Sintilimab-induced myocarditis suspected in a patient with esophageal cancer and followed septic shock: case report and literature review.

Background: Immune checkpoint inhibitors (ICIs) have become a prevalent tool in anti-tumor therapy in recent years. They may cause immune-related adverse events (irAEs) including potentially life-threatening cardiovascular toxicities such as myocarditis. Case presentation: In this report, we describe a 69-year-old man with recurrent esophageal cancer who developed myocarditis after receiving three cycles of sintilimab combined with nab-paclitaxel. Despite a rising cardiac troponin I (cTnI), he initially reported no discomfort. He was later suspected of having with sintilimab-induced myocarditis. Although treatment with methylprednisolone reduced his cTnI levels, he still experienced significant discomfort. Moreover, he developed pneumonia and septic shock. Conclusion: In our literature search to identify all reported cases of sintilimab-associated adverse events involving myocarditis, we found 14 patients, including those with esophageal cancer, thymoma, lung cancer, gastric cancer, hepatobiliary carcinoma, and chordoma. The primary treatment for ICI-induced cardiotoxicity is methylprednisolone. However, the long-term or high-dose use of steroids can also induce side effects, which have not been the focus of these case reports. This is the first reported case of asymptomatic immune-mediated myocarditis occurring during the treatment of esophageal cancer with sintilimab. It is also the first to address the side effects of methylprednisolone used in the treatment of sintilimab-related myocarditis. To facilitate an early diagnosis, regular monitoring is required during sintilimab treatment. We should also focus on the prevention and management of adverse effects related to steroid use.

Association between heart rate and mortality in patients with septic shock: an analysis revealed by time series data.

BACKGROUND: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. METHODS: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. RESULTS: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78-2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52-1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48-1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. CONCLUSION: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. .

Pediatric Sepsis - Sailing the Unchartered Waters with Omics.

How to cite this article: Baalaaji M. Pediatric Sepsis - Sailing the Unchartered Waters with Omics. Indian J Crit Care Med 2024;28(9):818-819.

Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study.

Aim and background: Corticosteroids are recommended for use in adult patients with septic shock requiring vasopressors for blood pressure maintenance. However, this predisposes them to hyperglycemia, which is associated with a poor outcome. This prospective randomized study compares the effect of continuous infusion with bolus hydrocortisone on blood glucose levels in septic shock. Materials and methods: Forty adult patients with sepsis and septic shock requiring vasopressor support were randomly allocated to either group C (continuous infusion of hydrocortisone 200 mg/day) or group B (intermittent bolus dose of hydrocortisone 50 mg IV 6 hourly). Blood glucose level (primary objective), number of hyperglycemic and hypoglycemic episodes, daily insulin requirement, shock reversal incidence, time to shock reversal, and nursing workload required to maintain blood glucose within the target range (82-180 mg/dL) were compared. Results: The mean blood glucose level was comparable in the two groups (136.5 ± 22.08 mg/dL in group C vs 135.85 ± 19.06 mg/dL in group B; p = 0.921). The number of hyperglycemic and hypoglycemic episodes (p = 1.000 each), insulin requirement/day (p = 1.000), and nursing workload (p = 0.751) were also comparable among groups. Shock reversal was seen in 7/20 (35%) patients in continuous group and 12/20 (60%) patients in bolus group (p = 0.113). Time to shock reversal (p = 0.917) and duration of ICU stay (p = 0.751) were also statistically comparable. Conclusion: Both the regimes of hydrocortisone, continuous infusion, and bolus dose, have comparable effects on blood glucose levels in patients with septic shock.The study was registered prospectively with ctri.nic.in (Ref. No. CTRI/2021/01/030342; registered on 8/1/2021). How to cite this article: Salhotra R, Sharahudeen A, Tyagi A, Rautela RS, Kemprai R. Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study. Indian J Crit Care Med 2024;28(9):837-841.

Hydrocortisone for Septic Shock, Bolus or Infusion: Pro, Con, May be.

How to cite this article: Todi S. Hydrocortisone for Septic Shock, Bolus or Infusion: Pro, Con, May be. Indian J Crit Care Med 2024;28(9):816-817.

Effect of low vs. high vancomycin trough level on the clinical outcomes of adult patients with sepsis or gram-positive bacterial infections: a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15-20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. METHOD: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. RESULTS: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41-2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23-0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73-3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31-1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73-1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62-0.90), p = 0.002]. CONCLUSION: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections.

Association of beta blockers and mortality in adults with septic shock: systematic review and meta-analysis of randomized clinical trial.

Introduction: Septic shock still entails significant morbidity and mortality, with the heart being affected due to catecholamine overexpression and direct injury from sepsis. Therefore, the effect of ß-blocking the receptors to improve performance is promising when attempting to reverse tachycardia and reduce mortality. Methods: We conducted a comprehensive search across five databases for studies published up to 28 January 2024, using a PICO strategy. Ten studies were identified for quantitative analysis and included in our meta-analysis. Results: Our meta-analysis evaluated 28-day in-hospital mortality risk across nine randomized controlled trials (RCTs) involving a total of 1,121 adults with septic shock. We found an association between ß-blocker use and reduced overall mortality (OR 0.57; 95% CI 0.34-0.98; I 2: 56%). This effect was significant in the esmolol subgroup (OR 0.47; 95% CI 0.26-0.82; I 2: 32%), but not in the landiolol subgroup (OR 0.98; 95% CI 0.0-1,284.5; I 2: 72%). Additionally, the intervention group shows a significant reduction in HR and lactate levels, as well as an increase in stroke volume index (SVI). Conclusion: In adults with septic shock, ß-blockers are associated with a reduction in 28-day in-hospital mortality, a benefit primarily observed with esmolol rather than landiolol. Furthermore, improvements in heart rate (HR) control, lactate levels, and SVI were noted. However, these findings should be interpreted with caution, and further high-quality RCTs comparing different ß-blockers are necessary to better elucidate these effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024513610.

Development and validation of a sepsis risk index supporting early identification of ICU-acquired sepsis: An observational study.

BACKGROUND: Sepsis is a threat to global health, and domestically is the major cause of in-hospital mortality. Due to increases in inpatient morbidity and mortality resulting from sepsis, healthcare providers (HCPs) would accrue significant benefits from identifying the syndrome early and treating it promptly and effectively. Prompt and effective detection, diagnosis, and treatment of sepsis requires frequent monitoring and assessment of patient vital signs and other relevant data present in the electronic health record. METHODS: This study explored the development of machine learning-based models to generate a novel sepsis risk index (SRI) which is an intuitive 0-100 marker that reflects the risk of a patient acquiring sepsis or septic shock and assists in timely diagnosis. Machine learning models were developed and validated using openly accessible critical care databases. The model was developed using a single database (from one institution) and validated on a separate database consisting of patient data collected across multiple ICUs. RESULTS: The developed model achieved an area under the receiver operating characteristic curve of 0.82 and 0.84 for the diagnosis of sepsis and septic shock, respectively, with a sensitivity and specificity of 79.1% [75.1, 82.7] and 73.3% [72.8, 73.8] for a sepsis diagnosis and 83.8% [80.8, 86.5] and 73.3% [72.8, 73.8] for a septic shock diagnosis. CONCLUSION: The SRI provides critical care HCPs with an intuitive quantitative measure related to the risk of a patient having or acquiring a life-threatening infection. Evaluation of the SRI over time may provide HCPs the ability to initiate protective interventions (e.g. targeted antibiotic therapy).

Hyperoxia in Sepsis and Septic Shock: A Comprehensive Review of Clinical Evidence and Therapeutic Implications.

Sepsis and septic shock are leading causes of mortality in intensive care units, characterized by a dysregulated immune response to infection, leading to severe organ dysfunction. Oxygen therapy is a cornerstone of supportive care in sepsis management, aimed at correcting hypoxemia and improving tissue oxygenation. However, the administration of supplemental oxygen must be carefully managed to avoid hyperoxia, which can lead to oxidative stress and additional tissue damage. This review aims to comprehensively analyze the clinical evidence regarding hyperoxia in the context of sepsis and septic shock, evaluating its potential therapeutic benefits and risks and discussing the implications for clinical practice. A thorough literature review included observational studies, randomized controlled trials (RCTs), meta-analyses, and clinical guidelines. The review focuses on the pathophysiology of sepsis, the mechanisms of hyperoxia-induced injury, and the clinical outcomes associated with different oxygenation strategies. The evidence suggests that while oxygen is crucial in managing sepsis, the risk of hyperoxia-related complications is significant. Hyperoxia has been associated with increased mortality and adverse outcomes in septic patients due to mechanisms such as oxidative stress, impaired microcirculation, and potential worsening of organ dysfunction. RCTs and meta-analyses indicate that conservative oxygen therapy may be beneficial in reducing these risks, though optimal oxygenation targets remain under investigation. This review highlights the importance of careful oxygen management in sepsis and septic shock, emphasizing the need for individualized oxygen therapy to avoid the dangers of hyperoxia. Further research is required to refine oxygenation strategies, establish clear clinical guidelines, and optimize outcomes for sepsis and septic shock patients. Balancing adequate oxygenation with the prevention of hyperoxia-induced injury is crucial in improving the prognosis of these critically ill patients.

The Values of PDK1 and LDH Levels in Patients with Sepsis and Septic Shock: A Prospective Observational Study.

Background: Metabolic changing is the significant host stress response during sepsis, but there is increasing evidence that uncontrolled metabolic reprogramming is a contributing factor to sepsis. Nevertheless, its association with outcome in patients with sepsis has been poorly investigated. As the key enzyme of metabolic reprogramming, the clinical value of PDK1 and LDH in patients with sepsis will be investigated in this study. Methods: We collected serum from 167 ICU patients within 24 hours of admission for a single-center prospective observational study. The levels of PDK1 and LDH were detected by enzyme-linked adsorption method. Pearson or Spearman coefficient for correlation analysis between PDK1, LDH and clinical indicators. Areas under the ROC curves for evaluation of mortality prediction. Kaplan-Meier survival curve analysis was performed, and Cox proportional hazards model was performed to determine the risk factors for 28-day mortality. Results: The PDK1/LDH in the septic shock group was statistically different between both the sepsis group and ICU control group, and had good correlation with ScvO2 and lactate. In predicting 28-day mortality in patients with sepsis, the best AUC was observed for PDK1/LDH, and was higher than the AUC for PDK1, lactate, and SOFA. Additionally, patients with lower PDK1/LDH had markerablely higher 28-day mortality. The multivariate Cox proportional hazards model revealed that PDK1/LDH < 0.1808 were the independent risk factors for 28-day mortality in sepsis. Conclusion: The level of PDK1/LDH at admission was markedly decreased in patients with septic shock, which can serve as a novel independent prognostic biomarker for predicting mortality.

Extracorporeal pediatric renal replacement therapy: diversifying application beyond kidney failure.

The utilization of extracorporeal renal replacement therapy (RRT), including continuous renal replacement therapy (CRRT) and hemodialysis (HD), beyond the treatment of volume overload and acute kidney injury (AKI) has witnessed a significant shift, demonstrating the potential to improve patient outcomes for a range of diseases. This comprehensive review explores the non-kidney applications for RRT platforms in critically ill children, focusing on diverse clinical scenarios such as sepsis, inborn errors of metabolism, liver failure, drug overdose, tumor lysis syndrome, and rhabdomyolysis. In the context of sepsis and septic shock, RRT not only facilitates fluid, electrolyte, and acid/base homeostasis, but may offer benefits in cytokine regulation, endotoxin clearance, and immunomodulation which may improve multi-organ dysfunction as well as hemodynamic challenges posed by this life-threatening condition. RRT modalities also have an important role in caring for children with inborn errors of metabolism, liver failure, and tumor lysis syndrome as they can control metabolic derangements with the efficient clearance of endogenous toxins in affected children. In cases of drug overdose, RRT is a crucial tool for rapid extracorporeal clearance of exogenous toxins, mitigating potential organ damage. The intricate interplay between liver failure and kidney function is examined, elucidating the role of RRT and plasma exchange in maintaining fluid and electrolyte balance when hepatic dysfunction complicates the clinical picture. Furthermore, RRT and HD are explored in the context of rhabdomyolysis, highlighting their utility in addressing AKI secondary to traumatic events and crush syndrome.

A case report of fatal Rickettsia japonica bloodstream infection in Zhejiang, China.

Japanese spotted fever (JSF) is an emerging acute febrile natural infectious disease caused by the neglected zoonotic pathogen Rickettsia japonica. Here we reported a 64-year-old female patient who initially presented to the local hospital with an intermittent fever of unknown origin (FUO). A systemic, evident edema and eschar on the skin of the patient's upper limb was observed. The patient was diagnosed with critical Rickettsia japonica bloodstream infection by Q-mNGS and treated with doxycycline, as well as symptomatic treatments. Unfortunately, the patient passed away as a result of complications of septic shock and multiple organ and acute respiratory failure. Delayed treatment resulting from the nonspecific clinical symptoms in the early stages of infection can lead to fatal complications. Q-mNGS is an emerging pathogen detection method with the advantages of comprehensive detection, high accuracy and sensitivity and should be promoted and applied by clinicians.

Japanese spotted fever is an emerging infectious disease caused by the bacteria Rickettsia japonica. The onset of symptoms in patients is very sudden once infected. Here, we reported a 64-year-old female patient who experienced recurrent fever with an unknown cause. The patient was diagnosed with Rickettsia japonica infection after testing and received antibiotic treatment. However, delays in treatment led to continuous worsening of the condition and ultimately death. We emphasize the value of early, broader testing in the diagnosis of rare infections to detect infection early.

[Fatal course of a fulminant gas gangrene of the right hemithorax]. / Letaler Verlauf eines fulminanten Gasgangräns des rechten Hemithorax.

The full clinical picture of a gas gangrene infection is an absolute rarity. The mechanism of development can be either traumatic or spontaneous (e.g., hematogenous seeding in occult colon carcinoma). In particular, the rare pathogen Clostridium septicum appears to be associated with spontaneously occurring gas gangrene. Diabetes mellitus is a significant risk factor. The mortality rate of the disease is around 50%, even with maximum therapeutic efforts, and the course of the disease is fulminant in the majority of cases. Initial symptoms are unspecific and make early diagnosis difficult. Treatment consists of high-dose antibiotics in combination with radical surgical debridement and, if necessary, supplementary hyperbaric oxygen therapy.

Rapid uptake of adjunctive corticosteroids for critically ill adults with septic shock following publication of ADRENAL trial. A multicenter, retrospective analysis of prescribing practices in Queensland Intensive Care Units.

BACKGROUND: Septic shock is common and associated with significant morbidity and mortality. The ADRENAL trial examined the use of hydrocortisone in patients with septic shock, demonstrating no difference in patient-centred outcomes but a decrease in the time to shock resolution. The change in clinical practice related to the publication of the ADRENAL trial is currently unknown. METHODS: A retrospective cohort study examining the use of hydrocortisone in patients with septic shock was conducted in 12 intensive care units (ICUs). A segmented linear regression was performed to identify a stepwise change in hydrocortisone administration and 90-day mortality associated with the publication of the ADRENAL trial. RESULTS: We included 4,198 patients with a mean age of 58 years (standard deviation, SD17), and the median noradrenaline equivalent score (NEE) was 0.07 µg/kg/min (IQR 0.02 - 0.17). Segmented regression analysis for hydrocortisone administration identified two breakpoints, 3 months before and 6 months after publication, leading to three periods: Pre-publication, Transition and Post-publication. Compared to the pre-publication period, the Transition and Post-publication cohorts had a higher proportion of hydrocortisone administration (28% vs. 34% vs. 43%; p < 0.0001). Furthermore, after adjustment for temporal change, the transition period had a significant change in the slope of the proportion of patients receiving hydrocortisone (-0.1% per month vs. +1.4% per month; p = 0.026), whereas this was not statistically significant during the post-publication period (+0.1% per month, p = 0.66). After adjusting for confounders, the Transition and Post-publication periods were independently associated with an increase in hydrocortisone (OR 1.4, 95% CI 1.14 - 1.77; p = 0.0015 and OR 2.03; 95% CI 1.74 - 2.36; p < 0.001, respectively). Furthermore, after adjusting for confounders, when compared to the Pre-transition period, the use of hydrocortisone was associated with a statistically significant decrease in 90-day mortality (14% vs. 24% absolute difference, aHR for hydrocortisone effect -0.81; 95% CI 0.65 - 0.99; p = 0.044). CONCLUSION: Publication of the ADRENAL trial changed clinical practice in Queensland ICUs with increased prescription of hydrocortisone for patients with septic shock with an associated reduction in mortality.

Magnitude of Septic Shock and its Associated Factors Among Critically Ill COVID-19 Patients at Addis Ababa COVID-19 Care Centers, Ethiopia.

Background: The coronavirus disease (COVID-19) pandemic imposed a major public health impact. Septic shock is one of the frequent complications encountered among critically ill COVID-19 patients, leading to poor healthcare outcomes. This study aimed at assessing the magnitude of septic shock and its associated factors. Methods and materials: An institution-based cross-sectional study was conducted retrospectively on 242 randomly selected COVID-19 patients admitted to three Addis Ababa COVID-19 care centers from September 2020 to October 2021. Septic shock was defined as a Sequential Organ Failure Assessment (SOFA) score ≥2 points and persisting hypotension requiring vasopressors to maintain a mean arterial pressure of ≥65 mmHg despite adequate volume resuscitation. Variables in the bivariate analysis were fitted to multiple regression analysis to eliminate confounders and determine independent risk factors for septic shock. In the multivariable analysis, statistical significance was declared at P < .05. Results: The prevalence of septic shock was found to be 39.3% (95% confidence interval [CI]: 33.1, 45.7). Advanced age (≥60 years) [AOR = 7.9; 95% CI: 2.3, 26.8], intensive care unit stay above 7 days [AOR = 6.2; 95%CI: 2.1, 18.7], invasive ventilation [AOR = 10; 95% CI: 3, 37], and chronic obstructive pulmonary disease (COPD) [AOR = 18; 95% CI: 7, 45] were significantly associated with increased septic shock among COVID-19 patients. Meanwhile, diabetes [AOR = 0.24; 95% CI: 0.08, 0.71] and cardiovascular diseases [AOR = 0.17; 95% CI: 0.07, 0.44] were associated with a decrease risk of septic shock. Conclusion: The prevalence of septic shock in critically ill COVID-19 patients was high and a major concern in this study, and it is independently associated with advanced age, prolonged stay in the intensive care unit, and COPD. Based on these findings, healthcare professionals should closely monitor and manage patients with COVID-19 who have a history of COPD, are older, or prolonged intensive care unit (ICU) stays to prevent septic shock and improve patient outcomes.

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

BACKGROUND: Septic 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. METHODS: This 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. DISCUSSION: This 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 REGISTRATION: This clinical trial has been registered at ChiCTR ( https://www.chictr.org.cn/ ) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial.

Hemoperfusion is a novel adjunct therapy that targets the dysregulated inflammatory events in severe sepsis. Previous studies have reported conflicting results on its efficacy and safety. This study was designed to assess the efficacy and safety of hemoperfusion among leptospirosis patients in septic shock and renal failure in terms of improvement in 28-day mortality, SOFA score, level of inflammatory markers, hemodynamics, and renal and pulmonary function. A total of 37 severe leptospirosis patients were enrolled and randomized into either standard medical therapy (SMT) alone, n = 20, or with hemoperfusion (HP), n = 17. Vital signs, urine output, vasopressor dose, PaO2/FiO2 (P/F) ratio, and biochemical parameters of patients from each treatment arm were compared. The hemoperfusion group showed a 36.84% (p = 0.017) risk reduction in 28-day mortality. Levels of procalcitonin, IL6, and lactate significantly decreased from baseline to day 7 in both groups. Statistically significant improvements in serum creatinine (p = 0.04) and PF ratio (p = 0.045) were observed in the hemoperfusion cohort. Intention-to-treat and per-protocol approaches showed that hemoperfusion increased the survival rate and decreased the mortality risk. This benefit for survival persisted even when patients were also receiving extracorporeal membrane oxygenation (ECMO), showing that hemoperfusion's benefits are independent of ECMO use. Hemoperfusion is a safe and effective adjunct therapy for managing severe sepsis. It promotes earlier renal and pulmonary function recovery and improves the survival of septic shock patients.

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.

Clinical Effect of Norepinephrine Combined with Esmolol Treatment in Patients with Septic Shock and Its Impact on Prognosis.

Objective: To unveil the influence of norepinephrine (NE) combined with esmolol treatment on cardiac function, hemodynamics, inflammatory factor levels, and prognosis in patients with septic shock. Methods: Ninety-six patients with septic shock admitted to our hospital from January 2021 to June 2023 were retrospectively analyzed and divided into the control and observation groups according to the different treatment methods. The control group was treated with standard anti-infection and fluid resuscitation, followed by NE administration [with an infusion rate of 0.1-0.5 µg/(kg-min)]. The observation group was treated with esmolol [starting pumping rate of 50 µg/(kg-min) and adjusting the pumping rate according to the target heart rate] in combination with the control group. Changes in hemodynamic parameters, including heart rate, mean arterial pressure, central venous pressure, cardiac index, stroke volume index, and systemic vascular resistance index, were monitored by pulse-indicating continuous cardiac output monitors before treatment (T0), 24h after treatment (T1), and 72h after treatment (T2); changes in cardiac function before and after 72h of treatment, indicators of inflammatory factors before and after treatment, and indicators of oxygenation metabolism were assessed; and adverse drug reactions during treatment were recorded in both groups. Results: NE combined with esmolol treatment improved the efficacy of patients with septic shock; was beneficial for the enhancement of blood perfusion in patients; improved the patient's cardiac function, reduced myocardial injury, and suppressed the inflammatory response in patients; improved the oxygenation metabolism and the prognosis of patients; did not significantly increase the adverse drug reactions of patients and had a better safety profile. Conclusion: NE combined with esmolol treatment can improve the efficacy of patients with septic shock, improve their cardiac function and hemodynamic indices, reduce myocardial injury and inflammatory response, and have a better safety profile, which is conducive to improving patient prognosis and reducing mortality.