Early Identification and Effective Management of Pediatric Sepsis

Integration of Metabolic and Inflammatory Mediator Profiles as a Potential Diagnostic Approach for Severe Sepsis in PICU

In patients diagnosed as sepsis on PICU admission, early and accurate identification of patients who will develop organ dysfunction (severe sepsis) is critical for effective management and positive outcome. A multiple marker approach would improve clinical utility compared with use of a single marker. The primary goal of this part of study is to define a combination of multiple markers, derived from novel biomarkers (nCD-64, IL-27, sTREM, HLA-DR, IL-10), metabolomics and routine clinical parameters, which could predict severe sepsis and determine the severity of disease.

We intend to enroll pediatric sepsis patients at four PICUs and divide them into two groups based on clinical outcomes: severe sepsis group (patients who progress into severe sepsis), sepsis group (patients who do not progress in to severe sepsis). We intend to perform predictive modeling using multivariable analyses of the novel biomarkers and derive a biomarker panel and algorithm for early diagnosis of severe sepsis. The predictive value of the biomarker panel for early identification of severe sepsis will be compared with established indices, such as PRISM III and pSOFA score.

Inclusion Criteria:

• The presence of at least two of the following four criteria, one of which must be abnormal temperature or leukocyte count:

  • Coreb temperature of >38.5°C or <36°C.
  • Tachycardia, defined as a mean heart rate >2 SD above normal for age in the absence of external stimulus, chronic drugs, or painful stimuli; or otherwise unexplained persistent elevation over a 0.5- to 4-hr time period OR for children <1 yr old: bradycardia, defined as a mean heart rate <10th percentile for age in the absence of external vagal stimulus, β-blocker drugs, or congenital heart disease; or otherwise unexplained persistent depression over a 0.5-hr time period.
  • Mean respiratory rate >2 SD above normal for age or mechanical ventilation for an acute process not related to underlying neuromuscular disease or the receipt of general anesthesia.
  • Leukocyte count elevated or depressed for age (not secondary to chemotherapy-induced leukopenia) or >10% immature neutrophils

• A suspected or proven (by positive culture, tissue stain, or polymerase chain reaction test) infection caused by any pathogen OR a clinical syndrome associated with a high probability of infection. Evidence of infection includes positive findings on clinical exam, imaging, or laboratory tests

Exclusion Criteria:

• patients without informed consent
• discharge within 48 hours