Faculty Collaboration Database

Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype. Crit Care Med 2016 Nov;44(11):2010-2017

Date

10/19/2016

Pubmed ID

27513537

Pubmed Central ID

PMC5201138

DOI

10.1097/CCM.0000000000001852

Scopus ID

2-s2.0-84991643950 (requires institutional sign-in at Scopus site)   76 Citations

Abstract

OBJECTIVE: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF).

DESIGN: PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts.

SETTING: Multiple PICUs in the United States.

INTERVENTIONS: Standard care.

MEASUREMENTS AND MAIN RESULTS: PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase. PERSEVERE-II had an AUC of 0.89 (0.85-0.93) and performed equally well across TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly enrolled subjects. Sample size calculations for a clinical trial testing the efficacy of plasma exchange for children with septic shock and TAMOF indicated PERSEVERE-II-based stratification could substantially reduce the number of patients necessary, when compared with no stratification.

CONCLUSIONS: Testing PERSEVERE in the context of septic shock phenotypes prompted a revision incorporating platelet count. PERSEVERE-II performs well upon testing, independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a prognostic enrichment tool.

Author List

Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald J, Checchia PA, Meyer K, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Raj SS, Gertz S, Howard K, Harmon K, Lahni P, Frank E, Hart KW, Nguyen TC, Lindsell CJ

Author

Rainer G. Gedeit MD Associate Chief Medical Officer in the Children's Administration department at Children's Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers
Chemokine CCL3
Child
Child, Preschool
Female
Granzymes
HSP70 Heat-Shock Proteins
Humans
Infant
Intensive Care Units, Pediatric
Interleukin-8
Male
Matrix Metalloproteinase 8
Models, Statistical
Multiple Organ Failure
Platelet Count
Prognosis
Risk Assessment
Shock, Septic
Thrombocytopenia
United States