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24 vs. 72 hours of hypothermia for pediatric cardiac arrest: A pilot, randomized controlled trial

  • Ericka L. Fink
    Correspondence
    Corresponding author at: Division of Pediatric Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Faculty Pavilion, 2nd floor, Pittsburgh, PA, 15224, USA.
    Affiliations
    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
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  • Robert S.B. Clark
    Affiliations
    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
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  • Rachel P. Berger
    Affiliations
    Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA

    Safar Center for Resuscitation Research, Pittsburgh, PA, USA
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  • Anthony Fabio
    Affiliations
    Department of Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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  • Derek C. Angus
    Affiliations
    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
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  • R. Scott Watson
    Affiliations
    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
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  • John J. Gianakas
    Affiliations
    Department of Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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  • Ashok Panigrahy
    Affiliations
    Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
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  • Clifton W. Callaway
    Affiliations
    Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Safar Center for Resuscitation Research, Pittsburgh, PA, USA
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  • Michael J. Bell
    Affiliations
    Pediatrics, Children’s National Medical Center, Washington, D.C. USA
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  • Patrick M. Kochanek
    Affiliations
    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
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      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.

      Abbreviations:

      HT (hypothermia), PICU (pediatric intensive care unit), RCT (randomized controlled trial), PCPCscore (Pediatric Cerebral Performance Category)

      Keywords

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