This study systematically evaluates the therapeutic efficacy of melatonin as an adjunctive therapy, aiming to determine its potential to reduce mortality and mitigate inflammatory responses in patients with sepsis.

A search was conducted across PubMed, Web of Science, Cochrane Library, and Embase databases. The Cochrane Collaboration Risk of Bias (ROB) tool was systematically employed to assess the potential for bias in the relevant studies. The I² statistic was employed to evaluate heterogeneity among the studies. Potential publication bias was assessed using Begg's test. Sensitivity analysis was performed to examine the stability of the results. Additionally, a GRADE evaluation of the evidence level.

This meta-analysis encompassed a total of seven randomized controlled trials involving 421 patients diagnosed with sepsis. The primary results indicated that the mortality rate in the intervention group was significantly lower than that in the control group, suggesting that melatonin may effectively reduce mortality among sepsis patients [OR = 0.42, 95 % CI: 0.23-0.77, P = 0.005]. Additionally, the CRP levels in the intervention group were markedly lower than those in the control group, providing evidence that melatonin possesses anti-inflammatory properties that may help decrease inflammatory markers in sepsis patients [SMD= -4.00, 95 % CI: -6.47 to -1.53, P = 0.001]. Furthermore, Secondary outcome results showed no statistically significant differences in sequential organ failure assessment (SOFA) scores, length of hospital stay, and adverse effects. A sensitivity analysis confirmed the robustness of the findings from the included studies. By applying the GRADE system to evaluate the quality of evidence, we found the evidence in four grades: one rated as high quality, one as medium quality, and three rated as low quality.

Melatonin, when used as an adjuvant therapy, significantly reduces mortality and lowers the levels of the inflammatory marker CRP in patients with sepsis, while also improving their physical condition. However, due to the limited number and quality of the articles, these conclusions warrant further verification through the conduct of additional high-quality research.

Sepsis is a common condition associated with significant morbidity and mortality. Emergency physicians play a key role in the diagnosis and management of this condition.

This paper evaluates key evidence-based updates concerning the management of sepsis and septic shock for the emergency clinician.

Sepsis is a life-threatening syndrome, and rapid diagnosis and management are essential. Antimicrobials should be administered as soon as possible, as delays are associated with increased mortality. Resuscitation targets include mean arterial pressure ≥ 65 mmHg, mental status, capillary refill time, lactate, and urine output. Intravenous fluid resuscitation plays an integral role in those who are fluid responsive. Balanced crystalloids and normal saline are both reasonable options for resuscitation. Early vasopressors should be initiated in those who are not fluid-responsive. Norepinephrine is the recommended first-line vasopressor, and if hypotension persists, vasopressin should be considered, followed by epinephrine. Administration of vasopressors through a peripheral 20-gauge or larger intravenous line is safe and effective. Steroids such as hydrocortisone and fludrocortisone should be considered in those with refractory septic shock.

An understanding of the recent updates in the literature concerning sepsis and septic shock can assist emergency clinicians and improve the care of these patients.

The impact of early antibiotics on mortality in patients with suspected sepsis in the emergency department (ED) remains debated, particularly in patients with less severe presentations or before infection confirmation.

To evaluate the association between time to antibiotic administration and 28-day in-hospital mortality among patients with suspected sepsis in the ED.

Post hoc analysis of the 1-bundle emergency department trial, a multicenter, stepped-wedge cluster-randomized controlled trial conducted in 23 EDs in France and Spain. A total of 872 patients with suspected sepsis were included between June 2022 and September 2023. All patients with available data on antibiotic administration were analyzed, and a subgroup of patients with no hypotension was also assessed.

Time to antibiotic administration. The effect of time to fluid resuscitation was also assessed.

The primary outcome was in-hospital mortality at 28 days. Secondary outcomes included all-cause 28-day mortality, ICU length of stay, number of days without vasopressors at day 28, and change in Sequential Organ Failure Assessment score at 72 h.

Among 872 patients (mean age 66 years; 41% female), 859 had available data on antibiotic administration (primary analysis) and 791 (92%) received antibiotics. The median time to antibiotic administration was 61 min (IQR 14-169), with 457 patients (58%) receiving antibiotics within 1 h. In-hospital mortality at 28 days was 14.7% for patients who did not received antibiotic within 1 h versus 9.6% for patients who did [adjusted odds ratio (aOR) 2.00 (1.24-3.23)]. There was an aOR of 1.06 (1.02-1.1) for each hour of delay for antibiotic administration. This effect was confirmed in patients without hypotension [aOR 2.02 (1.08-3.76) for patients who received antibiotics beyond 1 h]. Time to fluid resuscitation was not associated with 28-day in-hospital mortality.

In patients with suspected sepsis presenting to the ED antibiotic administration beyond 1 h was associated with a two-fold increased 28-day in-hospital mortality. This effect persisted in patients without hypotension.

Sepsis and septic shock are common conditions evaluated and managed in the emergency department (ED), and these conditions are associated with significant morbidity and mortality. There have been several recent updates in the literature, including guidelines, on the evaluation and diagnosis of sepsis and septic shock.

This is the first paper in a two-part series that provides emergency clinicians with evidence-based updates concerning sepsis and septic shock. This first paper focuses on evaluation and diagnosis of sepsis and septic shock.

The evaluation, diagnosis, and management of sepsis have evolved since the first definition in 1991. Current guidelines emphasize rapid diagnosis to improve patient outcomes. However, scoring systems have conflicting data for diagnosis, and sepsis should be considered in any patient with infection and abnormal vital signs, evidence of systemic inflammation (e.g., elevated white blood cell count or C-reactive protein), or evidence of end-organ dysfunction. The clinician should consider septic shock in any patient with infection and hypotension despite volume resuscitation or who require vasopressors to maintain a mean arterial pressure ≥ 65 mmHg. There are a variety of sources of sepsis but the most common include pulmonary, urinary tract, abdomen, and skin/soft tissue. Examples of other less common etiologies include the central nervous system (e.g., meningitis, encephalitis), spine (e.g., spinal epidural abscess, osteomyelitis), cardiac (e.g., endocarditis), and joints (e.g., septic arthritis). Evaluation may include biomarkers such as procalcitonin, C-reactive protein, and lactate, but these should not be used in isolation to exclude sepsis. Imaging is a key component of evaluation and should be based on the suspected source.

There have been several recent updates in the literature including guidelines concerning sepsis and septic shock; an understanding of these updates can assist emergency clinicians and improve the care of these patients.

We investigated the extent to which demographic characteristics, clinical care aspects, and relevant biomarkers predicted sepsis-related mortality among patients transferred from a rural, low-volume emergency department (ED) to an urban, high-volume, level-2 trauma center.

We conducted an observational study among adult severe sepsis patients (N = 242) who, within a community-based regional healthcare system, presented to one of the four rural, low-volume EDs and were subsequently transferred to the urban, high-volume, level-2 trauma center, and were identified as septic at either location. We evaluated in-hospital and 30 days after discharge mortality.

In-hospital mortality rate was predicted by previous admission to an ICU (OR 5.02, 95 % CI: 1.89-15.94, p = 0.002), identification of sepsis prior to transfer (OR 0.29, 95 % CI: 0.11-0.74, p = 0.01), and a moderately abnormal lactate level (OR 0.22, 95 % CI: 0.05-0.79, p = 0.03). Mortality 30 days after discharge was predicted by previous admission to an ICU (OR: 3.28, 95 % CI: 1.62-6.97, p = 0.001), abnormal red cell distribution width (OR: 2.23, 95 % CI: 1.11-4.60, p = 0.03), identification of sepsis prior to transfer (OR: 0.26, 95 % CI: 0.12-0.54, p < 0.001), and a moderately abnormal lactate (OR: 0.32, 95 % CI: 0.12-0.79, p = 0.02).

Early identification of sepsis, as well as attention to prior ICU admission or comorbidities and abnormal red cell distribution width, could facilitate better care and prevent mortality among patients with sepsis who are transferred from a rural, low-volume emergency department to an urban-high volume facility.

Sepsis is a serious threat to human life. Early prediction of high-risk populations for sepsis is necessary especially in elderly patients. Artificial intelligence shows benefits in early warning. The aim of the study was to construct an early machine warning model for elderly sepsis patients and evaluate its performance. We collected elderly patients from General Hospital of Ningxia Medical University emergency department and intensive care unit from 01 January 2021 to 01 August 2023. The clinical data was divided into a training set and a test set. A total of 2976 patients and 12 features were screened. We used 8 machine learning models to build the warning model. In conclusion, we developed a model based on XGBoost with an AUROC of 0.971, AUPRC of 0.862, accuracy of 0.95, specificity of 0.964 and F1 score of 0.776. Of all the features, baseline APTT played the most important role, followed by baseline lymphocyte count. Higher level of baseline APTT and lower level of baseline lymphocyte count may indicate higher risk of sepsis occurrence. We developed a high-performance early warning model for sepsis in old age based on machine learning in order to facilitate early treatment but also need further external validation.

Sepsis is one of the most challenging and complex clinical states, with persistently high mortality rates. Guidelines recommend the early identification of sepsis patients and immediate initiation of the Hour-1 Bundle treatment to reduce mortality from sepsis. Emergency nurses play a vital role in the early screening of sepsis. Studies indicate that mind mapping and In-Situ Simulation (ISS) training not only aid healthcare professionals in reinforcing theoretical knowledge retention but also enhance skills in coordination, task management, and communication during simulation exercises. This, in turn, promotes the effective implementation of various treatments during resuscitation. The combination of theoretical and practical training methods is more effective than a single training approach. In June 2023, our hospital's emergency department conducted training for emergency nurses on sepsis mind mapping combined with ISS.

To explore the effect of mind mapping combined with ISS training in promoting the emergency nurses' implementation of the Hour-1 Bundle in sepsis patients.

Using mind mapping and ISS training methods, 24 emergency nurses were divided into 6 groups for a 12-week training period. The study compared their pre- and post-training knowledge of sepsis, identification and diagnostic time, Hour-1 Bundle treatment completion rate, and non-technical skill scores. Post-training, the emergency nurses evaluated the effectiveness of the training.

The scores for sepsis knowledge among emergency nurses before and after training were 44.17 ± 9.21 and 60.42 ± 5.29, respectively. The identification and diagnostic times (hours) were 0.63 ± 0.18 and 0.49 ± 0.13, respectively. The Hour-1 Bundle treatment completion rates were 58.33% and 85.7%, respectively. There was a significant increase in all non-technical skill scores, with statistical significance (P < 0.05, P < 0.001). After two ISS trainings, the SET-M scores progressively increased, indicating a high satisfaction rate among nurses with the mind mapping and ISS training.

The combination of mind mapping and ISS training enables emergency nurses to identify sepsis earlier and promotes the effective implementation of the Hour-1 Bundle treatment in sepsis patients, while also enhancing their cognitive understanding of sepsis and non-technical skills.

This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED).

Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 h of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015-June 2022), were analysed. Drug resistance was interpreted using EUCAST-2023. Clinical features included age, sex, comorbidities (e.g., cancer, diabetes), infection source, presence of central venous catheters (CVC), ongoing therapies, and sepsis severity. Microbiological data included pathogen identification and antimicrobial susceptibility.

Antibiotic-susceptible Escherichia coli (29.5%) was the most common isolate, including extended-spectrum beta-lactamase (ESBL)-producing strains (11.3%), followed by methicillin-susceptible Staphylococcus aureus (MSSA, 8.4%). BSIs due to E. coli were more frequent in patients >60 years (43.9% vs. 27.3%, P < 0.001) and associated with ESBL production (OR = 2.202, P = 0.031) and urosepsis (OR = 1.688, P = 0.006). Younger patients (≤60 years) had more S. aureus-associated BSIs (22.4% vs. 10.8%, P < 0.001) and methicillin resistance (7.9% vs. 3.6%, P = 0.021). Carbapenem-resistant Enterobacterales were rare (2.1%-2.8%), predominantly involving Klebsiella pneumoniae. Onco-hematological patients had a lower multidrug-resistance prevalence (9.5% vs. 21.1%, P < 0.001).

Community-onset BSIs demonstrated substantial prevalence of resistant pathogens, including ESBL and MRSA, emphasizing the need for robust surveillance systems. Age is a critical factor in guiding empirical antibiotic therapy in the ED.

Sepsis-associated hypotension or shock is a critical stage of sepsis, and a current clinical emergency that has high mortality and multiple complications. A new restrictive fluid resuscitation therapy has been applied, and its influence on patients' renal function remains unclear. The purpose of this study is to evaluate the influence of restrictive fluid resuscitation on incidence of severe acute kidney injury (AKI) in adult patients with sepsis hypotension and shock compared with usual care.

Systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

PubMed, Embase, Web of Science and Cochrane Library were searched through 1 November 2024.

We included randomised controlled trials that compared restrictive fluid resuscitation with liberal fluid therapy on patients with sepsis-associated hypotension and shock, to find out their effect on the incidence of severe AKI. Severe AKI was defined as the AKI network score 2-3 or Kidney Disease Improving Global Outcomes stages 2 and 3.

Two independent reviewers used standardised methods to search, screen and code included trials. Risk of bias was assessed using the Cochrane Systematic Review Handbook for randomised clinical trials. Meta-analysis was conducted using random effects models. Sensitivity and subgroup analyses, trial sequential analysis (TSA), Egger's test and the trim-and-fill method were performed. Findings were summarised in GRADE evidence profiles and synthesised qualitatively.

Nine trials (3718 participants) were included in this research and the analysis was conducted in random effects model. There was a significant difference in the incidence of severe AKI (risk ratio 0.87, 95% CI 0.79 to 0.96, p=0.006; I2=0%) and the duration of mechanical ventilation (mean difference -41.14, 95% CI -68.80 to -13.48; p=0.004; I2=74%) between patients receiving restrictive fluid resuscitation and patients receiving liberal fluid resuscitation. TSA showed that the cumulative amount of participants met the required information size, the positive conclusion had been confirmed. The GRADE assessment results demonstrated moderate confidence in the incidence of severe AKI, as well as the results of all second outcomes except the Intensive Care Unit length of stay (ICU LOS), which received limited confidence. The result of incidence of worse AKI was rated as of high certainty.

It is conclusive that fluid restriction strategy is superior to usual care when it comes to reducing the incidence of severe AKI in sepsis-associated hypotension and shock. Shorter duration of ventilation is concerned with fluid restriction as well, but the heterogeneity is substantial. GRADE assessments confirmed moderate and above certainty. Traditional fluid resuscitation therapy has the potential to be further explored for improvements to be more precise and appropriate for a better prognosis.

CRD42023449239.

Sepsis remains the leading cause of death in intensive care units. Despite newer antimicrobial and supportive therapies, specific treatments are still lacking. Neutrophils are pivotal components of the effector phase of the host immune defense against pathogens and play a crucial role in the control of infections under normal circumstances. In addition to its anti-infective effects, the dysregulation and overactivation of neutrophils may lead to severe inflammation or tissue damage and are potential mechanisms for poor prognosis in sepsis. This review focuses on recent advancements in the understanding of the functional status of neutrophils across various pathological stages of sepsis to explore the mechanisms by which neutrophils participate in sepsis progression and provide insights for the treatment of sepsis by targeting neutrophils.

According to the 2018 bundle guidelines of the Surviving Sepsis Campaign, many emergency departments and intensive care units currently adopt the hour-1 bundle as a standard practice for sepsis management. However, recent studies on the hour-1 bundle for sepsis treatment have yielded inconsistent results, raising questions and challenges about its clinical efficacy.

This study will conduct a systematic review and meta-analysis to compare the impact of the hour-1 bundle and non-hour-1 bundle on the clinical outcomes in patients with sepsis and septic shock.

The protocol was prepared according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol (PRISMA-P) statement. The systematic review will be carried out in line with the statement of PRISMA. The following electronic databases will be searched: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. All clinical studies comparing the impact of the hour-1 bundle and non-hour-1 bundle on clinical outcomes in patients with sepsis and septic shock will be included. All stages of the literature search, study selection, data extraction, and quality assessment will be conducted independently by two reviewers. Any disagreements between the two reviewers will be resolved by discussion or arbitration by a third reviewer. The primary outcome will be short-term mortality, which involves in-hospital, 28-day, 30-day, and 90-day mortality corresponding to the definition used in each study. For quality assessment, the risk of bias specified by the Cochrane Collaboration and the methodological index for non-randomized studies will be used for randomized control trials (RCTs) and non-RCTs, respectively. Data synthesis will be performed via Review Manager 5.1.0.

This systematic review will integrate all relevant studies to quantitatively estimate the effect size and clarify the role of the hour-1 bundle in sepsis management, contributing new evidence-based guidance to the field.

Protocol registration and reporting: PROSPERO CRD42024579314.

Misdiagnosis or delayed diagnosis of paravertebral and/or iliopsoas abscess (PVIPA) has been frequently reported to be associated with unfavorable prognosis. We aimed to develop a scoring algorithm that can easily and accurately identify patients at greater risk for PVIPA among individuals with community-onset bloodstream infections.

In a multicenter, retrospective cohort study, the score was developed with the first four study years and validated with the remaining two years. Applying logistic regression, the score values of prediction determinants were derived from the adjusted odds ratios (AOR). The performance of the scoring algorithm was assessed with the receiver operating characteristic (ROC) curve.

In the derivation (3869 patients) and validation (1608) cohorts, patients with PVIPA accounted for 1.7% and 1.4%, respectively. In the derivation cohort, five independent predictors of PVIPA were recognized using multivariable analyses: time-to-defervescence > 5 days (AOR, 7.00; 2 points), Panton-Valentine Leukocidin (PVL)-producing Staphylococcus aureus (AOR, 5.98; 2 points), intravenous drug users (AOR, 2.60; 1 points), and comorbid hemato-oncology (AOR, 0.41; -1 point) or liver cirrhosis (AOR, 2.56; 1 points). In the derivation and validation cohorts, areas under ROC curves (95% confidence intervals) of the prediction algorithm are 0.83 (0.77-0.88) and 0.85 (0.80-0.90), and a cutoff score of + 2 represents sensitivity of 83.3% and 95.7%, specificity of 68.6% and 67.7%, positive predictive values of 4.4% and 4.1%, and negative predictive values of 99.6% and 99.9%, respectively.

Of a scoring algorithm with substantial sensitivity and specificity in predicting PVIPA, PVL-producing S. aureus and Time-to-defervescence > 5 days were crucial determinants.

Sepsis is a significant health burden on a global scale. Timely identification and treatment of sepsis can greatly improve patient outcomes, including survival rates. However, time-consuming laboratory results are often needed for screening sepsis. We aimed to develop a quick sepsis screening tool (qSepsis) based on patients' non-laboratory clinical data at the emergency department (ED) using machine learning (ML), and compare its performance with established clinical scores.

This retrospective study included patients admitted to the ED of Zhongnan Hospital of Wuhan University (Wuhan, China) from 1/1/2015 to 5/31/2022. Patients who were under 18 years of age, had cardiopulmonary arrest upon arrival at the ED, or had missing and abnormal medical record data were excluded. The qSepsis was derived by three ML algorithms, including logistic regression (LR), random forest (RF), and extreme gradient boosting (XGB). To benchmark the existing clinical tools for assessing the risk of sepsis in the ED, qSepsis was compared with the Systemic Inflammatory Response Syndrome (SIRS), the Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Modified Early Warning Score (MEWS). The external validation was performed with the Medical Information Mart for Intensive Care IV ED database (United States), and adopted the same inclusion and exclusion criteria. The predictive power of qSepsis and other clinical scores was measured using the area under the receiver operating characteristic curve (AUROC). The primary outcome of the study was the diagnosis of sepsis in the ED based on the Sepsis 3.0 criteria, which served as the basis for developing the qSepsis tool.

A total of 414,864 patients were finally included in the cohort (median ([IQR]) patient age, 43 (29, 60) years; 202,730 (48.87%) females, 212,134 (51.13%) males), and 200,089 in the external testing cohort (median (SD) patient age, 57 (39, 71) years; 107,427 (53.69%) females, 92,663 (46.31%) males). For internal testing, LR outperformed RF and XGB with an AUROC of 0.862 (95% CI, 0.855-0.869). In external testing, the AUROC decreased to 0.766 (95% CI, 0.758-0.774) for LR, 0.725 (95% CI, 0.717-0.733) for RF, and 0.735 (95% CI, 0.728-0.742) for XGB. In addition, the AUROC for the qSOFA, MEWS, and SIRS scores in external validation cohort were 0.579 (95% CI, 0.563-0.596), 0.600 (95% CI, 0.578-0.622), and 0.704 (95% CI, 0.683-0.725), respectively. The area under the precision-recall curve (AUPRC) for the qSepsis model was 0.213 (95% CI: 0.204-0.222). The AUPRC values for the other scores were as follows: SIRS, 0.071 (95% CI: 0.013-0.099); qSOFA, 0.096 (95% CI: 0.003-0.186); and MEWS, 0.083 (95% CI: 0.063-0.111).

This retrospective study demonstrated that qSepsis had better predictive performance in terms of AUROC and area under the precision-recall curve (AUPRC) compared to existing assessment scores. It has the potential to be used in pre-hospital settings with limited access to laboratory tests and in the ED for quick screening of patients with sepsis. However, due to its low positive predictive value (PPV), the false alarms may increase in actual clinical practice.

Transformation of Scientific and Technological Achievements Fund Project of Zhongnan Hospital of Wuhan University.

To systematically evaluate the efficacy and safety of norepinephrine in the treatment of septic shock.

Literature retrieval of eligible randomized controlled trials (RCTs) on norepinephrine in the treatment of septic shock was performed in three English databases including PubMed, Web of Science, and Medline from database establishment to October 1, 2023. The Cochrane risk bias tool was used to evaluate the quality of the included literature. RevMan 5.3 software was used for meta-analysis.

A total of 14 RCTs were included in this study, and the risk of bias was low. Our meta-analysis showed that the norepinephrine group had significantly better outcomes in reducing the 28-day mortality rate (RR = 0.92; 95% CI, 0.86 ~ 0.99; P = 0.03), the incidence of arrhythmia (RR = 0.54; 95% CI, 0.45 ~ 0.64; P < 0.0001), and the length of stay in intensive care unit (ICU) (MD =  - 1.03; 95% CI, - 1.85 to approximately - 0.21; P = 0.01) than those of the control group. However, there were no statistically significant differences in in-hospital mortality rate (RR = 0.97; 95% CI, 0.90 ~ 1.04; P = 0.4), the 90-day mortality rate (RR = 1.07; 95% CI, 0.97 ~ 1.18; P = 0.15), length of hospital stay (MD = 0.03; 95% CI, - 1.13 ~ 1.18; P = 0.96), and the rate of achieving target MAP (RR = 1.27; 95% CI, 0.72 ~ 2.26; P = 0.41) between the norepinephrine group and the control group.

Norepinephrine has the advantages of improving 28-day mortality, shortening ICU hospitalization time, and reducing the incidence of arrhythmia. It is a more effective choice for the treatment of septic shock than other vasopressors, and the incidence of arrhythmia is low.

Background and objective Sepsis is a life-threatening condition associated with high morbidity and mortality, and hence early recognition and treatment are crucial. The 2016 Sepsis-3 guidelines introduced the quick Sequential Organ Failure Assessment (qSOFA), but its low sensitivity limits early detection. The 2021 Surviving Sepsis Campaign Guidelines (SSCG) discourage relying solely on qSOFA and recommend additional tools such as the systemic inflammatory response syndrome (SIRS) score, the National Early Warning Score (NEWS), and the Modified Early Warning Score (MEWS) along with lactate measurement. This study assessed whether combining qSOFA with quantitative capillary refill time (Q-CRT) or lactate levels enhances early sepsis diagnosis in emergency departments. Methods This retrospective, multi-facility observational study was conducted at two hospitals in Yokohama, Japan. Patients with suspected infections who underwent Q-CRT measurement were included. Q-CRT was measured using a pulse oximeter-based device that records the time taken for blood flow to return to 90% after compression. Receiver operating characteristic (ROC) curves determined the area under the curve (AUC), sensitivity, and specificity. Statistical significance was set at p<0.05. Results Of the 357 patients who underwent Q-CRT measurement, 75 (21%) were suspected of having an infection, with 48 (64%) classified as having sepsis with organ dysfunction. Patients in the sepsis group had higher age, heart rate, lactate level, creatinine level, NEWS, MEWS, and Sequential Organ Failure Assessment (SOFA) scores compared to those without organ dysfunction. Among individual tools, the qSOFA, NEWS, and MEWS scores showed high AUCs (>0.8), while Q-CRT and lactate levels demonstrated moderate predictive accuracy with AUCs exceeding 0.7. The SIRS score had the lowest predictive ability, with an AUC of approximately 0.6. Combining qSOFA with Q-CRT or lactate levels significantly improved sensitivity and specificity. The qSOFA+Q-CRT combination resulted in an AUC of 0.821, sensitivity of 83.3%, and specificity of 81.4%, while the qSOFA+lactate combination yielded an AUC of 0.844, sensitivity of 87.5%, and specificity of 81.4%. These combinations exceeded 80% in both sensitivity and specificity, unlike the SIRS-based combinations, which showed limited improvement and specificity below 40%. While the qSOFA score alone demonstrated limited sensitivity, combining it with Q-CRT or lactate levels enhanced its predictive performance for early sepsis detection. This approach improved sensitivity without compromising specificity. The increase in sensitivity and specificity is likely due to Q-CRT and lactate identifying sepsis cases not detected by qSOFA, thereby making the combined approach more reliable for clinical use. Lactate levels are well-established markers associated with sepsis severity, and Q-CRT offers a non-invasive means of assessing peripheral perfusion. Conclusions Combining qSOFA with Q-CRT or lactate levels significantly improves early sepsis detection by enhancing both sensitivity and specificity. These combinations offer superior diagnostic accuracy compared to standalone tools, supporting their potential integration into clinical protocols for better patient outcomes. Further prospective studies are needed to validate these findings across diverse clinical settings.

Acute kidney injury (AKI) is common in sepsis and a urine output <0.5 mL/kg/h associated with increased mortality is incorporated into AKI diagnosis. We aimed to identify the urine-output threshold associated with increased AKI incidence and hypothesized that a higher urine output than a specified threshold, which differs from the predominantly used 0.5 mL/kg/h threshold, would be associated with an increased AKI incidence.

This was a post-hoc analysis of a nationwide prospective observational study. This study included adult patients newly diagnosed with sepsis and requiring intensive care. Urine output on the day of sepsis diagnosis was categorized as low, moderate, or high (<0.5, 0.5-1.0, and >1.0 mL/kg/h, respectively), and we compared AKI incidence, renal replacement therapy (RRT) requirement, and 28-day survival by category. Estimated probabilities for these outcomes were also compared after adjusting for patient background and hourly fluid administration.

Among 172 eligible patients, AKI occurred in 46.3%, 48.3%, and 53.1% of those with high, moderate, and low urine output, respectively. The probability of AKI was lower in patients with high urine output than in those with low output (43.6% vs 56.5%; P = .028), whereas RRT requirement was lower in patients with high and moderate urine output (11.7% and 12.8% vs 49.1%; P < .001). Patients with low urine output demonstrated significantly lower survival (87.7% vs 82.8% and 67.8%; P = .018). Cubic spline curves for AKI, RRT, and survival prediction indicated different urine-output thresholds, including <1.2 to 1.3 mL/kg/h for AKI and <0.6 to 0.8 mL/kg/h for RRT and mortality risk.

Urine output >1.0 mL/kg/h on the day of sepsis diagnosis was associated with lower AKI incidence. The urine-output threshold was higher for developing AKI than for RRT requirement or mortality.

To summarize the efficacy of midodrine as an adjunctive therapy in critically ill patients. Safety of midodrine was assessed as a secondary outcome.

We performed a systematic review and meta-analysis using a peer-reviewed search strategy combining the themes of vasopressor-dependent shock, critical care, and midodrine and including MEDLINE, Ovid Embase, CINAHL, and Cochrane library databases until September 14, 2023.

We included studies if they: 1) included patients with vasopressor-dependent shock, 2) were performed in the ICU, 3) evaluated oral midodrine therapy compared with placebo or usual care, and 4) evaluated one of the outcomes of interest.

We extracted data independently in duplicate using standardized data abstraction forms, which included the following specific variables: patient characteristics, age, sex, type of ICU, etiology of shock, number of patients, study inclusion and exclusion criteria, and geographical location. We also captured the type, dose, and duration of IV vasopressors, any cointervention used, and outcome data.

We identified seven randomized controlled trials (six included in the pooled analysis) and ten observational studies (four included in the pooled analysis) that met eligibility criteria. Adjunctive midodrine may decrease ICU length of stay (LOS) and there is low certainty of effect on hospital LOS. Midodrine may decrease IV vasopressor support duration, ICU mortality, and hospital mortality. Pooled observational data was based on very low certainty data for all outcomes of interest. The trial sequential analysis-informed required sample size was not met for ICU LOS or IV vasopressor duration and this contributed to Grading of Recommendations, Assessment, Development, and Evaluations assessments of imprecision for both outcomes.

Adjunctive midodrine may decrease ICU LOS, duration of IV vasopressor therapy, and mortality in critically ill patients. However, required sample sizes was not met to determine our outcomes of interest. Midodrine may increase risk of bradycardia. While midodrine may provide benefit for patient-centered outcomes, due to increased risk of adverse events, further large-scale studies are needed to inform and guide its routine use in the ICU.

The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases. Studies comparing early and late vasopressor administration in septic shock patients were included. The primary outcome was short-term mortality, and subgroup analyses were performed based on different initiation timings.

Eleven studies with 6,661 patients were included. Different studies define the 'early administration' timeframe variously, ranging from one to seven hours. No significant difference in short-term mortality was observed between early and late administration in the combined analysis of 3,757 patients from two RCTs and three quasi-experimental studies (OR: 0.66, 95% CI: [0.36, 1.19], I²: 82%). However, lower mortality was found in subgroups with early but not extremely early initiation (one to three hours, OR: 0.70, 95% CI: [0.60, 0.82], I²: 0%), and those using septic shock diagnosis as time zero (OR: 0.64, 95% CI: [0.48, 0.85], I²: 39%).

Our findings found that earlier initiation of vasopressor therapy, particularly within one to three hours after the diagnosis of septic shock, may be associated with reduced short-term mortality in certain subgroups. However, due to the heterogeneity in study definitions and potential confounding factors, these results should be interpreted cautiously. Further standardized investigations are warranted to precisely determine the optimal timing for vasopressor initiation to maximize survival outcomes in patients with septic shock.

To investigate the potential and evolving trends in fluid management for patients with sepsis, utilizing a bibliometric approach.

Scholarly articles pertaining to fluid therapy for sepsis patients were extracted from the Web of Science (WoS) database as of June 1, 2024. The R software package, "Bibliometrix," was utilized to scrutinize the primary bibliometric attributes and to construct a three-field plot to illustrate the relationships among institutions, nations, and keywords. The VOSviewer tool was employed for author analysis, keyword co-occurrence analysis, and data visualization. Additionally, CiteSpace was used to calculate citation bursts and keywords.

A comprehensive retrieval from the Web of Science (WoS) database yielded a total of 2,569 publications. The majority of these articles were predominantly published by two countries, namely the United States (US) and China. Among the myriad of journals, Critical Care and Journal for Intensive Care Medicine emerged as the most prolific. In terms of institutional contribution, the University of California System stood out as the most productive. Recent analysis of keywords revealed a significant citation burst for terms such as "balanced crystalloids" and "critically ill children".

There is a growing focus on the connection between fluid management and the treatment of sepsis, with research in this area being at an advanced stage.

Sepsis is a severe and life-threatening medical syndrome that can lead to organ failure and death. Despite advances in medical treatment, current therapies are often inadequate, with high septic mortality rates. Therefore, there is a critical need for reliable prognostic markers to be used in clinical settings to improve the management and outcomes of patients with sepsis. Recent studies have suggested that mitochondrial dynamics, including the processes of mitochondrial fission and fusion, are closely related to the severity of sepsis and the status of inflammation. By monitoring transcriptomic signals related to mitochondrial dynamics, new and reliable biomarkers can be engineered to more accurately predict sepsis survival risk. Such biomarkers would be invaluable in clinical settings, aiding healthcare providers in the early identification of high-risk patients and improving treatment strategies. To achieve this goal, we utilized the major mitochondrial fission regulatory protein dynamin-related protein 1 (Drp1, gene code DNM1L) and identified Drp1-associated genes that are enriched with sepsis survival genes. A 12-gene signature (GS) was established as a differentially expressed gene (DEG)-based GS. Next, we compared genes of proteins that interact with Drp1 to sepsis survival genes and identified 7 common genes, establishing a GS we term as protein-protein interaction (PPI)-based GS. To evaluate if these GSs can predict sepsis survival, we used publicly available human blood transcriptomic datasets from sepsis patients. We confirmed that both GSs can successfully predict sepsis survival in both discovery and validation cohorts with high sensitivity and specificity, with the PPI-based GS showing enhanced prognostic performance. Together, this study successfully engineers a new and validated blood-borne biomarker (PPI-based 7-gene GS) for sepsis survival risk prediction. This biomarker holds the potential for improving the early identification of high-risk sepsis patients and optimizing personalized treatment strategies to reduce sepsis mortality.

The study aimed to develop and validate a sepsis prediction model using structured electronic medical records (sEMR) and machine learning (ML) methods in emergency triage. The goal was to enhance early sepsis screening by integrating comprehensive triage information beyond vital signs. This retrospective cohort study utilized data from the MIMIC-IV database. Two models were developed: Model 1 based on vital signs alone, and Model 2 incorporating vital signs, demographic characteristics, medical history, and chief complaints. Eight ML algorithms were employed, and model performance was evaluated using metrics such as AUC, F1 Score, and calibration curves. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) methods were used to enhance model interpretability. The study included 189,617 patients, with 5.95% diagnosed with sepsis. Model 2 consistently outperformed Model 1 across most algorithms. In Model 2, Gradient Boosting achieved the highest AUC of 0.83, followed by Extra Tree, Random Forest, and Support Vector Machine (all 0.82). The SHAP method provided more comprehensible explanations for the Gradient Boosting algorithm. Modeling with comprehensive triage information using sEMR and ML methods was more effective in predicting sepsis at triage compared to using vital signs alone. Interpretable ML enhanced model transparency and provided sepsis prediction probabilities, offering a feasible approach for early sepsis screening and aiding healthcare professionals in making informed decisions during the triage process.

Delays in sepsis recognition contribute to delays in antibiotic administration, which lead to increased morbidity and mortality in patients with sepsis. Our objective was to create an Emergency Department (ED) Code Sepsis Nurse-led team to reduce the time to antibiotics and mortality in patients with sepsis.

This initiative was implemented at a community hospital in Southern California in response to previous undesirable sepsis outcomes. In fiscal year 2021, the ED Sepsis Nursing Team was launched with the goal of improving sepsis-related outcomes. The following interventions were implemented: First, a group of dedicated Sepsis Nurses with training specific to sepsis recognition was created, and an electronic ED-sepsis screening tool was developed and implemented. Next, the dedicated sepsis nurses designed and educated to a "Code Sepsis" activation process. The code triggered a multidisciplinary response and implementation of standing orders for blood cultures, lactate, complete blood count, complete metabolic panel, and chest x-ray or urinalysis if indicated. Finally, the Sepsis Team Registered Nurse (RN) Captain led house-wide monthly Sepsis Task Force meetings to improve unit-level engagement and to allow the team to have ownership over sharing wins and losses.

By Quarter 4 (Q4) of Fiscal Year 2021, door-to-antibiotic time for sepsis patients dropped from 196.7 min (Q1) to 144.7 (Q4). Additionally, mortality dropped below the health system average (10.4% vs. 13.5%), and Fiscal Year 2021 surpassed the readmissions benchmark of <1.0 at a rate of 0.5.

An RN-led, interprofessional response to accepted sepsis identification criteria enhanced staff and physician engagement and improved sepsis outcomes for patient mortality and hospital reporting outcomes. The process was adopted with very few obstacles that were easily overcome as the understanding of the role and its significance was realized.

Emergency laparotomy (EL) is associated with high morbidity and mortality, often exceeding 10%. This study evaluated the impact of the EMergency Laparotomy Audit (EMLA) interdisciplinary perioperative pathway on patient outcomes, hospital costs and length of stay (LOS) within a single centre.

A prospective cohort study was conducted from August 2020 to July 2023. The intervention team included specialist clinicians, hospital administrators and an in-hospital quality improvement team. Patients who underwent EL were divided into a pre-intervention control group (n=136) and a post-intervention group (n=293), and an 8-item bundle was implemented. Propensity scoring with a 1:1 matching method was utilised to reduce confounding and selection bias. The primary outcomes examined were LOS, hospitalis-ation costs and surgical morbidity, while secondary outcomes included 30-day mortality and adherence to the intervention protocol.

The utilisation of the EMLA perioperative care bundle led to a significant reduction in surgical complications (34.8% to 20.6%, P<0.01), a decrease in LOS by 3.3 days (15.4 to 12.1 days, P=0.03) and lower hospitalisation costs (SGD 40,160 to 30,948, P=0.04). Compliance with key interventions also showed improvement. However, there was no difference in 30-day mortality.

This study offers insights on how surgical units can implement systemic perioperative changes to improve outcomes for patients undergoing emergency laparotomy.

Cardiogenic shock is a life-threatening condition characterized by inadequate cardiac output, leading to end-organ hypoperfusion and associated mortality rates ranging between 40 and 50%. The critical role of microcirculatory impairments in the progression of organ failure during shock has been highlighted in several studies. Traditional therapies have often focused on stabilizing macrocirculation, neglecting microcirculatory dysfunction, which can result in persistent tissue hypoxia and poor outcomes. This review highlights the importance of assessing microcirculation in cardiogenic shock, including parameters such as skin perfusion, sublingual microcirculation, and lactate dynamics. Integrating microcirculatory assessments into clinical practice remains challenging due to the complexity of the methods and limited therapeutic options targeting microvascular perfusion. While advances in microcirculation-guided therapies hold promise for improving outcomes in cardiogenic shock, further research is needed to establish effective protocols.

Commercial off-the-shelf (COTS) intravenous fluid (IVF) containers contain residual air, introducing the risk of venous air embolism (VAE). Venous air embolism occurs when air displaces blood flow in vasculature. The danger from residual air is often negligible in terrestrial settings, where gravitational forces generate buoyancy, pushing residual air to the top of the IVF container. However, in microgravity there is no buoyancy to separate liquid and gas layers. We performed experiments to quantify the amount of air in COTS IVF containers (Experiment 1) and identify the variables that affect the stability of sterilely produced airless containers (Experiment 2).

Experiment 1: Residual air was quantified across varying volumes (100, 250, 500, and 1,000 mL), container design, and manufacturer (B. Braun, Baxter, ICU Medical, and Grifols) of 0.9% NaCl COTS IVFs. Each container was assessed for absolute volumes of air, as well as air:fluid ratios normalized to 1,000 mL. Experiment 2: 1,000 mL IVF containers from 3 manufacturers were filled with either (1) 100% saline or (2) 95% saline and 5% air by volume. Containers were stored for 168 days at 25°C or 40 °C. The containers were optically imaged to quantify the accumulation of air within each IVF container.

Experiment 1: There was a trend toward larger container sizes and greater absolute volumes of residual air (R2 = 0.964). However, the smallest air:volume ratio occurred in the Baxter 500 mL VIAFLO Container (18.9 ± 3.8 mL air; 2.3% air by volume), whereas the largest ratio occurred in the B. Braun 250 mL EXCEL Container (55.0 ± 9.3 mL; 22.0% air by volume). Experiment 2: By day 168, 6 experimental containers had ruptured and 100% of the surviving containers (30/36) had an increase in air as compared to baseline. Containers placed at 40 °C had a larger increase in air (27.7 ± 6.6 mL) compared to containers stored at 25 °C (7.5 ± 4.1 mL; P < .0001).

Residual air has a wide variety of volumes in COTS IVFs. The average amount of residual air is high enough to contribute to clinically significant VAEs, although unlikely to be fatal. If airless IVF containers are produced for exploration missions, a progressive increase in the amount of residual air should be expected. Extremes of temperatures and humidity will increase the reaccumulation of residual air and decrease the shelf-life of airless IVFs.

The molecular mechanism underlying the protective effects of DEX against sepsis-induced acute kidney injury (SAKI) remains to be elucidated.

We established S-AKI models in vivo via CLP and in vitro with LPS-induced HK-2 cells.

The Nrf2/SLC7A11/FSP1/CoQ10 pathway was inhibited in S-AKI both in vitro and in vivo. The overexpression of Nrf2 inhibited LPS-induced ferroptosis by activating the SLC7A11/FSP1/CoQ10 pathway. DEX ameliorated kidney tissue damage, as determined by a decrease in BUN, Cr, and inflammatory factor levels, along with renal tubule vacuolation and inflammatory cell infiltration in S-AKI mice. Additionally, DEX treatment significantly ameliorated ferroptosis in S-AKI in vitro and in vivo, as indicated by an improvement in mitochondrial shrinkage and disruption of cristae, a decrease in iron, ROS, MDA, and 4-HNE levels, and an increase in GSH and GPX4 levels. Mechanistically, DEX treatment restored the reduction of Nrf2 expression and nuclear translocation in S-AKI, as well as, the levels of downstream SLC7A11, FSP1, and CoQ10. Knocking down Nrf2 in vitro and administering brusatol in vivo eliminated the protective effect of DEX against S-AKI.

DEX mitigated ferroptosis and attenuated S-AKI by activating the Nrf2/SLC7A11/FSP1/CoQ10 pathway. Abbreviation: CLP: Cecal ligation puncture; LPS: Lipopolysaccharide; Nrf2: Nuclear factor-erythroid- 2-related factor 2; SLC7A11: Solute carrier family 7 member 11; FSP1: Ferroptosis suppressor protein 1; CoQ10: Coenzyme Q10; BUN: Blood urea nitrogen; Cr: Serum creatinine; ROS: Reactive oxygen species; MDA: Malondialdehyde; 4-HNE: 4-hydroxynonenal; GSH: Hlutathione; GPX4: Glutathione peroxidase 4.

Intravenous fluid (IVF) administration is a ubiquitous medical intervention. Although there are clear benefits to IVF in certain obstetric scenarios, IVF is often given in unindicated circumstances; the ongoing IVF shortage highlights an opportunity to reduce unindicated IVF in obstetrics. This document provides evidence-based recommendations to reduce IVF use within general obstetric practice. The three sections address IVF use within (1) antepartum care, (2) intrapartum care, and (3) postpartum care, including postpartum hemorrhage (PPH) risk reduction. Using the GRADE framework, we provide a summary of the available evidence surrounding use of IVF in obstetrics and recommend strategies to reduce IVF. We recommend transitioning intravenous (IV) antibiotics to IV push or oral when possible, discontinuing IVF bolus prior to neuraxial anesthesia or for the treatment of preterm labor, and avoiding unnecessary continuous IVF infusions. There may be further opportunities for fluid conservation with IV medications that could be given intramuscularly. These suggestions for IVF use reduction should be evaluated based on local need and capabilities as well as the characteristics and risk factors of the population. Patients with sepsis, PPH, burns, diabetic ketoacidosis, and hemodynamic instability should not have a reduction in IVF administration as these diagnoses have evidence-based resuscitation guidelines that include IVF. The recommendations presented may be applicable beyond the immediate IVF shortage and should be considered as an area for future research.

The use of albumin resuscitation in septic shock is only recommended in patients who have received large volumes of crystalloid resuscitation regardless of serum albumin concentration. The role of albumin is still largely debated and evidence to support its use still lacking.

The objective of this study was to evaluate whether albumin replacement increases the number of vasopressor-free days in patients with septic shock and hypoalbuminemia.

A retrospective analysis was conducted to assess the effect of albumin replacement in septic shock. Hypoalbuminemic patients with septic shock who received albumin were retrospectively compared with a cohort who did not. The primary outcome was number of vasopressor-free days at day 14 from shock presentation, which was analyzed using an adjusted linear regression model to adjust for confounders.

There was no difference in vasopressor-free days at day 14 in patients who received albumin versus those who did not, after adjusting for confounders of exposure (0.50, 95% CI = -0.97 to 1.97; P = 0.502). There also was no difference in secondary outcomes except for need for invasive mechanical ventilation (MV), which was significantly lower in patients who received albumin (61 [54.4%] vs 88 [67.7%]; P = 0.035).

We observed no difference in vasopressor-free days at day 14 in patients with hypoalbuminemia who received albumin compared with those who did not. However, patients who received albumin required significantly less MV although further studies are warranted to assess this effect.

Background/Objectives: Endotoxin, a component of lipopolysaccharide (LPS) from bacteria, disrupts the immune system, potentially leading to multiorgan failure. Unlike previous studies, we enrolled patients with mild clinical conditions after major abdominal surgery and assessed the predictive value of endotoxin activity (EA) levels for acute complications which occur within 7 days postoperatively. Also, the differential diagnostic value of EA was assessed in a subgroup of patients with abnormal liver function during the immediate postoperative period. Methods: Patients admitted to the surgical ICU of our institution following elective abdominal surgery were enrolled. Participants were classified into low/high postoperative EA groups based on EA cutoff values for predicting complications. Additionally, participants were categorized based on liver function assessed at ICU admission using total bilirubin (TB) levels. Abnormal liver function was defined as a TB level > 1.2 mg/dL. Results: 86 patients were analyzed. The EA cutoff for postoperative complications was 0.485, with 49 patients (57%) categorized in the low EA group (EA levels < 0.485) and 37 patients (43%) in the high EA group (EA levels ≥ 0.485). The high EA group experienced statistically worse outcomes, including longer ICU stays and higher mortality rates. Logistic regression analysis confirmed that EA levels and SOFA scores were significant predictors of postoperative complications. For patients with elevated TB, the EA cutoff value for postoperative complications was 0.515, which is higher than those obtained for the total patient cohort. Conclusions: EA level is a viable surveillance tool for detecting postoperative complications in the acute period among ICU patients undergoing major abdominal surgery, and must be interpreted carefully considering the patient's liver function.

The relationship between dysmagnesemia and all-cause mortality probability in individuals with acute kidney injury (AKI) have not been investigated. In this study, we evaluated the correlation of varying magnesium levels with mortality in older adults undergoing AKI.

Older adults receiving treatment at the Chinese PLA General Hospital between 2007 and 2018 were retrospectively recruited. All-cause mortality was evaluated at four preset magnesium concentrations: <0.8, 0.8-0.9, 0.9-1.0, and ≥ 1.0 mmol/L. Using multivariable-adjusted Cox assessment, the all-cause mortality risk was approximated by setting the reference magnesium concentration at 0.8-0.9 mmol/L.

Totally 744 participants were enrolled, whose median age was 88 years, with most of them being male (94.2%). Among them, 184 patients were assigned into the < 0.8 mmol/L group, 156 into the 0.8-0.9 mmol/L group, 206 into the 0.9-1.0 mmol/L group, and 198 into the ≥ 1.0 mmol/L group. After 28 days, the mortality rates in the four strata were 26.6, 17.9, 17.5, and 37.4%, respectively. The corresponding mortalities after 90 days were 42.4, 23.7, 26.7, and 45.5%, respectively. Compared with patients who had magnesium levels of 0.8-0.9 mmol/L, those with magnesium levels < 0.8 mmol/L (P = 0.048), and ≥ 1.0 mmol/L (P < 0.001) exhibited higher 28-day mortalities. Significant correlations also showed that patients with magnesium levels < 0.8 mmol/L (P = 0.017) and ≥ 1.0 mmol/L (P < 0.001) were significantly related to the increased 90-day mortality.

Magnesium levels outside the interval of 0.8-1.0 mmol/L were related to the higher risks of 28- and 90-day mortalities among older adults with AKI.

This review discusses the pivotal role of microcirculation in maintaining tissue oxygenation and waste removal and highlights its significance in various pathological conditions. It delves into the cellular mechanisms underlying hemodynamic coherence, elucidating the roles of the endothelium, glycocalyx, and erythrocytes in sustaining microcirculatory integrity. Furthermore, the review gives comprehensive information about microcirculatory changes observed in cardiac surgery, sepsis, shock, and COVID-19 disease. Through comprehensive exploration, the review underscores the intricate relationship between microcirculation, disease states, and clinical outcomes, emphasizing the importance of understanding and monitoring microvascular dynamics in critical care settings.

A dysregulated host response to infection resulting in life-threatening organ dysfunction defines the onset of sepsis. Unfortunately, sepsis is common, costly, and deadly. The Surviving Sepsis Campaign publishes regularly updated, evidence-informed, detection, and treatment guidelines culminating in time-sensitive care "bundles." The goal of these bundles is to expedite sepsis recognition because it is widely held that early treatment is life-saving. Hospitals are mandated to publicly report their bundle compliance, and this will soon be tied to hospital reimbursement. For these reasons, hospitals are creating sepsis emergency response teams which are a form of a rapid response team consisting of dedicated medical professionals who evaluate patients with suspected sepsis and initiate therapy when appropriate. Evidence to date support sepsis emergency response teams as a mechanism to improve bundle compliance, and potentially, patient outcome. Nevertheless, some elements of bundled sepsis care are controversial (e.g., intravenous fluid administration) as some argue that mandated treatment precludes personalized care. Herein, we briefly describe general sepsis emergency response team structure, review evidence supporting sepsis emergency response teams to improve bundle compliance and patient outcome and report our unique experience incorporating point of care ultrasound-to guide intravenous fluid-into a nursing-led sepsis team. We propose that our sepsis emergency response team approach allays concern that sepsis care is either bundled or personalized. Instead, incorporating point of care ultrasound into a nursing-led sepsis emergency response team increases bundle compliance and individualizes care.

Septic cardiomyopathy (SCM) arises as a consequence of sepsis-associated cardiovascular dysfunction, for which there is currently no specific targeted therapy available. Previous studies have demonstrated the beneficial therapeutic effect of berberine (BBR) on SCM; however, the underlying mechanisms of action remain unclear. The objective of this is to elucidate how BBR alleviates SCM.

Septic cardiomyopathy rat model was established by performing cecal ligation and puncture (CLP), while a cardiomyocyte injury model was provoked in H9C2 cells using lipopolysaccharide (LPS). Cardiac function was assessed through echocardiography, and myocardial histopathology was examined with hematoxylin-eosin (HE) staining. Cardiomyocyte viability was determined through Cell Counting Kit-8 (CCK8) assay, and measurement of ATP levels was done with an ATP assay kit. Mitochondrial ultrastructure was observed using transmission electron microscopy. Real-time polymerase chain reaction (RT-PCR) and Western blotting were employed to analyze the expression of Notch1 signaling pathway components and downstream molecules in myocardial tissues and cells.

In vivo, BBR markedly improved symptoms and cardiac function in SCM rats, leading to enhanced ATP content, and ameliorated mitochondrial structure. Additionally, BBR increased Notch1 protein expression in myocardial tissue of the rats. In vitro, BBR elevated the survival rates of H9C2 cell, improved mitochondrial morphology, and raised ATP levels. The mRNA expression of Notch1, Hes1, and Hes2, and Notch1 protein expression was upregulated by BBR. While these effects were reversed upon inhibiting the Notch1 signaling pathway.

BBR improves septic cardiomyopathy by modulating Notch1 signaling to protect myocardial mitochondria.

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. In this study, we investigate whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy or not. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted to the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant groups based on the bacteria's susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from the peak to the end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: the time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 h (p = 0.0057), and to 0%, it was 29 vs. 54 h (p = 0.0475). The time to reduce the dose from the maximum NEE to 75% was 8 vs. 12.5 h (p = 0.0733), and to 50% it was 13 vs. 21.5 h (p = 0.1081). Conclusions: In septic shock with bacteraemia, a faster catecholamine dose reduction indicates bacterial susceptibility to the initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of the appropriate initial empiric therapy.

Sepsis is a systemic condition caused by a dysregulated host response to infection and often associated with excessive release of proinflammatory cytokines resulting in multi-organ failure (MOF), including cardiac dysfunction. Despite a number of effective supportive treatments (e.g. ventilation, dialysis), there are no specific interventions that prevent or reduce MOF in patients with sepsis. To identify possible intervention targets, we re-analyzed the publicly accessible Gene Expression Omnibus accession GSE131761 dataset, which revealed an increased expression of spleen tyrosine kinase (SYK) in the whole blood of septic patients compared to healthy volunteers. This result suggests a potential involvement of SYK in the pathophysiology of sepsis. Thus, we investigated the effects of the highly selective SYK inhibitor PRT062607 (15mg/kg; i.p.) on sepsis-induced cardiac dysfunction and MOF in a clinically-relevant, murine model of sepsis. PRT062607 or vehicle (saline) was administered to 10-weeks-old C57BL/6 mice at 1h after the onset of sepsis induced by cecal ligation and puncture (CLP). Antibiotics (imipenem/cilastatin; 2mg/kg; s.c.) and analgesic (buprenorphine; 0.05mg/kg; i.p.) were administered at 6h and 18h post-CLP. After 24h, cardiac function was assessed in vivo by echocardiography and, after termination of the experiments, serum and cardiac samples were collected to evaluate the effects of SYK inhibition on the systemic release of inflammatory mediators and the degree of organ injury and dysfunction. Our results show that treatment of CLP-mice with PRT062607 significantly reduces systolic and diastolic cardiac dysfunction, renal dysfunction and liver injury compared to CLP-mice treated with vehicle. In addition, the sepsis-induced systemic inflammation (measured as an increase in inflammatory cytokines and chemokines in the serum) and the cardiac activation of NF-kB (IKK) and the NLRP3 inflammasome were significantly reduced in CLP-mice treated with PRT062607. These results demonstrate, for the first time, that SYK inhibition 1h after the onset of sepsis reduces the systemic inflammation, cardiac dysfunction and MOF, suggesting a potential role of the activation of SYK in the pathophysiology of sepsis. Novel therapeutic strategies that inhibit SYK activity may be of benefit in patients with diseases associated with local or systemic inflammation including sepsis.

Despite recent advances and global improvements in sepsis recognition and supportive care, mortality rates remain high, and adherence to sepsis bundle components in Korea is low. To address this, the Korean Sepsis Alliance, affiliated with the Korean Society of Critical Care Medicine, developed the first sepsis treatment guidelines for Korea based on a comprehensive systematic review and meta-analysis.

A de novo method was used to develop the guidelines. Methodologies included determining key questions, conducting a literature search and selection, assessing the risk of bias, synthesizing evidence, and developing recommendations. The certainty of evidence and the strength of recommendations were determined using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Draft recommendations underwent internal and external review processes and public hearings. The development of these guidelines was supported by a research grant from the Korean Disease Control and Prevention Agency.

In these guidelines, we focused on early treatments for adult patients with sepsis and septic shock. Through the guideline development process, 12 key questions and their respective recommendations were formulated. These include lactate measurement, fluid therapies, target blood pressure, antibiotic administration, use of vasopressors and dobutamine, extracorporeal membrane oxygenation, and echocardiography.

These guidelines aim to support medical professionals in making appropriate decisions about treating adult sepsis and septic shock. We hope these guidelines will increase awareness of sepsis and reduce its mortality rate.

Good sepsis management is key to successful sepsis therapy and optimal patient outcomes. Objectives: This study aimed to determine obstacles among nurses and doctors to implementing the hour-1 sepsis bundle in a secondary hospital in Indonesia.

This was a qualitative study with a phenomenological approach. Data were obtained from one-on-one in-depth interviews with 13 doctors and nurses in the intensive care unit and emergency department who were purposively sampled. Data were analyzed using content analysis.

Five main themes were revealed in the analysis: incomplete implementation of the hour-1 sepsis bundle, lack of knowledge about the hour-1 sepsis bundle, cost issues, lack of supporting facilities, and lack of coordination among health workers.

Optimizing regional health laboratories, optimizing the use of quick Sequential Organ Failure Assessment (qSOFA) and SOFA, and creating a series of sepsis protocols within the hospital are some solutions that secondary hospitals can implement to ensure appropriate management of sepsis cases. Involvement of health policyholders and hospital management is needed to address these challenges.

To evaluate whether the timing of initial antibiotic administration in patients with sepsis in hospital affects mortality.

This systematic review and meta-analysis included studies from inception up to 19 May 2022. Interventional and observational studies including adult human patients with suspected or confirmed sepsis and reported time of antibiotic administration with mortality were included. Data were extracted by two independent reviewers. Summary estimates were calculated by using random-effects model. The primary outcome was mortality.

We included 42 studies comprising 190,896 patients with sepsis. Pooled data showed that the OR for patient mortality who received antibiotics ≤1 hr was 0.83 (95 %CI: 0.67 to 1.04) when compared with patients who received antibiotics >1hr. Significant reductions in the risk of death in patients with earlier antibiotic administration were observed in patients ≤3 hrs versus >3 hrs (OR: 0.80, 95 %CI: 0.68 to 0.94) and ≤6 hrs vs 6 hrs (OR: 0.57, 95 %CI: 0.39 to 0.82).

Our findings show an improvement in mortality in sepsis patients with early administration of antibiotics at <3 and <6 hrs. Thus, these results suggest that antibiotics should be administered within 3 hrs of sepsis recognition or ED arrival regardless of the presence or absence of shock.