Dataset Information

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

ABSTRACT:

Objectives

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.

Design

We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015.

Setting

Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland.

Patients

Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old.

Interventions

None.

Measurements and main results

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.

Conclusions

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.

SUBMITTER: Schlapbach LJ

PROVIDER: S-EPMC10904004 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Schlapbach Luregn J LJ Goertz Sabrina S Hagenbuch Niels N Aubert Blandine B Papis Sebastien S Giannoni Eric E Posfay-Barbe Klara M KM Stocker Martin M Heininger Ulrich U Bernhard-Stirnemann Sara S Niederer-Loher Anita A Kahlert Christian R CR Natalucci Giancarlo G Relly Christa C Riedel Thomas T Aebi Christoph C Berger Christoph C Agyeman Philipp K A PKA

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20231025 3

<h4>Objectives</h4>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.<h4>Design</h4>We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015.<h4>S ...[more]

PMID: 37878412

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Project description:BackgroundSepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis.MethodsWe created 72-h SOFA score trajectories in patients with sepsis from four diverse intensive care unit (ICU) cohorts. We then used dynamic time warping (DTW) to compute heterogeneous SOFA trajectory similarities and hierarchical agglomerative clustering (HAC) to identify trajectory-based subphenotypes. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership at 6 and 24 h after being admitted to the ICU. The model was tested on three validation cohorts. Sensitivity analyses were performed with alternative clustering methodologies.ResultsA total of 4678, 3665, 12,282, and 4804 unique sepsis patients were included in development and three validation cohorts, respectively. Four subphenotypes were identified in the development cohort: Rapidly Worsening (n = 612, 13.1%), Delayed Worsening (n = 960, 20.5%), Rapidly Improving (n = 1932, 41.3%), and Delayed Improving (n = 1174, 25.1%). Baseline characteristics, including the pattern of organ dysfunction, varied between subphenotypes. Rapidly Worsening was defined by a higher comorbidity burden, acidosis, and visceral organ dysfunction. Rapidly Improving was defined by vasopressor use without acidosis. Outcomes differed across the subphenotypes, Rapidly Worsening had the highest in-hospital mortality (28.3%, P-value < 0.001), despite a lower SOFA (mean: 4.5) at ICU admission compared to Rapidly Improving (mortality:5.5%, mean SOFA: 5.5). An overall prediction accuracy of 0.78 (95% CI, [0.77, 0.8]) was obtained at 6 h after ICU admission, which increased to 0.87 (95% CI, [0.86, 0.88]) at 24 h. Similar subphenotypes were replicated in three validation cohorts. The majority of patients with sepsis have an improving phenotype with a lower mortality risk; however, they make up over 20% of all deaths due to their larger numbers.ConclusionsFour novel, clinically-defined, trajectory-based sepsis subphenotypes were identified and validated. Identifying trajectory-based subphenotypes has immediate implications for the powering and predictive enrichment of clinical trials. Understanding the pathophysiology of these differential trajectories may reveal unanticipated therapeutic targets and identify more precise populations and endpoints for clinical trials.

Project description:OBJECTIVES:Limited data exist about the timing and significance of mitochondrial alterations in children with sepsis. We therefore sought to determine if alterations in mitochondrial respiration and content within circulating peripheral blood mononuclear cells were associated with organ dysfunction in pediatric sepsis. DESIGN:Prospective observational study SETTING:: Single academic PICU. PATIENTS:One-hundred sixty-seven children with sepsis/septic shock and 19 PICU controls without sepsis, infection, or organ dysfunction. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Mitochondrial respiration and content were measured in peripheral blood mononuclear cells on days 1-2, 3-5, and 8-14 after sepsis recognition or once for controls. Severity and duration of organ dysfunction were determined using the Pediatric Logistic Organ Dysfunction score and organ failure-free days through day 28. Day 1-2 maximal uncoupled respiration (9.7?±?7.7 vs 13.7?±?4.1 pmol O2/s/10 cells; p = 0.02) and spare respiratory capacity (an index of bioenergetic reserve: 6.2?±?4.3 vs 9.6?±?3.1; p = 0.005) were lower in sepsis than controls. Mitochondrial content, measured by mitochondrial DNA/nuclear DNA, was higher in sepsis on day 1-2 than controls (p = 0.04) and increased in sepsis patients who had improving spare respiratory capacity over time (p = 0.005). Mitochondrial respiration and content were not associated with day 1-2 Pediatric Logistic Organ Dysfunction score, but low spare respiratory capacity was associated with higher Pediatric Logistic Organ Dysfunction score on day 3-5. Persistently low spare respiratory capacity was predictive of residual organ dysfunction on day 14 (area under the receiver operating characteristic, 0.72; 95% CI, 0.61-0.84) and trended toward fewer organ failure-free days although day 28 (? coefficient, -0.64; 95% CI, -1.35 to 0.06; p = 0.08). CONCLUSIONS:Mitochondrial respiration was acutely decreased in peripheral blood mononuclear cells in pediatric sepsis despite an increase in mitochondrial content. Over time, a rise in mitochondrial DNA tracked with improved respiration. Although initial mitochondrial alterations in peripheral blood mononuclear cells were unrelated to organ dysfunction, persistently low respiration was associated with slower recovery from organ dysfunction.

Project description:ObjectivesDevelop and test the performance of electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV and electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 scores.DesignRetrospective, single-center cohort derived from structured electronic health record data.SettingLarge, quaternary PICU at a freestanding, university-affiliated children's hospital.PatientsAll encounters with a PICU admission between January 1, 2009, and December 31, 2017, identified using electronic definitions of inpatient encounter.InterventionsNone.Measurements and main resultsThe main outcome was predictive validity of each score for hospital mortality, assessed as model discrimination and calibration. Discrimination was examined with the area under the receiver operating characteristics curve and the area under the precision-recall curve. Calibration was assessed with the Hosmer-Lemeshow goodness of fit test and calculation of a standardized mortality ratio. Models were recalibrated with new regression coefficients in a training subset of 75% of encounters selected randomly from all years of the cohort and the calibrated models were tested in the remaining 25% of the cohort. Content validity was assessed by examining correlation between electronic versions of the scores and prospectively calculated data (electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV) and an alternative informatics approach (Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score). The cohort included 21,335 encounters. Correlation coefficients indicated strong agreement between different methods of score calculation. Uncalibrated area under the receiver operating characteristics curves were 0.96 (95% CI, 0.95-0.97) for electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score and 0.87 (95% CI, 0.85-0.89) for electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV for inpatient mortality. The uncalibrated electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV standardized mortality ratio was 0.63 (0.59-0.66), demonstrating strong agreement with previous, prospective evaluation at the study center. The uncalibrated electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score standardized mortality ratio was 0.20 (0.18-0.21). All models required recalibrating (all Hosmer-Lemeshow goodness-of-fit, p < 0.001) and subsequently demonstrated acceptable goodness-of-fit when examined in a test subset (n = 5,334) of the cohort.ConclusionsElectronically derived intensive care acuity scores demonstrate very good to excellent discrimination and can be calibrated to institutional outcomes. This approach can facilitate both performance improvement and research initiatives and may offer a scalable strategy for comparison of interinstitutional PICU outcomes.

Dataset Information

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

Objectives

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

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

Similar Datasets

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