Higher Sepsis-related Organ Failure Assessment Research Articles

Construction and evaluation of short-term and long-term mortality risk prediction model for patients with sepsis based on MIMIC-IV database.

Given the high incidence and mortality rate of sepsis, early identification of high-risk patients and timely intervention are crucial. However, existing mortality risk prediction models still have shortcomings in terms of operation, applicability, and evaluation on long-term prognosis. This study aims to investigate the risk factors for death in patients with sepsis, and to construct the prediction model of short-term and long-term mortality risk. Patients meeting sepsis 3.0 diagnostic criteria were selected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and randomly divided into a modeling group and a validation group at a ratio of 7꞉3. Baseline data of patients were analyzed. Univariate Cox regression analysis and full subset regression were used to determine the risk factors of death in patients with sepsis and to screen out the variables to construct the prediction model. The time-dependent area under the curve (AUC), calibration curve, and decision curve were used to evaluate the differentiation, calibration, and clinical practicability of the model. A total of 14 240 patients with sepsis were included in our study. The 28-day and 1-year mortality were 21.45% (3 054 cases) and 36.50% (5 198 cases), respectively. Advanced age, female, high sepsis-related organ failure assessment (SOFA) score, high simplified acute physiology score II (SAPS II), rapid heart rate, rapid respiratory rate, septic shock, congestive heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, diabetes, malignant tumor, high white blood cell count (WBC), long prothrombin time (PT), and high serum creatinine (SCr) levels were all risk factors for sepsis death (all P<0.05). Eight variables, including PT, respiratory rate, body temperature, malignant tumor, liver disease, septic shock, SAPS II, and age were used to construct the model. The AUCs for 28-day and 1-year survival were 0.717 (95% CI 0.710 to 0.724) and 0.716 (95% CI 0.707 to 0.725), respectively. The calibration curve and decision curve showed that the model had good calibration degree and clinical application value. The short-term and long-term mortality risk prediction models of patients with sepsis based on the MIMIC-IV database have good recognition ability and certain clinical reference significance for prognostic risk assessment and intervention treatment of patients.

Association between predialysis creatinine and mortality in acute kidney injury patients requiring dialysis.

Creatinine is widely used to estimate renal function, but this is not practical in critical illness. Low creatinine has been associated with mortality in many clinical settings. However, the associations between predialysis creatinine level, Sepsis-related Organ Failure Assessment (SOFA) score, fluid overload, and mortality in acute kidney injury patients receiving dialysis therapy (AKI-D) has not been fully addressed. We extracted data for AKI-D patients in the eICU and MIMIC databases. We conducted a retrospective observational cohort study using the eICU dataset. The study cohort was divided into the high-creatine group and the low-creatinine group by the median value (4 mg/dL). The baseline patient information included demographic data, laboratory tests, medications, and comorbid conditions. The independent association of creatinine level with 30-day mortality was examined using multivariate logistic regression analysis. In sensitivity analyses, the associations between creatinine, SOFA score, and mortality were analyzed in patients with or without fluid overload. We also carried out an external validity using the MIMIC dataset. In all 1,600 eICU participants, the 30-day mortality rate was 34.2%. The crude overall mortality rate in the low-creatinine group (44.9%) was significantly higher than that in the high-creatinine group (21.9%; P < 0.001). In the fully adjusted models, the low-creatinine group was associated with a higher risk of 30-day mortality (odds ratio, 1.77; 95% confidence interval, 1.29-2.42; P < 0.001) compared with the high-creatinine group. The low-creatinine group had higher SOFA and nonrenal SOFA scores. In sensitivity analyses, the low-creatinine group had a higher 30-day mortality rate with regard to the BMI or albumin level. Fluid overloaded patients were associated with a significantly worse survival in the low-creatinine group. The results were consistent when assessing the external validity using the MIMIC dataset. In patients with AKI-D, lower predialysis creatinine was associated with increased mortality risk. Moreover, the mortality rate was substantially higher in patients with lower predialysis creatinine with concomitant elevation of fluid overload status.

Predictors of early mortality in critically ill patients with acute kidney injury necessitating renal replacement therapy: A cohort study.

Reliable prediction of early mortality after initiation of renal replacement therapy (RRT) in critically ill patients may inform decision-making regarding this treatment. Our primary objective was to identify predictors of mortality within 2days of starting RRT. Patients with acute kidney injury (AKI), receiving RRT, and admitted to intensive care units of one hospital were included. Associations between baseline risk factors and mortality at 2days and at hospital discharge were analyzed using logistic regression. Discrimination of both models was assessed. We included 626 patients, treated initially with intermittent RRT (n=300, 47.9%), continuous RRT (n=211, 33.7%), or sustained low-efficiency dialysis (n=115, 18.4%). Two-day mortality after starting RRT was 12.9% (n=81), and hospital mortality was 50.5% (n=316). Independent predictors of 2-day mortality included primary diagnostic category (p=0.004) and sepsis-related organ failure assessment (SOFA) score (odds ratio [OR] 1.36 per point, 95% confidence interval [CI] 1.24-1.50). Independent predictors of hospital mortality included SOFA (1.29, 95%CI 1.21-1.37), Charlson score (1.20, 95%CI 1.18-1.43), and interhospital transfer (OR 0.55, 0.38-0.81). C-statistics were 0.81 (2-day mortality) and 0.80 (hospital mortality). Higher SOFA was associated with 2-day mortality after RRT initiation and with hospital mortality. Discrimination in both models was modest.

Can we learn from others? The Swedish intensive care unit database for COVID-19 cases.

Can we learn from others? The Swedish intensive care unit database for COVID-19 cases.

Prevalence and Impact of Vitamin D Deficiency in Critically Ill Cancer Patients Admitted to the Intensive Care Unit.

Vitamin D deficiency is frequent in cancer patients and a risk factor for morbidity and mortality during critical illness. This single-center retrospective study analyzed 25-hydroxyvitamin D levels in critically ill cancer patients (n = 178; hematologic, n = 108; solid, n = 70) enrolled in a prospective ICU registry. The primary analysis was the prevalence of vitamin D deficiency (<20 ng/mL) and the severe deficiency (≤12 ng/mL). Secondary analyses included risk factors for vitamin D deficiency and its impact on ICU, hospital, and 1-year mortality. The prevalence of vitamin D deficiency and severe deficiency was 74% (95% CI: 67–80%) and 54% (95% CI: 47–61%). Younger age, relapsed/refractory disease, and a higher sepsis-related organ failure assessment (SOFA) score were independent risk factors for vitamin D deficiency (p < 0.05). After adjusting for relapsed/refractory disease, infection, the SOFA score, and the early need for life-supporting interventions, severe vitamin D deficiency was an independent predictor of hospital mortality (OR: 2.21, 95% CI: 1.03–4.72, p = 0.04) and 1-year mortality (OR: 3.40, 95% CI: 1.50–7.71, p < 0.01), but not of ICU mortality. Conclusion: Vitamin D deficiency is common in critically ill cancer patients requiring ICU admission, but its impact on short-term mortality in this group is uncertain. The observed association of severe vitamin D deficiency with the post-ICU outcome warrants clinical consideration and further study.

Epidemiology and Outcomes of Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: A Multicenter Retrospective Study

Background: Acute kidney injury (AKI) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). However, the epidemiological features and outcomes of AKI among COVID-19 patients with ARDS are unknown. Methods: We retrospectively recruited consecutive adult COVID-19 patients who were diagnosed with ARDS according to Berlin definition from 13 designated intensive care units in the city of Wuhan, China. Potential risk factors of AKI as well as the relation between AKI and in-hospital mortality were investigated. Results: A total of 275 COVID-19 patients with ARDS were included in the study, and 49.5% of them developed AKI during their hospital stay. In comparison with patients without AKI, patients who developed AKI were older, tended to have chronic kidney disease, had higher Sepsis-Related Organ Failure Assessment score on day 1, and were more likely to receive invasive ventilation and develop acute organ dysfunction. Multivariate analysis showed that age, history of chronic kidney disease, neutrophil-to-lymphocyte ratio, and albumin level were independently associated with the occurrence of AKI. Importantly, increasing AKI severity was associated with increased in-hospital mortality when adjusted for other potential variables: odds ratio of stage 1 = 5.374 (95% CI: 2.147–13.452; p < 0.001), stage 2 = 6.216 (95% CI: 2.011–19.210; p = 0.002), and stage 3 = 34.033 (95% CI: 9.723–119.129; p < 0.001). Conclusion: In this multicenter retrospective study, we found that nearly half of COVID-19 patients with ARDS experienced AKI during their hospital stay. The coexistence of AKI significantly increased the mortality of these patients.

The Value of Thromboelastography in the Diagnosis of Sepsis-Induced Coagulopathy.

Thromboelastography (TEG) is regularly used for monitoring abnormalities of the coagulation system in patients with sepsis. However, it is unclear whether TEG parameters are associated with sepsis-induced coagulopathy (SIC). Thus, we aimed to assess the diagnostic value of TEG for SIC. The medical records of patients who underwent TEG from January 2016 to December 2016 were analyzed retrospectively. The patients were divided into sepsis group and non-sepsis group. Baseline patient characteristics and coagulation function indexes were compared. Receiver–operating characteristic curve analysis was used to determine predictors of SIC. A total of 167 patients were included, of whom 84 had sepsis. The clot formation speed (K) was significantly higher(P < 0.001), and the maximum amplitude (MA) and angle were significantly lower (both P < 0.001) in the sepsis group than that in non-sepsis group. Patients with SIC had higher Sepsis-related Organ Failure Assessment scores than those patients without SIC (P < 0.001). The area under the curve of K for diagnosing SIC was 0.910. The area under the curve of angle and MA for excluding SIC was 0.895 and 0.882, respectively. Thus, TEG parameters have good diagnostic value for SIC.

Survival analysis of patients with sepsis in Brazil.

This study aimed to analyze the survival of septic patients and to assess prognostic factors. Patients with sepsis, severe sepsis, and septic shock were followed up and clinical and laboratory data were collected. The sepsis-related organ failure assessment (SOFA) score was calculated. RESULTS: The overall 30-day survival rates of patients with sepsis, severe sepsis, and septic shock were 86.3%, 72.5%, and 20%, respectively. Mortality was related to old age, septic shock, coagulopathy, lactate level, and high SOFA score among other factors. Identification of prognostic variables may reduce sepsis-related mortality.

Risk Factors for Early Mortality in Hemato-Oncological Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia

Introduction- Acinetobacter baumannii is a Gram-negative strictly aerobic non-fermentative coccobacillus, widely distributed in nature. Multidrug resistant strains, including carbapenem antibiotic resistant, have been associated with fulminant severe sepsis and high overall mortality rate, ranging between 25 and 54%. This is true mainly for intensive care unit (ICU) and immunocompromised patients. Although CRAB bacteremia has previously been reported, studies involving hemato-oncological patients have rarely been reported.Aim - To investigate factors associated with 7 day mortality, defined as death within 7 days of documented bacteremia among hemato-oncological patients with CRAB bacteremia in a tertiary medical center in Israel.Methods - A retrospective analysis of all patients with CRAB bacteremia treated in a large tertiary care hospital January 2008 to June 2018 was performed. Among them, 46 hemato-oncological patients were identified and analyzed.Baseline patient and infection characteristics were collected from electronic medical records. In addition, antibiotic management and outcomes were documented. Univariable and multivariable analysis of risk factors for 7 day mortality were performed. Variables statistically significant in the univariable analysis were introduced into the regression model.Results - A total of 46 hemato-oncological patients with CARB bacteremia were included in this study. At the time that bacteremia occurred - 18 (39.5%) patients were hospitalized in internal medicine departments, 4 (8.7%) patients in ICU, 13 (28.3%) patients in the hemato-oncology ward and 11 (23.9%) patients in the stem cell transplantation ward.Mean age of patients was 62.5±16.8 yr., with 20 (43.5%) males. The mean length of stay before bacteremia occurrence was 29 ± 42.8 days. The presumed sources of bacteremia were respiratory tract (n = 25, 54.5%), vascular catheter (n = 14, 30.5%), urinary tract (n = 2, 4%), and other/unknown sources (n = 5, 11%). The susceptibility of CRAB to colistin was 100%, 7 isolates were susceptible to ampicillin/sulbactam and 4 of 38 tested were susceptible to tigecycline.The overall 7 day mortality in patients with CARB bacteremia was 71.7% (33/46), with an overall 30 day mortality of 93.4% (43/46).Univariable analysis showed that the significant risk factors for 7 day mortality in hemato-oncological patients with CARB bacteremia was higher Sepsis-related Organ Failure Assessment (SOFA) score (Survivors group - median score - 7, IQR 4-10.5, non-survivors group - median score- 13, IQR 10.5-16, p<0.001). Protective factors included: Foley catheter insertion prior to bacteremia (11/33, 84.6% vs. 16/33, 48.5%, p=0.044), appropriate antibiotic therapy within 48h of bacteremia (11/13, 84.6% vs. 11/33, 33.3%, p=0.003) and central venous catheter removal (7/9, 77.8% vs. 4/22, 18.2%, p=0.003) all of which were associated with decreased risk for early mortality (Table 1).In multivariable analysis, factors remaining statistically significant were high SOFA score - associated with increased mortality (OR 2.021, 95% CI 1.246-3.277, p=0.004) and Foley catheter insertion prior to bacteremia as well as appropriate antibiotic therapy within 48h of bacteremia (OR 0.024, 0.001-0.593, p=0.023; OR 0.034, 95% CI 0.002-0.700, p=0.0028, respectively) associated with a decreased risk for 7 day mortality (Table 2).Discussion - Early administration of appropriate antibiotics, mainly colistin, resulted in decreased early mortality in CRAB bacteremia. Patients with Foley catheter had better survival, probably reflecting an undiagnosed urinary cause (which is usually associated with a better outcome). A more severe clinical presentation, represented by higher SOFA score, was associated with higher mortality, underlying the need for urgent treatment in this group of patients. Overall 30 day mortality is extremely high in this group of patients with a death toll of nearly 100%.Conclusions - Bacteremia with CRAB is often fulminant and fatal, particularly among hemato-oncological patients. Early implementation of appropriate antibiotics might improve outcome. Due to the severity of the infection and the high mortality rate, prevention of this catastrophic complication in hemato-oncological patients is crucial. DisclosuresNo relevant conflicts of interest to declare.

354 Central Venous Oxygen Saturation Related With Mitochondrial Dysfunction in Sepsis Patients

An increased mitochondrial oxidative stress has an association with blood lactate, ScvO2, delta CO2, and survival rate in patients with sepsis. This was a prospective, observational study. Patients who visited the emergency department with suspected sepsis were included. Blood lactate, central venous oxygen saturation (ScvO2), and venous-to-arterial carbon dioxide tension difference (delta CO2) were documented. In addition, mitochondrial oxidative stress assessed by MitoSOXTM and mitochondrial mass were determined from peripheral blood mononuclear cells (PBMCs) for determination of mitochondrial function in all patients. Forty-six patients were enrolled, of which 38 patients were diagnosed with sepsis (sepsis-related organ failure assessment (SOFA) score ≥ 2). Mitochondrial oxidative stress was increased in sepsis patients with high SOFA score (SOFA > 5), compared with low SOFA score (SOFA 2-5) (20.44 versus 13.14; P=0.04). When sepsis patients were categorized into 3 groups according to the ScvO2 levels; Low-ScvO2 (<70%, n=5), normal-ScvO2 (70-80%, n=9), and high-ScvO2 (>80%, n=6), our results showed that the level of mitochondrial oxidative stress was higher in the high ScvO2 group, compared with normal and low ScvO2 groups (P=0.01). Moreover, a strong linear relationship was observed between the ratio of mitochondrial oxidative stress/mitochondrial mass and ScvO2 (r=0.75; p=0.01). However, there was no correlation between mitochondrial oxidative stress and lactate or mitochondrial oxidative stress and delta CO2. Data also showed that the survival rate was not different among these groups. To our knowledge, this is the first demonstration that ScvO2 could be used as a marker for mitochondrial dysfunction in sepsis. Moreover, ScvO2 may potentially be useful for developing novel therapeutic strategies to attenuate mitochondrial dysfunction in sepsis patients.

Microbiology in burns patients with blood stream infections: trends over time and during the course of hospitalization

Background: Bloodstream infections (BSI) are a major cause of mortality in burns patients. Knowledge of the microbiology is crucial to direct empirical therapy. We sought to determine the causative microorganisms and antibiotic resistance in burns patients with BSI.Methods: All consecutive BSI episodes in a tertiary hospital burns unit from 2000 to 2014 were included. The following three subperiods were compared: 2000–2004, 2005–2009 and 2010–2014. Changes in BSI occurring during early and late hospitalization periods were evaluated.Results: A total of 103 BSI episodes were included. The cumulative incidence was 2.4 episodes/1000 patient days. A positive trend in the frequency of Gram-negative BSI, especially in the upsurge of Pseudomonas aeruginosa and Klebsiella spp. BSI after 2004, was observed. The most common causative pathogens in early BSI were Gram-positive microorganisms. P. aeruginosa and Klebsiella spp. became the predominant aetiology in the fourth week of hospitalization and beyond. There was a progressive increase in imipenem-resistant P. aeruginosa over time (0%, 67%, 75% in 2000–2004, 2005–2009, 2010–2014, respectively) and during the hospital stay (50% vs. 85.7%, in <7 days-BSI vs. >30 days-BSI, respectively). A higher SOFA (Sepsis-related Organ Failure Assessment) score was associated with Gram-negative BSI versus non-Gram-negative BSI (median: 2.5 vs. 0; p = 0.041).Conclusions: There is a changing trend in the types of pathogens causing BSI in burns patients over the 14-year period and during the course of hospitalization. The problematic increase in carbapenem-resistance highlights the need for new antimicrobial stewardship policies and antibiotic prescribing protocols.

Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing Escherichia coli bacteremia.

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR=0.30; p=0.021), presence of dementia (OR=54.51; p=0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR=1.69; p<0.001), presence of neutropenia (OR=12.94; p=0.049), and presence of a urinary tract infection (OR=0.07; p=0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies.

IntroductionBilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.MethodsThe data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.ResultsThe 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.ConclusionBilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.

Carbapenem-resistant Klebsiella pneumoniae infections in a Greek intensive care unit: Molecular characterisation and treatment challenges.

Acquisition of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) strains poses a major threat to critically ill patients. The objectives of this study were to describe the epidemiology of CP-Kp isolates as well as the clinical outcome associated with the corresponding infections and to identify risk factors for mortality of intensive care unit (ICU) patients in a Greek hospital. A prospective, observational study was conducted in a nine-bed general ICU over a 2-year period (April 2010-March 2012). Imipenem-resistant K. pneumoniae isolates recovered from clinical samples of ICU patients were prospectively collected and studied for the presence of carbapenemases. Isolates were submitted to molecular typing using pulsed-field gel electrophoresis (PFGE). In total, 61 CP-Kp isolates (48 KPC-producers and 13 VIM-producers) were recovered from 58 ICU patients. The majority of KPC-producers were classified into a single PFGE type, indicating potent clonal dissemination. Among the 32 infected patients, bacteraemia was diagnosed in 16. Tigecycline+colistin was the most common combination antimicrobial regimen. Infection-attributable mortality was 43.8%. Regarding mortality risk factors, non-survivors were older (P=0.080), all of them presented with septic shock (P=0.010) and they had higher Sepsis-related Organ Failure Assessment (SOFA) scores at infection onset (P=0.004) compared with survivors. Appropriate definitive treatment and combination regimens were not associated with patient survival. In conclusion, CP-Kp infections are associated with limited treatment options and high in-hospital mortality. Effective measures for preventing dissemination of respective isolates in the hospital setting are required.

Red blood cell transfusion in septic shock - clinical characteristics and outcome of unselected patients in a prospective, multicentre cohort

BackgroundTreating anaemia with red blood cell (RBC) transfusion is frequent, but controversial, in patients with septic shock. Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients.MethodsWe did a prospective cohort study at 7 general intensive care units (ICUs) including all adult patients with septic shock in a 5-month period.ResultsNinety-five of the 213 included patients (45%) received median 3 (interquartile range 2–5) RBC units during shock. The median pre-transfusion haemoglobin level was 8.1 (7.4–8.9) g/dl and independent of shock day and bleeding. Patients with cardiovascular disease were transfused at higher haemoglobin levels. Transfused patients had higher Simplified Acute Physiology Score (SAPS) II (56 (45-69) vs. 48 (37-61), p = 0.0005), more bleeding episodes, lower haemoglobin levels days 1 to 5, higher Sepsis-related Organ Failure Assessment (SOFA) scores (days 1 and 5), more days in shock (5 (3-10) vs. 2 (2-4), p = 0.0001), more days in ICU (10 (4-19) vs. 4 (2-8), p = 0.0001) and higher 90-day mortality (66 vs. 43%, p = 0.001). The latter association was lost after adjustment for admission category and SAPS II and SOFA-score on day 1.ConclusionsThe decision to transfuse patients with septic shock was likely affected by disease severity and bleeding, but haemoglobin level was the only measure that consistently differed between transfused and non-transfused patients.

Pseudomonas aeruginosa Ventilator-associated Pneumonia. Predictive Factors of Treatment Failure

The predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain. To describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP. From the multicenter OUTCOMEREA database (1997-2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence. A total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3-0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4-1.0]; P = 0.048). Neither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients

Vancomycin is frequently administered to critically ill patients by continuous infusion in order to optimise drug efficacy; however, there are few data available on the efficacy of this strategy in septic patients. In this retrospective analysis, 261 patients treated with continuous infusion of vancomycin in the Department of Intensive Care at Hôpital Erasme (Brussels, Belgium) were evaluated. Creatinine clearance (CLCr) was calculated from 24-h urine collection and normalised to body surface area. During the study period, 139 patients (53%) had insufficient vancomycin concentrations (<20μg/mL) on Day 1 and 87 patients (33%) on Day 2. Patients who had insufficient drug concentrations on Day 1 of therapy were more likely to be men, to have a higher CLCr and to have received lower loading and daily vancomycin doses than other patients, who received greater vasopressor support and had higher Sepsis-related Organ Failure Assessment scores. In multivariate regression analysis, high CLCr and male sex independently predicted the presence of insufficient vancomycin concentrations on Days 1 and 2 of therapy. Receiver operating characteristic curve analysis for CLCr showed an area under the concentration–time curve of 0.75 (95% confidence interval 0.69–0.81) to predict insufficient drug concentrations on Day 1 of therapy. A CLCr>120mL/min/1.73m2 had a sensitivity of 26%, a specificity of 94% and an 84% positive predictive value of 84% for vancomycin concentrations <20μg/mL. In conclusion, approximately one-half of the septic Intensive Care Unit patients treated with continuous infusion of vancomycin at currently recommended doses had insufficient drug concentrations in the early phase of therapy. A high CLCr was the variable most strongly associated with insufficient drug concentrations.

Risk factors and clinical analysis on acute hepatic dysfunction induced by sepsis

Objective To study the incidence,risk factors and clinical features of patients with acute hepatic dysfunction induced by sepsis. Methods One hundred and sixty patients with sepsis were assigned to two groups according to liver function: sepsis group and acute hepatic dysfunction group. Logistic regression analysis was used to study the risk factors.The comparison of plasma endothelin-1 ( ET-1 ) and sepsis-related organ failure assessment (SOFA) score between two groups was carried out.Results Of 160sepsis patients,25 (15.6％) patients were subjected to acute hepatic dysfunction induced by sepsis.Logistic regression analysis showed that long-term indulgence in wine drunk (OR =4.102,95％ CI 1.288 -13.063 ),history of cardiac insufficiency ( OR =4.109,95％ CI 1.352 - 12.493) and hypotension ( OR =5.833,95％ CI:1.712 - 19.868 ) were the significant risk factors.Though oxygenation index ( PaO2/FiO2),platelet (PLA) and Glasgow coma scale (GCS) were not different between two groups,the total bilirubin (Tbil),direct bilirubin (Dbil),creatitine (Cre),range of blood glucose variation (Rglu),lactic acid (Lac),plasma ET-1and SOFA score in acute hepatic dysfunction group were higher than those in sepsis group. Mortality rate in acute hepatic dysfunction group was higher than that in sepsis group.Conclusions Long-term drunk,history of cardiac insufficiency and hypotension are the risk factors in acute hepatic dysfunction induced by sepsis.Elevated arterial Lac and plasma ET-1 levels,and higher SOFA score in acute hepatic dysfunction group suggest poor prognosis. Key words: Sepsis; Endothelin-1; Acute hepatic dysfunction

Citrate anticoagulation for continuous venovenous hemofiltration*

Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. Randomized, nonblinded, controlled single-center trial. General intensive care unit of a teaching hospital. Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.

Effect of adjusting the immunosuppressants on the prognosis of the infection in the patients with liver transplantation

To explore the method of adjusting the immunosuppressants in serious infection after liver transplantation. With reference to sepsis-related organ failure assessment (SOFA), 2005.1-2007.12, when the patient's score > or =15, the immunosuppressants were withdrawn, and the patients were given powerful antibiotics and the other treatments in combination. They were further divided into two groups, SOFA 15-17 (group A, 10 cases) and > or =18 (group B, 16 cases). They were compared, and also with the patients without stoppage of immunosuppressants (group C, 13 cases, 2003.3-2004.12). After withdrawing the immunosuppressant, the rejection incidence and times, the changes in SOFA score and mortality and their relationships were analyzed. After adjusting the immunosuppressant and with control of serious infections, rejection occurred in 9 patients, with 5 cases in group A (50.0%), 4 in B (25.0%), none in C. The differences among groups showed statistically significant difference (chi(2)=8.0, P=0.02), but no difference was seen between group A and B (chi(2)=1.70, P=0.19). When the rejection developed, the SOFA score decreased obviously (9.78+/-3.14 vs. 17.22+/-1.86, t=6.10, P=0.00). The time of rejection was (17.56+/-2.60) days after stopping the immunosuppressant. All 25 deaths were due to serious infection with multiple organ dysfunction syndrome, but not rejection. Five deaths occurred in group A (50.0%), 7 in B (43.8%), 13 in C (100.0%). Not a single patient with rejection died from infection. Proper adjustment of the immunosuppressants could decrease the mortality (chi(2)=7.60, P=0.02). SOFA score could be used to guide the adjustment of the immunosuppressants, when SOFA> or =15, the immunosuppressants could be stopped, which would not increase the rejection incidence and decrease mortality. The lower the SOFA score is, the faster the patients recuperate better, but more rejection develops. In order to adjust the immunosuppressant in time, the period with high SOFA score should be shortened.