Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Influence of dialysis modality and membrane flux on quality of life in hemodialysis patients

Background: The quality of life in patients undergoing hemodialysis is significantly disturbed. There are data that hemodiafiltration (HDF) may be more effective than conventional hemodialysis in the removal of uremic toxins and may reduce frequency and severity of intradialytic and postdialysis adverse symptoms in patients. Also, some researchers suggest advantages of using high-flux membranes compared with low-flux. Objective: The aim of this study was to examine whether hemodialysis modality and membrane flux, independent of membrane biocompatibility, make differences in quality of life in patients. Methods: In our cross-sectional study, we evaluated 124 patients who were divided, based on therapy, into three groups: online HDF, high-flux hemodialysis, and low-flux hemodialysis. Data were collected using the Short Form-36 questionnaire combined with special questionnaire, which included demographic and clinically related questions. Results: Health-related quality of life was better in patients on HDF compared with patients on hemodialysis, especially compared with low-flux hemodialysis patients in most of the scales and in both dimensions: physical component scale and mental component scale. There were no statistically significant differences in Short Form-36 domains between high-flux hemodialysis and low-flux hemodialysis. Conclusion: Our data suggest the potential advantages of HDF with regard to influence on quality of life, which is sufficient to justify further research in prospective and longitudinal study design. © 2012 Informa Healthcare USA, Inc

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Sideritis raeseri spp. raeseri Boiss & Heldr is a native plant from the Mediterranean region that is used due to its medicinal and culinary properties. The aim of this study was to evaluate the effects of ethanol extract of S. raeseri on the blood pressure, vascular and cardiac contractions. Arterial blood pressure was registered directly from the carotid artery in the anaesthetized rabbits. Aortic rings and the spontaneously beating atria were mounted in tissue bath. An intravenous injection of extract of S. raeseri (0.025-7.5 mg/kg) caused a dose dependent decrease of the arterial pressure and heart rate, with EC 50 value of 24.31±3.87 mg/kg and 88.14±7.51 mg/kg, respectively. In aortic preparations precontracted with KCl (80 mM), the extract of S. raeseri (0.005-1.5 mg/ml) elicited a vasodilatator action (EC 50 0.11±0.008 mg/ml). In spontaneously beating rat atria, the extract of S. raeseri (0.005-1.5 mg/ml) produced decrease of chronotropic and inotropic activity (with EC 50 value of 0.63±0.03 mg/ml and 0.40±0.08 mg/ml). Administration of verapamil induced inhibition of force and rate of the atrial contraction. These results demonstrate that the ethanol extract of Sideritis raeseri spp. raeseri Boiss & Heldr can produce hypotension, vasodilatation, negative chronotropic and inotropic effects. K e y w o r d s : Sideritis raeseri, hypotension, vasorelaxation, cardiodepressant, blood pressure, isolated aorta, phenols, flavonoids MATERIALS AND METHODS Reagents Heparine sodium salt (Hemofarm, Serbia) and urethane (Pliva, Croatia) were used. Verapamil was obtained from the Sigma Chemical Company, St. Louis, MO, USA. All drugs were dissolved in distilled water. Vegetal material The aerial parts of cultivated S. raeseri spp. raeseri were collected in the phase of full flowering, from the experimental field at the Institute for Medicinal Plants Research in Pancevo, Serbia. Preparation of plant extract Upper 20 cm of the plants were harvested and open-air dried in the shadow. Air-dried and powdered aerial parts were extracted with 96% ethanol in Soxhlet apparatus. The extracts were filtered and evaporated in vacuum to dryness. For experimental purposes the plant extract was first dissolved in ethanol (20% m/m), than diluted with distilled water to the appropriate concentration. Ethanol, at the same concentrations, had no effect on blood pressure and contractility of isolated vessels and atria in the control experiments. Animals and treatment In this study, rabbits (around 1 kg) and Wistar albino rats (200-250 g) were used obtained from the Animal Research Center of Medical Faculty, University of Nis, Serbia. The animals were housed in stainless steel cages under standard laboratory conditions. These animals were maintained at 20-24°C with a 12 h light-dark cycle at least 1 week before the experiment. All animals had free access to food and water. All experimental procedures with animals were in compliance with the European Council Directive of November 24, 1986 (86/609/EEC). Blood pressure measurement in anaesthetized rabbits The rabbits were anesthetized intravenously with urethane (750 mg/kg). The animals were implanted with carotid arterial catheter for blood pressure recording. The arterial catheter was connected to a blood pressure transducer (P-1000-A) coupled with a Narcophysiograph (NARCO Bio system, Houston, USA) for measurement arterial pressure. The blood pressure and heart rate were recorded before and after the administration of the plant extract. Arterial pressure was allowed to return to the resting level between injections. Changes in blood pressure were recorded as the difference between the steady state values before and the peak readings after the injection. Animals were treated with S. raeseri ethanol extract, which was administered in a rising concentrations (0.025-7.5 mg/kg) at intervals of 15-20 min. Isolation of the rat aorta and recording of contractions The thoracic aorta ring preparations from rats were used. Aortic rings were mounted in 10 ml tissue bath containing a Krebs solution at 37°C and aerated with carbogen. The composition of the Krebs solution was (mM): NaCl 118.2, KCl 4.7, CaCl 2 2.5, MgSO 4 1.2, KH 2 PO 4 1.3, NaHCO 3 25.0, glucose 11.7. Before the experiments, an equilibrium period of 60 min was given. High K + (80 mM) doses were used to induce sustained contractions. The extract of S. raeseri (0.005-1.5 mg/ml) was than added to the organ bath, and the relaxation was evaluated as percentage of the induced vasoconstriction. In the second experimental series, the aortic rings were precontracted with high K + , and verapamil was then added (0.015-1.5 µg/ml). Tension changes in the tissue were recorded using a transducer (TSZ-04-E, Experimetria Ltd, Budapest, Hungary) and analyzed with a SPEL Advanced ISOSYS Data Acquisition System (Experimetria Ltd, Budapest, Hungary). Isolation of the rat atria and recording of contractions Rat atria were dissected out cleaned off fatty tissue. The spontaneously beating atria were suspended in 10 ml tissue baths, containing Krebs solution for isolated atria, maintained at 36±1°C and continuously aerated with a carbogen. The composition of Krebs solution was (mM): NaCl 137, KCl 2.81, CaCl 2 1.8, MgCl 2 0.1, NaH 2 PO 4 0.417, NaHCO 3 11.9, glucose 11.1. The force and rate of isolated atria were recorded using a transducer (TSZ-04-E, Experimetria Ltd, Budapest, Hungary) and analyzed with a SPEL Advanced ISOSYS Data Acquisition System (Experimetria Ltd, Budapest, Hungary). In the first experimental series, after an equilibrium period of 30 min, the extract of S. raeseri (0.005-1.5 mg/ml) was added cumulatively. In the second experimental series, rat atria were incubated with verapamil (0.3-3 µM). The effect on force and rate of contractions was determined as percent of the pretreated control. Statistical analysis The results were expressed as mean ±standard deviation of six determinations. Statistical evaluation was performed using the Student`s t-test. A probability value of p<0.05 was considered to be significant. The mean effective doses EC 50 that is the concentration which elicited 50% of maximal response, was established by regression analysis. RESULTS Effects of the extract on blood pressure In anaesthetized rabbits the baseline mean blood pressure did not vary, and the value of the pressure was 97.84±3.14 mmHg. Intravenous administration of the ethanol extract of S. raeseri (0.025-7.5 mg/kg) immediately caused dose-dependent decreases in systolic, diastolic and mean arterial blood pressure. The plant extract at doses of 7.5 mg/kg induced a significant fall in the blood pressure of 35.02±5.28% (p<0.01), with EC 50 value of 24.31±3.87 mg/kg Effects of the extract on isolated aorta In isolated rat aorta preparations cumulative addition of the ethanol extract of S. raeseri (0.005-1.5 mg/ml) caused the relaxation of the sustained contractions induced by KCl in a concentration-dependent manner. The plant extract at the concentration of 1.5 mg/ml caused an inhibitory effect of 79.13±6.85%, with EC 50 0.11±0.008 mg/ml 532 Effects of the extract on isolated atria The administrations of the ethanol extract of S. raeseri (0.005-1.5 mg/ml) to the spontaneously beating atria, caused negative inotropic and chronotropic effects. In isolated rat atria the plant extract at the concentration of 1.5 mg/ml decreased the rate of contraction for 69.59±5.11% (with EC 50 value of 0.63±0.03 mg/ml) and the force for 72.95±6.45% (with EC 50 value of 0.40±0.08 mg/ml) DISCUSSION The study demonstrates that the ethanol extract of S. raeseri has a hypotensive effect in rabbits, a negative inotropic and chronotropic effect in isolated rat atria and a vasorelaxant effect in isolated rat aorta. The intravenous injection of the ethanol extracts of S. raeseri induced a dose-dependent decrease of the blood pressure and heart rate of anaesthetized rabbits. The hypotensive effect was short-term and the blood pressure reached the basal value in about 2-3 min. The blood pressure is a product of cardiac output and vascular resistance hence the extract of S. raeseri was studied for its possible inhibitory effects on isolated rat aorta and atria. When tested on the high K + induced contractions of rat aorta, extract of S. raeseri showed a dose dependent vasorelaxant effect. The high KCl induced contraction is due to membrane depolarization, leading to the increase of the calcium influx through voltage-dependent channels The results demonstrated that the plant extract induced a negative chronotropic and inotropic effects on the spontaneously contracting cardiac tissues of atria. The cardio-inhibitory effect of the extract of S. raeseri was concentration dependent and reversible after washing, suggesting that the inhibition was not due to the damage of the myocardial cells by the extract. The phytochemical analysis on the samples of the genus Sideritis revealed the presence of flavones and terpenoids Literature data report that flavones and terpenoids, in other plants, to exhibit activities in cardiovascular system. Presence of such compounds in S. raeseri might possibly contribute in the hypotensive and cardio-inhibitory effects of plant extract. It was known that the aglycones apigenin exhibited endotheliumdependent vasodilatatory activities in isolated rat aorta (24). The sesquiterpene extracted from the medicinal plant Petasites formosanus in anesthetized rats produced a dose-dependent hypotensive effect (25). The hypotensive effect of other plants of Lamiaceae family has been reported. The essential oil from aerial parts of Mentha x villosa in rats induced endothelium-dependent hypotensive and vasorelaxing effects (26). Matsubara et al. (27) shown that compound from Orthosiphon aristatus (Lamiaceae) caused hypotensive, negative chronotropic and vasodilatory effects. The results demonstrate that the ethanol extract of Sideritis raeseri spp. raeseri Boiss & Heldr can produce hypotension, vasodilatation, negative chronotropic and inotropic effects. Vasorelaxant, negative chronotropic and inotropic actions can be responsible for the hypotensive effect of the ethanol extract of Sideritis raeseri. Based on our results, Sideritis raeseri may be phytotherapeutically used, after full pharmacological and toxicological evaluation, as an alternative drug to synthetic hypotensive agents