Implementation of an Automated Sepsis Screening Tool in a Children's Hospital Emergency Department: A Cost Analysis.

OBJECTIVE: To determine the effect of implementation of an automated sepsis screening tool on the median cost of affected patient encounters. STUDY DESIGN: This retrospective cohort study used propensity score-matched comparison groups to assess the difference in median cost for comparable affected patient encounters before and after the implementation of an automated sepsis screening tool in a large US children's hospital emergency department (ED) with >90 000 annual visits. All patient encounters in 2018 impacted by the automated sepsis screening tool were included and compared with a propensity score-matched comparison group drawn from patient encounters in 2012 that might have been affected by the screening tool had it been active at that time. The main outcome was the change in the median cost for comparable affected patient encounters. RESULTS: The overall median cost for those affected by an automated sepsis screening tool decreased by 21.2%, from $6454 (IQR, $968-$21 697) to $5084 (IQR, $802-$16 618). The median cost for encounters with an associated International Classification of Diseases sepsis code decreased by 51.1%, from $58 685 (IQR, $32 224-$134 895) to $28 672 (IQR, $16 796-$60 657). CONCLUSIONS: The median cost for comparable patient encounters decreased with implementation of an automated sepsis screening tool in the pediatric ED. Costs were decreased even more substantially for patients with sepsis. In addition to improving outcomes, an automated sepsis screening tool appears to be at least cost-effective and may be cost-saving, an incentive for more widespread use of this technology.

Antimicrobial Therapy in Pediatric Sepsis: What Is the Best Strategy?

Pediatric sepsis is a relevant cause of morbidity and mortality in this age group. Children are affected differently in high and low-income countries. Antibiotics are crucial for the treatment of sepsis, but indiscriminate use can increase resistance worldwide. The choice of a correct empiric therapy takes into consideration the site of infection, local epidemiology, host comorbidities and recent antibiotic exposure. Antibiotics should be administered in the first hour for patients with septic shock, and always intravenously or via intraosseous access. Culture results and clinical improvement will guide de-escalation and length of treatment. New diagnostic methods can help improve the prescription of adequate treatment. Prevention of sepsis includes vaccination and prevention of healthcare-associated infections. More research and education for awareness of sepsis is needed to improve care.

Reverse Engineering of the Pediatric Sepsis Regulatory Network and Identification of Master Regulators.

Sepsis remains a leading cause of death in ICUs all over the world, with pediatric sepsis accounting for a high percentage of mortality in pediatric ICUs. Its complexity makes it difficult to establish a consensus on genetic biomarkers and therapeutic targets. A promising strategy is to investigate the regulatory mechanisms involved in sepsis progression, but there are few studies regarding gene regulation in sepsis. This work aimed to reconstruct the sepsis regulatory network and identify transcription factors (TFs) driving transcriptional states, which we refer to here as master regulators. We used public gene expression datasets to infer the co-expression network associated with sepsis in a retrospective study. We identified a set of 15 TFs as potential master regulators of pediatric sepsis, which were divided into two main clusters. The first cluster corresponded to TFs with decreased activity in pediatric sepsis, and GATA3 and RORA, as well as other TFs previously implicated in the context of inflammatory response. The second cluster corresponded to TFs with increased activity in pediatric sepsis and was composed of TRIM25, RFX2, and MEF2A, genes not previously described as acting in a coordinated way in pediatric sepsis. Altogether, these results show how a subset of master regulators TF can drive pathological transcriptional states, with implications for sepsis biology and treatment.

Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study.

OBJECTIVES: Oxidative stress is known to participate in the progression of sepsis. Definite data regarding the behavior of oxidative stress biomarkers in pediatric sepsis is still lacking. This study hypothesized that oxidative stress occurs in pediatric sepsis and that the magnitude of the redox derangement is associated with worse clinical progression. METHODS: Forty-two previously healthy pediatric patients with sepsis and a group of control subjects were included. Oxidative stress and inflammatory activity biomarkers were determined in blood samples. Patients were prospectively followed until their discharge or death. RESULTS: Patients with non-severe and severe sepsis showed higher levels of plasmatic antioxidant capacity, lower erythrocyte thiol index, lower superoxide dismutase and catalase activities, higher glutathione peroxidase activity, and higher plasmatic F2-isoprostanes concentration than controls. Patients with severe sepsis had higher NF-kappaB activation than those with non-severe sepsis. Although we observed changes in some biomarkers in patients with worse clinical evolution, the explored biomarkers did not correlate with clinical estimators of outcome. DISCUSSION: Oxidative stress occurs in pediatric sepsis, resulting in oxidative damage. The explored biomarkers are not useful as outcome predictors in the studied population. The behavior of these biomarkers still needs to be addressed in broader groups of pediatric patients with sepsis.