Genotypes and Phenotypes in Pediatric SIRS and Sepsis
Condition: Systemic Inflammatory Response Syndrome (SIRS); Sepsis
MeSH terms: Sepsis; Toxemia; Systemic Inflammatory Response Syndrome
Study type: Observational

Summary: 
      The aim of this investigation is to longitudinally quantify host gene expression and serum
      proteins in children with infectious and non-infectious SIRS. The investigators hypothesize
      that children with non-infectious SIRS, with bacterial infection associated SIRS, or with
      viral infection associated SIRS will exhibit distinct patterns of host gene expression and
      serum proteins. The investigators further hypothesize that it should be possible to discover
      sets of mRNA or protein biomarkers that will permit unambiguous diagnosis of non-infectious
      SIRS, SIRS associated with bacterial infection, and SIRS associated with viral infection.
    

Detailed description: 
      The investigators will undertake a proof-of-concept, pilot, prospective, observational trial
      that aims to recruit ~90 children from the Seattle Children's Hospital Pediatric Intensive
      Care Unit (PICU) and Cardiac Intensive Care Unit (CICU). The study will plan to recruit 30
      children who are scheduled for surgery to repair congenital cardiac malformations, 15 - 25
      immunocompetent children with culture positive sepsis, and 15 - 25 immunocompromised children
      with culture positive sepsis, and 30-40 children who are polymerase chain reaction (PCR)
      positive for viral respiratory pathogens (RSV, influenza, parainfluenza, rhinovirus, etc),
      and who meet the eligibility criteria. In total, accounting for culture negative bacterial
      sepsis (estimated 40%), the investigators plan to enroll 50 children with sepsis, 30-40 with
      viral sepsis, and 20 children undergoing surgery for congenital heart disease.

      Demographic data will be collected at the time of ICU admission. Illness severity will be
      quantified by PRISM III and day 1 PELOD scores. Additional measures of sepsis severity will
      include oxygenation index, saturation index and duration of mechanical ventilation,
      vasoactive inotropic score and duration of vasoactive-inotropic support and highest serum
      creatinine on day 1. Resource utilization will be measured as PICU and hospital duration of
      stay.

      For all children enrolled in the study, blood samples will be obtained on study days 1, 2 and
      3. For children with sepsis, if cultures remain sterile or PCR negative, no additional
      research blood samples will be obtained. For children with sepsis and a positive culture or
      positive PCR by study day 3, additional blood samples will be obtained on the day of PICU
      discharge.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        INSI group: children who had congenital cardiac defect corrective surgery requiring
        cardiopulmonary bypass, known to induce an INSI response for ~24 hours thereafter. All
        children in this group were immune competent and culture negative.

        CSSS group: children with confirmed or highly suspected infection (microbial culture
        orders, antimicrobial prescription), SIRS criteria (including fever/hypothermia and
        leukocytosis/leukopenia), and at least cardiovascular ± pulmonary organ dysfunction.

        Viral Infection group: children with severe respiratory dysfunction in the presence of PCR
        -documented viral infection.
      
Biospecimen description: 
      Type 1: whole blood (2.5 mL) collected daily into PAXgene Blood RNA tube (PreAnalytiX, Ref #
      7621650). Type 2: whole blood (1 mL) collected daily into serum separation tube (BD
      Vacutainer SST™ Tube with Silica Clot Activator, Polymer Gel, Silicone-Coated Interior, Ref #
      367983). Type 3: whole blood (1 mL) collected on day 1 into lavender top Vacutainer (BD
      Vacutainer, lavender top, K2 EDTA 7.2mg, Ref # 367861).
    
Keywords: inflammation; sepsis; pediatric; transcripts; serum proteins; cardiopulmonary bypass