Comparison of a Computable Pediatric Sepsis Phenotype Tool in Argentinian and U.S. Cohorts.

Abstract

Objective: Sepsis is a leading cause of mortality in low- and middle-income countries. This study identifies computable pediatric sepsis phenotypes (PedSep A, B, C, and D) previously derived in a U.S. cohort in a new independent Argentine cohort to assess plausibility for its use in personalized clinical trials in Pan-American children.

Design: This retrospective cohort study uses data from the Argentinian ESSPED2 (Estudio Sepsis y Shock Séptico Pediátrico 2) Registry and the Phenotyping Pediatric Sepsis-Induced Multiple Organ Failure U.S. study.

Setting: The Argentine cohort was recruited from 51 PICUs between September 15 and December 15, 2021. The U.S. cohort involved nine PICUs between 2015 and 2017.

Patients: The Argentine cohort included 99 sepsis patients aged 1 month to 18 years, and the U.S. cohort included 404 sepsis patients, aged 44 weeks of gestation to 18 years.

Interventions: None.

Measurements and main results: Membership in the PedSep A, B, C, or D phenotype was identified using a computable tool ( https://pedsepsis.pitt.edu ) requiring 25 bedside variables at 24 hours. Phenotype prevalence and mortality were compared between Argentine and U.S. cohorts. Heterogeneity of treatment responses and power analyses were performed in the combined cohort. Mortality rates were 20 of 99 (20.2%) in Argentina and 45 of 404 (11.14%) in the United States ( p = 0.025). Mortality was highest in PedSep D computable phenotype, with 9 of 28 (32.14%) in Argentina and 19 of 56 (33.93%) in the United States ( p = 1.0). Heterogeneity of treatment response to anti-inflammatory therapies was observed in PedSep D compared with PedSep A, B, and C children ( p < 0.05). Sample size calculations support the requirement for 55 PedSep D patients per arm to demonstrate reduction in mortality with dexamethasone or methylprednisolone with gammaglobulin compared with placebo.

Conclusions: The PedSep computable tool can identify PedSep D children for enrollment in combined Argentina-U.S. randomized controlled trials evaluating effectiveness of anti-inflammatory treatment in hyperinflammatory sepsis.