To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI).

Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality. Cox regression analysis assessed the risk of mortality across different MPP levels, adjusting for potential confounders. Subgroup analyses and sensitivity analyses were conducted to ensure the robustness of the findings.

A total of 2318 patients with SA-AKI were stratified into five MPP trajectories by GBTM. Patients in Traj-1 and Traj-2, characterized by consistently low MPP (<60 mmHg), demonstrated markedly higher 90-d mortality (62.86% and 26.98%). RCS curves revealed a non-linear inverse relationship between MPP and 90-d mortality, identifying 60 mmHg as the optimal threshold. Patients with MPP ≤ 60 mmHg exhibited significantly elevated 90-d mortality compared to those with MPP > 60 mmHg (29.81% vs. 20.88%). Cox regression analysis established Traj-1 and Traj-2 as independent risk factors for increased mortality relative to Traj-3 (60-70 mmHg), with hazard ratios (HRs) of 4.67 (95%-CI 3.28-6.67) and 1.45 (95%-CI 1.20-1.76). MPP > 60 mmHg was significantly associated with reduced 90-d mortality (HR 0.65, 95%-CI 0.55-0.77). Subgroup and PSM analyses supported these findings.

Dynamic MPP trajectory serves as a valuable prognostic biomarker for SA-AKI. Early monitoring of MPP trends offers critical insights into renal perfusion management, potentially improving outcomes in SA-AKI.

Pyroptosis is considered to play an important role in the occurrence, development and prognosis of septic acute kidney injury (SAKI). We aimed to explore the specific molecular mechanism of S-nitrosoglutathione (SNG) regulating pyroptosis of kidney tubular epithelial cells (KTECs).

By constructing a mice model of sepsis, we pretreated them with SNG and used biochemical methods to detect the levels of serum inflammatory factors and mitochondrial reactive oxygen species (mtROS), assessed the severity of kidney injury and KTECs mitochondrial damage, and detected the expression of KTECs pyroptosis-related proteins and sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway proteins.

The kidney injury caused by sepsis was significantly aggravated, and the levels of IL-1β, IL-6, IL-18, TNF-α, malondialdehyde (MDA) and mtROS were all increased, accompanied by the decrease of SIRT3 and SOD2 proteins, while NOD-like receptor with pyrin domain 3 (NLRP3), gasdermin D (GSDMD), Caspase-1 proteins expression and the number of KTECs apoptotic cells were all increased. However, after SNG pretreatment, the levels of IL-1β, IL-6, IL-18, TNF-α, MDA and mtROS were all significantly decreased, the expression of SIRT3 and SOD2 proteins were increased, NLRP3, GSDMD, Caspase-1 proteins expression and the number of KTECs apoptotic cells were decreased.

SNG protects SAKI by regulating the SIRT3/SOD2/mtROS signaling pathway to inhibit the pyroptosis of KTECs.

This study aimed to investigate the prognostic impact of completing 30 mL/kg fluid resuscitation within 1 h in elderly septic shock patients.

This was a multicenter prospective observational cohort study. We applied logistic regression to assess the impact of completing 30 mL/kg fluid resuscitation within 1 h on respiratory support escalation including new-onset mechanical ventilation, bilevel positive airway pressure (BiPAP), and high-flow nasal cannula (HFNC) as well as heart failure (HF). We plotted Kaplan-Meier (K-M) curves to evaluate survival in patients completing 30 mL/kg fluid resuscitation within 1 h. We performed mediation analyses to determine the influence of HF on mortality associated with completing 30 mL/kg fluid resuscitation within 1 h.

Completing 30 mL/kg fluid resuscitation within 1 h increased the odds ratios of new-onset BiPAP (adjusted OR = 3.411; 95% confidence interval (CI) = [1.526, 7.620]) and HFNC (adjusted OR = 2.576; 95% CI = [1.252, 5.297]) within 24 h as well as the odds ratio of HF (adjusted OR = 2.291; 95% CI = [1.266, 4.149]). The adjusted K-M curve showed that patients completing 30 mL/kg fluid resuscitation within 1 h had higher 30-d mortality than those completing it over longer periods. The mediation effect suggested that completing 30 mL/kg fluid resuscitation within 1 h could be fatal primarily because it increased the risk of HF.

For elderly patients with septic shock, completing 30 ml/kg of fluid resuscitation within 1 h ought to be more cautious, particularly considering the patient's cardiac function and overall clinical status.

Maternal sepsis continues to be a maternal health problem associated with 75,000 deaths per year worldwide, representing a greater burden in low- and middle-income countries (LMICs). Although the Shock Index (SI) has been widely studied in postpartum hemorrhage and in non-obstetric populations, it has not yet been widely studied in sepsis. We aimed to identify the relationship between Shock Index and suspected sepsis in pregnant and postpartum patients to explore the use of Shock index in the context of maternal sepsis and its relationship with sepsis-related outcomes.

A single-center, retrospective, case-control study was conducted, including pregnant and postpartum patients attended between June 2015 and December 2020 in a high-complexity university hospital. This study was conducted in a High Obstetric Complexity Unit (UACO) in the southwest region of Colombia. Pregnant or postpartum women with infectious processes of obstetric or non-obstetric origins were included. Cases had sepsis diagnosis; controls showed infection process and systemic inflammatory response signs without confirmed sepsis. Those with unconfirmed infections and preterm conditions were excluded. A logistic regression model was conducted to examine the association between maternal factors and sepsis diagnosis, and significant variables were determined through univariate analysis and included in a multivariate model.

A total of 640 patients were included (343 cases and 297 controls), sepsis was significantly associated with a higher shock index at admission SI ≥ 0.9 (85.4% vs 75%, p = 0.001). No correlation was found between the Shock Index and C-reactive protein (CRP), leukocyte count, or ICU length of stay. The area under the receiver operating characteristic curve (AUROC) analysis identified a Shock Index of 1 as the optimal cutoff point, while the cutoff point of 0.9 demonstrated the highest sensitivity (85%). An SI ≥ 0.9 increased the risk of sepsis 1.94 times (95% CI 1.31-2.91, p = 0.001) and remained significant in the adjustment model (OR_adj 2.18, 95% CI 1.42-3,32, p < 0.001). Incidence of maternal sepsis, incidence of maternal complications, and perinatal outcomes were measured with a SI ≥ 0.9.

Our findings underscore the importance of using the Shock Index with a cutoff point of 0.9 as a predictive tool for sepsis in pregnant patients, emphasizing the need for timely intervention and continuous monitoring of patients.

This study investigates the impact of tryptophan substitution on the properties of the Medisin family peptide MS-PT. By substituting hydrophobic amino acids in MS-PT1 with tryptophan, a series of derivative peptides were synthesized. Among them, the 7W peptide stood out with its unique N-terminal random curl and α-helix structure. In vitro, 7W effectively inhibited the secretion of pro-inflammatory cytokines like IL-6 and TNF-α in LPS-induced Membrane-Proximal Macrophages (MPMs) by blocking the MAPK/NF-κB signaling pathway. It also exhibited stronger antimicrobial activity against Gram-positive bacteria compared to the parent peptide MS-PT1, with good safety as indicated by a low hemolysis rate. In vivo, in the CLP-induced sepsis mouse model, 7W alleviated lung and liver injury, suppressed the expression of inflammatory factors in serum and tissues, and had a relatively long plasma half-life of 46.8 h. Mechanistically, 7W interacted preferentially with bacterial mimic membranes and LPS, and its anti-inflammatory effect might be mediated by binding to TLR4. These findings not only clarify the role of tryptophan substitution in modulating peptide properties but also offer a new strategy for the development of multifunctional antimicrobial peptides, suggesting that 7W has great potential as a therapeutic agent for sepsis and other inflammatory diseases.

Severe Acute Pancreatitis (SAP) is characterized by an abrupt onset of pancreatic inflammation, which may induce damage to other organs, and is associated with significant morbidity and mortality. Despite the considerable disease burden, specific treatments to stop progression or prevent occurrence are limited. Currently, there is a paucity of comprehensive studies that thoroughly explore metabolic dysregulation in SAP, particularly those that emphasize changes in outcomes. Nuclear magnetic resonance (NMR) based metabolomics coupled with multivariate analysis was applied to serum samples of 20 survivors and 30 non-survivors of SAP to identify metabolic changes linked to different outcomes. The discriminant analysis of serum samples of SAP survivors and non-survivors revealed isoleucine, leucine, valine, arginine, lactate, and 3-hydroxybutyrate as significant metabolites elevated in the non-survivors. These identified metabolites had shown a significant positive correlation with clinical severity scores in the Pearson correlation analysis. Pathway analysis revealed disruptions in amino acid metabolism, driven by protein catabolism to fulfill the patient's energy requirements. This study highlights the importance of metabolomics in unraveling the molecular and physiological mechanisms underlying SAP. These findings offer valuable insights for clinicians to develop treatment strategies that target metabolic pathways in SAP, potentially for improving patient outcomes.

Diuretics remain the cornerstone therapy of critically ill patients with volume overload as a result of cardiac failure, acute kidney injury or aggressive fluid resuscitation. This review summarises the principles of applied renal physiology, describing the mechanisms of action, the clinical applications, and the adverse effects of commonly used diuretics during critical illness. Loop diuretics, and in particular furosemide, remain the most popular, despite evidence of any effect on mortality or, indeed, on the need for renal replacement therapy. The efficacy of loop diuretics after administration depends on three factors. Firstly, the tubular concentration of the diuretic: continuous infusion of furosemide seems to provide a higher and more stable tubular concentration of furosemide with respect to bolus injection. Secondly, the interaction with albumin both in the plasma and in the renal tubule: despite a strong physiological rationale supporting this approach, albumin supplementation in hypoalbuminaemic patients does not seem to result in a higher diuretic efficacy. Thirdly, diuretic resistance, which can be addressed by optimising loop diuretic dose and by using combination therapy with other agents, including thiazides or thiazide-like diuretics or carbonic anhydrase inhibitors. These drugs constitute a useful adjunct to overcome loop diuretic resistance. Other agents such as distal potassium-sparing diuretics and osmotic diuretics can also be considered. The latter have been used successfully in hypokalaemia, rhabdomyolysis-associated acute kidney injury or to prevent ischaemia-reperfusion injury in kidney transplantation. Finally, this review provides the basic concepts of the interplay between acid-base equilibrium and diuretic therapy.

Intravenous fluid resuscitation forms a crucial part of the sepsis bundle. However, the perception is that patients with comorbidities such as congestive heart failure, chronic kidney disease, and cirrhosis receive lower volumes due to concerns regarding potential for fluid overload. We review outcomes relating to resuscitation with conservative versus liberal volumes in specific patient populations.

We searched MEDLINE, Embase+Embase Classic, Cochrane library, Web of Science, CINAHL Complete, and ClinicalTrials.gov for studies that compared outcomes related to different volumes of resuscitation in adult patients with sepsis, along with congestive heart failure, chronic kidney disease, cirrhosis. The primary outcome was all-cause mortality up to 30 days post-discharge. Secondary outcomes included length of stay, intubation rates and duration, and use of vasopressors.

A total of 37 observational studies were included. We found no statistically significant difference in all-cause mortality (Odds Ratio [OR] 1.01; 95 % Confidence Interval [CI] 0.86-1.19), rates of ICU admission (Risk Ratio [RR] 0.89; 95 % CI 0.70-1.11), hospital length of stay (Mean Difference [MD] -0.01; 95 % -0.18-0.15), ICU length of stay (MD -0.06; 95 % CI -0.30-0.18), intubation rates (OR 1.00; 95 % 0.76-1.32), duration of mechanical ventilation (MD 0.01; 95 % CI -0.31-0.32) or use of vasopressors (RR 0.81; 95 % CI 0.64-1.02).

Among patients with comorbid conditions presenting with sepsis, we found no differences in outcomes related to the volume of fluid administered. Further evidence is needed to guide decisions regarding volume of fluid to administer in these patient populations given the lack of high certainty evidence.

Postoperative infection remains a serious problem for patients undergoing open-heart surgery and is associated with poor prognosis and mortality.

To determine the incidence, characteristics and associated risk factors for nosocomial infections in adult cardiac surgery patients and to develop a nomogram prediction model.

Data were retrospectively collected from patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) at a tertiary hospital in 2023. Patients were divided into an infected group (N = 130) and a non-infected group (N = 192). Multivariate logistic regression analysis was used to analyse the independent risk factors for healthcare-associated infections after cardiac surgery under CPB.

Of the 1584 patients, 130 (8.21%) developed postoperative infections (infection group). Lower respiratory tract was the most common site of infection (N = 74, 56.9%), while Gram-negative bacteria were the predominant isolates overall (N = 81, 62.3%). Among the Gram-negative bacteria, Acinetobacter baumannii was the most frequently identified, whereas Staphylococcus aureus was the leading strain among Gram-positive bacteria. Multivariate logistic regression analysis of the 322 patients included in the study revealed that CPB duration, American Society of Anaesthesiologists score, procalcitonin concentration on the first postoperative day, monocyte:lymphocyte ratio, preinfection mechanical ventilation duration, and preinfection central venous catheterization duration were the six independent predictors of postoperative infection. The area under the receiver operating characteristic curve was 0.824 (0.778-0.870), and the model showed good predictive performance.

A nomogram has been developed to predict postoperative infection via commonly available data. This tool could assist clinicians in optimising the perioperative care of patients undergoing cardiac surgery with CPB, but further external validation is needed.

A good knowledge of the theoretical foundations of medicine helps students and physicians to better recognize and treat patients with complex medical conditions, including sepsis and septic shock. The article describes the authors' experience in implementing the analysis of sepsis and septic shock using a high-fidelity simulated clinical scenario in the course of pathological physiology for preclinical medical students. The unique aspect of our approach is the integration of core physiology concepts, such as homeostasis, causality, structure-function relationships, and fundamental pathophysiology concepts (e.g., etiology, pathogenesis, cell and tissue damage, inflammation, symptoms, and syndromes) in the analysis of the patient's condition on the high-fidelity simulator with preclinical medical students. According to the students' feedback, the use of a high-fidelity simulator to analyze the sepsis and septic shock scenario increased their interest in the class, improved their motivation to learn the material, and helped them adapt in a safe environment to making decisions based on a large amount of data about a complex patient condition in a time-sensitive situation.NEW & NOTEWORTHY The authors applied core theoretical concepts of physiology and the fundamental concepts of pathological physiology for teaching sepsis and septic shock clinical scenarios on the high-fidelity simulator in the course of pathological physiology for preclinical medical students. It elevated students' interest and motivation, enhanced the educational experience, and prepared students better for real-world clinical decision-making. We consider that this idea might be an inspiration to colleagues and invite further discussion.

Intravenous fluids are among the most commonly prescribed drugs. Many preparations classified by composition as crystalloids or colloids, of natural or synthetic origin, are available in clinical practice. Guidelines favor crystalloids as first-choice fluids in most clinical situations, mainly because of the lack of advantage of using colloids in reducing mortality and organ complications and generating higher treatment costs. This review focuses on the evidence for the use of colloids in selected clinical conditions.

Background: Sepsis is a life-threatening clinical condition often seen in intensive care units, leading to multi-organ dysfunction. Myocardial injury is a prevalent complication, significantly increasing mortality among sepsis patients. Although heparin is used in sepsis management, its specific effects on myocardial injury and the role of neutrophil extracellular traps (NETs) in this context remain insufficiently understood. Aim: This study investigates the role of unfractionated heparin (UFH) combined with DNase I in reducing myocardial injury in a septic mouse model. Methods: A cecal ligation and puncture (CLP)-induced sepsis model was established in C57BL/6 mice to study myocardial injury. The experimental groups included treatments with UFH, UFH with DNase I, and NETs introduction. Myocardial injury was assessed using hematoxylin and eosin staining, enzyme linked immunosorbent assay for injury markers (creatine kinase MB [CK-MB] and lactate dehydrogenase [LDH]), and Western blotting for inflammatory proteins (TNF-α and IL-6). Differential proteomic analysis using data independent acquisition mass spectrometry and pathway enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were conducted to identify molecular pathways and key proteins affected by the treatments. Results: Single UFH treatment increased the formation of NETs, upregulated TNF-α and IL-6, and increased CK-MB and LDH, worsening myocardial injury. The combination of UFH and DNase I significantly reduced myocardial injury, suppressing NETs formation and inflammation. Proteomic analysis identified crucial pathways related to NETs, metabolism, and complement and coagulation cascades, with proteins Ccn1 and Tagln highlighted as potential therapeutic targets. Conclusion: UFH combined with DNase I effectively alleviates myocardial injury in septic mice by modulating NETs formation and associated inflammatory processes. This study may provide new insights and options for the early use of heparin in the treatment of septic patients, particularly in cases with a higher risk of myocardial injury.

Ampicillin/sulbactam, a combination of a β-lactam and β-lactamase inhibitor, is widely used in clinical settings. However, therapeutic drug monitoring (TDM) of ampicillin is not commonly performed, particularly in intensive care units (ICUs). The purpose of this study was to develop and validate a rapid and cost-effective high-performance liquid chromatography (HPLC)-ultraviolet spectrometry method to quantify ampicillin in human serum and evaluate its clinical application in ICU patients.

Sample cleanup included a protein precipitation protocol, followed by chromatographic separation on a C18 reverse-phase HPLC column within 12.5 minutes using gradient elution of the mobile phase. The assay was validated according to the German Society of Toxicology and Forensic Chemistry criteria. Clinical applications involved the retrospective analysis of TDM data from ICU patients receiving continuous infusion of ampicillin/sulbactam, including the attainment of target ranges and individual predicted and observed pharmacokinetics.

The method was robust, with linear relations between the peak area responses and drug concentrations in the range of 2-128 mg/L. The coefficient of variation for precision and the bias for accuracy (both interday and intraday) were less than 10%. Clinical application revealed variable pharmacokinetics of ampicillin in ICU patients (clearance of 0.5-31.2 L/h). TDM-guided dose adjustments achieved good therapeutic drug exposure, with 92.9% of the samples being within the optimal (16-32 mg/L) or quasioptimal (8-48 mg/L) range.

This method provides a practical solution for the routine TDM of ampicillin, facilitating individualized dosing strategies to ensure adequate therapeutic drug exposure. Given its simplicity, cost-effectiveness, and clinical relevance, HPLC-ultraviolet spectrometry holds promise for broad implementation in hospital pharmacies and clinical laboratories.

Omitted doses are a subset of medication administration errors which have the potential to cause severe harm. Sepsis is a clinical condition where dose omissions or delays in medicines administration can be fatal. Automated dispensing cabinets (ADCs) provide a medicines management solution which keeps track of stock in real time and can automatically generate orders, reducing the likelihood of medication stockouts. This study aims to assess the impact of ADC implementation on the rate of omitted doses due to unavailability of ward stock medicines. Secondary aims are to investigate the effect of ADCs on omitted doses of first dose antimicrobials. Due doses data was compiled from the electronic prescribing and medicines administration (EPMA) system for ten wards pre-ADC implementation between July and September 2022 and was compared with data post-ADC implementation between July and September 2023. Omitted doses were selected and filtered for those marked 'drug not available'. Ward stock lists were used to determine which omitted doses were for medicines held as ward stock. A secondary analysis filtered this data further to isolate omitted doses of ward stock medicines which were systemically administered antimicrobials. The overall number of prescribed doses during the pre-implementation period was comparable to those in the post-implementation period. There was a total of 393 omitted doses of ward stocked medicines due to unavailability pre-ADC implementation, and 817 post-ADC implementation. This represents an omission rate due to unavailability of ward stock medicines as a percentage of all prescribed doses, of 0.08 % pre-ADC and 0.18 % post-ADC implementation. Statistical analysis showed no difference (p = 0.1655). There was also no statistical difference in omitted doses of ward stocked antimicrobials pre vs post-ADC implementation (p = 0.3363). It has been identified that a potential way to reduce rates of omitted doses is by optimising stock stored in each cabinet. This research is encouraging and may warrant further data collection once stock optimisation has occurred.

Background: Neutrophil percentage-to-albumin ratio (NPAR) has been proven to correlate with the poor prognosis of various diseases. This study aims at investigating the prognostic value of NPAR for septic cholangitis patients from Medical Information Mart Intensive Care IV database. Methods: Overall, 329 adult septic cholangitis patients were retrospectively included, of whom 82 experienced deaths within 30 days. Cox regression, restricted cubic spline, and Kaplan-Meier curves were employed to evaluate the association between NPAR and 30-day mortality. Hazard ratio (HR) and 95% confidential interval (95% CI) were calculated. Receiver operating characteristic curves and integrated discrimination improvement analysis were utilized to assess the predictive efficacy of NPAR. Results: NPAR was significantly associated with 30-day mortality in multivariable Cox analysis (HR = 1.52, 95% CI = 1.16-1.99, P = 0.003). Kaplan-Meier curves indicated NPAR in the second quartile (range from 2.55-2.93) demonstrated the lowest mortality (log-rank test: P < 0.001). RCS curves showed a U-shaped relationship between NPAR and 30-day mortality, and an inflection point of appropriately 2.73 was discovered. HRs and 95% CIs on the left and right sides of the inflection point, were 0.299 (0.114-0.781, P = 0.014) and 1.955 (1.362-2.807, P < 0.001), respectively. NPAR exhibited a moderate Receiver operating characteristic (0.668) for the prediction of 30-day mortality. Importantly, addition of the NPAR into illness score models can significantly improve the predictive ability. Conclusions: A U-shaped nonlinear association was observed between NPAR and 30-day all-cause mortality in septic cholangitis patients. NPAR emerged as a potential marker for the prognosis of critical cholangitis patients.

This study aims to investigate the effects of continuous renal replacement therapy (CRRT) combined with ulinastatin on cytokine levels and prognosis in patients with sepsis. The control and study groups (40 cases each) were established. The control group received CRRT alone, while the study group received CRRT plus ulinastatin treatment, with both groups being treated for 7 days. We compared the following parameters before and after treatment between the two groups: Sequential Organ Failure Assessment (SOFA) scores, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, renal function indicators [cystatin C (CysC), blood urea nitrogen (BUN), and serum creatinine (SCr)], inflammatory factors [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and procalcitonin (PCT)], and immune function parameters (CD4+, CD8+, CD4+/CD8+ ratio). Additionally, we recorded adverse reactions and 28-day mortality rates in both groups. After 7 days of treatment, the study group showed significantly lower SOFA scores, APACHE II scores, serum levels of CysC, BUN, Scr, TNF-α, CRP, PCT, and peripheral blood CD8+ compared to the control group, while demonstrating higher peripheral blood CD4+ and CD4+/CD8+ ratio. During the treatment period, there was no significant difference in the incidence of adverse reactions between the two groups. However, the 28-day mortality rate was significantly lower in the study group compared to the control group. For patients with sepsis, the combination of CRRT and ulinastatin therapy can significantly improve disease severity, inflammatory factors, renal function, and immune function, while reducing mortality rate.

Hematologic malignancies are a global public health concern, with high mortality rates in patients requiring critical care. The role of chemotherapy during intensive care unit (ICU) admission in this context remains unclear. This study aimed to analyze trends in survival rates based on chemotherapy timing and examine patient characteristics, ICU treatments, and clinical outcomes in each group. Using the Japanese Diagnosis Procedure Combination inpatient database, data from 21,837 patients aged ≥ 18 years who were hospitalized for hematologic malignancies and admitted to ICUs between April 1, 2012, and March 31, 2022, were analyzed. Patients were categorized based on chemotherapy timing as follows: no chemotherapy (NC), chemotherapy before ICU admission (CB), chemotherapy during ICU admission (CD), and chemotherapy after ICU discharge (CA). Mortality trends were assessed, with in-hospital mortality as the primary outcome variable. The CB group had the highest mortality rate, which decreased over time (61.2% in 2012 to 46.2% in 2021). The CD group had stable mortality rates (24.2% in 2012 and 22.6% in 2021), with a notable proportion of patients (55.4%) discharged home. These findings highlight the need for further investigation into the factors influencing ICU outcomes in patients receiving chemotherapy.

We examined the effect of a high-target mean arterial pressure (MAP) on septic shock in a previously underrepresented region.

A multicentre, pragmatic, open-label, randomised controlled trial was conducted in 29 hospitals in Japan, where the prevalence of chronic hypertension among older individuals is 66.9%. Patients who were diagnosed with septic shock, aged ≥ 65 years, and admitted to an intensive care unit were randomised 1:1 to the high (target MAP = 80-85 mmHg) or control (target MAP = 65-70 mmHg) groups from 1 July 2021 to 12 December 2023. The target MAP was maintained for 72 h or until vasopressors were no longer required. The primary outcome was the 90-day all-cause mortality. Secondary outcomes included organ support-free days and adverse events.

The trial was terminated early on the basis of the interim analysis results, suggesting the harm of the high-target strategy. Of the 518 patients, 258 were in the high-target group, and 260 were in the control group. By 90 days after randomisation, 101 patients (39.3%) in the high-target group and 74 (28.6%) in the control group had died from any cause (risk difference = 10.7; 95% confidence interval, 2.6-18.9). Renal replacement therapy-free days at 28 days were shorter in the high-target group. No clinical benefits for any outcome were observed in any subpopulation, including those with known chronic hypertension.

Among older patients with septic shock, high-target MAP significantly increased mortality compared with standard care.

UMIN Clinical Trials Registry; UMIN000041775; 13 September 2020.

In septic shock, the optimal timing of adjunctive vasopressin initiation shock is unknown. We aimed to assess the effect of its early initiation for patients with septic shock.

We conducted a multicenter target trial emulation to estimate the intensive care unit (ICU) mortality effect of early (≤ 6 h) adjunctive vasopressin compared with usual care. Eligible patients had septic shock diagnosed within 6 h of ICU admission. The primary outcome of this study was 30-day ICU mortality. Subgroup analyses were conducted to test the interaction of early vasopressin start with peak norepinephrine-equivalent dose (NED) at 6 h, APACHE score, peak lactate at 6 h and invasive mechanical ventilation. Secondary outcomes were the impact of delayed vasopressin introduction on 30-day ICU mortality and effect of NED at vasopressin start on 30-day ICU mortality. We used the parametric g-formula to emulate a target trial.

Overall, 3,105 patients fulfilled the inclusion criteria. Mean age was 62 years and mean APACHE III score was 83. In the first six hours of vasopressor therapy, 1,864 (60%) patients were invasively ventilated. Estimated 30-day ICU mortality was 19.34% (95%CI, 17.0 to 21.68) in the no vasopressin group and 18.45% (95%CI, 16.26 to 20.63) in the early vasopressin group; relative risk 0.95 (95%CI, 0.93 to 0.98). The estimated 30-day ICU mortality effect of starting vasopressin was particularly strong at lower norepinephrine doses (< 0.25 µg.kg-1.min-1) and significant at lower norepinephrine doses than recommended by the Surviving Sepsis Campaign Guidelines. Vasopressin administration progressively increased over the study period, from 35.2% (95%CI, 30.0 to 40.5) in 2015 to 45.1% (95%CI, 40.7 to 49.6) in 2021 (ß =  + 1.3% per year; 95%CI, + 0.46 to + 2.16, p = 0.011). Patients had progressively lower norepinephrine equivalent dose (ß = - 0.05 µg.kg-1.min-1 per year; 95%CI, - 0.09 to - 0.002, p = 0.038) and lower total SOFA score (ß = - 0.1 point per year; 95%CI, - 0.18 to - 0.07, p < 0.001) at vasopressin start.

In this emulation of a hypothetical target trial, patients with septic shock benefited from early vasopressin administration. These findings can help design prospective randomised-control trials of early adjunctive vasopressin use in septic shock.

Sepsis is a life-threatening condition resulting from an imbalanced immune response to an infection that causes over 10 million deaths annually, particularly in low and middle-income countries. Current clinical management of sepsis relies on infection control, homeostasis restoration, and systemic corticosteroid therapy. Unfortunately, while beneficial, corticosteroid regimens, including dexamethasone, can lead to adverse effects such as neurological and metabolic complications, limiting their use. In this work, we decided to develop a scalable production method using only approved and cost-effective materials. We also conceived our formulation to be freeze-drying friendly to allow its use within various healthcare systems. Following those concepts, we designed DSPE-PEG(2000)-based micelles to encapsulate dexamethasone, and improve its in vivo efficacy by extending blood circulation time and targeting innate blood immune cells. First, the physicochemical properties, stability, in vitro release kinetics, and efficacy of dexamethasone-loaded micelles were comprehensively measured to demonstrate the platform's robustness. The therapeutic in vivo efficacy of dexamethasone-loaded micelles and their ability to increase animal survival was exhibited in two murine sepsis models, an endotoxemia model, and the cecal ligation and puncture model. Various biodistribution and ex vivo fluorescence imaging assays revealed that using micelles led to an improved blood circulation time and a preferential accumulation within immune cells that could explain the enhanced efficacy of dexamethasone-loaded micelles compared to the soluble form of the drug used clinically. Altogether, our results indicate that this robust micellar delivery system can potentially improve the anti-inflammatory therapy of dexamethasone, offering a safer and more effective alternative to conventional corticosteroid regimens in sepsis.

Patients with intracerebral hemorrhage (ICH) are highly susceptible to sepsis. This study evaluates the efficacy of machine learning (ML) models in predicting sepsis risk in intensive care units (ICUs) patients with ICH. We conducted a retrospective analysis on ICH patients using the MIMIC-IV database, randomly dividing them into training and validation cohorts. We identified sepsis prognostic factors using Least Absolute Shrinkage and Selection Operator (LASSO) and backward stepwise logistic regression. Several machine learning algorithms were developed and assessed for predictive accuracy, with external validation performed using the eICU Collaborative Research Database (eICU-CRD). We analyzed 2,214 patients, including 1,550 in the training set, 664 in the validation set, and 513 for external validation using the eICU-CRD. The Random Forest (RF) model outperformed others, achieving Area Under the Curves (AUCs) of 0.912 in training, 0.832 in internal validation, and 0.798 in external validation. Neural Network and Logistic Regression models recorded training AUCs of 0.840 and 0.804, respectively. ML models, especially the RF model, effectively predict sepsis in ICU patients with ICH, enabling early identification and management of high-risk cases.

Existing guidelines emphasize the importance of initial fluid resuscitation therapy in sepsis management. However, in previous meta-analyses, there have been inconsistencies in differentiating between spontaneously breathing and mechanically ventilated septic patients.

To consolidate the literature on the predictive accuracy of changes in the inferior vena cava diameter (∆IVC) for fluid responsiveness in septic patients.

The Embase, Web of Science, Cochrane Library, MEDLINE, PubMed, Wanfang, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and VIP (Weipu) databases were comprehensively searched. Statistical analyses were performed with Stata 15.0 software and Meta-DiSc 1.4.

Twenty-one research studies were deemed suitable for inclusion. The sensitivity and specificity of ∆ IVC were 0.84 (95% CI 0.76, 0.90) and 0.87 (95% CI 0.80, 0.91), respectively. With respect to the distensibility of the inferior vena cava (dIVC), the sensitivity was 0.79 (95% CI 0.68, 0.86), and the specificity was 0.82 (95% CI 0.73, 0.89). For collapsibility of the inferior vena cava (cIVC), the sensitivity and specificity values were 0.92 (95% CI 0.83, 0.96) and 0.93 (95% CI 0.86, 0.97), respectively.

The results indicated that ∆IVC is as a dependable marker for fluid responsiveness in sepsis patients. dIVC and cIVC also exhibited high levels of accuracy in predicting fluid responsiveness in septic patients.

Identification of prognostic biomarkers for critical illness are essential to improving mortality in the context of precision medicine. The purpose of this study was to evaluate the prognostic value of interleukin-6 (IL-6) and platelet-derived growth factor AA(PDGF-AA) in predicting 28-day mortality in critically ill patients.

199 critically ill patients were recruited from the emergency department of the Beijing Chaoyang Hospital, Capital Medical University, between October 2020 and April 2021. IL-6, PDGF-AA and other markers were tested immediately, and the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated within 24h of admission to the emergency department. Patients were divided into survival and non-survival groups according to clinical outcomes for 28 days. The quantitative detections of IL-6 and PDGF-AA were performed using the Luminex assay. Spearman correlation, logistic regression, and receiver operating characteristic curve (ROC) analyses were conducted for comparison.

Among 199 patients, 139 died and 60 survived within 28 days, IL-6 and PDGF-AA levels were higher in the non-survival group (P<0.05). IL-6 levels correlated with PDGF-AA levels in the non-survival group (P<0.001). IL-6 and PDGF-AA were independent predictors off 28-day mortality in critically ill patients (OR=1.003, 1.002). Combination of IL-6 and SOFA can make an AUROC of 0.892 with a specificity of 91.4%. Combination of IL-6, PDGF-AA and SOFA can make an AUROC of 0.905 with a specificity of 91.5%.

This study highlights the importance of monitoring serum levels of IL-6 and PDGF-AA in critically ill patients. Compared with the marker alone, combinations with other conventional risk factors have better predictive values.

The aim of the study was to develop and validate an algorithm based on procalcitonin (PCT) monitoring to predict the prognosis of patients with sepsis.

The design was a retrospective and observational prospective study.

The study was set in intensive care units (ICUs) in 2 different hospitals in Spain.

Patients in the study included 101 patients with sepsis aged ≥18 years.

In the retrospective study, PCT results from patients admitted to the ICU in 2011-2012 were collected. In the prospective study, PCT was determined at specific time points as indicated by the algorithm from March 2018 to April 2019. The primary outcome measure, 28-day mortality, was the main variable of interest.

The study developed an algorithm based on early PCT monitoring for predicting the prognosis of patients with sepsis. The algorithm was initially developed retrospectively in 1 cohort and subsequently validated prospectively in another cohort.

The developed algorithm provides information on the prognosis of patients with sepsis, distinguishing between those with a good prognosis and those with a poor prognosis (defined as mortality).

Bloodstream infections frequently cause sepsis, a condition that can lead to organ dysfunction and death. Rapid antimicrobial susceptibility testing (AST) results are critical for appropriate medical intervention and to either de-escalate or escalate antibiotics to appropriate therapy. We describe the results from a multicenter clinical study evaluating the performance of the eQUANT system (Avails Medical, Inc., Menlo Park, CA). The eQUANT system generates a 0.5 McFarland equivalent suspension, the eMcFarland, directly from a positive blood culture bottle for use with downstream disk diffusion AST, thereby saving up to 24 hours compared to traditional AST workflow. A combination of fresh, prospectively collected clinical (42) and contrived (525) blood cultures were tested, and results for disk diffusion using the Avails eQUANT eMcFarland suspension as the inoculum were compared to disk diffusion results the next day using the standard 0.5 McFarland suspension prepared from plate subculture. Thirteen species of gram-negative rods were evaluated against 12 antibiotics. From the 2,679 pairs of AST results, overall categorical agreement was 95.0%. Overall very major errors, major errors, and minor errors were 0.15%, 0.60%, and 4.48%, respectively. The Avails eQUANT system has the potential to significantly accelerate the standard of care by eliminating the need for subculture.IMPORTANCERapid reporting of antimicrobial susceptibility test results for bacterial isolates from blood cultures is critical for timely implementation of optimal antimicrobial therapy and improves outcomes of sepsis patients. In this study, we demonstrate the accuracy and performance characteristics of the eQUANT system, which generates a 0.5 McFarland equivalent suspension, the eMcFarland, directly from a positive blood culture bottle for use with downstream disk diffusion antimicrobial susceptibility testing (AST). Using the eMcFarland suspension allows for accurate and standardized reporting of disk diffusion AST results from positive blood cultures.

This study aimed to investigate the effects of lidocaine on sepsis-induced acute lung injury and its underlying mechanisms.

Thirty C57BL/6 mice were divided into three groups: SHAM, CLP, and LD. The sepsis-induced acute lung injury model was established using cecal ligation and puncture (CLP) surgery, while SHAM mice underwent a sham operation without ligation or puncture. Mice in the LD group were administered lidocaine (10 mg/kg) intravenously through the tail vein. The SHAM and CLP groups were treated with an equal volume of 0.9% sterile saline solution. All mice were sacrificed 24 hours after surgery, and lung tissue and blood samples were collected for subsequent analysis. The wet/dry weight ratio (W/D ratio) was measured to evaluate lung edema. Lung injury and apoptosis were assessed using HE staining and TUNEL assay. The concentrations of inflammatory cytokines IL-6, TNF-α, and HMGB1 were measured by ELISA. The expression of JAK2, STAT3, p-STAT3, Bcl-2, HMGB1, and Bax was analyzed by western blot.

The W/D ratio in the CLP group was significantly higher than the SHAM group, indicating increased lung edema. Pathological examination revealed obvious lung injury, and apoptosis was evident in the CLP group. The expression of HMGB1, IL-6, and TNF-α in lung tissue increased by 24 hours after CLP surgery. Additionally, the levels of JAK2, STAT3, p-STAT3, HMGB1, and Bax were significantly increased, while Bcl-2 expression was reduced. However, lidocaine administration reversed these changes.

Intravenous lidocaine effectively alleviated acute lung injury in septic mice. The anti-inflammatory effects of lidocaine may be attributed to its suppression of the JAK2/STAT3 signaling pathway and its anti-apoptotic effects.

This study aims to investigate the relationship between the triglyceride-glucose (TyG) index in patients with early sepsis-associated acute kidney injury (SA-AKI) and the risk of in-hospital mortality.

Secondary data analysis.

This study analysed secondary data from the Medical Information Mart for Intensive Care (MIMIC) 2008-2022.

A total of 1632 participants were enrolled in the final analysis.

A secondary data analysis study was conducted using data from the MIMIC IV 3.0 database. Participants were divided into four groups based on the quartiles of the TyG index. The primary outcome was all-cause in-hospital mortality. The association between the TyG index and in-hospital mortality among SA-AKI patients was assessed using multivariate COX proportional hazards regression analysis and restricted cubic spline regression analysis. Subgroup and sensitivity analyses were performed to verify the robustness of results.

A total of 1632 patients were included in the study. The in-hospital mortality rate was 31.13%, and the intensive care unit (ICU) mortality rate was 25.25%. Multivariate COX regression analysis showed that the TyG index was independently associated with an increased risk of in-hospital mortality (HR 1.14 (95% CI 1.02 to 1.27); p=0.02) and ICU mortality (HR 1.17; (95% CI 1.04 to 1.32); p=0.01). The restricted cubic spline regression model indicated that the risk of in-hospital and ICU mortality increased linearly with the increase in the TyG index. Sensitivity analysis demonstrated that the effect size and direction were consistent across different subgroups, and the results were stable.

A high TyG index is associated with increased mortality during hospitalisation in patients with SA-AKI. Larger-scale prospective studies are needed to confirm these findings.

Predicting fluid responsiveness is challenging in infants. It is however crucial to avoid unnecessary volume expansion, which can lead to fluid overload. We tested the hypothesis that the stroke volume changes induced by a calibrated abdominal compression (ΔSV-AC) could predict fluid responsiveness in infants without cardiac disease.

This prospective single center study of diagnostic test accuracy was conducted in a general pediatric intensive care unit (PICU). Children under the age of two with acute circulatory failure and requiring a 10 mL.kg-1 crystalloid volume expansion over 20 min, ventilated or not ventilated, were eligible. Stroke volume was measured by transthoracic echocardiography at baseline, during a gentle calibrated abdominal compression (22 mmHg for 30 s), and after volume expansion. The area under the receiver operating characteristic curve (AUROC) of ΔSV-AC was measured to predict fluid responsiveness, defined as a 15% stroke volume increase after volume expansion.

Twenty-seven cases of volume expansion were analyzed, in 21 patients. Seventeen VE cases were administrated to spontaneously breathing children. Fluid responsiveness was observed in 12 cases. The AUROC of ΔSV-AC was 0.93 (95% confidence interval (95%CI) 0.82-1). The best threshold value for ΔSV-AC was 9.5%. At this threshold value, sensitivity was 92% (95%CI 62-100), specificity was 87% (95%CI 60-98), positive and negative predictive values were 85% (95%CI 60-95) and 93% (95%CI 66-99) respectively.

Echocardiographic assessment of stroke volume changes induced by a calibrated abdominal compression is a promising method to predict fluid responsiveness in infants without cardiac disease hospitalized in PICU.

ClinicalTrials.gov registration number NCT05919719, June 22, 2023, retrospectively registered, https://clinicaltrials.gov/study/NCT05919719 .

Sepsis is a disease affecting microcirculation, reflected in temperature changes between the core and the skin. This study explores correlation of this gradient using infrared thermography (IRT) with mortality and markers of hypoperfusion in patients admitted with sepsis and septic shock and its changes with resuscitation.

We conducted a prospective, single center observational study on patients admitted in the Department of Emergency Medicine of a tertiary care center in Karnataka, India. These patients were enrolled based on the inclusion criteria and infrared thermography was performed and cases were followed up after 28 days. Adults presenting to the emergency medicine department with clinically suspected sepsis or septic shock were enrolled and infrared thermography was performed. A final sample size of 187 cases was analyzed after retrospectively excluding patients with any exclusion criteria.

Patients underwent thermal imaging of all four limbs on arrival and after 3  hours of resuscitation. Core temperature was measured using a tympanic thermometer. Infrared thermography was performed, and limb temperature was extracted from the images. Other parameters including mean arterial pressure and lactate were recorded and SOFA score was calculated.

The temperature gradients were correlated with 7 and 28-day mortality along with markers of hypoperfusion including mean arterial pressure and serum lactate levels.

A total of 187 patients were included, with a mean SOFA score of 5. Forty four patients (23.5%) died within 7-days. 28-day mortality was 31%. Temperature gradients of core to knee > 8.85°F (p = 0.003) and core to great toe > 12.25°F (p = 0.020) on arrival were found to be correlated with 7-day mortality. Core to knee temperature gradient was found to correlate with 48-hour mortality(p < 0.013). Core to index finger gradient on arrival correlated with vasopressor requirement within 48h (p = 0.020). Core to index finger temperature gradient had a negative correlation with mean arterial pressure (spearman coefficient - 0.286, p = < 0.001), and a positive correlation with lactate (0.281, p = < 0.001), SOFA score (0.242, p = 0.001), qSOFA score (0.167, p = 0.023).

Core-to-knee and core-to-toe temperature gradients using IRT significantly correlate with 7-day mortality. IRT can be a useful adjunct to predict clinical courses in patients with sepsis and septic shock.

Sepsis, septic shock, and cardiogenic shock are life-threatening conditions associated with high mortality rates, but differentiating them is complex because they share certain symptoms. Using the Medical Information Mart for Intensive Care (MIMIC)-III database and artificial intelligence (AI), we aimed to increase diagnostic precision, focusing on Bayesian network classifiers (BNCs) and comparing them with other AI methods. Data from 5970 adults, including 950 patients with cardiogenic shock, 1946 patients with septic shock, and 3074 patients with sepsis, were extracted for this study. Of the original 51 variables included in the data records, 12 were selected for constructing the predictive model. The data were divided into training and validation sets at an 80:20 ratio, and the performance of the BNCs was evaluated and compared with that of other AI models, such as the one rule classifier (OneR), classification and regression tree (CART), and an artificial neural network (ANN), in terms of accuracy, sensitivity, specificity, precision, and F1-score. The BNCs exhibited an accuracy of 87.6% to 91.5%. The CART model demonstrated a notable 91.6% accuracy when only three decision levels were used, whereas the intricate ANN model reached 90.5% accuracy. Both the BNCs and the CART model allowed clear interpretation of the predictions. BNCs have the potential to be valuable tools in diagnostic tasks, with an accuracy, sensitivity, and precision comparable, in some cases, to those of ANNs while demonstrating superior interpretability.

The optimal timing for initiating norepinephrine in septic shock is debated. This updated systematic review and meta-analysis aimed to evaluate the impact of early versus delayed norepinephrine initiation on mortality and clinical outcomes in adults with septic shock.

A systematic search in Pubmed, EMbase and the Cochrane Library to identify eligible randomized controlled trials, propensity score matching (PSM) and observational studies that compare early norepinephrine initiation with non-early norepinephrine initiation in patients with acute circulatory failure. The primary outcome was mortality in intensive care unit. Secondary outcomes included intensive care unit length of stay, fluid volume received at 6 h, norepinephrine dose, mechanical ventilation-free days, renal replacement therapy free days, and time to achieve a targeted mean arterial pressure (MAP). Meta-analysis and subgroup analysis were conducted to calculate odds ratio (OR) or mean difference with 95% confidence interval (95%CI) using random-effect model. Trial sequential analysis was conducted to evaluate the conclusiveness of evidence.

Ten studies (two RCT, three PSM and five observational studies) involving 4767 patients were included. Early norepinephrine significantly reduced mortality in RCT (OR 0.49, 95%CI 0.25-0.96; I2 = 45%, p = 0.04), pooled RCT and PSM (OR 0.65, 95%CI 0.42-0.99; I2 = 74%, p = 0.05), and observational studies (OR 0.71, 95%CI 0.54-0.94; I2 = 66%). The trial sequential analysis indicated more data are needed. Subgroup analyses showed reduced mortality with early norepinephrine when lactate was ≤ 3mmol/L and administered within 1 h. Secondary outcomes showed a reduced fluid volume at 6h (RCT + PSM: mean difference -502 mL, 95%CI -899 to -106; I2 = 91%, p = 0.01), faster MAP target achievement (RCT + PSM: mean difference -1.30h, 95%CI -1.75 to -0.85; I2 = 0%, p < 0.01), more mechanical ventilation-free days (RCT + PSM: mean difference 3.99 days, 95%CI 2.42-5.57; I2 = 32%, p < 0.01) and smaller cumulative norepinephrine dose (Observational: mean difference -3.44 mcg/kg, 95%CI -6.13 to -0.76; I2 = 0%, p = 0.01) in the early initiation group compare to the non-early initiation group.

Early norepinephrine introduction in septic shock is associated with reduced mortality, decreased fluid volume administered at 6 h, faster time to achieve MAP target and more mechanical ventilation-free days. However, the trial sequential analysis indicates that further RCT are still needed to confirm these findings.

Purpose: Peripheral intravenous catheter (PIVC)-administered noradrenaline offers faster treatment for septic shock but risks complications like phlebitis. We aimed to investigate the relationship between the total noradrenaline dose administered via PIVCs and the development of phlebitis by considering the influence of noradrenaline as a time-dependent covariate. Methods: A post hoc analysis was conducted on prospective multicenter cohort data from 23 intensive care units in Japan. The total noradrenaline dose was included as a time-dependent variable in a multilevel Cox regression model, and smoothing splines assessed nonlinear relationships. The primary endpoint was phlebitis. Directed acyclic graphs were used to define confounding factors for the analysis. Results: The analysis included 3410 PIVCs from 1351 patients, with noradrenaline administered to 70 patients (5.2%) with 91 PIVCs (2.6%). The median dwell time and interquartile range of PIVCs was 46.2 h (21.3-82.9). No significant association was observed between the total noradrenaline dose and the occurrence of phlebitis through analysis using the multilevel Cox regression model with time-dependent covariate, which assumed the linear relationship between phlebitis occurrence and the total noradrenaline dose (hazard ratio 1.06, 95% confidence interval [CI] 0.93-1.20). Spline curve analysis suggested a nonlinear relationship between the total noradrenaline dose and phlebitis, and the risk of phlebitis increased when the total administered dose of noradrenaline exceeded 6 mg as the lower limit of the 95% CI exceeded the significant threshold of 1.0. Sensitivity analyses, including additional potential risk factors, showed consistent results compared with those of the primary analysis. Conclusions: Administering noradrenaline within a total dose not exceeding 6 mg reduces the risk of phlebitis, potentially allowing safer administration through PIVCs. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR): UMIN000028019.

Acute circulatory failure plays a major role in the development of sepsis-related organ dysfunction. Current 'bundles' of the Surviving Sepsis Campaign (SSC) include the administration of a fluid loading of 30 mL/kg in the presence of hypotension within the first hour of sepsis identification. The impact of haemodynamic assessment using echocardiography at the early phase of management of septic patients in the Emergency Department (ED) on patient-centred outcomes is unknown.

This is a two-parallel arm randomised trial with blinded assessment comparing early haemodynamic assessment using transthoracic echocardiography aimed at guiding therapeutic management to standard of care according to current SSC recommendations in septic patients during initial management in 13 French EDs. Patients with suspected or documented infection and a qualifying quick Sequential Organ Failure Assessment (qSOFA) score (haemodynamic criterion required: systolic blood pressure≤100 mm Hg) will be 1:1 randomised after 500 mL of fluid loading initiation. In the intervention group, echocardiography will allow identifying the haemodynamic profile at the origin of sepsis-induced circulatory failure and monitoring the efficacy and tolerance of fluid resuscitation, or of any other therapeutic intervention according to a predefined therapeutic algorithm. The control group will receive conventional 30 mL/kg fluid resuscitation (unless pulmonary venous congestion) according to SSC recommendations. Primary outcome will be the course of organ dysfunction assessed by the crude change in the modified SOFA score between baseline and 24 hours after randomisation. Secondary outcomes will be the nature of therapeutic interventions resulting from echocardiography (fluid loading, early initiation of vasopressor support or inotrope), the prevalence of the different haemodynamic profiles, the evolution of lactatemia, the safety of the initial therapeutic, the proportion of patients who develop secondarily septic shock, the orientation of patients after ED discharge and both day 7 and in-hospital mortality. We plan to randomise 312 patients.

Approved by the Ethics Committee CPP Ouest V on 18 January 2021 (ref: 20/075-2-20.10.16.57638). The dissemination plan includes presentations at scientific conferences and publication of results in a peer-reviewed journal.

NCT04580888.