TY - JOUR
T1 - Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country∗
AU - Ishaque, Sidra
AU - Famularo, Stephen Thomas
AU - Saleem, Ali Faisal
AU - Siddiqui, Naveed Ur Rehman
AU - Kazi, Zaubina
AU - Parkar, Sadia
AU - Hotwani, Aneeta
AU - Thomas, Neal J.
AU - Thompson, Jill Marie
AU - Lahni, Patrick
AU - Varisco, Brian
AU - Yehya, Nadir
N1 - Funding Information:
Drs. Famularo’s, Kazi’s, Parkar’s, Thompson’s, and Yehya’s institutions received funding from the National Heart, Lung, and Blood Institute. Drs. Kazi, Parkar, Thompson, and Yehya received support for article research from the National Institutes of Health. Drs. Parkar’s and Yehya’s institutions received funding from Pfizer outside of the scope of this work. Dr. Thomas received funding from Bayer AG. The remaining authors have disclosed that they do not have any potential conflicts of interest.
Publisher Copyright:
Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - 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.
AB - 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.
KW - biomarker
KW - children
KW - low- and middle-income countries
KW - prognostic enrichment
KW - sepsis
UR - http://www.scopus.com/inward/record.url?scp=85164248899&partnerID=8YFLogxK
U2 - 10.1097/PCC.0000000000003244
DO - 10.1097/PCC.0000000000003244
M3 - Article
C2 - 37092821
AN - SCOPUS:85164248899
SN - 1529-7535
VL - 24
SP - 563
EP - 573
JO - Pediatric Critical Care Medicine
JF - Pediatric Critical Care Medicine
IS - 7
ER -