Validation of Adult Sepsis Event and Epidemiologic Analysis of Sepsis Prevalence and Mortality Using Adult Sepsis Event's Electronic Health Records-Based Sequential Organ Failure Assessment Criteria: A Single-Center Study in South Korea.

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.

Pre-Sepsis Length of Hospital Stay and Mortality: A Nationwide Multicenter Cohort Study.

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.

Polymicrobial bloodstream infections per se do not increase mortality compared to monomicrobial bloodstream infections in sepsis patients: a Korean nationwide sepsis cohort study.

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.

Shock indices are associated with in-hospital mortality among patients with septic shock and normal left ventricular ejection fraction.

BACKGROUND: The understanding of shock indices in patients with septic shock is limited, and their values may vary depending on cardiac function. METHODS: This prospective cohort study was conducted across 20 university-affiliated hospitals (21 intensive care units [ICUs]). Adult patients (≥19 years) with septic shock admitted to the ICUs during a 29-month period were included. The shock index (SI), diastolic shock index (DSI), modified shock index (MSI), and age shock index (Age-SI) were calculated at sepsis recognition (time zero) and ICU admission. Left ventricular (LV) function was categorized as either normal LV ejection fraction (LVEF ≥ 50%) or decreased LVEF (<50%). RESULTS: Among the 1,194 patients with septic shock, 392 (32.8%) who underwent echocardiography within 24 h of time zero were included in the final analysis (normal LVEF: n = 246; decreased LVEF: n = 146). In patients with normal LVEF, only survivors demonstrated significant improvement in SI, DSI, MSI, and Age-SI values from time zero to ICU admission; however, no notable improvements were found in all patients with decreased LVEF. The completion of vasopressor or fluid bundle components was significantly associated with improved indices in patients with normal LVEF, but not in those with decreased LVEF. In multivariable analysis, each of the four indices at ICU admission was significantly associated with in-hospital mortality (P < 0.05) among patients with normal LVEF; however, discrimination power was better in the indices for patients with lower lactate levels (≤ 4.0 mmol/L), compared to those with higher lactate levels. CONCLUSIONS: The SI, DSI, MSI, and Age-SI at ICU admission were significantly associated with in-hospital mortality in patients with septic shock and normal LVEF, which was not found in those with decreased LVEF. Our study emphasizes the importance of interpreting shock indices in the context of LV function in septic shock.

Early Sepsis-Associated Acute Kidney Injury and Obesity.

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.

Inhibition of α-melanocyte-stimulating hormone-induced melanogenesis and molecular mechanisms by polyphenol-enriched fraction of Tagetes erecta L. flower.

BACKGROUND: The pursuit for safe and efficacious skin-whitening agents has prompted a dedicated exploration of plant-derived compounds. Notably, Tagetes erecta L. flowers have been used as a medicinal extract and possessed in vitro mushroom tyrosinase activity. However, whether polyphenol-enriched fraction extracted from T. erecta L. flowers (TE) regulates melanogenesis within cellular and animal models has not yet been investigated. PURPOSE: This study aimed to investigate the effect of TE as a prospective inhibitor of melanogenesis. METHODS: Through advanced UPLC-QTof/MS analysis, the components of TE were analyzed. Anti-melanogenic effects of TE were evaluated in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells by measuring cell viability assay, extracellular and intracellular melanin biosynthesis, cyclic adenosine monophosphate (cAMP) production, and melanogenesis-related gene and protein expression. Zebrafish larvae were employed for in vivo studies, assessing both heart rate and melanogenesis. Furthermore, molecular docking analyses were employed to predict the interaction between TE components and the melanocortin 1 receptor (MC1R). Direct binding activity of TE components to MC1R was compared with [Nle4, d-Phe7]-MSH (NDP-MSH). RESULTS: TE was found to contain significant phenolic compounds such as patulitrin, quercetagetin, kaempferol, patuletin, and isorhamnetin. This study revealed that TE effectively inhibits melanin biosynthesis in both in vitro and in vivo models. This inhibition was attributed to interference of TE with the cAMP-cAMP response element-binding protein (CREB)-microphthalmia-associated transcription factor (MITF)-tyrosinase pathway, which plays a pivotal role in regulating melanogenesis. Importantly, TE exhibited the remarkable ability to curtail α-MSH-induced melanogenesis in zebrafish larvae without impacting heart rates. Molecular docking analyses predicted that the components of TE possibly interact with the melanocortin 1 receptor, suggesting their role as potential inhibitors of melanin biosynthesis. However, through the direct binding activity compared with NDP-MSH, any TE components did not directly bind to MC1R, suggesting that TE inhibits α-MSH-induced melanogenesis by inhibiting the cAMP-mediated intracellular signaling pathway. The assessment of anti-melanogenic activity, conducted both in vitro and in vivo, revealed that patulitrin and patuletin exhibited significant inhibitory effects on melanin formation, highlighting their potency as major contributors. DISCUSSION: This investigation demonstrated the considerable potential of TE as a natural remedy endowed with remarkable anti-melanogenic properties. The demonstrated capacity of TE to attenuate melanin production by modulating the cAMP-CREB-MITF-tyrosinase pathway underscores its central role in management of disorders associated with excessive pigmentation. Importantly, the implications of these findings extend to the cosmetics industry, where TE emerges as a prospective and valuable ingredient for the formulation of skin-whitening products. The elucidated interactions between TE components and MC1R not only provide insight into a potential mechanism of action but also elevate the significance of this study. In summary, this study not only contributes to our comprehension of pigmentation-related conditions but also firmly establishes TE as a secure and natural strategy for the regulation of melanin production. The innovative aspects of TE propel it into the forefront of potential interventions, marking a noteworthy advancement in the pursuit of effective and safe solutions for pigmentation disorders.

Clinical effects of bacteremia in sepsis patients with community-acquired pneumonia.

BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.

The Association Between Tachycardia and Mortality in Septic Shock Patients According to Serum Lactate Level: A Nationwide Multicenter Cohort Study.

BACKGROUND: This study aimed to evaluate whether the effect of tachycardia varies according to the degree of tissue perfusion in septic shock. METHODS: Patients with septic shock admitted to the intensive care units were categorized into the tachycardia (heart rate > 100 beats/min) and non-tachycardia (≤ 100 beats/min) groups. The association of tachycardia with hospital mortality was evaluated in each subgroup with low and high lactate levels, which were identified through a subpopulation treatment effect pattern plot analysis. RESULTS: In overall patients, hospital mortality did not differ between the two groups (44.6% vs. 41.8%, P = 0.441), however, tachycardia was associated with reduced hospital mortality rates in patients with a lactate level ≥ 5.3 mmol/L (48.7% vs. 60.3%, P = 0.030; adjusted odds ratio [OR], 0.59, 95% confidence interval [CI], 0.35-0.99, P = 0.045), not in patients with a lactate level < 5.3 mmol/L (36.5% vs. 29.7%, P = 0.156; adjusted OR, 1.39, 95% CI, 0.82-2.35, P = 0.227). CONCLUSION: In septic shock patients, the effect of tachycardia on hospital mortality differed by serum lactate level. Tachycardia was associated with better survival in patients with significantly elevated lactate levels.

Impact of sepsis on Eastern Cooperative Oncology Group performance status among fully ambulatory patients: a prospective nationwide multicenter cohort.

Background: Investigations of the impact of sepsis on the Eastern Cooperative Oncology Group performance status (ECOG PS) of fully ambulatory patients are scarce. Methods: This is a retrospective analysis of prospectively collected nationwide data on septic patients recruited from 19 hospitals of the Korean Sepsis Alliance between August 2019 and December 2020. Adult septic patients with good ECOG PS (i.e., 0 or 1) before sepsis were enrolled in this study. The change in ECOG PS and the prevalence of disability (ECOG PS ≥2) at hospital discharge were recorded. Results: Of the 4,145 septic patients, 1,735 (41.9%) patients who had ECOG PS of 0 or 1 before sepsis and eventually survived to discharge were selected. After treatment for sepsis, the ECOG PS deteriorated in 514 (29.6%) patients; 376 (21.7%) patients had poor ECOG PS (i.e., ≥2) at hospital discharge. The proportion of patients with poor ECOG PS at hospital discharge increased with increases in the initial sequential organ failure assessment (SOFA) score and lactate level. Furthermore, poor ECOG PS at hospital discharge was found in young patients (aged <65 years, 17.4%), those with no history of cancer (18.2%) or with low comorbidities [Charlson comorbidity index (CCI) ≤2; 13.6%], and those without septic shock (19.9%). In multivariable analysis, age, solid cancer, immunocompromised condition, SOFA score, mechanical ventilation, and use of inappropriate empirical antibiotics (odds ratio: 1.786; 95% confidence interval: 1.151-2.771) were significant risk factors for poor ECOG PS. Conclusions: One in five septic patients who were fully ambulatory before sepsis were not functionally independent at hospital discharge. Incomplete functional recovery was also seen in a substantial proportion of younger patients, those with low comorbidities, and those without septic shock. However, the adequacy of empirical antibiotics may improve the functional status in such patients.

Impact of a cumulative positive fluid balance during the first three ICU days in patients with sepsis: a propensity score-matched cohort study.

BACKGROUND: The optimal strategy for fluid management during the first few days of ICU in sepsis patients remains controversial. We aimed to investigate the impact of cumulative fluid balance during the first three days of ICU on the mortality of patients with sepsis. METHODS: This study analyzed prospectively collected data from the Korean Sepsis Alliance Database, which registered 11,981 sepsis patients from 20 hospitals. We selected three propensity score-matched cohorts consisting of patients with a negative or positive cumulative fluid balance during the first three ICU days: from ICU admission to the first midnight as the D1 cohort, until the second midnight as the D2 cohort, and until the third midnight as the D3 cohort. The propensity score for fluid balance was calculated using covariates including the amount of fluid output during the first three ICU days. The primary outcome was mortality at day 28 in the ICU. RESULTS: From a total of 11,981 patients, 2516 patients were included for propensity score matching. After matching in a 1:1 ratio, there were 483, 373, and 392 matched pairs of patients assigned to the D1, D2, and D3 cohorts, respectively. In the D1 cohort, there were no significant differences in mortality at day 28 (hazard ratio [HR], 1.17; 95% confidence interval [CI] 0.85-1.60; P = 0.354) between the two groups. The positive fluid groups in both the D2 (HR, 2.13; 95% CI 1.48-3.06; P < 0.001) and D3 (HR, 1.56; 95% CI 1.10-2.22; P = 0.012) cohorts had significantly higher mortality rates than the negative fluid groups. CONCLUSIONS: In patients with sepsis, a positive fluid balance on the first ICU day was not associated with mortality at day 28. In contrast, cumulative positive fluid balances on the second and third ICU days were associated with higher mortality at day 28.

Potent inhibition of human tyrosinase inhibitor by verproside from the whole plant of Pseudolysimachion rotundum var. subintegrum.

Affinity-based ultrafiltration-mass spectrometry coupled with ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry was utilised for the structural identification of direct tyrosinase ligands from a crude Pseudolysimachion rotundum var. subintegrum extract. False positives were recognised by introducing time-dependent inhibition in the control for comparison. The P. rotundum extract contained nine main metabolites in the UPLC-QTOF-MS chromatogram. However, four metabolites were reduced after incubation with tyrosinase, indicating that these metabolites were bound to tyrosinase. The IC50 values of verproside (1) were 31.2 µM and 197.3 µM for mTyr and hTyr, respectively. Verproside showed 5.6-fold higher efficacy than that of its positive control (kojic acid in hTyr). The most potent tyrosinase inhibitor, verproside, features a 3,4-dihydroxybenzoic acid moiety on the iridoid glycoside and inhibits tyrosinase in a time-dependent and competitive manner. Among these three compounds, verproside is bound to the active site pocket with a docking energy of -6.9 kcal/mol and four hydrogen bonding interactions with HIS61 and HIS85.

Influence of gender on age-associated in-hospital mortality in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study.

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.

Serial evaluation of the serum lactate level with the SOFA score to predict mortality in patients with sepsis.

In patients with sepsis, outcome prediction plays an important role in influencing therapeutic decision making. In this nationwide, prospective, observational cohort study of sepsis patients conducted between September 2019 and December 2020, we evaluated a novel scoring system using serial Sequential Organ Failure Assessment (SOFA) scores and serum lactate to accurately predict mortality in sepsis. Based on the serum lactate score (Lac-score), patients were assigned to 5 categories: lactate < 2, ≥ 2 to < 4, ≥ 4 to < 8, ≥ 8 to < 12, and ≥ 12 mmol/L. Lac-SOFA score was defined as the sum of Lac-score and SOFA score. After screening 7113 patients, 379 were excluded and 6734 were included in analysis. In-hospital mortality AUROC for serial Lac-SOFA score from initial to ICU day 3 was significantly higher than that for serial SOFA score (initial, 0.679 vs. 0.656, day 1, 0.723 vs. 0.709, day 2, 0.760 vs. 0.747, and day 3, 0.797 vs. 0.781; DeLong's test, p < 0.001). The initial Lac-SOFA score significantly correlated with in-hospital mortality when the patients were divided into five classes based on 5-point intervals (p < 0.05). Serial evaluation of lactate levels with the SOFA score may improve the predictive accuracy of the SOFA score for determining mortality risk in sepsis patients.

Association between the timing of ICU admission and mortality in patients with hospital-onset sepsis: a nationwide prospective cohort study.

BACKGROUND: Based on sparse evidence, the current Surviving Sepsis Campaign guideline suggests that critically ill patients with sepsis be admitted to the intensive care unit (ICU) within 6 h. However, limited ICU bed availability often makes immediate transfer difficult, and it is unclear whether all patients will benefit from early admission to the ICU. Therefore, the purpose of this study was to determine the association between the timing of ICU admission and mortality in patients with hospital-onset sepsis. METHODS: This nationwide prospective cohort study analyzed patients with hospital-onset sepsis admitted to the ICUs of 19 tertiary hospitals between September 2019 and December 2020. ICU admission was classified as either early (within 6 h) or delayed (beyond 6 h). The primary outcome of in-hospital mortality was compared using logistic regression adjusted for key prognostic factors in the unmatched and 1:1 propensity-score-matched cohorts. Subgroup and interaction analyses assessed whether in-hospital mortality varied according to baseline characteristics. RESULTS: A total of 470 and 286 patients were included in the early and delayed admission groups, respectively. Early admission to the ICU did not significantly result in lower in-hospital mortality in both the unmatched (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 0.99-1.85) and matched cohorts (aOR, 1.38; 95% CI, 0.94-2.02). Subgroup analyses showed that patients with increasing lactate levels (aOR, 2.10; 95% CI, 1.37-3.23; P for interaction = 0.003), septic shock (aOR, 2.06; 95% CI, 1.31-3.22; P for interaction = 0.019), and those who needed mechanical ventilation (aOR, 1.92; 95% CI, 1.24-2.96; P for interaction = 0.027) or vasopressor support (aOR, 1.69; 95% CI, 1.17-2.44; P for interaction = 0.042) on the day of ICU admission had a higher risk of mortality with delayed admission. CONCLUSIONS: Among patients with hospital-onset sepsis, in-hospital mortality did not differ significantly between those with early and delayed ICU admission. However, as early intensive care may benefit those with increasing lactate levels, septic shock, and those who require vasopressors or ventilatory support, admission to the ICU within 6 h should be considered for these subsets of patients.

Obesity Paradox and Functional Outcomes in Sepsis: A Multicenter Prospective Study.

OBJECTIVES: In Asian populations, the correlation between sepsis outcomes and body mass is unclear. A multicenter, prospective, observational study conducted between September 2019 and December 2020 evaluated obesity's effects on sepsis outcomes in a national cohort. SETTING: Nineteen tertiary referral hospitals or university-affiliated hospitals in South Korea. PATIENTS: Adult patients with sepsis ( n = 6,424) were classified into obese ( n = 1,335) and nonobese groups ( n = 5,089). MEASUREMENTS AND RESULTS: Obese and nonobese patients were propensity score-matched in a ratio of 1:1. Inhospital mortality was the primary outcome. After propensity score matching, the nonobese group had higher hospital mortality than the obese group (25.3% vs 36.7%; p < 0.001). The obese group had a higher home discharge rate (70.3% vs 65.2%; p < 0.001) and lower median Clinical Frailty Scale (CFS) (4 vs 5; p = 0.007) at discharge than the nonobese group, whereas the proportion of frail patients at discharge (CFS ≥ 5) was significantly higher in the nonobese group (48.7% vs 54.7%; p = 0.011). Patients were divided into four groups according to the World Health Organization body mass index (BMI) classification and performed additional analyses. The adjusted odds ratio of hospital mortality and frailty at discharge for underweight, overweight, and obese patients relative to normal BMI was 1.25 ( p = 0.004), 0.58 ( p < 0.001), and 0.70 ( p = 0.047) and 1.53 ( p < 0.001), 0.80 ( p = 0.095), and 0.60 ( p = 0.022), respectively. CONCLUSIONS: Obesity is associated with higher hospital survival and functional outcomes at discharge in Asian patients with sepsis.

HYPOTENSION AT THE TIME OF SEPSIS RECOGNITION IS NOT ASSOCIATED WITH INCREASED MORTALITY IN SEPSIS PATIENTS WITH NORMAL LACTATE LEVELS.

ABSTRACT: Background and Objective: Although sepsis is heterogeneous, data on sepsis patients with normal lactate levels are very limited. We explored whether hypotension at the time of sepsis recognition (i.e., time zero) was significant in terms of survival when lactate levels were normal in sepsis patients. Patients and Design: This was a prospective multicenter observational study conducted in 19 hospitals (20 intensive care units [ICUs]). Adult sepsis patients with normal lactate levels (≤2 mmol/L) admitted to ICUs were divided by the mean arterial pressure at time zero into hypotensive (<65 mm Hg) and nonhypotensive groups (≥65 mm Hg). Measurements and Results: Of 2,032 patients with sepsis (not septic shock), 617 with normal lactate levels were included in the analysis. The hypotensive group (n = 237) was characterized by higher rates of abdominal or urinary infections, and bacteremia, whereas the nonhypotensive group (n = 380) was characterized by higher rates of pulmonary infections and systemic inflammatory response. However, the Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment score (excluding the cardiovascular score) were not different between the groups. During sepsis resuscitation, the rates of antibiotic administration within 1, 3, and 6 h of time zero were higher in the hypotensive than nonhypotensive group ( P < 0.05 for all time points), and the amounts of pre-ICU fluids given were also higher in the hypotensive group. However, despite a higher rate of vasopressor use in the hypotensive group, ICU and in-hospital mortality rates were not different between the groups (12.7% vs. 13.9% [ P = 0.648] and 19.4% vs. 22.4% [ P = 0.382], respectively). In multivariable analysis, the use of appropriate antibiotics and early lactate measurement were significant risk factors for in-hospital mortality. Conclusions: In sepsis patients with normal lactate levels, neither hypotension nor vasopressor use adversely impacted the hospital outcome. Our results emphasize the importance of early interventions and appropriate use of antibiotics regardless of whether a patient is or is not hypotensive.

Clinical outcomes and prognostic factors of patients with sepsis caused by intra-abdominal infection in the intensive care unit: a post-hoc analysis of a prospective cohort study in Korea.

BACKGROUND: Sepsis is the most common cause of death in hospitals, and intra-abdominal infection (IAI) accounts for a large portion of the causes of sepsis. We investigated the clinical outcomes and factors influencing mortality of patients with sepsis due to IAI. METHODS: This post-hoc analysis of a prospective cohort study included 2126 patients with sepsis who visited 16 tertiary care hospitals in Korea (September 2019-February 2020). The analysis included 219 patients aged > 19 years who were admitted to intensive care units owing to sepsis caused by IAI. RESULTS: The incidence of septic shock was 47% and was significantly higher in the non-survivor group (58.7% vs 42.3%, p = 0.028). The overall 28-day mortality was 28.8%. In multivariable logistic regression, after adjusting for age, sex, Charlson Comorbidity Index, and lactic acid, only coagulation dysfunction (odds ratio: 2.78 [1.47-5.23], p = 0.001) was independently associated, and after adjusting for each risk factor, only simplified acute physiology score III (SAPS 3) (p < 0.001) and continuous renal replacement therapy (CRRT) (p < 0.001) were independently associated with higher 28-day mortality. CONCLUSIONS: The SAPS 3 score and acute kidney injury with CRRT were independently associated with increased 28-day mortality. Additional support may be needed in patients with coagulopathy than in those with other organ dysfunctions due to IAI because patients with coagulopathy had worse prognosis.

Time-to-antibiotics and clinical outcomes in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study.

BACKGROUND: Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. METHODS: This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. RESULTS: Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61-0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44-0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64-1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. CONCLUSION: Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

Preexisting Clinical Frailty Is Associated With Worse Clinical Outcomes in Patients With Sepsis.

OBJECTIVES: Frailty is a multidimensional syndrome or state of increased vulnerability to poor resolution of homoeostasis following a stressor event. Frailty is common in patients with sepsis. Sepsis and frailty are both associated with older age and chronic medical conditions. However, there is limited evidence about the direct association between frailty and sepsis. The aim of this study is to determine the association between preexisting clinical frailty and clinical outcomes in patients with sepsis. DESIGN: A nationwide propensity score-matched cohort study analyzing data prospectively collected between September 2019 and February 2020. SETTING: Nineteen tertiary or university-affiliated hospitals in South Korea. PATIENTS: Adult patients who were diagnosed with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Frailty status was assessed using the Clinical Frailty Scale. All patients were classified as "frail" (Clinical Frailty Scale score, 5-9) or "nonfrail" (Clinical Frailty Scale score, 1-4). Propensity score matching identified comparable nonfrail patients. The primary outcome was inhospital mortality. Multivariable logistic regression analysis was used to evaluate the association between frailty and inhospital mortality. The propensity score-matched cohort comprised 468 nonfrail patients and 468 frail patients; all covariate imbalances were alleviated. In the matched cohort (mean age, 69 ± 14 yr), 27.2% had septic shock at presentation. Inhospital mortality was 34.2% in the frail group and 26.9% in the nonfrail group (p = 0.019). The adjusted odds ratio for inhospital mortality in the frail group compared with the nonfrail group was 2.00 (95% CI, 1.39-2.89; p < 0.001). Among the patients who survived to discharge, the frail group was less likely to be discharged home compared with the nonfrail group, 64.0% versus 81.3%, respectively (p < 0.001). CONCLUSIONS: In patients with sepsis, preexisting clinical frailty is associated with worse clinical outcomes than that in nonfrail patients, including inhospital mortality and discharge to home.

Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data.

OBJECTIVES: To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. DESIGN: Prospective, multicenter, observational study. SETTING: Sixteen tertiary or university hospitals in the Republic of Korea. PATIENTS: Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26-2.65). CONCLUSIONS: Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.