Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype.

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.

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@article{Wong2016PediatricSB, title={Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype.}, author={Hector R Wong and Natalie Z. Cvijanovich and N. G. Ahmad Anas and Geoffrey L. Allen and Neal J. Thomas and Michael Theodore Bigham and Scott Weiss and Julie C. Fitzgerald and Paul A. Checchia and Keith G Meyer and Michael W. Quasney and Mark W. Hall and Rainer G Gedeit and Robert J Freishtat and Jeffrey E. Nowak and Shekhar S. Raj and Shira J. Gertz and Kelli A Howard and Kelli K Harmon and Patrick M. Lahni and Erin C Frank and Kimberly Ward Hart and Trung Nguyen and Christopher J Lindsell}, journal={Critical care medicine}, year={2016}, volume={44 11}, pages={2010-2017} }