Severe Septic Patients Research Articles

High Mortality in Severe Sepsis and Septic Shock Patients with Do-Not-Resuscitate Orders in East Asia.

BackgroundSevere sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan.MethodsA retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care.ResultsSixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66–14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p <0.001). Regarding ICU interventions, arterial and central venous catheterization were more commonly used in DNR patients than in non-DNR patients.ConclusionsFrom the Asian perspective, septic patients placed on DNR orders on ICU admission had exceptionally high mortality. In contrast to Western reports, DNR patients received more ICU interventions, reflecting more aggressive approach to dealing with this patient population. The findings in some ways reflect differences between East and West cultures and suggest that DNR status is an important confounder in ICU studies involving severely septic patients.

Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study.

To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock. This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality. The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79% (15 patients) in the protein C zymogen group and 67% (12 patients) in the placebo group (p=0.40) and for a concomitant safety issue: ICU mortality was 79% (15 patients) in the protein C zymogen group vs 39% (7 patients) in the placebo group (p=0.020), and 30-day mortality was 68 vs 39% (p=0.072). Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

Non Activated Protein C Supplementation in Septic Pediatric Hematological Patients.

The purpose of the study was to examine safety and efficacy of non-activated Protein C (PC) supplementation in our cohort of septic pediatric hematological patients. We conducted a retrospective study of 22 septic patients receiving human plasma-derived PC concentrate from 2008 to 2015 at our Pediatric Oncology Center (Bari, Italy). The Surviving sepsis campaign definitions for sepsis, severe sepsis and septic shock were used to define the patients’ septic status. For each patient, we calculated Lansky performance status scale (LPSS) and a risk score defined the Hematologic risk score (HRS) that we created in 2007. Patients were defined as High risk for severe sepsis/septic shock in case of HRS>3. HRS<3 identified low risk patients. Baseline serum PC levels, PC administration dosage and duration and days until a 20% improvement in LPSS. Observed baseline serum PC levels (bPC) blood concentrations ranged from 31 to 80%. Patients received PC supplementation in case of low age-related bPC levels or >10% PC concentration decrease within 12 hours from the first evaluation. All patients received 80 U/kg/day PC, intravenously, every twenty-four hours. No drug-related adverse event was observed. The observed sepsis-related mortality rate in our cohort was 9%. PC supplementation in our cohort appeared to be safe, and, probably due to prompt PC administration, we observed an overall mortality that was much lower than expected mortality in cancer severe septic patients.

The incidences of organ dysfunction in the early resuscitation of severe sepsis and septic shock patients:a retrospective analysis

To investigate the potential risk factors of organ dysfunction and mortality in the early resuscitation of severe sepsis and septic shock patients. Data were retrospectively analyzed from patients with severe sepsis and septic shock receiving non-cardiac operation and admitted to Department of Critical Care Medicine of the Second Affiliated Hospital of Kunming Medical University from January 1st,2013 to December 31st,2015.The patients were divided into the senior group (≥ 65 years old) and the younger group (＜ 65 years old),the high-procalcitonin (PCT) group (PCT ＞ 100 μg/L) and the control group (PCT ≤ 100 μg/L).The stage of early resuscitation was set to the first 6 hours. The diagnostic time and the incidence of acute respiratory distress syndrome (ARDS),acute kidney injury (AKI),and cardiac insufficiency were observed, which also included the usage of continuous renal replacement therapy (CRRT).The total fluid volume and the time of vasopressor usage during the first 6 hours of early goal-directed therapy (EGDT) were also recorded, which aslo included the 28-day mortality. 512 patients with severe sepsis and septic shock receiving non-cardiac operation were treated according to the guidelines of "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock:2012".EGDT was used during the early resuscitation. The incidence of ARDS, AKI, and cardiac insufficiency was 80.9％ (414/512),71.3％ (365/512),and 61.9％ (317/512) respectively. There were 205 senior patients and 307 younger, as well as 154in high-PCT group and 358 in control group. The 28-day mortality was 30.3％ (155 died).90.8％ of patients (376/414)combined with ARDS were diagnosed before EGDT.95.1％ of patients (347/365) combined with AKI were diagnosed before EGDT, among whom 14.0％ (51/365) were treated with CRRT.153 senior patients combined with cardiac insufficiency were diagnosed no longer than 12 hours after EGDT. Compared with the younger group, the incidences of ARDS and cardiac insufficiency were higher in the senior group [85.9％ (176/205) vs.77.5％ (238/307),82.9％(170/205) vs.32.9％ (147/307),both P ＜ 0.05],so were the time of vasopressor usage during EGDT (hours:5.81 ±0.28vs.5.68 ± 0.52,P ＜ 0.05) was prolonged markedly and the 28-day mortality [42.9％ (88/205) vs.21.8％ (67/307),P ＜0.05] was increased significantly. But the incidence of AKI and the total fluid volume during EGDT were not significantly different between the senior group and the younger group [incidence of AKI:74.1％ (152/205) vs.69.4％ (213/307),total fluid volume (mL):2 769 ± 1 589 vs.2 804± 1 611,both P ＞ 0.05].Compared with the control group, the incidence of ARDS was higher in the high-PCT group [86.4％ (133/154) vs.78.5％ (281/358),P ＜ 0.05].But the incidences of AKI and cardiac insufficiency were not significantly differentiated between the high-PCT group and the control group [77.9％ (120/154) vs.68.4％ (245/358),58.4％ (90/154) vs.63.4％ (227/358),both P ＞ 0.05].Multiple logistic regression analysis showed that the risk factors of increase in mortality in patients with severe sepsis and septic shock included old age [odds ratio (OR) =1.782,95％ confidence interval (95％CI) =1.173-2.708,P =0.007],ARDS (OR =1.786,95％CI =1.028-3.102,P =0.040),AKI (OR =1.878,95％CI =1.145-3.079,P =0.012),and cardiac insufficiency (OR =4.177,95％CI =2.505-6.966,P =0.000),except for gender (OR =1.112,95％CI =0.736-1.680,P =0.614). In the senior postoperative patients with severe sepsis or septic shock, the incidence of ARDS and cardiac insufficiency, and the mortality were increased. The incidence of ARDS was correlated to the severity of infection.Old age, surgery, and EGDT could be the potential risk factors of cardiac insufficiency.

The association between blood glucose levels and matrix-metalloproteinase-9 in early severe sepsis and septic shock.

BackgroundHyperglycemia is a frequent and important metabolic derangement that accompanies severe sepsis and septic shock. Matrix-Metalloproteinase 9 (MMP-9) has been shown to be elevated in acute stress hyperglycemia, chronic hyperglycemia, and in patient with sepsis. The objective of this study was to examine the clinical and pathogenic link between MMP-9 and blood glucose (BG) levels in patients with early severe sepsis and septic shock.MethodsWe prospectively examined 230 patients with severe sepsis and septic shock immediately upon hospital presentation and before any treatment including insulin administration. Clinical and laboratory data were obtained along with blood samples for the purpose of this study. Univariate tests for mean and median distribution using Spearman correlation and analysis of variance (ANOVA) were performed. A p value ≤ 0.05 was considered statistically significant.ResultsPatients were grouped based on their presenting BG level (mg/dL): BG <80 (n = 32), 80–120 (n = 53), 121–150 (n = 38), 151–200 (n = 23), and > 201 (n = 84). Rising MMP-9 levels were significantly associated with rising BG levels (p = 0.043). A corresponding increase in the prevalence of diabetes for each glucose grouping from 6.3 to 54.1 % (p = 0.0001) was also found. As MMP-9 levels increased a significantly (p < 0.001) decreases in IL-8 (pg/mL) and ICAM-1 (ng/mL) were noted.ConclusionThis is the first study in humans demonstrating a significant and early association between MMP-9 and BG levels in in patients with severe sepsis and septic shock. Neutrophil affecting biomarkers such as IL-8 and ICAM-1 are noted to decrease as MMP-9 levels increase. Clinical risk stratification using MMP-9 levels could potentially help determine which patients would benefit from intensive versus conventional insulin therapy. In addition, antagonizing the up-regulation of MMP-9 could serve as a potential treatment option in severe sepsis or septic shock patients.

Serum caspase 3 levels are associated with early mortality in severe septic patients

ObjectiveHigher caspase 3 activity has been found in lymphocytes of septic patients than of healthy controls. However, an association between serum caspase 3 levels at moment of severe sepsis diagnosis and mortality in septic patients has not been previously demonstrated, and this was the main objective of the present study. MethodsThis is an observational study of 216 patients with severe sepsis in 6 Spanish intensive care units. We collected serum samples at moment of severe sepsis diagnosis to determine levels of caspase 3 and caspase-cleaved cytokeratin (CCCK) 18. End point was 30-day mortality. ResultsWe found higher serum caspase 3 levels (P<.001) and caspase-cleaved cytokeratin 18 (P=.001) in nonsurvivors (n=76) than in survivors (n=140). Multiple binary logistic regression analysis showed that serum caspase 3 levels greater than 0.25 ng/mL were associated with 30-day mortality (odds ratio, 6.51; 95% confidence interval, 3.32-12.77; P<.001). Receiver operating characteristic analysis showed that the area under the curve to predict 30-day mortality for serum caspase 3 levels was 0.73 (95% confidence interval, 0.67-0.79; P<.001). ConclusionsThe major novel findings of our study were that there is an association between serum caspase 3 levels at moment of severe sepsis diagnosis and mortality in septic patients and that serum caspase 3 levels could be used as prognostic biomarker, and further studies are needed to corroborate these findings.

Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay

We evaluate the association of intravenous fluid resuscitation initiation within 30 minutes of severe sepsis or septic shock identification in the emergency department (ED) with inhospital mortality and hospital length of stay. We also compare intravenous fluid resuscitation initiated at various times from severe sepsis or septic shock identification's association with the same outcomes. This was a review of a prospective, observational cohort of all ED severe sepsis or septic shock patients during 13 months, captured in a performance improvement database at a single, urban, tertiary care facility (90,000 ED visits/year). The primary exposure was initiation of a crystalloid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification. Secondary analysis compared intravenous fluid initiated within 30, 31 to 60, or 61 to 180 minutes, or when intravenous fluid resuscitation was initiated at greater than 180 minutes or not provided. Of 1,866 subjects, 53.6% were men, 72.5% were white, mean age was 72 years (SD 16.6 years), and mean initial lactate level was 2.8 mmol/L. Eighty-six percent of subjects were administered intravenous antibiotics within 180 minutes; 1,193 (64%) had intravenous fluid initiated within 30 minutes. Mortality was lower in the within 30 minutes group (159 [13.3%] versus 123 [18.3%]; 95% confidence interval [CI] 1.4% to 8.5%), as was median hospital length of stay (6 days [95% CI 6 to 7] versus 7 days [95% CI 7 to 8]). In multivariate regression that included adjustment for age, lactate, hypotension, acute organ dysfunction, and Emergency Severity Index score, intravenous fluid within 30 minutes was associated with lower mortality (odds ratio 0.63; 95% CI 0.46 to 0.86) and 12% shorter length of stay (hazard ratio=1.14; 95% CI 1.02 to 1.27). In secondary analysis, mortality increased with later intravenous fluid resuscitation initiation: 13.3% (≤30 minutes) versus 16.0% (31 to 60 minutes) versus 16.9% (61 to 180 minutes) versus 19.7% (>180 minutes). Median hospital length of stay also increased with later intravenous fluid initiation: 6 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 8 days) versus 8 days (95% CI 7 to 9 days). The time of intravenous fluid resuscitation initiation was associated with improved mortality and could be used as an easier obtained alternative to intravenous fluid completion time as a performance indicator in severe sepsis and septic shock management.

ENDOCRINE AND METABOLIC ALTERATIONS MAY UNDERLIE MORTALITY OF SEVERE SEPSIS AND SEPTIC SHOCK PATIENTS ADMITTED TO ICU.

The study evaluated endocrinal and metabolic response to sepsis and its applicability for the prediction of outcome of septic patients. Patients were 39 adult with severe infections and within 24 h after onset or suspected clinical tissue hypoperfusion. At enrollment patients were evaluated for acute physiology and chronic health evaluation II score (APACHE II) and Glasgow Coma Scale (GCS). Global hemodynamic parameters including systolic blood pressure (SBP), heart rate (HR) and central venous pressure (CVP) were recorded and monitored. All patients were managed at ICU due to Surviving Sepsis Campaign guidelines. ELISA estimated serum copeptin, macrophage migration inhibitory factor (MIF) and total cortisol (TC) and blood lactate levels. Study outcome was survival rate via 28 days (28-D SR) and best predictor for it. The results showed that 22 patients passed total hospital stay uneventfully for a total survival rate of 56.4%. Seventeen patients died; 10 during ICU stay and 7 during word stay. At admission serum markers levels were significantly higher in survivors and non-survivors compared to controls and in non-survivors compared to survivors. Survival showed negative significant correlation with age, high blood lactate and serum copeptin, TC and MIF levels. Survival showed positive significant correlation with SBP, CVP and urine output. ROC curve and Regression analyses defined high at admission serum copeptin and blood lactate levels as significant predictors for mortality of septic patients.

Evolution of serum hyaluronan and syndecan levels in prognosis of sepsis patients

ObjectivesEndothelial glycocalyx shedding has been recognized as a contributor in sepsis pathophysiology. Hence, we attempted to analyze hyaluronan and syndecan (glycocalyx components) as markers of morbidity and prognosis of sepsis by performing serial measurements in these patients. Design and methodsSubjects were community acquired sepsis, severe sepsis and septic shock patients (150) admitted to ICU of our tertiary care hospital and controls were 50 healthy volunteers. Serum concentrations of markers were measured on days 1, 3, 5, 7 of ICU admission. Survival was assessed after 90days. Statistical analysis was performed by SPSS version 17. ResultsHyaluronan and syndecan levels were significantly elevated in all categories of sepsis patients as compared to healthy controls (p<0.001). Levels of both markers were increased in severe sepsis and septic shock patients as compared to sepsis patient group at all time-points. Hyaluronan and syndecan differentiated survivors from non-survivors (p<0.001). Unlike non-survivors, in the survivor group, median hyaluronan and syndecan levels decreased significantly (p<0.001) in subsequent measurements. ROC analysis for the prediction of mortality identified cut-offs of 441ng/ml and 898ng/ml for hyaluronan and syndecan respectively. The specificity and negative predictive values were 90% and 90% for hyaluronan and 86% and 91% for syndecan respectively. Kaplan Meier curves revealed similar results. Both markers correlated significantly with APACHE II and SOFA scores. ConclusionsThese observations indicate that serial measurements of hyaluronan and syndecan are significant prognostic markers for morbidity and survival in sepsis. Future therapeutic interventional possibilities need to be explored in experimental interventional prospective multi-centric trials.

Septic patients with mitochondrial DNA haplogroup JT have higher respiratory complex IV activity and survival rate

ObjectiveThe influence of mitochondrial deoxyribonucleic acid (mtDNA) haplogroup or oxidative phosphorylation system (OXPHOS) function on survival of septic patients has been scarcely studied. However, the association between mtDNA haplogroup, OXPHOS capacity at diagnosis of severe sepsis, and survival has been not previously reported, and that was the objective of the present study. MethodsThis was a prospective, multicenter, observational study. Blood samples from 198 patients at diagnosis of severe sepsis were analyzed to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The end point of the study was 30-day survival. ResultsSeptic patients with mtDNA haplogroup JT showed higher 30-day survival than those with mtDNA haplogroup non-JT (31/38 [81.6%] vs 99/160 [61.9%]; P= .02). Septic patients with mtDNA haplogroup JT showed higher platelet CIV specific activity than those with mtDNA haplogroup non-JT (P= .002). ConclusionsThe main novel finding of our study, including the largest series providing data on platelet CIV specific activity according to mtDNA haplogroup in severe septic patients, was that those with mtDNA haplogroup JT showed higher survival and higher platelet CIV specific activity at diagnosis of severe sepsis than patients with mtDNA haplogroup non-JT.

Prognostic utility of plasma lactate measured between 24 and 48h after initiation of early goal-directed therapy in the management of sepsis, severe sepsis, and septic shock.

BackgroundBased on the proven efficacy of lactate in predicting mortality and morbidity in sepsis when measured early in the resuscitative protocol, our group hypothesized that this utility extends later in the course of care. This study sought to investigate the prognostic potential of plasma lactate clearance measured 24–48 h after the initiation of treatment for nonsurgical patients with sepsis, severe sepsis, and septic shock.MethodsPlasma lactate values, measured 24–48 h after the initiation of treatment, were collected in nonsurgical septic, severe septic, and septic shock patients. The primary outcome was 30-day mortality, while secondary outcomes included requirements for vasopressors and boluses of intravenous fluids. Analysis of these three outcomes was performed while controlling for clinical severity as measured by Sequential Organ Failure Assessment (SOFA), renal dysfunction, and hepatic dysfunction. Lactate clearance was defined as the percent change in plasma lactate levels measured after 24–48 h of treatment from the plasma lactate level at initial presentation.ResultsTwo hundred twenty-nine nonsurgical patients were divided into two groups, clearers (above median lactate clearance [31.6 %]) and nonclearers (below median lactate clearance [31.6 %]). The adjusted odds ratio of mortality in clearers compared to nonclearers was 0.39 (CI 0.20–0.76) (p = 0.006). For vasopressor requirement, the adjusted odds ratio was 0.41 (CI 0.21–0.79) in clearers compared to nonclearers (p = 0.008). For intravenous fluid bolus requirement, the adjusted odds ratio was 0.81 (CI 0.48–1.39) in clearers compared to nonclearers (p = 0.45).ConclusionsLower plasma lactate clearance 24–48 h after the initiation of treatment is associated with higher 30-day mortality and requirements for vasopressors in nonsurgical septic patients and may be a useful noninvasive measurement for guiding late-sepsis treatment. Further investigation looking at mechanisms and therapeutic targets to improve lactate clearance in late sepsis may improve patient mortality and outcomes.

Diagnostic Accuracy of NT-ProBNP for Heart Failure with Sepsis in Patients Younger than 18 Years.

This clinical study investigated plasma NT-proBNP levels as a potential predictor of heart failure in pediatric patients with sepsis. Plasma NT-ProBNP levels of 211 pediatric patients with sepsis and 126 healthy children were measured. Patients were stratified as with heart failure (HF) or without heart failure (non-HF). Patients were graded as having sepsis, severe sepsis, or septic shock. The optimal cut-off values of plasma NT-ProBNP for heart failure were determined by analyzing the receiver operating characteristic (ROC). In the HF, non-HF and control groups, the median plasma NT-proBNP levels were 3640, 656, and 226 ng/L, respectively. For all patients with sepsis, the optimal diagnostic cut-off value was 1268 ng/L for differentiating heart failure. In the severe sepsis patients and septic shock patients, the optimal diagnostic cut-off values were 1368 ng/L and 1525 ng/L, respectively. This report is the first one to reveal that NT-proBNP may predict heart failure in children with sepsis. It provides an important clinical reference for the diagnosis of heart failure in pediatric patients with sepsis, and enables monitoring septic children for cardiac involvement.

Higher serum level of myoglobin could predict more severity and poor outcome for patients with sepsis

BackgroundThere have been sporadic case reports published focusing on myoglobin and sepsis. However, there are no systematic studies evaluating the correlation between myoglobin level and sepsis. This study investigated the correlation between the serum myoglobin level and the severity of septic patients. Next, we assessed the predictive value of the serum myoglobin level for the prognosis of septic patients. MethodsSeventy septic patients were included and subdivided into the following 3 groups: sepsis group, severe sepsis group, and septic shock group. We collected blood samples at 0, 6, 12, 18, and 24hours after admission. The serum levels of myoglobin, C-reactive protein, and procalcitonin were analyzed. We also evaluated the levels of malondialdehyde, which is a biomarker for oxidative stress. ResultsThe data indicate that the myoglobin level increased gradually within 24hours after admission. The median myoglobin levels of the sepsis, severe sepsis, and septic shock groups were 635.7, 903.6, and 1094.8μg/L, respectively (P<.05). The elevated myoglobin level was positively correlated with Sequential Organ Failure Assessment score, C-reactive protein, and procalcitonin level in septic patients. The increased myoglobin level was also associated with the mortality of septic patients. The Kaplan-Meier survival curves indicated that patients with high myoglobin levels had an elevated mortality rate. Moreover, an elevated myoglobin level indicated more oxidative stress. ConclusionsThe myoglobin level can be detected in the early stage of sepsis and may serve as a potential biomarker for evaluating sepsis severity and further prognosis.

Success of applying early goal-directed therapy for septic shock patients in the emergency department.

BackgroundSince early goal-directed therapy (EGDT) became standard care in severe sepsis and septic shock patients in intensive care units many years ago, we suppose that the survival rate of severe sepsis and septic shock patients improves if the resuscitative procedure is quickly implemented and is initiated in the emergency room.ObjectiveWe aimed at recording emergency department time to improve our patient care system as well as determine the rate at which EGDT goals can be achieved. The second analysis is to find out how much we can improve the survival rate.MethodsThis was a prospective observational study in an emergency room setting at a tertiary care facility where EGDT was applied for resuscitation of severe sepsis and septic shock patients. The data recorded were the initial vital signs, APACHE II (Acute Physiology and Chronic Health Evaluation II) score, SAP II (Simplified Acute Physiology II) score, SOFA (Sequential Organ Failure Assessment) score, time at which EGDT goals were achieved (central venous oxygen saturation [ScvO2] >70%), initial and final diagnosis, and outcome of treatment. The t-test and Mann–Whitney U-test were used to compare between the achieved goal and nonachieved goal groups.ResultsThere were 63 cases of severe sepsis in the study period. Only 55 patients submitted a signed consent form and had central line insertion. Twenty-eight (50.9%) cases were male. Thirty-nine (70.9%) patients achieved the goal, and the mean SAP II score was 8. There were no statistically significant differences between the two groups (P-value =0.097). Thirty of the 39 patients (70.9%) survived in the achieved goal group, which was a statistically significant improvement of the survival rate when compared with only one of 16 patients (6.3%) surviving in the nonachieved goal group (P<0.001).

Hypoalbuminemia, Low Base Excess Values, and Tachypnea Predict 28-Day Mortality in Severe Sepsis and Septic Shock Patients in the Emergency Department.

PurposeThe objective of this study was to develop a new nomogram that can predict 28-day mortality in severe sepsis and/or septic shock patients using a combination of several biomarkers that are inexpensive and readily available in most emergency departments, with and without scoring systems.Materials and MethodsWe enrolled 561 patients who were admitted to an emergency department (ED) and received early goal-directed therapy for severe sepsis or septic shock. We collected demographic data, initial vital signs, and laboratory data sampled at the time of ED admission. Patients were randomly assigned to a training set or validation set. For the training set, we generated models using independent variables associated with 28-day mortality by multivariate analysis, and developed a new nomogram for the prediction of 28-day mortality. Thereafter, the diagnostic accuracy of the nomogram was tested using the validation set.ResultsThe prediction model that included albumin, base excess, and respiratory rate demonstrated the largest area under the receiver operating characteristic curve (AUC) value of 0.8173 [95% confidence interval (CI), 0.7605–0.8741]. The logistic analysis revealed that a conventional scoring system was not associated with 28-day mortality. In the validation set, the discrimination of a newly developed nomogram was also good, with an AUC value of 0.7537 (95% CI, 0.6563–0.8512).ConclusionOur new nomogram is valuable in predicting the 28-day mortality of patients with severe sepsis and/or septic shock in the emergency department. Moreover, our readily available nomogram is superior to conventional scoring systems in predicting mortality.

Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients.

Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients.

Empiric Antibiotic Therapy for Severe Sepsis and Septic Shock.

A retrospective study was conducted to investigate the validity and the effectiveness of early empiric antibiotic and de-escalation therapy for the treatment of severe sepsis and septic shock patients in the intensive care unit (ICU). Patients admitted to the ICU at Chiba University Hospital from January 1, 2010, to December 31, 2012, for the treatment of severe sepsis or septic shock were selected for analysis. One-hundred and ten patients were enrolled for the analysis. Carbapenems were selected most frequently (57.3%), followed by cephalosporins (22.7%), and penicillins (21.8%). Empiric antibiotic therapy was appropriate for 85 (77.3%) patients. Mortality rates for patients with inappropriate empiric therapy was 36.8%, whereas mortality rates for patients with appropriate empiric therapy was 17.5%. Among the patients with appropriate empiric antibiotic administration, de-escalation was associated with lower mortality rates of 5.0% for severe sepsis and 9.7% for septic shock patients. The mortality rates for the no de-escalation group were 19.0% and 35.7%, respectively. Empiric antibiotic therapy was acceptable for severe sepsis and septic shock patients treated in the ICU. The appropriate selection of empiric antibiotics was related to a greater rate of de-escalation and better survival. The risk of multi-drug-resistant bacterial infections was not as high as expected, but will need further attention in the future.

The Effect of Early Goal-Directed Therapy On Outcome in Adult Severe Sepsis And Septic Shock Patients: A Meta-Analysis of Randomised Clinical Trials

The Effect of Early Goal-Directed Therapy On Outcome in Adult Severe Sepsis And Septic Shock Patients: A Meta-Analysis of Randomised Clinical Trials

Hydrocortisone in treatment of severe sepsis and septic shock with acute respiratory distress syndrome: a randomised controlled trial

and improve PaO2/FiO2 ratio at the 3 rd day after treatment (273.9+126.9 vs 227.6+110.3, P = 0.007). The incidence of hyperglycemia was also higher in the study group. Mortality in the study group was lower although statistical difference was not reached (25.5% vs 31.3%, P = 0.37). Conclusions Hydrocortisone improved outcomes; namely organ support-free days, vasopressor-dependent days and oxygenation, in severe sepsis or septic shock patients with ARDS. There was a trend toward mortality reduction in the study group but the statistical significant was not reached. (ClinicalTrials.gov number, NCT01284452)

Patterns of organic dysfunction in severe sepsis and septic shock patients admitted to the ICU from the emergency department: a 4-year retrospective cohort

Mortality rates for severe sepsis and septic shock are decreasing through the years worldwide. Most of this improvement in mortality is associated with protocols for early recognition, resuscitation and adequate initial antibiotic choice in patients presenting with sepsis to the emergency department.