Browsing by keyword "sepsis"
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An evaluation of the diagnostic accuracy of the 1991 American College of Chest Physicians/Society of Critical Care Medicine and the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine/American College of Chest Physicians/American Thoracic Society/Surgical Infection Society sepsis definitionOBJECTIVES: Limited research has been conducted to compare the test characteristics of the 1991 and 2001 sepsis consensus definitions. This study assessed the accuracy of the two sepsis consensus definitions among adult critically ill patients compared to sepsis case adjudication by three senior clinicians. DESIGN: Observational study of patients admitted to intensive care units. SETTING: Seven intensive care units of an academic medical center. PATIENTS: A random sample of 960 patients from all adult intensive care unit patients between October 2007 and December 2008. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sensitivity, specificity, and the area under the receiver operating characteristic curve for the two consensus definitions were calculated by comparing the number of patients who met or did not meet consensus definitions vs. the number of patients who were or were not diagnosed with sepsis by adjudication. The 1991 sepsis definition had a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which were 96.9% and 58.3%, respectively. The areas under the receiver operating characteristic curve for the two definitions were not statistically different (0.778 and 0.776, respectively). The sensitivities and areas under the receiver operating characteristic curve of both definitions were lower at the 24-hr time window level than those of the intensive care unit stay level, though their specificities increased slightly. Fever, high white blood cell count or immature forms, low Glasgow coma score, edema, positive fluid balance, high cardiac index, low PaO2/FIO2 ratio, and high levels of creatinine and lactate were significantly associated with sepsis by both definitions and adjudication. CONCLUSIONS: Both the 1991 and the 2001 sepsis definition have a high sensitivity but low specificity; the 2001 definition has a slightly increased sensitivity but a decreased specificity compared to the 1991 definition. The diagnostic performances of both definitions were suboptimal. A parsimonious set of significant predictors for sepsis diagnosis is likely to improve current sepsis case definitions.
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Atrial Fibrillation Prediction from Critically Ill Sepsis PatientsSepsis is defined by life-threatening organ dysfunction during infection and is the leading cause of death in hospitals. During sepsis, there is a high risk that new onset of atrial fibrillation (AF) can occur, which is associated with significant morbidity and mortality. Consequently, early prediction of AF during sepsis would allow testing of interventions in the intensive care unit (ICU) to prevent AF and its severe complications. In this paper, we present a novel automated AF prediction algorithm for critically ill sepsis patients using electrocardiogram (ECG) signals. From the heart rate signal collected from 5-min ECG, feature extraction is performed using the traditional time, frequency, and nonlinear domain methods. Moreover, variable frequency complex demodulation and tunable Q-factor wavelet-transform-based time-frequency methods are applied to extract novel features from the heart rate signal. Using a selected feature subset, several machine learning classifiers, including support vector machine (SVM) and random forest (RF), were trained using only the 2001 Computers in Cardiology data set. For testing the proposed method, 50 critically ill ICU subjects from the Medical Information Mart for Intensive Care (MIMIC) III database were used in this study. Using distinct and independent testing data from MIMIC III, the SVM achieved 80% sensitivity, 100% specificity, 90% accuracy, 100% positive predictive value, and 83.33% negative predictive value for predicting AF immediately prior to the onset of AF, while the RF achieved 88% AF prediction accuracy. When we analyzed how much in advance we can predict AF events in critically ill sepsis patients, the algorithm achieved 80% accuracy for predicting AF events 10 min early. Our algorithm outperformed a state-of-the-art method for predicting AF in ICU patients, further demonstrating the efficacy of our proposed method. The annotations of patients' AF transition information will be made publicly available for other investigators. Our algorithm to predict AF onset is applicable for any ECG modality including patch electrodes and wearables, including Holter, loop recorder, and implantable devices.
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Development and Validation of an Automated Algorithm to Detect Atrial Fibrillation Within Stored Intensive Care Unit Continuous Electrocardiographic Data: Observational StudyBACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia during critical illness, representing a sepsis-defining cardiac dysfunction associated with adverse outcomes. Large burdens of premature beats and noisy signal during sepsis may pose unique challenges to automated AF detection. OBJECTIVE: The objective of this study is to develop and validate an automated algorithm to accurately identify AF within electronic health care data among critically ill patients with sepsis. METHODS: This is a retrospective cohort study of patients hospitalized with sepsis identified from Medical Information Mart for Intensive Care (MIMIC III) electronic health data with linked electrocardiographic (ECG) telemetry waveforms. Within 3 separate cohorts of 50 patients, we iteratively developed and validated an automated algorithm that identifies ECG signals, removes noise, and identifies irregular rhythm and premature beats in order to identify AF. We compared the automated algorithm to current methods of AF identification in large databases, including ICD-9 (International Classification of Diseases, 9th edition) codes and hourly nurse annotation of heart rhythm. Methods of AF identification were tested against gold-standard manual ECG review. RESULTS: AF detection algorithms that did not differentiate AF from premature atrial and ventricular beats performed modestly, with 76% (95% CI 61%-87%) accuracy. Performance improved (P=.02) with the addition of premature beat detection (validation set accuracy: 94% [95% CI 83%-99%]). Median time between automated and manual detection of AF onset was 30 minutes (25th-75th percentile 0-208 minutes). The accuracy of ICD-9 codes (68%; P=.002 vs automated algorithm) and nurse charting (80%; P=.02 vs algorithm) was lower than that of the automated algorithm. CONCLUSIONS: An automated algorithm using telemetry ECG data can feasibly and accurately detect AF among critically ill patients with sepsis, and represents an improvement in AF detection within large databases.
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ICU Admission Source as a Predictor of Mortality for Patients With SepsisPURPOSE: Sepsis is the leading noncardiac cause of intensive care unit (ICU) death. Pre-ICU admission site may be associated with mortality of ICU patients with sepsis. This study quantifies mortality differences among patients with sepsis admitted to an ICU from a hospital ward, emergency department (ED), or an operating room (OR). METHODS: We conducted a retrospective cohort study of 1762 adults with sepsis using ICU record data obtained from a clinical database of an academic medical center. Survival analysis provided crude and adjusted hazard rate ratio (HRR) estimates comparing hospital mortality among patients from hospital wards, EDs, and ORs, adjusted for age, sex, and severity of illness. RESULTS: Mortality of patients with sepsis differed based on the pre-ICU admission site. Compared to patients admitted from an ED, patients admitted from hospital wards had higher mortality (HRR: 1.35; 95% confidence interval [CI]: 1.09-1.68) and those admitted from an OR had lower mortality (HRR: 0.37; 95% CI: 0.23-0.58). CONCLUSION: Patients with sepsis admitted to an ICU from a hospital ward experienced greater mortality than patients with sepsis admitted to an ICU from an ED. These findings indicate that there may be systematic differences in the selection of patient care locations, recognition, and management of patients with sepsis that warrant further investigation.
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Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharideDuring screening of genes upregulated by lipopolysaccharide (LPS; endotoxin) treatment of bone marrow-derived mouse macrophages, it was unexpectedly found that cholesterol 25-hydroxylase (Ch25h) was strongly upregulated. Treatment of macrophages with 10 ng/ml of LPS for 2 h resulted in a 35-fold increase in the expression of Ch25h. In contrast, LPS treatment did not increase the expression of Cyp27a1 or Cyp7b1. The increased Ch25h expression was found to be independent of Myeloid differentiation protein 88 signaling but dependent on Toll-like receptor 4 signaling. LPS treatment of macrophages caused a 6- to 7-fold increase in cellular 25-hydroxycholesterol concentration. When macrophages were treated with increasing concentrations of 25-hydroxycholesterol, a dose-dependent release of CCL5 into the culture medium was observed. Intravenous injection of LPS in eight healthy volunteers resulted in an increase in plasma 25-hydroxycholesterol concentration. The possibility is discussed that 25-hydroxycholesterol may have a role in the inflammatory response, in addition to its more established role in the regulation of cholesterol homeostasis.
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Recent Trends in Sepsis Mortality, Associations between Initial Source of Sepsis and Hospital Mortality, and Predictors of Sepsis Readmission in Sepsis SurvivorsBackground: Sepsis, a leading cause of US deaths, is associated with high mortality, although advances in early recognition and treatment have increased survivorship. Many aspects of sepsis pathophysiology and epidemiology have not been fully elucidated; the heterogeneous nature of infections that lead to sepsis has made fully characterizing the underlying epidemiology challenging. Methods: The University HealthSystem Consortium (UHC) from 2011-2014 and the Cerner HealthFacts® database from 2008-2014 were used. We examined associations between infection source and in-hospital mortality in the UHC dataset, stratified by age and presenting sepsis stage. We examined recent temporal trends in present-on-admission (POA) sepsis diagnoses and mortality and predictors of 30-day sepsis readmissions following sepsis hospitalizations using the HealthFacts® dataset. Results: Patients with sepsis due to genitourinary or skin, soft tissue, or bone sources had lower mortality than patients with sepsis due to respiratory sources regardless of age or presenting sepsis stage. Overall diagnoses of sepsis increased from 2008-2014; however, POA diagnoses and case fatality rates decreased. Factors that predicted re-hospitalization for sepsis included discharge to hospice, admission from or discharge to a skilled nursing facility, and abdominal infection. Conclusion: Further investigation will reveal more detail to explain the impact of infection source on in-hospital sepsis mortality for all age groups and sepsis stages. Decreasing mortality rates for all POA sepsis stages and all age groups suggest current approaches to sepsis management are having broad impact. Sepsis survivors are at significant risk for re-hospitalization; further studies are needed to understand the post discharge risks and needs of survivors.
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The Role of RIPK1 Kinase Activity in Regulating Inflammation and Necroptotic DeathNecroptosis, a type of regulated necrotic cell death, involves cell membrane permeabilization and has been implicated in various acute and chronic pro-inflammatory diseases, including ischemia-reperfusion injury and neurodegenerative diseases. By using in vitro reconstitution studies and a chemical inhibitor, the kinase activity of the serine/threonine kinase RIPK1 had been shown to regulate necroptotic signaling downstream of TNF and Toll-like receptors (TLRs). To investigate the contribution of RIPK1 kinase activity to inflammation and necroptosis in vivo, we generated kinase inactive RIPK1 knock-in mice. Utilizing fibroblasts and macrophages from these mice, we demonstrate that RIPK1 kinase activity is required for necroptotic complex formation and death induction downstream of TNFR1 and TLRs 3 and 4. We show that RIPK1 kinase inactive mice are resistant to TNF-induced shock and exhibit impaired upregulation of TNF-induced cytokines and chemokines in vitro and in vivo. By using bone marrow reconstitution experiments, we demonstrate that RIPK1 kinase activity in a non-hematopoietic lineage drives TNF-induced lethality. We establish that RIPK1 kinase activity is required for TNF-induced increases in intestinal and vascular permeability and clotting, and implicate endothelial cell necroptosis as an underlying factor contributing to TNF/zVAD-induced shock. Thus, work in this thesis reveals that RIPK1 kinase inhibitors may have promise in treating shock and sepsis.
