Septic Shock Patients Research Articles

Septic shock in the prehospital setting: a scoping review.

Septic shock (SS) is a potential life-threatening condition in which an early identification and immediate therapy stand out as the main cornerstones to improve survival chance; in this context, emergency medical services (EMS) become key to reduce the time between diagnosis and management in the ICU or emergency department. However, guidelines for the prehospital management of SS patients remains unclear, and literature around this topic is scant. Our scoping review was conducted following the PICO framework and a search strategy related to septic shock management and diagnosis in prehospital settings was executed in PubMed, Scopus and Virtual Health Library; articles in English and Spanish from 2015, onwards, were screened by the authors and selected by mutual consensus. Our aim is to analyze the prehospital management strategies of SS reported in the literature, and to showcase and summarize the screening tools, demographic factors, clinical manifestations and prognostic factors of SS in the prehospital setting.

Abstract 4119250: Partial versus Full ECMO Support in Combined Cardiogenic and Septic Shock – ELSO Registry Analysis

Background: There remains paucity of data on patient outcomes with combined cardiogenic and septic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. While guidelines exist on target VA-ECMO flow in cardiogenic shock patients, optimal (partial versus full) flow in combined shock remains largely unknown. Methods: We queried the Extracorporeal Life Support Organization registry to identify patients in combined cardiogenic and septic shock supported with VA-ECMO between 2017 and 2022. Patients were categorized into either partial or full ECMO support based on ECMO flow at 24 hours indexed to body surface area. Partial support was defined as < 2.2 liters/m2 while full support was ≥2.2 liters/m2. Patients with other forms of mechanical circulatory support, VA-ECMO as bridge to advanced therapies or discharged on VA-ECMO were excluded from the analysis. Primary outcome of interest was survival to discharge. Baseline characteristics including center volumes and Charlson co-morbidity index were compared between survivors and non survivors. Predictors of mortality were identified using multivariable logistical regression model. Results: A total of 452 patients with combined shock supported with VA-ECMO were identified. Overall mortality was 63%. Patients that survived to discharge were younger (46.3 vs 53 years, p < 0.001) and had lower BMI (29.3 vs 31.1, p = 0.041), Charlson co-morbidity index (1.4 vs 2.0, p = 0.01) and rates of pre-ECMO cardiac arrest (28.7% vs 39.4%, p = 0.023). Survivors were also more likely to be at high [> 25 ECMO runs per year] volume centers compared to low [≤ 10 ECMO runs per year] volume centers (62.3% vs 20.4%, p = 0.04). Patients receiving full ECMO support had a higher likelihood of survival to discharge than partial support (42.6% vs 33.8%, p = 0.063), although it did not reach statistical significance. [Table 1] Indexed VA-ECMO flow at 24 hours was also associated with improved outcomes when assessed as continuous variable. [ Figure 1] Advanced age [aOR 1.02, 95% CI 1.01-1.04, p < 0.001], pre-ECMO cardiac arrest [aOR 1.71, 95% CI 1.11-2.65, p = 0.016] and baseline Charlson co-morbidity index [aOR 1.13, 95% CI 1.01-1.28, p = 0.043] were all associated with increased mortality after adjustment for baseline differences. Conclusion: Mortality among patients requiring VA-ECMO for combined cardiogenic and septic shock is high. Full circulatory support may be associated with improved survival in this cohort.

Evaluation of Severe ultrasound and gene diagnosis in cardiac index and shock patient index of shock patients.

The kidney is the most vulnerable organ in severe patients. In severe cases, the fatality rate of acute kidney damage is as high as 30% ∼ 60%. Severe ultrasound is a non-invasive method to evaluate renal blood flow. It can give a semi-quantitative score of renal blood flow and measure the Resistance Index (RI), which can reflect renal artery blood flow to a certain extent. There is little literature on hemodynamic regulation in septic shock patients, but almost no research report on the relationship between hemodynamics and RI exists. Therefore, this paper proposed the analysis of severe ultrasound and gene diagnosis in cardiac index and peripheral vascular RI of shock patients. This paper mainly expounded on detecting renal function parameters and RI in patients with viral shock to understand further the correlation between them and renal flow and RI. It could be seen from the experimental results that the P values before and after resuscitation in the two groups with and without elevated Cardiac Output (CO) were 0.41 and 0.12, respectively, which were more significant than 0.05. RI had no apparent relationship with CO, and RI could not be used as an evaluation index for patients with early septic shock.

PP143 Topic: AS14–Infections: Sepsis and Septic Shock/Antimicrobial Stewardship/Tropical and Parasite Infections/Other: RISK FACTORS ASSOCIATED TO MORTALITY IN SEPTIC SHOCK PATIENTS WHEN ADMITED TO A PEDIATRIC INTENSIVE CARE UNIT.

PP143 Topic: AS14–Infections: Sepsis and Septic Shock/Antimicrobial Stewardship/Tropical and Parasite Infections/Other: RISK FACTORS ASSOCIATED TO MORTALITY IN SEPTIC SHOCK PATIENTS WHEN ADMITED TO A PEDIATRIC INTENSIVE CARE UNIT.

Nursing Care for Septic Shock Patients Using Indonesian Nursing Standards: A Case Reports

Aims: This case report aimed to identify gaps in applying the Nursing Standard Guidelines of the Indonesian Association in critical care, specifically focusing on patients with septic shock. Methods: This study used a case report with a nursing care approach that includes an assessment to evaluation. Nursing care was provided to a patient who was experiencing septic shock, was on a ventilator, and had experienced organ failure. Results: A 63-year-old man on mechanical ventilator was diagnosed with septic shock caused by community-acquired pneumonia. The nursing diagnoses for this case included impaired spontaneous ventilation related to respiratory muscle weakness, ineffective airway clearance related to the accumulation of secretions, peripheral tissue perfusion disorders related to changes in fluid regulation, and risk of infection. The study identified inappropriate nursing diagnoses, such as 'impaired spontaneous ventilation for patients on mechanical ventilation. Conclusion: This study concludes that there are still several gaps in diagnosing and managing clinical conditions in critical cases. The nursing problem of impaired spontaneous ventilation should not have been identified as the patient was already on a ventilator. Additionally, there was no actual diagnosis for impaired organ perfusion or infection. This case report recommends further developing the Nursing Standard Guidelines of the Indonesian Nursing Association to optimize coverage of critical care. Recommendations include revising the Indonesian Nursing Diagnosis Standards to align with critical care needs. This enhancement will help nurses and clinicians in critical care not experience confusion when applying the current guidelines.

Reevaluating vitamin C in sepsis and septic shock: a potential benefit in severe cases?

Vitamin C (Ascorbic acid) has evolved as an emergent co-intervention for sepsis and septic shock patients. Multiple studies discussed the pathophysiological value of vitamin C to reserve endothelial functionality and improve microcirculatory flow in these patients. Nevertheless, most randomized clinical trials failed to show the clinical impact of adding vitamin C to sepsis and septic shock. Pneumonia is the most common infection to induce sepsis and septic shock, which could be an acute respiratory distress syndrome. Preliminary in-vitro data support the role of vitamin C in mitigating the risk of acute respiratory distress syndrome (ARDS) development. This review aims to compare and contrast these trials and explore differences in their patients' populations, methodologies, and outcomes, emphasizing pneumonia-induced sepsis and septic shock.

Proprotein Convertase Subtilisin Kexin 9 Inhibitor in Severe Sepsis and Septic Shock Patients in a Phase II Prospective Cohort Study—Preliminary Results

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection that has a high mortality rate. Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease secreted by the liver. Its binding to the low-density lipoprotein (LDL) receptor enhances its degradation, causing an increase in LDL levels in the blood. Objectives: Administering a PCSK9 inhibitor leading to an increase in lipid uptake by the liver may positively affect septic patients due to the increased removal of endotoxins. Methods: This preliminary study aimed to examine the safety of PCSK9 inhibitor use in septic and septic shock patients. We treated five septic patients in the intensive care unit with 300 mg of alirocumab following serious adverse events for 28 days. Results: Four of our patients did not experience any adverse events, and all of them survived. One patient died after discharge from the intensive care unit, and this death was presumably not related to the study drug. The patients rapidly recovered from the inflammatory stage of sepsis. Conclusions: Alirocumab appears safe in severe sepsis and septic shock patients. The outcome data are promising. Only a basic safety profile can be assessed based on this pilot study. Further study with a PCSK-9 inhibitor in septic or septic shock patients is required to further determine its benefit in ICU patients.

Identifying septic shock subgroups to tailor fluid strategies through multi-omics integration

Fluid management remains a critical challenge in the treatment of septic shock, with individualized approaches lacking. This study aims to develop a statistical model based on transcriptomics to identify subgroups of septic shock patients with varied responses to fluid strategy. The study encompasses 494 septic shock patients. A benefit score is derived from the transcriptome space, with higher values indicating greater benefits from restrictive fluid strategy. Adherence to the recommended strategy is associated with a hazard ratio of 0.82 (95% confidence interval: 0.64–0.92). When applied to the baseline hospital mortality rate of 16%, adherence to the recommended fluid strategy could potentially lower this rate to 13%. A proteomic signature comprising six proteins is developed to predict the benefit score, yielding an area under the curve of 0.802 (95% confidence interval: 0.752–0.846) in classifying patients who may benefit from a restrictive strategy. In this work, we develop a proteomic signature with potential utility in guiding fluid strategy for septic shock patients.

Factors Promoting Lipopolysaccharide Uptake by Synthetic Lipid Droplets.

Lipoproteins are essential in removing lipopolysaccharide (LPS) from blood during bacterial inflammation. The physicochemical properties of lipoproteins and environmental factors can impact LPS uptake. In this work, synthetic lipid droplets containing triglycerides, cholesterols, and phospholipids, were prepared to mimic lipoproteins. The physicochemical properties of these lipid droplets, such as charges, sizes, and lipid compositions, were altered to understand the underlying factors affecting LPS uptake. The amphiphilic LPS could spontaneously adsorb on the surface of lipid droplets without lipopolysaccharide binding protein (LBP); however, the presence of LBP can increase LPS uptake. The positively charged lipid droplets also enhance the uptake of negatively charged LPS. Most interestingly, the LPS uptake highly depends on the concentrations of Ca 2+ near the physiological conditions, but the impact of Mg 2+ ions was not significant. The increase of Ca 2+ ions can improve LPS uptake by lipid droplets; this result suggested that Ca 2+ may play an essential role in LPS clearance. Since septic shock patients typically suffer from hypocalcemia and low levels of lipoproteins, the supplementation of Ca 2+ ions along with synthetic lipoproteins may be a potential treatment for severe sepsis.

The association between integrating echocardiography use in the management of septic shock patients and outcomes in the intensive care unit: a systematic review and meta-analysis.

Septic shock in critically ill patients can increases morbidity and mortality. We aimed to study the effect on outcomes when integrating point of care (POC) echocardiography in the management of septic shock patients in the Intensive Care Unit (ICU) who are being treated according to the Surviving Sepsis Campaign (SSC) guidelines. An electronic search of MEDLINE through PubMed, clinical trials.gov and google scholar was conducted for the period from January 1990-January 2024 to identify studies of septic shock adult and pediatric patients in the ICU managed according to SSC guidelines with or without POC echocardiography. Three reviewers extracted data independent of each other. Cochrane collaboration tool was used for bias assessment. Random effect meta-analysis used to pool data. A total of 1701 articles identified. Seven studies included in the final report with a total of 3885 patients. POC echocardiography guided septic shock management was associated with lower in-hospital and 28-day mortality (sOR = 0.82 [95%CI: 0.71-0.95], p = 0.01), more frequent initiation of inotropic support (sOR = 2.42 [95%CI 1.92-3.03], p < 0.0001) and shorter time to achieve lactate clearance (SMD = - 0.87h [95%CI - 1.23h to - 0.51h], p < 0.0001). Summary estimates did not achieve significance for effect of POC echocardiography on 24-h fluid intake (SMD = - 2.11ml [95%CI - 5.93ml to 1.72ml], p = 0.28) on mechanical ventilation-free days (SMD = 0.03days [95%CI - 0.04 to 0.10], p = 0.94). Shock reversal time analysis was less meaningful due to the small number of studies reporting outcome. POC echocardiography guided management in septic shock patients in the ICU can lead to a decrease in mortality, increase in initiation of inotropic support, and a decrease in lactate clearance time. Larger cohort studies and data collection and analysis are needed for further understanding and optimizing standardization of protocols for POC echocardiography use in septic shock patients in the ICU.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Surviving Sepsis Campaign guideline update:problems and progress

Sepsis is a clinical syndrome, the core of which is the disorder of the host's response to infection. Sepsis progresses to septic shock, which can lead to increased mortality, so early identification and standardized management are particularly important. Over the past 30 years, the definition of septic shock has gradually changed, with efforts to improve the identification and screening of early septic shock, and to emphasize the importance of organ dysfunction in patients with septic shock. The birth of the rescue systemic infection movement has played an important role in the management of septic shock patients. Although the cluster management of septic shock patients has reduced the overall mortality of septic shock patients, the management still faces many challenges. How to provide personalized treatment to patients, especially some controversial treatments, is still a major area for us to consider and explore.

Early Mortality Stratification with Serum Albumin and the Sequential Organ Failure Assessment Score at Emergency Department Admission in Septic Shock Patients.

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

Immunometabolic Chaos in Septic Shock.

Septic shock is associated with over 40% mortality. The immune response in septic shock is tightly regulated by cellular metabolism and transitions from early hyper-inflammation to later hypo-inflammation. Patients are susceptible to secondary infections during hypo-inflammation. The magnitude of the metabolic dysregulation and the effect of plasma metabolites on the circulating immune cells in septic shock are not reported. We hypothesized that the accumulated plasma metabolites affect the immune response in septic shock during hypo-inflammation. Our study took a unique approach. Using peripheral blood from adult septic shock patients and healthy controls, we studied: 1. Whole blood stimulation ± E. Coli lipopolysaccharide (LPS: endotoxin) to analyze plasma TNF protein, and 2. Plasma metabolomic profile by Metabolon. Inc. 3. We exposed peripheral blood mononuclear cells (PBMCs) from healthy controls to commercially available carbohydrate, amino acid, and fatty acid metabolites and studied the response to LPS. We report that: 1. The whole blood stimulation of the healthy control group showed a significantly upregulated TNF protein, while the septic shock group remained endotoxin tolerant, a biomarker for hypo-inflammation. 2. A significant accumulation of carbohydrate, amino acid, fatty acid, ceramide, sphingomyelin, and TCA cycle pathway metabolites in septic shock plasma. 3. In vitro exposure to five metabolites repressed while two metabolites upregulated the inflammatory response of PBMCs to LPS. We conclude that the endotoxin-tolerant phenotype of septic shock is associated with a simultaneous accumulation of plasma metabolites from multiple metabolic pathways, and these metabolites fundamentally influence the immune response profile of circulating cells.

Effect of timing of intubation on clinical outcomes of patients with septic shock: a retrospective cohort study.

Evidence-based data regarding the timing of the application of invasive mechanical ventilation among adults with septic shock is insufficient. The guidelines fail to provide clear advice about the optimal time to initiate this support. Consequently, we aimed to investigate whether early intubation could improve survival rates in septic shock patients. We conducted a retrospective analysis of the MIMIC-IV database to evaluate the effectiveness of early intubation on mortality in a cohort of septic shock patients. Adults diagnosed with septic shock, according to the Sepsis-3 definition, were included. They were categorized into an early intubation group (first 8h after vasopressor initiation) and a non-early intubation group (unexposed). A propensity score matching (PSM) analysis was used to balance the baseline characteristics between the two groups. The primary outcomes were 30-day and 90-day all-cause mortality rates. In addition, we employed the restricted cubic spline to analyze the potential non-linear relationship between the timing of intubation and 30-day or 90-day all-cause mortality. A total of 6864 adult patients, of whom 2048 were intubated in the first 8h, were evaluated in the final cohort. Following a 1:1 PSM procedure, 2786 patients were successfully paired. At 30days, 288 of 1393 patients (20.7%) in the early intubation group and 381 of 1393 patients (27.4%) in the non-early intubation group had died (hazard ratio [HR] 0.717; 95% confidence interval [CI] 0.616-0.836; p < 0.001). Similarly, the results also showed that early intubation was associated with a lower 90day all-cause mortality rate (HR 0.761; 95% CI 0.663-0.874; p < 0.001). Furthermore, ICU and hospital lengths of stay were significantly different between the groups (3.6 [1.9, 7.1] vs. 2.3 [1.3, 4.3]; p < 0.001 and 8.9 [5.4, 15.1] vs. 7.2 [4.5, 12.0]; p < 0.001). In the subgroup analysis, we further confirmed the robustness of our findings. Additionally, we found that the timing of intubation is inversely U-shaped correlated to the 30day all-cause mortality rate. Among adult patients with septic shock, the early initiation of invasive mechanical ventilation could improve clinical outcomes. The timing of intubation demonstrated an inverse U-shaped association with the 30day all-cause mortality rate, with the peak risk of death occurring at 50.5h after septic shock.

Efficacy of methylene blue in refractory septic shock: study protocol for a multicenter, randomized, placebo-controlled trial

BackgroundSeptic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors.MethodsThis study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors.DiscussionThis protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making.Trial registrationThis clinical trial has been registered at ChiCTR (https://www.chictr.org.cn/) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

Corticosteroids for Managing Pediatric Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

Biomarkers as Predictors of Mortality in Sepsis and Septic Shock for Patients Admitted to Emergency Department: Who Is the Winner? A Prospective Study

Background/Objectives: Sepsis and septic shock remain significant contributors to high early mortality rates among patients admitted to the emergency department (ED). The objective of this study was to identify among newer biomarkers those with the highest sensitivity in early mortality prediction. Methods: This prospective, unicentric, observational study enrolled 47 adult patients admitted to the ED between November 2020 and December 2022. This study monitored the kinetics of the older and newer biomarkers, including azurocidin (AZU1), soluble triggering receptor expressed on myeloid cells (sTREM), soluble urokinase-type plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6), and their capacity in predicting mortality. Results: SuPAR showed the most significant predictive utility for early prognosis of mortality in the ED, with an area under the curve (AUC) of 0.813 (95% CI: 0.672 to 0.912), a cutoff value &gt; 8168 ng/mL, sensitivity of 75%, and specificity of 81.48% (p &lt; 0.001). IL-6 and PCT showed comparable prognostic accuracy, whereas hsCRP and AZU1 demonstrated lower predictive performance. Conclusions: In our study, suPAR, IL-6, and PCT showed good predictive value for short-term mortality in sepsis and septic shock patients.

Visualizing the assumptions of network meta-analysis.

Network meta-analysis (NMA) incorporates all available evidence into a general statistical framework for comparing multiple treatments. Standard NMAs make three major assumptions, namely homogeneity, similarity, and consistency, and violating these assumptions threatens an NMA's validity. In this article, we suggest a graphical approach to assessing these assumptions and distinguishing between qualitative and quantitative versions of these assumptions. In our plot, the absolute effect of each treatment arm is plotted against the level of effect modifiers, and the three assumptions of NMA can then be visually evaluated. We use four hypothetical scenarios to show how violating these assumptions can lead to different consequences and difficulties in interpreting an NMA. We present an example of an NMA evaluating steroid use to treat septic shock patients to demonstrate how to use our graphical approach to assess an NMA's assumptions and how this approach can help with interpreting the results. We also show that all three assumptions of NMA can be summarized as an exchangeability assumption. Finally, we discuss how reporting of NMAs can be improved to increase transparency of the analysis and interpretability of the results.

The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study.

Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality. A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality. A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation. The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.