Diagnostic Identification of Acute Brain Dysfunction in Pediatric Sepsis and Septic Shock in the Electronic Health Record: A Comparison of Four Definitions in a Reference Dataset.

OBJECTIVES: Acute brain dysfunction (ABD) in pediatric sepsis has a prevalence of 20%, but can be difficult to identify. Our previously validated ABD computational phenotype (CPABD) used variables obtained from the electronic health record indicative of clinician concern for acute neurologic or behavioral change. We tested whether the CPABD has better diagnostic performance to identify confirmed ABD than other definitions using the Glasgow Coma Scale or delirium scores. DESIGN: Diagnostic testing in a curated cohort of pediatric sepsis/septic shock patients. SETTING: Quaternary freestanding children's hospital. SUBJECTS: The test dataset comprised 527 children with sepsis/septic shock managed between 2011 and 2021 with a prevalence (pretest probability) of confirmed ABD of 30% (159/527). MEASUREMENTS AND MAIN RESULTS: CPABD was based on use of neuroimaging, electroencephalogram, and/or administration of new antipsychotic medication. We compared the performance of the CPABD with three GCS/delirium-based definitions of ABD-Proulx et al, International Pediatric Sepsis Consensus Conference, and Pediatric Organ Dysfunction Information Update Mandate. The posttest probability of identifying ABD was highest in CPABD (0.84) compared with other definitions. CPABD also had the highest sensitivity (83%; 95% CI, 76-89%) and specificity (93%; 95% CI, 90-96%). The false discovery rate was lowest in CPABD (1-in-6) as was the false omission rate (1-in-14). Finally, the prevalence threshold for the definitions varied, with the CPABD being the definition closest to 20%. CONCLUSIONS: In our curated dataset of pediatric sepsis/septic shock, CPABD had favorable characteristics to identify confirmed ABD compared with GCS/delirium-based definitions. The CPABD can be used to further study the impact of ABD in studies using large electronic health datasets.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Racial Differences in the Diagnosis of Lyme Disease in Children.

Black children with Lyme disease compared with children of other races were less likely to have an erythema migrans lesion diagnosed (adjusted odds ratio, 0.34; 95% confidence interval, .14-.79) but more likely to have a swollen joint (adjusted odds ratio, 3.68; 95% confidence interval, 2.13-6.36) after adjustment for age and local Lyme incidence.

Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study.

OBJECTIVE: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants. STUDY DESIGN: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias. RESULTS: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias. CONCLUSIONS: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Pediatric sepsis screening in US hospitals.

Sepsis is a major cause of morbidity and mortality in children. While adverse outcomes can be reduced through prompt initiation of sepsis protocols including fluid resuscitation and antibiotics, provision of these therapies relies on clinician recognition of sepsis. Recognition is challenging in children because early signs of shock such as tachycardia and tachypnea have low specificity while hypotension often does not occur until late in the clinical course. This narrative review highlights the important context that has led to the rapid growth of pediatric sepsis screening in the United States. In this review, we (1) describe different screening tools used in US emergency department, inpatient, and intensive care unit settings; (2) highlight details of the design, implementation, and evaluation of specific tools; (3) review the available data on the process of integrating sepsis screening into an overall sepsis quality improvement program and on the effect of these screening tools on patient outcomes; (4) discuss potential harms of sepsis screening including alarm fatigue; and (5) highlight several future directions in sepsis screening, such as novel tools that incorporate artificial intelligence and machine learning methods to augment sepsis identification with the ultimate goal of precision-based approaches to sepsis recognition and treatment. IMPACT: This narrative review highlights the context that has led to the rapid growth of pediatric sepsis screening nationally. Screening tools used in US emergency department, inpatient, and intensive care unit settings are described in terms of their design, implementation, and clinical performance. Limitations and potential harms of these tools are highlighted, as well as future directions that may lead to a more precision-based approach to sepsis recognition and treatment.

A Clinical Prediction Rule for Bacterial Musculoskeletal Infections in Children with Monoarthritis in Lyme Endemic Regions.

STUDY OBJECTIVE: Children with a bacterial musculoskeletal infection (MSKI) require prompt identification and treatment. In Lyme disease endemic areas, children with an MSKI can present similarly to those with Lyme arthritis. Our goal was to derive a clinical prediction rule to accurately identify children at a low risk for an MSKI. METHODS: We enrolled children with monoarthritis presenting to 1 of 6 Pedi Lyme Net centers and performed a procalcitonin (PCT) and a first-tier Lyme C6 enzyme immunoassay (EIA) test. Our primary outcome was an MSKI (septic arthritis, osteomyelitis, or pyomyositis). Using recursive partitioning with k-fold cross validation, we derived a clinical prediction rule to identify children at a low risk of an MSKI. We calculated the accuracy of our novel rule in a derivation cohort. RESULTS: Of the 735 children in the derivation cohort with an available research biosample, 39 (5%) had an MSKI (18 had septic arthritis, 20 had osteomyelitis, and 1 had pyomyositis), 260 (37%) had Lyme arthritis, and 436 (53%) had other inflammatory arthritis. Children with a PCT level of more than or equal to 0.50 ng/mL and those with a C-reactive protein (CRP) level of more than or equal to 0.6 mg/dL with a negative Lyme C6 EIA were classified as not low risk for an MSKI. Of the 451 (61%) children categorized as low risk, none had an MSKI (sensitivity 100%, 95% confidence interval 91.0% to 100%; specificity 74.2%, 95% confidence interval 70.5% to 77.6%). CONCLUSION: A novel clinical decision rule that includes PCT, CRP, and a first-tier Lyme EIA was highly sensitive for MSKIs. Although broader external validation is required, the application of this rule may safely reduce invasive testing, procedures, and treatment for low risk children.

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.

Prevalence of and Associations With Avascular Necrosis After Pediatric Sepsis: A Single-Center Retrospective Study.

OBJECTIVES: Avascular necrosis (AVN) is a rare, but serious, complication after sepsis in adults. We sought to determine if sepsis is associated with postillness diagnosis of AVN, as well as potential-associated risk factors for AVN in children with sepsis. DESIGN: Retrospective observational study. SETTING: Single academic children's hospital. PATIENTS: Patients less than 18 years treated for sepsis or suspected bacterial infection from 2011 to 2017. Patients who developed AVN within 3 years after sepsis were compared with patients who developed AVN after suspected bacterial infection and with patients with sepsis who did not develop AVN. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: AVN was determined using International Classification of Diseases, 9th Edition/10th Edition codes and confirmed by chart review. The prevalence of AVN after sepsis was 0.73% (21/2,883) and after suspected bacterial infection was 0.43% (53/12,276; risk difference, 0.30; 95% CI, 0.0-0.63; p = 0.05). Compared with 43 sepsis controls without AVN, AVN in the 21 sepsis cases was associated with being older, having sickle cell disease and malignancy, higher body mass index, unknown source of infection, and low platelet count in the first 7 days of sepsis. Half of sepsis patients were treated with corticosteroids, and higher median cumulative dose of steroids was associated with AVN (23.2 vs 5.4 mg/kg; p < 0.01). Older age at infection (odds ratio [OR], 1.3; 95% CI, 1.1-1.4), malignancy (OR, 8.8; 95% CI, 2.6-32.9), unknown site of infection (OR, 12.7; 95% CI, 3.3-48.6), and minimal platelet count less than 100,000/µL in first 7 days of sepsis (OR, 5.0; 95% CI, 1.6-15.4) were identified as potential risk factors for AVN after sepsis following adjustment for multiple comparisons. CONCLUSIONS: Although rare, sepsis was associated with a higher risk of subsequent AVN than suspected bacterial infection in children. Older age, malignancy, unknown site of infection, and minimum platelet count were potential risk factors for AVN after sepsis.

Validation of a Computational Phenotype to Identify Acute Brain Dysfunction in Pediatric Sepsis.

OBJECTIVES: To validate a computational phenotype that identifies acute brain dysfunction (ABD) based on clinician concern for neurologic or behavioral changes in pediatric sepsis. DESIGN: Retrospective observational study. SETTING: Single academic children's hospital. PATIENTS: Four thousand two hundred eighty-nine index sepsis episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An existing computational phenotype of ABD was optimized to include routinely collected variables indicative of clinician concern for acute neurologic or behavioral change (completion of CT or MRI, electroencephalogram, or new antipsychotic administration). First, the computational phenotype was compared with an ABD reference standard established from chart review of 527 random sepsis episodes to determine criterion validity. Next, the computational phenotype was compared with a separate validation cohort of 3,762 index sepsis episodes to determine content and construct validity. Criterion validity for the final phenotype had sensitivity 83% (95% CI, 76-89%), specificity 93% (90-95%), positive predictive value 84% (77-89%), and negative predictive value 93% (90-96%). In the validation cohort, the computational phenotype identified ABD in 35% (95% CI 33-36%). Content validity was demonstrated as those with the ABD computational phenotype were more likely to have characteristics of neurologic dysfunction and severe illness than those without the ABD phenotype, including nonreactive pupils (15% vs 1%; p < 0.001), Glasgow Coma Scale less than 5 (44% vs 12%; p < 0.001), greater than or equal to two nonneurologic organ dysfunctions (50% vs 25%; p < 0.001), and need for intensive care (81% vs 65%; p < 0.001). Construct validity was demonstrated by higher odds for mortality (odds ratio [OR], 6.9; 95% CI, 5.3-9.1) and discharge to rehabilitation (OR, 11.4; 95% CI 7.4-17.5) in patients with, versus without, the ABD computational phenotype. CONCLUSIONS: A computational phenotype of ABD indicative of clinician concern for new neurologic or behavioral change offers a valid retrospective measure to identify episodes of sepsis that involved ABD. This computational phenotype provides a feasible and efficient way to study risk factors for and outcomes from ABD using routinely collected clinical data.

Multisystem Inflammatory Syndrome in Children: Examining Emerging Data and Identifying Key Knowledge Gaps.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a syndrome of abnormal immune response after severe acute respiratory syndrome coronavirus 2 infection that can result in organ dysfunction including severe cardiovascular compromise in children. Increased evidence supports a clinical and laboratory profile in MIS-C distinct from Kawasaki disease, with MIS-C typically occurring in older children and with more prominent gastrointestinal and neurologic symptoms, as well as increased inflammation, lymphopenia, and cardiac injury on laboratory testing. However, high-level evidence regarding best practices for treatment and long-term outcomes in MIS-C is limited.

Analysis of Missed Sepsis Patients in a Pediatric Emergency Department With a Vital Sign-Based Electronic Sepsis Alert.

OBJECTIVE: To characterize the cohort of missed sepsis patients since implementation of an electronic sepsis alert in a pediatric emergency department (ED). METHODS: Retrospective cohort study in a tertiary care children's hospital ED from July 1, 2014, to June 30, 2017. Missed patients met international consensus criteria for severe sepsis requiring intensive care unit admission within 24 hours of ED stay but were not treated with the sepsis pathway/order set in the ED. We evaluated characteristics of missed patients compared with sepsis pathway patients including alert positivity, prior intensive care unit admission, and laboratory testing via medical record review. Outcomes included timeliness of antibiotic therapy and need for vasoactive medications. RESULTS: There were 919 sepsis pathway patients and 53 (5%) missed patients during the study period. Of the missed patients, 41 (77%) had vital signs that flagged the sepsis alert. Of these 41 patients, 13 (32%) had a documented sepsis huddle where the team determined that the sepsis pathway was not indicated and 28 (68%) had no sepsis alert-related documentation. Missed patients were less likely to receive timely antibiotics (relative risk, 0.4; 95% confidence interval, 0.3-0.7) and more likely to require vasoactive medications (relative risk, 4.3; 95% confidence interval, 2.9-6.5) compared with sepsis patients. CONCLUSIONS: In an ED with an electronic sepsis alert, missed patients often had positive sepsis alerts but were not treated for sepsis. Missed patients were more likely than sepsis pathway patients to require escalation of care after admission and less likely to receive timely antibiotics.

Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area.

OBJECTIVE: In Lyme disease endemic areas, Lyme and septic arthritis often present similarly. A published septic knee arthritis clinical prediction rule includes 2 high-risk predictors: absolute neutrophil count of 10,000 cells/mm3 or greater and erythrocyte sedimentation rate of 40 mm/h or greater. The objective of the study was to externally validate this prediction rule in a multicenter prospective cohort. METHODS: We enrolled a prospective cohort of children with knee monoarthritis undergoing evaluation for Lyme disease at 1 of 8 Pedi Lyme Net emergency departments located in endemic areas. We defined a case of septic arthritis with a positive synovial fluid culture or a synovial fluid white blood cell count of 50,000 or greater per high powered field with a positive blood culture and Lyme arthritis with a positive or equivocal C6 EIA, followed by a positive supplemental immunoblot. Other children were classified as having inflammatory arthritis. We report the performance of the septic arthritis clinical prediction rule in our study population. RESULTS: Of the 543 eligible children, 13 had septic arthritis (2.4%), 234 Lyme arthritis (43.1%), and 296 inflammatory arthritis (54.5%). Of the 457 children (84.2%) with available laboratory predictors, all children with septic arthritis were classified as high risk (sensitivity, 100%; 95% confidence interval [CI], 77.2%-100%; specificity, 68.1%; 95% CI, 63.6-73.3; negative predictive value, 278/278 [100%]; 95% CI, 98.6%-100%). Of the 303 low-risk children, 52 (17.2%) underwent diagnostic arthrocentesis. CONCLUSIONS: The septic knee arthritis clinical prediction rule accurately distinguished between septic and Lyme arthritis in an endemic area. Clinical application may reduce unnecessary invasive diagnostic procedures.

Electrocardiogram as a Lyme Disease Screening Test.

OBJECTIVE: To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease. STUDY DESIGN: We performed an 8-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease as the presence of an erythema migrans lesion or a positive 2-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and atrioventricular (AV) block or any ECG evidence of carditis. RESULTS: Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis, of whom 24 had AV block (20 first-degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (OR 4.7, 95% CI 1.8-12.1) and any ECG evidence of carditis (OR 2.3, 95% CI 1.2-4.3) were both associated with diagnosis of Lyme disease. CONCLUSIONS: ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.

Association of early hypotension in pediatric sepsis with development of new or persistent acute kidney injury.

OBJECTIVE: To determine how hypotension in the first 48 h of sepsis management impacts acute kidney injury (AKI) development and persistence. STUDY DESIGN: Retrospective study of patients > 1 month to < 20 years old with sepsis in a pediatric ICU between November 2012 and January 2015 (n = 217). All systolic blood pressure (SBP) data documented within 48 h after sepsis recognition were collected and converted to percentiles for age, sex, and height. Time below SBP percentiles and below pediatric advanced life support (PALS) targets was calculated by summing elapsed time under SBP thresholds during the first 48 h. The primary outcome was new or persistent AKI, defined as stage 2 or 3 AKI present between sepsis day 3-7 using Kidney Disease: Improving Global Outcomes creatinine definitions. Secondary outcomes included AKI-free days (days alive and free of AKI) and time to kidney recovery. RESULTS: Fifty of 217 sepsis patients (23%) had new or persistent AKI. Patients with AKI spent a median of 35 min under the first SBP percentile, versus 4 min in those without AKI. After adjustment for potential confounders, the odds of AKI increased by 9% with each doubling of minutes spent under this threshold (p = 0.03). Time under the first SBP percentile was also associated with fewer AKI-free days (p = 0.02). Time spent under PALS targets was not associated with AKI. CONCLUSIONS: The duration of severe systolic hypotension in the first 48 h of pediatric sepsis management is associated with AKI incidence and duration when defined by age, sex, and height norms, but not by PALS definitions. Graphical abstract.

Eliminating Lumbar Puncture for Low-Risk Febrile Infants: A Quality Improvement Initiative.

BACKGROUND: Bacterial meningitis in low-risk febrile young infants (FYIs) aged >28 days has become increasingly rare. Routine performance of lumbar puncture (LP) in these infants is associated with adverse consequences and may be unnecessary. We modified our clinical practice guideline (CPG) to reduce the number of FYIs 29 to 56 days old who receive LP. METHODS: This quality improvement project sought to modify a preexisting CPG to diagnose and manage FYIs 0 to 56 days old that eliminated routine performance of LP in children 29 to 56 days old who were considered low-risk for serious bacterial infection. The change was implemented by making adjustments to the online CPG. A statistical process control chart was used to assess the affect of the initiative on our primary outcome of LP rate in this population of FYIs. RESULTS: Postimplementation of the CPG initiative, 71% of FYIs 29 to 56 days old did not receive LP, compared with 42% preimplementation. This practice change was also associated with fewer hospitalizations, lower median emergency department (ED) length of stay, and fewer 72-hour ED revisits. Over 3 years of sustained practice, 1/713 (0.1%; 95% confidence interval, 0%-0.8%) low-risk FYI returned within 72 hours and was subsequently treated for probable bacterial meningitis, although cerebrospinal fluid culture was negative for bacterial growth. CONCLUSIONS: A change in CPG reduced the number of LPs performed in febrile infants 29 to 56 days old. This change resulted in fewer LPs, hospitalizations, ED revisits, and a lower ED length of stay for FYIs 29 to 56 days old.

Elevated Heart Rate and Risk of Revisit With Admission in Pediatric Emergency Patients.

OBJECTIVE: The aim of this study was to identify emergency department (ED) heart rate (HR) values that identify children at elevated risk of ED revisit with admission. METHODS: We performed a retrospective cohort study of patients 0 to 18 years old discharged from a tertiary-care pediatric ED from January 2013 to December 2014. We created percentile curves for the last recorded HR for age using data from calendar year 2013 and used receiver operating characteristic (ROC) curves to characterize the performance of the percentiles for predicting ED revisit with admission within 72 hours. In a held-out validation data set (calendar year 2014 data), we evaluated test characteristics of last-recorded HR-for-age cut points identified as promising on the ROC curves, as well as those identifying the highest 5% and 1% of last recorded HRs for age. RESULTS: We evaluated 183,433 eligible ED visits. Last recorded HR for age had poor discrimination for predicting revisit with admission (area under the curve, 0.61; 95% confidence interval, 0.58-0.63). No promising cut points were identified on the ROC curves. Cut points identifying the highest 5% and 1% of last recorded HRs for age showed low sensitivity (10.1% and 2.5%) with numbers needed to evaluate of 62 and 50, respectively, to potentially prevent 1 revisit with admission. CONCLUSIONS: Last recorded ED HR discriminates poorly between children who are and are not at risk of revisit with admission in a pediatric ED. The use of single-parameter HR in isolation as an automated trigger for mandatory reevaluation prior to discharge may not improve revisit outcomes.

Test Characteristics of Cerebrospinal Fluid Gram Stain to Identify Bacterial Meningitis in Infants Younger Than 60 Days.

ABSTRACT: In our cohort of 20,947 infants aged 60 days or younger, cerebrospinal fluid Gram stain had a sensitivity of 34.3% (95% confidence interval, 28.1%-41.1%) and a positive predictive value of 61.4% (95% confidence interval, 52.2%-69.8%) for positive cerebrospinal fluid culture, suggesting that Gram stain alone may lead to both underdiagnosis and overdiagnosis of bacterial meningitis.

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/µL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/µL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/µL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.