Arterial Catheter-Associated Proximal Ischemic Injury in Critically Ill Children: Evidence of Endothelial Dysfunction and Immune Dysregulation
Pediatric Critical Care Medicine, 2026
Demopoulos A., Weber M., Liu H., Traynor D., Sayed S., Famularo S., Arroyo T., Conlon T., Henrickson S., Lindell R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD Pediatrics | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
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.