Kate F Kernan1, Rachel P Berger2, Robert S B Clark3, R Scott Watson4, Derek C Angus5, Ashok Panigrahy6, Clifton W Callaway7, Michael J Bell8, Patrick M Kochanek3, Ericka L Fink3, Dennis W Simon9. 1. Critical Care Medicine UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States; Children's Neuroscience Institute, University of Pittsburgh, Pittsburgh, PA, United States. 2. Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States. 3. Critical Care Medicine UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Children's Neuroscience Institute, University of Pittsburgh, Pittsburgh, PA, United States. 4. Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States; Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, United States. 5. Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, United States. 6. Radiology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States. 7. Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, United States; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 8. Division of Pediatric Critical Care Medicine, Children's National Hospital, Washington, DC, United States. 9. Critical Care Medicine UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Children's Neuroscience Institute, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: simondw2@upmc.edu.
Abstract
AIM: We hypothesized that serum biomarkers of inflammation including chemokine, cytokine, pituitary hormones, and growth factors following cardiac arrest in children would independently associate with 6-month neurologic outcome. METHODS: In this prospective observational single center study of children with in-hospital and out-of-hospital cardiac arrest surviving to intensive care unit admission, serum was obtained twice per 24 h period between 0 h and 96 h and once at approximately 196 h post-cardiac arrest. Inflammatory mediators, hormones, and growth factors were analyzed by Luminex Multiplex Bead Immunoassay. We recorded demographics, resuscitation characteristics, and Pediatric Cerebral Performance Category (PCPC) at 6 months. We analyzed the association and area under the curve (AUC) of biomarker levels with favorable (PCPC 1-3) or unfavorable (PCPC 4-6, or >1 increase from baseline) outcome. RESULTS: Forty-two children (50% female; median age of 2.5 [IQR: 0.4-10.2]) were enrolled and 18 (42%) died prior to 6-month follow up. Receiver operator curves for initial levels of ciliary neurotrophic factor (CNTF, AUC 0.84, 95% CI 0.73-0.96, p < 0.001) and interleukin (IL-17, AUC 0.84, 95% CI 0.73-0.97, p < 0.001) best classified favorable versus unfavorable 6-month outcome. In multivariable analysis, initial levels of CNTF and IL-17 remained associated with 6-month PCPC. Peak levels of interferon-γ-inducible protein 10 (IP-10), CNTF, and hepatocyte growth factor (HGF) were also independently associated with outcome. CONCLUSION: Increased serum concentrations of CNTF and IL-17 associated with unfavorable 6-month neurologic outcome of children surviving cardiac arrest. Further investigation of the prognostic utility and roles of CNTF and IL-17 in the pathophysiology of post-cardiac arrest syndrome are warranted. This project is registered with clinicaltrials.gov (NCT00797680) as "Duration of Hypothermia for Neuroprotection after Pediatric Cardiac Arrest: A Randomized, Controlled Trial".
AIM: We hypothesized that serum biomarkers of inflammation including chemokine, cytokine, pituitary hormones, and growth factors following cardiac arrest in children would independently associate with 6-month neurologic outcome. METHODS: In this prospective observational single center study of children with in-hospital and out-of-hospital cardiac arrest surviving to intensive care unit admission, serum was obtained twice per 24 h period between 0 h and 96 h and once at approximately 196 h post-cardiac arrest. Inflammatory mediators, hormones, and growth factors were analyzed by Luminex Multiplex Bead Immunoassay. We recorded demographics, resuscitation characteristics, and Pediatric Cerebral Performance Category (PCPC) at 6 months. We analyzed the association and area under the curve (AUC) of biomarker levels with favorable (PCPC 1-3) or unfavorable (PCPC 4-6, or >1 increase from baseline) outcome. RESULTS: Forty-two children (50% female; median age of 2.5 [IQR: 0.4-10.2]) were enrolled and 18 (42%) died prior to 6-month follow up. Receiver operator curves for initial levels of ciliary neurotrophic factor (CNTF, AUC 0.84, 95% CI 0.73-0.96, p < 0.001) and interleukin (IL-17, AUC 0.84, 95% CI 0.73-0.97, p < 0.001) best classified favorable versus unfavorable 6-month outcome. In multivariable analysis, initial levels of CNTF and IL-17 remained associated with 6-month PCPC. Peak levels of interferon-γ-inducible protein 10 (IP-10), CNTF, and hepatocyte growth factor (HGF) were also independently associated with outcome. CONCLUSION: Increased serum concentrations of CNTF and IL-17 associated with unfavorable 6-month neurologic outcome of children surviving cardiac arrest. Further investigation of the prognostic utility and roles of CNTF and IL-17 in the pathophysiology of post-cardiac arrest syndrome are warranted. This project is registered with clinicaltrials.gov (NCT00797680) as "Duration of Hypothermia for Neuroprotection after Pediatric Cardiac Arrest: A Randomized, Controlled Trial".
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