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Search Results: 1 - 10 of 402648 matches for " Mette M Berger "
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Feed the ICU patient 'gastric' first, and go post-pyloric only in case of failure
Mette M Berger, Ludivine Soguel
Critical Care , 2010, DOI: 10.1186/cc8862
Abstract: Randomised trials contribute to the determination of optimal nutritional treatment strategies. In a well-designed study reported in the previous issue of Critical Care, White and colleagues [1] have investigated the impact of gastric versus post-pyloric (PP) route on early enteral feeding efficiency. Several interesting results are presented. First, the authors achieved a remarkable 80% successful blind PP tube placement. They showed that the usual delay in initiation of PP feeding due to tube placement techniques [2] can be minimized by bedside tube placement by trained nurses. But although gastric enteral nutrition (EN) can be initiated faster (median 2.3 hours earlier than the PP), achieving the energy target 3.6 hours earlier, the difference is minor. The authors should be congratulated on a very efficient feeding protocol: to be able to initiate EN within 3 to 13 hours of admission and to achieve the target 3 to 5 hours later is great. Complications did not differ significantly between groups (pneumonias: 5 in the gastric group versus 11 in the PP group).The authors attempted to solve the controversy of 'gastric versus post-pyloric' feeding in critical illness, after several contradictory studies and two non-conclusive meta-analyses, by randomly assigning the patients to either feeding method from the start. They (apparently) observed a lower daily energy deficit, with trends toward smaller gastric residual volumes in the gastric group. Unfortunately, despite a good design, minimization regarding variables impacting on their main outcome, namely gastroparesis, was absent and the results are not as straightforward as claimed: the problem of group severity unevenness complicates the interpretation as in several other studies [3]. The authors were unlucky to enrol patients with a more severe condition into the PP group: the difference between median APACHE II (Acute Physiology and Chronic Health Evaluation II) scores of 24.5 and 30 is clinically relevant. Furtherm
Best timing for energy provision during critical illness
Mette M Berger, Claude Pichard
Critical Care , 2012, DOI: 10.1186/cc11229
Abstract: Confusion has arisen in recent years among ICU specialists because of the publication of conflicting results about the respective merits of hypo- and hypercaloric feeding [5]. Indeed, some studies suggest that feeding the critically ill patient is deleterious in terms of glycemic control and clinical outcome [6-8], whereas other trials confirm that acute malnutrition causes complications and increases mortality at levels of energy deficit that are current in clinical practice [2,3,9-11].The principal issue appears to be the need to be able to prescribe within the first 24-48 hours an optimal and individualized energy and protein target, and to monitor achievement of this goal.Prediction of the optimal energy target is relatively difficult in critically ill patients because of the high variability in resting energy expenditure during the course of severe illness as a result of alterations induced by shock, sedation, fever, reduction of lean body mass, surgical procedures, etc. A reasonable prediction requires knowledge of the accurate pre-illness weight and body height, but this information is frequently missing. When an actual body weight is available, it is generally inaccurate as a result of fluid accumulation following resuscitation. The actual weight is also frequently increased by excess fat mass, which nobody wants to feed (Figure 1).Guidelines recommend that energy expenditure be measured on an individual basis by indirect calorimetry. The underlying physiological principle is that calculation of energy expenditure from the measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2) reflects the energy needs at the cellular level. The essential assumption is that under steady state conditions, respiratory gas exchange is in equilibrium with gas exchange within the mitochondria, thus indirectly measuring oxidative phosphorylation. Energy requirements are then extrapolated using the Weir equation [12]:The limitations and obstacles to measuremen
Gastrointestinal failure score in critically ill patients
Mette M Berger, Mauro Oddo, Jer?me Lavanchy, Corinne Longchamp, Frederik Delodder, Marie-Denise Schaller
Critical Care , 2008, DOI: 10.1186/cc7120
Abstract: Organ dysfunction is an evolving state: its expression and conditions vary. An ideal score should be specific, be sensitive, be objective, reflect a comprehensive measure of the system, be inexpensive, be abnormal in one direction, and be a continuous variable [3]. The proposed items do not fulfill these criteria. In addition, the items' applicability in different diagnostic categories is questionable. Furthermore, the study population, which is small for the elaboration of a score, is not representative of a general intensive care unit population, with very few cases of respiratory failure or shock, an unusual high proportion of comas (30%), and high mortality.Food intolerance assessment depends on unit protocols. Failure of progression should therefore be assessed as per protocol rather than as 50% of needs. Withholding feeds does not reflect the patient's physiological alterations, but is a medical decision not necessarily reflecting disease severity.A major problem is to consider the GIF score as a continuous variable, which it is not. This oversight explains the limited impact on the receiver operating characteristic curve of the score alone or in combination. A GIF score ≥ 3 was associated with a sharp increase of intensive care unit mortality: this reflects the strong impact of intra-abdominal hypertension (IAH) and abdominal compartment syndrome on mortality [4]. Indeed, the fact that food intolerance alone is not an independent predictor of outcome supports this interpretation, questioning the rationale for its aggressive prevention or treatment. The GIF score should have been used as a categorical variable, with a dichotomization (≥ 3 or <3 points), enabling answering the question of whether the score itself had prognostic value or whether only IAH and abdominal compartment syndrome were independent predictors. Alternatively, testing separately IAH, abdominal compartment syndrome, and GIF as dichotomized variables in the regression model, and calculation o
Substitution of exudative trace element losses in burned children
Pascal Stucki, Marie-Hélène Perez, Jacques Cotting, Alan Shenkin, Mette M Berger
Critical Care , 2010, DOI: 10.1186/cc9198
Abstract: Major burn injuries are associated with trace element deficiencies, which lead to impaired wound healing and infectious complications. Low plasma levels of zinc (Zn) and copper (Cu) are inadequately compensated for during hospitalization [1], and enteral supplements are unsuccessful in correcting the status [2]. Additionally, there are currently no clear recommendations regarding trace element requirements in children. The aim of the present study was to determine if our trace element supplementation policy for adults adapted to total body surface area would achieve normalization of plasma concentrations of trace elements in burned children.Burned children admitted to the paediatric and adult ICU were enrolled after approval by the Institutional Ethics Committee and parental informed consent. Park-land formula was used for fluid resuscitation during the first 24 hours in addition to basal fluid requirements (1,800 ml/m2). Target nutrition from 36 to 48 hours was: 3 to 5 year olds, 70 to 90 kcal/kg/day; over 5 year olds, 50 to 70 kcal/kg/day; teenagers, 40 kcal/kg/day. A normal saline solution containing Cu, selenium (Se), and Zn (Table 1) [3] was infused continuously first within 12 hours of injury and then over 8 hours per day for 7 to 15 days at a dose of 250 ml/1.70 m2/day along with a standard parenteral multi-trace element preparation. In addition, children admitted to the paediatric ICU received vitamin C 30 mg/kg/day and vitamin E 1.5 mg/kg/day; teenagers managed in the adult ICU received vitamin C 10.8 mg/kg/day and vitamin E 8.3 mg/kg/day (Table 1). The length of mechanical ventilation, and ICU and hospital length of stay were recorded.The characteristics of all those enrolled, mean daily total trace element dose, per kilogram dose, and duration of supplementation are shown in Table 2. Figure 1 shows the individual plasma values of the four patients while in the ICU. Both teenagers (patients 3 and 4) who received additional enteral trace elements had the lo
Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients
Mette M Berger, Ludivine Soguel, Alan Shenkin, Jean-Pierre Revelly, Christophe Pinget, Malcolm Baines, René L Chioléro
Critical Care , 2008, DOI: 10.1186/cc6981
Abstract: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 μg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo.Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 ± 3.2 versus -4.2 ± 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.Clinical Trials.gov RCT Register: NCT00515736.Critically ill patients are generally exposed to an increased oxidative stress, which is proportional to the severity of their condition [1,2]. A network of functionally overlapping antioxidant (AOX) defense mechanisms aims at protecting cells from reactive oxygen and nitric oxide species. It is formed by trace-element-dependent enzymes such as superoxide dismutase, catalase, and glutathione peroxidase (GPX) (selenium, zinc, manganese, copper, and iron), thiol donors, and their prec
Prospective monitoring of cefepime in intensive care unit adult patients
Thomas M Chapuis, Eric Giannoni, Paul A Majcherczyk, René Chioléro, Marie-Denise Schaller, Mette M Berger, Saskia Bolay, Laurent A Décosterd, Denis Bugnon, Philippe Moreillon
Critical Care , 2010, DOI: 10.1186/cc8941
Abstract: Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) ≥ 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis.Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC ≥ 50%) for the pathogens recovered in this study (MIC ≤ 4 mg/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC ≥ 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest.These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr ≥ 50 ml/minute infected by pathogens with cefepime MICs ≤ 4 mg/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs.An empiric study in which the pharmac
Effects of endotoxin on lactate metabolism in humans
Burkhard Michaeli, Alexandre Martinez, Jean-Pierre Revelly, Marie-Christine Cayeux, René L Chioléro, Luc Tappy, Mette M Berger
Critical Care , 2012, DOI: 10.1186/cc11444
Abstract: Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose.In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged.LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production.ClinicalTrials.gov NCT01647997Sepsis and inflammation elicit a whole set of neuroendocrine, metabolic, and systemic responses that belong to the organism's defense mechanisms [1,2]. However, when excessive, these responses may also exert deleterious effects [3]. Hyperlactatemia represents one prominent component of the metabolic stress response but shows marked inter-individual variations [4-6]. In critically ill patients, hyperlactatemia has been shown to be related to both the severity of the underlying condition and in-hospital mortality [7].The mechanisms underlying the development of hyperlactatemia in sepsis remain poorly understood: increased production or decreased clearance or a combination of both are possible [8]. A rise in p
Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials
Mette M Berger, Philippe Eggimann, Daren K Heyland, René L Chioléro, Jean-Pierre Revelly, Andrew Day, Wassim Raffoul, Alan Shenkin
Critical Care , 2006, DOI: 10.1186/cc5084
Abstract: Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20.The patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023).Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.Although the incidence of non-pulmonary infections has decreased in severely burned patients [1], nosocomial pneumonia, including ventilator-associated pneumonia (VAP), remains an important cause of morbidity and mortality [2,3]. During critical illness, oxidative stress is proportional to the severit
Ny antologi giver inspiration til brug af portfolio
Anne Mette M?rcke
Dansk Universitetspaedagogisk Tidsskrift , 2008,
Biased and G protein-independent signaling of chemokine receptors
Olav Larsen,Mette M. Rosenkilde
Frontiers in Immunology , 2014, DOI: 10.3389/fimmu.2014.00277
Abstract: Biased signaling or functional selectivity occurs when a 7TM receptor preferentially activates one of several available pathways. It can be divided into three distinct forms: ligand bias, receptor bias, and tissue or cell bias, where it is mediated by different ligands (on the same receptor), different receptors (with the same ligand) or different tissues or cells (for the same ligand-receptor pair). Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may not be absolute, i.e. full versus no activation. Here we discuss biased signaling in the chemokine system, including the structural basis for biased signaling in chemokine receptors, as well as in class A 7TM receptors in general. This includes overall helical movements and the contributions of micro-switches based on recently published 7TM crystals and molecular dynamics studies. All three forms of biased signaling are abundant in the chemokine system. This challenges our understanding of “classic” redundancy inevitably ascribed to this system, where multiple chemokines bind to the same receptor and where a single chemokine may bind to several receptors – in both cases with the same functional outcome. The ubiquitous biased signaling confer a hitherto unknown specificity to the chemokine system with a complex interaction pattern that is better described as promiscuous with context-defined roles and different functional outcomes in a ligand-, receptor- or cell/tissue-defined manner. As the low number of successful drug development plans implies, there are great difficulties in targeting chemokine receptors; in particular with regard to receptor antagonists as anti-inflammatory drugs. Un-defined and putative non-selective targeting of the complete cellular signaling system could be the underlying cause of lack of success. Therefore, biased ligands could be the solution.
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