Ericka L Fink1, Robert S B Clark2, Rachel P Berger3, Anthony Fabio4, Derek C Angus5, R Scott Watson6, John J Gianakas4, Ashok Panigrahy7, Clifton W Callaway8, Michael J Bell9, Patrick M Kochanek2. 1. Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA; Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA; Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, PA, USA. Electronic address: finkel@ccm.upmc.edu. 2. Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA; Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA. 3. Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA. 4. Department of Epidemiology, University of Pittsburgh School of Medicine, 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. Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA USA. 7. Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. 8. Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, Pittsburgh, PA, USA. 9. Pediatrics, Children's National Medical Center, Washington, D.C. USA.
Abstract
AIM: Children surviving cardiac arrest (CA) lack proven neuroprotective therapies. The role of biomarkers in assessing response to interventions is unknown. We hypothesized that 72 versus 24 h of hypothermia (HT) would produce more favorable biomarker profiles after pediatric CA. METHODS: This single center pilot randomized trial tested HT (33 ± 1 °C) for 24 vs. 72 h in 34 children with CA. Children comatose after return of circulation aged 1 week to 17 years and treated with HT by their physician were eligible. Serum was collected twice daily on days 1-4 and once on day 7. Mortality was assessed at 6 months. RESULTS: Patient characteristics, baseline biomarker concentrations, and adverse events were similar between groups. Eight (47%) and 4 (24%) children died in the 24 h and 72 h groups, p = .3. Serum neuron specific enolase (NSE) concentration was increased in the 24 vs. 72 h group at 84 h-96 h (median [interquartile range] 47.7 [3.9, 79.9] vs. 1.4 [0.0, 11.1] ng/ml, p = .02) and on day 7 (18.2 [3.2, 74.0] vs. 2.6 [0.0, 12.8] ng/ml, p = .047). Serum S100b was increased in the 24 h vs. 72 h group at 12 h-24 h, 36 h-84 h, and on day 7, all p < 0.05. HT duration was associated with S100b (but not NSE or MBP) concentration on day 7 in multivariate analyses. CONCLUSION: Serum biomarkers show promise as theragnostic tools in pediatric CA. Our biomarker and safety data also suggest that 72 h duration after pediatric CA warrants additional exploration.
AIM: Children surviving cardiac arrest (CA) lack proven neuroprotective therapies. The role of biomarkers in assessing response to interventions is unknown. We hypothesized that 72 versus 24 h of hypothermia (HT) would produce more favorable biomarker profiles after pediatric CA. METHODS: This single center pilot randomized trial tested HT (33 ± 1 °C) for 24 vs. 72 h in 34 children with CA. Children comatose after return of circulation aged 1 week to 17 years and treated with HT by their physician were eligible. Serum was collected twice daily on days 1-4 and once on day 7. Mortality was assessed at 6 months. RESULTS: Patient characteristics, baseline biomarker concentrations, and adverse events were similar between groups. Eight (47%) and 4 (24%) children died in the 24 h and 72 h groups, p = .3. Serum neuron specific enolase (NSE) concentration was increased in the 24 vs. 72 h group at 84 h-96 h (median [interquartile range] 47.7 [3.9, 79.9] vs. 1.4 [0.0, 11.1] ng/ml, p = .02) and on day 7 (18.2 [3.2, 74.0] vs. 2.6 [0.0, 12.8] ng/ml, p = .047). Serum S100b was increased in the 24 h vs. 72 h group at 12 h-24 h, 36 h-84 h, and on day 7, all p < 0.05. HT duration was associated with S100b (but not NSE or MBP) concentration on day 7 in multivariate analyses. CONCLUSION: Serum biomarkers show promise as theragnostic tools in pediatric CA. Our biomarker and safety data also suggest that 72 h duration after pediatric CA warrants additional exploration.
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