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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 46  |  Issue : 2  |  Page : 133-138

Serum S100B protein as a prognostic biomarker for neurological outcome after in-hospital cardiac arrest in children


1 Department of Benha Children Specialized Hospital, Benha, Egypt
2 Department of Pediatrics, Tanta Faculty of Medicine, Tanta University, Tanta, Egypt
3 Department of Clinical Pathology, Tanta Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission29-Mar-2018
Date of Acceptance20-Jun-2018
Date of Web Publication31-Oct-2018

Correspondence Address:
Ahmed M Abd Elsalam
Benha Children Specialized Hospital, Benha, 13516
Egypt
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DOI: 10.4103/tmj.tmj_37_17

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  Abstract 


Background Survivors of cardiac arrest often require lengthy intensive care admission, rehabilitation, and ongoing treatment of chronic complications as a result of poor function outcomes. S100B protein has emerged as a candidate peripheral biomarker of blood–brain barrier permeability and central nervous system injury.
Aim This study aimed to evaluate the serum levels of S100B protein as a prognostic biomarker for predicting neurological outcome after in-hospital cardiac arrest and cardiopulmonary resuscitation (CPR) in children.
Patients and methods Thirty infants and children underwent CPR after in-hospital cardiac arrest; blood samples for the evaluation of S100B were drawn after 1 and 24 h after initiation of CPR. Neurological assessment for survivors was done 6 months after cardiac arrest using the cerebral performance category (CPC) score, which was used also immediately following CPR for all patients (including those who died 24 h after CPR). Fifteen healthy children were enrolled as a control group.
Results There was highly significant increase of serum S100B protein in postarrest patients at 1 and 24 h as compared with the control group (P<0.001); significant increase in patients at 1 h as compared with patients at 24 h (P<0.05); and highly significant increase of serum S100B protein in dead patients (n=25) as compared with survivors (n=5) (P<0.001). There was highly significant positive correlation between the duration of CPR and the CPC score and S100B protein level (P<0.001).The cutoff value of S100B protein at 1 h (as a prognostic biomarker) was 1430 ng/l with 76% sensitivity and 94% specificity, whereas the cutoff value of S100B protein at 24 h was 227 ng/l with 75% sensitivity and 91% specificity.
Conclusion S100B protein was potentially useful as a prognostic biomarker (with high sensitivity and specificity) for neurological outcome after cardiac arrest, as its levels significantly correlated with CPC score of the survivors 6 months after cardiac arrest and with the duration of CPR.

Keywords: biomarker, cardiac arrest, cerebral performance category score, cardiopulmonary resuscitation, S100B


How to cite this article:
Abd Elsalam AM, AboElezz AA, El-Bendary AS, Zoair AM. Serum S100B protein as a prognostic biomarker for neurological outcome after in-hospital cardiac arrest in children. Tanta Med J 2018;46:133-8

How to cite this URL:
Abd Elsalam AM, AboElezz AA, El-Bendary AS, Zoair AM. Serum S100B protein as a prognostic biomarker for neurological outcome after in-hospital cardiac arrest in children. Tanta Med J [serial online] 2018 [cited 2018 Dec 15];46:133-8. Available from: http://www.tdj.eg.net/text.asp?2018/46/2/133/244685




  Introduction Top


Cardiac arrest is defined as the absence of either palpable pulse or both pulse and respiration [1]. Hypoxic brain injury remains a leading cause of mortality and morbidity after cardiopulmonary arrest with return of spontaneous circulation (ROSC) [2]. Survivors of cardiac arrest often require lengthy intensive care admission, rehabilitation, and ongoing treatment of chronic complications as a result of poor function outcomes. However, correct prediction of such outcomes remains elusive [3].

S100B is a calcium-binding protein expressed mainly in human astroglial cells. As astroglia are as sensitive as neurons to hypoxia, serum S100B level has the potential to be a surrogate marker for neuronal damage to blood–brain barrier and it is eliminated by the kidneys [4]. It has an estimated biological half-life of 2 h, thus a constant elevation of S100B level in the serum reflects its continuous release from damaged tissue [5].

Over the last decade, S100B protein has emerged as a candidate peripheral biomarker of blood–brain barrier permeability and central nervous system (CNS) injury [6].

The objective of this work was to evaluate the serum levels of S100B protein as a prognostic biomarker for predicting neurological outcome after in-hospital cardiac arrest and cardiopulmonary resuscitation (CPR) in children.


  Patients and methods Top


This prospective study included 30 children with in-hospital cardiac arrest. They were chosen from those admitted at Tanta Pediatric Intensive Care Unit, Pediatric Department, Tanta University Hospital, in the period from August 2015 to November 2016.Their age ranged from 1 month to 4 years and they were 20 boys and 10 girls. Fifteen healthy children, matched for age and sex were enrolled as a control group. Their age ranged from 2 months to 4 years and they were 10 boys and five girls.

Inclusion criteria were infants and children aged from 1 month to 18 years after CPR from in-hospital cardiac arrest.

Exclusion criteria were infants and children whose arrest was triggered by acute hemorrhage, those with multiple congenital anomalies, syndromes, CNS diseases, children died before 24 h after cardiac arrest, or following open heart surgery.

Informed consent was taken from parents of all patients and the study was approved by the local ethics committee.

All postarrest children in this study were subjected to the following:
  1. CPR (Basic AND Advanced Life Support adapted from the American Heart Association, 2015).
  2. Complete history taking.
  3. Thorough clinical examination.
  4. Complete pediatric ICU care including routine management protocol.
  5. Serum S100B protein analysis:


Human S100B ELISA Kit is a sandwich enzyme immunoassay for the quantitative measurement of human S100B which is supplied and manufactured by Chongqing Biospes (7F, Bldg B, High-tech Venture Park, # 107 ErlangChuangye Rd, Jiulongpo District, Chongqing, 400039, China). It was measured after the first hour of cardiac arrest and after 24 h.

Neurological assessment for survivors was done 6 months after cardiac arrest using the cerebral performance category (CPC) score, which was used also immediately following CPR for all patients (including those who died 24 h after CPR).

CPC score definition [7]:
  1. Conscious and alert with normal function or only slight disability.
  2. Conscious and alert with moderate disability.
  3. Conscious with severe disability.
  4. Comatose or persistent vegetative state.
  5. Brain dead or death from other causes.


Statistical analysis

Statistical analysis was performed using the mean, SD, Student’s t-test, χ2-test, analysis of variance test, and correlation coefficient (r). Receiver operating characteristic curve was computed in SPSS (version 20) (International Business Machines Corp., New Orchard Road Armonk, New York, USA) [8].


  Results Top


The mean serum S100B protein in the control group was 101.25±3.545 ng/l (range: 97–107 ng/l), whereas the mean serum S100B protein in patients at 1 h was 1770.58±876.14 ng/l (range: 309–2676 ng/l) and at 24 h was 948.042±797.767 ng/l (range: 99.5–2225 ng/l), with highly significant increase of serum S100B protein in postarrested patients at 1 and 24 h as compared with the control group (P<0.001), and with significant increase in patients at 1 h as compared with the patients at 24 h (P<0.05) ([Figure 1] and [Table 1] and [Table 2]).
Figure 1 Comparison between serum S100B protein levels (ng/l) in patients at 1 and 24 h after cardiac arrest and the control group.

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Table 1 Demographic data of patients and control group

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Table 2 Comparison of the serum S100B protein levels (at 1 and 24 h) and different assessment scores between survived and dead patients

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There were significant differences between the causes of cardiac arrest regarding S100 B protein levels at 1 and 24 h, Glasgow Coma Scale (GCS) after ROSC, Sequential Organ Failure Assessment (SOFA) scoring, and Pediatric Risk of Mortality (PRISM) III score at 24 h (P<0.05),with the highest levels and worst scores in the sepsis group and lowest levels and best scores in the respiratory group ([Table 3]).
Table 3 Comparison between categories of the cause of cardiac arrest regarding serum S100B protein levels and different assessment scores

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There was highly significant positive correlation between the duration of CPR and the CPC score, and also there was highly significant positive correlation between the duration of CPR and S100B protein level (P<0.001) ([Figure 2],[Figure 3],[Figure 4]).
Figure 2 Relation between the duration of cardiopulmonary resuscitation (CPR) (min) and the cerebral performance category (CPC) score.

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Figure 3 Correlation between the duration of cardiopulmonary resuscitation (CPR) (min) and the cerebral performance category (CPC) score.

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Figure 4 Correlation between the duration of cardiopulmonary resuscitation (CPR) (min) and S100B protein level (ng/l).

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The cutoff value of S100B protein at 1 h (as a prognostic biomarker) was 1430 ng/l with 76% sensitivity and 94% specificity and the area under the curve was 0.857, whereas the cutoff value of S100B protein at 24 h was 227 ng/l with 75% sensitivity and 91% specificity and the area under the curve was 1.00 ([Table 4]).
Table 4 Cutoff values, sensitivity, specificity, and area under the curve of serum S100B protein (as a prognostic biomarker) and different assessment scores of patients

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  Discussion Top


Brain damage is one of the major causes of morbidity and mortality after cardiac arrest and CPR in hospitalized patients. Early assessment of brain damage and prediction of cerebral outcome after cardiac arrest may affect postarrest treatment strategies [9].

Identifying the neurological prognostic factors after CPR in patients with cardiac arrest as early and accurately as possible is urgently needed to determine the therapeutic strategies after successful CPR and avoid medical futility [10].

S100B protein has been found to be a promising marker for CNS injury. Owing to its estimated biological half-life of 2 h, elevated levels of S100B protein in patients with documented brain damage may reflect its release from the damaged tissue [11].

There are two hypotheses that S100B protein in patient’s serum increases after cardiac arrest. First, cardiac arrest may lead to inadequate blood flow perfusion for the brain tissue which causes indirect brain damage. Second, the injury of myocardial tissue caused by cardiac arrest will release S100B protein. Researchers are in favor of the first hypothesis because the CNS is the major system generating and releasing the S100B protein in vivo. Furthermore, the limited content of the S100B protein in myocardial cells indicates that the S100B protein cannot be a major factor [12],[13].

In our study, serum S100B protein was significantly higher among patients (at 1 and 24 h after cardiac arrest) than the control group, and this is in agreement with the studies by Delgado et al. [14] and Martins et al. [15], who reported that S100B levels were higher in critically ill patients than in healthy control group and there was significant difference between survivor and nonsurvivor levels of S100B protein. Moreover, Kleindienst et al. [16] have reported that the secretion of S100B protein can be enhanced by a number of factors and/or conditions in case of brain damage as large amounts of S100B protein are being passively released with a fraction of protein being diffused into the cerebrospinal fluid and blood.

The current study has shown that poor prognosis or death was significantly higher among patients with serum S100 B protein level 1430 ng/l or higher at 1 h (sensitivity 76%, specificity 94%) and 227 ng/l or higher at 24 h (sensitivity 75%, specificity 91%) after cardiac arrest, concomitant with GCS of 8 or less, SOFA scoring of 40 or more, and PRISM III score of 9 or more at 24 h. This is in agreement with the studies by Pfeifer et al. [9] and Helánová et al. [17].

In this study, neurological assessment was done after 6 months for survivors using the CPC score, showing bad outcome or death in children with high postcardiac arrest S100B protein levels and long duration CPR and good outcome in children with low postcardiac arrest S100B protein levels and short duration CPR. This is in agreement with Böttiger et al. [11], who have reported that the duration of cardiac arrest and cerebral ischemia in these patients might have been longer than in those without brain damage.

Moreover, Pfeifer et al. [9] have measured S100B protein for the evaluation of cerebral damage after cardiac arrest, and reported that biochemical markers suggestive of cerebral damage after cardiac arrest may serve as a hallmark for future patient monitoring, which was highlighted by the fact that the combination of GCS with the neuroprotein levels (GCS<6 and S100B≥1500 ng/l) leads to a higher sensitivity and prognostic value for poor neurological outcome than single markers alone, and this is in accordance with the results of our study as we used a combination of different assessment scores (GCS, SOFA, PRISM III).

According to our study, there was positive correlation between the duration of CPR and the neurological outcome, evaluated via the CPC score, showing that good outcome occurred in patients who received CPR in less than 30 min. This is in agreement with Rosén et al. [18], who reported that the patient group with good outcome had significantly shorter time of CPR.

The present study reported that the cause of cardiac arrest affected the level of the S100B protein and the outcome, because all survivors who had a cardiac arrest due to respiratory cause had low S100B protein levels (323.4±13.1 ng/l at 1 h and 134.1±47.4 ng/l at 24 h), whereas high S100B protein levels were noted in the sepsis group (2188.9±66 ng/l at 1 h and 1466±74 ng/l at 24 h), with bad outcome and death.

Our study has also shown that children with poor prognosis who died had mean values of GCS after ROSC 6.600, SOFA scoring at 11.20, PRISM III score of 47.10 at 24 h, and their S100B protein level at 1 h was 2060.50 ng/l and at 24 h was 1109.10 ng/l, with significant differences as compared with survivors.

This is in agreement with the studies by Ohtaki et al. [19] and Bouvier et al. [20], who found significant correlation between S100B and the severity of brain injury determined by GCS. On the other hand, Cakir et al. [21] have found nonsignificant correlation between S100B and GCS.


  Conclusion Top


The present study has shown that S100B protein was potentially useful as a prognostic biomarker (with high sensitivity and specificity) for neurological outcome after in-hospital cardiac arrest, as its levels significantly correlated with CPC score of the survivors 6 months after cardiac arrest and with the duration of CPR.

Study limitations

The limitations of the study are the relatively small sample size and the lack of long-term follow-up using more than one biomarker, and neuroimaging studies that are required to evaluate the neurodevelopmental outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Abu-Sultaneh S, Hehir DA, Murkowski K, Ghanayem NS, Liedel J, Hoffmann RG et al. Changes in cerebral oxygen saturation correlate with S100B in infants undergoing cardiac surgery with cardiopulmonary bypass. Pediatr Crit Care Med 2014; 15:219–228.  Back to cited text no. 6
    
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Marginean IC, Stanca DM, Vacaras V, Soritau O, Margiean M, Muresanu DF. Plasma S100B level after acute spontaneous intracerebral hemorrhage. Stroke 2006; 37:2837–2839.  Back to cited text no. 14
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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