International Pediatric Sepsis Consensus Conference Research Articles

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.

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. Diagnostic testing in a curated cohort of pediatric sepsis/septic shock patients. Quaternary freestanding children's hospital. 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). 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%. 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.

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

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. To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. 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. 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. 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. 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. 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.

Experience of a therapeutic plasma exchange program in a pediatric intensive care unit: A single-center retrospective observational study from Canada

Background: Pediatric intensive care units (PICUs) may not have timely access to therapeutic plasma exchange (TPE) for critically ill patients. The purpose of this study was to evaluate the common indications for TPE in a smaller tertiary PICU-developed TPE program and to evaluate the associated predictors of mortality. We hypothesized that a PICU-developed TPE program could provide timely access for a wide breadth of pathologies and can be delivered safely. Subjects and Methods: This was a retrospective case-comparison within-cohort study in a PICU from Canada. Data from pediatric patients between October 2015 and January 2022 was examined. The study included all patients &lt; 18 years admitted to the PICU and requiring TPE. Multiorgan dysfunction syndrome (MODS) was defined to agree with the International Pediatric Sepsis Consensus Conference. Proportions, medians, and interquartile ranges (IQR) were calculated where appropriate. Results: Twenty-five patients with a median age of 14 years underwent 118 acute TPE runs. The most common diagnosis (24%) was MODS. The median time from PICU admission to initiation of TPE was 38 h (IQR: 5–113.5) hours. The median PICU length of stay was 10 (IQR: 5.5–26) days. Twenty percent (n = 5) of patients who received TPE acutely in the PICU required chronic TPE. There were no adverse events. Conclusions: TPE may be delivered quickly and safely from a small PICU for many indications, with MODS being the most common.

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction. We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015. Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland. Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old. None. We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores, measured at blood culture sampling, to predict 30-day mortality. We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Percentage with organ dysfunction ranged from 32.7% (IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy for identification of 30-day mortality was area under the curve (AUC) 0.87 (95% CI, 0.82-0.92) for IPSCC, 0.83 (0.76-0.89) for PELOD-2, 0.85 (0.78-0.92) for pSOFA, and 0.85 (0.78-0.91) for PODIUM. When restricting scores to neurologic, respiratory, and cardiovascular dysfunction, the adjusted AUC was 0.89 (0.84-0.94) for IPSCC, 0.85 (0.79-0.91) for PELOD-2, 0.87 (0.81-0.93) for pSOFA, and 0.88 (0.83-0.93) for PODIUM. IPSCC, PELOD-2, pSOFA, and PODIUM performed similarly to predict 30-day mortality. Simplified scores restricted to neurologic, respiratory, and cardiovascular dysfunction yielded comparable performance.

Serum YKL-40 as a Potential Biomarker for Sepsis in Term Neonates-A Pilot Study.

Although YKL-40 is a promising diagnostic biomarker of sepsis in adults, its value in neonatal sepsis is not known. The study objectives included assessing the levels and diagnostic value of serum YKL-40 in term neonates with sepsis and comparing YKL-40 with other commonly used inflammatory biomarkers. In this pilot case-control study, 45 term neonates (30 septic and 15 non-septic, as controls), 4 to 28 days old, were prospectively studied. The International Pediatric Sepsis Consensus Conference criteria were applied to diagnose sepsis. During the acute phase (admission) and remission of sepsis, blood samples were collected from cases (while from controls they were only collected once) for routine laboratory tests, cultures, and the measurement of serum YKL-40 levels via Elisa. In the acute phase of sepsis, YKL-40 levels were significantly elevated in comparison with remission (p = 0.004) and controls (p = 0.003). YKL-40 levels did not differ significantly between patients in remission and controls (p = 0.431). Upon admission, YKL-40 levels correlated positively with white blood count, absolute neutrophil count, and CRP levels. Via ROC analysis, it was shown that YKL-40 levels upon admission were a significant indicator of sepsis (AUC = 0.771; 95% CI 0.632-0.911; p = 0.003). Serum YKL-40 might be considered as an adjuvant biomarker of sepsis in term neonates.

A single-center PICU present status survey of pediatric sepsis-related acute respiratory distress syndrome.

To describe the incidence, clinical features, outcomes, and mortality risk factors of sepsis associated with acute respiratory distress syndrome (ARDS) in pediatric patients. Patients were included in the study if they met the 2005 version of the International Pediatric Sepsis Consensus Conference and met the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition within 48 h of sepsis diagnosis. Patients were classified as mild, moderate, and severe by the worst oxygenation index (OI) within 72 h of sepsis-related ARDS diagnosis. Between January 1, 2015 and March 13, 2020, 9836 patients were admitted to the pediatric intensive care unit(PICU) of the Children's Hospital of Chongqing Medical University and 828 (8.4%) were identified with sepsis and 203 (24.5%) met the PALICC definition with a PICU mortality rate of 24.6% (50/203) and a 90-day mortality rate of 40.9% (83/203). After adjusting for septic shock, the pediatric logistic organ dysfunction 2 (PELOD-2), high-frequency oscillation ventilation (HFOV), and continuous renal replacement therapy (CRRT), the variables that retained an independent association with increased 90-day mortality in pediatric sepsis-related ARDS included ARDS severity, the pediatric risk of mortality III (PRISM III), number of organ dysfunctions and use of vasoactive drug types during PICU stay. PICU mortality in pediatric sepsis-related ARDS was high (24.6%) and severity of hypoxemia based on the worst OI value 72 h after meeting the PALICC definition accurately stratified the patient outcomes. ARDS severity, PRISM III score, comorbid multiorgan dysfunction, and use of multiple vasoactive drugs during PICU stay were independent risk factors for 90-day mortality in pediatric sepsis-related ARDS.

International Perspective on a Revised Pediatric Sepsis Definition.

International Perspective on a Revised Pediatric Sepsis Definition.

Therapeutic Drug Monitoring of Antibiotics in Critically Ill Children: An Observational Study in a Pediatric Intensive Care Unit.

Septic critically ill children are at a high risk of inadequate antibiotic exposure, requiring them to undergo therapeutic drug monitoring (TDM). The aim of this study was to describe the use of TDM for antibiotics in critically ill children. The authors conducted a single-center observational study between June and December 2019, with all children treated with antibiotics in a pediatric intensive care unit located in a French university hospital. Standard clinical and laboratory data were recorded. Blood samples were collected for routine laboratory tests, and plasma antibiotic levels were assayed using validated analytical methods. A total of 209 children received antibiotics. TDM was performed in 58 patients (27.8%) who had a greater mean organ dysfunction (according to the International Pediatric Sepsis Consensus Conference) (3 versus 1 in the non-TDM group; P < 0.05) and were treated with antibiotics for longer. A total of 208 samples were analyzed. The median [interquartile range] assay turnaround time was 3 (1-5) days, and 48 (46.2%) of the 104 initial antibiotic concentration values were below the pharmacokinetic/pharmacodynamic targets. A total of 34 (46%) of the 74 off-target TDM measurements available before the end of the antibiotic treatment prompted dose adjustment. This dose adjustment increased the proportion of on-target TDM measurements (70% versus 20% without adjustment). Subsequent measurements of the minimum inhibitory concentration showed that the use of the European Committee on Antimicrobial Susceptibility Testing's epidemiological cutoff values led to underestimation of pharmacokinetic/pharmacodynamic target attainment in 10 cases (20%). TDM seems to be an effective means of optimizing antibiotic exposure in critically ill children. This requires timely plasma antibiotic assays and minimum inhibitory concentration measurements. It is important to define which patients should undergo TDM and how this monitoring should be managed.

Epidemiology and outcomes of multiple organ dysfunction syndrome following pediatric trauma.

Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database. We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status. Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1-43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4-5.3). Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma. Prognostic and Epidemiological; Level III.

Are platelet indices promising ratios for predicting pediatric septic shock prognosis?

The aim of the present study was to determine the prognostic value of thrombocytopenia, platelet indices (MPV/PLT and PDW/PLT) in children with septic shock. Septic shock is one of the major causes of mortality among children worldwide. A retrospective analysis was made of children admitted to the pediatric intensive care unit between November 2010 and December 2019. Two hundred four children were included; they were diagnosed with septic shock according to the international pediatric sepsis consensus conference criteria. The MPV/platelet ratio and PDW/platelet ratios were estimated as the MPV and PDW values divided by the platelet count on the first three days of hospitalization. The clinical outcome was 28-day mortality. MPV/PLT and PDW/PLT ratios were found to be significantly higher in the non-survivors than survivor (p≤0.001). In the multivariate logistic regression analysis, higher MPV/platelet ratios at 72h (OR: 7.41; 95% CI: 1.25-43.7; p=0.027) and PDW/platelet ratios at 72h (OR: 2.9; 95% CI: 1.13-7.50; p=0.027) were significant risk factors for mortality. Platelet indices are useful laboratory parameters in septic shock. MPV/PLT and PDW/PLT ratios can be promising reliable markers for 28-day mortality in children with septic shock (Tab. 4, Fig. 1, Ref. 29).

Patterns of Organ Dysfunction in Critically Ill Children Based on PODIUM Criteria.

The goal of this study was to determine the incidence, prognostic performance, and generalizability of the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) organ dysfunction criteria using electronic health record (EHR) data. Additionally, we sought to compare the performance of the PODIUM criteria with the organ dysfunction criteria proposed by the 2005 International Pediatric Sepsis Consensus Conference (IPSCC). Retrospective observational cohort study of critically ill children at 2 medical centers in the United States between 2010 and 2018. We assessed prevalence of organ dysfunction based on the PODIUM and IPSCC criteria for each 24-hour period from admission to 28 days. We studied the prognostic performance of the criteria to discriminate in-hospital mortality. Overall, 22 427 PICU admissions met inclusion criteria, and in-hospital mortality was 2.3%. The cumulative incidence of each PODIUM organ dysfunction ranged from 15% to 30%, with an in-hospital mortality of 6% to 10% for most organ systems. The number of concurrent PODIUM organ dysfunctions demonstrated good-to-excellent discrimination for in-hospital mortality (area under the curve 0.87-0.93 for day 1 through 28) and compared favorably to the IPSCC criteria (area under the curve 0.84-0.92, P < .001 to P = .06). We present the first evaluation of the PODIUM organ dysfunction criteria in 2 EHR databases. The use of the PODIUM organ dysfunction criteria appears promising for epidemiologic and clinical research studies using EHR data. More studies are needed to evaluate the PODIUM criteria that are not routinely collected in structured format in EHR databases.

Diagnostic Value of Mid Regional Proadrenomedullin as a Sepsis Biomarker in Pediatric Patients with Cancer-Related Chemotherapy

The aim of this study was to analyze the diagnostic value of mid regional proadrenomedullin as a sepsisbiomarker in pediatric patients with cancer-related chemotherapy. This cross-sectional observationalstudy was located in General Hospital Dr. Soetomo Surabaya from September until December 2020.International Pediatric Sepsis Consensus Conference criteria was used to define sepsis term on 2 studygroups. Serum mid regional proadrenomedullin has been drawn from 60 subjects (41 in-ward pediatricpatients) and measured on sandwich enzyme-linked immunosorbent assay from Elabscience® HumanMid Regional Proadrenomedullin. Humareader Single Plus® was used to measure the optical density.ROC analysis was used to find out cut off value, sensitivity, specificity, positive predictive value, negativepredictive value, negative likelihood ratio, positive likelihood ratio, and accuracy, respectively. Statisticsdeclared significant if p&lt;0.05 (95% CI). Between groups, temperature and heart rate were statisticallydifferent (p&lt;0.001; 95% CI). The median difference of mid regional proadrenomedullin between groupswas significant (p&lt;0.05; 95% CI). Cut off value 2,88 nmol/L, sensitivity 60.0%, specificity 56.67%,positive predictive value 58.06%, negative predictive value 58.62%, positive likelihood ratio 1.38,negative likelihood ratio 0.71 and diagnostic accuracy 59.33% was obtained while area under curvewas 0.707, respectively. Sepsis in children with cancer –related chemotherapy has not well diagnosedby serum mid regional proadrenomedullin.

PELOD-2 Score Mortality Prediction Ability in Children with Multiple Organ Dysfunction

This study evaluates PELOD-2 score mortality prediction ability in children with multiple organ dysfunction. The descriptive cross-sectional study was carried out on 110 children with Multiple Organ Dysfunction at the Pediatric intensive care unit in Vietnam National Children’s Hospital from 1st January 2015 to 31th June 2016. The study results show that the average PELOD-2 score was high (8.8 ± 3.85 points); the PELOD-2 score of the mortality group was significantly higher than the survivor group with 7.07 ± 2.37 and 10.43 ± 4,28, respectively; mortality rate was directly proportional to PELOD-2 score; the PELOD-2 score could separate the mortality group from the survivor group with the area under the ROC curve of 0.76 and the cut-point PELOD-2 score of 8.5. If children with multiple organ dysfunction had over 10 points of PELOD-2 score, their mortality prediction value was nearly the same as the actual mortality rate. The study concludes that PELOD-2 score was significantly correlated with associated multiple organ dysfunction syndrome and useful in predicting mortality.&#x0D; Keywords: Multiple organ dysfunction, PELOD-2 score.&#x0D; References&#x0D; [1] B. Goldstein, B. Giroir, A. Randolph, International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics. Pediatric Critical Care Medicine, Vol. 6, 2005, pp. 2-8.[2] J. D. Wilkinson et al., Mortality Associated with Multiple Organ System Failure and Sepsis in Pediatric Intensive Care Unit, The Journal of Pediatrics, Vol. 111, 1987, pp. 324-328[3] J. A. Tantaleán et al., Multiple Organ Dysfunction Syndrome in Children, Pediatric Critical Care Medicine, Vol. 4, 2003, pp. 181-185[4] T. K. Hao, Clinical Characteristics and Prognostic Value of PELOD Score in Pediatric Population With Multi-Organ Dysfunction, 11th Pediatric National Conference, 2014 (in Vietnamese).[5] S. Leteurtre et al., PELOD-2: An Update of the Pediatric Logistic Organ Dysfunction Score, Critical Care Medicine, Vol. 41, 2013, pp. 1761-1773.[6] J. P. Gonçalves et al., Performance of PRISM III and PELOD-2 Scores in A Pediatric Intensive Care Unit, European Journal of Pediatrics, Vol. 174, 2016, pp. 1305-1310.[7] T. K. Hao, Evaluation of PMODS Score in Patients with Multi-organ Dysfunction Syndrome at A Pediatric Intensive Care Unit, Journal of Practical Medicine, Vol. 805, 2012 (in Vietnamese).

Early Prediction of Multiple Organ Dysfunction in the Pediatric Intensive Care Unit.

Objective: The objective of the study is to build models for early prediction of risk for developing multiple organ dysfunction (MOD) in pediatric intensive care unit (PICU) patients.Design: The design of the study is a retrospective observational cohort study.Setting: The setting of the study is at a single academic PICU at the Johns Hopkins Hospital, Baltimore, MD.Patients: The patients included in the study were <18 years of age admitted to the PICU between July 2014 and October 2015.Measurements and main results: Organ dysfunction labels were generated every minute from preceding 24-h time windows using the International Pediatric Sepsis Consensus Conference (IPSCC) and Proulx et al. MOD criteria. Early MOD prediction models were built using four machine learning methods: random forest, XGBoost, GLMBoost, and Lasso-GLM. An optimal threshold learned from training data was used to detect high-risk alert events (HRAs). The early prediction models from all methods achieved an area under the receiver operating characteristics curve ≥0.91 for both IPSCC and Proulx criteria. The best performance in terms of maximum F1-score was achieved with random forest (sensitivity: 0.72, positive predictive value: 0.70, F1-score: 0.71) and XGBoost (sensitivity: 0.8, positive predictive value: 0.81, F1-score: 0.81) for IPSCC and Proulx criteria, respectively. The median early warning time was 22.7 h for random forest and 37 h for XGBoost models for IPSCC and Proulx criteria, respectively. Applying spectral clustering on risk-score trajectories over 24 h following early warning provided a high-risk group with ≥0.93 positive predictive value.Conclusions: Early predictions from risk-based patient monitoring could provide more than 22 h of lead time for MOD onset, with ≥0.93 positive predictive value for a high-risk group identified pre-MOD.

Disseminated Intravascular Coagulation Predicts Adverse Outcomes in Children with Suspected Sepsis in the Emergency Department

Background: In disseminated intravascular coagulation (DIC), hemostatic dysregulation causes microvascular clotting and consumptive coagulopathy, resulting in hemorrhage and organ failure. It has been difficult to dissect the effects of DIC from the underlying predisposing condition, but DIC has been reported as an independent predictor of poor outcomes in adult sepsis (Voves, et al, Blood Coagulation and Fibrinolysis 2006). Epidemiologic studies demonstrate an increasing prevalence of sepsis in children, and biomarkers predicting outcomes are needed to guide prevention and treatment. We assessed the influence of DIC score on illness severity and mortality in children with suspected sepsis. Methods: This retrospective study used a clinical sepsis registry of pediatric patients presenting with suspected sepsis to the Emergency Department (ED) at Children's Hospital Colorado between April 1, 2012 and June 26, 2017. Exclusion criteria included: age <60 days or >18 years of age, transfer from another facility, and hospital length of stay (LOS) < 24 hours. Clinical data including age, gender, DIC score components (platelet count, fibrinogen, prothrombin time, D-dimer), use of vasopressors, mechanical ventilation, hospital and pediatric intensive care unit (PICU) length of stay, and presence of end-organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference were extracted from the electronic medical record. In patients with multiple ED encounters, the first encounter with a full DIC evaluation was chosen for analysis. DIC scores were calculated based on the International Society of Thrombosis and Hemostasis (ISTH) criteria, with a score ≥ 5 indicating overt DIC. The influence of overt DIC on vasopressor use (primary outcome), 30-day mortality, and 1-year mortality were evaluated using univariate logistic regression. PICU and hospital LOS in those with and without overt DIC were compared using t-tests. Results : Of 1585 children with potential sepsis, 324 (20.4%) were fully evaluated for DIC within 24 hours; 47/324 (14.5%) were positive for overt DIC. Vasopressor use and mortality frequencies in each category are listed in Table 1. Patients evaluated for DIC were more ill than those who were not, with increased risk of vasopressor use, mortality, mechanical ventilation, end-organ dysfunction, and longer hospital and PICU length of stay (p < 0.005 for each). Among patients who had full DIC evaluations within 24 hours, children with overt DIC compared with those without had increased odds of vasopressor use (OR 2.52, 95% CI 1.34, 4.72, p=0.004), and 1-year mortality (OR 2.88, 95% CI 1.23, 6.77, p=0.014). The odds of death within 30 days of admission were insignificantly increased in overt DIC (OR 2.63, 95% CI 0.66, 10.55, p=0.17). Patients with overt DIC had longer average hospital length of stay (18 vs. 10 days, p=0.02) and PICU stay (7.5 vs. 4 days, p=0.03) compared to those with DIC scores < 5. Conclusions: Among pediatric patients with suspected sepsis, clinical assessment for DIC as well as laboratory confirmation of overt DIC are predictive of higher rates of vasopressor use, longer hospital and PICU lengths of stay, and increased 1 year mortality. These data suggest that the ISTH DIC score can be a valuable objective tool to predict risks for adverse outcomes in children presenting with suspected sepsis. [Display omitted] DisclosuresWarren:Bayer Hemophilia Awards Program: Research Funding; CSL Behring Heimburger Award: Research Funding.

Correlation between syndecan-1 level and PELOD-2 score and mortality in pediatric sepsis.

Objective:To analyze the correlation between glycocalyx disruption measured via the serum syndecan-1 level and organ dysfunctions assessed by the PELOD-2 score and to evaluate its association with mortality in pediatric sepsis.Methods:We performed a prospective observational study in a tertiary public hospital. Sixty-eight pediatric patients diagnosed with sepsis according to International Pediatric Sepsis Consensus Conference criteria were consecutively recruited. We performed measurements of day 1 and day 5 serum syndecan-1 levels and PELOD-2 score components. Patients were followed up to 28 days following sepsis diagnosis.Results:Overall, the syndecan-1 level was increased in all subjects, with a significantly higher level among septic shock patients (p = 0.01). The day 1 syndecan-1 level was positively correlated with the day 1 PELOD-2 score with a correlation coefficient of 0.35 (p = 0.003). Changes in syndecan-1 were positively correlated with changes in the PELOD-2 score, with a correlation coefficient of 0.499 (p < 0.001) during the first five days. Using the cutoff point of day 1 syndecan-1 ≥ 430ng/mL, organ dysfunction (PELOD-2 score of ≥ 8) could be predicted with an AUC of 74.3%, sensitivity of 78.6%, and specificity of 68.5% (p = 0.001).Conclusion:The day 1 syndecan-1 level was correlated with the day 1 PELOD-2 score but not 28-day mortality. Organ dysfunction (PELOD-2 ≥ 8) could be predicted by the syndecan-1 level in the first 24 hours of sepsis, suggesting its significant pathophysiological involvement in sepsis-associated organ dysfunction.

Serum Ferritin Predicts Neither Organ Dysfunction Nor Mortality in Pediatric Sepsis Due to Tropical Infections.

Objective: To evaluate serial ferritin levels measured in the initial 72 h of admission as a biomarker for new and progressive multi organ dysfunction syndrome (NPMODS) and mortality (unfavorable outcomes) in critically ill children with sepsis due to tropical infections.Material and Methods: In this prospective observational study from a tertiary care teaching hospital in India, children 3 month to 12 years with a diagnosis of acute febrile illness and any two features suggesting tropical infections [cytopenia (platelet count <1,00,000/cu.mm, total leucocyte count <4,000/cu.mm), hepatomegaly and/or splenomegaly, lymphadenopathy, systemic signs (rash, edema), respiratory distress, and encephalopathy not accounted by localized infection] were eligible for inclusion. Children with known or suspected disorder of iron metabolism were excluded. Primary outcome was to determine the association of serial ferritin levels with mortality and NPMODS. Secondary outcomes included estimation of the prevalence of hyperferritinemia and comparison of risk prediction scores with serial ferritin measurement in predicting unfavorable outcomes.Measurements and Main Results: In the 202 children enrolled, diagnosis could be established in 133 (65.8%) children. Scrub typhus and dengue were the most common infections. Median (IQR) ferritin measured at admission (n = 183) and on day 3 (n = 120) of hospital stay were 798 (378, 3,205) μg/L and 429 (213,680) μg/L, respectively. Majority (n = 180, 89.1%) had MODS at admission defined as per International pediatric sepsis consensus conference. NPMODS occurred in 47 (23.3%) children of whom 37 (18.3%) died. Children with three or less organ dysfunctions had lower mortality. Neither admission ferritin values nor the percentage change over 72 h was different between children with favorable and unfavorable outcomes. Pediatric Risk of Mortality (PRISM-III) and daily Pediatric Logistic Organ Dysfunction score (dPELOD2 score) were significantly different in those with unfavorable outcomes. Admission ferritin levels and percentage change in 72 h had poor discriminatory power for mortality with AUC of 0.53 (0.53, 0.67) and 0.50 (0.50, 0.64), respectively. dPELOD2 had the best discriminatory power for mortality with AUC of 0.89 (0.89, 0.95).Conclusions: Serial ferritin estimation predicted neither organ dysfunction nor mortality in pediatric sepsis with tropical infections. dPELOD-2 and PRISM-III predicted unfavorable outcomes better than ferritin. The current diagnostic criteria for MODS overestimated organ dysfunctions in tropical infections and hence may need modification with further validation in this epidemiological cohort.

EFFECT OF FISH-OIL-ENRICHED INTRAVENOUS LIPID EMULSION ON SYSTEMIC INFLAMMATORY RESPONSE SYNDROME IN POST INTESTINAL SURGERY CHILDREN

Intravenous lipid emulsions (IVLE) is one of the compositions of the parenteral nutrition (PN) that recommended in children who cannot meet their caloric requirements especially after small intestinal surgery and diff erentiated by their infl ammatory eff ects. The fi rst generation IVLE is proinfl ammatory, the second and the third are infl ammatory neutral, while the fourth (fi sh-oil-enriched) is anti-infl ammatory. The objective of this study is to investigate the eff ect of fi shoil enriched IVLE on systemic infl ammatory response syndrome (SIRS) in children after small intestinal surgery. A retrospective study using medical record was undertaken in children after small intestinal surgery admitted Dr. Soetomo Hospital, Surabaya in 2016-2017. Children with duodenal and jejunoileal atresia who had PN for at least three days were included. The types of IVLE used are FOLE and non-FOLE. Defi nition of SIRS was based on International Pediatric Sepsis Consensus Conference in 2005. A total of 25 children were included in this study. There were 44% children received FOLE and 48% received non-FOLE while 8% children received no IVLE. Median duration and dose of IVLE was 8 (5-15,5) days and 1,8 (1,25-2) g/kg/day. SIRS was signifi cantly more common in girls (OR 9 95%CI 1,3-63,0; p=0,036) and in the non-FOLE children (OR 8,0 95% CI 1,24 – 51,50; p=0,022).

Admission platelet count and indices as predictors of outcome in children with severe Sepsis: a prospective hospital-based study

BackgroundSepsis is still one of the main causes of infants and children mortality especially in developing, economically challenged countries with limited resources. Our objective in this study was to determine, the prognostic value of platelet count, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) in critically ill infants and children with severe sepsis, as they are readily available biomarkers, that can guide clinicians during managing of severe sepsis.MethodsSixty children were included; they were diagnosed with severe sepsis according to the international pediatric sepsis consensus conference criteria. At admission to Pediatric intensive care unit, complete blood count with platelet count and parameters (MPV, PDW and PCT) and C-reactive protein (CRP) level were determined for all children. Also, assessment of the Pediatric Risk of Mortality (PRISM III) score was done to all. These children were followed up till discharge from hospital or death. Accordingly, they were grouped into: (1) Survivor group: included 41 children. (2) Non-survivor group: included 19 children.ResultsPlatelet count and PCT were significantly lower (p < 0.001) and MPV was significantly higher in non-survivor than survivors (p = 0.004). MPV/PLT, MPV/PCT, PDW/PLT, PDW/PCT ratios were found to be significantly higher in the non-survivors than survivor (p < 0.001 in all). PCT with sensitivity = 94.74%, was the most sensitive platelet parameter for prediction of death, while MPV/PCT was the most sensitive ratio (sensitivity = 94.7%).ConclusionThrombocytopenia, platelet indices and their ratios, especially plateletcrit and MPV/PCT, are readily available, sensitive, prognostic markers, that can identify the severe sepsis patients with poorest outcome.

AB011. Sepsis in pediatrics: current concepts of terminology and management

: Sepsis is one of the leading causes of mortality among children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics and we wanted to highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. The definition of pediatric sepsis is currently in a state of evolution. For the past two decades, sepsis has been defined as “systemic inflammatory response syndrome (SIRS) caused by infection” both for adults and children. International pediatric sepsis consensus conference in 2015 revised the adult SIRS criteria for children. New sepsis criteria were advocated as “Sepsis-3” in 2017, which redefined “as life-threatening organ dysfunction caused by a dysregulated host response to infection”. Unfortunately, this change in the definition of sepsis is applied to adult population at this moment, consensus definition in children are not well established. The epidemiology of pediatric sepsis varies from study to study probably because of their different era, population, and diagnostic criteria. Sepsis is often diagnosed too late, because the clinical symptoms and laboratory signs that are currently used for the diagnosis of sepsis, like raised temperature, increased pulse or breathing rate, or white blood cell count are unspecific. In children, the signs and symptoms may be subtle and deterioration rapid. Early sepsis treatment is cost effective, reducing hospital and Critical Care bed days for patients. The current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment. New knowledge was added regarding the hemodynamic management and the timely use of antimicrobials. The early administration of antibiotics and hemodynamic stabilization with fluid resuscitation and inotropic/vasopressor support are like both wheels of a vehicle for the initial management of sepsis. The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection. The management of pediatric sepsis would be expected to make further progress.