28: BIOMARKER-BASED RISK STRATIFICATION IN PEDIATRIC SEPSIS FROM A LOW-MIDDLE-INCOME COUNTRY

Abstract

Introduction: Most biomarker studies of sepsis and acute respiratory distress syndrome (ARDS) originate from high-income countries per World Bank classification, whereas mortality risk is higher in low- and middle-income countries. In children, the second iteration of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American pediatric intensive care units (PICUs) for prognosis, with areas under the receiver operating characteristic (AUROC) curve of > 0.80 for discriminating 28-day mortality. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country, as well as the utility of other select biomarkers. Methods: This was a prospective cohort study of children (age < 18 years) from Aga Khan University Hospital (AKUH) meeting modified pediatric Sepsis-3 criteria (pSOFA ≥ 2 and lactate > 2) between 11/2020 and 2/2022. Plasma was collected < 24 hours of PICU admission and biomarkers measured via single- and multiplex ELISAs. The AUROC for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between PERSEVERE-II risk strata (low, medium, and high mortality risk), between survivors and non-survivors, and between those with and without ARDS. Projecting 15% mortality, 73 subjects were needed to detect AUROC > 0.80 at α = 0.05 and power = 0.90. Results: We enrolled 86 subjects with 20 (23%) 28-day non-survivors. PERSEVERE-II discriminated mortality with an AUROC of 0.83 (95% CI 0.72 to 0.94). Non-survivors had higher plasma angiopoietin-2 (ANG2), soluble thrombomodulin (sTM), and plasminogen activator inhibitor 1 (PAI1; all rank-sum p < 0.05), with increasing ANG2 across worsening PERSEVERE-II risk strata. Children who met ARDS criteria within 96 hours had elevated soluble receptor for advanced glycation end-products (sRAGE) and surfactant protein D (SPD; both rank-sum p < 0.05). Conclusions: PERSEVERE-II performs well in septic children from AKUH, representing the first validation of PERSEVERE-II in a low-middle income country. ANG2, sTM, and PAI1 were elevated in non-survivors, and sRAGE and SPD elevated in subjects with ARDS, suggesting a biomarker profile comparable to that of adult and pediatric sepsis and ARDS from high income countries.