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Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis.

ABSTRACT: Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear.To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction.Analysis of infection-related hospitalizations from the 2005 hospital discharge data of 7 US states and infection-related emergency department visits from the 2003-2007 National Hospital Ambulatory Care Survey.Age- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction.Of 8,661,227 non-childbirth-related discharges, 2,261,857 were associated with an infection, and of these, 381,787 (16.8%) had severe sepsis. Black patients had a 67% higher age- and sex-standardized severe sepsis rate than did white patients (9.4; 95% confidence interval [CI], 9.3-9.5 vs 5.6; 95% CI, 5.6-5.6 per 1000 population; P < .001) and 80% higher standardized mortality (1.8, 95% CI, 1.8-1.9 vs 1.0, 95% CI, 1.0-1.1 per 1000 population; P < .001). The higher severe sepsis rate was explained by both a higher infection rate in black patients (47.3; 95% CI, 47.1-47.4 vs 34.0; 95% CI, 33.9-34.0 per 1000 population; incidence rate ratio, 1.39; P < .001) and a higher risk of developing acute organ dysfunction (age- and sex-adjusted odds ratio [OR], 1.29; 95% CI, 1.27-1.30; P < .001). Differences in infection presented broadly across different sites and etiology of infection and for community- and hospital-acquired infections and occurred despite a lower likelihood of being admitted for infection from the emergency department (adjusted OR, 0.70; 95% CI, 0.64-0.76; P < .001). The higher risk of organ dysfunction persisted but was attenuated after adjusting for age, sex, comorbid conditions, poverty, and hospital effect (OR, 1.14; 95% CI, 1.13-1.16; P < .001). Racial disparities in infection and severe sepsis incidence and mortality rates were largest among younger adults (eg, the proportion of invasive pneumococcal disease occurring in adults < 65 years was 73.9% among black patients vs 44.5% among white patients, P < .001).Racial differences in severe sepsis are explained by both a higher infection rate and a higher risk of acute organ dysfunction in black than in white individuals.

SUBMITTER: Mayr FB

PROVIDER: S-EPMC3910506 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis.

Mayr Florian B FB Yende Sachin S Linde-Zwirble Walter T WT Peck-Palmer Octavia M OM Barnato Amber E AE Weissfeld Lisa A LA Angus Derek C DC

JAMA 20100601 24

<h4>Context</h4>Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear.<h4>Objective</h4>To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction.<h4>Design, setting, and participants</h4>Analysis of infection-related ...[more]

PMID: 20571016

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Project description:IntroductionSepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain.MethodsWe conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death.ResultsA total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, DeltaSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days.ConclusionsWe found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.

Project description:OBJECTIVES:To estimate the impact of each of six types of acute organ dysfunction (hepatic, renal, coagulation, neurologic, cardiac, and respiratory) on long-term mortality after surviving sepsis hospitalization. DESIGN:Multicenter, retrospective study. SETTINGS:Twenty-one hospitals within an integrated healthcare delivery system in Northern California. PATIENTS:Thirty thousand one hundred sixty-three sepsis patients admitted through the emergency department between 2010 and 2013, with mortality follow-up through April 2015. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Acute organ dysfunction was quantified using modified Sequential Organ Failure Assessment scores. The main outcome was long-term mortality among sepsis patients who survived hospitalization. The estimates of the impact of each type of acute organ dysfunction on long-term mortality were based on adjusted Cox proportional hazards models. Sensitivity analyses were conducted based on propensity score-matching and adjusted logistic regression. Hospital mortality was 9.4% and mortality was 31.7% at 1 year. Median follow-up time among sepsis survivors was 797 days (interquartile range: 384-1,219 d). Acute neurologic (odds ratio, 1.86; p < 0.001), respiratory (odds ratio, 1.43; p < 0.001), and cardiac (odds ratio, 1.31; p < 0.001) dysfunction were most strongly associated with short-term hospital mortality, compared with sepsis patients without these organ dysfunctions. Evaluating only patients surviving their sepsis hospitalization, acute neurologic dysfunction was also most strongly associated with long-term mortality (odds ratio, 1.52; p < 0.001) corresponding to a marginal increase in predicted 1-year mortality of 6.0% for the presence of any neurologic dysfunction (p < 0.001). Liver dysfunction was also associated with long-term mortality in all models, whereas the association for other organ dysfunction subtypes was inconsistent between models. CONCLUSIONS:Acute sepsis-related neurologic dysfunction was the organ dysfunction most strongly associated with short- and long-term mortality and represents a key mediator of long-term adverse outcomes following sepsis.

Project description:ObjectivesTo evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis.DesignRetrospective cohort study examining data from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective trial (NCT00049764).SettingOne hundred and four pediatric centers in 18 countries.SubjectsChildren with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384).InterventionsNone.Measurements and main resultsPoor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a "poor" functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and 2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6-8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0-9.ConclusionsIn this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an individual's clinical course are associated with poor functional outcome 28 days after onset of severe sepsis. These characteristics may provide opportunity for intervention in order to improve functional outcome in pediatric patients with severe sepsis. Decline in functional status 28 days after onset of severe sepsis is a frequent and potentially clinically meaningful event. Utilization of functional status as the primary outcome in future pediatric sepsis clinical trials should be considered.

Project description:OBJECTIVES:To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. DESIGN:Secondary analysis of a prospective, cross-sectional, point prevalence study. SETTING:International, multicenter PICUs. PATIENTS:Pediatric patients with severe sepsis identified on five separate days over a 1-year period. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). CONCLUSIONS:Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

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.

Dataset Information

Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis.

Publications

Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis.

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