Septic Shock Research Articles

Managing Necrotizing Soft-Tissue Infection in Breast Cancer: A Case of Emergency Toilet Mastectomy.

BACKGROUND This case report presents a rare instance of advanced breast cancer presenting with superimposed necrotizing soft-tissue infection (NSTI) and sepsis, uniquely managed with an emergency toilet mastectomy. Toilet mastectomies have become increasingly rare and controversial in modern surgical oncology and are generally limited to palliative indications. This report contributes to the limited literature on NSTI of the breast in the setting of malignancy and highlights the potential utility of toilet mastectomy as a palliative option for carefully selected patients with advanced breast cancer complicated by infection. CASE REPORT A 71-year-old woman presented with a large fungating right breast mass after 50 years of receiving no health care. She was septic, with clinical signs of NSTI. Emergency surgical intervention involved a toilet mastectomy with extensive debridement. Histopathological analysis confirmed high-grade invasive ductal carcinoma of the breast with skin involvement, ER/PR-positive, HER2-negative, pT4bN0Mx. Cultures were consistent with type 1 NSTI. The postoperative course was complicated, requiring prolonged ICU care, multiple debridements, and advanced wound management. Significant complications included septic shock, acute kidney injury, and wound dehiscence. CONCLUSIONS This case is notable for 3 key aspects: (1) NSTI and sepsis are rare but serious complications of advanced breast cancer, underscoring the need for clinicians to maintain a high index of suspicion for this condition; (2) timely and aggressive management of NSTI, regardless of its association with underlying malignancy, is critical for reducing morbidity and mortality; and (3) toilet mastectomy, although less commonly performed today, remains an appropriate palliative intervention in select cases.

Empyema after radiation therapy for cutaneous squamous cell carcinoma in a patient with scleroderma

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a non-melanomatous neoplasm of the skin that is more likely to develop in immunosuppressed patients or those with autoimmune diseases. Individuals with connective tissue disorders in particular, such as scleroderma, are particularly at an increased risk of developing cancer due to chronic inflammation, tissue damage, genetic susceptibility, and immunosuppressive therapy. Additionally, treatment of cSCC with surgery and radiation therapy, especially in those with autoimmune connective tissue disorders, presents an increased risk of adverse effects, including infection. Case Report: A 74-year-old woman with a history of systemic scleroderma and cSCC status post Mohs surgical resection and radiation therapy presented with an 8-cm forehead lesion at the site of excised cSCC. One year earlier, she underwent Mohs surgery after biopsy-proven cSCC of the forehead with resulting clear margins. Radiation therapy was recommended as nerve involvement was discovered within the resected tumor. Magnetic resonance imaging of the brain revealed a right parafalcine subdural empyema with peripheral blood and intraoperative cultures positive for Streptococcus intermedius and Candida albicans. Her hospitalization was complicated by the development of acute hypoxic respiratory failure and septic shock. Ultimately, her family chose to focus on her comfort and she passed peacefully from complications of septic shock. Conclusion: This case highlights a rare infection after treatment of cSCC which emphasizes that treatment of malignant skin lesions in patients with scleroderma can be challenging. Shared decision-making with a thorough assessment of risks should be emphasized with every patient before proceeding with treatment.

Early Prediction of Septic Shock in Emergency Department Using Serum Metabolites.

Early recognition of septic shock is crucial for improving clinical management and patient outcomes, especially in the emergency department (ED). This study conducted serum metabolomic profiling on ED patients diagnosed with septic shock (n = 32) and those without septic shock (n = 92) using a high-resolution mass spectrometer. By implementing a supervised machine learning algorithm, a prediction model based on a panel of metabolites achieved an accuracy of 87.8%. Notably, when employed on a low-resolution instrument, the model maintained its predictive performance with an accuracy of 84.2%. These results demonstrate the potential of metabolite-based algorithms to identify patients at high risk of septic shock. Our proposed workflow aims to optimize risk assessment and streamline clinical management processes in the ED, holding promise as an efficient routine test to promote timely intensive interventions and reduce septic shock mortality.

Time to administer polymyxin B hemoperfusion and hemodynamics in patients with septic shock requiring high-dose norepinephrine: a predetermined analysis of a prospective cohort study

BackgroundDelayed administration of polymyxin B hemoperfusion (PMX-HP) for septic shock could diminish its efficacy in real-world clinical settings.MethodsBEAT-SHOCK (BEst Available Treatment for septic SHOCK) registry is a prospective registry consisting of 309 adult patients with septic shock requiring high-dose norepinephrine (≥ 0.2 μg/kg/min). This predetermined analysis included 82 patients treated with PMX-HP. They were grouped according to the median time from intensive care unit (ICU) admission to administration of PMX-HP: the early administration group (n = 40) and the late administration group (n = 42). The primary outcome was short-term hemodynamic status, including mean arterial pressure and vasoactive-inotropic score (VIS; calculated from doses of dopamine, dobutamine, norepinephrine, epinephrine, vasopressin, milrinone, and levosimendan) within 48 h after ICU admission.ResultsThe median time from ICU admission to administration of PMX-HP was 265 min (interquartile range [IQR]: 113–480). The median ages were 70 (IQR: 59–81) and 72 (IQR: 64–80) years (P = 0.77), and 21/40 (53%) and 25/42 (60%) patients were male (P = 0.52) in the early and late administration groups, respectively. The dose of norepinephrine at ICU admission was 0.33 (IQR: 0.24–0.47) and 0.30 (IQR: 0.22–0.34) μg/kg/min in the early and late administration groups, respectively (P = 0.17). Within 48 h after ICU admission, mean arterial pressure was significantly higher at 6 h and 8 h, and VIS was significantly lower at 8 h and thereafter in the early administration group. Within a 28-day period, there were 23 (IQR: 21–25) and 21 (IQR: 0–24) vasopressor/inotrope-free days (P = 0.027), and 18 (IQR: 1–23) and 14 (IQR: 0–19) ICU-free days (P = 0.025) in the early and late administration groups, respectively. The cumulative mortality at 90 days was 15.3% in the early administration group and 31.3% in the late administration group (adjusted hazard ratio 0.38; 95% confidence interval 0.13–1.09).ConclusionsIn patients with septic shock, early administration of PMX-HP was associated with higher mean arterial pressure and lower VIS within 48 h after ICU admission. Additionally, it may be associated with an improved clinical course, represented by more ICU-free and vasopressor/inotrope-free days.Trial registration UMIN Clinical Trial Registry on 1 November 2019 (registration no. UMIN000038302).

Influence of age-adjusted shock index trajectories on 30-day mortality for critical patients with septic shock

BackgroundSeptic shock poses a high mortality risk in critically ill patients, necessitating precise hemodynamic monitoring. While the age-adjusted shock index (ASI) reflects hemodynamic stability, the prognostic value of its dynamic trajectory remains unexplored. This study evaluates whether dynamic 24-h ASI trajectories predict 30-day mortality in septic shock patients.MethodsThis retrospective cohort study extracted data from the MIMIC-IV (derivation cohort, n = 2,559) and eICU-CRD (validation cohort, n = 2,177) databases. The latent category trajectory model (LCTM) classified ASI changes within 24 h of intensive care unit (ICU) admission. The association between ASI trajectory categories and 30-day mortality was evaluated using Kaplan-Meier (KM) method and Cox proportional-hazard models, reported as hazard ratios (HRs) and 95% confidence intervals (CIs).ResultThree distinct ASI trajectories were explored: persistently low (Classes 1), initial high ASI sharply decreasing followed by instability (Classes 2), and steady ASI increase (Classes 3). KM curve revealed significantly higher 30-day mortality in Class 2 (32.1%) and Class 3 (38.7%) than Class 1 (12.3%) (P < 0.001). After fully adjusting for covariates, Class 2 (HR = 1.68, 95% CI: 1.25–2.25, P = 0.001) and Class 3 (HR = 1.87, 95% CI: 1.26–2.77, P = 0.002) showed elevated mortality risks in the derivation cohort. Validation cohort results were consistent (Class 2: HR = 1.92, 95% CI: 1.38–2.68, P = 0.001) and (Class 3: HR = 1.66, 95% CI: 1.09–2.54, P = 0.019). Triple-robust analyses and subgroup analyses confirmed the reliability of the results.ConclusionDynamic 24-h ASI trajectories independently predict 30-day mortality in patients with septic shock, with unstable or rising patterns signaling high-risk subgroups. This underscores the clinical utility of real-time ASI monitoring for early risk stratification and tailored intervention.

Causes of death in adults living with HIV in South Africa: A single-centre postmortem study

Background: Mortality among people living with HIV (PLWH) in developing settings remains elevated, despite high coverage with antiretroviral therapy (ART), with 70% – 80% being virally suppressed (VS).Objectives: This study aimed to determine cause-specific mortality in PLWH in South Africa.Method: An autopsy study with detailed medical record review was undertaken in PLWH dying in hospital. Minimally invasive autopsies were performed on 38 VS and 21 unsuppressed PLWH (≥ 18 years) dying in hospital between May 2018 and April 2022. We assessed clinical and histological findings to determine underlying, contributing, and immediate causes of death (CODs).Results: Median CD4 counts were 180 and 42 cells/mm3 in patients with and without VS respectively. Leading immediate CODs in both VS and unsuppressed PLWH were respiratory failure, sepsis, and septic shock; leading contributing CODs in decreasing order of frequency in both groups were acute kidney injury (AKI), bacterial pneumonia, immunological failure, gastroenteritis and current tuberculosis. Leading underlying CODs in both groups were hypertension, current tuberculosis, malignancies, and chronic obstructive pulmonary disease. VS was associated with lower risk of septic shock and AKI.Conclusion: VS on ART appeared to reduce risk of death from specific pathologies. However, infections, multi-organ failure, non-AIDS-defining malignancies, and metabolic diseases remain important CODs. Incomplete immune reconstitution appears to be a key contributor to premature death.

Case Report: Complete recovery of a patient with occult septic shock following supranormal vasopressor and inotrope therapy informed by the novel ‘pressure field method’ for managing hemodynamics

Complete recovery of a patient with occult septic shock and left ventricular ejection fraction of 10% was achieved following management informed by continuous measurement and visualization of the patient’s ‘pressure field’. The ‘pressure field’ visualizes mean perfusion pressure as the product of stroke volume and a beat-to-beat measure of vascular tone, termed systemic elastance. The pressure field guided the titration of inotropes and vasopressors at high doses, including norepinephrine equivalents >2.5 μg/kg/min, to restore the patient’s estimated pre-morbid pressure field values. Urine output was maintained throughout with no ileus. We hypothesize that pressure field management assists in individualizing care for patients with septic shock and improves outcomes.

Crescentic Glomerulonephritis Possibly Caused by COVID-19 Infection

Background: The COVID-19 (coronavirus disease 2019) pandemic has presented a serious challenge to nephrologists, since it can lead to severe kidney injury in the form of acute tubular necrosis, with many patients requiring renal replacement therapy. This is predominantly seen in people who develop severe respiratory manifestations like ARDS (acute respiratory distress syndrome) from the viral infection, a cytokine storm or septic shock with unstable hemodynamics. It also presents with various glomerular injuries, mainly collapsing glomerulopathy in high-risk APOL1 (Apolipoprotein L1) genotype patients, thrombotic microangiopathy-related renal failure due to hyper coagulopathy and occasionally pauci-immune glomerulonephritis due to immune dysregulation. All the glomerular disorders that are caused by COVID-19 infection have been described under the designation COVAN (COVID-19-associated nephropathy). Proteinuria is a predominant presentation in glomerular disorders. Gross hematuria and AKI without any respiratory symptoms from COVID-19 infection have not been described so far in the literature. We are presenting one such rare case here. Methods: We have encountered a rare case of gross hematuria and severe acute renal failure. His serological work up was negative for all autoimmune etiologies that can cause Glomerulonephritis. He was found to have infection-related crescentic glomerulonephritis due to active COVID-19 infections discovered via kidney biopsy. He tested positive for SARS-CoV-2 but didn’t have any clinical respiratory symptoms. He has responded well to treatment with a steroid taper and antiviral medication (Remdesivir). This is a very rare renal manifestation of COVID-19 infection. Results: COVID-19 infection can result in crescentic glomerulonephritis. This can be diagnosed by kidney biopsy which shows extensive c3 deposits, tubuloreticular inclusion bodies along with crescentic lesions. This responds to treatment with steroids and Antiviral agents. Conclusions: Crescentic Glomerulonephritis should be considered as a possible etiology for severe acute kidney injury with hematuria in patients with active covid-19 infection without any respiratory symptoms. Kidney biopsy helps in diagnosing it and responds to treatment with steroids and antivirals.

Unraveling Pediatric Group A Streptococcus Meningitis: Lessons from Two Case Reports and a Systematic Review

Streptococcus pyogenes meningitis is a rare invasive disease, accounting for less than 2% of bacterial meningitis. We presented two case reports and conducted a systematic review using PUBMED, covering the database from its inception up to 31 December 2024, of pediatric cases of Streptococcus pyogenes meningitis. Only case reports and case series were included. Differences in clinical and laboratory parameters were compared between uneventful course and complicated admissions. A total of 57 cases were included. The median age at diagnosis was 4 years. A primary infection focus outside the brain was identified in 61.39% of cases. S. pyogenes was identified from cerebrospinal fluid in 66.66% of cases and from blood in 15.79%. Septic shock occurred in 24.56% of cases, and 36.84% had brain anatomical anomalies. All patients received broad-spectrum empiric antibiotics, while protein-synthesis inhibitors were administered in 26.31% of cases. A total of 17% of patients died, and 28.07% experienced sequelae. The identification of S. pyogenes from blood and a Phoenix Sepsis Score ≥ 2 were significantly associated with a complicated clinical course. Our findings may offer useful insights for the clinical management of Streptococcus pyogenes meningitis.

PCSK9 deficiency promotes the development of peripheral neuropathy.

PCSK9 induces the hepatic degradation of the low-density lipoprotein receptor (LDLR), thereby increasing the concentration of LDL-cholesterol in the blood. Beyond its effects on LDL, recent studies have reported pleiotropic effects of PCSK9, notably in septic shock, vascular inflammation, viral infection, and cancer. While the functional and structural integrity of peripheral nerves are critically influenced by circulating lipids, the impact of PCSK9 on the peripheral nervous system remains unknown. In this study, we investigated the consequences of PCSK9 deficiency on peripheral nerves. We found that PCSK9 deletion in mice leads to peripheral neuropathy, characterized by reduced thermal and mechanical pain sensations. PCSK9 deficient mice also presented with skin structural changes, including a reduction in the number of nociceptive Schwann cells, Remak fiber axonal swelling, as well as hypomyelination of small nerve fibers. Interestingly, the peripheral nerves of PCSK9-deficient mice showed an upregulation of CD36, a fatty acid transporter, which correlated with increased nerve lipid content, structural mitochondrial abnormalities, and acylcarnitine accumulation. Our findings demonstrate that PCSK9 plays a critical role in peripheral nerves by regulating lipid homeostasis and its deficiency results in symptoms related to peripheral neuropathy.

Predicting in-hospital mortality in patients with alcoholic cirrhosis complicated by severe acute kidney injury: development and validation of an explainable machine learning model

BackgroundAt present, there are no specialized models for predicting mortality risk in patients with alcoholic cirrhosis complicated by severe acute kidney injury (AKI) in the ICU. This study aims to develop and validate machine learning models to predict the mortality risk of this population during hospitalization.MethodsA retrospective analysis was conducted on 856 adult patients with alcoholic cirrhosis complicated by severe AKI, utilizing data from the MIMIC-IV database. Within the dataset, 627 patients from the period 2008–2016 were designated as the training cohort, whereas 229 patients from 2017 to 2019 comprised the temporal external validation cohort. Feature selection was conducted utilizing LASSO regression, which was subsequently followed by the development of eight distinct machine learning models. The performance of these models in the temporal external validation cohort was rigorously assessed using the area under the receiver operating characteristic curve (AUROC) to determine the optimal model. The model was interpreted using the SHAP method, and nomograms were subsequently constructed. A comprehensive evaluation was performed from the perspectives of discrimination (assessed via AUROC and AUPRC), calibration (using calibration curves), and clinical utility (evaluated through DCA curves).ResultsLASSO regression identified nine key features: total bilirubin, acute respiratory failure, vasopressin, septic shock, oliguria, AKI stage, lactate, fresh frozen plasma transfusion, and norepinephrine. In the temporal external validation cohort, the Lasso-LR model achieved the highest AUROC value of 0.809, establishing it as the optimal model. We developed both a static nomogram and a web-based dynamic nomogram (https://zhangjingyu123456.shinyapps.io/dynnomapp/) for visualization purposes. In the nomogram model, the AUROC for the training cohort and temporal external validation cohort were 0.836 (95% CI: 0.802-0.870) and 0.809 (95% CI: 0.754–0.865), respectively. The calibration slope and Brier score for the training cohort were 1.000 and 0.146, respectively; for the temporal external validation cohort, these values were 0.808 and 0.177, respectively. The DCA curves indicate that the model has certain clinical application value.ConclusionThe Lasso-LR model exhibits robust predictive capability for in-hospital mortality among patients with alcoholic cirrhosis complicated by AKI, offering valuable prognostic insights and individualized treatment decision support for healthcare professionals.

Utility of core to peripheral temperature gradient using infrared thermography in the assessment of patients with sepsis and septic shock in the emergency medicine department

ObjectiveSepsis 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.DesignWe 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.InterventionsPatients 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.Outcome measure(s)The temperature gradients were correlated with 7 and 28-day mortality along with markers of hypoperfusion including mean arterial pressure and serum lactate levels.ResultsA 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).ConclusionsCore-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.

Septic shock caused by Elizabethkingia miricola in an elderly trauma patient: a case report and systematic literature review

ObjectiveElizabethkingia miricola is a rarely encountered pathogen in clinical settings, predominantly causing infections in immunocompromised individuals. To advance the understanding of E. miricola infection, we present a case of E. miricola infection and conduct a literature review.MethodsWe report a case of pulmonary infection caused by E. miricola in a 90-year-old trauma patient, marking the first documented instance of treatment with eravacycline. We also conducted a systematic review of the relevant literature. A comprehensive search was performed using the PubMed and Web of Science databases up to November 2024. A qualitative synthesis was conducted on all available case reports and case series related to E. miricola infections.ResultsA total of 63 cases from 21 studies were included in this systematic review. According to these case reports, infections caused by E. miricola most commonly occur in the lungs (34/63), bloodstream (6/63), and urinary tract (4/63). Risk factors for E. miricola infection include immunodeficiency, prolonged hospitalization in the intensive care unit (ICU), prolonged mechanical ventilation, and the use of broad-spectrum antibiotics. Notably, a considerable proportion of cases (17/63) are hospital-acquired.ConclusionElizabethkingia miricola represents a rare but highly lethal opportunistic pathogen. Early identification and treatment with sensitive antibiotics are required to improve the prognosis of patients. The present case and literature review provide options for the diagnosis and treatment of similar cases in the future and serve as a reference for preventing and controlling the occurrence and spread of nosocomial infections.Systematic review registrationhttps://pubmed.ncbi.nlm.nih.gov/, https://www.webofscience.com/wos/.

A Closer Look at Periocular Necrotizing Fasciitis: A Systematic Review of Literature

Background: Periocular necrotizing fasciitis (PNF) is a rare but life-threatening emergency that requires immediate recognition, as delayed diagnosis can worsen patient outcomes. To address this critical issue, we conducted the largest and most comprehensive systematic review to date, providing valuable insights into the diagnosis and treatment of PNF to improve clinical practice and patient prognosis. Methods: A search on Pubmed, Scopus, Embase, and WOS from January 2013 to August 2024 was performed. Only the cases of NF affecting the periocular region were included with no age limitations. Article selection and data extraction were performed independently by two investigators to avoid bias. Bias on individual studies is low as they represent case reports or case series, and publication bias is partially addressed including all the large case series even if no individual data could be retrieved. Results: The cohort included a total of 183 patients with PNF, with detailed patient-specific data for 107 individuals and only aggregated data for another 76. The average age at diagnosis was 54.2 years, and females constituted 44% of the population sample. Notably, 49.6% of the patients were immunocompromised. Streptococcus pyogenes was the predominant causative organism, identified in 79.8% of the cases. Most infections were unilateral (72.1%) without extension beyond the periocular area (54.7%). Most patients (89.6%) underwent surgical debridement alongside intravenous antibiotics. Septic shock occurred in 26.8% of the patients, and the overall mortality rate was 4.9%. Visual acuity was unaffected in 67.5% of the patients, though 18.2% progressed to blindness on the affected side. Reconstructive efforts predominantly involved skin grafting, both free and local pedunculate flaps as well as secondary healing in some instances. Conclusions: This systematic review summarizes the understanding of periocular necrotizing fasciitis’ (PNF) demographic trends, clinical manifestations, causative pathogens, and patient outcomes. Vigilance for PNF should be heightened when the clinical assessment of the patient’s eyelids reveals rapidly spreading edema and induration, subcutaneous emphysema, or necrotic bullae and/or eschar. Prompt identification and expedited intervention, including debridement and targeted antibiotic therapy, critically influence prognosis. Despite optimal management, patients may still suffer from significant aesthetic impairment, severe complications such as vision loss, or death due to septic shock.

Extended Hematological Parameters and Short-Term Mortality in Sepsis Patients: A Retrospective Study

Background/Objectives: Sepsis has a high mortality rate, with septic shock exceeding 50%. The most common score for diagnosis and prognosis in sepsis is the Sepsis-related Organ Failure Assessment (SOFA). This study aimed to identify hematological parameters for the prediction of intensive care unit (ICU) mortality. Methods: This study collected demographic and clinical data from sepsis patients, including age, sex, infection site, length of stay, the SOFA, and ICU mortality. The standard laboratory panel included, among others, complete blood count with differential and reticulocyte panel. Intergroup differences were analyzed using Student’s t-test, Mann–Whitney U test, Pearson’s χ2, and Fisher’s test where applicable. The AUROC was used for evaluating the predictive value of hematological parameters. Multiple logistic regression was performed to exclude the impact of potential confounding factors. Results: This study analyzed data from 190 sepsis patients hospitalized in the ICU, excluding patients with other conditions significantly affecting mortality. The median age was 65.0 (IQR 51.0–71.0) years. The sexes were almost perfectly balanced. The sites of infection were mostly the abdominal cavity, lungs, and urinary tract. The short-term mortality rate was 30%, with higher SOFA scores and significant differences in leukocyte, platelet, and erythrocyte parameters between survivors and non-survivors. The percentage of nucleated red blood cells (NRBCs) showed the highest AUROC. Conclusions: The only reliable hematological parameter for predicting ICU mortality in sepsis patients may be the percentage of NRBCs. The presence of NRBCs in a blood smear is linked to a worse prognosis.

Early norepinephrine for patients with septic shock: an updated systematic review and meta-analysis with trial sequential analysis

BackgroundThe 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.MethodsA 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.ResultsTen 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.ConclusionEarly 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.

Comparison of different AI systems for diagnosing sepsis, septic shock, and cardiogenic shock: a retrospective study

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.

Liberal transfusion strategies reduce sepsis risk and improve neurological recovery in acute brain injury: an updated systematic review and meta-analysis

PurposeTo advocate for a Liberal Transfusion Strategy (LTS) in neurocritical care patients with Acute Brain Injury (ABI) and provide updated evidence for optimizing transfusion thresholds in clinical guidelines.BackgroundAnemia frequently complicates ABI management, often necessitating red blood cell transfusions. However, the optimal hemoglobin (Hb) threshold for transfusion remains controversial. While earlier meta-analyses indicated no significant differences between LTS and restrictive transfusion strategies (RTS), emerging randomized controlled trials (RCTs) emphasize the need for reappraisal within neurocritical care.MethodsThis meta-analysis included five RCTs involving 2399 patients (1,191 LTS; 1208 RTS) with ABI (subarachnoid hemorrhage, traumatic brain injury, or intracerebral hemorrhage). LTS was defined as transfusion at Hb ≤ 10–9 g/dL, and RTS as transfusion at Hb ≤ 7–8 g/dL. Outcomes assessed included sepsis or septic shock, ICU mortality, unfavorable functional outcomes at six months, venous thromboembolism (VTE), acute respiratory distress syndrome (ARDS), and in-hospital mortality.ResultsRTS significantly increased the risk of sepsis or septic shock (relative risk [RR]: 1.42; 95% confidence interval [CI] 1.08–1.86; p = 0.01) and unfavorable functional outcomes at six months (RR 1.13; 95% CI 1.06–1.21; p = 0.0003). No significant differences were observed in ICU mortality (RR 1.00; 95% CI 0.84–1.20; p = 0.96), VTE (RR: 0.88; 95% CI 0.56–1.38; p = 0.58), ARDS (RR 1.05; 95% CI 0.69–1.61; p = 0.81), or in-hospital mortality (RR 0.98; 95% CI 0.76–1.26; p = 0.89). Heterogeneity was minimal (I2 < 25%).ConclusionLTS demonstrates the potential to enhance safety and functional recovery in ABI patients by mitigating sepsis risk and promoting favorable neurologic outcomes. Further high-powered RCTs are warranted to validate these findings and refine transfusion protocols.

Impact of early haemodynamic assessment by echocardiography on organ dysfunction and outcome of patients admitted to the emergency department with sepsis or septic shock: protocol of a multicentre randomised controlled trial (GENESIS).

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.

Critical Care Approach to Severe Tetanus with Septic Shock: A Case Report

Introduction: Tetanus, caused by Clostridium tetani neurotoxin, remains a life-threatening condition, particularly in regions with suboptimal vaccination coverage. Severe tetanus often necessitates intensive care unit (ICU) admission due to profound muscle spasms, respiratory failure, and autonomic nervous system dysfunction. Concomitant septic shock further complicates management and worsens prognosis. This report details the critical care management of a patient presenting with severe tetanus complicated by septic shock. Case presentation: A 41-year-old male presented with generalized muscle rigidity, trismus, and recurrent severe spasms following a puncture wound from bamboo 10 days prior. He had no prior tetanus immunization history. Upon admission, he exhibited signs of respiratory distress (Sp90% on a 15L non-rebreather mask) and septic shock (tachycardia, hypotension requiring vasopressors, SOFA score 7). Diagnosis of severe tetanus (Ablett Grade III) with respiratory failure and septic shock was made. Management involved immediate intubation, mechanical ventilation, administration of human tetanus immunoglobulin (HTIG), intravenous metronidazole, aggressive sedation with benzodiazepines (diazepam infusion) and neuromuscular blockade (vecuronium infusion), hemodynamic support with intravenous fluids and noradrenaline infusion, early tracheostomy, and comprehensive supportive care including nutritional support and VTE prophylaxis. His ICU stay was complicated by autonomic instability and ventilator-associated pneumonia (VAP). Conclusion: Managing severe tetanus complicated by septic shock requires a prompt, multidisciplinary critical care approach. Key elements include securing the airway, controlling spasms and rigidity, neutralizing toxins, eradicating the source, managing autonomic instability, aggressive sepsis management according to current guidelines, and providing meticulous supportive care. Despite significant challenges, a favorable outcome is possible with comprehensive ICU management.