Afebrile status at the time of emergency department visit is associated with delayed antibiotic therapy in patients with sepsis (revised).

OBJECTIVES: To determine whether there is a difference in antibiotic administration time and prognosis in afebrile sepsis patients compared to febrile sepsis patients. METHODS: This was retrospective multicenter observational study. Data collected from three referral hospitals. Data were collected from May 2014 through February 2016 under the SEPSIS-2 criteria and from March 2016 to April 2020 under the newly released SEPSIS-3 criteria. Patients were divided into two groups based on body temperature: afebrile (<37.3 °C) and febrile (≥37.3 °C). The relationship between initial body temperature and 28-day mortality were analyzed using multivariable logistic regression. The subgroup analysis was conducted on patients with complete Hour-1 bundle performance records. RESULTS: We included 4293 patients in this study. Initial body temperatures in 28-day survivors were significantly higher than in 28-day non-survivors (37.5 °C ± 1.2 °C versus 37.1 °C ± 1.2 °C, p < 0.01). Multivariable logistic regression analysis was performed in afebrile and febrile sepsis patients. Adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.76 (95% Confidence interval 1.46-2.12). As a result of performing the Hour-1 bundle, the number of patients who received antibiotics within 1 h was smaller in the afebrile sepsis patients (323/2076, 15.6%) than in the febrile sepsis patients (395/2156, 18.3%) (p = 0.02). In the subgroup analysis of patients with complete Hour-1 bundle performance records adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.68 (95% Confidence interval 1.34-2.11). The febrile sepsis patients received antibiotics faster than the afebrile sepsis patients (175.5 ± 207.9 versus 209.3 ± 277.9, p < 0.01). CONCLUSIONS: Afebrile sepsis patients were associated with higher 28-day mortality compared to their febrile counterparts and were delayed in receiving antibiotics. This underscores the need for improved early detection and treatment strategies for the afebrile sepsis patients.

The usefulness of lactate/albumin ratio, C-reactive protein/albumin ratio, procalcitonin/albumin ratio, SOFA, and qSOFA in predicting the prognosis of patients with sepsis who presented to EDs.

PURPOSE: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock. MATERIALS AND METHODS: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated. RESULTS: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17). CONCLUSION: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality.

Circulating mitochondrial N-formyl peptides contribute to secondary nosocomial infection in patients with septic shock.

Secondary infections typically worsen outcomes of patients recovering from septic shock. Neutrophil [polymorphonuclear leukocytes (PMNs)] migration to secondarily inoculated sites may play a key role in inhibiting progression from local bacterial inoculation to secondary infection. Mitochondrial N-formyl peptide (mtFP) occupancy of formyl peptide receptor-1 (FPR1) has been shown to suppress PMN chemotaxis. Therefore, we studied the association between circulating mtFPs and the development of secondary infection in patients with septic shock. We collected clinical data and plasma samples from patients with septic shock admitted to the intensive care unit for longer than 72 h. Impacts of circulating nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) upon clinical outcomes were analyzed. Next, the role of ND6 in PMN chemotaxis was investigated using isolated human PMNs. Studying plasma samples from 97 patients with septic shock, we found that circulating ND6 levels at admission were independently and highly associated with the development of secondary infection (odds ratio = 30.317, 95% CI: 2.904 to 316.407, P = 0.004) and increased 90-d mortality (odds ratio = 1.572, 95% CI: 1.002 to 2.465, P = 0.049). In ex vivo experiments, ND6 pretreatment suppressed FPR1-mediated PMN chemotactic responses to bacterial peptides in the presence of multiple cytokines and chemokines, despite increased nondirectional PMN movements. Circulating mtFPs appear to contribute to the development of secondary infection and increased mortality in patients with septic shock who survive their early hyperinflammatory phase. The increased susceptibility to secondary infection is probably partly mediated by the suppression of FPR1-mediated PMN chemotaxis to secondary infected sites.

Combination Therapy of Niacin and Apocynin Attenuates Lung Injury During Sepsis in Rats.

INTRODUCTION: Oxidative stress contributes to tissue injury through reactive oxygen species-dependent signaling pathways during sepsis. We studied therapeutic benefits of the combination therapy of niacin, which increased reduced glutathione levels, and apocynin, which suppressed reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity, in septic rats. MATERIALS AND METHODS: Polymicrobial sepsis was induced through cecal ligation and puncture (CLP) with antibiotics in male Sprague-Dawley rats (n = 189). The rats were randomly divided into sham, CLP, CLP + niacin, CLP + apocynin, and CLP + niacin + apocynin groups. Six hours after CLP, vehicle, niacin (360 mg/kg through the orogastric tube), and/or apocynin (20 mg/kg through intraperitoneal injection) were administered. The occurrence of mortality for 72 h after CLP was observed. Next, a separate set of animals was euthanized at 24 h post-CLP for lung tissue analyses. RESULTS: Combination therapy with niacin and apocynin significantly improved survival in rats with sepsis (75.0% versus 28.8%, P = 0.006) but monotherapy with niacin or apocynin did not. Monotherapy with niacin and apocynin appeared to increase NADPH levels and decrease Nox levels and activity, respectively, but failed to show statistical significances. However, combination therapy significantly decreased Nox levels and activity, increased NADPH and glutathione levels, decreased intranuclear nuclear factor-κB (NF-κB) p65 levels, reduced inflammatory cytokine expression and malondialdehyde levels, and attenuated histological lung injuries. CONCLUSIONS: Combination therapy with niacin and apocynin synergistically attenuated lung injuries and improved survival in rats with sepsis through niacin-induced glutathione redox cycle activation and apocynin-induced Nox suppression.

A simple scoring rule to predict survival to discharge after out of hospital cardiac arrest at the time of ED arrival.

BACKGROUND: It is important to be able to predict the chance of survival to hospital discharge upon ED arrival in order to determine whether to continue or terminate resuscitation efforts after out of hospital cardiac arrest. This study was conducted to develop and validate a simple scoring rule that could predict survival to hospital discharge at the time of ED arrival. METHODS: This was a multicenter retrospective cohort study based on a nationwide registry (Korean Cardiac Arrest Research Consortium) of out of hospital cardiac arrest (OHCA). The study included adult OHCA patients older than 18 years old, who visited one of 33 tertiary hospitals in South Korea from September 1st, 2015 to June 30th, 2020. Among 12,321 screened, 5471 patients were deemed suitable for analysis after exclusion. Pre-hospital ROSC, pre-hospital witness, shockable rhythm, initial pH, and age were selected as the independent variables. The dependent variable was set to be the survival to hospital discharge. Multivariable logistic regression (LR) was performed, and the beta-coefficients were rounded to the nearest integer to formulate the scoring rule. Several machine learning algorithms including the random forest classifier (RF), support vector machine (SVM), and K-nearest neighbor classifier (K-NN) were also trained via 5-fold cross-validation over a pre-specified grid, and validated on the test data. The prediction performances and the calibration curves of each model were obtained. Pre-processing of the registry was done using R, model training & optimization using Python. RESULTS: A total of 5471 patients were included in the analysis. The AUROC of the scoring rule over the test data was 0.7620 (0.7311-0.7929). The AUROCs of the machine learning classifiers (LR, SVM, k-NN, RF) were 0.8126 (0.7748-0.8505), 0.7920 (0.7512-0.8329), 0.6783 (0.6236-0.7329), and 0.7879 (0.7465-0.8294), respectively. CONCLUSION: A simple scoring rule consisting of five, binary variables could aid in the prediction of the survival to hospital discharge at the time of ED arrival, showing comparable results to conventional machine learning classifiers.

Modified Cardiovascular Sequential Organ Failure Assessment Score in Sepsis: External Validation in Intensive Care Unit Patients.

BACKGROUND: There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients. METHODS: A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively. RESULTS: We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677-0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611-0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715-0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration. CONCLUSION: In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality.

Modified cardiovascular SOFA score in sepsis: development and internal and external validation.

BACKGROUND: The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score. METHODS: We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock. RESULTS: We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%). CONCLUSIONS: Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.

Relationship between time of emergency department admission and adherence to the Surviving Sepsis Campaign bundle in patients with septic shock.

BACKGROUND: Nighttime hospital admission is often associated with increased mortality risk in various diseases. This study investigated compliance rates with the Surviving Sepsis Campaign (SSC) 3-h bundle for daytime and nighttime emergency department (ED) admissions and the clinical impact of compliance on mortality in patients with septic shock. METHODS: We conducted an observational study using data from a prospective, multicenter registry for septic shock provided by the Korean Shock Society from 11 institutions from November 2015 to December 2017. The outcome was the compliance rate with the SSC 3-h bundle according to the time of arrival in the ED. RESULTS: A total of 2049 patients were enrolled. Compared with daytime admission, nighttime admission was associated with higher compliance with the administration of antibiotics within 3 h (adjusted odds ratio (adjOR), 1.326; 95% confidence interval (95% CI), 1.088-1.617, p = 0.005) and with the complete SSC bundle (adjOR, 1.368; 95% CI, 1.115-1.678; p = 0.003), likely to result from the increased volume of all patients and sepsis patients admitted during daytime hours. The hazard ratios of the completion of SSC bundle for 28-day mortality and in-hospital mortality were 0.750 (95% CI 0.590-0.952, p = 0.018) and 0.714 (95% CI 0.564-0.904, p = 0.005), respectively. CONCLUSION: Septic shock patients admitted to the ED during the daytime exhibited lower sepsis bundle compliance than those admitted at night. Both the higher number of admitted patients and the higher patients to medical staff ratio during daytime may be factors that are responsible for lowering the compliance.

Hypernatremia is associated with poor long-term neurological outcomes in out-of-hospital cardiac arrest survivors.

BACKGROUND: Brain oedema after cardiac arrest is strongly associated with poor neurological outcomes. Excessive sodium supplementation may increase serum osmolarity and facilitate brain oedema development in cardiac arrest survivors. We aimed to investigate the association of serum sodium levels with long-term neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. METHODS: This retrospective observational study used a multicentre prospective cohort registry of OHCA survivors collected between December 2013 and February 2018. We analyzed the association of serum sodium levels at the return of spontaneous circulation (ROSC) (Sodium 0H) and at 24 h after ROSC (Sodium 24H) with 1-year neurological outcomes in OHCA survivors. Patients with 1-year cerebral performance categories (CPC) 1 and 2 were included in the good outcome group while those with CPC 3, 4, and 5 were included in the poor outcome group. RESULTS: Among 277 patients, 84 (30.3%) and 193 (69.7%) were in the good and poor outcome groups, respectively. Compared with the good outcome group, the poor outcome group showed significantly higher Sodium 24H levels (140 mEq/L vs. 137.4 mEq/L, p < 0.001). Increased serum sodium levels per 1 mEq/L increased the risk of poor 1-year CPC by 13% (adjusted odds ratio = 1.13; 95% CI, 1.04⎼1.23; p = 0.004). CONCLUSIONS: Relatively high Sodium 24H levels showed a strong and independent association with poor long-term neurological outcomes in OHCA survivors. These findings may be applied in therapeutic strategies for improving neurological outcomes in OHCA survivors.

Clinical Differences Between Stroke and Stroke Mimics in Code Stroke Patients.

BACKGROUND: The code stroke system is designed to identify stroke patients who may benefit from reperfusion therapy. It is essential for emergency physicians to rapidly distinguish true strokes from stroke mimics to activate code stroke. This study aimed to investigate the clinical and neurological characteristics that can be used to differentiate between stroke and stroke mimics in the emergency department (ED). METHODS: We conducted a retrospective observational study of code stroke patients in the ED from January to December 2019. The baseline characteristics and the clinical and neurological features of stroke mimics were compared with those of strokes. RESULTS: A total of 409 code stroke patients presented to the ED, and 125 (31%) were diagnosed with stroke mimics. The common stroke mimics were seizures (21.7%), drug toxicity (12.0%), metabolic disorders (11.2%), brain tumors (8.8%), and peripheral vertigo (7.2%). The independent predictors of stroke mimics were psychiatric disorders, dizziness, altered mental status, and seizure-like movements, while current smoking, elevated systolic blood pressure, atrial fibrillation on the initial electrocardiogram, hemiparesis as a symptom, and facial palsy as a sign suggested a stroke. In addition, the likelihood of a stroke in code stroke patients tended to increase as the number of accompanying deficits increased from the following set of seven focal neurological deficits: hemiparesis (or upper limb monoparesis), unilateral limb sensory change, facial palsy, dysarthria, aphasia (or neglect), visual field defect, and oculomotor disorder (P < 0.001). CONCLUSION: Some clinical and neurological characteristics have been identified to help differentiate stroke mimics from true stroke. In particular, the likelihood of stroke tended to increase as the number of accompanying focal neurological deficits increased.

Development of a prediction model for clinically important outcomes of acute diverticulitis.

OBJECTIVE: Acute diverticulitis (AD) is a common disease with various outcomes. When AD is diagnosed in the emergency department (ED), the ED clinician must determine the patient's treatment strategy whether the patient can be discharged, needs to be admitted to the general ward, ICU, or needs surgical consultation. This study aimed to identify potential risk factors for clinically important outcomes (CIOs) and to develop a prediction model for CIOs in AD to aid clinical decision making in the ED. METHODS: Retrospective data from between 2013 and 2017 in an ED in an urban setting were reviewed for adult AD. Potential risk factors were age, sex, past medical history, symptoms, physical exams, laboratory results, and imaging results. A CIO was defined as a case with one of the following outcomes: hospital death, ICU admission, surgery or invasive intervention, and admission for 7 or more days. The prediction model for CIOs was developed using potential risk factors. Model discrimination and calibration were assessed using the area under the curve (AUC) and 95% confidence intervals (CIs) and the Hosmer-Lemeshow (HL) test, respectively. Model validation was conducted using 500 random bootstrap samples. RESULTS: Of the final 337 AD patients, 63 patients had CIOs. Six potential factors (age, abdominal pain (≥ 3 days), anorexia, rebound tenderness, white blood cell count (> 15,000/µl), C-reactive protein (> 10 mg/dL), and CT findings of a complication) were used for the final model. The AUC (95% CI) for CIOs was 0.875 (0.826-0.923), and χ2 was 2.969 (p-value = 0.936) with the HL test. Validation using bootstrap samples resulted in an optimism-corrected AUC of 0.858 (0.856-0.861). CONCLUSION: A prediction model for clinically important outcomes of AD visiting a single ED showed good discrimination and calibration power with an acceptable range.

Diagnostic accuracy of lactate levels after initial fluid resuscitation as a predictor for 28 day mortality in septic shock.

PURPOSE: The aim of the study was to investigate the diagnostic accuracy of initial and post-fluid resuscitation lactate levels in predicting 28 day mortality. MATERIALS AND METHODS: We retrospectively analyzed a multi-center registry of suspected septic shock cases that was prospectively collected between October 2015 and December 2018 from 11 Emergency Departments. The primary outcome was 28 day mortality. The diagnostic performance of the initial and post-fluid resuscitation lactate levels as a predictor for 28 day mortality was assessed. RESULTS: A total of 2568 patients were included in the final analysis. The overall 28 day mortality rate was 23%. The area under the receiver operating characteristic curve (AUROC) of initial lactate for predicting 28 day mortality was 0.66 (95% CI, 0.64-0.69) and that of after fluid administration lactate was 0.70 (95% CI, 0.67-0.72), and there was a significant difference (p < 0.001). The optimal cutoff point of lactate after fluid administration was 4.4 mmol/L. Compared with this, the Sepsis-3 definition with a lactate level of 2 mmol/L or more was relatively more sensitive and less specific for predicting 28 day mortality. CONCLUSION: The post-fluid resuscitation lactate level was more accurate than the initial lactate level in predicting 28 day mortality in patients with suspected septic shock.

Serum total carbon dioxide as a prognostic factor for 28-day mortality in patients with sepsis.

OBJECTIVE: Metabolic acidosis is commonly associated with the disease severity in patients with sepsis or septic shock. This study was performed to investigate the association between serum total carbon dioxide (TCO2) concentration and 28-day mortality in patients with sepsis. METHODS: This study was a multicenter retrospective cohort study of patients with sepsis or septic shock. The relationships between serum TCO2 and 28-day mortality, bicarbonate, pH, lactate, and anion gap were determined with cubic spline curves. The patients were divided into four groups according to their serum TCO2 concentration: Group I (TCO2 > 20 mmol/l), Group II (15 < TCO2 ≤ 20 mg/dl), Group III (10 < TCO2 ≤ 15 mmol/l), and Group IV (TCO2 ≤ 10 mmol/l). RESULTS: A total of 3168 patients were included in the analysis, and the overall mortality rate was 24.1%. Serum TCO2 concentrations below 20 mmol/l showed an almost linear correlation with mortality as well as with lactate, bicarbonate, and pH. The 28-day mortality rates of Group I, II, III, and IV were 18.3%, 23.6%, 32.6%, and 50.0%, respectively (p < .001). In Multivariable Cox proportional hazard regression analysis, the groups with lower serum TCO2 concentrations had a higher risk of 28-day mortality compared with Group I: Group II (Hazard ratio (HR), 1.35; 95% confidence interval (CI), 1.11-1.64), Group III (HR, 1.74; 95% CI, 1.37-2.21), and Group IV (HR, 2.72; 95% CI, 2.03-3.64). CONCLUSIONS: Serum TCO2 concentrations of 20 mmol/l or less were associated with 28-day mortality in patients with sepsis.

Prediction of Neurological Outcomes in Out-of-hospital Cardiac Arrest Survivors Immediately after Return of Spontaneous Circulation: Ensemble Technique with Four Machine Learning Models.

BACKGROUND: We performed this study to establish a prediction model for 1-year neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients who achieved return of spontaneous circulation (ROSC) immediately after ROSC using machine learning methods. METHODS: We performed a retrospective analysis of an OHCA survivor registry. Patients aged ≥ 18 years were included. Study participants who had registered between March 31, 2013 and December 31, 2018 were divided into a develop dataset (80% of total) and an internal validation dataset (20% of total), and those who had registered between January 1, 2019 and December 31, 2019 were assigned to an external validation dataset. Four machine learning methods, including random forest, support vector machine, ElasticNet and extreme gradient boost, were implemented to establish prediction models with the develop dataset, and the ensemble technique was used to build the final prediction model. The prediction performance of the model in the internal validation and the external validation dataset was described with accuracy, area under the receiver-operating characteristic curve, area under the precision-recall curve, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Futhermore, we established multivariable logistic regression models with the develop set and compared prediction performance with the ensemble models. The primary outcome was an unfavorable 1-year neurological outcome. RESULTS: A total of 1,207 patients were included in the study. Among them, 631, 139, and 153 were assigned to the develop, the internal validation and the external validation datasets, respectively. Prediction performance metrics for the ensemble prediction model in the internal validation dataset were as follows: accuracy, 0.9620 (95% confidence interval [CI], 0.9352-0.9889); area under receiver-operator characteristics curve, 0.9800 (95% CI, 0.9612-0.9988); area under precision-recall curve, 0.9950 (95% CI, 0.9860-1.0000); sensitivity, 0.9594 (95% CI, 0.9245-0.9943); specificity, 0.9714 (95% CI, 0.9162-1.0000); PPV, 0.9916 (95% CI, 0.9752-1.0000); NPV, 0.8718 (95% CI, 0.7669-0.9767). Prediction performance metrics for the model in the external validation dataset were as follows: accuracy, 0.8509 (95% CI, 0.7825-0.9192); area under receiver-operator characteristics curve, 0.9301 (95% CI, 0.8845-0.9756); area under precision-recall curve, 0.9476 (95% CI, 0.9087-0.9867); sensitivity, 0.9595 (95% CI, 0.9145-1.0000); specificity, 0.6500 (95% CI, 0.5022-0.7978); PPV, 0.8353 (95% CI, 0.7564-0.9142); NPV, 0.8966 (95% CI, 0.7857-1.0000). All the prediction metrics were higher in the ensemble models, except NPVs in both the internal and the external validation datasets. CONCLUSION: We established an ensemble prediction model for prediction of unfavorable 1-year neurological outcomes in OHCA survivors using four machine learning methods. The prediction performance of the ensemble model was higher than the multivariable logistic regression model, while its performance was slightly decreased in the external validation dataset.

Hypochloraemia is associated with 28-day mortality in patients with septic shock: a retrospective analysis of a multicentre prospective registry.

OBJECTIVES: Hyperchloraemia is associated with poor clinical outcomes in sepsis patients; however, this association is not well studied for hypochloraemia. We investigated the prevalence of chloride imbalance and the association between hypochloraemia and 28-day mortality in ED patients with septic shock. METHODS: A retrospective analysis of data from 11 multicentre EDs in the Republic of Korea prospectively collected from October 2015 to April 2018 was performed. Initial chloride levels were categorised as hypochloraemia, normochloraemia and hyperchloraemia, according to sodium chloride difference adjusted criteria. The primary outcome was 28-day mortality. A multivariate logistic regression model adjusting for age, sex, comorbidities, acid-base state, sepsis-related organ failure assessment (SOFA) score, lactate and albumin level was used to test the association between the three chloride categories and 28-day mortality. RESULTS: Among 2037 enrolled patients, 394 (19.3%), 1582 (77.7%) and 61 (3.0%) patients had hypochloraemia, normochloraemia and hyperchloraemia, respectively. The unadjusted 28-day mortality rate in patients with hypochloraemia was 27.4% (95% CI, 23.1% to 32.1%), which was higher than in patients with normochloraemia (19.7%; 95% CI, 17.8% to 21.8%). Hypochloraemia was associated with an increase in the risk of 28-day mortality (adjusted OR (aOR), 1.36, 95% CI, 1.00 to 1.83) after adjusting for confounders. However, hyperchloraemia was not associated with 28-day mortality (aOR 1.35, 95% CI, 0.82 to 2.24). CONCLUSION: Hypochloraemia was more frequently observed than hyperchloraemia in ED patients with septic shock and it was associated with 28-day mortality.

Pulse Oximeter Plethysmograph Variation During Hemorrhage in Beta-Blocker-Treated Swine.

BACKGROUND: Beta-blockers blunt the stress response to hemorrhage. Our aim was to investigate the feasibility of noninvasive pulse oximeter plethysmographic waveform variation (PoPV) for predicting blood volume loss in an esmolol-treated swine hemorrhagic shock model. MATERIALS AND METHODS: Controlled hemorrhage was induced in eight male domestic pigs. In four pigs, a total of 15% and 30% blood volume was drawn step-by-step over 10 min in each step (controlled hemorrhage-only pigs). In the other four pigs, the heart rate (HR) was reduced and maintained by 30% from baseline by esmolol infusion before controlled hemorrhage (esmolol-treated pigs). Diagnostic abilities of HR, pulse pressure variation (PPV), PoPV, and mean arterial pressure for 15% and 30% blood volume loss were determined by the area under the receiver operating characteristic curve (AUC). RESULTS: PoPV was well correlated with PPV in controlled hemorrhage-only pigs (r = 0.717) and esmolol-treated pigs (r = 0.532). In controlled hemorrhage-only pigs, HR (AUC = 0.841 and 0.864), PPV (0.878 and 0.843), and PoPV (0.779 and 0.793) accurately predicted 15% and 30% of blood volume loss. In esmolol-treated pigs, the diagnostic ability of HR was decreased (AUC = 0.766 and 0.733). However, diagnostic abilities of PPV (0.848 and 0.804) and PoPV (0.808 and 0.842) were not deteriorated. CONCLUSIONS: The diagnostic ability of HR for blood volume loss was blunted by esmolol. However, those of PPV and PoPV were not altered. PoPV may be considered to be a useful noninvasive tool to predict blood volume loss in injured patients taking beta-blockers.

Emergency physician-based intensive care unit for critically ill patients visiting emergency department.

BACKGROUND: To provide a prompt and optimal intensive care to critically ill patients visiting our emergency department (ED), we set up and ran a specific type of emergency intensive care unit (EICU) managed by emergency physician (EP) intensivists. We investigated whether this EICU reduced the time interval from ED arrival to ICU transfer (ED-ICU interval) without altering mortality. METHODS: This was a retrospective study conducted in a tertiary referral hospital. We collected data from ED patients who were admitted to the EICU (EICU group) and other ICUs including medical, surgical, and cardiopulmonary ICUs (other ICUs group), from August 2014 to July 2017. We compared these two groups with respect to demographic findings, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ED-ICU interval, ICU mortality, and hospital mortality. RESULTS: Among the 3440 critically ill patients who visited ED, 1815 (52.8%) were admitted to the EICU during the study period. The ED-ICU interval for the EICU group was significantly shorter than that for the other ICUs group by 27.5% (5.0 ±â€¯4.9 vs. 6.9 ±â€¯5.4 h, p < 0.001). In multivariable analysis, the ICU mortality (odds ratio = 1.062, 95% confidence interval 0.862-1.308, p = 0.571) and hospital mortality (odds ratio = 1.093, 95% confidence interval 0.892-1.338, p = 0.391) of the EICU group were not inferior to those of the other ICUs group. CONCLUSIONS: The EICU run by EP intensivists reduced the time interval from ED arrival to ICU transfer without altering hospital mortality.

Relative tachycardia is associated with poor outcomes in post-cardiac arrest patients regardless of therapeutic hypothermia.

BACKGROUND: To investigate whether the relationship between heart rate and neurological outcome is independent of therapeutic hypothermia (TH) and whether heart rate is related to hemodynamic instability post-cardiac arrest. METHODS: Retrospective review of an out-of-hospital cardiac arrest registry was performed. The primary exposure was heart rate quartiles at 24 h post-cardiac arrest. The primary outcome was a poor neurological outcome, which was defined as having a cerebral performance category (CPC) of 3-5 at 28 days. Secondary outcomes were mean blood pressure and serum lactate at 24 h and Sequential Organ Failure Assessment (SOFA) scores at admission. RESULTS: In total, 155 patients were enrolled. The proportion of patients with a poor CPC was significantly greater in higher heart rate quartiles; similar results were observed in patients who did and did not undergo TH. Serum lactate levels at 24 h were significantly higher in the 3rd and 4th quartile groups than in the 1st quartile group. Additionally, SOFA scores were significantly higher in the 4th quartile group than in the 1st and 3rd quartile groups. CONCLUSIONS: Relative tachycardia is associated with poor neurological outcomes in post-cardiac arrest patients, independent of TH, and with higher serum lactate levels and admission SOFA scores.

Prognostic performance of disease severity scores in patients with septic shock presenting to the emergency department.

BACKGROUND: An accurate disease severity score that can quickly predict the prognosis of patients with sepsis in the emergency department (ED) can aid clinicians in distributing resources appropriately or making decisions for active resuscitation measures. This study aimed to compare the prognostic performance of quick sequential organ failure assessment (qSOFA) with that of other disease severity scores in patients with septic shock presenting to an ED. METHODS: We performed a prospective, observational, registry-based study. The discriminative ability of each disease severity score to predict 28-day mortality was evaluated in the overall cohort (which included patients who fulfilled previously defined criteria for septic shock), the newly defined sepsis subgroup, and the newly defined septic shock subgroup. RESULTS: A total of 991 patients were included. All disease severity scores had poor discriminative ability for 28-day mortality. The sequential organ failure assessment and acute physiology and chronic health evaluation II scores had the highest area under the receiver-operating characteristic curve (AUC) values, which were significantly higher than the AUC values of other disease severity scores in the overall cohort and the sepsis and septic shock subgroups. The discriminative ability of each disease severity score decreased as the mortality rate of each subgroup increased. CONCLUSIONS: All disease severity scores, including qSOFA, did not display good discrimination for 28-day mortality in patients with serious infection and refractory hypotension or hypoperfusion; additionally, none of the included scoring tools in this study could consistently predict 28-day mortality in the newly defined sepsis and septic shock subgroups.

Niacin and Selenium Attenuate Brain Injury After Cardiac Arrest in Rats by Up-Regulating DJ-1-Akt Signaling.

OBJECTIVES: To determine neuroprotective effects and mechanism of the combination therapy of niacin and selenium in cardiac arrest rats. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Rat cortex neurons and male Sprague-Dawley rats (n = 68). INTERVENTIONS: In rat cortex neurons underwent 90 minutes of oxygen-glucose deprivation and 22.5 hours of reoxygenation, effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 µM) were investigated. The role of DJ-1 was determined using DJ-1 knockdown cells. In cardiac arrest rats, posttreatment effects of the combination therapy of niacin (360 mg/kg) and selenium (60 µg/kg) were evaluated. MEASUREMENTS AND MAIN RESULTS: In oxygen-glucose deprivation and 22.5 hours of reoxygenation cells, combination therapy synergistically activated the glutathione redox cycle by a niacin-induced increase in glutathione reductase and a selenium-induced increase in glutathione peroxidase activities and reduced hydrogen peroxide level. It increased phosphorylated Akt and intranuclear Nuclear factor erythroid 2-related factor 2 expression and attenuated neuronal injury. However, these benefits were negated by DJ-1 knockdown. In cardiac arrest rats, combination therapy increased DJ-1, phosphorylated Akt, and intranuclear nuclear factor erythroid 2-related factor 2 expression, suppressed caspase 3 cleavage, and attenuated histologic injury in the brain tissues. It also improved the 7-day Neurologic Deficit Scales from 71.5 (66.0-74.0) to 77.0 (74.-80.0) (p = 0.02). CONCLUSIONS: The combination therapy of clinically relevant doses of niacin and selenium attenuated brain injury and improved neurologic outcome in cardiac arrest rats. Its benefits were associated with reactive oxygen species reduction and subsequent DJ-1-Akt signaling up-regulation.