Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.
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SUBMITTER: Weiss SL
PROVIDER: S-EPMC4213742 | biostudies-literature | 2014 Nov
REPOSITORIES: biostudies-literature
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Project description:Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis.Retrospective observational study.Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013.One hundred sixty patients aged ?21 years treated for severe sepsis.None.We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137?min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3?h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ?1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3?h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3?h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ?1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3?h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0).Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ?1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.
| S-EPMC5468469 | biostudies-literature
Project description:Objective: To evaluate serial ferritin levels measured in the initial 72 h of admission as a biomarker for new and progressive multi organ dysfunction syndrome (NPMODS) and mortality (unfavorable outcomes) in critically ill children with sepsis due to tropical infections. Material and Methods: In this prospective observational study from a tertiary care teaching hospital in India, children 3 month to 12 years with a diagnosis of acute febrile illness and any two features suggesting tropical infections [cytopenia (platelet count <1,00,000/cu.mm, total leucocyte count <4,000/cu.mm), hepatomegaly and/or splenomegaly, lymphadenopathy, systemic signs (rash, edema), respiratory distress, and encephalopathy not accounted by localized infection] were eligible for inclusion. Children with known or suspected disorder of iron metabolism were excluded. Primary outcome was to determine the association of serial ferritin levels with mortality and NPMODS. Secondary outcomes included estimation of the prevalence of hyperferritinemia and comparison of risk prediction scores with serial ferritin measurement in predicting unfavorable outcomes. Measurements and Main Results: In the 202 children enrolled, diagnosis could be established in 133 (65.8%) children. Scrub typhus and dengue were the most common infections. Median (IQR) ferritin measured at admission (n = 183) and on day 3 (n = 120) of hospital stay were 798 (378, 3,205) μg/L and 429 (213,680) μg/L, respectively. Majority (n = 180, 89.1%) had MODS at admission defined as per International pediatric sepsis consensus conference. NPMODS occurred in 47 (23.3%) children of whom 37 (18.3%) died. Children with three or less organ dysfunctions had lower mortality. Neither admission ferritin values nor the percentage change over 72 h was different between children with favorable and unfavorable outcomes. Pediatric Risk of Mortality (PRISM-III) and daily Pediatric Logistic Organ Dysfunction score (dPELOD2 score) were significantly different in those with unfavorable outcomes. Admission ferritin levels and percentage change in 72 h had poor discriminatory power for mortality with AUC of 0.53 (0.53, 0.67) and 0.50 (0.50, 0.64), respectively. dPELOD2 had the best discriminatory power for mortality with AUC of 0.89 (0.89, 0.95). Conclusions: Serial ferritin estimation predicted neither organ dysfunction nor mortality in pediatric sepsis with tropical infections. dPELOD-2 and PRISM-III predicted unfavorable outcomes better than ferritin. The current diagnostic criteria for MODS overestimated organ dysfunctions in tropical infections and hence may need modification with further validation in this epidemiological cohort.
| S-EPMC7747694 | biostudies-literature
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.
| S-EPMC7341116 | biostudies-literature
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.
| S-EPMC7261134 | biostudies-literature
Project description:To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis.Retrospective cohort study.Tertiary care children's hospital from January 1, 2012, to March 31, 2014.Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included.The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4).Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.
| S-EPMC5008999 | biostudies-literature
Project description:MotivationSepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking.ResultsThis study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care.Availability and implementationCode available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9236580 | biostudies-literature
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.
| S-EPMC2646323 | biostudies-literature
Project description:BackgroundDementia increases the risk of death in older patients hospitalized for acute illnesses. However, the effect of dementia on the risks of developing acute organ dysfunction and severe sepsis as well as on the risk of hospital mortality in hospitalized older patients remains unknown, especially when treatments for these life-threatening situations are considered.MethodsIn this population-based cohort study, we analyzed 41,672 older (? 65 years) patients, including 3,487 (8.4%) with dementia, from the first-time admission claim data between 2005 and 2007 for a nationally representative sample of one million beneficiaries enrolled in the Taiwan National Health Insurance Research Database. Outcomes included acute organ dysfunction, severe sepsis, and hospital mortality. The effect of dementia on outcomes was assessed using multivariable logistic regression.ResultsDementia was associated with a 32% higher risk of acute organ dysfunction (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.19-1.46), a 50% higher risk of severe sepsis (aOR 1.50, 95% CI 1.32-1.69) and a 28% higher risk of hospital mortality (aOR 1.28, 95% CI 1.10-1.48) after controlling age, sex, surgical condition, comorbidity, principal diagnosis, infection status, hospital level, and length of hospital stay. However, the significant adverse effect of dementia on hospital mortality disappeared when life-support treatments, including vasopressor use, hemodialysis, mechanical ventilation, and intensive care, were also controlled.ConclusionsIn hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe sepsis and hospital mortality. However, after intervention using life-support treatments, dementia only exhibited a minor role on short-term mortality.
| S-EPMC3414444 | biostudies-literature
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.
| S-EPMC9250715 | biostudies-literature
Project description:We investigated the effect of antibiotic timing on outcomes based on changes in surrogate markers of organ failure, including platelet, serum bilirubin, serum creatinine levels, and the PaO₂/FiO₂ (P/F) ratio. This was a single-center, retrospective observational study of critically ill septic patients who presented to the emergency department (ED). The study period extended from August 2008 to September 2016. The primary outcomes included changes in platelet, serum bilirubin, serum creatinine levels, and the P/F ratio (δ-platelet, δ-serum bilirubin, δ-serum creatinine, and δ-P/F ratio were calculated as values measured on Day 3; values measured at ED enrollment). A multivariable linear regression model was developed to assess variables related to outcomes (δ-platelet, δ-serum bilirubin, δ-serum creatinine, and δ-P/F ratio). We analyzed 1784 patients who met the inclusion criteria. The overall 28-day mortality was 14% (n = 256/1784). On multivariable linear regression analysis, the hourly delay in antibiotic therapy was significantly associated with a decrease in δ-platelet count (coefficient, -1.741; standard error, 0.740; p = 0.019), and an increase in δ-serum bilirubin (coefficient, 0.054; standard error, 0.021; p = 0.009). In contrast, it was not associated with δ-creatinine (coefficient, 0.008; standard error, 0.010; p = 0.434) or the δ-P/F ratio (coefficient, -0.797; standard error, 1.858; p = 0.668). The hourly delay of antibiotic therapy was associated with decreased platelet count and increased serum bilirubin concentration in critically ill septic patients during the first three days of ED admission.
| S-EPMC6406307 | biostudies-literature