Septic Shock Patients Research Articles

Major endothelial damage markers identified from hemadsorption filters derived from treated patients with septic shock - endoplasmic reticulum stress and bikunin may play a role.

In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction. Plasma materials enriched to hemadsorption filters (CytoSorb®) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry. Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage. Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin - cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution.

Ivabradine in Septic Shock: A Narrative Review.

In patients with septic shock, compensatory tachycardia initially serves to maintain adequate cardiac output and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation. This sustained elevation in heart rate and altered heart rate variability, indicative of autonomic dysfunction, is a well-established independent predictor of adverse outcomes in critical illness. Elevated heart rate exacerbates myocardial oxygen demand, reduces ventricular filling time, compromises coronary perfusion during diastole, and impairs the isovolumetric relaxation phase of the cardiac cycle, contributing to ventricular-arterial decoupling. This also leads to increased ventricular and atrial filling pressures, with a heightened risk of arrhythmias. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (If or "funny" current), mitigates heart rate by modulating diastolic depolarization slope without affecting contractility. By exerting a selective chronotropic effect devoid of negative inotropic properties, ivabradine shows potential for improving hemodynamics in septic shock patients with cardiac dysfunction. This review evaluates the plausible mechanisms and existing evidence regarding the utility of ivabradine in managing patients with septic shock.

A Systematic Review and Meta-Analysis of the Timing of Vasopressor Therapy in Patients with Septic Shock: Assessing Clinical Outcomes and Implication

Background Septic shock, is associated with a high mortality rate and increased expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. There is still a controversy on when each vasopressor should be administered. Therefore, we conducted this review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated lower incidence of mortality and shorter duration to achieve target mean arterial pressure in the early vs. late epinephrine groups (OR:0.44; 95%CI: 0.35–0.55; p<0.00001 and MD:-1.17; 95%CI:-2.00– -0.34; p=0.0006). However, the length of ICU stay didn’t differ between the early and late norepinephrine group (MD:0.55; 95%CI: -0.52–1.62; p=0.31). The subgroup analyses show that early vasopressin is associated with a decreased mortality than late administration (OR:0.60; 95%CI:0.41–0.90; p=0.01). Similarly, the pooled analysis has shown that early concomitant administration of vasopressin and norepinephrine is associated with a shorter duration to achieve target MAP than norepinephrine alone (MD:-3.15; 95%CI:-4.40– -1.90;p<0.00001). Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.

Sepsis and Septic Shock in Patients Undergoing Thyroidectomy: Incidence, Risk Factors, and Outcomes

IntroductionPostoperative sepsis represents a rare complication following thyroidectomy. We aimed to explore the incidence, risk factors, sources, and outcomes of postoperative sepsis and septic shock among adult patients undergoing thyroidectomy. MethodsData from the American College of Surgeons National Surgical Quality Improvement Program were used in this retrospective cohort study. Patients aged ≥18 y who underwent elective thyroidectomy between 2005 and 2019 were included. Multivariable binary logistic regression models were computed to explore risk factors and outcomes of 30-d sepsis and septic shock. ResultsAmong the 180,373 included patients, 0.1% developed sepsis or septic shock. Male gender, low body mass index, American Society of Anesthesiologists classes 3-5, functional dependence, smoking, diabetes mellitus, pulmonary disease, inpatient surgery, malignant indication, clean-contaminated wound classification, and operation time ≥150 min were significant risk factors for development of sepsis or septic shock. Common infectious sources of sepsis included surgical site infections (29.6%), pneumonia (18.6%), urinary tract infections (16.2%), and multiple infections (6.9%). Patients with postoperative sepsis or septic shock were significantly more likely to develop complications, including wound disruption, stroke, cardiac and renal complications, thromboembolism, prolonged length of stay, unplanned reoperation, and mortality. ConclusionsSepsis is rare following thyroidectomy. Our study provides insight into risk factors and procedural characteristics which may contribute to the development of postoperative sepsis or septic shock in this population.

The outcome of using first oral funny current inhibitor drug in septic shock patients

The outcome of using first oral funny current inhibitor drug in septic shock patients

Neo-epitope detection identifies extracellular matrix turnover in systemic inflammation and sepsis: an exploratory study

BackgroundSepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironment. Conversely, uncontrolled turnover can contribute to tissue damage. Systemic Inflammation is implicated to play a role in the regulation of ECM turnover, but the relationship between the two is largely unclear.MethodsWe performed an exploratory study in 10 healthy male volunteers who were intravenously challenged with 2 ng/kg lipopolysaccharide (LPS, derived from Escherichia coli) to induce systemic inflammation. Plasma samples were collected before (T0) and after (T 1 h, 3 h, 6 h and 24 h) the LPS challenge. Furthermore, plasma was collected from 43 patients with septic shock on day 1 of ICU admission. Circulating neo-epitopes of extracellular matrix turnover, including ECM degradation neo-epitopes of collagen type I (C1M), type III (C3M), type IV (C4Ma3), and type VI (C6M), elastin (ELP-3) and fibrin (X-FIB), as well as the ECM synthesis neo-epitopes of collagen type III (PRO-C3), collagen type IV (PRO-C4) and collagen type VI (PRO-C6) were measured by ELISA. Patient outcome data were obtained from electronic patient records.ResultsTwenty-four hours after LPS administration, all measured ECM turnover neo-epitopes, except ELP-3, were increased compared to baseline levels. In septic shock patients, concentrations of all measured ECM neo-epitopes were higher compared to healthy controls. In addition, concentrations of C6M, ELP-3 and X-FIB were higher in patients with septic shock who ultimately did not survive (N = 7) compared to those who recovered (N = 36).ConclusionECM turnover is induced in a model of systemic inflammation in healthy volunteers and was observed in patients with septic shock. Understanding interactions between systemic inflammation and ECM turnover may provide further insight into mechanisms underlying acute and persistent organ failure in sepsis.

Electrical cardiometry assessment of cardiac output compared to echocardiography in septic shock patients

Background Cardiac output (CO) measurement is essential for guiding therapeutic decisions in critically ill patients. Electrical cardiometry (EC), which is based on thoracic electrical bioimpedance, can measure CO in a continuous and noninvasive way. The benefits of EC are continuous monitoring, low time consumption, portability, and user independence. Transthoracic echocardiography has been a noninvasive method to assess CO despite being noncontiguous and operator dependent. Aim This study aimed to compare EC and echocardiography (Echo) in measuring CO in septic shock patients and assess the reliability and accuracy of EC for noninvasive CO monitoring. Patients and methods Fifty adult patients were admitted to the Critical Care Medicine Department, diagnosed with septic shock according to the surviving sepsis campaign, and fulfilling the inclusion and exclusion criteria from January 2023 to October 2023, and they were subjected to EC, Echo, and ECG recording. Results There was a strong positive significant correlation between CO measurements by echo and EC (r=0.988, P<0.001), and there was a strong positive significant correlation between stroke volume (SV) measurements by echo and EC (r=0.999, P<0.001). Also, there was a strong positive significant correlation between SV and CO measured by both techniques (r=0.782, P<0.001) (r=0.790, P<0.001, respectively). Conclusion Compared to Echo, EC can be used as a continuous, noninvasive method for monitoring CO and SV, as it provides accurate and reliable measurements.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study

BackgroundSeveral studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response.MethodsThirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80–85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions).ResultsCRT decreased significantly with both tests (from 5 [3.5–7.6] to 4 [2.4–5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3–5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin.ConclusionsOur findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

Association of copeptin levels with patient prognosis and survival in sepsis syndromes: a meta-analysis.

Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential significance in diagnosing sepsis. To investigate the levels of copeptin in patients with sepsis syndromes and evaluate its relation with patient prognosis and mortality. Four databases were searched for literature published from inception to the 8th of November 2022. Original research articles where copeptin was measured in sepsis patients and compared with controls were included. Data extraction and synthesis: study characteristics, levels of copeptin in the participants, and copeptin assay description were extracted. Levels of copeptin in patients were pooled and compared with controls in terms of the standard mean difference (SMD) generated using a random-effects model. Fifteen studies met the selection criteria. Copeptin levels were significantly higher in patients with sepsis, severe sepsis, and septic shock as compared to controls [(SMD: 1.49, 95% CI: 0.81-2.16, P<0.0001), (SMD: 1.94, 95% CI: 0.34-3.54, P=0.02), and (SMD: 2.17, 95% CI: 0.68-3.66, P=0.004), respectively]. The highest copeptin levels were noted in septic shock patients. The admission copeptin levels were significantly lower in survivors as compared to nonsurvivors (SMD: -1.73; 95% CI: -2.41 to -1.06, P<0.001). Copeptin was significantly elevated in sepsis, severe sepsis, and septic shock. Survivors had a significantly lower copeptin during admission. Copeptin offered an excellent predictability to predict 1-month mortality. Measuring the copeptin in sepsis patients can aid treating physicians to foresee patients' prognosis.

Extracorporeal Membrane Oxygenation as Circulatory Support in Adult Patients with Septic Shock: A Systematic Review.

The utilization of extracorporeal membrane oxygenation (ECMO) in adult patients experiencing septic shock is a subject of ongoing debate within the medical community. This study aims to comprehensively address this issue through a systematic review conducted in accordance with the PRISMA guidelines. The primary objective of this study is to assess the outcomes of ECMO utilization in adult patients diagnosed with septic shock, thereby providing insights into the potential benefits and uncertainties associated with this treatment modality. Our research encompassed a thorough search across electronic databases for relevant English-language articles published up until April 2023. The inclusion criteria were based on studies reporting on ECMO usage in adult patients with septic shock. Among the eligible studies meeting these criteria, a total of eleven were included in our analysis, involving a cohort of 512 patients. The mean age of the participants was 53.4 years, with 67.38% being male. In the pooled analysis, the mean survival rate following ECMO treatment was found to vary significantly across different ECMO modalities. Patients receiving venovenous-ECMO (VV-ECMO) and veno-venous-arterial ECMO (VVA-ECMO) demonstrated higher survival rates (44.5% and 44.4%, respectively) compared to those receiving venoarterial-ECMO (VA-ECMO) at 25% (p<0.05). A chi-square test of independence indicated that the type of ECMO was a significant predictor of survival (χ2(2) = 6.63, p=0.036). Additionally, patients with septic shock stemming from respiratory failure demonstrated survival rates ranging from 39% to 70%. Predictors of mortality were identified as older age and the necessity for cardiopulmonary resuscitation (CPR). In septic shock patients, ECMO outcomes align with established indications like respiratory and cardiogenic shock. VV-ECMO and VVA-ECMO suggest better prognoses, though the optimal mode remains uncertain. Patient selection should weigh age and CPR need. Further research is vital to determine ECMO's best approach for this population.

Constructing a predictive model for the death risk of patients with septic shock based on supervised machine learning algorithms

To construct and validate the best predictive model for 28-day death risk in patients with septic shock based on different supervised machine learning algorithms. The patients with septic shock meeting the Sepsis-3 criteria were selected from Medical Information Mart for Intensive Care-IV v2.0 (MIMIC-IV v2.0). According to the principle of random allocation, 70% of these patients were used as the training set, and 30% as the validation set. Relevant predictive variables were extracted from three aspects: demographic characteristics and basic vital signs, serum indicators within 24 hours of intensive care unit (ICU) admission and complications possibly affecting indicators, functional scoring and advanced life support. The predictive efficacy of models constructed using five mainstream machine learning algorithms including decision tree classification and regression tree (CART), random forest (RF), support vector machine (SVM), linear regression (LR), and super learner [SL; combined CART, RF and extreme gradient boosting (XGBoost)] for 28-day death in patients with septic shock was compared, and the best algorithm model was selected. The optimal predictive variables were determined by intersecting the results from LASSO regression, RF, and XGBoost algorithms, and a predictive model was constructed. The predictive efficacy of the model was validated by drawing receiver operator characteristic curve (ROC curve), the accuracy of the model was assessed using calibration curves, and the practicality of the model was verified through decision curve analysis (DCA). A total of 3 295 patients with septic shock were included, with 2 164 surviving and 1 131 dying within 28 days, resulting in a mortality of 34.32%. Of these, 2 307 were in the training set (with 792 deaths within 28 days, a mortality of 34.33%), and 988 in the validation set (with 339 deaths within 28 days, a mortality of 34.31%). Five machine learning models were established based on the training set data. After including variables at three aspects, the area under the ROC curve (AUC) of RF, SVM, and LR machine learning algorithm models for predicting 28-day death in septic shock patients in the validation set was 0.823 [95% confidence interval (95%CI) was 0.795-0.849], 0.823 (95%CI was 0.796-0.849), and 0.810 (95%CI was 0.782-0.838), respectively, which were higher than that of the CART algorithm model (AUC = 0.750, 95%CI was 0.717-0.782) and SL algorithm model (AUC = 0.756, 95%CI was 0.724-0.789). Thus above three algorithm models were determined to be the best algorithm models. After integrating variables from three aspects, 16 optimal predictive variables were identified through intersection by LASSO regression, RF, and XGBoost algorithms, including the highest pH value, the highest albumin (Alb), the highest body temperature, the lowest lactic acid (Lac), the highest Lac, the highest serum creatinine (SCr), the highest Ca2+, the lowest hemoglobin (Hb), the lowest white blood cell count (WBC), age, simplified acute physiology score III (SAPS III), the highest WBC, acute physiology score III (APS III), the lowest Na+, body mass index (BMI), and the shortest activated partial thromboplastin time (APTT) within 24 hours of ICU admission. ROC curve analysis showed that the Logistic regression model constructed with above 16 optimal predictive variables was the best predictive model, with an AUC of 0.806 (95%CI was 0.778-0.835) in the validation set. The calibration curve and DCA curve showed that this model had high accuracy and the highest net benefit could reach 0.3, which was significantly outperforming traditional models based on single functional score [APS III score, SAPS III score, and sequential organ failure assessment (SOFA) score] with AUC (95%CI) of 0.746 (0.715-0.778), 0.765 (0.734-0.796), and 0.625 (0.589-0.661), respectively. The Logistic regression model, constructed using 16 optimal predictive variables including pH value, Alb, body temperature, Lac, SCr, Ca2+, Hb, WBC, SAPS III score, APS III score, Na+, BMI, and APTT, is identified as the best predictive model for the 28-day death risk in patients with septic shock. Its performance is stable, with high discriminative ability and accuracy.

Serum Magnesium Levels in Patients Admitted with Septic Shock and Their Correlation with Outcome

Objective: To evaluate the initial serum magnesium levels of critically ill septic shock patients upon admission to the intensive care unit (ICU) and correlate these levels with the patients' requirements and outcomes, including ventilator support, length of stay in the ICU, occurrence of cardiac arrhythmias, and mortality rates.Methods: This was an observational study involving 60 patients who were admitted to the medical Intensive Care Unit (ICU) for septic shock. Serum magnesium levels were measured upon admission to the ICU. A comparison was made between patients with normal and abnormal magnesium levels at the time of admission to evaluate the need for vasopressor support, the average duration of assisted ventilation and dialysis, the incidence of arrhythmia, the average length of ICU stay, and mortality rates.Results: Out of the 60 cases studied, there were 42 males (70.00%) and 18 females (30.00%), resulting in a M:F ratio of 1:0.42. The mean age of both male and female patients was found to be comparable. The need for assisted ventilation and renal replacement therapy was found to be comparable in patients with normal and abnormal serum magnesium levels. The number of days for which assisted ventilation was required, the incidence of arrhythmia, the mean duration of ICU and hospital stay, and mortality were significantly higher in patients with abnormal magnesium levels at the time of ICU admission (P&lt;0.05).Conclusion: Abnormal serum magnesium levels are associated with increased morbidity and mortality in critically ill septic shock patients admitted to the ICU.

Assessing corticosteroid utilization and mortality risk in septic shock: insights from network meta-analysis

BACKGROUND: Despite current guidelines recommending corticosteroid administration in septic shock management, there is ongoing controversy regarding their impact on mortality rates and the most effective corticosteroid type. OBJECTIVES: To assess corticosteroid use and mortality risk in septic shock via network meta-analysis. METHODS: A comprehensive network meta-analysis was undertaken by retrieving articles from PubMed, Embase, and Scopus databases. Pertinent data encompassing baseline characteristics of articles, definitions of sepsis, types of corticosteroids employed, and mortality rates were systematically extracted from each article. The Manthel Hanzhel method alongside a network meta-analysis approach was employed to evaluate the influence of corticosteroid administration on mortality risk among individuals diagnosed with septic shock. RESULTS: Our analysis comprised a total of 50 articles. While indirect comparison failed to yield statistically significant results regarding the reduction in mortality risk, direct comparison indicated that corticosteroid administration was linked to a decreased risk of mortality among septic shock individuals (OR: 0.80; 95%CI: 0.68, 0.93; p Egger: 0.0550; p Heterogeneity: 0.0010; p: 0.0040). Furthermore, among all the types of corticosteroids analyzed, only the hydrocortisone and fludrocortisone combination demonstrated an association with reduced mortality risk in septic shock patients. Individuals receiving this combination therapy exhibited decreased likelihood of mortality compared to those receiving a placebo (OR: 0.78; 95%CI: 0.64, 0.96; p Egger: 0.3082; p Heterogeneity: 0.8570; p: 0.0190). CONCLUSION: Our study emphasizes the significance of corticosteroid therapy, particularly highlighting the hydrocortisone and fludrocortisone combination, for septic shock management.

Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients

BackgroundMicrovascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. MethodsThis cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. ResultsThe SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 μm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45–336) vs. 48 ng/mL (IQR 9–85); p = 0.052], CD44s [796ρg/mL (IQR 512–1995) vs. 526ρg/mL (IQR 287–750); p = 0.036], TBML [734ρg/mL (IQR 237–2396) vs. 95ρg/mL (IQR 63–475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04–1.40) vs. 0.07 ρg/mg (IQR 0.02–0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). ConclusionSDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.

Evaluating the predictive value of initial lactate/albumin ratios in determining prognosis of sepsis patients.

Sepsis remains a significant clinical challenge owing to its complex pathophysiology and variable prognosis. The early identification of patients at a higher risk of poor outcomes can be crucial for improving treatment strategies. This study aimed to evaluate the predictive value of early serum lactate and albumin levels and the lactate/albumin (L/A) ratio for 28-day prognosis in patients with sepsis. Patients diagnosed with sepsis between January 2021 and December 2022 were evaluated using a retrospective cohort methodology. Inclusion followed the International Consensus on sepsis and septic shock (Sepsis-3) guidelines and patients were selected based on well-defined criteria. Variables such as lactate, albumin, and the L/A ratio were documented within the first 24 hours of admission. Statistical analyses were performed using various tools, including the nonparametric Mann-Whitney U test and receiver operating characteristic curves. A total of 301 patients were divided into the survival (n = 167) and death (n = 134) groups. Notable differences were detected in the incidence of pulmonary infection, shock, lactate, albumin, and the L/A ratio. The L/A ratio was identified as a key predictor with an area under the curve of 0.868, an optimal cutoff value of >0.17, a sensitivity of 56.21%, and a specificity of 94.18%. Significant disparities in mortality rates and survival times were observed for the lactate, albumin, and L/A levels. This study underscores the predictive value of early serum lactate and albumin levels and the L/A ratio for 28-day prognosis in patients with sepsis, with the L/A ratio showing a superior predictive capability. These findings highlight the importance of L/A ratio as a robust and precise marker for evaluating the future clinical course of patients with sepsis, potentially aiding early detection and management.

Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

Positive correlation between echocardiographic tricuspid E peak velocity and central venous pressure in dogs: A preliminary study.

In the absence of vascular obstruction, central venous pressure (CVP) is a hydrostatic pressure in the cranial and caudal vena cava, providing valuable information about cardiac function and intravascular volume status. It is also a component in evaluating volume resuscitation in patients with septic shock and monitoring patients with right heart disease, pericardial disease, or volume depletion. Central venous pressure is calculated in dogs by invasive central venous catheterization, which is considered high-risk and impractical in critically ill patients. This study aimed to investigate the feasibility of using echocardiographic tricuspid E/E' as a noninvasive method to estimate CVP in anesthetized healthy dogs under controlled hypovolemic conditions. Ten male mixed-breed dogs were included in the study after a thorough health assessment. For hypovolemia induction, blood withdrawal was performed, and echocardiographic factors of the tricuspid valve, including peak E and E' velocities, were measured during CVP reduction. Repeated measures analysis of variance and Bonferroni post hoc tests were employed to compare the average difference between measured echocardiographic indices and CVP values derived from catheterization and intermittent measurement methods. Spearman's ρ correlation coefficient was used to evaluate the correlation between echocardiographic indices and CVP. E peak velocity had a significant negative correlation with venous blood pressure phases (r=-0.44, P=.001), indicating a decrease in peak E velocity with progressive CVP reduction. However, tricuspid valve E' peak velocity and E/E' did not correlate with CVP, suggesting that these parameters are not reliable for CVP estimation in dogs.

Clinical characteristics and risk factors for septic shock in patients with pyometra: A retrospective multicenter cohort study

BackgroundPyometra is a disease characterized by the collection of pus in the uterus. The clinical characteristics and etiology of pyometra have not been sufficiently described. In this study, we investigated the clinical characteristics, epidemiology, outcomes, and risk factors of septic shock in patients with pyometra. MethodsPatients with pyometra admitted to one of four university-affiliated hospitals between January 2010 to August 2022 were enrolled. Pyometra cases associated with peripartum infection and surgical site infection were excluded. Clinical characteristics and outcomes of pyometra were described, and pyometra patients with or without septic shock were compared. ResultsA total of 192 patients was included. Twenty-eight-day all-cause mortality was 5.0%, and the 1-year recurrence rate was 6.3%. Median patient age was 77.5 years. The two most common symptoms were abdominal pain (49.0%) and vaginal discharge (47.9%). Escherichia coli (40.1%), Klebsiella pneumoniae (16.7%), and Streptococcus spp.(16.0%) were the pathogens most frequently isolated by conventional culture; those isolated from polymerase chain reaction were Mycoplasma hominis (48.0%), and Ureaplasma spp. (32.0%). In multivariable analysis, fever, uterine perforation, and dementia were associated with increased incidence of septic shock, while vaginal discharge was associated with a lower incidence of septic shock. ConclusionsOur findings suggest that pyometra is a unique gynecological infectious syndrome in post-menopausal individuals. The most common associated pathogens are similar to those involved in urinary tract infections rather than those of sexually transmitted diseases. Decreased cognitive function could delay early diagnosis of pyometra and lead to septic shock and higher mortality.

IMPACT OF NOREPINEPHRINE DOSAGE INCREASE AND VOLUME EXPANSION ON CAPILLARY REFILL TIME IN SEPTIC SHOCK PATIENTS

Background: When evaluating patients with acute circulatory failure, one clinical feature that may be quickly determined at the bedside is the capillary refill time (CRT).Objective: The objective of this observational study was to describe the changes in CRT that occur as a result of volume expansion and increased dosages of norepinephrine, along with related macro-circulatory variables, in patients suffering from septic shock. Study Design: This was an observational study. Setting: The study was conducted at Bahria Town International Hospital Lahore and Services Institute of Medical Sciences. Duration of Study: The study was conducted over six months from January 2, 2023, to July 30, 2023. Methods: We measured mean arterial pressure (MAP), cardiac index (CI), and five consecutive CRT readings in 40 septic shock patients. These measurements were taken before and after a 500 mL saline infusion in 20 patients and before and after an increase in norepinephrine dosage in another 20 patients. Results: The "norepinephrine" group had lower SAPS II and SOFA scores than the "volume expansion" group. When all patients were assessed together, volume expansion significantly lowered heart rate while increasing MAP, diastolic arterial pressure, CI, CVP, and CRT. Fluid-induced increases in CI of ≥ 15% were observed in 11 patients (55%). In fluid responders, fluid infusion significantly raised MAP by 31% (11-49%) and CI by 26% (20-42%). Increased norepinephrine levels may lower CRT in patients with a baseline value of fewer than 3 seconds. Increasing norepinephrine has a low possibility of decreasing CRT in patients with baseline CRT ≥ 3 seconds if the MAP increase is &lt;15%. However, the decrease in CRT is inconsistent in patients with baseline CRT ≥ 3 seconds when norepinephrine increases MAP by ≥ 15%. Univariate regression analysis revealed a correlation between the absolute value of CRT and lactate levels, heart rate, norepinephrine dosage, gender, SAPS II, and ICU mortality. In a multivariate analysis that included all physiological parameters with a p-value &lt;0.1 in univariate linear regression, only lactate upon admission had a significant association with the absolute value of CRT. Conclusion: CRT uncommonly improves with therapy in individuals with septic shock and prolonged CRT when volume expansion raises cardiac output by &lt;15% and increasing the dosage of norepinephrine increases MAP by &lt;15%. CRT's response varies when there are significant effects of fluid infusion on cardiac output and norepinephrine on MAP; in some patients, it decreases while remaining consistent in others. CRT functions as an indicator of microcirculation in this context.

Composite adverse events compared early versus conventional cessation of hydrocortisone in patients with septic shock: Randomized-controlled trial (The CESSHYDRO study)

Background: Intravenous hydrocortisone has benefits in the treatment of septic shock patients, but there are adverse events mentioned in the secondary outcomes of several studies, such as hyperglycemia, hypernatremia, secondary infection, and muscle weakness. In addition, there are no recommendations regarding the precise duration and steps to discontinue hydrocortisone administration. The CESSHYDRO trial evaluates the adverse outcomes of intravenous hydrocortisone between early cessation versus conventional cessation of hydrocortisone in septic shock patients. Methods: The CESSHYDRO trial is a single-center, double-blind, randomized controlled clinical trial conducted at Siriraj Hospital. One hundred and eighty septic shock patients receiving vasopressors and hydrocortisone at least 200 mg/day with hemodynamic stability will be included. The patients are randomized into 2 groups: intervention A (early cessation of hydrocortisone) and intervention B (conventional cessation). The primary outcomes were composite adverse events, including hyperglycemia, hypernatremia, muscle weakness, and new infections. Hypothesis: We hypothesize that early cessation of hydrocortisone in patients with septic shock would reduce composite adverse events including hyperglycemia, hypernatremia, muscle weakness, and the new onset of infection. Ethics and dissemination: The trial receives ethical approval from Siriraj Hospital, Mahidol University (COA No.SI012/2023). Trial registration: ClinicalTrials.govNCT05818826. Registered on April 19, 2023.