title: Serum biomarkers of brain injury to classify outcome after pediatric cardiac arrest*.
abstract: OBJECTIVE
  Morbidity and mortality in children with cardiac arrest largely result from neurologic injury. Serum biomarkers of brain injury can potentially measure injury to neurons (neuron-specific enolase), astrocytes (S100b), and axons (myelin basic protein). We hypothesized that serum biomarkers can be used to classify outcome from pediatric cardiac arrest.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  Single tertiary pediatric hospital.
  
  
  METHODS
  Forty-three children with cardiac arrest.
  
  
  METHODS
  None.
  
  
  RESULTS
  We measured serum neuron-specific enolase, S100b, and myelin basic protein on days 1-4 and 7 after cardiac arrest. We recorded demographics, details of the cardiac arrest and resuscitation, and Pediatric Cerebral Performance Category at hospital discharge and 6 months. We analyzed the association of biomarker levels at 24, 48, and 72 hours with favorable (Pediatric Cerebral Performance Category 1-3) or unfavorable (Pediatric Cerebral Performance Category 4-6) outcome and mortality. Forty-three children (49% female; mean age of 5.9 ± 6.3) were enrolled and 17 (40%) died. Serum S100b concentrations peaked earliest, followed by neuron-specific enolase and finally myelin basic protein. Serum neuron-specific enolase and S100b concentrations were increased in the unfavorable versus favorable outcome group and in subjects who died at all time points (all p < 0.05). Serum myelin basic protein at 24 and 72 hours correctly classified survival but not good versus poor outcome. Using best specificity, serum S100b and neuron-specific enolase had optimal positive and negative predictive values at 24 hours to classify both favorable versus unfavorable outcome and survival, whereas serum myelin basic protein's best accuracy occurred at 48 hours. Receiver operator curves for serum S100b and neuron-specific enolase to classify favorable versus unfavorable outcome at 6 months were superior to clinical variables.
  
  
  CONCLUSIONS
  Preliminary data show that serum S100b, neuron-specific enolase, and myelin basic protein may aid in outcome classification of children surviving cardiac arrest.
authors.affiliation: 1Department of Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. 2Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. 3Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA. 4Statistical Analysis and Measurement Consultants, Inc., Lanexa, VA. 5Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. 6Department of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Ericka L
authors.initials: EL
authors.lastname: Fink
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Berger
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Robert S
authors.initials: RS
authors.lastname: Watson
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.forename: Rudolph
authors.initials: R
authors.lastname: Richichi
authors.forename: Ashok
authors.initials: A
authors.lastname: Panigrahy
authors.forename: Clifton W
authors.initials: CW
authors.lastname: Callaway
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bell
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood* / Q000209:etiology / Q000401:mortality*; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D006323:Heart Arrest / Q000097:blood* / Q000150:complications / Q000401:mortality* / Q000628:therapy; D017052:Hospital Mortality; D006776:Hospitals, Pediatric; D006801:Humans; D015278:Intensive Care Units, Pediatric; D008297:Male; D004676:Myelin Basic Protein / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D010751:Phosphopyruvate Hydratase