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Serum Biomarkers of Brain Injury to Classify Outcome After Pediatric Cardiac Arrest*

Fink, Ericka L. MD, MS1; Berger, Rachel P. MD, MPH2; Clark, Robert S. B. MD1; Watson, Robert S. MD, MPH1; Angus, Derek C. MD, MPH3; Richichi, Rudolph PhD4; Panigrahy, Ashok MD5; Callaway, Clifton W. MD, PhD6; Bell, Michael J. MD1; Kochanek, Patrick M. MD1

doi: 10.1097/01.ccm.0000435668.53188.80
Pediatric Critical Care

Objectives: 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.

Design: Prospective observational study.

Setting: Single tertiary pediatric hospital.

Patients: Forty-three children with cardiac arrest.

Interventions: None.

Measurements and Main 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.

Supplemental Digital Content is available in the text.

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.

* See also p. 753.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Dr. Fink’s institution received funding from the National Institutes of Health (NIH), Laerdal Foundation, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Fink received support for article research from the NIH. Dr. Fink is supported by K12 HD047349 from National Institute of Child Health and Human Development, K23 NS065132 from National Institute of Neurological Disorders and Stroke, and the Laerdal Foundation. Dr. Berger is employed by the University of Pittsburgh; provides expert testimony for any civil or criminal court which subpoenas her; received honoraria for giving Grand Rounds and keynote addresses at conferences; receives support for the development of education materials from the PA Department of Public Welfare; and received support for travel (sometimes gives Grand Rounds and other lectures at other institutions and receives reimbursement for travel expenses). Dr. Berger’s institution received grant support from the NIH, PA Department of Public Welfare, and the Casey Foundation and received support for development of educational presentations from PA Department of Public Welfare. Dr. Callaway has patents and royalties with Medtronic ERS, related to timing of defibrillation, licensed to a manufacturer of defibrillators. Dr. Callaway received grant support from the NIH (NIH-U01 Resuscitation Outcomes Consortium; NIH-U01 Neurological Emergencies Treatment Trials) and DoD (Testing and Validation of a Biomedical Detector Device); lectured for Sudden Cardiac Arrest Association, Take Heart America, Society for Critical Care Medicine, St. Mary’s Hospital—Seoul, South Korea, and the Hypothermia and Resuscitation Training Institute; received royalties from patents related to defibrillation; and received support for travel from the American Heart Association. Dr. Callaway’s institution has patent with Medtronic and received royalties from patents related to defibrillation. Dr. Kochanek’s institution received grant support from the NIH and the U.S. Army. Dr. Kochanek is a copatent holder on a biomarker patent to detect child abuse and received support for research from the NIH. Drs. Berger and Kochanek are provisional copatent holders on a biomarker panel for abusive head trauma in infants. This publication was also made possible by 5UL1 RR024153-04 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at Information on Re-engineering the Clinical Research Enterprise can be obtained from The remaining authors have disclosed that they do not have any potential conflicts of interest.

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© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins