Dataset Information

Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry.

ABSTRACT:

Background

Patients after out-of-hospital cardiac arrest (OHCA) are at increased risk for mortality and poor neurological outcome. We assessed the additive impact of interleukin 6 (IL-6) at admission to neuron-specific enolase (NSE) at day 3 for prognosis of 30-day mortality and long-term neurological outcome in OHCA patients.

Methods

A total of 217 patients from the HAnnover COoling REgistry with return of spontaneous circulation (ROSC) after OHCA and IL-6 measurement immediately after admission during 2017-2020 were included to investigate the prognostic value and importance of IL-6 in addition to NSE obtained on day 3. Poor neurological outcome was defined by cerebral performance category (CPC) ≥ 3 after 6 months.

Results

Patients with poor outcome showed higher IL-6 values (30-day mortality: 2,224 ± 524 ng/l vs 186 ± 15 ng/l, p < 0.001; CPC ≥ 3 at 6 months: 1,440 ± 331 ng/l vs 180 ± 24 ng/l, p < 0.001). IL-6 was an independent predictor of mortality (HR = 1.013/ng/l; 95% CI 1.007-1.019; p < 0.001) and poor neurological outcome (HR = 1.004/ng/l; 95% CI 1.001-1.007; p = 0.036). In ROC-analysis, AUC for IL-6 was 0.98 (95% CI 0.96-0.99) for mortality, but only 0.76 (95% CI 0.68-0.84) for poor neurological outcome. The determined cut-off value for IL-6 was 431 ng/l for mortality (NPV 89.2%). In patients with IL-6 > 431 ng/l, the combination with NSE < 46 μg/l optimally identified those individuals with potential for good neurological outcome (CPC ≤ 2).

Conclusion

Elevated IL-6 levels at admission after ROSC were closely associated with 30-day mortality. The combination of IL-6 and NSE provided clinically important additive information for predict poor neurological outcome at 6 months.

SUBMITTER: Akin M

PROVIDER: S-EPMC9194609 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry.

Akin Muharrem M Sieweke Jan-Thorben JT Garcheva Vera V Martinez Carolina Sanchez CS Adel John J Plank Pia P Zandian Paris P Sühs Kurt-Wolfram KW Bauersachs Johann J Schäfer Andreas A

Frontiers in cardiovascular medicine 20220531

<h4>Background</h4>Patients after out-of-hospital cardiac arrest (OHCA) are at increased risk for mortality and poor neurological outcome. We assessed the additive impact of interleukin 6 (IL-6) at admission to neuron-specific enolase (NSE) at day 3 for prognosis of 30-day mortality and long-term neurological outcome in OHCA patients.<h4>Methods</h4>A total of 217 patients from the HAnnover COoling REgistry with return of spontaneous circulation (ROSC) after OHCA and IL-6 measurement immediately ...[more]

PMID: 35711345

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Project description:BackgroundSerum neuron-specific enolase (NSE) is the only recommended biomarker for multimodal prognostication in postcardiac arrest patients, but low sensitivity of absolute NSE threshold limits its utility. This study aimed to evaluate the prognostic performance of serum NSE for poor neurologic outcome in out-of-hospital cardiac arrest (OHCA) survivors based on their initial rhythm and to determine the NSE cutoff values with false positive rate (FPR) < 1% for each group.MethodsThis study included OHCA survivors who received targeted temperature management (TTM) and had serum NSE levels measured at 48 h after return of spontaneous circulation in the Korean Hypothermia Network, a prospective multicenter registry from 22 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. The primary outcome was poor outcome at 6 month, defined as a cerebral performance category of 3-5.ResultsOf 623 patients who underwent TTM with NSE measured 48 h after the return of spontaneous circulation, 245 had an initial shockable rhythm. Median NSE level was significantly higher in the non-shockable group than in the shockable group (104.6 [40.6-228.4] vs. 25.9 [16.7-53.4] ng/mL, P < 0.001). Prognostic performance of NSE assessed by area under the receiver operating characteristic curve to predict poor outcome was significantly higher in the non-shockable group than in the shockable group (0.92 vs 0.86). NSE cutoff values with an FPR < 1% in the non-shockable and shockable groups were 69.3 (sensitivity of 42.1%) and 102.7 ng/mL (sensitivity of 76%), respectively.ConclusionNSE prognostic performance and its cutoff values with FPR < 1% for predicting poor outcome in OHCA survivors who underwent TTM differed between shockable and non-shockable rhythms, suggesting postcardiac arrest survivor heterogeneity. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02827422.

Project description:This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30?minutes.The ROSC (n?=?26) and non-ROSC (n?=?26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0-2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07-0.94, P?=?0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93-0.99, P?=?0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r?=?0.31, P?=?0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.

Project description:BackgroundPrognostication after cardiac arrest (CA) needs a multimodal approach, but the optimal method is not known. We tested the hypothesis that the combination of neuron-specific enolase (NSE) and neuroimaging could improve outcome prediction after CA treated with targeted temperature management (TTM).MethodsA retrospective observational cohort study was performed on patients who underwent at least one NSE measurement between 48 and 72 hr; received both a brain computed tomography (CT) scan within 24 hr and diffusion-weighted magnetic resonance imaging (DW-MRI) within 7 days after return of spontaneous circulation (ROSC); and were treated with TTM after out-of-hospital CA between 2009 and 2017 at the Seoul St. Mary's Hospital in Korea. The primary outcome was a poor neurological outcome at 6 months after CA, defined as a cerebral performance category of 3-5.ResultsA total of 109 subjects underwent all three tests and were ultimately included in this study. Thirty-four subjects (31.2%) experienced good neurological outcomes at 6 months after CA. The gray matter to white matter attenuation ratio (GWR) was weakly correlated with the mean apparent diffusion coefficient (ADC), PV400 and NSE (Spearman's rho: 0.359, -0.362 and -0.263, respectively). NSE was strongly correlated with the mean ADC and PV400 (Spearman's rho: -0.623 and 0.666, respectively). Serum NSE had the highest predictive value among the single parameters (area under the curve (AUC) 0.912, sensitivity 70.7% for maintaining 100% specificity). The combination of a DWI parameter (mean ADC or PV400) and NSE had better prognostic performance than the combination of the CT parameter (GWR) and NSE. The addition of the GWR to a DWI parameter and NSE did not improve the prediction of neurological outcomes.ConclusionThe GWR (≤ 24 hr) is weakly correlated with the mean ADC (≤ 7 days) and NSE (highest between 48 and 72 hr). The combination of a DWI parameter and NSE has better prognostic performance than the combination of the GWR and NSE. The addition of the GWR to a DWI parameter and NSE does not improve the prediction of neurological outcomes after CA treatment with TTM.

Project description:BackgroundPrediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population.MethodsThis study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5.ResultsA total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58-0.84 versus 0.83).ConclusionNSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials. While combinations of serial NSE measurements may provide an increase in overall prognostic information, it is unclear whether actual clinical prognostication with low false-positive rates is improved by application of serial measurements in persistently unconscious patients. The findings of this study should be confirmed in another prospective cohort.Trial registrationNCT01020916.

Project description: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.

Dataset Information

Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry.

Background

Methods

Results

Conclusion

Publications

Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry.

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