Abstract
Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a “Think globally, act locally” approach is required.
Key Points
- Limitations of Current Pediatric Sepsis Definitions: Existing criteria, including Sepsis-3 definitions, were developed using data primarily from high-income countries (HICs), limiting their relevance in LMICs, where pediatric sepsis epidemiology differs significantly.
- Need for Early Recognition and Standardized Criteria: Pediatric sepsis progresses rapidly, requiring early detection strategies. However, the lack of universally validated measures to distinguish infection from sepsis complicates timely intervention.
- Impact of Resource Availability: Sepsis recognition and management depend on local resources, including access to laboratory diagnostics, antimicrobial therapies, and intensive care. A flexible definition must accommodate these disparities while ensuring effective triage.
- Biological and Age-Related Factors: The host immune response, pathogen burden, and comorbidities like malnutrition, sickle cell disease, and HIV vary widely in children, influencing disease progression and therapeutic responses.
- Pathogen-Specific Considerations: Unlike adult sepsis, pediatric cases involve a broader range of etiologies, including bacterial, viral, fungal, and parasitic infections, necessitating diagnostic approaches that consider regional disease burdens.
- Challenges in Differentiating Sepsis from Severe Infections: In many settings, “sepsis” is used synonymously with severe infections, leading to inconsistencies in coding, clinical decision-making, and epidemiological surveillance.
- Development of Context-Specific Criteria: Sepsis definitions should align with different levels of healthcare, from primary care to tertiary ICUs, ensuring that clinical indicators remain applicable across diverse healthcare systems.
- Biomarker-Based Risk Stratification: Biomarkers such as C-reactive protein (CRP) and ferritin have shown potential in stratifying pediatric sepsis severity and guiding targeted therapeutic interventions.
- Integration of Social Determinants of Health (SDOH): Socioeconomic factors, healthcare access, and environmental exposures significantly impact sepsis outcomes, emphasizing the need for context-sensitive risk models.
- Global Data Collection and Research Priorities: The Taskforce recommends developing global collaborative databases to refine sepsis criteria, improve phenotyping, and enhance predictive modeling for treatment response.
