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Background: Early risk stratification is crucial due to septic patients' heterogeneity. Serum albumin level may reflect the severity of sepsis and host status. This study aimed to evaluate the prognostic ability of the initial sequential organ failure assessment (SOFA) score alone and combined with serum albumin levels for predicting 28-day mortality in patients with septic shock. Methods: We conducted an observational study using a prospective, multicenter registry of septic shock patients between October 2015 and May 2022 from 12 emergency departments in the Korean Shock Society and the results were validated by examining those from the septic shock cohort in Asan Medical Center. The primary outcome was 28-day mortality. The area under the receiver operating characteristic (ROC) curve was used to compare the predictive values of SOFA score alone and SOFA score combined with serum albumin level. Results: Among 5805 septic shock patients, 1529 (26.3%) died within 28 days. Mortality increased stepwise with decreasing serum albumin levels (13.6% in albumin ≥3.5, 20.7% in 3.5–3.0, 29.7% in 3.0–2.5, 44.0% in 2.5–2.0, 56.4% in <2.0). The albumin SOFA score was calculated by adding the initial SOFA score to the 4 points assigned for albumin levels. ROC analysis for predicting 28-day mortality showed that the area under the curve for the albumin SOFA score was 0.71 (95% CI 0.70–0.73), which was significantly higher than that of the initial SOFA score alone (0.68, 95% CI: 0.67–0.69). Conclusions: The combination of the initial SOFA score with albumin can improve prognostic accuracy for patients with septic shock, suggesting the albumin SOFA score may be used as an early mortality stratification tool. [ABSTRACT FROM AUTHOR]

Purpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis. Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility. Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028). Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

A reliable prognostic score for minimizing futile treatments in advanced cancer patients with septic shock is rare. A machine learning (ML) model to classify the risk of advanced cancer patients with septic shock is proposed and compared with the existing scoring systems. A multi-center, retrospective, observational study of the septic shock registry in patients with stage 4 cancer was divided into a training set and a test set in a 7:3 ratio. The primary outcome was 28-day mortality. The best ML model was determined using a stratified 10-fold cross-validation in the training set. A total of 897 patients were included, and the 28-day mortality was 26.4%. The best ML model in the training set was balanced random forest (BRF), with an area under the curve (AUC) of 0.821 to predict 28-day mortality. The AUC of the BRF to predict the 28-day mortality in the test set was 0.859. The AUC of the BRF was significantly higher than those of the Sequential Organ Failure Assessment score and the Acute Physiology and Chronic Health Evaluation II score (both p < 0.001). The ML model outperformed the existing scores for predicting 28-day mortality in stage 4 cancer patients with septic shock. However, further studies are needed to improve the prediction algorithm and to validate it in various countries. This model might support clinicians in real-time to adopt appropriate levels of care. [ABSTRACT FROM AUTHOR]

This study aimed to determine the impact of modifications in emergency department (ED) practices caused by the coronavirus disease 2019 (COVID-19) pandemic on the clinical outcomes and management of patients with septic shock. We performed a retrospective study. Patients with septic shock who presented to the ED between 1 January 2018 and 19 January 2020 were allocated to the pre-COVID-19 group, whereas those who presented between 20 January 2020 and 31 December 2020 were assigned to the post-COVID-19 group. We used propensity score matching to compare the sepsis-related interventions and clinical outcomes. The primary outcome measure was in-hospital mortality. Of the 3697 patients included, 2254 were classified as pre-COVID-19 and 1143 as post-COVID-19. A total of 1140 propensity score-matched pairings were created. Overall, the in-hospital mortality rate was 25.5%, with no statistical difference between the pre- and post-COVID-19 groups (p = 0.92). In a matched cohort, the post-COVID-19 group had delayed lactate measurement, blood culture test, and infection source control (all p < 0.05). There was no significant difference in time to antibiotics (p = 0.19) or vasopressor administration (p = 0.09) between the groups. Although sepsis-related interventions were delayed during the COVID-19 pandemic, there was no significant difference in the in-hospital mortality between the pre- and post-COVID-19 groups. [ABSTRACT FROM AUTHOR]

The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients with septic shock from a prospective multicenter trial and institutional sepsis registry between April 2018 and January 2020. The primary outcome was 28-day mortality. The patients were categorized into vitamin C deficiency and normal groups based on a vitamin C cutoff level of 11.4 mmol/L. Multivariable Cox regression analysis was performed to examine the association between vitamin C levels and 28-day mortality. A total of 165 patients was included for analysis and 77 (46.7%) had vitamin C deficiency. There was no significant difference in the 28-day mortality rate between the vitamin C deficiency group and the normal group (23.4% (n = 18/77) vs. 13.6% (n = 12/88), p = 0.083). Multivariable Cox proportional hazard analysis showed vitamin C deficiency to be associated with increased risk of 28-day mortality (adjusted hazard ratio, 2.65, 95% confidence interval (CI), 1.08–6.45; p = 0.032). Initial vitamin C deficiency was associated with a higher risk of 28-day mortality in patients with septic shock after adjusting for intravenous administration of vitamin C and thiamine, baseline characteristics, laboratory findings, and severity of illness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: An index combining respiratory rate and oxygenation (ROX) has been introduced, and the ROX index is defined as the ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate. In sepsis, hypoxemia and tachypnea are commonly observed. We performed this study to investigate the association between the ROX index and 28-day mortality in patients with sepsis or septic shock.Methods: This retrospective study included 2862 patients. The patients were divided into three groups according to the ROX index: Group I (ROX index >20), Group II (ROX index >10 and ≤ 20), and Group III (ROX index ≤10).Results: The median ROX index was significantly lower in the nonsurvivors than in the survivors (12.8 and 18.2, respectively) (p < 0.001). The 28-day mortality rates in Groups I, II and III were 14.5%, 21.3% and 34.4%, respectively (p < 0.001). In the multivariable Cox regression analysis, Group III had an approximately 40% higher risk of death than Group I during the 28-day period (hazard ratio = 1.41, 95% confidence interval 1.13-1.76). The area under the curve of the ROX index was significantly higher than that of the quick Sequential Organ Failure Assessment score (p < 0.001).Conclusions: The ROX index was lower in nonsurvivors than in survivors, and a ROX index less than or equal to 10 was an independent prognostic factor for 28-day mortality in patients with sepsis or septic shock. Therefore, the ROX index could be used as a prognostic marker in sepsis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock.Methods: The ascorbic acid and thiamine effect in septic shock (ATESS) trial was a multi-centre, double-blind, randomized, controlled trial conducted in four academic emergency departments, enrolling adult patients with septic shock from December 2018 through January 2020. Patients were randomly assigned in a 1:1 ratio to either the treatment group [intravenous vitamin C (50 mg/kg, maximum single dose 3 g) and thiamine (200 mg) administration every 12 h for a total of 48 h] or the placebo group (identical volume of 0.9% saline with the same protocol). The primary outcome was Δ Sequential Organ Failure Assessment (SOFA) score (SOFA score at enrolment-SOFA score after 72 h). Eighteen secondary outcomes were predefined, including shock reversal and 28-day mortality.Results: A total of 111 patients were enrolled, of which 53 were assigned to the treatment group and 58 were assigned to the placebo group. There was no significant difference in ΔSOFA scores between the treatment group and the placebo group [3, interquartile range (IQR) - 1 to 5 vs. 3, IQR 0-4, respectively, p = 0.96]. Predefined secondary outcomes were also not significantly different between the groups.Conclusion: In this study, vitamin C and thiamine administration in the early phase of septic shock did not improve organ function compared with placebo, despite improvements in vitamin C and thiamine levels. [ABSTRACT FROM AUTHOR]

This study evaluated the prognostic ability of lactate normalization achieved within 6 and 24 h from septic shock recognition. Data from a septic shock registry from October 2015 to February 2017 were reviewed. The study included 2,102 eligible septic shock patients to analyze the prognostic ability of lactate normalization, defined as a follow-up lactate level <2 mmol/L within six hours of bundle therapy and within 24 hours of delayed normalization. The primary outcome was 28-day mortality. The overall 28-day mortality rate was 21.4%. The rates of lactate normalization within 6 and 24 h were significantly higher in the survivor groups than in the non-survivor group (42.4% vs. 23.4% and 60.2% vs. 31.2%; P<0.001, respectively). Multivariate logistic regression analysis showed that both 6- and 24-h lactate normalization were independent predictors (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.45–0.75, p<0.001 and OR 0.42, 95% CI 0.33–0.54, p<0.001, respectively). When we could not achieve the lactate normalization, the sensitivity, specificity, positive, and negative predictive value to predict mortality were 76.6%, 42.4%, 26.5% and 87.0% respectively for 6-h normalization, and 68.8%, 60.2%, 32.0% and 87.7% respectively for 24-h normalization. Besides 6-h lactate normalization, 24-h delayed lactate normalization was associated with decreasing mortality in septic shock patients. Lactate normalization may have a role in early risk stratification and as a therapeutic target. [ABSTRACT FROM AUTHOR]

There is a lack of evidence-based guidelines for the administration methods of ceftriaxone in emergency departments (EDs), resulting in the reliance on individual institutional protocols for decision-making. This study was performed to compare the effects of administering ceftriaxone via intravenous push (IVP) and intravenous piggyback (IVPB) on 28-day mortality in patients with sepsis. This was a retrospective study of patients aged 18 years or older with sepsis or septic shock who visited an ED and were treated with ceftriaxone as an initial antibiotic between March 2010 and February 2019. Patients were divided into the IVP group and the IVPB group based on the administration method. The primary outcome was 28-day mortality, and multivariable Cox proportional hazards regression analysis was performed to evaluate the relationship between antibiotic administration methods and 28-day mortality. During the study period, a total of 939 patients were included in the final analysis, and the overall mortality rate was 12.2%. The antibiotic administration time was significantly lower in the IVP group than in the IVPB group, and the rates of antibiotic administration within 1 h and within 3 h were higher in the IVP group than in the IVPB group (p < 0.05). However, there was no significant difference in 28-day mortality between the two groups (hazard ratio 1.07, 95% confidence interval 0.69–1.65). IVP administration of ceftriaxone reduced the time of antibiotic administration compared with IVPB, but there was no difference in 28-day mortality. [ABSTRACT FROM AUTHOR]

This study aimed to address the impact of 1-hr bundle achievement on outcomes in septic shock patients. Secondary analysis of multicenter prospectively collected data on septic shock patients who had undergone protocolized resuscitation bundle therapy at emergency departments was conducted. In-hospital mortality according to 1-h bundle achievement was compared using multivariable logistic regression analysis. Patients were also divided into 3 groups according to the time of bundle achievement and outcomes were compared to examine the difference in outcome for each group over time: group 1 (≤1 h reference), group 2 (1–3 h) and group 3 (3–6 h). In total, 1612 patients with septic shock were included. The 1-h bundle was achieved in 461 (28.6%) patients. The group that achieved the 1-h bundle did not show a significant difference in in-hospital mortality compared to the group that did not achieve the 1-h bundle on multivariable logistic regression analysis (<1 vs. >1 h) (odds ratio = 0.74, p = 0.091). However, 3- and 6- h bundle achievements showed significantly lower odds ratios of in-hospital mortality compared to the group that did not achieve the bundle (<3 vs. >3 h, <6 vs. >6 h, odds ratio = 0.604 and 0.458, respectively). There was no significant difference in in-hospital mortality over time for group 2 and 3 compared to that of group 1. One-hour bundle achievement was not associated with improved outcomes in septic shock patients. These data suggest that further investigation into the clinical implications of 1-h bundle achievement in patients with septic shock is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Aim of study: The effects of therapeutic hypothermia (HT) during experimental sepsis may be influenced by disease severity. We experimentally investigated the effect of therapeutic HT on varying disease severity in a septic rat model. Materials and methods: An adult male Sprague-Dawley rat model of intra-abdominal sepsis was used. To modify the disease severity, we used two different models; a moderate severe sepsis model (MSSM) and a severe septic shock model (SSSM). All rats were randomized to a hypothermia group (HT, 30–32°C) or a normothermia group (NT, 36–38°C) 1h after sepsis induction in each model. HT was maintained for 4h and rewarming was conducted for 2h. Survival time was recorded for up to 12h in the SSSM group and 24h in the MSSM group. Acute lung and liver injury, cytokine, and malondialdehyde (MDA) levels were investigated 7h after sepsis induction. Hemodynamic profiles were also evaluated. Results: In the SSSM, there were survival benefits and reduced acute lung and liver injury with therapeutic HT. Therapeutic HT was also associated with significantly reduced levels of plasma interleukin-6 and tissue malondialdehyde (MDA) levels in the liver and lung compared with the NT group in the SSSM. There was a tendency for the mean arterial pressure to be higher in the HT group compared to the NT group in the SSSM. In MSSM, however, there was no such beneficial effect. Conclusion: In this rat model of severe septic shock, therapeutic HT showed beneficial effects. In contrast, therapeutic HT did not show protective effect in the moderate sepsis model. [Copyright &y& Elsevier]

Background: Current sepsis guidelines recommend administration of antibiotics within 1 hour of emergency department (ED) triage. However, the quality of the supporting evidence is moderate, and studies have shown mixed results regarding the association between antibiotic administration timing and outcomes in septic shock. We investigated to evaluate the association between antibiotic administration timing and in-hospital mortality in septic shock patients in the ED, using propensity score analysis.Methods: An observational study using a prospective, multicenter registry of septic shock, comprising data collected from 10 EDs, was conducted. Septic shock patients were included, and patients were divided into 4 groups by the interval from triage to first antibiotic administration: group 1 (≤1 hour; reference), 2 (1-2 hours), 3 (2-3 hours), and 4 (>3 hours). The primary endpoint was in-hospital mortality. After inverse probability of treatment weighting, the outcomes of the groups were compared.Results: A total of 2250 septic shock patients were included, and the median time to first antibiotic administration was 2.29 hours. The in-hospital mortality of groups 2 and 4 were significantly higher than those of group 1 (odds ratio [OR] 1.248; 95% confidence interval [CI], 1.053-1.478; P = .011; OR 1.419; 95% CI, 1.203-1.675; P < .001, respectively), but those of group 3 was not (OR 1.186; 95% CI, 0.999-1.408; P = .052). Subgroup analyses of patients (n = 2043) with appropriate antibiotics presented similar results.Conclusions: In patients with septic shock, rapid administration of antibiotics was generally associated with a decrease in in-hospital mortality, but no "every hour delay" was seen. [ABSTRACT FROM AUTHOR]