Search

Background: The distinction between culture-positive sepsis and culture-negative sepsis regarding clinical characteristics and outcomes remains contentious. We aimed to elucidate these differences using large-scale nationwide data., Methods: This prospective cohort study analyzed data from the Korean Sepsis Alliance registry, comprising 21 intensive care units (ICUs) across 20 hospitals from September 2019 to December 2021. Patients meeting the Sepsis-3 criteria were included., Results: Among 11,981 sepsis patients, 3501 were analyzed, all of whom were referred to the ICU through the emergency department (mean age: 72 ± 13 years; 1976 [56%] males). Of these, 2213 (63%) were culture-positive sepsis and 1288 (37%) were culture-negative sepsis. Compared to the culture-positive sepsis group, the culture-negative sepsis group exhibited less severe illness, with lower Sequential Organ Failure Assessment scores and less deteriorated vital signs. While pulmonary-origin sepsis was common in both groups, culture-negative patients primarily presented with pulmonary infections and had a higher incidence of respiratory failure. In comparison to the culture-positive sepsis group, blood cultures and the administration of empirical antibiotics were performed less promptly in the culture-negative sepsis group. Patients with culture-negative sepsis also showed lower compliance with fluid resuscitation (98.4% vs. 96.9%, p = 0.038; culture-positive sepsis vs. culture-negative sepsis) and received vasopressors earlier (31.1% vs. 35.9%, p = 0.012). In-hospital mortality did not differ significantly between the two groups (31.6% vs. 34.9%, p = 0.073); however, in patients with septic shock, culture-negative sepsis had higher mortality rates (37.6% vs. 45.1%, p = 0.029). The apparent appropriateness of empirical antibiotics in the culture-negative septic shock was higher than that of the culture-positive septic shock (85.2% vs. 96.8%, p < 0.001). Culture-negativity independently predicted poor prognosis in septic shock patients (OR: 1.462, 95% CI [1.060-2.017], p = 0.021)., Conclusion: In patients with septic shock, culture-negativity was associated with increased mortality, despite the paradoxically higher appropriateness of empirical antibiotics than culture-positive patients. These contradictory findings suggest that the current criteria for determining the appropriateness of empirical antibiotic therapy may not be valid for culture-negative sepsis., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the Institutional Review Board of each participating hospital, including Inje University Sanggye Paik Hospital (Approval No. 2018-08-014-013), and the requirement for obtaining patient informed consent was waived because of the observational nature of the study. Additionally, the patient’s information was anonymized and de-identified prior to analysis. Consent for publication: Not applicable. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Despite the clinical importance of sepsis-associated acute kidney injury (SA-AKI), little is known about its epidemiology. We aimed to investigate the incidence and outcomes of SA-AKI, as well as the risk factors for mortality among patients with severe SA-AKI in critically ill patients., Methods: This secondary multicenter, observational, prospective cohort analysis of sepsis in South Korea evaluated patients aged ≥ 19 years admitted to intensive care units with a diagnosis of sepsis. The primary outcome was the incidence of SA-AKI, defined using the new consensus definition of the Acute Disease Quality Initiative 28 Workgroup. Secondary outcomes were in-hospital mortality and risk factors for in-hospital mortality., Results: Between September 2019 and December 2022, 5100 patients were admitted to intensive care units with a diagnosis of sepsis, and 3177 (62.3%) developed SA-AKI. A total of 613 (19.3%), 721 (22.7%), and 1843 (58.0%) patients had stage 1, 2, and 3 SA-AKI, respectively. Severe SA-AKI (stages 2 and 3 combined) was associated with an increased risk of in-hospital mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle was associated with a decreased risk of in-hospital mortality in severe SA-AKI (adjusted odds ratio, 0.62; 95% confidence interval, 0.48-0.79; P < 0.001)., Conclusions: Of the patients admitted to the intensive care unit for sepsis, 62.3% developed SA-AKI. Severe SA-AKI was associated with an increased risk of mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle can potentially improve outcomes in these patients., Competing Interests: Declarations. Availability of data and materials: No datasets were generated or analysed during the current study. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate: This study was approved by the institutional review boards of each participating hospital, including the Seoul National University Bundang Hospital (IRB number: B-1810-500-402). The requirement for informed consent was waived because of the noninterventional, observational nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: The potential adverse effects associated with invasive mechanical ventilation (MV) can lead to delayed decisions on starting MV. We aimed to explore the association between the timing of MV and the clinical outcomes in patients with sepsis ventilated in intensive care unit (ICU)., Methods: We analyzed data of adult patients with sepsis between September 2019 and December 2021. Data was collected through the Korean Sepsis Alliance from 20 hospitals in Korea. Patients who were admitted to ICU and received MV were included in the study. Patients were divided into 'early MV' and 'delayed MV' groups based on whether they were on MV on the first day of ICU admission or later. Propensity score matching was applied, and patients in the two groups were compared on a 1:1 ratio to overcome bias between the groups. Outcomes including ICU mortality, hospital mortality, length of hospital and ICU stay, and organ failure at ICU discharge were compared., Results: Out of 2440 patients on MV during ICU stay, 2119 'early MV' and 321 'delayed MV' cases were analyzed. The propensity score matching identified 295 patients in each group with similar baseline characteristics. ICU mortality was lower in 'early MV' group than 'delayed MV' group (36.3% vs. 46.4%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; p = 0.015). 'Early MV' group had lower in-hospital mortality, shorter ICU stay, and required tracheostomy less frequently than 'delayed MV' group. Multivariable logistic regression model identified 'early MV' as associated with lower ICU mortality (odds ratio, 0.38; 95% confidence interval, 0.29-0.50; p < 0.001)., Conclusion: In patients with sepsis ventilated in ICU, earlier start (first day of ICU admission) of MV may be associated with lower mortality., (© 2024. The Author(s).)

Objectives: In 2018, the Centers for Disease Control and Prevention introduced the Adult Sepsis Event (ASE) definition, using electronic health records (EHRs) data for surveillance and sepsis quality improvement. However, data regarding ASE outside the United States remain limited. We therefore aimed to validate the diagnostic accuracy of the ASE and to assess the prevalence and mortality of sepsis using ASE., Design: Retrospective cohort study., Setting: A single center in South Korea, with 2732 beds including 221 ICU beds., Patients: During the validation phase, adult patients who were hospitalized or visiting the emergency department between November 5 and November 11, 2019, were included. In the subsequent phase of epidemiologic analysis, we included adult patients who were admitted from January to December 2020., Interventions: None., Measurements and Main Results: ASE had a sensitivity of 91.6%, a specificity of 98.3%, a positive predictive value (PPV) of 57.4%, and a negative predictive value of 99.8% when compared with the Sepsis-3 definition. Of 126,998 adult patient hospitalizations in 2020, 6,872 cases were diagnosed with sepsis based on the ASE (5.4% per year), and 893 patients were identified as having sepsis according to the International Classification of Diseases , 10th Edition (ICD-10) (0.7% per year). Hospital mortality rates were 16.6% (ASE) and 23.5% (ICD-10-coded sepsis). Monthly sepsis prevalence and hospital mortality exhibited less variation when diagnosed using ASE compared with ICD-10 coding (coefficient of variation [CV] for sepsis prevalence: 0.051 vs. 0.163, Miller test p < 0.001; CV for hospital mortality: 0.087 vs. 0.261, p = 0.001)., Conclusions: ASE demonstrated high sensitivity and a moderate PPV compared with the Sepsis-3 criteria in a Korean population. The prevalence of sepsis, as defined by ASE, was 5.4% per year and was similar to U.S. estimates. The prevalence of sepsis by ASE was eight times higher and exhibited less monthly variability compared with that based on the ICD-10 code., Competing Interests: Drs. Lim and Lee received support for article research from the Korea Disease Control and Prevention Agency (fund code 2019E280500, 2020E280700, 2021-10-026 to Dr. Lim). They disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Various electrocardiographic changes occur during sepsis, but data on the clinical importance of a low QRS voltage in sepsis are still limited. We aimed to evaluate the association between low QRS voltage identified early in sepsis and mortality in patients with sepsis. Between September 2019 and December 2020, all consecutive adult patients diagnosed with sepsis in the emergency room or general ward at Samsung Medical Center were enrolled. Patients without a 12-lead electrocardiogram recorded within 48 h of recognition of sepsis were excluded. In 432 eligible patients, 12-lead electrocardiogram was recorded within the median of 24 min from the first recognition of sepsis, and low QRS voltage was identified in 115 (26.6%) patients. The low QRS group showed more severe organ dysfunction and had higher levels of N-terminal pro-brain natriuretic peptide. The hospital mortality was significantly higher in the low QRS voltage group than in the normal QRS voltage group (49.6% vs. 28.1%, p < 0.001). Similarly, among the 160 patients who required intensive care unit admission, significantly more patients in the low QRS group died in the intensive care unit (35.9% vs. 18.2%, p = 0.021). Low QRS voltage was associated with increased hospital mortality in patients with sepsis., (© 2024. The Author(s).)

There are numerous prognostic predictive models for evaluating mortality risk, but current scoring models might not fully cater to sepsis patients' needs. This study developed and validated a new model for sepsis patients that is suitable for any care setting and accurately forecasts 28-day mortality. The derivation dataset, gathered from 20 hospitals between September 2019 and December 2021, contrasted with the validation dataset, collected from 15 hospitals from January 2022 to December 2022. In this study, 7436 patients were classified as members of the derivation dataset, and 2284 patients were classified as members of the validation dataset. The point system model emerged as the optimal model among the tested predictive models for foreseeing sepsis mortality. For community-acquired sepsis, the model's performance was satisfactory (derivation dataset AUC: 0.779, 95% CI 0.765-0.792; validation dataset AUC: 0.787, 95% CI 0.765-0.810). Similarly, for hospital-acquired sepsis, it performed well (derivation dataset AUC: 0.768, 95% CI 0.748-0.788; validation dataset AUC: 0.729, 95% CI 0.687-0.770). The calculator, accessible at https://avonlea76.shinyapps.io/shiny&#95;app&#95;up/ , is user-friendly and compatible. The new predictive model of sepsis mortality is user-friendly and satisfactorily forecasts 28-day mortality. Its versatility lies in its applicability to all patients, encompassing both community-acquired and hospital-acquired sepsis., (© 2024. The Author(s).)

Background: Although several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO 2 ) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension., Methods: From the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO 2 (PaO 2  ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO 2 (PaO 2  < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality., Results: The median values of PaO 2 over the first three ICU days in 1211 liberal and 1211 conservative PaO 2 groups were, respectively, 107.2 (92.0-134.0) and 84.4 (71.2-112.0) in day 1110.0 (93.4-132.0) and 80.0 (71.0-100.0) in day 2, and 106.0 (91.9-127.4) and 78.0 (69.0-94.5) in day 3 (all p-values < 0.001). The liberal PaO 2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65-0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67-0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73-0.97; p-value = 0.020) were lower in the liberal PaO 2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO 2 of around 100 mm Hg., Conclusions: In critically ill patients with sepsis, higher PaO 2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO 2 ., (© 2024. The Author(s).)

Background: Prolonged length of hospital stay (LOS) is associated with an increased risk of hospital-acquired conditions and worse outcomes. We conducted a nationwide, multicenter, retrospective cohort study to determine whether prolonged hospitalization before developing sepsis has a negative impact on its prognosis., Methods: We analyzed data from 19 tertiary referral or university-affiliated hospitals between September 2019 and December 2020. Adult patients with confirmed sepsis during hospitalization were included. In-hospital mortality was the primary outcome. The patients were divided into two groups according to their LOS before the diagnosis of sepsis: early- (< 5 days) and late-onset groups (≥ 5 days). Conditional multivariable logistic regression for propensity score matched-pair analysis was employed to assess the association between late-onset sepsis and the primary outcome., Results: A total of 1,395 patients were included (median age, 68.0 years; women, 36.3%). The early- and late-onset sepsis groups comprised 668 (47.9%) and 727 (52.1%) patients. Propensity score-matched analysis showed an increased risk of in-hospital mortality in the late-onset group (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.69-5.34). The same trend was observed in the entire study population (aOR, 1.85; 95% CI, 1.37-2.50). When patients were divided into LOS quartile groups, an increasing trend of mortality risk was observed in the higher quartiles ( P for trend < 0.001)., Conclusion: Extended LOS before developing sepsis is associated with higher in-hospital mortality. More careful management is required when sepsis occurs in patients hospitalized for ≥ 5 days., Competing Interests: Dr. Lim received financial support for research from the Korea Disease Control and Prevention Agency. The remaining authors have disclosed that they do not have any potential competing interests., (© 2024 The Korean Academy of Medical Sciences.)

Background: There is limited information about the outcomes of polymicrobial bloodstream infections in patients with sepsis. We aimed to investigate outcomes of polymicrobial bloodstream infections compared to monomicrobial bloodstream infections., Methods: This study used data from the Korean Sepsis Alliance Registry, a nationwide database of prospective observational sepsis cohort. Adult sepsis patients with bloodstream infections from September 2019 to December 2021 at 20 tertiary or university-affiliated hospitals in South Korea were analyzed., Results: Among the 3,823 patients with bloodstream infections, 429 of them (11.2%) had polymicrobial bloodstream infections. The crude hospital mortality of patients with sepsis with polymicrobial bloodstream infection and monomicrobial bloodstream infection was 35.7% and 30.1%, respectively (p = 0.021). However, polymicrobial bloodstream infections were not associated with hospital mortality in the proportional hazard analysis (HR 1.15 [0.97-1.36], p = 0.11). The inappropriate use of antibiotics was associated with increased mortality (HR 1.37 [1.19-1.57], p < 0.001), and source control was associated with decreased mortality (HR 0.51 [0.42-0.62], p < 0.001)., Conclusions: Polymicrobial bloodstream infections per se were not associated with hospital mortality in patients with sepsis as compared to monomicrobial bloodstream infections. The appropriate use of antibiotics and source control were associated with decreased mortality in bloodstream infections regardless of the number of microbial pathogens., (© 2024. The Author(s).)

Background: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department., Methods: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine). The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley's additive explanations (SHAP)., Results: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756-0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626-0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results., Conclusion: Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Importance: The prevalence of obesity is increasing in the intensive care unit (ICU). Although obesity is a known risk factor for chronic kidney disease, its association with early sepsis-associated acute kidney injury (SA-AKI) and their combined association with patient outcomes warrant further investigation., Objective: To explore the association between obesity, early SA-AKI incidence, and clinical outcomes in patients with sepsis., Design, Setting, and Participants: This nationwide, prospective cohort study analyzed patients aged 19 years or older who had sepsis and were admitted to 20 tertiary hospital ICUs in Korea between September 1, 2019, and December 31, 2021. Patients with preexisting stage 3A to 5 chronic kidney disease and those with missing body mass index (BMI) values were excluded., Exposures: Sepsis and hospitalization in the ICU., Main Outcomes and Measures: The primary outcome was SA-AKI incidence within 48 hours of ICU admission, and secondary outcomes were mortality and clinical recovery (survival to discharge within 30 days). Patients were categorized by BMI (calculated as weight in kilograms divided by height in meters squared), and data were analyzed by logistic regression adjusted for key characteristics and clinical factors. Multivariable fractional polynomial regression models and restricted cubic spline models were used to analyze the clinical outcomes with BMI as a continuous variable., Results: Of the 4041 patients (median age, 73 years [IQR, 63-81 years]; 2349 [58.1%] male) included in the study, 1367 (33.8%) developed early SA-AKI. Obesity was associated with a higher incidence of SA-AKI compared with normal weight (adjusted odds ratio [AOR], 1.40; 95% CI, 1.15-1.70), as was every increase in BMI of 10 (OR, 1.75; 95% CI, 1.47-2.08). While obesity was associated with lower in-hospital mortality in patients without SA-AKI compared with their counterparts without obesity (ie, underweight, normal weight, overweight) (AOR, 0.72; 95% CI, 0.54-0.94), no difference in mortality was observed in those with SA-AKI (AOR, 0.85; 95% CI, 0.65-1.12). Although patients with obesity without SA-AKI had a greater likelihood of clinical recovery than their counterparts without obesity, clinical recovery was less likely among those with both obesity and SA-AKI., Conclusions and Relevance: In this cohort study of patients with sepsis, obesity was associated with a higher risk of early SA-AKI and the presence of SA-AKI modified the association of obesity with clinical outcomes.

Background: Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group., Methods: This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19-50 years, 50-80 years, and ≥ 80 years old individuals., Results: During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02-1.29). Interestingly, in the age 19-50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35-0.93)]. For female, the risk of death remained relatively stable until around age 80 (P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 (P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19-50 groups (adjusted OR = 0.29, 95% CI = 0.12-0.69)., Conclusions: Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis., (© 2023. The Author(s).)

Background: Hospital-onset sepsis is associated with a higher in-hospital mortality rate than community-onset sepsis. Many hospitals have implemented rapid response teams (RRTs) for early detection and timely management of at-risk hospitalized patients. However, the effectiveness of an all-day RRT over a non-all-day RRT in reducing the risk of in-hospital mortality in patient with hospital-onset sepsis is unclear. We aimed to determine the effect of the RRT's operating hours on in-hospital mortality in inpatient patients with sepsis., Methods: We conducted a nationwide cohort study of adult patients with hospital-onset sepsis prospectively collected from the Korean Sepsis Alliance (KSA) Database from 16 tertiary referral or university-affiliated hospitals in South Korea between September of 2019 and February of 2020. RRT was implemented in 11 hospitals, of which 5 (45.5%) operated 24-h RRT (all-day RRT) and the remaining 6 (54.5%) had part-day RRT (non-all-day RRT). The primary outcome was in-hospital mortality between the two groups., Results: Of the 405 patients with hospital-onset sepsis, 206 (50.9%) were admitted to hospitals operating all-day RRT, whereas 199 (49.1%) were hospitalized in hospitals with non-all-day RRT. A total of 73 of the 206 patients in the all-day group (35.4%) and 85 of the 199 patients in the non-all-day group (42.7%) died in the hospital (P = 0.133). After adjustments for co-variables, the implementation of all-day RRT was associated with a significant reduction in in-hospital mortality (adjusted odds ratio 0.57; 95% confidence interval 0.35-0.93; P = 0.024)., Conclusions: In comparison with non-all-day RRTs, the availability of all-day RRTs was associated with reduced in-hospital mortality among patients with hospital-onset sepsis., (© 2022. The Author(s).)

Continuous infusion of beta-lactam antibiotics has emerged as an alternative for the treatment of sepsis because of the favourable pharmacokinetics of continuous infusion. This study aimed to evaluate the survival benefits of continuous vs. intermittent infusion of piperacillin-tazobactam in critically ill patients with sepsis. We retrospectively conducted a single-centre study of continuous infusion vs. intermittent infusion of piperacillin-tazobactam for adult patients who met the Sepsis-3 criteria and were treated at a medical ICU within 48 h after hospitalisation between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 28 days. A total of 157 patients (47 in the continuous group and 110 in the intermittent group) met the inclusion criteria for evaluation. The 28-day mortality rates were 12.8% in the continuous group and 27.3% in the intermittent group (p = 0.07). However, after adjustment for potential covariables, patients in the continuous group (12.8%) showed significantly lower mortality at 28 days than those in the intermittent group (27.3%; adjusted hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.13–0.79; p = 0.013). In sepsis patients, continuous infusion of piperacillin-tazobactam may confer a benefit regarding the avoidance of mortality at 28 days compared with intermittent infusion. [ABSTRACT FROM AUTHOR]