Abstract
IntroductionThe first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage. These steps are usually left to the physician’s judgment, as there is no accepted biomarker available. We aimed to determine biomarker phenotypes that differentiate children with sepsis who require intensive care from those who do not.MethodsWe conducted a prospective, observational nested cohort study at two pediatric intensive care units (PICUs) and one pediatric emergency department (ED). Children ages 2–17 years presenting to the PICU or ED with sepsis or presenting for procedural sedation to the ED were enrolled. We used the judgment of regional pediatric ED and PICU attending physicians as the standard to determine triage location (PICU or ED). We performed metabolic and inflammatory protein mediator profiling with serum and plasma samples, respectively, collected upon presentation, followed by multivariate statistical analysis.ResultsNinety-four PICU sepsis, 81 ED sepsis, and 63 ED control patients were included. Metabolomic profiling revealed clear separation of groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.89, area under the receiver operating characteristic curve (AUROC) of 0.96 (standard deviation [SD] 0.01), and predictive ability (Q2) of 0.60. Protein mediator profiling also showed clear separation of the groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.78 and AUROC of 0.88 (SD 0.03). Combining metabolomic and protein mediator profiling improved the model (Q2 =0.62), differentiating PICU sepsis from ED sepsis with accuracy of 0.87 and AUROC of 0.95 (SD 0.01). Separation of PICU sepsis or ED sepsis from ED controls was even more accurate. Prespecified age subgroups (2–5 years old and 6–17 years old) improved model accuracy minimally. Seventeen metabolites or protein mediators accounted for separation of PICU sepsis and ED sepsis with 95 % confidence.ConclusionsIn children ages 2–17 years, combining metabolomic and inflammatory protein mediator profiling early after presentation may differentiate children with sepsis requiring care in a PICU from children with or without sepsis safely cared for outside a PICU. This may aid in making triage decisions, particularly in an ED without pediatric expertise. This finding requires validation in an independent cohort.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1026-2) contains supplementary material, which is available to authorized users.
Highlights
The first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage
Neuromuscular Cardiac Respiratory Pediatric Risk of Mortality (PRISM) III score pediatric logistic organ dysfunction score (PELOD) score white blood cells (WBC) count (109/Litre) Platelet count (109/Litre) Creatinine Lactate Lowest systolic blood pressure (SBP) Lowest mean arterial pressure (MAP) pH Sepsis developed after first pediatric intensive care unit (PICU) day Site of infection Pneumonia without microbiological confirmation Microbiologically confirmed Clinically diagnosed Mechanical ventilation on first day Inotrope/vasopressor infusion on first day Duration of mechanical ventilation after enrollment
These results were obtained in children, and regionalization of clinical experience in pediatric emergency department (ED) and PICUs leaves most hospitals where children present without the specialized expertise to make timely diagnostic and triage decisions [16, 17]
Summary
The first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage. These steps are usually left to the physician’s judgment, as there is no accepted biomarker available. Sepsis is a leading cause of mortality in children worldwide [1]. Researchers in one study found an 81 % increase in hospitalizations for severe sepsis between 1995 and 2005 [4,5,6]. In a recent multicenter study, investigators found that 34 % of survivors of severe sepsis had a decline in their functional status at 28 days, and 18 % were determined to have a “poor” functional outcome (moderate, severe, or vegetative disability) [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
