Ericka L Fink1, Rachel P Berger2, Robert S B Clark3, R Scott Watson4, Derek C Angus5, Ashok Panigrahy6, Rudolph Richichi7, Clifton W Callaway8, Michael J Bell3, Stefania Mondello9, Ronald L Hayes10, Patrick M Kochanek3. 1. Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA; Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA. Electronic address: finkel@ccm.upmc.edu. 2. Child Advocacy, Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. 3. Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA. 4. Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, USA; Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, PA, USA. 5. Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, PA, USA. 6. Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. 7. Statistical Analysis and Measurement Consultants, Inc., Lanexa, VA, USA. 8. Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA. 9. Neurosciences, University of Messina, Messina, Italy. 10. Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA.
Abstract
INTRODUCTION: Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest. METHODS: Single center prospective study. Serum biomarkers were measured at 2 time points during the initial 72 h in children after cardiac arrest (n=19) and once in healthy children (controls, n=43). We recorded demographics and details of the cardiac arrest and resuscitation. We determined the associations between serum biomarker concentrations and Pediatric Cerebral Performance Category (PCPC) at 6 months (favorable (PCPC 1-3) or unfavorable (PCPC 4-6)). RESULTS: The initial assessment (time point 1) occurred at a median (IQR) of 10.5 (5.5-17.0)h and the second assessment (time point 2) at 59.0 (54.5-65.0)h post-cardiac arrest. Serum UCH-L1 was higher among children following cardiac arrest than among controls at both time points (p<0.05). Serum GFAP in subjects with unfavorable outcome was higher at time point 2 than in controls (p<0.05). Serum UCH-L1 at time point 1 (AUC 0.782) and both UCH-L1 and GFAP at time point 2 had good classification accuracy for outcome (AUC 0.822 and 0.796), p<0.05 for all. CONCLUSION: Preliminary data suggest that serum UCH-L1 and GFAP may be of use to prognosticate outcome after pediatric cardiac arrest at clinically-relevant time points and should be validated prospectively.
INTRODUCTION:Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest. METHODS: Single center prospective study. Serum biomarkers were measured at 2 time points during the initial 72 h in children after cardiac arrest (n=19) and once in healthy children (controls, n=43). We recorded demographics and details of the cardiac arrest and resuscitation. We determined the associations between serum biomarker concentrations and Pediatric Cerebral Performance Category (PCPC) at 6 months (favorable (PCPC 1-3) or unfavorable (PCPC 4-6)). RESULTS: The initial assessment (time point 1) occurred at a median (IQR) of 10.5 (5.5-17.0)h and the second assessment (time point 2) at 59.0 (54.5-65.0)h post-cardiac arrest. Serum UCH-L1 was higher among children following cardiac arrest than among controls at both time points (p<0.05). Serum GFAP in subjects with unfavorable outcome was higher at time point 2 than in controls (p<0.05). Serum UCH-L1 at time point 1 (AUC 0.782) and both UCH-L1 and GFAP at time point 2 had good classification accuracy for outcome (AUC 0.822 and 0.796), p<0.05 for all. CONCLUSION: Preliminary data suggest that serum UCH-L1 and GFAP may be of use to prognosticate outcome after pediatric cardiac arrest at clinically-relevant time points and should be validated prospectively.
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