Emergency Department Sepsis Triage Scoring Tool Elements Associated With Hypotension Within 24 Hours in Children With Fever and Tachycardia.

OBJECTIVE: Pediatric sepsis screening is becoming the standard of care for children presenting to the emergency department (ED) and has been shown to improve recognition of severe sepsis, but it is unknown if these screening tools can predict progression of disease. The objective of this study was to determine if any elements of a sepsis triage trigger tool were predictive of progression to hypotensive shock in children presenting to the ED with fever and tachycardia. METHODS: This study is a retrospective case-control study of children ≤18 years presenting to an ED with fever and tachycardia, comparing those who went on to develop hypotensive shock in the subsequent 24 hours (case) to those who did not (control). Primary outcome was the proportion of encounters where the patient had specific abnormal vital signs or clinical signs as components of the sepsis triage score. The secondary outcomes were the proportion of encounters where the patient had a sepsis risk factor. RESULTS: During the study period, there were 94 patients who met case criteria and 186 controls selected. In the adjusted multivariable model, the 2 components of the sepsis triage score that were more common in case patients were the presence of severe cerebral palsy (adjusted odds ratio, 9.4 [3.7, 23.9]) and abnormal capillary refill at triage (adjusted odds ratio, 3.1 [1.4, 6.9]). CONCLUSIONS: Among children who present to a pediatric ED with fever and tachycardia, those with prolonged capillary refill at triage or severe cerebral palsy were more likely to progress to decompensated septic shock, despite routine ED care.

Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock.

STUDY OBJECTIVE: To determine whether the receipt of more than or equal to 30 mL/kg of intravenous fluid in the first hour after emergency department (ED) arrival is associated with sepsis-attributable mortality among children with hypotensive septic shock. METHODS: This is a retrospective cohort study set in 57 EDs in the Improving Pediatric Sepsis Outcomes quality improvement collaborative. Patients less than 18 years of age with hypotensive septic shock who received their first intravenous fluid bolus within 1 hour of arrival at the ED were propensity-score matched for probability of receiving more than or equal to 30 mL/kg in the first hour. Sepsis-attributable mortality was compared. We secondarily evaluated the association between the first-hour fluid volume and sepsis-attributable mortality in all children with suspected sepsis in the first hour after arrival at the ED, regardless of blood pressure. RESULTS: Of the 1,982 subjects who had hypotensive septic shock and received a first fluid bolus within 1 hour of arrival at the ED, 1,204 subjects were propensity matched. In the matched patients receiving more than or equal to 30 mL/kg of fluid, 26 (4.3%) of 602 subjects had 30-day sepsis-attributable mortality compared with 25 (4.2%) of 602 receiving less than 30 mL/kg (odds ratio 1.04, 95% confidence interval 0.59 to 1.83). Among the patients with suspected sepsis regardless of blood pressure, 30-day sepsis-attributable mortality was 3.0% in those receiving more than or equal to 30 mL/kg versus 2.0% in those receiving less than 30 ml/kg (odds ratio 1.52, 95% confidence interval 0.95 to 2.44.) CONCLUSION: In children with hypotensive septic shock receiving a timely first fluid bolus within the first hour of ED care, receiving more than or equal to 30 mL/kg of bolus intravenous fluids in the first hour after arrival at the ED was not associated with mortality compared with receiving less than 30 mL/kg.

Standardized Protocol Is Associated With a Decrease in Continuous Albuterol Use and Length of Stay in Critical Status Asthmaticus.

OBJECTIVES: The primary aim of this study was to reduce duration of continuous albuterol and hospital length of stay in critically ill children with severe status asthmaticus. DESIGN: Observational prospective study from September 2012 to May 2016. SETTING: Medicine ICU and intermediate care unit. PATIENTS: Children greater than 2 years old with admission diagnosis of status asthmaticus admitted on continuous albuterol and managed via a standardized protocol. INTERVENTIONS: The protocol was an iterative algorithm for escalation and weaning of therapy. The algorithm underwent three revisions. Iteration 1 concentrated on reducing duration on continuous albuterol; iteration 2 concentrated on reducing hospital length of stay; and iteration 3 concentrated on reducing helium-oxygen delivered continuous albuterol. Balancing measures included adverse events and readmissions. MEASUREMENTS AND RESULTS: Three-hundred eighty-five patients were treated as follows: 123, 138, and 124 in iterations 1, 2, and 3, respectively. Baseline data was gathered from an additional 150 patients prior to protocol implementation. There was no difference in median age (6 vs 8 vs 7 vs 7 yr; p = 0.130), asthma severity score (9 vs 9 vs 9 vs 9; p = 0.073), or female gender (42% vs 41% vs 43% vs 48%; p = 0.757). Using statistical process control charts, the mean duration on continuous albuterol decreased from 24.9 to 17.5 hours and the mean hospital length of stay decreased from 76 to 49 hours. There was no difference in adverse events (0% vs 1% vs 4% vs 0%; p = 0.054) nor in readmissions (0% vs 0% vs 1% vs 2%; p = 0.254). CONCLUSIONS: Implementation of a quality improvement protocol in critically ill patients with status asthmaticus was associated with a decrease in continuous albuterol duration and hospital length of stay.

Timing of Antibiotic Administration in Pediatric Sepsis.

OBJECTIVES: Antibiotic administration within 1 hour of hypotension has been shown to reduce mortality. It is unknown whether antibiotics before hypotension in children who eventually meet criteria for septic shock improves outcomes. This study assesses whether antibiotic timing from the time of meeting criteria for sepsis in children with septic shock impacts morbidity and mortality. METHODS: This is a retrospective study of children 18 years or younger presenting to a tertiary free-standing children's hospital emergency department with sepsis that subsequently progressed to septic shock and were admitted to an intensive care unit from 2008 to 2012. The time when the patient met criteria for sepsis to the time of first antibiotic administration was assessed and correlated with patient morbidity and mortality. RESULTS: Among 135 children (median age, 13.1 years), 34 (25%) were previously healthy, whereas 49 (36%) had 2 or more medical comorbidities. Twenty-seven children (20%) had positive blood cultures, 17 (13%) had positive urine cultures, and 34 (25%) had chest x-ray findings that were interpreted as pneumonia. Among the 42 (31%) with antibiotics within 1 hour from criteria for sepsis, there was higher mortality (4/42 vs 0/93, P = 0.009), more organ dysfunction, longer time on a vasoactive infusion, and increased intensive care unit and hospital lengths of stay (all P < 0.05). CONCLUSIONS: Children with criteria for sepsis who subsequently progressed to septic shock who received antibiotics within 1 hour of meeting sepsis criteria had increased mortality, length of stay, and organ dysfunction.

Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor as Novel Biomarkers for Poor Outcomes in Children With Severe Sepsis and Septic Shock.

Vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase (sFLT), are biomarkers of endothelial activation. Vascular endothelial growth factor and sFLT have been associated with sepsis severity among adults, but pediatric data are lacking. The goal of this study was to assess VEGF and sFLT as predictors of outcome for children with sepsis. METHODS: Biomarkers measured for each patient at time of presentation to the emergency department were compared in children with septic shock versus children with sepsis without shock. For children with septic shock, the associations between biomarker levels and clinical outcome measures, including intensive care unit and hospital length of stay, vasoactive inotrope score, and measures of organ dysfunction, were assessed. RESULTS: Soluble fms-like tyrosine kinase and VEGF were elevated in children with septic shock (n = 73) compared with those with sepsis (n = 93). Elevated sFLT but not VEGF was associated with longer intensive care unit length of stay (P = 0.003), longer time requiring vasoactive agents (P < 0.001), higher maximum vasoactive inotrope score (P < 0.001), and higher maximum pediatric logistic organ dysfunction score (P < 0.001). CONCLUSIONS: Vascular endothelial growth factor and sFLT measured in the emergency department are elevated in children with septic shock, and elevated sFLT but not VEGF is associated with worse clinical outcomes.

Systemic Angiopoietin-1/2 Dysregulation in Pediatric Sepsis and Septic Shock.

Background: Angiopoietin-1 and -2 are vascular growth factors that exert opposing effects on endothelial activation and dysfunction. The aim of this study was to assess the association of these biomarkers with outcomes in children with sepsis. Methods: Biomarkers were assayed from the blood collected in an emergency department prior to any intervention. Predictor variables were Ang-1 and Ang-2 levels and the Ang-2/Ang-1 ratio. Outcomes included mortality, length of time on vasopressors, and ICU and hospital lengths of stay. The Pediatric RISk of Mortality III Score was calculated. A vasoactive inotrope score was calculated every 12 hours. Results: Forty-five children with sepsis and 49 with septic shock were analyzed. The median Ang-2 was higher in septic shock. The Ang-2/Ang-1 ratio was approximately 2-fold greater in those with septic shock. The Ang-2/Ang-1 ratio was associated with higher doses of vasoactive agents at 12 hours and longer ICU length of stay. In septic shock, for every 0.35 unit increase in the Ang-2/Ang-1 ratio, the PRISM III score increased by 1. Conclusions: The Ang-2/Ang-1 ratio was higher in children with septic shock. Ang-2/Ang-1 was associated with higher vasoactive agents, longer ICU length of stay, and correlated with the severity of illness score.

Performance of an Automated Screening Algorithm for Early Detection of Pediatric Severe Sepsis.

OBJECTIVES: To create and evaluate a continuous automated alert system embedded in the electronic health record for the detection of severe sepsis among pediatric inpatient and emergency department patients. DESIGN: Retrospective cohort study. The main outcome was the algorithm's appropriate detection of severe sepsis. Episodes of severe sepsis were identified by chart review of encounters with clinical interventions consistent with sepsis treatment, use of a diagnosis code for sepsis, or deaths. The algorithm was initially tested based upon criteria of the International Pediatric Sepsis Consensus Conference; we present iterative changes which were made to increase the positive predictive value and generate an improved algorithm for clinical use. SETTING: A quaternary care, freestanding children's hospital with 404 inpatient beds, 70 ICU beds, and approximately 60,000 emergency department visits per year PATIENTS:: All patients less than 18 years presenting to the emergency department or admitted to an inpatient floor or ICU (excluding neonatal intensive care) between August 1, 2016, and December 28, 2016. INTERVENTION: Creation of a pediatric sepsis screening algorithm. MEASUREMENTS AND MAIN RESULTS: There were 288 (1.0%) episodes of severe sepsis among 29,010 encounters. The final version of the algorithm alerted in 9.0% (CI, 8.7-9.3%) of the encounters with sensitivity 72% (CI, 67-77%) for an episode of severe sepsis; specificity 91.8% (CI, 91.5-92.1%); positive predictive value 8.1% (CI, 7.0-9.2%); negative predictive value 99.7% (CI, 99.6-99.8%). Positive predictive value was highest in the ICUs (10.4%) and emergency department (9.6%). CONCLUSIONS: A continuous, automated electronic health record-based sepsis screening algorithm identified severe sepsis among children in the inpatient and emergency department settings and can be deployed to support early detection, although performance varied significantly by hospital location.

A Pilot Study of the Association of Amino-Terminal Pro-B-Type Natriuretic Peptide and Severity of Illness in Pediatric Septic Shock.

OBJECTIVES: Biomarkers that can measure illness severity and predict the risk of delayed recovery may be useful in guiding pediatric septic shock. Amino-terminal pro-B-type natriuretic peptide has not been assessed in pediatric septic patients at the time of presentation to the emergency department prior to any interventions. The primary aim was to assess if emergency department amino-terminal pro-B-type natriuretic peptide is associated with worse outcomes and severity of illness. DESIGN: Prospective observational pilot study. SETTINGS: Tertiary free-standing children's hospital. PATIENTS: Children 0-17 years old with a diagnosis of septic shock were enrolled. Patients with preexisting cardiac and renal dysfunction were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Amino-terminal pro-B-type natriuretic peptide analysis was performed on samples obtained in the emergency department prior to any intervention. The association between biomarkers and clinical outcomes and illness severity using Pediatric RISk of Mortality 3 were assessed. Eighty-two patients with septic shock underwent analysis. The median (interquartile range) amino-terminal pro-B-type natriuretic peptide levels was 394 pg/mL (102-1,392 pg/mL). Each decile change increase in amino-terminal pro-B-type natriuretic peptide was associated with a change in ICU length of stay by 8.7%, (95% CI, 2.4-15.5), hospital length of stay by 5.7% (95% CI, 0.4-11.2), organ dysfunction by 5.1% (95% CI, 1.8-8.5), a higher inotropic score at 12, 24, and 36 hours, and longer time requiring vasoactive agents. There was a significant correlation between baseline amino-terminal pro-B-type natriuretic peptide and the Pediatric RISk of Mortality 3 score (Spearman rho = 0.247; p = 0.029). CONCLUSIONS: This pilot study shows an association between emergency department amino-terminal pro-B-type natriuretic peptide on presentation and worse septic shock outcomes and amino-terminal pro-B-type natriuretic peptide levels correlates with an ICU severity score.

Quality improvement in pediatric sepsis.

PURPOSE OF REVIEW: Although there is abundant literature detailing the impact of quality improvement in adult sepsis, the pediatric literature is lacking. Despite consensus definitions for sepsis, which patients along the sepsis spectrum should receive aggressive management and the exact onset of sepsis ('time zero') are not clearly established. In the adult emergency department (ED), sepsis onset is defined as the time of entry into the ED; however, this definition cannot be applied to hospitalized patients or patients who evolve during their ED course. Since the time of sepsis onset will dictate the timeliness of subsequent process measures, the variable definitions in the literature make it difficult to generalize findings among prior studies. RECENT FINDINGS: Despite the variation in defining time zero, aggressive fluid administration, timely antibiotics, and compliance with sepsis bundles have been shown to improve mortality and to reduce hospital and intensive care length of stay. In addition, early identification tools show promise in beginning to define sepsis onset and retrospective search tools may allow improved case finding of those children of concern for sepsis. SUMMARY: Quality improvement in pediatric sepsis is evolving. As we continue to define quality measures, we must standardize the definition of sepsis onset. This definition should be applicable to any treatment venue to ensure measures can be evaluated across all settings. In addition, we must delineate which patients along the sepsis spectrum should be candidates for timely interventions and standardize other outcome measures beyond mortality.

Intravenous Fluid Bolus Rates Associated with Outcomes in Pediatric Sepsis: A Multi-Center Analysis.

Purpose: Pediatric sepsis guidelines recommend rapid intravenous fluid (IVF) bolus administration rates (BAR). Recent sepsis studies suggest that rapid BAR may be associated with increased morbidity. We aimed to describe the association between emergency department (ED) IVF BAR and clinical outcomes in pediatric sepsis. Patients and Methods: Secondary post-hoc analysis of retrospective cohort data from 19 hospitals in the Pediatric Septic Shock Collaborative (PSSC) database. Patients with presumed septic shock were defined by severe sepsis/septic shock diagnostic codes, receipt of septic shock therapies, or floor-to-ICU transfers within 12 hours from ED admission for septic shock. Patients (2 months-21 years) with complete data on weight, antibiotic receipt, bolus timing, and bolus volumes were included. The primary outcome was 30-day mortality. Associations between BAR and mortality and secondary (intubation or non-invasive positive pressure ventilation = NIPPV) outcomes were assessed using unadjusted and adjusted logistic regression. Results: The PSSC database included 6731 patients; 3969 met inclusion and received a median ED volume of 40.2 mL/kg. Seventy-six (1.9%) patients died, 151 (3.8%) were intubated, and 235 (5.9%) had NIPPV administered. The median BAR was 25.7 mL/kg/hr. For each 20 mL/kg/hr increase in BAR, the adjusted odds ratio (aOR) for 30-day mortality [aOR = 1.11 (95% CI 1.01, 1.23)], intubation [aOR = 1.25 (95% CI 1.09, 1.44)], and NIPPV [aOR = 1.20 (95% CI 1.05, 1.38)] significantly increased. Conclusion: Faster ED IVF bolus administration rates in this pediatric sepsis database were associated with higher adjusted odds of death, intubation and NIPPV. Controlled trials are needed to determine if these associations are replicable.

Pediatric Septic Shock Collaborative Improves Emergency Department Sepsis Care in Children.

OBJECTIVES: The pediatric emergency department (ED)-based Pediatric Septic Shock Collaborative (PSSC) aimed to improve mortality and key care processes among children with presumed septic shock. METHODS: This was a multicenter learning and improvement collaborative of 19 pediatric EDs from November 2013 to May 2016 with shared screening and patient identification recommendations, bundles of care, and educational materials. Process metrics included minutes to initial vital sign assessment and to first and third fluid bolus and antibiotic administration. Outcomes included 3- and 30-day all-cause in-hospital mortality, hospital and ICU lengths of stay, hours on increased ventilation (including new and increases from chronic baseline in invasive and noninvasive ventilation), and hours on vasoactive agent support. Analysis used statistical process control charts and included both the overall sample and an ICU subgroup. RESULTS: Process improvements were noted in timely vital sign assessment and receipt of antibiotics in the overall group. Timely first bolus and antibiotics improved in the ICU subgroup. There was a decrease in 30-day all-cause in-hospital mortality in the overall sample. CONCLUSIONS: A multicenter pediatric ED improvement collaborative showed improvement in key processes for early sepsis management and demonstrated that a bundled quality improvement-focused approach to sepsis management can be effective in improving care.