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Arterial Catheter-Associated Proximal Ischemic Injury in Critically Ill Children: Evidence of Endothelial Dysfunction
Amelia Demopoulos1, Mark D Weber1,2, Hongyan Liu3
1Division of Critical Care Medicine, Department of Anesthesia and Critical Care, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Insights
Arterial catheter-associated proximal ischemic injury (ACAPII) in pediatric patients with multiple organ dysfunction syndrome (MODS) is linked to immune dysregulation and endothelial dysfunction. These proteomic differences may offer therapeutic targets for preventing ACAPII.
Area of Science:
- Pediatric critical care medicine
- Proteomics and systems biology
- Vascular access complications
Background:
- Arterial catheter-associated proximal ischemic injury (ACAPII) is a severe complication in critically ill children requiring arterial access.
- Understanding the underlying mechanisms of ACAPII is crucial for developing preventative strategies.
- Multiple organ dysfunction syndrome (MODS) presents complex physiological challenges in pediatric patients.
Purpose of the Study:
- To investigate proteomic differences in plasma samples from critically ill children with MODS who developed ACAPII versus those who did not.
- To identify mechanistic pathways contributing to the pathogenesis of ACAPII in this vulnerable population.
- To test the hypothesis that plasma proteome profiles at MODS onset differ between ACAPII and non-ACAPII groups.
Main Methods:
- A single-center cohort study was conducted in a pediatric intensive care unit (PICU).
- Plasma samples were collected within 48 hours of MODS onset from pediatric patients.
- Proteomic analysis utilized Olink proximity extension assay, followed by gene set enrichment analysis.
Main Results:
- ACAPII developed in 7.6% of MODS patients with arterial access.
- Six immune dysregulation pathways (including STAT signaling and cytokine-mediated apoptosis) and five endothelial dysfunction pathways were significantly enriched in ACAPII cases.
- Eighteen plasma proteins were differentially expressed in ACAPII patients, supporting roles for endothelial injury and immune dysregulation.
Conclusions:
- Immune dysregulation and endothelial dysfunction pathways are associated with ACAPII in pediatric MODS patients.
- These identified pathways precede the clinical manifestation of ACAPII, suggesting a potential therapeutic window.
- Further research into these pathways could lead to novel treatments for preventing ACAPII.
Objectives:
Arterial catheter-associated proximal ischemic injury (ACAPII) is a rare but serious complication in critically ill pediatric patients who require arterial access. In a cohort of critically ill children with multiple organ dysfunction syndrome (MODS), we investigated proteomic differences in children who developed ACAPII with the aim of identifying mechanistic pathways that may contribute to the pathogenesis of this complication. We hypothesized that the plasma proteome at MODS onset would differ between children who later develop ACAPII and those who do not.
Design:
Single-center cohort study of pediatric patients with MODS defined by modified Proulx criteria who underwent arterial catheter placement. We obtained plasma samples within 48 hours of MODS onset. Grading of ACAPII was completed by the hospital vascular access team using standardized criteria. Proteomic analysis was performed using Olink proximity extension assay. Gene set enrichment analysis was used to identify mechanistic pathways enriched in ACAPII cases.
Setting:
Single-center academic PICU.
Patients:
Pediatric patients with MODS and arterial access at Children's Hospital of Philadelphia from January 2020 to December 2022.
Interventions:
None.
Measurements And Main Results:
Five of 66 (7.6%) MODS patients with arterial access developed ACAPII. Age, severity of illness, and organ dysfunction profiles did not differ between injured and noninjured patients. Six pathways of immune dysregulation, involving Signal Transducer and Activator of Transcription signaling and cytokine-mediated apoptosis, were enriched in patients with ACAPII ( p < 0.0001). Five pathways associated with endothelial dysfunction were also significantly altered in ACAPII patients ( p < 0.0001). Differential expression analysis identified 18 plasma proteins associated with injury after adjustment for age and severity of illness (false discovery rate p < 0.05), supporting the hypothesis that endothelial injury and immune dysregulation may contribute to ACAPII pathogenesis.
Conclusions:
In a small pediatric cohort, we identified pathways of immune dysregulation and endothelial dysfunction associated with ACAPII. Because these factors precede ACAPII, there may be a window for treatment.
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