International Consensus Criteria for Pediatric Sepsis and Septic Shock.

ImportanceSepsis 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.ObjectiveTo update and evaluate criteria for sepsis and septic shock in children.Evidence reviewThe 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.FindingsBased 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 relevanceThe 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

Hypofibrinogenemia Is Associated With Poor Outcome and Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in Pediatric Severe Sepsis*

ObjectivesSome children with sepsis exhibit a sustained hyperinflammatory response that can trigger secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Although hypofibrinogenemia is a shared feature of sepsis and hemophagocytic lymphohistiocytosis, there are no data about fibrinogen as a biomarker to identify children with sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap. We hypothesized that hypofibrinogenemia is associated with poor outcomes and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome and has utility as a screening biomarker for this sepsis phenotype.DesignA retrospective cohort study of patients less than or equal to 21 years treated for severe sepsis from January 2012 to December 2014.SettingEmergency department and PICU at a single academic children's hospital.PatientsConsecutive patients with greater than or equal to one episode of hypofibrinogenemia (serum fibrinogen < 150 mg/dL) within 7 days of sepsis were compared with a random sample of patients without hypofibrinogenemia using an a priori sample size target of 190. Thirty-eight patients with hypofibrinogenemia were compared with 154 without hypofibrinogenemia.InterventionsNone.Measurements and main resultsThe primary outcome was "complicated course" (composite of 28-d mortality or ≥ two organ failures at 7 d). Secondary outcomes were 28-day mortality and fulfillment of diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. We used Wilcoxon rank-sum, Fisher exact test, and multivariable logistic regression to compare patients with versus without hypofibrinogenemia. Patients with hypofibrinogenemia were more likely to have a complicated course (73.7% vs 29.2%; p < 0.001), 28-day mortality (26.3% vs 7.1%, p = 0.002), and meet diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (21.1% vs 1.3%; p < 0.001). After controlling for confounders, hypofibrinogenemia remained associated with complicated course (adjusted odds ratio, 8.8; 95% CI, 3.5-22.4), mortality (adjusted odds ratio, 6.0; 95% CI, 2.0-18.1), and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (adjusted odds ratio, 27.6; 95% CI, 4.4-173).ConclusionsHypofibrinogenemia was independently associated with poor outcome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome in pediatric sepsis. Measurement of fibrinogen may provide a pragmatic biomarker to identify children with possible sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap for whom further diagnostic testing and consideration of adjunctive immunomodulatory therapies should be considered

Machine learning models for early sepsis recognition in the neonatal intensive care unit using readily available electronic health record data.

BackgroundRapid antibiotic administration is known to improve sepsis outcomes, however early diagnosis remains challenging due to complex presentation. Our objective was to develop a model using readily available electronic health record (EHR) data capable of recognizing infant sepsis at least 4 hours prior to clinical recognition.Methods and findingsWe performed a retrospective case control study of infants hospitalized ≥48 hours in the Neonatal Intensive Care Unit (NICU) at the Children's Hospital of Philadelphia between September 2014 and November 2017 who received at least one sepsis evaluation before 12 months of age. We considered two evaluation outcomes as cases: culture positive-positive blood culture for a known pathogen (110 evaluations); and clinically positive-negative cultures but antibiotics administered for ≥120 hours (265 evaluations). Case data was taken from the 44-hour window ending 4 hours prior to evaluation. We randomly sampled 1,100 44-hour windows of control data from all times ≥10 days removed from any evaluation. Model inputs consisted of up to 36 features derived from routine EHR data. Using 10-fold nested cross-validation, 8 machine learning models were trained to classify inputs as sepsis positive or negative. When tasked with discriminating culture positive cases from controls, 6 models achieved a mean area under the receiver operating characteristic (AUC) between 0.80-0.82 with no significant differences between them. Including both culture and clinically positive cases, the same 6 models achieved an AUC between 0.85-0.87, again with no significant differences.ConclusionsMachine learning models can identify infants with sepsis in the NICU hours prior to clinical recognition. Learning curves indicate model improvement may be achieved with additional training examples. Additional input features may also improve performance. Further research is warranted to assess potential performance improvements and clinical efficacy in a prospective trial

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 impr

Seasonality of Acute Lyme Disease in Children

Due to the life cycle of its vector, Lyme disease has known seasonal variation. However, investigations focused on children have been limited. Our objective was to evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States. We enrolled children presenting to one of eight Pedi Lyme Net participating emergency departments. Cases were classified based on presenting symptoms: early (single erythema migrans (EM) lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis). We defined a case of Lyme disease by the presence of an EM lesion or a positive two-tier Lyme disease serology. To measure seasonal variability, we estimated Fourier regression models to capture cyclical patterns in Lyme disease incidence. While most children with early or early-disseminated Lyme disease presented during the summer months, children with Lyme arthritis presented throughout the year. Clinicians should consider Lyme disease when evaluating children with acute arthritis throughout the year