Numerous studies have shown that patients admitted on weekends or holidays have higher mortality rates and poorer prognoses than those admitted on weekdays. However, the specific impact of the weekend effect on patients with sepsis remains unclear and requires further investigation.

This study included adult patients with sepsis who were first admitted to the ICU and stayed for ≥24 hours, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV (version 2.2),with the data collection period from 2008 to 2019. Data on age, gender, type of ICU admission, vital signs, disease severity scores, and medications were collected, with patients categorized into weekend and weekday admission groups. The primary outcome was 28-day mortality, while secondary outcomes included 90-day mortality, hospital mortality, ICU mortality, and survival days without vasoactive drugs, ventilator, or ICU stay. COX regression analyses with propensity score matching (PSM) were employed to assess the impact of weekend admissions on the survival of septic patients in the ICU.

A total of 20,261 septic patients met the inclusion criteria, with 14,469 in the weekday group and 5,792 in the weekend group. The weekend admission group showed no statistically significant differences in 28-day mortality, hospital mortality, ICU mortality, survival days without vasoactive drugs, survival days without ventilator, survival days without ICU, and length of ICU stay compared to the weekday group. Subgroup analyses for 28-day mortality revealed that key baseline characteristics such as gender, age, BMI, race, ICU type, hypertension, diabetes mellitus, and SOFA score did not independently influence the prognosis of patients with sepsis based on weekend admission.

The study found no significant weekend effect on the prognosis of septic patients admitted to the ICU, based on both univariate and multivariate analyses.

Critically ill patients are at risk of bleeding from stress ulcers. Comprehensive information regarding United Kingdom stress ulcer prophylaxis (SUP) practices are not available and may change over time. We aimed to describe SUP practices in 2020 and reevaluate the position in 2024.

Critical care pharmacists provided observed SUP practice data for UK adult critical care units via an electronic repository in 2020 and 2024. One response was accepted from each critical care unit at each time point. Data collected included trigger criteria for commencing SUP, primary medication class used, primary SUP cessation criteria, and level of nutritional intake (if part of cessation criteria).

There were high response rates of 70.3% (2020) and 66.7% (2024) of registered UK adult critical care units. Few differences in primary SUP trigger criteria between 2020 and 2024 were seen, with small differences in the categories of 'SUP not used' (p = 0.002) and 'Shock' (p = 0.027) driving statistical significance (χ2(7, 454) = 16.76, p = 0.019). There was a significant change in the primary medication class used for SUP (H2 receptor antagonist 49.4% 2020, vs 0.4% 2024, proton pump inhibitor 44.7% 2020 vs 97.8% 2024; χ2(2, 458) = 159.62, p < 0.001). Primary SUP cessation criteria was 'Patient fed' (66.8% 2020, 64.6% 2024), with most describing this threshold as met when the patient receives full enteral feed (72.0% 2020, 78.8% 2024).

The UK has moved towards proton pump inhibitors as the primary SUP medication class. SUP is most frequently discontinued on establishment of enteral nutrition.

Sepsis is a severe and life-threatening condition marked by excessive inflammation, mitochondrial dysfunction, and epithelial barrier disruption, often leading to Acute Lung Injury (ALI). Mitophagy, a cellular mechanism that removes damaged mitochondria, plays a vital role in maintaining mitochondrial health during sepsis. In this study, we investigated the protective effects of Urolithin-A against ALI and sepsis. In LPS-stimulated RAW264.7 macrophages, Urolithin-A significantly reduced mitochondrial dysfunction, Reactive Oxygen Species (ROS), Nitric Oxide (NO) production, and apoptosis. Additionally, it enhanced mitophagy by upregulating PINK1, Parkin, and LC3-II, which helped preserve mitochondrial function. In vivo, Urolithin-A treatment in mouse models of ALI and sepsis reduced lung injury and inflammation, as shown by improved ALI scores, decreased wet/dry lung weight ratios, and lower levels of inflammatory markers such as iNOS, IL-1β, and MPO. Urolithin-A also improved epithelial barrier integrity and upregulated anti-apoptotic markers, demonstrating its ability to alleviate sepsis-induced lung damage. These findings suggest that Urolithin-A holds significant promise as a therapeutic agent for managing inflammatory lung conditions associated with sepsis.

Background: Adjunctive vasopressors are added to norepinephrine in one-third of adults with septic shock in the United States. However, effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. We sought to synthesize the direct evidence for adjunctive vasopressor administration in adults with septic shock. Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to June 7, 2023. We included randomized clinical trials of adults with septic shock comparing adjunctive treatment with a vasopressin analogue, angiotensin II, methylene blue, hydroxocobalamin, or catecholamine analog to standard care vasopressors. The primary outcome was short-term mortality (at or before 28-30 days or intensive care discharge). Secondary outcomes included kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Random-effects meta-analyses were conducted to derive risk ratios (RRs) and 95% CIs. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Results: Of 6,763 records, 17 trials (3,813 participants) were included. Compared with standard care, adjunctive vasopressor administration may reduce short-term mortality risk (RR, 0.92 [95% CI, 0.85-1.00], low certainty, 17 trials [3618 participants]) and likely reduces kidney replacement therapy receipt (RR, 0.92 [95% CI, 0.84-1.01], moderate certainty, eight trials [2,408 participants]). Adjunctive vasopressor treatment may increase risk of digital/peripheral ischemia (RR, 2.44 [95% CI, 1.17-5.10], low certainty, nine trials [2,981 participants]) and venous thromboembolism (RR, 16.48 [95% CI, 0.96-283.17], low certainty, one trial [321 participants]). There was some evidence that the pooled estimate for short-term mortality was different (interaction P = 0.13) for trials adjudicated as low risk of bias (RR, 0.95 [95% CI, 0.87-1.05]) compared with trials adjudicated as some concerns or high risk of bias (RR, 0.82 [95% CI, 0.69-0.97]). The findings were robust to multiple sensitivity and subgroup analyses. Conclusions: In adults with septic shock, adjunctive vasopressors may lower short-term death risk and likely lower kidney replacement therapy risk, but may increase risk of adverse effects. In the United States, adjunctive vasopressor use prevalence in septic shock is disconnected from the low evidence certainty for a favorable mortality-to-risk profile.

Background: Sepsis-associated acute kidney injury (AKI) is linked to increased mortality and prolonged hospital stays. The exact relationship between central venous pressure (CVP) and AKI remains unclear. We explored the correlation between CVP and AKI in septic shock patients. Methods: This retrospective study included adult patients with septic shock admitted to Mayo Clinic Rochester between 2006 and 2018. CVP levels were measured at 6, 12, 24, and 48 h after the diagnosis of sepsis, and patients were stratified into two groups based on CVP levels (CVP < 8 or ≥8 mmHg). Results: Of 5600 patients with septic shock, 3128 patients without AKI on admission are included. One-thousand-and-ninety-eight patients (35.1%) developed AKI within a median of 4.4 days. The median CVP levels and frequency of elevated CVP at 6, 12, 24, and 48 h are significantly higher in the AKI group. Elevated CVP (≥8 mmHg) at 6, 12, 24, and 48 h is associated with AKI incidence, even after adjusting for mean arterial pressure (MAP) levels. This association, after multivariable adjustments, only remains significant at 12 h with an odds ratio (OR) of 1.60 (95% CI, 1.26-2.05), p < 0.001 and 48 h with an OR of 1.60 (95% CI, 1.29-1.99), p < 0.001. Conclusions: Our findings indicate that CVP ≥ 8 mmHg is strongly associated with an increased risk of AKI, even after adjusting for MAP at the 12 and 48 h time points. These findings underscore a critical 12 or 48h window for interventions to lower CVP.

Sepsis is a severe condition associated with high mortality, and hospital performance is variable. The objective of this study was to develop geospatial sepsis clusters, identify sources of variation between clusters, and test the hypothesis that redistributing sepsis patients from low-performing hospitals to higher-performing hospitals within a cluster will improve sepsis outcomes.

We conducted a cohort study of age-qualifying Medicare beneficiaries using administrative claims data from 2013 to 2015. We calculated risk-standardized mortality for hospitals then used a clustering algorithm to define geospatial cluster boundaries based on care-seeking and interhospital transfer patterns. Finally, we used simulation to model the effect of reallocating sepsis patients to higher-performing hospitals within the same cluster.

None.

We included 1,125,308 patients, and they were grouped into 222 regional clusters. High-performing clusters were located largely in the Midwest, and they tended to be in less urban regions with smaller hospitals. In our simulation, the most impactful strategy was reassigning cases from the lowest-performing hospital in a cluster to the highest-performing hospital in the cluster, which was predicted to prevent 1705 deaths per year in the United States. This aggregate benefit was lower than the 5702 deaths predicted from reducing mortality by 1% absolute in hospitals in the lower half of the performance distribution.

Geospatial clusters provide insight into regional approaches to system-based acute care. In a simulation study, targeted sepsis regionalization appears less effective than local performance improvement in reducing preventable sepsis deaths.

The adrenocorticotropic hormone (ACTH) test diagnoses relative adrenal insufficiency (RAI) or critical illness-related corticosteroid insufficiency (CIRCI). Initially, guidelines recommended corticosteroid/glucocorticoid (GC) therapy for septic patients with RAI, but later trials did not show a survival benefit, leading to updated guidelines that abandon targeting RAI or CIRCI. Recent studies with an RAI mouse model showed a clear survival benefit from GC therapy in mice with RAI, suggesting that inconclusive GC clinical trials might be due to issues with the ACTH test rather than targeting RAI. To investigate, we performed the ACTH test in septic mice. Interestingly, the ACTH test identified most mice as having adrenal insufficiency in early and middle stages of sepsis, even those with a normal adrenal stress response. Surprisingly, the ACTH test increased inflammatory cytokines to lethal levels, moderately increasing mortality in septic mice. This study revealed significant flaws in the ACTH test for diagnosing RAI/CIRCI. It not only fails to correctly identify these conditions, leading to misguided use of GCs, but also induces a lethal inflammatory response in sepsis. These findings suggest that inconclusive GC therapy trials may be due to the problematic nature of the ACTH test rather than ineffectiveness of targeting RAI/CIRCI.

Sepsis remains a significant global health threat with a disproportionate burden in low-income countries including those in sub-Saharan Africa where case fatality rates are as high as 30% to 50%. Defined as a severe systemic response to infection, sepsis leads to widespread immune dysregulation and organ dysfunction, including adrenal insufficiency. Critical illness-related corticosteroid insufficiency (CIRCI) arises from dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids, all of which can occur during sepsis. Clinical trials of corticosteroids for the treatment of patients with sepsis and septic shock have shown improvements in shock reversal, and in some studies, patient survival; however, their role in the treatment of sepsis in sub-Saharan Africa is unknown. The incidence of sepsis in sub-Saharan Africa is compounded by high rates of human immunodeficiency virus (HIV) and co-infections, including tuberculosis (TB), which is the leading cause of sepsis. Both HIV and TB can cause immune dysregulation and adrenal insufficiency, which may exacerbate CIRCI and prolong shock. Existing sepsis research has been predominantly conducted in high-income countries and has largely excluded people living with HIV or TB. Therefore, there is a need to better understand sepsis and CIRCI pathophysiology in the context of specific regional host and pathogen characteristics. In this narrative review, we explored the pathophysiology of sepsis in sub-Saharan Africa including the existing literature on the immune response to sepsis and the prevalence of adrenal insufficiency in patients with HIV and TB, with a focus on the implications for corticosteroid management. We found a compelling need to further evaluate corticosteroids for the treatment of sepsis in Africa.

Increasingly, acute care surgeons have taken over the management of general surgery consult patients in the hospital, many of whom present with sepsis and/or in septic shock. In this article, we will discuss the intricacies of sepsis management for acute care surgery. The underlying tenants of sepsis management will be outlined with specific attention to the nuances associated with surgical patients. Ultimately, when a surgical problem is identified, this management will culminate with the need for specific source control - the unique aspect when a surgical as opposed to a medical disease process is the cause of sepsis. However, surgeons must also be competent in the other components of sepsis management including antimicrobial therapy and hemodynamic support. This article is designed for the surgeon or for any provider caring for patients with a potential acute care surgical problem, recognizing that different practice settings will vary with regard to resource availability for laboratory tests, invasive monitoring, diagnostics, and surgeon availability.

Fluid is an essential component of initial resuscitation in sepsis or burns. Meanwhile, the optimal strategy of titrating fluids for both of the two conditions remains uncertain. In this bibliometric analysis, we compared the similarities and differences in fluid resuscitation between sepsis and burns in recent publications.

Literatures related to fluid resuscitation in either sepsis or burns were searched in the Web of Science database Core Collection from January 1, 1992, to December 31, 2022. CiteSpace and VOSviewer was used for bibliometric analysis.

A total of 1,549 and 468 publications on fluid resuscitation in sepsis and burns were retrieved from 1992 to 2022. Based on the occurrences, 341 and 86 high-frequency keywords were screened out from sepsis and burns publications, respectively, which were similarly categorized into 5 clusters [i.e. "mechanisms of hypovolemia" (cluster 1), "titration of fluid" (cluster 2), "outcomes or complications" (cluster 3), "pathophysiological alternations" (cluster 4), and "fluid types and others" (cluster 5)]. The high-frequency keywords of the top 20 were more concentrated in cluster 3 and cluster 2, with "mortality" ranked the top in both sepsis and burns literature. Significantly, 3 keywords in cluster 2 ranked in the top 5, including "goal directed resuscitation" (the 3rd), fluid responsiveness (the 4th) and fluid balance (the 5th) in sepsis literature, while the keywords of "microvascular exchange" (cluster 1) and "abdominal compartment syndrome" (ACS, cluster 3) ranked at the second and the fifth place in burns publications. Keyword burst analysis demonstrated that the keyword with the highest burst strength (BS) was "formula" (BS = 5.88, 2008-2014), followed by management (BS = 4.79, 2012-2022), ACS (BS = 4.76, 2006-2010), and fluid creep (BS = 4.74, 2011-2016) in burn publications, but they were dobutamine (BS = 12.31, 1992-2008), cardiac output (BS = 9.79, 1993-2001), catecholamine (BS = 9.54, 1993-2006), and consumption (BS = 7.52, 1992-2006) in sepsis literature. Moreover, the most frequently cited article in either sepsis or burns was categorized into cluster 2, that investigated goal-directed fluid therapy for sepsis and formula improvement for burns resuscitation.

It was demonstrated that the research priorities in titrating fluid were mainly concentrated on targeting hemodynamics in sepsis vs. improving formula (which briefly calculates the increased microvascular permeability) in burns, while concerning of "outcomes and complications" in fluid resuscitation similarly after 1992. However, hemodynamics and microvascular permeability have been simultaneously well considered in few previous studies regarding fluid resuscitation in either sepsis or burns.

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.

Blood products frequently are administered to critically ill patients. Considering recent trials and practice variability, a comprehensive review of current evidence was deemed essential to offer pertinent guidance to critical care practitioners. This American College of Chest Physicians (CHEST) guidelines panel examined the literature on RBC transfusions among critically ill patients overall and specific subgroups, including patients with gastrointestinal bleeding, acute coronary syndrome (ACS), cardiac surgery, isolated troponin elevation, and septic shock, to provide evidence-based recommendations.

A panel of experts developed six Population, Intervention, Comparator, and Outcome questions addressing RBC transfusions in critically ill patients and performed a comprehensive evidence review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the recommendations.

The initial search identified a total of 3,082 studies, and after the initial screening, 38 articles were reviewed. Among them, 23 studies met inclusion criteria, comprising 22 randomized controlled trials and one cohort study. Based on the analysis of these studies, the panel formulated two strong and four conditional recommendations. The overall quality of evidence for recommendations ranged from very low to moderate.

In most critically ill patients, a restrictive strategy was preferable to a permissive approach because it does not increase the risk of death or complications, but does decrease RBC use significantly. Data from critically ill subpopulations also supported a restrictive approach, except in patients with ACS, for whom favoring a restrictive approach could increase adverse outcomes.

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.

Septic management presented a tremendous challenge due to heterogeneous host responses. We aimed to develop a risk model for early septic stratification based on transcriptomic signature. Here, we combined genes OLAH, LY96, HPGD, and ABLIM1 into a prognostic risk score model, which demonstrated exceptional performance in septic diagnosis (AUC = 0.99-1.00) and prognosis (AUC = 0.61-0.70), outperforming that of Mars and SRS endotypes. Also, the model unveiled immunosuppressive status in high-risk patients and a poor response to hydrocortisone in low-risk individuals. Single-cell transcriptome analysis further elucidated expression patterns and effects of the four genes across immune cell types, illustrating integrated host responses reflected by this model. Upon distinct transcriptional profiles of risk subgroups, we identified fenretinide and meloxicam as therapeutic agents, which significantly improved survival in septic mice models. Our study introduced a risk model that optimized risk stratification and drug repurposing of sepsis, thereby offering a comprehensive management approach.

The developments in intensive care medicine documented in the Deutsche Medizinische Wochenschrift over the decades have significantly improved survival rates in severe conditions and pushed the boundaries of what is possible in acute medicine. By analyzing past issues and articles, this article shows how the Deutsche Medizinische Wochenschrift has acted as a mirror of the dynamic landscape of intensive care medicine.

This study aimed to assess the impact of the timing of low-dose hydrocortisone adjuvant therapy initiation on clinical outcomes in patients with septic shock by a systematic review and meta-analysis.

We conducted a comprehensive search of all randomized controlled trials (RCTs) and cohort studies available in the PubMed, Web of Science, and Embase databases. The search included articles published from the founding of these databases until August 1, 2024. The purpose of the search was to compare the results of initiating low-dose hydrocortisone (HC) adjuvant therapy at different time periods. The main reported results included short-term mortality (ICU mortality and hospital mortality) as key outcomes, and secondary outcomes such as the rate of renal replacement treatment continuous renal replacement therapy (CRRT), length of stay in the intensive care unit (ICU), and rate of shock reversal.

Seven trials, with a total of 3063 patients, were included. The main finding of this meta-analysis indicates that the early treatment group, which received low-dose hydrocortisone, had a lower ICU mortality rate compared to the late treatment group. Additionally, the hospital mortality rate in the early treatment group was lower than that in the late treatment group. There was a correlation between the timing of beginning of HC and the short-term mortality of patients with septic shock. The secondary findings indicated that there were no notable disparities in the rates of CRRT, the rate of reversing shock, and the duration of stay in the ICU.

Administering low doses of HC early on can decrease the risk of death in septic shock patients in the short-term mortality. There were no substantial disparities observed in the rate of CRRT, the rate of reversal of shock, and the duration of stay in the ICU. Additional extensive RCTs are required to validate this conclusion.

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.

Sepsis-associated acute lung injury (SA-ALI) is a common complication in patients with sepsis, contributing to high morbidity and mortality. Excessive inflammation and oxidative stress are crucial contributors to lung injury in sepsis. This study aims to examine the protective effects of moderate hypothermia on SA-ALI and explore the underlying mechanisms.

Sepsis was induced in rats through cecal ligation and puncture followed by intervention with moderate hypothermia (32-33.9°C). Blood, bronchoalveolar lavage fluid, and lung tissues were collected 12 hours post-surgery. Inflammatory responses, oxidative injury, SA-ALI-related pathophysiological processes, and Keap1/GSK3β/Nrf2/GPX4 signaling in septic rats were observed by ELISA, lung W/D ratio, immunohistochemistry, immunofluorescence, histological staining, Western blotting, RT-qPCR, and TEM assays.

Moderate hypothermia treatment alleviated lung injury in septic rats, reflected in amelioration of pathological changes in lung structure and improved pulmonary function. Further, moderate hypothermia reduced arterial blood lactate production and suppressed the expression of inflammatory factors IL-1β, IL-6, and TNF-α; downregulated ROS, MDA, and redox-active iron levels; and restored GSH and SOD content. TEM results demonstrated that moderate hypothermia could mitigate ferroptosis in PMVECs within lung tissue. The underlying mechanism may involve regulation of the Keap1/Nrf2/SLC7A11/GPX4 signaling pathway, with the insulin pathway PI3K/Akt/GSK3β also playing a partial role.

Collectively, we illustrated a novel potential therapeutic mechanism in which moderate hypothermia could alleviate ferroptosis induced by excessive inflammation and oxidative stress via the regulation of Keap1/GSK3β/Nrf2/GPX4 expression, hence ameliorating acute lung injury in sepsis.

To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion.

This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization.

A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days-6.0 days vs. median=5.0 days, IQR: 3.0 days-8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3-2.0 mmol/L vs. median=0.0 mmol/L, IQR: -0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3-2.2 mmol/L vs. median=0.4 mmol/L, IQR: -0.4 to 1.6 mmol/L, respectively; P=0.001).

SFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency.Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435.

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate as a biomarker and its influence on immune cell dynamics, emphasizing its critical role in modulating immune responses during sepsis. Mechanistically, key lactate transporters like MCT1, MCT4, and the receptor GPR81 are crucial in mediating these effects. HIF-1α also plays a significant role in lactate-driven immune modulation. Additionally, lactate affects immune cell function through post-translational modifications such as lactylation, acetylation, and phosphorylation, which alter enzyme activities and protein functions. These interactions between lactate and immune cells are central to understanding sepsis-associated immune dysregulation, offering insights that can guide future research and improve therapeutic strategies to enhance patient outcomes.

Infection is very common in burn patients because they lose the primary barrier from microorganism invasion, the skin. While there are attempts to prevent infections, topical antimicrobials and systemic prophylaxis tend to lead to more resistant organisms. After the initial resuscitation, the most common cause of death is from sepsis and multiple organ dysfunction syndrome. The diagnosis is difficult in the burn population because the constant exposure from the open wound leads to an inflammatory response that leads to persistent hypermetabolism. This paper reviews the current understanding and treatment of infection and sepsis in burns.

Congenital heart disease (CHD) is one of the most common inborn disorders, with a prevalence of 0.8-1.2%. Affected children are often malnourished due to increased dietary requirements. This may lead to severe long-term complications. Several authoritative organizations have published guidelines addressing nutritional intervention in children with CHD. We aimed to systematically assess the consistency of recommendations, the methodological quality of these guidelines, and the quality of evidence supporting each recommendation. PubMed, Embase, the Cochrane Database, World Health Organization Global Index Medicus, and 16 scientific societies' websites were searched for the period until September 2023. The guideline quality was assessed using the AGREE II tool. After screening 765 records, only 2 guidelines published in 2013 and 2022 met our inclusion criteria. The main reason for exclusion was the absence of any system for rating the evidence. The main issues concerned the lack of implementation advice or tools and the lack of criteria to measure the application of guideline recommendations. The included guidelines were of good quality and within specific recommendations, both publications were largely in agreement, and the score for the overall assessment was high (83%). There is a pressing need for comprehensive, multi-threaded guidelines incorporating implementation strategies and methods for the performance assessment of children with malnutrition and CHD.

The correlation between lipid profiles and sepsis has received increasing attention. The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is one of the key lipid profiles. However, in-depth exploration of the correlation between NHHR and the mortality risk of patients with sepsis is limited.

Data from the MIMIC-IV (v2.2) database, we review the NHHR relevance and the sepsis severity index using Spearman's correlation analysis. Additionally, we research NHHR associated with sepsis patients' survival rate of 28 days using Cox regression analyses of continuous and categorical models. To further validate our findings, we conducted subgroup and sensitivity analyses.

The study involved 3,142 patients diagnosed with sepsis, according to 28 days after in-hospital survival condition, divided into two groups. In this study, 2932 patients were in the survival group and 210 patients died within 28 days (mortality group). Of note, the mean NHHR of patients in the mortality group exceeded that of the survival group (3.5 vs. 2.9). Additionally, NHHR was positively correlated with the severity index. After adjusting for demographic and laboratory data, an increased NHHR was positively correlated with higher sepsis mortality risk (OR = 1.06; 95% CI: 1.02-1.11; P = 0.013). Subgroup analysis shown the same results. Contributors were be categorized into two groups based on NHHR levels, with a threshold of 2.61. Contrast the mortality risk between low-NHHR group and high-NHHR group, high-NHHR show greater mortality risk on 28-day, 60-day, 90-day, in ICU, and in hospital.

Elevated NHHR is to be correlated with an increased risk of mortality in patients with sepsis. Further research on NHHR may contribute to advancements in sepsis prevention and treatment.

Early diagnosis and prompt management are essential to enhance the outcomes of patients with sepsis and septic shock. Over the past two decades, evidence-based guidelines have guided appropriate treatment and recommended the implementation of a bundle strategy to deliver fundamental treatments within the initial hours of care. Shortly after its introduction, the implementation of a bundle strategy has led to a substantial decrease in mortality rates across various health care settings. The primary advantage of these bundles is their universality, making them applicable to all patients with sepsis. However, this same quality also represents their primary disadvantage as it fails to account for the significant heterogeneity within the septic patient population. Recently, the individualization of treatments included in the bundle has been suggested as a potential strategy for further improving the prognosis of patients with sepsis. New strategies for the early identification of microorganisms and their resistance patterns, advanced knowledge of antibiotic kinetics in critically ill patients, more conservative fluid therapy in specific patient populations, and early use of alternative vasopressors to catecholamines, as well as tailored source control based on patient conditions and site of infection, are potential approaches to personalize initial care for specific subgroups of patients. These innovative methodologies have the potential to improve the management of septic shock. However, their implementation in clinical practice should be guided by solid evidence. Therefore, it is imperative that future research evaluate the safety, efficacy, and cost-effectiveness of these strategies.

Background: This study aims to investigate the safety and efficacy of guideline-directed fluid resuscitation (GDFR) compared with conservative fluid management in end-stage renal disease (ESRD) patients with sepsis by evaluating 90-day mortality and intubation rate. Methods: Following PRISMA guidelines, a systematic review was conducted across multiple databases using specific keywords and controlled vocabulary. The search strategy, implemented until October 1, 2023, aimed to identify studies examining fluid resuscitation in ESRD patients with sepsis. The review process was streamlined using Covidence software. A fourth reviewer resolved discrepancies in study inclusion. A random-effects model with the generic Mantel-Haenszel method was preferred for integrating odds ratios (ORs). Sensitivity analysis and publication bias analysis were performed. Results: Of the 1274 identified studies, 10 were selected for inclusion, examining 1184 patients, 593 of whom received GDFR. Four studies were selected to investigate the intubation rate, including 304 patients. No significant mortality or intubation rate difference was spotted between both groups [OR = 1.23; confidence interval (CI) = 0.92-1.65; I2 = 0% and OR = 1.91; CI = 0.91-4.04]. In most studies, sensitivity analysis using the leave-one-out approach revealed higher mortality and intubation rates. The Egger test results indicated no statistically significant publication bias across the included studies. Conclusion: Our research contradicts the common assumption about the effectiveness of GDFR for sepsis patients with ESRD. It suggests that this approach, while not superior to the conservative strategy, may potentially be harmful.

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients.

Sepsis is understood as the result of initiating systemic inflammation derived from an inadequate host response against pathogens. In its acute phase, sepsis is marked by an exacerbated reaction to infection, tissue damage, organ failure, and metabolic dysfunction. Among these, hypoglycemia, characterized by disorders of the gluconeogenesis pathway, is related to one of the leading causes of mortality in septic patients. Recent research has investigated the involvement of sympathetic efferent neuroimmune pathways during systemic inflammation. These pathways can be stimulated by several centrally administered drugs, including Angiotensin-(1-7) (Ang-(1-7)). Therefore, the present study aims to evaluate the effects of central treatment with Ang-(1-7) on hypoglycemia during endotoxemia. For this, male Wistar Hannover rats underwent stereotaxic surgery for intracerebroventricular (i.c.v.) administration of Ang-(1-7) and cannulation of the jugular vein for lipopolysaccharide (LPS) injection. Our results demonstrate that LPS was capable of inducing hypoglycemia and that prior central treatment with Ang-(1-7) attenuated this effect. Our data also show that Ang-(1-7) reduced plasma concentrations of TNF-α, IL-1β, IL-6, and nitric oxide, in addition to the decrease and increase of hepatic IL-6 and IL-10 respectively, in animals subjected to systemic inflammation by LPS, resulting in the reduction of systemic and hepatic inflammation, thus attenuating the deleterious effects of LPS on phosphoenolpyruvate carboxykinase protein content. In summary, the data suggest that central treatment with Ang-(1-7) attenuates hypoglycemia induced by endotoxemia, probably through anti-inflammatory action, leading to reestablishing hepatic gluconeogenesis.

Early detection and management of sepsis are crucial for patient survival. Emergency departments (EDs) play a key role in sepsis management but face challenges in timely response due to high patient volumes. Sepsis alert systems are proposed to expedite diagnosis and treatment initiation per the Surviving Sepsis Campaign guidelines.

To review and analyze the association of sepsis alert systems in EDs with patient outcomes.

A thorough search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1, 2004, to November 19, 2023.

Studies that evaluated sepsis alert systems specifically designed for adult ED patients were evaluated. Inclusion criteria focused on peer-reviewed, full-text articles in English that reported on mortality, ICU admissions, hospital stay duration, and sepsis management adherence. Exclusion criteria included studies that lacked a control group or quantitative reports.

The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Two independent reviewers conducted the data extraction using a standardized form. Any disagreements were resolved through discussion. The data were synthesized using a random-effects model due to the expected heterogeneity among the included studies.

Key outcomes included mortality, intensive care unit admissions, hospital stay duration, and adherence to the sepsis bundle.

Of 3281 initially identified studies, 22 (0.67%) met inclusion criteria, encompassing 19 580 patients. Sepsis alert systems were associated with reduced mortality risk (risk ratio [RR], 0.81; 95% CI, 0.71 to 0.91) and length of hospital stay (standardized mean difference [SMD], -0.15; 95% CI, -0.20 to -0.11). These systems were also associated with better adherence to sepsis bundle elements, notably in terms of shorter time to fluid administration (SMD, -0.42; 95% CI, -0.52 to -0.32), blood culture (SMD, -0.31; 95% CI, -0.40 to -0.21), antibiotic administration (SMD, -0.34; 95% CI, -0.39 to -0.29), and lactate measurement (SMD, -0.15; 95% CI, -0.22 to -0.08). Electronic alerts were particularly associated with reduced mortality (RR, 0.78; 95% CI, 0.67 to 0.92) and adherence with blood culture guidelines (RR, 1.14; 95% CI, 1.03 to 1.27).

These findings suggest that sepsis alert systems in EDs were associated with better patient outcomes along with better adherence to sepsis management protocols. These systems hold promise for enhancing ED responses to sepsis, potentially leading to better patient outcomes.

Infections are common complications in patients following liver transplantation (LTX). The early diagnosis and prognosis of these infections is an unmet medical need even when using routine biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Therefore, new approaches are necessary.

In a prospective, observational pilot study, we monitored 30 consecutive patients daily between days 0 and 13 following LTX using the 29-mRNA host classifier IMX-BVN-3b that determine the likelihood of bacterial infections and viral infections. True infection status was determined using clinical adjudication. Results were compared to the accuracy of CRP and PCT for patients with and without bacterial infection due to clinical adjudication.

Clinical adjudication confirmed bacterial infections in 10 and fungal infections in 2 patients. 20 patients stayed non-infected until day 13 post-LTX. IMX-BVN-3b bacterial scores were increased directly following LTX and decreased until day four in all patients. Bacterial IMX-BVN-3b scores detected bacterial infections in 9 out of 10 patients. PCT concentrations did not differ between patients with or without bacterial, whereas CRP was elevated in all patients with significantly higher levels in patients with bacterial infections.

The 29-mRNA host classifier IMX-BVN-3b identified bacterial infections in post-LTX patients and did so earlier than routine biomarkers. While our pilot study holds promise future studies will determine whether these classifiers may help to identify post-LTX infections earlier and improve patient management.

German Clinical Trials Register: DRKS00023236, Registered 07 October 2020, https://drks.de/search/en/trial/DRKS00023236.

This study aimed to explore the therapeutic effect and potential mechanism of heparin-binding protein (HBP) reduction on sepsis-related acute lung injury.

We utilized a murine model of sepsis-induced by intraperitoneal injection of lipopolysaccharides (LPS) in C57BL/6J mice divided into four groups: Control, LPS, Anti-HBP, and ceftriaxone (CEF). Following sepsis induction, Anti-HBP or CEF treatments were administered, and survival rates were monitored for 48 h. We then used reverse-transcription quantitative PCR to analyze the expression levels of HBP in lung tissues, immunohistochemistry for protein localization, and Western blotting for protein quantification. Pulmonary inflammation was assessed using enzyme-linked immunosorbent assays of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and interferon-γ). The activation state of the aryl hydrocarbon receptor (AhR) signaling pathway was determined via Western blotting, evaluating both cytoplasmic and nuclear localization of AhR and the expression of cytochrome P450 1A1 protein by its target gene.

Anti-HBP specifically reduced HBP levels. The survival rate of mice in the Anti-HBP and CEF groups was much higher than that in the LPS group. The severity of lung injury and pulmonary inflammatory response in the Anti-HBP and CEF groups was significantly lower than that in the LPS group. AhR signaling pathway activation was observed in the Anti-HBP and CEF groups. Additionally, there was no significant difference in the above indices between the Anti-HBP and CEF groups.

HBP downregulation in lung tissues significantly improved LPS-induced lung injury and the pulmonary inflammatory response, thereby prolonging the survival of sepsis mice, suggesting activation of the AhR signaling pathway. Moreover, the effect of lowering the HBP level was equivalent to that of the classical antibiotic CEF.

Not applicable.

To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment.

This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022. The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed.

Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 18% (45/250). A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48). Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI. Coagulase-negative staphylococci (CoNS) and Escherichia coli were the most commonly isolated GPB and GNB, respectively. A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32).

BSIs are still a common and severe complication after allo-HSCT. In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high. Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD.

To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice.

Review and task force position statements with necessary guidance.

A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem.

A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.

The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided.

There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences.

A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU).

A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model.

Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance.

Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost. Short term risks-hepatic/renal dysfunction, intermediate effects-concomitant superinfections, and long-term risks-potentiating antimicrobial resistance (AMR), are all possible consequences of antimicrobial administration. These risks are increased by longer periods of treatment and unnecessarily broad treatment courses. Recently, the literature has focused on multiple strategies to determine the appropriate duration of antimicrobial therapy. Further, there is a clinical shift to multi-modal approaches to determine the most suitable timepoint at which to end an antibiotic course. An approach utilising biomarker assays and an inter-disciplinary team of pharmacists, nurses, physicians, and microbiologists appears to be the way forward to develop sound clinical decision-making surrounding antibiotic treatment.

Septic shock remains a potentially life-threatening complication among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. There is a paucity of information on the clinical characteristics, outcome and prognostic factors of septic shock patients after allo-HSCT. We aimed to describe the clinical characteristics of septic shock after allo-HSCT and its associated health outcomes and to evaluate the role of patient demographics, transplantation-related laboratory and clinical variables associated with the short-term mortality of septic shock after allo-HSCT. We retrospectively studied 242 septic shock patients from 6105 consecutive patients allografted between 2007 and 2021. We assessed 29 risk factors as candidate predictors and used multivariable logistic regression to establish clinical model. The primary outcome was 28-day mortality. The median age of the subjects was 34 (IQR 24 to 45) years. A total of 148 patients (61.2%) had positive blood cultures. Gram-negative bacilli accounted for 61.5% of the positive isolates, gram-positive cocci accounted for 12.2%, and fungi accounted for 6.1%. Coinfections were found in 30 (20.3%) patients. Escherichia coli was the dominant isolated pathogen (31.1%), followed by Pseudomonas spp. (12.8%) and Klebsiella pneumoniae (10.1%). With a median follow-up of 34 (IQR: 2 to 528) days, a total of 142 (58.7%) patients died, of whom 118 (48.8%) died within the first 28 days after septic shock diagnosis, 131 (54.1%) died within 90 days, and 141 (58.3%) died within 1 year. A large majority of deaths (83.1% [118/142]) occurred within 28 days of septic shock diagnosis. Finally, 6 independent predictive variables of 28-day mortality were identified by multivariable logistic regression: time of septic shock, albumin, bilirubin, PaO2/FiO2, lactate, and sepsis-induced coagulopathy. Patients with late onset shock had higher 28-day mortality rates (64.6% versus 25.5%, P < .001) and more ICU admission (32.6% versus 7.1%, P < .001) than those with early onset shock. We highlight the poor survival outcomes in patients who develop septic shock, emphasizing the need for increasing awareness regarding septic shock after allo-HSCT. The information from the current study may help to assist clinicians in identifying high-risk patients.

Early identification of sepsis is particularly important in the emergency department (ED). However, data on the diagnosis of sepsis in the ED are scanty, especially within the Italian context. To quantify sepsis incidence and recognition in the ED from Lombardy, Italy, we used EUOL data from the Regional Emergency Agency for the years 2017-2022. Sepsis was identified based on the ED discharge diagnosis; recognized sepsis cases were those assigned to a high-priority code at triage, while unrecognized ones were those assigned to a low priority code. Odds ratios (ORs) for sepsis recognition according to various patient characteristics were estimated using multivariable mixed-effects logistic regression models. The rate of sepsis diagnosis in ED was 1.9 per 1000 (6626 patients) in 2017 and increased to 3.4 per 1000 in 2022 (11,508 patients). In 2022, 67% of sepsis cases were correctly identified. Death in the ED was more frequent in patients with recognized sepsis (10.4%) than in those with unrecognized sepsis (2.3%). The probability of sepsis being recognized at ED admission was higher in men (multivariable OR: 1.06), in individuals with advanced age (OR: 1.71 for age ≥ 90 years vs < 60), and in those with access to the second (OR: 1.48) and third ED level (OR: 1.87). Conversely, it was lower in patients arriving at the ED through autonomous transportation (OR: 0.36). This large real-world analysis indicates an increase in sepsis cases referred to the ED in recent years. About one-third of sepsis cases are not correctly identified at triage, although more severe cases appear to be promptly recognized.

Sepsis-related mortality is decreasing over time after the introduction of "Surviving Sepsis Campaign" Guidelines in 2004. The last Guidelines version collects 93 recommendations, but several interventions supported by randomized evidence of mortality reduction are not included.

We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies.

We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit.

Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.