jeppesen ◽

Anne Dilani Schrøder ◽

Eldar Søreide ◽

...

Keyword(s):

Cardiac Arrest ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management ◽

Randomised Study

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Prognostic value of neuron-specific enolase after cardiac arrest and targeted temperature management

Critical Care ◽

10.1186/cc14517 ◽

2015 ◽

Vol 19 (Suppl 1) ◽

pp. P437 ◽

Cited By ~ 1

Author(s):

K Streitberger ◽

C Leithner ◽

CJ Ploner ◽

C Storm

Keyword(s):

Cardiac Arrest ◽

Prognostic Value ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management

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Serum Neuron-Specific Enolase Thresholds for Predicting Postcardiac Arrest Outcome

Neurology ◽

10.1212/wnl.0000000000012967 ◽

2021 ◽

Vol 98 (1) ◽

pp. e62-e72

Author(s):

Kartavya Sharma ◽

Merin John ◽

Song Zhang ◽

Gary Gronseth

Keyword(s):

Cardiac Arrest ◽

Life Support ◽

Meta Analysis ◽

Neuron Specific Enolase ◽

Prediction Intervals ◽

Sensitivity Analyses ◽

Temperature Management ◽

Poor Outcome ◽

Multiple Thresholds ◽

Serum Neuron Specific Enolase

Background and ObjectivesTo determine thresholds of serum neuron-specific enolase (NSE) for prediction of poor outcome after cardiac arrest with >95% specificity using a unique method of multiple thresholds meta-analysis.MethodsData from a systematic review by the European Resuscitation Council (ERC 2014) were updated with literature searches from PubMed, Cochrane, and Scopus until August 2020. Search terms included the MeSH terms “heart arrest” and “biomarkers” and the text words “cardiac arrest,” “neuron specific enolase,” “coma” and “prognosis.” Cohort studies with comatose cardiac arrest survivors aged >16 years undergoing targeted temperature management (TTM) and NSE levels within 96 hours of resuscitation were included. Poor outcome was defined as cerebral performance category 3–5 at hospital discharge or later. Studies without extractable contingency tables were excluded. A multiple thresholds meta-analysis model was used to generate summary receiver operating characteristic curves for various time points. NSE thresholds (and 95% prediction intervals) for >95% specificity were calculated. Evidence appraisal was performed using a method adapted from the American Academy of Neurology grading criteria.ResultsData from 11 studies (n = 1,982) at 0–24 hours, 21 studies (n = 2,815) at 24–48 hours, and 13 studies (n = 2,557) at 48–72 hours was analyzed. Areas under the curve for prediction of poor outcomes were significantly larger at 24–48 hours and 48–72 hours compared to 0–24 hours (0.82 and 0.83 vs 0.64). Quality of evidence was very low for most studies because of the risk of incorporation bias—knowledge of NSE levels potentially influenced life support withdrawal decisions. To minimize falsely pessimistic predictions, NSE thresholds at the upper 95% limit of prediction intervals are reported. For prediction of poor outcome with specificity >95%, upper limits of the prediction interval for NSE were 70.4 ng/mL at 24–48 hours and 58.6 ng/mL at 48–72 hours. Sensitivity analyses excluding studies with inconsistent TTM use or different outcome criteria did not substantially alter the results.ConclusionsNSE thresholds for highly specific prediction of poor outcome are much higher than generally used. Future studies must minimize bias by masking treatment teams to the results of potential predictors and by prespecifying criteria for withdrawal of life support.

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