Clinical Outcome Of Septic Patients Research Articles

Association between acetaminophen administration and clinical outcomes in patients with sepsis admitted to the ICU: a retrospective cohort study.

Sepsis, affecting over 30 million people worldwide each year, is a key mortality risk factor in critically ill patients. There are significant regional discrepancies in its impact. Acetaminophen, a common over-the-counter drug, is often administered to control fever in suspected infection cases in intensive care units (ICUs). It is considered generally safe when used at therapeutic levels. Despite its widespread use, there's inconsistent research regarding its efficacy in sepsis management, which creates uncertainties for ICU doctors about its possible advantages or harm. To address this, we undertook a retrospective cohort study utilizing the MIMIC-IV database to examine the correlation between acetaminophen use and clinical outcomes in septic patients admitted to the ICU. We gathered pertinent data on sepsis patients from the MIMIC-IV database. We used propensity score matching (PSM) to pair acetaminophen-treated patients with those who were not treated. We then used Cox Proportional Hazards models to examine the relationships between acetaminophen use and factors such as in-hospital mortality, 30-day mortality, hospital stay duration, and ICU stay length. The data analysis involved 22,633 sepsis patients. Post PSM, a total of 15,843 patients were matched; each patient not receiving acetaminophen treatment was paired with two patients who received it. There was a correlation between acetaminophen and a lower in-hospital mortality rate (HR 0.443; 95% CI 0.371-0.530; p < 0.001) along with 30-day mortality rate (HR 0.497; 95% CI 0.424-0.583; p < 0.001). Additionally, it correlated with a decrease in the duration of hospitalization [8.4 (5.0, 14.8) vs. 9.0 (5.1, 16.0), p < 0.001] and a shorter ICU stay [2.8 (1.5, 6.0) vs. 3.1 (1.7, 6.5); p < 0.05]. The use of acetaminophen may lower short-term mortality in critically ill patients with sepsis. To confirm this correlation, future research should involve multicenter randomized controlled trials.

Association of early dietary fiber intake and mortality in septic patients with mechanical ventilation based on MIMIC IV 2.1 database: a cohort study

BackgroundWhether early dietary fiber intake in septic patients is associated with a better clinical prognosis remains unclear, especially the time and the amount. Therefore, we assessed the association between early dietary fiber intake and clinical outcomes in septic patients by examining an extensive database.MethodsWe conducted a retrospective cohort study using data from the MIMIC IV 2.1 database, focusing on consecutive septic patients requiring mechanical ventilation in medical or mixed medical-surgical ICUs. We collected patient demographics and nutritional data. Dietary fiber amounts were calculated according to enteral nutrition instructions from manufacturers within the first 72 h after admission. After adjusting for covariates, we employed restricted cubic spline (RCS) regression to investigate the relationship between fiber intake (FI) and 28-day mortality. Patients were categorized into three groups based on their fiber index (FI) within 72 h of admission: low fiber index (LFI) group when FI was < 3 g/(%), medium fiber index (MFI) group when FI ranged from 3 to 35 g(%), and high fiber index (HFI) group when FI ≥ 35 g(%). Univariate and multivariate Cox proportional hazards regression models were utilized to assess the association between early FI and 28-day mortality. We ultimately employed Kaplan–Meier (KM) curves and log-rank test visually represent the association between FI and 90-day mortality. The second outcomes include ICU-acquired infections and the hospital and ICU death, length of hospital and ICU stay, and length of mechanical ventilation.ResultsAmong 1057 subjects, 562 (53.2%) were male, with a median age of 64.8 years (IQR 53.4–75.2). We observed a J-shaped relationship between FI and 28-day mortality. The MFI group exhibited the lowest 28-day mortality [adjusted HR 0.64 (0.45–0.91), p = 0.013] and the lowest rate of hospital mortality [adjusted OR 0.60 (0.39–0.93), p = 0.022], with no statistically significant differences noted in the HFI group when compared to the LFI group. Similar patterns were observed for 60-day and 90-day mortality. However, no statistically significant differences were observed in other secondary outcomes after adjusting for covariates.ConclusionEarly medium fiber index intake improved 28-day mortality and lower hospital mortality in septic M/SICU patients on mechanical ventilation.

PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

The Role of Gut Microbiota in the Clinical Outcome of Septic Patients: State of the Art and Future Perspectives.

Sepsis is a life-threatening multiple-organ dysfunction caused by a dysregulated host response to infection, with high mortality worldwide; 11 million deaths per year are attributable to sepsis in high-income countries. Several research groups have reported that septic patients display a dysbiotic gut microbiota, often related to high mortality. Based on current knowledge, in this narrative review, we revised original articles, clinical trials, and pilot studies to evaluate the beneficial effect of gut microbiota manipulation in clinical practice, starting from an early diagnosis of sepsis and an in-depth analysis of gut microbiota.

Repositioning linifanib as a potent anti-necroptosis agent for sepsis

Sepsis is a systemic inflammatory syndrome (SIRS) caused by acute microbial infection, and it has an extremely high mortality rate. Tumor necrosis factor-α (TNF-α)-induced necroptosis contributes to the pathophysiology of sepsis, so inhibiting necroptosis might be expected to improve clinical outcomes in septic patients. Here we predicted candidate drugs for treating sepsis in silico by combining genes differentially expressed in septic patients and controls combined with interrogation of the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 perturbation database. Sixteen candidate drugs were screened out through bioinformatics analysis, and the top candidate linifanib was validated in cellular and mouse models of TNF-α-induced necroptosis. Cell viability was measured using a luminescent ATP assay, while the effects of linifanib on necroptosis were investigated by western blotting, immunoprecipitation, and RIPK1 kinase assays. Linifanib effectively protected cells from necroptosis and rescued SIRS mice from TNF-α-induced shock and death. In vitro, linifanib directly suppressed RIPK1 kinase activity. In vivo, linifanib effectively reduced overexpressed IL-6, a marker of sepsis severity, in the lungs of SIRS mice. Our preclinical evidence using an integrated in silico and experimental drug repositioning approach supports the potential clinical utility of linifanib in septic patients. Further clinical validation is now warranted.

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.

Clinical Outcome of Septic Patients With Heart Failure With Preserved Ejection Fraction Presenting to the Emergency Department of a Tertiary Hospital: A Retrospective Cohort Study.

Background: Patients with heart failure with preserved ejection fraction (HFpEF) may be at a higher risk of mortality from sepsis than patients without heart failure.Objective: The aim of this study is to compare sepsis-related morbidity and mortality between patients with HFpEF and patients without heart failure presenting to the emergency department (ED) of a tertiary medical center.Design: Single-center retrospective cohort study conducted at an academic ED between January 1, 2015 and December 31, 2018.Patients: Patients with a diagnosis of sepsis were included.Main Measures: Bivariate and multivariate analyses were performed to look at differences in demographics, infection, and treatment parameters as well as outcomes of patients with sepsis. The primary outcome of the study was in-hospital mortality. Secondary outcomes included ED mortality, lengths of stay, and treatment differences between both groups.Key Results: A total of 1,092 patients presented with sepsis to the ED, of which 305 (27.93%) had HFpEF. There was no significant difference in in-hospital mortality between the two groups (40.7% vs. 37.4%; p = 0.314). However, there was a significant increase in ED mortality for septic HFpEF patients compared to non-heart failure patients (2.4 vs. 0.4%; p = 0.003). Septic HFpEF patients presenting to the ED were older than non-heart failure patients (76.84 vs. 68.44 years old; p < 0.0001). On the other hand, there was no significant increase in the use of vasopressors in the first 24 h between both groups. There was a significantly higher rate of intubation in the first 48 h for septic HFpEF patients (17.5 vs. 8.9%; p < 0.0001). Finally, there was significantly less intravenous fluid requirement at 6 h (1.94 L vs. 2.41L; p < 0.0001) and 24 h (3.11 L vs. 3.54L; p = 0.004) for septic patients with HFpEF compared to non-heart failure patients.Conclusion: Septic HFpEF patients experienced an increase in ED mortality, intubation, and steroid use compared to septic non-heart failure patients.

Is Vitamin C or HAT Therapy Effective in Treating Sepsis? A Mini Review

Background: One of the most common causes of mortality in critical patients admitted to the intensive care unit (ICU) is sepsis. In recent years, the administration of high doses of vitamin C and HAT (hydrocortisone, ascorbic acid and thiamine) therapy has attracted much attention in patients with sepsis.&#x0D; Objectives: The current article reviews the beneficial effects of HAT therapy in light of research conducted in this area. Methods: A general search for electronic databases was developed. The human studies of the influence of HAT therapy in critically ill patients were evaluated.&#x0D; Results: The results indicated that HAT therapy may improve clinical outcome in septic patients; however, widespread use of these therapeutic approaches in sepsis requires large clinical trials in order to more confidently recommend this therapeutic approach in septic patients admitted to intensive care units.&#x0D; Conclusions: HAT therapy may improve clinical outcome in septic critically ill patients.

An overview of positive cultures and clinical outcomes in septic patients: a sub-analysis of the Prehospital Antibiotics Against Sepsis (PHANTASi) trial

BackgroundSepsis remains one of the most important causes of morbidity and mortality worldwide. In approximately 30–50% of cases of suspected sepsis, no pathogen is isolated, disabling the clinician to treat the patient with targeted antimicrobial therapy. Studies investigating the differences in the patient outcomes between culture-positive and culture-negative sepsis patients have only been conducted in subgroups of sepsis patients and results are ambiguous.MethodsThis is a sub-analysis of the PHANTASi (Prehospital Antibiotics Against Sepsis trial), a randomized controlled trial that focused on the effect of prehospital antibiotics in sepsis patients. We evaluated the outcome of cultures from different sources and determined what the clinical implications of having a positive culture compared to negative cultures were for patient outcomes. Furthermore, we looked at the effect of antibiotics on culture outcomes.Results1133 patients (42.6%) with culture-positive sepsis were identified, compared to 1526 (56.4%) patients with culture-negative sepsis.28-day mortality (RR 1.43 [95% CI 1.11–1.83]) and 90-day mortality (RR 1.41 [95% CI 1.15–1.71]) were significantly higher in culture-positive patients compared to culture-negative patients.Culture-positive sepsis was also associated with ≥ 3 organ systems affected during the sepsis episode (RR 4.27 [95% CI 2.78–6.60]). Patients who received antibiotics at home more often had negative blood cultures (85.9% vs. 78%) than those who did not (p < 0.001).ConclusionsOur results show that culture-positive sepsis is associated with a higher mortality rate and culture-positive patients more often have multiple organ systems affected during the sepsis episode.Trial registrationThe PHANTASi trial is registered at ClinicalTrials.gov, number NCT01988428. Date of registration: November 20, 2013.

Computed Tomography Evidence of Psoas Muscle Atrophy Without Concomitant Tendon Wasting in Early Sepsis

BackgroundMorphomic studies have demonstrated a correlation between sarcopenia and clinical outcomes in septic patients. However, tendon morphomics has not yet been studied in this context. The purpose of the present study was to evaluate tendon morphology in septic patients through analytic morphomics. We hypothesized that morphomic analyses would reveal concomitant muscle and tendon wasting in sepsis patients. The results of this study may help to implement different rehabilitation modalities for critically ill patients. Materials and methodsThe volume and fat content of bilateral psoas muscles and tendons were measured on abdominal computed tomography scans of 25 ICU septic and 25 control trauma patients admitted to the University of Michigan between 2011 and 2012. Univariate and multivariate analyses were performed to determine the relationship between psoas muscle and tendon morphometric data, and the association with clinical variables such as smoking and comorbidities. ResultsAverage psoas muscle volume was 12.21 ± 5.6 cm3 for control patients and 9.318 ± 3.3 cm3 in septic patients (P = 0.0023). The average psoas muscle/fat ratio for septic patients was 0.0288 ± 0.071 cm3, compared with 0.0107 ± 0.008 cm3 in the control group (P = 0.075). Average tendon volume in the septic population (0.508 ± 0.191 cm3) was not different than the control cohort (0.493 ± 0.182 cm3) (P = 0.692). ConclusionsOur results demonstrate significantly smaller psoas muscle volume in septic patients than in age-, gender-, and BMI-matched trauma patients but no demonstrable change in tendon morphology between patient groups. These findings begin to define the boundaries of clinical application within the field of morphomics.

Four-oil intravenous lipid emulsion effect on plasma fatty acids, inflammatory markers and clinical outcomes in septic patients

Rationale: Data in critically ill patients on the effect of intravenous lipid emulsions (LE) containing omega-3 polyunsaturated fatty acids (PUFA) are scarce and shows conflicting results. This study compared the effects of two LE’s in critically ill adult intensive care unit (ICU) patients.

Fish Oil-Containing Lipid Emulsions in Adult Parenteral Nutrition: A Review of the Evidence.

There is evidence from laboratory and animal studies that fish oil-containing intravenous lipid emulsions (FOC-IVLEs) have a beneficial effect on inflammation and the immune response, suggesting a possible clinical benefit. Clinical studies of FOC-IVLEs have reported mixed results. The aim of this review is to present findings from recent randomized controlled clinical trials and other quality clinical studies investigating the effects of administering intravenous fish oil alone or as part of a multilipid emulsion and to examine the quality of these studies in an objective, evidence-based manner. Studies comparing FOC-IVLEs with other IVLEs in adults were included. Thirty-four clinical studies were evaluated: 19 investigated levels of inflammatory and immune markers as an endpoint; 13 investigated rates of infection or sepsis; 3 investigated clinical outcomes in septic patients; and 29 investigated general clinical outcomes. There was conflicting evidence for a beneficial effect of fish oil on levels of inflammatory and immune markers and some evidence that fish oil decreased the rate of postoperative atrial fibrillation. Studies generally reported few statistical differences in clinical outcomes and rates of infection and sepsis with FOC-IVLEs as compared with other IVLEs. The quality of reporting was generally poor, and the presented evidence for comparisons between FOC-IVLEs and other IVLEs was inconclusive or weak. There is very little high-quality evidence that FOC-IVLEs have a more beneficial effect than other IVLEs on clinical outcomes in adult patients.

Metabolic Inflammatory Complex in Sepsis: Septic Cachexia as a Novel Potential Therapeutic Target.

Despite several decades of focused investigation, sepsis remains a major cause of mortality in critically ill patients. Advancements in intensive care have enabled more patients to survive the acute phase of sepsis than previously, but a growing number of them progress to chronic critical illness. The failure of previous randomized clinical trials of anti-inflammatory agents to show any pro-survival benefit in septic patients underscores current thought that simple anti-inflammatory strategies are ineffective because the inhibitory effect of anti-inflammatory agents undermines the immune response to pathogens. New strategies with the dual capability of ameliorating inflammation in organs while stimulating antimicrobial activity are eagerly awaited. On the other hand, the metabolic alterations associated with systemic inflammatory response, including mitochondrial dysfunction and metabolic shift, are closely linked through a nexus of signaling pathways and signaling molecules. Preventing these metabolic derangements may be an alternative way to control excessive inflammation, an intriguing possibility that has not been fully explored. New insight into the molecular pathogenesis of sepsis and sepsis-associated chronic critical illness has led to the recognition of septic cachexia, a life-threatening form of metabolic inflammatory complex associated with multiple organ dysfunction. The potential for septic cachexia to serve as a novel target disease state to improve the clinical outcome of septic patients is discussed in this review.

Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study

BackgroundSevere sepsis and septic shock are often lethal syndromes, in which the autonomic nervous system may fail to maintain adequate blood pressure. Heart rate variability has been associated with outcomes in sepsis. Whether systolic blood pressure (SBP) variability is associated with clinical outcomes in septic patients is unknown. The propose of this study is to determine whether variability in SBP correlates with vasopressor independence and mortality among septic patients.MethodsWe prospectively studied patients with severe sepsis or septic shock, admitted to an intensive care unit (ICU) with an arterial catheter. We analyzed SBP variability on the first 5-min window immediately following ICU admission. We performed principal component analysis of multidimensional complexity, and used the first principal component (PC1) as input for Firth logistic regression, controlling for mean systolic pressure (SBP) in the primary analyses, and Acute Physiology and Chronic Health Evaluation (APACHE) II score or NEE dose in the ancillary analyses. Prespecified outcomes were vasopressor independence at 24 h (primary), and 28-day mortality (secondary).ResultsWe studied 51 patients, 51% of whom achieved vasopressor independence at 24 h. Ten percent died at 28 days. PC1 represented 26% of the variance in complexity measures. PC1 was not associated with vasopressor independence on Firth logistic regression (OR 1.04; 95% CI: 0.93–1.16; p = 0.54), but was associated with 28-day mortality (OR 1.16, 95% CI: 1.01–1.35, p = 0.040).ConclusionsEarly SBP variability appears to be associated with 28-day mortality in patients with severe sepsis and septic shock.

Implementation of short incubation MALDI-TOF MS identification from positive blood cultures in routine diagnostics and effects on empiric antimicrobial therapy

BackgroundResults of blood culture (BC) diagnostics should be swiftly available to guide treatment of critically ill patients. Conventional BC diagnostics usually performs species identification of microorganisms from mature solid medium colonies. Species identification might be speed up by using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) of biomass from shortly incubated solid media.MethodsThis single-center analysis compared the applicability of MALDI-TOF-based species identification from shortly incubated cultures in laboratory routine vs. conventional diagnostics and assessed its effects of on empiric antibiotic therapy.ResultsMedian time between detection of BCs as “positive” by incubators and further processing (e.g. microscopy) was 6 h 21 min. Median time between microscopy and result reporting to the ward was 15 min. Including 193 BCs, MALDI-TOF from shortly incubated biomass resulted in significantly faster (p > 0.001) species identification. Species results became available for clinicians after a median of 188 min (231 min for Gram-positive bacteria, 151 min for Gram-negative bacteria) compared to 909 min (n = 192 BCs) when conventional diagnostics was used. For 152/179 bacteremia episodes (85%) empiric antibiotic therapy had already been started when the microscopy result was reported to the ward; microscopy led to changes of therapies in 14/179 (8%). In contrast, reporting the bacterial species (without antibiogram) resulted in therapeutic adjustments in 36/179 (20%). Evaluating these changes revealed improved therapies in 26/36 cases (72%).ConclusionsSpecies identification by MALDI-TOF MS from shortly incubated subcultures resulted in adjustments of empiric antibiotic therapies and might improve the clinical outcome of septic patients.

Serum sPD-L1, Upregulated in Sepsis, May Reflect Disease Severity and Clinical Outcomes in Septic Patients.

We aimed to find the correlation between serum sPD-L1 (soluble programmed cell death L-1 ligand) and sepsis. Totally 91 consecutive patients with sepsis were performed in a 15-bed medical intensive care unit (ICU) of the second affiliated hospital, Xi'an Jiaotong University in Xi'an, China, between February 2015 and May 2016. Healthy controls (HC) consisted of 29 healthy volunteer. Baseline demographic data were recorded. Blood samples were collected through an indwelling central venous or by peripheral venipuncture. Serum sPD-L1 and sPD-1 levels were determined with enzyme-linked immunosorbent assay kits (Elabscience Biotechnology Co. Ltd, Wuhan, China). SPSS19.0 software (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. Kaplan-Meier survival analysis and Cox regression analysis were also performed. Serum sPD-L1 levels and sPD-1 levels were significantly increased in septic patients compared with HC (P=0.000). Serum sPD-L1 levels were significantly increased in non-survivors compared with survivors (P<0.05), but there was no statistically difference on serum sPD-1 levels between non-survivors and survivors (P>0.05). Serum sPD-L1 levels were correlated with absolute lymphocyte (ALC), platelets and SOFA scores. Serum sPD-L1/sPD-1 levels were negatively correlated with ALC and platelets, and SOFA scores. The prognostic accuracy of the sPD-L1 level to predict 28-day mortality was similar to that of the APACHE-II scores and SOFA scores. Cox regression analysis showed that sPD-L1 was an independent prognostic factor. Serum sPD-L1 is upregulated in sepsis and may reflect disease severity and clinical outcomes in patients. Serum sPD-L1 may be an independent prognostic factor for sepsis.

A Retrospective Study on the Compliance with Surviving Sepsis Campaign Guideline in Patients with Sepsis Admitted to Intensive Care Unit in Hong Kong

The global incidence of sepsis is increasing due to earlier recognition, but mortality from sepsis still remains high. Local data on the management according to the Surviving Sepsis Campaign Care Bundle is still lacking. Hence, this study looks at the epidemiology, patient characteristics and management of septic patients admitted to intensive care unit (ICU) in a regional hospital in Hong Kong. Clinical records of all patients admitted to ICU of Tseung Kwan O Hospital from 1st January to 30th June, 2014 were screened. There were 108 patients who fulfilled the inclusion criteria, corresponding to incidence of 32%. There were 62% males with a mean age of 63.6 years. Most patients (34.3%) were diagnosed in emergency department and the majority (46%) were transferred to ICU within 3 h of diagnosis, whereas 44% were transferred >6 h after diagnosis and 10% were transferred between 3-6 h. Most common source of infection was respiratory (26%), followed by blood (15.7%) and urinary tract (7%). Three-hour bundle compliance: measurement of lactate (0%), blood culture before antibiotics (56%), administration of antibiotics (100%) and administration of intravenous fluids volume to 30 ml/kg (21%). Six-hour bundle compliance: Vasopressor use (89%), central venous pressure monitoring (68%), central venous oxygen saturation measurement (0%). The hospital mortality rate was 26.8%. In conclusion, mortality of sepsis is high. Relentless effort is needed to boost the adherence to Sepsis Care Bundle, especially the measurement of serum lactate. Protocols, checklists, education and simulation training are possible means to improve the quality of care and clinical outcome of septic patients.

The Role of Cell-Free Plasma DNA in Critically Ill Patients with Sepsis

Background: The identification of highly reliable outcome predictors in severe sepsis is important to define disease severity, predict bedside prognosis and monitor response to treatment. Cell-free plasma DNA (cfDNA) has been recently proposed as a possible prognostic marker of clinical outcome in septic patients. In this study, we investigated the prognostic value of cfDNA in patients with sepsis and its possible correlation with caspase-3, IL-6 and IL-18 levels. Methods: We enrolled 34 patients admitted to the intensive care unit (ICU). Out of these 34, 27 patients were septic and 7 were non-septic. cfDNA was extracted from plasma and quantified by real time PCR. Plasma levels of caspase-3, IL-6 and IL-18 were measured by ELISA. Results: We observed significantly higher levels of cfDNA in septic patients. No significant differences were found between cfDNA levels in patients with Gram+, Gram- and fungal infections. Out of the 27 septic patients, 12 developed acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), and cfDNA levels resulted to be higher in this group. Out of the 27 septic patients, 11 had a negative outcome during the ICU stay. The cfDNA concentrations at admission were higher in non-survivors than in survivors. Caspase-3, IL-6 and IL-18 levels were significantly higher in septic patients when compared to these levels in non-septic patients and correlated with cfDNA levels. Conclusion: cfDNA can be considered a good prognostic marker of clinical outcome in septic patients. Its levels increase in case of AKI complicating sepsis, in particular if CRRT is needed, and are associated with poor outcome. Caspase-3, IL-6 and IL-18 levels are higher in septic patients and correlate to cfDNA concentrations.

Clinical outcome of septic patients with undetectable vitamin D levels at ICU admission

Septic patients with very low vitamin D (VD) levels are expected to most benefit from supplementation strategies but few data are available in this specific population.[1]

How to choose the therapeutic goals to improve tissue perfusion in septic shock.

The early recognition and treatment of severe sepsis and septic shock is the key to a successful outcome. The longer the delay in starting treatment, the worse the prognosis due to persistent tissue hypoperfusion and consequent development and worsening of organ dysfunction. One of the main mechanisms responsible for the development of cellular dysfunction is tissue hypoxia. The adjustments necessary for adequate tissue blood flow and therefore of oxygen supply to metabolic demand according to the assessment of the cardiac index and oxygen extraction rate should be performed during resuscitation period, especially in high complexity patients. New technologies, easily handled at the bedside, and new studies that directly assess the impact of macro-hemodynamic parameter optimization on microcirculation and in the clinical outcome of septic patients, are needed.