(847) Endothelial Damage and Immune Dysregulation Are Associated With Arterial Line Injuries in Children

Introduction: Arterial catheter associated proximal ischemic injury (ACAPII) is an increasingly recognized harm event which can occur in children with multiple organ dysfunction syndrome (MODS) who require peripheral arterial access. Known risk factors for ACAPII include age, severity of illness, and high-dose vasopressors. We hypothesized that the plasma proteome would differ between children with and without ACAPII, and these proteomic differences would reflect the mechanism of injury.

Methods: Through a PICU QI project, 99 patients with peripheral arterial lines were prospectively evaluated for ACAPII. Of these children, 66 patients were co-enrolled in a separate cohort study that profiled the plasma proteome of children with MODS using Olink proximity extension assay. To compare the plasma proteome between injured and non-injured patients, we identify differentially expressed proteins by ANOVA after adjustment for age and Pediatric Logistic Organ Dysfunction (PELOD)-2 score. We then used Gene Set Enrichment Analysis (GSEA) to evaluate mechanistic pathway differences between injured and non-injured patients.

Results: ACAPII occurred in 8% of MODS patients. Age, severity of illness, Proulx organ dysfunctions, survival, and cumulative PELOD-2 score did not differ between patients with and without ACAPII. After adjustment for age and PELOD-2 score, 18 plasma proteins were differentially expressed between injured and uninjured patients (p < 0.05). Six pathways of immune dysregulation were enriched in injured patients (all p< 0.0001), with increased normalized enrichment scores (NES) corresponding to STAT pathway activation (GSEA systematic names M25299 [NES +2.04] and M17411 [NES +1.70]), cytokine signaling (M27827 [NES +1.87] and M27605 [NES +1.77]), and programmed cell death (M22647 [NES +1.51] and M46792 [NES +1.46]). Five pathways associated with endothelial function had reduced NES in injured patients (all p< 0.0001), corresponding to expression of cell surface markers (M1242 [NES -2.46], M16441 [NES -2.14], and M9232 [NES -1.73]) and extracellular matrix integrity (M610 [NES -1.98] and M27219 [NES -1.77]).

Conclusions: Immune dysregulation and endothelial dysfunction pathways are associated with arterial catheter associated proximal ischemic injury in children with multiple organ dysfunction syndrome.