Testing the Prognostic Accuracy of the Updated Pediatric Sepsis Biomarker Risk Model

Abstract

BackgroundWe previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort.ObjectiveTo test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort.MethodsStudy subjects were recruited from multiple pediatric intensive care units in the United States. Biomarkers were measured in 182 pediatric subjects with septic shock using serum samples obtained during the first 24 hours of presentation. The accuracy of PERSEVERE 28-day mortality risk estimate was tested using diagnostic test statistics, and the net reclassification improvement (NRI) was used to test whether PERSEVERE adds information to a physiology-based scoring system.ResultsMortality in the test cohort was 13.2%. Using a risk cut-off of 2.5%, the sensitivity of PERSEVERE for mortality was 83% (95% CI 62–95), specificity was 75% (68–82), positive predictive value was 34% (22–47), and negative predictive value was 97% (91–99). The area under the receiver operating characteristic curve was 0.81 (0.70–0.92). The false positive subjects had a greater degree of organ failure burden and longer intensive care unit length of stay, compared to the true negative subjects. When adding PERSEVERE to a physiology-based scoring system, the net reclassification improvement was 0.91 (0.47–1.35; p<0.001).ConclusionsThe updated version of PERSEVERE estimates mortality probability reliably in a heterogeneous test cohort of children with septic shock and provides information over and above a physiology-based scoring system.

Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

“…PERSEVERE consists of a decision tree incorporating five stratification biomarkers and age to assign a mortality probability for children with septic shock. Recently, the prognostic accuracy of PERSEVERE was prospectively validated in an independent cohort [44]. A temporal version of PERSEVERE has been derived and validated, which considers biomarker changes over time to assign a reliable probability of poor outcome [45].…”

Could Biomarkers Direct Therapy for the Septic Patient?

“…Wong et al (2014) have begun to use panels of biomarkers to stratify pediatric septic shock patients to predict risk, and to possibly inform on therapeutic decisions (Wong et al, 2015a,b). For example, the pediatric sepsis biomarker risk model study used a panel consisting of C-C chemokine ligand 3, IL-8, heat shock protein 70 kDa 1B, granzyme B, and matrix metalloproteinase-8 to stratify pediatric sepsis patients based on mortality probability .…”

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology

“…PERSEVERE-based stratification can serve as a benchmark for quality improvement efforts focused on sepsis outcomes. By comparing actual mortality with the PERSEVERE-derived mortality probability, caregivers can evaluate objectively if their care processes are improving upon the predicted outcome [7]. PERSEVERE can also be used for stratified analyses of clinical trials and treatment outcomes.…”

“…We recently developed and validated a sepsis outcome risk stratification tool for children with septic shock called the pediatric sepsis biomarker risk model (PERSEVERE) [6,7]. Importantly, the derivation and validation procedures included full-term neonates.…”