Prognostication Biomarkers in Pediatric Cardiac Arrest
Condition: Cardiac Arrest
MeSH terms: Heart Arrest
Study type: Observational

Summary: 
      This multicenter study will validate a panel of serum, imaging, and clinical biomarkers to
      classify patient outcome early after out-of-hospital pediatric cardiac arrest. Results are
      expected to have a positive and immediate impact in advancing clinical care and outcomes for
      these children. This work will provide clinicians, families, and researchers with superior
      tools to assess the severity of brain injury early after resuscitation in order to know who
      is at risk of brain injury and may benefit from neuroprotective interventions, to monitor
      response to these interventions, to plan rehabilitation strategy, and to optimize the design
      of research studies that test novel interventions to improve neurological outcome after
      cardiac arrest.
    

Detailed description: 
      Children with cardiac arrest (CA) have mortality rates of 50-90%, largely due to neurological
      failure as part of the post-resuscitation syndrome. There is a critical gap of knowledge and
      tools to accurately classify outcome after pediatric CA. Physical examination and laboratory
      testing inadequately assess the severity of neurologic injury and outcome. Hazards of
      misclassification include risking adverse effects from ineffective therapies and
      non-treatment of ostensibly well patients who later are found to have neurologic deficits.
      Early and accurate identification of the eventual severity of neurologic injury would allow
      for timely neuroprotective interventions and/or more targeted testing of new therapies in
      specific risk populations. The long term objective is to improve the neurological outcome of
      children surviving CA. In this study, investigators will model and validate serum and imaging
      biomarkers of brain injury with empirical support, and assess their accuracy together with
      clinical variables in classifying outcome after pediatric CA. The central hypothesis is that
      serum and imaging biomarkers of brain injury, together with clinical variables, will
      critically aid in the early classification of favorable outcome after pediatric CA (Vineland
      Adaptive Behavior Scales score [VABS] > 70) 1 year after pediatric CA in a multicenter
      prospective study (8-12 centers and 248 subjects). Strong preliminary data supports this
      hypothesis, and biomarkers will be tested for outcome classification accuracy in the
      following 3 specific aims:

      Aim 1) Serum biomarkers of neuronal (neuron specific enolase and ubiquitin carboxy-terminal
      hydrolase-L1) and glial injury (S100b and glial fibrillary acidic protein) Aim 2) Regional
      (occipital-parietal cortex, basal ganglia, and thalamus) brain MRI (T1/T2 and
      diffusion-weighted imaging) and magnetic resonance spectroscopy (MRS) biomarkers of neuronal
      injury (N-acetyl-aspartate) and energy failure (lactate) Aim 3 will model the combination of
      strong serum and imaging biomarkers of brain injury with clinical variables. We will assess
      serum biomarkers of brain mitochondrial injury with potential for novel therapeutic targets
      (cardiolipin and oxidized cardiolipin) in an exploratory aim. This proposed research is
      innovative, because a combined panel of serum and imaging biomarkers with clinical variables
      to accurately classify outcome after pediatric CA will be prospectively developed and
      optimized. These proposed aims leverage recent pilot successes and should generate accurate
      and reliable models of biomarkers that markedly improve post-resuscitation clinical care in
      children after CA. Furthermore, these results are expected to have a positive impact in
      advancing neurocritical care for these children, with forthcoming development of a serum
      biomarker point of care test and biomarker panels that will accurately classify risk of
      unfavorable outcome for clinicians and researchers needing to stratify by severity of injury,
      to monitor response to therapy, and ultimately to assist in their rehabilitation and
      recovery.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children with cardiac arrest
      
Biospecimen description: 
      Serum and blood clot stored for future biomarker and DNA analysis