Dataset Information

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.

ABSTRACT:

Objectives

Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis.

Design

Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure.

Setting

Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.

Patients

Children with severe sepsis and indwelling arterial or central venous catheters.

Interventions

Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge.

Measurements and main results

Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08).

Conclusions

These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.

SUBMITTER: Carcillo JA

PROVIDER: S-EPMC8121153 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.

Carcillo Joseph A JA Berg Robert A RA Wessel David D Pollack Murray M Meert Kathleen K Hall Mark M Newth Christopher C Lin John C JC Doctor Allan A Shanley Tom T Cornell Tim T Harrison Rick E RE Zuppa Athena F AF Reeder Ron W RW Banks Russell R Kellum John A JA Holubkov Richard R Notterman Daniel A DA Dean J Michael JM

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20191201 12

<h4>Objectives</h4>Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortalit ...[more]

PMID: 31568246

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Project description:ObjectivesWe hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis.DesignProspective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes.SettingTertiary children's hospital PICU.PatientsOne hundred consecutive severe sepsis admissions.InterventionsClinical data were recorded daily, and blood was collected twice weekly.Measurements and main resultsMultiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002).ConclusionsOur approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

Project description:ObjectivesAcute disorders of consciousness (DoC) in pediatric severe sepsis are associated with increased risk of morbidity and mortality. We sought to examine the frequency of and factors associated with DoC in children with sepsis-induced organ failure.DesignSecondary analysis of the multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS).SettingNine tertiary care PICUs in the United States.PatientsChildren less than 18 years old admitted to a PICU with severe sepsis and at least one organ failure during a PICU stay.InterventionsNone.Measurements and main resultsThe primary outcome was frequency of DoC, defined as Glasgow Coma Scale (GCS) less than 12 in the absence of sedatives during an ICU stay, among children with severe sepsis and the following: single organ failure, nonphenotypeable multiple organ failure (MOF), MOF with one of the PHENOMS phenotypes (immunoparalysis-associated MOF [IPMOF], sequential liver failure-associated MOF, thrombocytopenia-associated MOF), or MOF with multiple phenotypes. A multivariable logistic regression analysis was performed to evaluate the association between clinical variables and organ failure groups with DoC. Of 401 children studied, 71 (18%) presented with DoC. Children presenting with DoC were older (median 8 vs 5 yr; p = 0.023), had increased hospital mortality (21% vs 10%; p = 0.011), and more frequently presented with both any MOF (93% vs 71%; p < 0.001) and macrophage activation syndrome (14% vs 4%; p = 0.004). Among children with any MOF, those presenting with DoC most frequently had nonphenotypeable MOF and IPMOF (52% and 34%, respectively). In the multivariable analysis, older age (odds ratio, 1.07; 95% CI, 1.01-1.12) and any MOF (3.22 [1.19-8.70]) were associated with DoC.ConclusionsOne of every five children with severe sepsis and organ failure experienced acute DoC during their PICU stay. Preliminary findings suggest the need for prospective evaluation of DoC in children with sepsis and MOF.

Project description:Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Project description:ObjectivesSepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes.DesignRetrospective cohort study.SettingOne hundred eleven U.S. hospitals in the Cerner HealthFacts dataset.PatientsAdults hospitalized in 2013-2015.InterventionsNone.Measurements and main resultsWe identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/μL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach's alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities.ConclusionsThe Adult Sepsis Event's eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria.

Project description:ImportanceThe Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children.ObjectivesTo adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection.Design, setting, and participantsThis retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison.ExposuresOrgan dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions.Main outcomes and measuresThe primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection.ResultsIn all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range [IQR]) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course.Conclusions and relevanceThe pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.

Dataset Information

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.

Objectives

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.

Similar Datasets

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