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Comparison of Methods for Identification of Pediatric Severe Sepsis and Septic Shock in the Virtual Pediatric Systems Database.

ABSTRACT: OBJECTIVES:To compare the performance of three methods of identifying children with severe sepsis and septic shock from the Virtual Pediatric Systems database to prospective screening using consensus criteria. DESIGN:Observational cohort study. SETTING:Single-center PICU. PATIENTS:Children admitted to the PICU in the period between March 1, 2012, and March 31, 2014. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:During the study period, all PICU patients were prospectively screened daily for sepsis, and those meeting consensus criteria for severe sepsis or septic shock on manual chart review were entered into the sepsis registry. Of 7,459 patients admitted to the PICU during the study period, 401 met consensus criteria for severe sepsis or septic shock (reference standard cohort). Within Virtual Pediatric Systems, patients identified using "Martin" (n = 970; ? = 0.43; positive predictive value = 34%; F1 = 0.48) and "Angus" International Classification of Diseases, 9th Edition, Clinical Modification codes (n = 1387; ? = 0.28; positive predictive value = 22%; F1 = 0.34) showed limited agreement with the reference standard cohort. By comparison, explicit International Classification of Diseases, 9th Edition, Clinical Modification codes for severe sepsis (995.92) and septic shock (785.52) identified a smaller, more accurate cohort of children (n = 515; ? = 0.61; positive predictive value = 57%; F1 = 0.64). PICU mortality was 8% in the reference standard cohort and the cohort identified by explicit codes; age, illness severity scores, and resource utilization did not differ between groups. Analysis of discrepancies between the reference standard and Virtual Pediatric Systems explicit codes revealed that prospective screening missed 66 patients with severe sepsis or septic shock. After including these patients in the reference standard cohort as an exploratory analysis, agreement between the cohort of patients identified by Virtual Pediatric Systems explicit codes and the reference standard cohort improved (? = 0.73; positive predictive value = 70%; F1 = 0.75). CONCLUSIONS:Children with severe sepsis and septic shock are best identified in the Virtual Pediatric Systems database using explicit diagnosis codes for severe sepsis and septic shock. The accuracy of these codes and level of clinical detail available in the Virtual Pediatric Systems database allow for sophisticated epidemiologic studies of pediatric severe sepsis and septic shock in this large, multicenter database.

SUBMITTER: Lindell RB

PROVIDER: S-EPMC6336511 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Comparison of Methods for Identification of Pediatric Severe Sepsis and Septic Shock in the Virtual Pediatric Systems Database.

Lindell Robert B RB Nishisaki Akira A Weiss Scott L SL Balamuth Fran F Traynor Danielle M DM Chilutti Marianne R MR Grundmeier Robert W RW Fitzgerald Julie C JC

Critical care medicine 20190201 2

<h4>Objectives</h4>To compare the performance of three methods of identifying children with severe sepsis and septic shock from the Virtual Pediatric Systems database to prospective screening using consensus criteria.<h4>Design</h4>Observational cohort study.<h4>Setting</h4>Single-center PICU.<h4>Patients</h4>Children admitted to the PICU in the period between March 1, 2012, and March 31, 2014.<h4>Interventions</h4>None.<h4>Measurements and main results</h4>During the study period, all PICU pati ...[more]

PMID: 30394917

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Project description:Importance:The global patterns and distribution of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock remain poorly described. Objective:We performed a systematic review and meta-analysis of studies of children with severe sepsis and septic shock to elucidate the patterns of CFRs in developing and developed countries over time. We also described factors associated with CFRs. Data Sources:We searched PubMed, Web of Science, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central systematically for randomized clinical trials and prospective observational studies from earliest publication until January 2017, using the keywords "pediatric," "sepsis," "septic shock," and "mortality." Study Selection:Studies involving children with severe sepsis and septic shock that reported CFRs were included. Retrospective studies and studies including only neonates were excluded. Data Extraction and Synthesis:We conducted our systematic review and meta-analysis in close accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled case-fatality estimates were obtained using random-effects meta-analysis. The associations of study period, study design, sepsis severity, age, and continents in which studies occurred were assessed with meta-regression. Main Outcomes and Measures:Meta-analyses to provide pooled estimates of CFR of pediatric severe sepsis and septic shock over time. Results:Ninety-four studies that included 7561 patients were included. Pooled CFRs were higher in developing countries (31.7% [95% CI, 27.3%-36.4%]) than in developed countries (19.3% [95% CI, 16.4%-22.7%]; P < .001). Meta-analysis of CFRs also showed significant heterogeneity across studies. Continents that include mainly developing countries reported higher CFRs (adjusted odds ratios: Africa, 7.89 [95% CI, 6.02-10.32]; P < .001; Asia, 3.81 [95% CI, 3.60-4.03]; P < .001; South America, 2.91 [95% CI, 2.71-3.12]; P < .001) than North America. Septic shock was associated with higher CFRs than severe sepsis (adjusted odds ratios, 1.47 [95% CI, 1.41-1.54]). Younger age was also a risk factor (adjusted odds ratio, 0.95 [95% CI, 0.94-0.96] per year of increase in age). Earlier study eras were associated with higher CFRs (adjusted odds ratios for 1991-2000, 1.24 [95% CI, 1.13-1.37]; P < .001) compared with 2011 to 2016. Time-trend analysis showed higher CFRs over time in developing countries than developed countries. Conclusions and Relevance:Despite the declining trend of pediatric severe sepsis and septic shock CFRs, the disparity between developing and developed countries persists. Further characterizations of vulnerable populations and collaborations between developed and developing countries are warranted to reduce the burden of pediatric sepsis globally.

Project description:The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the microcirculation during severe sepsis.Prospective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 to December 2011, with severe sepsis and at least two sepsis-induced organ failures occurring within 48 hours from the onset of sepsis, who received an infusion of aPC (24 mcg/kg/h for 96 hours) (aPC group). Patients with contraindications to aPC administration were also monitored (no-aPC group).At baseline (before starting aPC infusion, T0), after 24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 6 hours after the end of aPC infusion (T2), general clinical and hemodynamic parameters were collected and the sublingual microcirculation was evaluated with sidestream dark-field imaging. Total vessel density (TVD), perfused vessel density (PVD), De Backer score, microvascular flow index (MFIs), the proportion of perfused vessels (PPV) and the flow heterogeneity index (HI) were calculated for small vessels. The perfused boundary region (PBR) was measured as an index of glycocalyx damage. Variables were compared between time points and groups using non parametric or parametric statistical tests, as appropriate.In the 13 aPC patients mean arterial pressure (MAP), base excess, lactate, PaO2/FiO2 and the Sequential Organ Failure Assessment (SOFA) score significantly improved over time, while CI and ITBVI did not change. MFIs, TVD, PVD, PPV significantly increased over time and the HI decreased (p?<?0.05 in all cases), while the PBR did not change. No-aPC patients (n?=?9) did not show any change in the microcirculation over time. A positive correlation was found between MFIs and MAP. TVD, PVD and De Backer score negatively correlated with norepinephrine dose, and the SOFA score negatively correlated with MFIs, TVD and PVD.aPC significantly improves the microcirculation in patients with severe sepsis/septic shock.NCT01806428.

Project description:ObjectivesTo assess the prevalence of immunocompromised diagnoses among children with severe sepsis and septic shock, and to determine the association between immunocompromised diagnoses and clinical outcomes after adjustment for demographics and illness severity.DesignRetrospective multicenter cohort study.SettingEighty-three centers in the Virtual Pediatric Systems database.PatientsChildren with severe sepsis or septic shock admitted to a participating PICU between January 1, 2012, and December 31, 2016.InterventionsNone.Measurements and main resultsAcross 83 centers, we identified 10,768 PICU admissions with an International Classification of Diseases, 9th Revision, Clinical Modification code for severe sepsis or septic shock; 3,021 of these patients (28%) had an immunocompromised diagnosis. To evaluate variation across centers and determine factors associated with PICU mortality, we used mixed-effect logistic regression models. Among patients without hematopoietic cell transplant, congenital immunodeficiency (adjusted odds ratio, 1.90; 95% CI, 1.24-2.92), multiple prior malignancies (adjusted odds ratio, 1.86; 95% CI, 1.15-2.99), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 3.09; 95% CI, 1.91-4.98) were associated with an increased odds of PICU mortality. Among patients with prior hematopoietic cell transplant, liquid malignancy (adjusted odds ratio, 3.15; 95% CI, 2.09-4.74), congenital immunodeficiency (adjusted odds ratio, 6.94; 95% CI, 3.84-12.53), multiple prior malignancies (adjusted odds ratio, 3.54; 95% CI, 1.80-6.95), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 2.79; 95% CI, 1.36-5.71) were associated with an increased odds of PICU mortality. PICU mortality varied significantly by center, and a higher mean number of sepsis patients per month in a center was associated with lower PICU mortality (adjusted odds ratio, 0.94; 95% CI, 0.90-0.98). PICU resource utilization varied by immunocompromised diagnosis and history of hematopoietic cell transplant, and among survivors immunocompromised patients have shorter median PICU length of stay compared with patients without immunocompromised diagnoses (p < 0.001).ConclusionsImmunocompromised diagnoses are present in 28% of children with severe sepsis or septic shock. Multiple prior malignancies, hemophagocytic lymphohistiocytosis, congenital immunodeficiency, and hematopoietic cell transplant are independently associated with an increased odds of PICU mortality in children with severe sepsis or septic shock. Significant variation exists in PICU mortality among centers despite adjustment for immunocompromised diagnoses, known risk factors for sepsis-related mortality, and center-level sepsis volume.

Project description:BACKGROUND:While the process of sepsis-induced immunosuppression is now well described in adults, very little information is available on immune functions in pediatric sepsis. The current study investigated this in children with septic shock by performing immunomonitoring, including both innate (monocyte human leukocyte antigen-DR, mHLA-DR, expression) and adaptive immunity (lymphocyte subsets count), as well as cytokine concentrations (IL-6, IL-8, IL-10, IL-1Ra, TNF-?, IFN-?). Subsequent objectives were to assess the associations between inflammatory response, potential immunosuppression and secondary acquired infection occurrence. METHODS:Single-center prospective observational study, including children aged between 1 month and 18 years admitted to pediatric intensive care unit (PICU) for septic shock. Age-matched controls were children hospitalized for elective surgery without any infectious criteria. Blood was sampled at day 1-2, 3-5, and 7-9 after sepsis onset. mHLA-DR and lymphocyte subsets count were measured by flow cytometry and cytokine concentrations by Luminex technology. RESULTS:A total of 26 children and 30 controls were included. Patients had lymphopenia, and mHLA-DR levels were significantly lower than controls at each time point (p?<?0.0001). All cytokines peaked at day 1-2. Children with secondary acquired infection had lower day 3-5 mHLA-DR and higher pro-inflammatory cytokine concentrations (IL-6, IL-8 and TNF-?) at day 1-2 compared to children without secondary acquired infection. CONCLUSIONS:The higher initial inflammatory cytokine production was, the more innate immunity was altered, while evaluated by low mHLA-DR expression. Children with decreased mHLA-DR expression developed more secondary acquired infections. Upon confirmation in multicenter cohorts, these results pave the way for immunostimulation for the most immunosuppressed children in order to prevent nosocomial infections in PICU. Trial registration PedIRIS study NCT02848144. Retrospectively registered 28 July 2016.

Dataset Information

Comparison of Methods for Identification of Pediatric Severe Sepsis and Septic Shock in the Virtual Pediatric Systems Database.

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Comparison of Methods for Identification of Pediatric Severe Sepsis and Septic Shock in the Virtual Pediatric Systems Database.

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