Diagnosis of overt disseminated intravascular coagulation: a comparative study using criteria from the International Society versus the Korean Society on Thrombosis and Hemostasis

PURPOSE: Since 1993, Koreans have used diagnostic criteria set by the Korean Society on Thrombosis and Hemostasis (KSTH) in the diagnosis of overt disseminated intravascular coagulation (DIC). In 2001, the Scientific and Standardization Committee (SCC) of the International Society on Thrombosis and Hemostasis (ISTH) proposed new diagnostic criteria for the diagnosis of overt DIC. We wanted to compare the use of the ISTH versus KSTH criteria in the diagnosis of overt DIC. MATERIALS AND METHODS: We enrolled 131 patients over the age of 15 years, who had been admitted and diagnosed as having DIC from May 2000 to April 2005 at the Youngdong Severance Hospital, Seoul, Korea. Of the 131 patients, there were 71 males and 60 females, with a median age of 61 years. Hemostatic tests, including platelet counts, PT, aPTT, fibrinogen level and D-dimer, were evaluated based on the respective scoring systems. To assess the concordance between the two diagnostic systems, we used the Student's t-test and the K-coefficient. RESULTS: There were 79 patients compatible with the ISTH criteria and 63 patients with the KSTH criteria. Sixty-one patients were compatible with both diagnostic systems. The grade of agreement, or concordance rate, was 84.7% and the K-coefficient, or interrater reliability, was as low as 0.6 without significance. However, if we scored 1 point for a fibrinogen level of 100-150 mg/dL, and 2 points for a level below 100 mg/dL, for the ISTH criteria, then 63 patients were compatible with both diagnostic systems, and the concordance rate increased to 85.5% and the K-coefficient to 0.71 with significance. CONCLUSION: To achieve good agreement between the ISTH and KSTH diagnostic systems for overt DIC, we highly recommend changing the plasma fibrinogen cut-off value in the ISTH criteria from 100mg/dL to 150 mg/dL and scoring up to 2 points for a level below 100 mg/dL.     

Criteria for diagnosing DIC

The differences between reagents of prothrombin time (PT), fibrinogen and fibrin and fibrinogen degradation products(FDP) were examined in patients with disseminated intravascular coagulation (DIC) and without DIC. The sensitivity of the PT ratio for DIC is lowered by the PT reagent with a high international sensitivity index, and the difference between PT reagents was marked. The sensitivity of PT-international normalized ratio (INR) for DIC was higher than that of the PT ratio and the difference between reagents in PT-INR was low. Though the difference between reagents for fibrinogen is slight, the usefulness in diagnosing DIC is also slight. Though the sensitivity of FDP for DIC was good, the difference between FDP reagents was marked. Therefore, standardization of PT and FDP seems to be necessary. Concordance of overt-DIC diagnostic criteria by the International Society of Thrombosis and Haemostasis (ISTH) and DIC diagnostic criteria of Japanese Ministry of Health and Welfare (JMHW) was about 70%, and overt-DIC diagnostic criteria of ISTH seemed to diagnose the typical type of DIC diagnosed by JMHW criteria. Finally, the diagnostic criteria of non-overt DIC are expected to become increasingly important.     

Diagnosis of DIC based on evidence

The diagnosis of disseminate intravascular coagulation (DIC) was first based on the detection of microthrombi, but it currently involves analysis of hemostatic abnormalities by various laboratory tests and further studies are needed to simplify diagnosis of DIC. There are three diagnostic criteria for DIC developed by the International Society of Thrombosis Haemostasis (ISTH), the Japanese Association for Acute Medicine (JAAM) and the Japanese Ministry Health and Welfare. These diagnostic criteria consist of the scoring system by the same global coagulation tests. From ROC analysis, the ability for diagnosis of DIC is similar among three diagnostic criteria. ISTH diagnostic criteria has high specificity and low sensitivity, but JAAM criteria has low specificity and high sensitivity. Several molecular hemostatic markers such as thrombin antithrombin complex, D-dimer, soluble fibrine (SF) and plasmin-plasmin inhibitor complex have to be adopted for further improvement of diagnostic criteria for DIC. Finally, prospective study for new diagnostic criteria for DIC should be carried out in infectious diseases by molecular hemostatic markers.     

Prognostic Value of Estimated Plasma Volume Status in Patients With Sepsis

BackgroundIn patients with sepsis, timely risk stratification is important to improve prognosis. Although several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. The objective of this study was to evaluate the prognostic value of estimated plasma volume status (ePVS) in patients admitted to the intensive care unit (ICU) with sepsis or septic shock.MethodsThis single-center, prospective observational study, included 100 patients admitted to the ICU with sepsis or septic shock. Informed consent, blood samples, and co-morbidity data were obtained from the patients on admission, and the severity of sepsis was recorded. The primary outcome was in-hospital mortality and multivariable logistic regression analysis was used to adjust for confounding factors to determine the significant prognostic factor.ResultsThe in-hospital mortality was 47%. The ePVS was correlated with the amount of total fluids administered 24 hours before the ICU admission. The mean ePVS in patients who died was higher than in those who survived (7.7 ± 2.1 dL/g vs. 6.6 ± 1.6 dL/g, P = 0.003). To evaluate the utility of ePVS in predicting in-hospital mortality, a receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 7.09 dL/g, with an area under the curve of 0.655. In the multivariate analysis, higher ePVS was significantly associated with higher in-hospital mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.04–1.85, P = 0.028). The Kaplan-Meier curve showed that an ePVS value above 7.09 was associated with an increased risk of in-hospital mortality compared with the rest of the population (P = 0.004).ConclusionThe ePVS was correlated with the amount of intravenous fluid resuscitation and may be used as a simple and novel prognostic factor in patients with sepsis or septic shock who are admitted to the ICU.     

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.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.     

Clinical outcome and predictors of mortality in children with sepsis,severe sepsis,and septic shock from Rohtak,Haryana: A prospective observational study

Background:

Information regarding early predictive factors for mortality and morbidity in sepsis is limited from developing countries.

Methods:

A prospective observational study was conducted to determine the clinical outcome and predictors of mortality in children with sepsis, severe sepsis, and septic shock. Children aged 1 month to 14 years admitted to a tertiary care pediatric intensive care unit (PICU) with a diagnosis of sepsis, severe sepsis, or septic shock were enrolled in the study. Hemodynamic and laboratory parameters which discriminate survivors from nonsurvivors were evaluated.

Results:

A total of 50 patients (30 [60%] males) were enrolled in the study, of whom 21 (42%) were discharged (survivors) and rest 29 (58%) expired (nonsurvivor). Median (interquartile range) age of enrolled patients were 18 (6, 60) months. Mortality was not significantly predicted individually by any factor including age (odds ratio [OR] [95% confidence interval [CI]]: 0.96 [0.91-1.01], P = 0.17), duration of PICU stay (OR [95% CI]: 1.18 [0.99-1.25], P = 0.054), time lag to PICU transfer (OR [95% CI]: 1.02 [0.93-1.12], P = 0.63), Pediatric Risk of Mortality (PRISM) score at admission (OR [95% CI]: 0.71 [0.47-1.04], P = 0.07) and number of organ dysfunction (OR [95% CI]: 0.03 [0.01-1.53], P = 0.08).

Conclusion:

Mortality among children with sepsis, severe sepsis, and septic shock were not predicted by any individual factors including the time lag to PICU transfer, duration of PICU stay, presence of multiorgan dysfunction, and PRISM score at admission.     

Could a protocol based on early goal-directed therapy improve outcomes in patients with severe sepsis and septic shock in the Intensive Care Unit setting?

Context:

Sepsis is a disease with high incidence and mortality. Among the interventions of the resuscitation bundle, the early goal-directed therapy (EGDT) is recommended.

Aims:

The aim was to evaluate outcomes in patients with severe sepsis and septic shock using EGDT in real life compared with patients who did not undergo it in the Intensive Care Unit (ICU) setting.

Settings and Design:

retrospective and observational cohort study at tertiary hospital.

Subjects and Methods:

All the patients admitted to ICU were screened for severe sepsis or septic shock and included in a registry and followed. The patients were allocated in two groups according to submission or not to EGDT.

Results:

A total of 268 adult patients with severe sepsis or septic shock were included. EGDT was employed in 97/268 patients. The general mortality was higher in no early goal-directed therapy (no-EGDT) then in EGDT groups (49.7% vs. 37.1% [P = 0.04] in hospital and 40.4% vs. 29.9% [P = 0.08] in the ICU, respectively. The general length of stay [LOS] in the no-EGDT and EGDT groups was 45.0 ± 59.8 vs. 29.1 ± 30.1 days [P = 0.002] in hospital and 17.4 ± 19.4 vs. 9.1 ± 9.8 days [P < 0.001] in the ICU, respectively).

Conclusions:

Our study shows reduced mortality and LOS in patients submitted to EGDT in the ICU setting. A simplified EGDT without central venous oxygen saturation is an important tool for sepsis management.     

Survival analysis of 314 episodes of sepsis in medical intensive care unit in university hospital: impact of intensive care unit performance and antimicrobial therapy

Aim

To evaluate epidemiology of sepsis in medical intensive care unit (ICU) in an university hospital, and the impact of ICU performance and appropriate empirical antibiotic therapy on survival of septic patients.

Methods

Observational, partly prospective study conducted over 6 years assessed all patients meeting the criteria for sepsis at ICU admission at the Sisters of Mercy Hospital in Zagreb. Clinical presentation of sepsis was defined according to 2001 International Sepsis Definitions Conference. Demographic data, admission category, source of infection, severity of sepsis, ICU or hospital stay and outcome, ICU performance, and appropriateness of empirical antibiotic therapy were analyzed.

Results

The analysis included 314 of 5022 (6.3%) patients admitted to ICU during the study period. There were 176 (56.1%) ICU survivors. At the ICU admission, sepsis was present in 100 (31.8%), severe sepsis in 89 (28.6%), and septic shock in 125 (39.8%) patients with mortality rates 17%, 33.7%, 72.1%, respectively. During ICU treatment, 244 (77.7%) patients developed at least one organ dysfunction syndrome. Of 138 (43.9%) patients who met the criteria for septic shock, 107 (75.4) were non-survivors (P<0.001). Factors associated with in-ICU mortality were acquisition of sepsis at another department (odds ratio [OR] 0.06; 95% confidence interval [CI], 0.02-0.19), winter season (OR 0.42; 0.20-0.89), limited mobility (OR 0.28; 0.14-0.59), ICU length of stay (OR 0.82; 0.75-0.91), sepsis-related organ failure assessment (SOFA) score on day 1 (OR 0.80; 0.72-0.89), history of global heart failure (OR 0.33; 0.16-0.67), chronic obstructive pulmonary disease (COPD)-connected respiratory failure (OR 0.50; 0.27-0.93), septic shock present during ICU treatment (OR 0.03; 0.01-0.10), and negative blood culture at admission (OR 2.60; 0.81-6.23). Microbiological documentation of sepsis was obtained in 235 (74.8%) patients. Urinary tract infections were present in 168 (53.5%) patients, followed by skin or soft tissue infections in 58 (18.5%) and lower respiratory tract infections in 44 (14.0%) patients. Lower respiratory tract as focus of sepsis was connected with worse outcome (P<0.001). Empirical antibiotic treatment was considered adequate in 107 (60.8%) survivors and 42 (30.4%) non-survivors. Patients treated with adequate empirical antibiotic therapy had significantly higher survival time in hospital (log-rank, P = 0.001).

Conclusion

The mortality rate of sepsis was unacceptably high. The odds for poor outcome increased with acquisition of sepsis at another department, winter season, limited mobility, higher SOFA score on day 1, history of chronic global heart failure, COPD-connected respiratory failure, and septic shock present during ICU treatment, whereas longer ICU length of stay, positive blood culture, and adequate empirical antibiotic therapy were protective factors.Sepsis is a systemic response of the host to infectious stimuli, which consists of clinical, hemodynamic, biochemical, and inflammatory components (1,2). When an organ system begins to fail because of sepsis, the condition is considered severe and is one of the leading causes of death in the critically ill, with the mortality rate of 28-55% (3). The death rates in some subgroups of patients with sepsis-induced organ failure have decreased, even though there is no specific therapy (2). The reduced mortality may be due to changes in the definition of sepsis, better detection and treatment of the underlying infection, or improved supportive care (4). Effective treatment of organ failure is essential because the average risk of death increases by 15-20% with failure of each additional organ (5). The host response is perhaps as important as the site of infection or the type of microorganism causing sepsis. The lung is the most common site of infection, followed by abdominal and urinary tract organs (6). Positive blood cultures are accepted as the evidence of serious infection, but they are positive in only 30% of patients (6). Antimicrobial drugs are necessary, but not sufficient for the treatment of sepsis. Around 10% of the patients do not receive prompt antibiotic therapy for causative pathogen, and their mortality rate is 10-15% higher than in those who receive immediate, appropriate antibiotic therapy (5). The adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome, although early mortality rate is unaffected by the appropriate empirical antibiotic therapy (7). The application of proven medical and technological interventions in a standard therapeutical algorithm is important in everyday performance of intensive care unit (ICU) (8). Since epidemiology and surveillance data significantly differ between medical and surgical ICU patients (9), each ICU has to assess its own epidemiological data and establish critical pathways for the management and treatment of patients with sepsis (10).Our aim was to evaluate the epidemiology of sepsis syndrome in the medical ICU at University Hospital and the impact of ICU performance and adequate empirical antibiotic therapy on the outcome in patients with sepsis.     

Impact of positive fluid balance on mortality and length of stay in septic shock patients

Background:

Fluid management is important in critically patients. The aim of this study was to determine the relationship between fluid balance and adverse outcomes of septic shock.

Methods:

A retrospective study was conducted in the medical Intensive Care Unit (ICU) of a tertiary university hospital in Thailand, over a 7-year period.

Results:

A total of 1048 patients with an ICU mortality rate of 47% were enrolled. The median cumulative fluid intake at 24, 48, and 72 h from septic shock onset were 4.2, 7.7, and 10.5 L, respectively. Nonsurvivors had a significantly higher median cumulative fluid intake at 24, 48, and 72 h (4.6 vs. 3.9 L, 8.2 vs. 7.1 L, and 11.4 vs. 9.9 L, respectively, P < 0.001 for all). Nonsurvivors also had a significantly higher cumulative and mean fluid balance within 72 h (5.4 vs. 4.4 L and 2.8 vs. 1.6 L, P < 0.001 for both). In multivariate logistic regression analysis, mean fluid balance quartile within 72 h, was independently associated with an increase in ICU and hospital mortality. Quartile 3 and 4 have statistically significant increases in mortality compared with quartile 1 (odds ratio [95% confidence interval] 3.04 [1.9–4.48] and 4.16 [2.49–6.95] for ICU mortality and 2.75 [1.74–4.36] and 3.16 [1.87–5.35] for hospital mortality, respectively, P < 0.001 for all). In addition, the higher amount of mean fluid balance was associated with prolonged ICU stays.

Conclusions:

Positive fluid balance over 3 days is associated with increased ICU and hospital mortality along with prolonged ICU stays in septic shock patients.     

Impact of infection on admission and of the process of care on mortality of patients admitted to the Intensive Care Unit: the INFAUCI study

A prospective, cohort, clinical, observational study was performed in 14 Intensive Care Units (ICUs) to evaluate the contemporary epidemiology, morbi-mortality and determinants of outcome of the population with an infection on admission. All 3766 patients admitted during a consecutive 12-month period were screened. Their median age was 63 [26–83], 61.1% were male and 69.8% had significant comorbidities. On admission to the ICU 1652 patients (43.9%) had an infection, which was community acquired in 68.2% (one-fifth with healthcare-associated criteria) and ward-acquired in the others. Roughly half presented to the ICU with septic shock. As much as 488 patients with community-acquired infections were deemed stable enough to be first admitted to the ward, but had similar mortality to unstable patients directly admitted to the ICU (35.9% vs. 35.1%, p 0.78). Only 48.3% of this infected population had microbiological documentation and almost one-quarter received inappropriate initial antibiotic therapy. This, along with comorbidities, was a main determinant of mortality. Overall, infected patients on admission had higher mortality both in the ICU (28.0% vs. 19.9%, p <0.001) and in the hospital (38.2% vs. 27.5%, p <0.001) and even after being discharged to the ward (14.2% vs. 9.6%, p <0.001). Also, patients not infected on admission who acquired an infection in the ICU, had an increased risk of dying in the hospital (odds ratio 1.41 [1.12–1.83]). Consequently, infection, regardless of its place of acquisition, was associated with increased mortality. Improving the process of care, especially first-line antibiotic appropriateness, and preventing ICU-acquired infections, may lead to better outcomes.     

Multiplex cytokine profiling in patients with sepsis

A major goal for the clinical research in sepsis is mapping the various mediators driving the systemic manifestations of infection. Identifying relevant mediators responsible for the physiological alterations during sepsis may offer diagnostic and therapeutic opportunities. We aimed to explore the novel approach of simultaneously measuring several biomolecules using the multiplex technique and to study its relevance in diagnosing and monitoring septic patients. In 30 patients fulfilling American College of Chest Physicians and the Society of Critical Care Medicine sepsis criteria, we simultaneously measured 17 cytokines during the first 7 days after admission. We analysed the results with respect to the presence of septic shock and survival. Five patients died during the study. We found a significant positive correlation between the monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1β and interleukin (IL)-8 levels in the first 3 days and Sepsis-related Organ Failure Assessment score on day 1. Most cytokines showed no significant difference between patients with mild or severe sepsis. The initial levels of MIP-1β and granulocyte macrophage colony-stimulating factor were lower in patients with septic shock than in patients without shock. IL-8 and MCP-1 early after admission were higher in the non-survivors (p < 0.05). In the multivariate logistical regression, the initial levels of IL-8 were the most predictive for fatal outcome. Moreover, IL-1β, IL-6, IL-8, IL-12, interferon-γ, granulocyte colony-stimulating factor and tumour necrosis factor-α exhibited persistent increases in non-survivors. The simultaneous evaluation of multiple cytokines in sepsis may identify complex cytokine patterns that reflect the systemic response associated with shock and mortality.     

Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis

Introduction:

Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.

Methodology:

We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.

Results:

A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I² =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I² = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I² = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I² = 0%).

Conclusion:

The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.     

Microalbuminuria: A novel biomarker of sepsis

Context:

Diffused endothelial dysfunction in sepsis leads to an increase in systemic capillary permeability, the renal component manifesting as microalbuminuria. The degree of microalbuminuria correlates with the severity of the acute insult, the quantification of which may serve to predict sepsis and mortality in critically ill patients.

Aims:

To evaluate whether the degree of microalbuminuria could differentiate patients with sepsis from those without and predict mortality in critically ill patients.

Settings and Design:

Prospective, non-interventional study in a 20-bed Intensive Care Unit (ICU) of a tertiary care hospital.

Methods and Materials:

After exclusions, between Jan-May 2007, 94 consecutive adult patients were found eligible. Albumin-creatinine ratio (ACR, mg/g) was measured in urine samples collected on ICU admission (ACR1) and at 24 hours (ACR2).

Results:

Patients were classified into two groups: those with sepsis, severe sepsis and septic shock (n = 30) and those without sepsis [patients without systemic inflammatory response syndrome (SIRS) and with SIRS due to noninfectious causes] (n = 64). In the sepsis group, median ACR1 [206.5 (IQR129.7-506.1)] was significantly higher compared to the non sepsis group [76.4 (IQR29-167.1)] (P = 0.0016, Mann Whitney). The receiver operating characteristics (ROC) curve analysis showed that at a cut off value 124 mg/g, ACR1 may be able to discriminate between patients with and without sepsis with a sensitivity of 80%, specificity of 64.1%, positive predictive value (PPV) of 51.1% and negative predictive value (NPV) of 87.3%. The median ACR2 [154 (IQR114.4-395.3)] was significantly higher (P = 0.004) in nonsurvivors (n = 13) as compared to survivors [50.8 (IQR 21.6-144.7)]. The ROC curve analysis revealed that ACR2 at a cut-off of 99.6 mg/g could predict ICU mortality with sensitivity of 85%, specificity of 68% with a NPV of 97% and PPV of 30%.

Conclusion:

Absence of significant microalbuminuria on ICU admission is unlikely to be associated with sepsis. At 24 hours, absence of elevated levels of microalbuminuria is strongly predictive of ICU survival, equivalent to the time-tested APACHE II scores.     

Sepsis induced immunosuppression: Implications for secondary infections and complications

Sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis. This review explores the basis for sepsis related immune dysfunction and discusses its clinical implications for the treating intensivist. Recent trends indicate that a significant proportion of septic patients succumb to the complications of secondary infections and chronic critical care illness from the initial bout of sepsis. Therefore care-givers in the ICU need to be aware of the impediments posed by sepsis-related immune dysfunction that can impair recovery in patients with sepsis and contribute to sepsis-related mortality.     

Left atrial function for outcome prediction in severe sepsis and septic shock: An echocardiographic study

Left ventricular function and B-type natriuretic peptide (BNP) assessments are used to predict mortality in septic patients. Left atrial function has never been used to prognosticate outcome in septic patients.

Objectives:

To assess if deterioration of left atrial function in patients with severe sepsis and septic shock could predict mortality.

Methods:

We studied 30 patients with severe sepsis or septic shock with a mean age of 49.8±16.17. Echocardiographic parameters were measured on admission, Day 4, and Day 7, which comprised left ventricular ejection fraction (EF), and atrial function that is expressed as atrial ejection force (AEF). All patients were subjected to BNP assay as well. Multivariate analyses adjusted for APACHE II score was used for mortality prediction.

Results:

The underlying source for sepsis was lung in 10 patients (33%), blood in 7 patients (23.3%), abdomen in 7 patients (23.7%), and 3 patients (10%) had UTI as a cause of sepsis. Only one patient had CNS infection. In-hospital mortality was 23.3% (7 patients). Admission EF showed a significant difference between survivors and non survivors, 49.01±6.51 vs.. 56.44±6.93% (P<0.01). On the other hand, admission AEF showed insignificant changes between the same groups, 10.9±2.81 vs. 9.41±2.4 k/dynes P=0.21, while BNP was significantly higher in the non survivors, 1123±236.08 vs. 592.7±347.1 pg/ml (P<0.001). The predicatable variables for mortality was Acute Physiology and Chronic Health Evaluation II score, BNP, then EF.

Conclusion:

In septic patients, left atrial function unlike the ventricular function and BNP levels can not be used as an independent predictor of mortality.     

Earliest Bedside Assessment of Hemodynamic Parameters and Cardiac Biomarkers: Their Role as Predictors of Adverse Outcome in Patients with Septic Shock

Background: Early assessment and aggressive hemodynamic treatment have been shown to increase the survival of patients in septic shock. Current and past sepsis guidelines recommend a resuscitation protocol including central venous pressure (CVP), mean arterial blood pressure (MAP), urine output and central venous oxygen saturation (ScvO₂) for resuscitation within the first six hours. Currently, the established severity score systems like APACHE II score, SOFA score or SAPS II score predict the outcome of critically ill patients on the bases of variables obtained only after the first 24 hours. The present study aims to evaluate the risk of short-term mortality for patients with septic shock by the earliest possible assessment of hemodynamic parameters and cardiac biomarkers as well as their role for the prediction of the adverse outcome.Methods: 52 consecutive patients treated for septic shock in the intensive care unit of one centre (Marien Hospital Herne, Ruhr University Bochum, Germany) were prospectively enrolled in this study. Hemodynamic parameters (MAP, CVP, ScvO₂, left ventricular ejection fraction, Hematocrit) and cardiac biomarkers (Troponin I) at the ICU admission were evaluated in regard to their influence on mortality. The primary endpoint was all-cause mortality within 28 days after the admission.Results: A total of 52 patients (31 male, 21 female) with a mean age of 71.4±8.5 years and a mean APACHE II score of 37.0±7.6 were enrolled in the study. 28 patients reached the primary endpoint (mortality 54%). Patients presenting with hypotension (MAP <65 mmHg) at ICU admission had significantly higher rates of 28-day mortality as compared with the group of patients without hypotension (28-day mortality rate 74 % vs. 32 %, p<0.01). Furthermore, the patients in the hypotension present group had significantly higher lactate concentration (p=0.002), higher serum creatinin (p=0.04), higher NTproBNP (p=0.03) and after the first 24 hours higher APACHE II scores (p=0.04). A MAP <65 mmHg was the only hemodynamic parameter significantly predicting the primary endpoint (OR: 4.1, CI: 1.1 - 14.8, p=0.008), whereas the remaining hemodynamic variables CVP, ScvO₂, Hematocrit, Troponin I and left ventricular ejection fraction (LVEF) seemed to have no influence on survival. Besides, non-survivors had a significantly higher age (74.1±9.0 vs. 68.4±6.9, p=0.01). If hypotension coincided with an age ≥72 years, the 28-day mortality rate escalated to 88%.Conclusions: In our study, we identified a risk group with an exceedingly high mortality rate: the patients with an age ≥72 years and presenting with hypotension (MAP <65 mmHg). These data can be easily obtained at the time of the very first patient contact. As a result, an aggressive and a more effective treatment can be initiated within the first minutes of the primary care, possibly reducing organ failure and short-term mortality in this risk group.     

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90–100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb^® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (?0.4 µg/kg/min; p = 0.03) and 12 h (?0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.     

Prediction of Respiratory Failure and Mortality in COVID-19 Patients Using Long Pentraxin PTX3

The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5–33.3) versus 6.6 ng/mL (IQR 2.9–12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23–3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09–2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33–4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03–2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone.     

The influence of context and process when implementing e-health

Background

Revised consensus sepsis definitions have been published in 2003. The present study was performed to compare the prevalence of different stages of sepsis and ICU mortality rates and find out the case mix within the same collective of postoperative/posttraumatic patients applying either the original 1992 ACCP/SCCM or the revised 2003 SCCM/ESICM/ACCP/ATS/SIS sepsis definitions.

Methods

Retrospective observational single-centre study in surgical critically ill patients admitted to an University adult ICU. From 01/2007 to 12/2007, 742 patients were surveyed daily computer-assisted with respect to different stages of sepsis.

Results

Within the same patient collective, applying the 2003 definitions instead of the 1992 definitions, prevalence of severe sepsis (61 vs. 56) and septic shock (205 vs. 162) was higher (p < 0.001). In patients with septic shock according to the 2003 definitions, mortality rate of 22% was lower than that of 27%, when the 1992 definitions were used. Risk of death was increased for those patients classified to be in septic shock with any of the definitions (OR 6.5, p = 0.001). Sensitivity to predict deaths was slightly higher with the 2003 definitions (92%) than with the 1992 definitions (88%), and specificity was lower (31% vs. 49%).

Conclusion

The prevalence and mortality rates of various sepsis severity stages differ if defined by the 1992 or the 2003 definitions. Thus, transferring conclusions drawn from data sets regarding severity of sepsis generated with the 1992 definitions to the same population applying the 2003 definitions may be misleading. The 1992 definitions may under-classify patients with severe sepsis.     

Decreased levels of alpha-1-acid glycoprotein are related to the mortality of septic patients in the emergency department

OBJECTIVE:

To determine the validity of alpha-1-acid glycoprotein as a novel biomarker for mortality in patients with severe sepsis.

METHODS:

We prospectively included patients with severe sepsis or septic shock at the emergency department at a single tertiary referral teaching hospital. All of the patients were enrolled within the first 24 hours of emergency department admission, and clinical data and blood samples were obtained. As the primary outcome, we investigated the association of serum levels of alpha-1-acid glycoprotein and 96-hour mortality with logistic regression analysis and generalized estimating equations adjusted for age, sex, shock status and Acute Physiology and Chronic Health Evaluation II score.

RESULTS:

Patients with septic shock had lower alpha-1-acid glycoprotein levels at the time of emergency department admission compared to patients without shock (respectively, 149.1±42.7 vs. 189.8±68.6; p = 0.005). Similarly, non-survivors in the first 96 hours were also characterized by lower levels of alpha-1-acid glycoprotein at the time of emergency department admission compared to survivors (respectively, 132.18±50.2 vs. 179.8±61.4; p = 0.01). In an adjusted analysis, alpha-1-acid glycoprotein levels ≤120 mg/dL were significantly associated with 96-hour mortality (odds ratio = 14.37; 95% confidence interval = 1.58 to 130.21).

CONCLUSION:

Septic shock patients exhibited lower circulating alpha-1-acid glycoprotein levels than patients without shock. Alpha-1-acid glycoprotein levels were independently associated with 96-hour mortality in individuals with severe sepsis.