P4.019: Gaps in Pediatric Sepsis Definitions and Diagnosis: A Systematic Review of the Literature Since the 2005 Consensus

Background: Despite the 2005 International Pediatric Sepsis Consensus Conference establishing standardized definitions for pediatric sepsis, significant gaps persist in their clinical application and diagnostic accuracy. Emerging evidence suggests these definitions may fail to capture important sepsis phenotypes, particularly in neonates and immunocompromised children, leading to delayed recognition and treatment. This systematic review evaluates the evolution of pediatric sepsis definitions since the 2005 consensus, identifies persistent diagnostic challenges across age groups and clinical settings, and examines novel biomarkers and clinical tools that may improve early identification. Addressing these gaps is critical for reducing the global burden of pediatric sepsis mortality and morbidity, which remains unacceptably high despite decades of research.

Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library from January 2005 to June 2024, using terms including "pediatric sepsis," "sepsis definitions," "diagnostic criteria," and "sepsis biomarkers." Studies were included if they evaluated sepsis definitions in children (0-18 years), proposed modifications to diagnostic criteria, or assessed novel diagnostic approaches. Two reviewers independently screened records, extracted data, and assessed study quality using QUADAS-2 for diagnostic studies and Newcastle-Ottawa Scale for observational studies. Data synthesis included quantitative analysis of definition performance characteristics and qualitative thematic analysis of identified gaps.

Results: From 3,417 screened articles, 62 studies met inclusion criteria. Analysis revealed three critical gaps: (1) current definitions demonstrate poor sensitivity (range 58-72%) for neonatal and adolescent sepsis, (2) immunocompromised children are systematically underrepresented in diagnostic criteria, and (3) vital sign thresholds fail to account for developmental physiology (misclassifying 22-35% of cases). Biomarker combinations (e.g., presepsin with procalcitonin) showed superior accuracy to clinical criteria alone (AUC 0.89 vs 0.73, p< 0.001), while machine learning models incorporating electronic health record data improved early detection by 18-24%. However, only 12% of studies validated findings in low-resource settings where most pediatric sepsis deaths occur. Thematic analysis identified four recurring challenges: developmental variability, comorbidity-specific thresholds, lack of gold standards, and implementation barriers in diverse clinical environments.

Conclusion: Nearly two decades after the 2005 consensus, pediatric sepsis definitions remain inadequate for many high-risk populations and clinical scenarios. While novel diagnostic approaches show promise, their real-world implementation requires addressing fundamental gaps in developmental pathophysiology and healthcare system readiness. We propose three urgent priorities: (1) developmentally-stratified diagnostic criteria, (2) comorbidity-specific sepsis algorithms, and (3) pragmatic validation of biomarkers in diverse settings. These advances must be coupled with implementation research to ensure equitable adoption across healthcare systems. Until these gaps are addressed, clinicians should maintain high suspicion for sepsis even when formal criteria are not met, particularly in vulnerable pediatric populations. This review provides a roadmap for the next generation of pediatric sepsis definitions that must balance precision with practical utility across the global healthcare spectrum.