Outcome Of Septic Patients Research Articles

Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy.

As a life-threatening multiple organ dysfunction attributable to maladjusted host immune responses to infection, sepsis is usually the common pathway to serious prognosis and death for numerous infectious diseases all over the world. Sepsis-associated encephalopathy (SAE) is frequently complicated by septic conditions, and is one of the most important reasons for increased mortality and poor outcomes in septic patients which is still an urgent clinical problem need to be solved. In this research, a conspicuously discovery of treatment-related translational use for berberine was elaborated. The results revealed that berberine treatment significantly restored cognitive impairment in sepsis mice. Reduced expression levels of TNF-α, IL-1α, and C1qA were exhibited in the hippocampus of the berberine treatment group, and attenuated effect of declining neo-neuron, activation of microglia and astrocytes in the hippocampus of mice with sepsis were also found. Moreover, berberine inhibits microglia-stressed A1 astrocytes by inhibiting HMGB1 signaling was revealed, then the molecular mechanism of HMGB1/RAGE signaling inhibition leads to the better outcome of SAE was elucidated. To summarize, this research indicated that berberine targets HMGB1/RAGE signaling to inhibit microglia-stressed A1 astrocyte and neo-neuron decline, which consequently alleviates sepsis-induced cognitive impairment. Collectively, berberine may serve as potential therapeutic drug and HMGB1/RAGE signaling would be a novel target for medicine development for treating SAE.

Admission Blood Glucose Is Associated With the 30-Days Mortality in Septic Patients: A Retrospective Cohort Study.

Background: Sepsis, as one of the severe diseases, is frequently observed in critically ill patients, especially concurrent with diabetes. Whether admission blood glucose is associated with the prognosis, and outcome of septic patients is still debatable.Methods: We retrospectively reviewed and analyzed the demographic characteristics of septic patients in the Medical Information Mart for Intensive Care III (MIMIC III, version 1.4) between June 2001 and October 2012. The Chi-square and Fisher's exact tests were used for the comparison of qualitative variables among septic patients with different glucose levels and the 30-day mortality in septic patients with diabetes or not. Univariate and stepwise multivariate Cox regression analyses were used to determine the risk factors for 30-day mortality. Kaplan-Meier analysis was conducted to reveal the different 30-day survival probabilities in each subgroup.Results: A total of 2,948 septic patients (910 cases with diabetes, 2,038 cases without diabetes) were ultimately included in the study. The 30-day mortality was 32.4% (956/2,948 cases) in the overall population without any difference among diabetic and non-diabetic septic patients (p = 1.000). Admission blood glucose levels <70 mg/dl were only observed to be significantly associated with the 30-day mortality of septic patients without diabetes (hazard ratio (HR) = 2.48, p < 0.001). After adjusting for confounders, age >65 years (HR = 1.53, p = 0.001), the Sequential Organ Failure Assessment (SOFA) score >5 (HR = 2.26, p < 0.001), lactic acid >2 mmol/L (Lac, HR = 1.35, p = 0.024), and platelet abnormality (<100 k/ul: HR = 1.49; >300 k/ul: HR = 1.36, p < 0.001) were the independent risk factors for 30-day mortality in septic patients with diabetes. In non-diabetes population, age >65 years (HR = 1.53, p < 0.001), non-White or non-Black patients (HR = 1.30, p = 0.004), SOFA score >5 (HR = 1.56, p < 0.001), blood glucose <70 mg/dl (HR = 1.91, p = 0.003), anion gap (AG) >2 mmol/L (HR = 1.60, p < 0.001), Lac (HR = 1.61, p < 0.001), urea nitrogen >21 mg/dl (HR = 1.45, p = 0.001), alanine aminotransferase (ALT, HR = 1.31, p = 0.009), total bilirubin >1.2 mg/dl (HR = 1.20, p = 0.033), and low hemoglobin (HR = 1.34, p = 0.001) were the independent risk factors for 30-day mortality.Conclusions: Our results indicate admission blood glucose, especially in terms of <70 mg/dl, is the key signaling in predicting the worse 30-day survival probability of septic patients without diabetes, which could help clinicians to make a more suitable and precise treatment modality in dealing with septic patients.

Impact of Permissive Hypoxia and Hyperoxia Avoidance on Clinical Outcomes in Septic Patients Receiving Mechanical Ventilation: A Retrospective Single-Center Study.

Background Septic patients often require mechanical ventilation due to respiratory dysfunction, and effective ventilatory strategies can improve survival. The effects of the combination of permissive hypoxia and hyperoxia avoidance for managing mechanically ventilated patients are unknown. This study examines these effects on outcomes in mechanically ventilated septic patients. Methods In a retrospective before-and-after study, we examined adult septic patients (aged ≥18 years) requiring mechanical ventilation at a university hospital. On April 1, 2017, our mechanical ventilation policy changed from a conventional oxygenation target (SpO2: ≥96%) to more conservative targets with permissive hypoxia (SpO2: 88-92% or PaO2: 60 mmHg) and hyperoxia avoidance (reduced oxygenation for PaO2 > 110 mmHg). Patients were divided into a prechange group (April 2015 to March 2017; n = 83) and a postchange group (April 2017 to March 2019; n = 130). Data were extracted from clinical records and insurance claims. Using a multiple logistic regression model, we examined the association of the postchange group (permissive hypoxia and hyperoxia avoidance) with intensive care unit (ICU) mortality after adjusting for variables such as Sequential Organ Failure Assessment (SOFA) score and PaO2/FiO2 ratios. Results The postchange group did not have significantly lower adjusted ICU mortality (0.67, 0.33-1.43; P = 0.31) relative to the prechange group. However, there were significant intergroup differences in mechanical ventilation duration (prechange: 11.0 days, postchange: 7.0 days; P = 0.01) and ICU stay (prechange: 11.0 days, postchange: 9.0 days; P = 0.02). Conclusions Permissive hypoxia and hyperoxia avoidance had no significant association with reduced ICU mortality in mechanically ventilated septic patients. However, this approach was significantly associated with shorter mechanical ventilation duration and ICU stay, which can improve patient turnover and ventilator access.

Estimation of D lactat level as amarker of bacterial translocation in gut failure incritically ill pediatric patients

Abstract Background Sepsis is defined as life-threatening multi organ failure caused by a dysregulated host response to infection leading to development of gut failure, D-lactate is produced by indigenous bacteria in the gastrointestinal tract lactoferrin is important constitute of human milk and other body fluid act to improve gut function. Aim of the Work To test effect of lactoferrin supplementation for improving gut barrier function, prognosis and the outcome of septic patients using D lactate as a marker of bacterial translocation in sepsis with gut failure. Patients and Methods After ethical committee approval and informed consent from the parents, this double armed single blinded therapeutic clinical trial study was conducted on 40 Egyptian children admitted to PICUs of Ain Shams University Hospitals, by diagnosis sepsis and gut failure, twenty of them weren't supplemented with LF (group 1) and the other twenty were supplemented with it (group 2). D lactate level was measured in plasma using ELISA. Results The study show highly significant difference between Patient and control group in D lactate level, and we found no statistical difference before and after giving lactoferrin in our septic patient who weren’t in treatment of sepsis and gut failure. And we found plasma D lactate higher in non survivors with p value.048. and cut of point&amp;lt; 43.9 mmol\L Conclusion Lactoferrin supplementation was not beneficial in pediatric septic patient with gut failure and did not improve outcome or prognosis of patients, D lactate can be used as a predictor of intestinal failure severity and mortality. D lactate may be predictor of gut failure in sepsis and mortality

HYDROCORTISONE, VITAMIN C, AND THIAMINE SUPPLEMENTATION VS PLACEBO IN PATIENTS WITH SEPSIS

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: While retrospective studies have shown conflicting outcomes in septic patients who received hydrocortisone, vitamin C, and thiamine compared to placebo, randomized controlled trials (RCTs) failed to show significant differences between the two groups in 30-day and in hospital mortality, hospital length of stay, and change in sequential organ failure (SOFA) score. We conducted a systematic review and meta-analysis to evaluate the beneficial effect of hydrocortisone, vitamin C, and thiamine compared to placebo in septic patients. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane databases from inception through March 2021 for RCTs comparing hydrocortisone, vitamin C, and thiamine vs placebo in septic patients. Outcome of interests were 30-day and in hospital mortality, hospital length of stay, and change in SOFA score from hospital presentation and day 3 or day 4. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The random-effects model was used for all variables, and publication bias was assessed using Egger's test. RESULTS: Three RCTs published between April 2020 and February 2021 examining 717 patients were included in our analysis. The outcomes of these studies evaluated 30-day and in hospital mortality, hospital length of stay, and change in SOFA score from hospital presentation. Our analysis showed no significant difference in 30-day and in hospital mortality rates between the treatment group and placebo group with relative risk ratio of 0.975 (95% CI 0.766 to 1.241) (I2 =0.000) and 1.066 (95% CI 0.724 to 1.571) (I2=0.000) respectively. Our analysis also suggested no difference in the length of hospital stay and change is SOFA score from hospital presentation to day 3 or day 4 in the two groups with standardized mean difference of -0.031 (95% CI -0.204 to 0.141, P-value = 0.722) and 0.074 (95% CI -0.234 to 0.381, P-value = 0.639). CONCLUSIONS: Our analysis suggests no significant improvement in 30-day and in hospital mortality rate, hospital length of stay, or change in SOFA score in septic patients treated with hydrocortisone, vitamin C and thiamine compared to placebo. CLINICAL IMPLICATIONS: Hydrocortisone, vitamin C and thiamine administration provides no mortality benefit, decrease in hospital stay, or improvement in SOFA scores in patients with sepsis. DISCLOSURES: No relevant relationships by Mohammad Darweesh, source=Web Response No relevant relationships by chris haas, source=Web Response No relevant relationships by Ibrahim Haddad, source=Web Response No relevant relationships by Metri Haddaden, source=Web Response

The expression of STEAP4 in peripheral blood predicts the outcome of septic patients.

BackgroundSepsis is a systemic disease characterized by extensive inflammatory responses and impaired organ function, which are characteristics that make it easily missed and complex to treat. A large number of laboratory and clinical studies on the diagnosis and treatment of sepsis have been continuously carried out, confirming the importance of mitochondrial function during the development of sepsis. STEAP4 is an important metalloreductase in mitochondria, which is involved in the biogenesis and respiratory chain of mitochondria. The role of STEAP4 in inflammation remains controversial. Research in this field may contribute to the development of new diagnostic and treatment options for sepsis.MethodsThe expression of STEAP4 was measured in the peripheral blood of patients with severe sepsis and compared with healthy controls. Cell and mouse inflammatory models were established to detect the expression of STEAP4 and other inflammatory cytokines.Results(I) The expression of STEAP4 in the peripheral blood of patients with severe sepsis is higher than that of healthy volunteers (P<0.01), which is related to the SOFA score and transaminase. (II) STEAP4 has a certain predictive effect on the outcome of patients [area under curve (AUC) =0.696, P<0.05, 95% CI: 0.528 to 0.833]. (III) Inflammation led to increased expression of STEAP4 gene in RAW264.7 cells and mouse liver tissue.ConclusionsThe expression of STEAP4 is elevated in the early stage of sepsis and the degree of its elevation can be used to predict the clinical outcome of sepsis patients.

Intensive Care Unit Volume of Sepsis Patients Does Not Affect Mortality: Results of a Nationwide Retrospective Analysis.

There is little research evaluating outcomes from sepsis in intensive care units (ICUs) with lower sepsis patient volumes as compared to ICUs with higher sepsis patient volumes. Our objective was to compare the outcomes of septic patients admitted to ICUs with different sepsis patient volumes. We included all patients from the eICU-CRD database admitted for the management of sepsis with blood lactate ≥ 2mmol/L within 24 hours of admission. Our primary outcome was ICU mortality. Secondary outcomes included hospital mortality, 30-day ventilator free days, and initiation of renal replacement therapy (RRT). ICUs were grouped in quartiles based on the number of septic patients treated at each unit. 10,716 patients were included in our analysis; 272 (2.5%) in low sepsis volume ICUs, 1,078 (10.1%) in medium-low sepsis volume ICUs, 2,608 (24.3%) in medium-high sepsis volume ICUs, and 6,758 (63.1%) in high sepsis volume ICUs. On multivariable analyses, no significant differences were documented regarding ICU and hospital mortality, and ventilator days in patients treated in lower versus higher sepsis volume ICUs. Patients treated at lower sepsis volume ICUs had lower rates of RRT initiation as compared to high volume units (medium-high vs. high: OR = 0.78, 95%CI = 0.66-0.91, P-value = 0.002 and medium-low vs. high: OR = 0.57, 95%CI = 0.44-0.73, P-value < 0.001). The previously described volume-outcome association in septic patients was not identified in an intensive care setting.

Association of fluid balance trajectories with clinical outcomes in patients with septic shock: a prospective multicenter cohort study

BackgroundSeptic shock has a high incidence and mortality rate in Intensive Care Units (ICUs). Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload (FO), which is associated with poor clinical outcomes. A single point value of fluid cannot provide enough fluid information. The aim of this study was to investigate the impact of fluid balance (FB) latent trajectories on clinical outcomes in septic patients.MethodsPatients were diagnosed with septic shock during the first 48 h, and sequential fluid data for the first 3 days of ICU admission were included. A group-based trajectory model (GBTM) which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB. The primary outcomes were hospital mortality, organ dysfunction, major adverse kidney events (MAKE) and severe respiratory adverse events (SRAE). We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes.ResultsNine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis, and three latent FB trajectories were detected. 64 (6.5%), 841 (85.3%), and 81 (8.2%) patients were identified to have decreased, low, and high FB, respectively. Compared with low FB, high FB was associated with increased hospital mortality [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.22–2.17], organ dysfunction [odds ratio (OR) 2.18, 95% CI 1.22–3.42], MAKE (OR 1.80, 95% CI 1.04–2.63) and SRAE (OR 2.33, 95% CI 1.46–3.71), and decreasing FB was significantly associated with decreased MAKE (OR 0.46, 95% CI 0.29–0.79) after adjustment for potential covariates.ConclusionLatent subgroups of septic patients followed a similar FB progression. These latent fluid trajectories were associated with clinical outcomes. The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.

Recognition in Emergency Department of Septic Patients at Higher Risk of Death: Beware of Patients without Fever.

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed.

TIGIT modulates sepsis-induced immune dysregulation in mice with preexisting malignancy.

TIGIT is a recently identified coinhibitory receptor that is upregulated in the setting of cancer and functionally contributes to the impairment of antitumor immunity. However, its role during sepsis is unknown. Because patients with cancer are 10 times more likely to die of sepsis than previously healthy (PH) patients with sepsis, we interrogated the role of TIGIT during sepsis in the context of preexistent malignancy. PH mice or cancer (CA) mice inoculated with lung carcinoma cells were made septic by cecal ligation and puncture (CLP). We found that sepsis induced TIGIT upregulation predominantly on Tregs and NK cells in both PH and CA mice. Anti-TIGIT Ab improved the 7-d survival of CA septic mice but not PH mice after CLP. Treatment of CA septic animals but not PH septic animals with anti-TIGIT mAb significantly reversed sepsis-induced loss of CD4+ T cells, CD8+ T cells, Foxp3+ Treg, and CD19+ B cells in the spleen, which was the result of decreased caspase-3+ apoptotic cells. In sum, we found that anti-TIGIT Ab reversed sepsis-induced T cell apoptosis in CA septic mice and led to a significant survival benefit, suggesting its use as a potential immunotherapy to improve outcomes in septic patients with cancer.

Prognostic value of hemodynamic indices in patients with sepsis after fluid resuscitation.

BACKGROUNDSepsis usually causes hemodynamic abnormalities. Hemodynamic index is one of the factors to identify the severity of sepsis and an important parameter to guide the procedure of fluid resuscitation. The present study investigated whether the assessment of hemodynamic indices can predict the outcomes of septic patients undergoing resuscitation therapy.AIMTo evaluate the prognostic value of hemodynamic indices in patients with sepsis after fluid resuscitation.METHODSA retrospective study was conducted in 120 patients with sepsis at Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University between October 2016 and October 2019. All patients were treated with sodium chloride combined with dextran glucose injection for fluid resuscitation. Patients’ hemodynamic parameters were monitored, including heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), mean arterial pressure (MAP), central venous pressure (CVP), and central venous oxygen saturation. The prognostic value of hemodynamic indices was determined based on the prognosis status.RESULTSDuring fluid resuscitation, 86 patients developed septic shock and 34 did not. Ninety-nine patients survived and 21 patients died at 28 d after the treatment. Heart rate, CI, mean arterial pressure, SVRI, and CVP were higher in patients with septic shock and patients who died from septic shock than in non-shock patients and patients who survived, and central venous oxygen saturation was lower in patients with shock and patients who died than in non-shock patients and the survivors (P < 0.05). When prognosis was considered as a dependent variable and hemodynamic parameters was considered as independent variables, the results of a logistic regression analysis showed that CI, SVRI, and CVP were independent risk factors for septic shock, and CI was an independent risk factor for 28-d mortality (P < 0.05).CONCLUSIONHemodynamic indices can be used to evaluate the prognosis of septic patients after fluid resuscitation.

Expression of Exhaustion Markers on CD8+ T-Cell Patterns Predict Outcomes in Septic Patients Admitted to the ICU.

There is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis. Observational prospective study. Two ICUs in a teaching hospital (France). Eighty patients with sepsis admitted to the ICU. Quantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ). Using unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes. Easy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.

Ratio of serum procalcitonin to monocytic HLA-DR as a reliable parameter in prognosis prediction of sepsis

BackgroundWe evaluated the prognostic potential of the ratio of serum procalcitonin to monocytic HLA-DR for 28-day mortality in sepsis. MethodsIn this retrospective study, a total of 91 patients with sepsis were enrolled. Clinical and laboratory data detected on admission (D0) and 7 days thereafter (D7) including the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment (admission SOFA), serum lactate, D-dimer, mHLA-DR, procalcitonin, platelet and white blood cell count, neutrophil-to-lymphocyte ratio were collected. The PCT/mHLA-DR ratio, the changes in mHLA-DR and WBC on day 7 compared with those on the day of admission and PCT clearance were calculated. Receiver operating characteristic curves, Kaplan-Meier survival curves, DeLong test and Cox regression analyses were used to assess and compare their predictive values. ResultsAmong all studied parameters, D7-PCT/mHLA-DR showed the best discriminatory property to differentiate survivors from non-survivors and was identified as an independent predictor of 28-day mortality. ConclusionThe D7-PCT/mHLA-DR ratio was more sensitive than either biomarker alone in predicting fatal outcome in septic patients. Combining pro-inflammatory and immunosuppression biomarkers might improve the prognostic accuracy in sepsis.

Protective effects of farnesyltransferase inhibitor on sepsis-induced morphological aberrations of mitochondria in muscle and increased circulating mitochondrial DNA levels in mice

Sepsis remains a leading cause of mortality in critically ill patients and is characterized by multi-organ dysfunction. Mitochondrial damage has been proposed to be involved in the pathophysiology of sepsis. In addition to metabolic impairments resulting from mitochondrial dysfunction, mitochondrial DNA (mtDNA) causes systemic inflammation as a damage-associated molecular pattern when it is released to the circulation. Metabolic derangements in skeletal muscle are a major complication of sepsis and negatively affects clinical outcomes of septic patients. However, limited knowledge is available about sepsis-induced mitochondrial damage in skeletal muscle. Here, we show that sepsis induced profound abnormalities in cristae structure, rupture of the inner and outer membranes and enlargement of the mitochondria in mouse skeletal muscle in a time-dependent manner, which was associated with increased plasma mtDNA levels. Farnesyltransferase inhibitor, FTI-277, prevented sepsis-induced morphological aberrations of the mitochondria, and blocked the increased plasma mtDNA levels along with improved survival. These results indicate that protein farnesylation plays a role in sepsis-induced damage of the mitochondria in mouse skeletal muscle. Our findings suggest that mitochondrial disintegrity in skeletal muscle may contribute to elevated circulating mtDNA levels in sepsis.

Early Recognition and Management of Sepsis in the Elderly: A Case Study.

Sepsis is a life-threatening and debilitating sickness in the elderly. This case study explores the importance of adequate assessment of patients on their initial presentation to the emergency department, during hospitalization, and before discharge. The clinical evaluation, recognition, and management of sepsis continue to be essential for patient survival to prevent and decrease the mortality rate. Some changes go on in the elderly organ systems and can lead to delay in identifying and treatment implementation. The use of the Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3) to anticipate outcomes in septic patients and the use of the Survival Sepsis Campaign for treatment guidelines promptly to improve outcomes are crucial. This article aims to inform clinicians and nurses of the importance of early recognition of subtle signs and symptoms and the management of sepsis in the elderly.

Growth Arrest-Specific Gene 6 Administration Ameliorates Sepsis-Induced Organ Damage in Mice and Reduces ROS Formation In Vitro.

Sepsis is a widespread life-threatening disease, with a high mortality rate due to inflammation-induced multiorgan failure (MOF). Thus, new effective modulators of the immune response are urgently needed to ameliorate the outcome of septic patients. As growth arrest-specific gene 6 (Gas6)/Tyro3, Axl, MerTK (TAM) receptors signaling has shown immunomodulatory activity in sepsis, here we sought to determine whether Gas6 protein injection could mitigate MOF in a cecal slurry mouse model of sepsis. Mice, divided into different groups according to treatment—i.e., placebo (B), ampicillin (BA), Gas6 alone (BG), and ampicillin plus Gas6 (BAG)—were assessed for vitality, histopathology and cytokine expression profile as well as inducible nitric oxide synthase (iNOS), ALT and LDH levels. BAG-treated mice displayed milder kidney and lung damage and reduced levels of cytokine expression and iNOS in the lungs compared to BA-treated mice. Notably, BAG-treated mice showed lower LDH levels compared to controls. Lastly, BAG-treated cells of dendritic, endothelial or monocytic origin displayed reduced ROS formation and increased cell viability, with a marked upregulation of mitochondrial activity. Altogether, our findings indicate that combined treatment with Gas6 and antibiotics ameliorates sepsis-induced organ damage and reduces systemic LDH levels in mice, suggesting that Gas6 intravenous injection may be a viable therapeutic option in sepsis.

O052 / #846: SEPSIS ASSOCIATED AKI PHENOTYPES ARE ASSOCIATED WITH UNIQUE PATIENT OUTCOMES

Aims & Objectives: Although sepsis associated acute kidney injury (S-AKI) is generally associated with poor patient outcomes, the majority of epidemiology utilize an all-inclusive and binary classification for AKI. The clinical phenotype of AKI, however, varies considerably. We sought to delineate the associations of AKI phenotypes with outcomes in septic patients. Methods: Post-hoc analysis of a multi-national study of critically ill children. AKI was defined by KDIGO stage in the first 48 hours. Temporal phenotype was defined as transient (return to baseline by 48 hours) or persistent (injury beyond 48 hours). Severity phenotype was delineated as mild (stage 1) or severe (stage 2-3). The primary outcome was mortality censored at 28-days. ICU course complexity was assessed by mechanical ventilation, length of stay, and use of extracorporeal therapy. Results: Sepsis was present in 757 (15.4%), AKI in 1275 (26.1%), and S-AKI in 307 (6.3%) of 4898 patients (male, 54.8%). S-AKI was associated with increased mortality versus sepsis alone (12.1% vs. 4.7%, p-value <0.001). Mortality in S-AKI varied by AKI duration: persistent (13.9%), transient (12.1%) (p<0.001 vs. no AKI for both). Mortality also varied by AKI severity: severe (18.6%), mild (4.4%) (p<0.001 versus no AKI only for severe). Sub-phenotyping associated with unique mortality incidence: mild-transient (4.4%), mild-persistent (9.4%), severe-transient (21.6%), and severe-persistent (15.8%). Complex ICU outcome ranged from 15% to 55% between the S-AKI phenotypes versus 34.5% for “any” S-AKI. Conclusions: Our data indicate clinical S-AKI subphenotypes are associated with unique outcomes. Refinement in S-AKI classification may allow population enrichment facilitating biologic analysis, trial design, and targeted therapeutics.

IMPACT OF TIMING OF RENAL REPLACEMENT THERAPY INITIATION ON OUTCOME OF ACUTE KIDNEY INJURY IN SEPTIC PATIENTS

Objective: To identify whether the timing of initiation of continuous renal replacement therapy affects outcome in septic patients with acute kidney injury in term of 28 days mortality.&#x0D; Study Design: Cross sectional analytical study.&#x0D; Place and Duration of Study: This research was conducted at department of Anaesthesiology and critical careunit of the Aga Khan University Hospital, Karachi, from Oct 2018 to Jun 2019.&#x0D; Methodology: The study reviewed all adult patients aged &gt;18 years who developed acute kidney injury afterseptic shock and required continuous renal replacement therapy in surgical intensive care unit. Considering thevalue of blood urea nitrogen, patients were classified into two groups. One was in early group that‟s was defined as blood urea nitrogen value of &lt;100 mg/dl just before continuous renal replacement therapy initiation while the patients who have blood urea nitrogen value of ≥100 mg/dl just prior to continuous renal replacement therapy initiation were classified as late group. Kaplan-Meier survival analysis was performed and median survival was computed.&#x0D; Results: Forty patients were included for analysis. There were thirty patients (75%) in early group in whomcontinuous renal replacement therapy was started with mean blood urea nitrogen of 66 ± 20.2 mg/dL and 10(25%) patients were in late group with mean blood urea nitrogen of 137 ± 28.4 mg/dL. The overall survival ratesin both groups were 49.6%, and 10.4% at 10 and 25 days, respectively. Median survival time was not statisticallysignificant between early and late continuous renal replacement...........

Persistently higher serum sCD40L levels are associated with outcome in septic patients

BackgroundSoluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and surgical sepsis patients (SS) during the first 3 days after intensive care unit (ICU) admission and to observe the association between sCD40L and mortality.MethodsTime changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with those in 19 SWS patients. Serum sCD40L concentration was detected by ELISA. Survival at 28 days served as the endpoint.ResultsSS had significantly higher sCD40L levels than SWS and control patients. We observed an association between sCD40L levels ≥1028.75 pg/mL at day 2 and 28-day mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P = 0.007). We could not discover any significant differences in sex, presence of septic shock, site of infection, length of stay in the ICU, PaO2/FiO2 ratio, incidence of AKI, ARDS, or type of surgery between nonsurvivors and survivors.ConclusionsSeptic patients show persistently higher circulating sCD40L levels in the first 3 days after ICU admission, and serum sCD40L levels are associated with the mortality of patients with sepsis. Thus, serum sCD40L may be used as a reliable biomarker and therapeutic target in sepsis.

Role of central venous-arterial PCO2 difference in prediction of clinical outcome in ICU septic patients

ABSTRACT Background: Identification of tissue hypoxia and hypoperfusion plays an important role in the management of critically ill patients. Although the venous-arterial PCO2 difference (ΔPCO2) cannot serve as a marker of tissue hypoxia, it is considered a marker of the adequacy of venous blood flow (Cardiac output). The present study aimed to evaluate the role of venous-arterial PCO2 gradient in prediction of outcome in septic patients admitted to ICU. Patients and methods: 100 adult patients fulfilled the criteria of severe sepsis or septic shock admitted to Emergency Intensive Care Unit, were divided in two groups according to ΔPCO2. The high ΔpCO2 group (ΔpCO2 > 6 mmHg) included 58 patients and the normal ΔpCO2 (ΔpCO2 ≤ 6 mmHg) included 42 patients. Clinical scoring systems were recorded. Clinical outcome including organ dysfunction and mortality was recorded. Results: The high ΔPCO2 group showed significant lower blood glucose level (p = 0.038) than the normal ΔPCO2 group. Serum lactate, heart rate, and APACHE score were significantly higher in high ΔPCO2 group than normal ΔPCO2 group (p, 0.012, 0.013, and 0.020, respectively). As regard to the clinical outcome, patient mortality was significantly higher (p = 0.042) in high ΔPCO2 group than normal ΔPCO2 group and the number of organ dysfunction was higher in high ΔPCO2 group than normal ΔPCO2 group but not reached a significant level (p = 0.625). Conclusions: ΔPCO2 is a reliable index for early prediction of clinical outcome including organ dysfunction and mortality in patients with sepsis and septic shock.