Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country∗

Sidra Ishaque, Stephen Thomas Famularo, Ali Faisal Saleem, Naveed Ur Rehman Siddiqui, Zaubina Kazi, Sadia Parkar, Aneeta Hotwani, Neal J. Thomas, Jill Marie Thompson, Patrick Lahni, Brian Varisco, Nadir Yehya

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Objectives: Most biomarker studies of sepsis originate from high-income countries, whereas mortality risk is higher in low- and middle-income countries. The second version of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American PICUs for prognosis. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country. Due to uncertainty regarding how well PERSEVERE-II would perform, we also assessed the utility of other select biomarkers reflecting endotheliopathy, coagulopathy, and lung injury. Design: Prospective cohort study. Setting: PICU in Aga Khan University Hospital in Karachi, Pakistan. Patients: Children (< 18 yr old) meeting pediatric modifications of adult Sepsis-3 criteria between November 2020 and February 2022 were eligible. Interventions: None. Measurements and Main Results: Plasma was collected within 24 hours of admission and biomarkers quantified. The area under the receiver operating characteristic curve for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between survivors and nonsurvivors and between subjects with and without acute respiratory distress syndrome. In 86 subjects (20 nonsurvivors, 23%), PERSEVERE-II discriminated mortality (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.72-0.94) and stratified the cohort into low-, medium-, and high-risk of mortality. Biomarkers reflecting endotheliopathy (angiopoietin 2, intracellular adhesion molecule 1) increased across worsening risk strata. Angiopoietin 2, soluble thrombomodulin, and plasminogen activator inhibitor 1 were higher in nonsurvivors, and soluble receptor for advanced glycation end-products and surfactant protein D were higher in children meeting acute respiratory distress syndrome criteria. Conclusions: PERSEVERE-II performs well in septic children from Aga Khan University Hospital, representing the first validation of PERSEVERE-II in a low-middle income country. Patients possessed a biomarker profile comparable to that of sepsis from high-income countries, suggesting that biomarker-based enrichment strategies may be effective in this setting.

Original languageEnglish
Pages (from-to)563-573
Number of pages11
JournalPediatric Critical Care Medicine
Issue number7
Publication statusPublished - 1 Jul 2023


  • biomarker
  • children
  • low- and middle-income countries
  • prognostic enrichment
  • sepsis


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