Immune System Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT: Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions. OBJECTIVE: To evaluate evidence for criteria that define immune system dysfunction in critically ill children and associations with adverse outcomes and develop consensus criteria for the diagnosis of immune system dysfunction in critically ill children. DATA SOURCES: We conducted electronic searches of PubMed and Embase from January 1992 to January 2020, using medical subject heading terms and text words to define immune system dysfunction and outcomes of interest. STUDY SELECTION: Studies of critically ill children with an abnormality in leukocyte numbers or function that is currently measurable in the clinical laboratory in which researchers assessed patient-centered outcomes were included. Studies of adults or premature infants, animal studies, reviews and commentaries, case series (≤10 subjects), and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION: Data were abstracted from eligible studies into a standard data extraction form along with risk of bias assessment by a task force member. RESULTS: We identified the following criteria for immune system dysfunction: (1) peripheral absolute neutrophil count <500 cells/μL, (2) peripheral absolute lymphocyte count <1000 cells/μL, (3) reduction in CD4⁺ lymphocyte count or percentage of total lymphocytes below age-specific thresholds, (4) monocyte HLA-DR expression <30%, or (5) reduction in ex vivo whole blood lipopolysaccharide-induced TNFa production capacity below manufacturer-provided thresholds. LIMITATIONS: Many measures of immune system function are currently limited to the research environment. CONCLUSIONS: We present consensus criteria for the diagnosis of immune system dysfunction in critically ill children.