Dataset Information

The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis.

ABSTRACT: 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.

SUBMITTER: Schuler A

PROVIDER: S-EPMC5953770 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis.

Schuler Alejandro A Wulf David A DA Lu Yun Y Iwashyna Theodore J TJ Escobar Gabriel J GJ Shah Nigam H NH Liu Vincent X VX

Critical care medicine 20180601 6

<h4>Objectives</h4>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.<h4>Design</h4>Multicenter, retrospective study.<h4>Settings</h4>Twenty-one hospitals within an integrated healthcare delivery system in Northern California.<h4>Patients</h4>Thirty thousand one hundred sixty-three sepsis patients admitted through the emergency department between ...[more]

PMID: 29432349

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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:Rationale & objectiveSepsis-associated acute kidney injury often leads to acute kidney disease (AKD), predisposing patients to long-term complications such as chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), or mortality. Risk stratification of patients with AKD represents an opportunity to assist with prognostication of long-term kidney complications.Study designSingle-center retrospective cohort.Setting & participants6,290 critically ill patients admitted to the intensive care unit with severe sepsis or septic shock. Patients were separated into cohorts based on incident acute kidney injury or not, and survivors identified who were alive and free of KFRT up to 90 days.PredictorsAKD stage (0A, 0C, or ≥1) using the last serum creatinine concentration available by discharge or up to 90 days postdischarge.OutcomeTime to development of incident CKD, progression of CKD, KFRT, or death.Analytical approachMultivariable Cox proportional hazards models.ResultsPatients surviving kidney injury associated with sepsis often fail to return to baseline kidney function by discharge: 577/1,231 (46.9%) with stage 0C or 1 or greater AKD. AKD stage was significantly associated with the composite primary outcome. Stages 0C AKD and 1 or greater AKD were significantly and progressively associated with the primary outcome when compared with stage 0A AKD (adjusted HR [aHR], 1.74; 95% CI, 1.32-2.29, and aHR, 3.25; 95% CI, 2.52-4.20, respectively). Additionally, stage 1 or greater AKD conferred higher risk above stage 0C AKD (aHR, 1.87; 95% CI, 1.44-2.43). CKD incidence or progression and KFRT, more so than mortality, occurred with greater frequency in higher stages of AKD.LimitationsRetrospective design, single center, exclusion of patients with KFRT within 90 days of discharge, potential ascertainment bias, and inability to subclassify above AKD stage 1.ConclusionsRisk stratification using recommended AKD stages at hospital discharge or shortly thereafter associates with the development of long-term kidney outcomes following sepsis-associated acute kidney injury.

Project description:ContextSevere 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.ObjectiveTo 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.Design, setting, and participantsAnalysis 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.Main outcome measureAge- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction.ResultsOf 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).ConclusionRacial 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.

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:ObjectivesSepsis has been called a "disease of the elderly," and as in-hospital mortality has decreased, more sepsis survivors are progressing into poorly characterized long-term outcomes. The purpose of this study was to describe the current epidemiology of sepsis in older adults compared with middle-aged and young adults.DesignProspective longitudinal study with young (≤45 years), middle-aged (46-64 years), and older (≥65 years) patient groups.SettingUniversity tertiary medical center.ParticipantsA total of 328 adult surgical intensive care unit (ICU) sepsis patients.MeasurementsPatients were characterized by (1) baseline demographics and predisposition, (2) septic event, (3) hospital outcomes and discharge disposition, (4) 12-month mortality, and (5) Zubrod Performance Status, physical function (Short Physical Performance Battery and handgrip strength), and cognitive function (Hopkins Verbal Learning Test, Controlled Oral Word Association, and Mini-Mental Status Examination) at 3-, 6-, and 12-month follow-up. Loss to follow-up was due to death (in 68), consent withdrawal (in 32), and illness and scheduling difficulties: month 3 (in 51), month 6 (in 29), and month 12 (in 20).ResultsCompared with young and middle-aged patients, older patients had (1) significantly more comorbidities at presentation (eg, chronic renal disease 6% vs 12% vs 21%), intra-abdominal infections (14% vs 25% vs 37%), septic shock (12% vs 25% vs 36%), and organ dysfunctions; (2) higher 30-day mortality (6% vs 4% vs 17%) and fewer ICU-free days (median = 25 vs 23 vs 20); (3) more progression into chronic critical illness (22% vs 34% vs 42%) with higher poor disposition discharge to non-home destinations (19% vs 40% vs 62%); (4) worse 12-month mortality (11% vs 14% vs 33%); and (5) poorer Zubrod Performance Status and objectively measured physical and cognitive functions with only slight improvement over 12-month follow-up.ConclusionCompared with younger patients, older sepsis survivors suffer both a higher persistent disability burden and 12-month mortality.

Dataset Information

The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis.

Publications

The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis.

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