Clinical Protocol Validation to Identify Prognostic Markers for Critical Care Pediatric Patients
Condition: Sepsis
Study type: Observational

Summary: 
      The purpose of this study is to monitor the respiratory, metabolic and nutritional status of
      critically ill pediatric patients undergoing mechanical ventilation and to correlate the
      clinical and physiopathological findings with inflammatory activity measurements in order to
      identify prognostic biomarkers.
    

Detailed description: 
      Background: Acute Respiratory Distress Syndrome (ARDS) is a frequent cause of respiratory
      failure in the pediatric intensive care unit (ICU). Bedside respiratory and metabolic
      monitoring has reduced both morbidity and mortality of children with ARDS in the ICU, and
      allowed precise evaluation of the gravity of ARDS in individual patients. Recent advances
      indicate that some ARDS patients present specific, genetically determined profiles of
      cytokine production, but it is unclear how these relate to systemic inflammation and the
      gravity of ARDS. It is necessary to define the correlation between genotype, systemic
      inflammation and prognosis in this group of patients, ir order to define whether they should
      be targeted for more aggressive anti-inflammatory and immunomodulatory therapy.

      Objectives: 1) To evaluate metabolic expenditure,bioelectrical impedance (BIA) and
      respiratory function in critically ill children undergoing mechanical ventilation. 2) To
      correlate the metabolic and respiratory parameters with duration of mechanical ventilation,
      weaning, nutritional status,Phase angle (PA) of BIA, PRISMI and PIM 2 scores in the same
      children.3) To determine the presence of polymorphisms in the genes for TNF-alfa (- 308 and
      -863), IL-1ra, IL-6, MIF, LTalfa, il-10 and CD14 in the same children. 4) To define
      functional parameters of systemic inflammation, including plasma levels of TNF-alfa, IL-1ra,
      IL-6 and translocation of NF-kappa B in the same children. 5) To correlate genomic and
      immunological data with PRISM I and PIM 2 scores, PA and mortality.

      Methodology: 1) Study Design: A cohort of patients undergoing mechanical ventilation will be
      submitted to metabolic and respiratory monitoring, and to monitoring of systemic inflammation
      by measurement of plasma cytokines and NF-kB translocation in peripheral blood leukocytes; a
      cross-sectional study of cytokine gene polymorphisms will be carried out int hte same
      population. 2)Subjects: 1000 children, aged 1 mo to 17 yr. Group A: 200 children with ARDS;
      Group B: 400 children with respiratory failure unrelated to ARDS; Group C (controls): 400
      children undergoing preoperatory exams at surgical ward for elective surgery. 3) Methods:
      Metabolic monitoring: determination of VCO2, VO2, RQ, EEM through indirect calorimetry.
      Bioelectrical impedance: determination of resistance, reactance and phase angle. Respiratory
      monitoring: determination of respiratory parameters through capnography, pulse oxymetry, and
      assessment of respiratory mechanics. Genomic analysis: restriction site mapping and
      allele-specific amplification by PCR. Immunological evaluation: measurement of plasma
      cytokines by luminex multiple essays and analysis of NF-kB activation.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        children in intensive care unit
      
Biospecimen description: 
      DNA extracts from blood or oral swab
    
Keywords: PICU; BIA; Phase angle; RQ; EEM; Compliance; Resistance; Curves; Polymorphisms; NF-kappa B; Scores; PIM 2; PRISM I