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Endothelial Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference
Richard W Pierce1, John S Giuliano1, Jane E Whitney2
1Section of Pediatric Critical Care Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
Insights
Current biomarkers cannot diagnose endothelial dysfunction in critically ill children with multiple organ dysfunction syndrome. Future research needs more specific biomarkers for endothelial function in pediatric critical illness.
Area of Science:
- Pediatric Critical Care Medicine
- Vascular Biology
- Biomarker Discovery
Background:
- Endothelial dysfunction is a critical factor in pediatric multiple organ dysfunction syndrome (pMODS).
- Accurate diagnosis of endothelial dysfunction in pMODS is challenging due to a lack of specific biomarkers.
- Understanding endothelial dysfunction is crucial for improving outcomes in critically ill children.
Purpose of the Study:
- To review and synthesize literature on endothelial dysfunction in critically ill children with pMODS.
- To develop a consensus definition and diagnostic criteria for endothelial dysfunction using biomarkers.
- To identify reliable biomarkers for diagnosing endothelial dysfunction in pMODS.
Main Methods:
- Comprehensive literature searches of PubMed and Embase (1992-2020).
- Inclusion of studies evaluating critically ill children, endothelial dysfunction, and relevant outcomes.
- Exclusion of adult studies, premature infants, animal studies, and non-English literature.
Main Results:
- Identified 62 studies with 84 assessments of endothelial-derived biomarkers.
- Biomarkers evaluated were indirectly linked to endothelial functions (e.g., inflammation, coagulation).
- Most biomarkers lacked specificity for vascular segments and organ systems; literature quality was low.
Conclusions:
- No single or combination of current biomarkers can diagnose endothelial dysfunction in pediatric multiple organ dysfunction syndrome.
- Future research must focus on biomarkers with direct links to endothelial functions and organ-specific relevance.
- Development of specific, reliable diagnostic criteria for endothelial dysfunction in pMODS is needed.
Objectives:
To review, analyze, and synthesize the literature on endothelial dysfunction in critically ill children with multiple organ dysfunction syndrome and to develop a consensus biomarker-based definition and diagnostic criteria.
Data Sources:
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, using a combination of medical subject heading terms and key words to define concepts of endothelial dysfunction, pediatric critical illness, and outcomes.
Study Selection:
Studies were included if they evaluated critically ill children with endothelial dysfunction, evaluated performance characteristics of assessment/scoring tools to screen for endothelial dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants (≤36 weeks gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and non-English language studies with the inability to determine eligibility criteria were excluded.
Data Extraction:
Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment.
Data Synthesis:
We identified 62 studies involving 84 assessments of endothelial derived biomarkers indirectly linked to endothelial functions including leukocyte recruitment, inflammation, coagulation, and permeability. Nearly all biomarkers studied lacked specificity for vascular segment and organ systems. Quality assessment scores for the collected literature were low.
Conclusions:
The Endothelial Subgroup concludes that there exists no single or combination of biomarkers to diagnose endothelial dysfunction in pediatric multiple organ dysfunction syndrome. Future research should focus on biomarkers more directly linked to endothelial functions and with specificity for vascular segment and organ systems.
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