Clinical Protocol Validation to Identify Prognostic Markers for Critical Care Pediatric Patients

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.