Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]

INTRODUCTION: Microcirculatory blood flow, and notably gut perfusion, is important in the development of multiple organ failure in septic shock. We compared the effects of dopexamine and norepinephrine (noradrenaline) with those of epinephrine (adrenaline) on gastric mucosal blood flow (GMBF) in patients with septic shock. The effects of these drugs on oxidative stress were also assessed. METHODS: This was a prospective randomized study performed in a surgical intensive care unit among adults fulfilling usual criteria for septic shock. Systemic and pulmonary hemodynamics, GMBF (laser-Doppler) and malondialdehyde were assessed just before catecholamine infusion (T(0)), as soon as mean arterial pressure (MAP) reached 70 to 80 mmHg (T(1)), and 2 hours (T(2)) and 6 hours (T(3)) after T(1). Drugs were titrated from 0.2 μg kg(-1 )min(-1 )with 0.2 μg kg(-1 )min(-1 )increments every 3 minutes for epinephrine and norepinephrine, and from 0.5 μg kg(-1 )min(-1 )with 0.5 μg kg(-1 )min(-1 )increments every 3 minutes for dopexamine. RESULTS: Twenty-two patients were included (10 receiving epinephrine, 12 receiving dopexamine–norepinephrine). There was no significant difference between groups on MAP at T(0), T(1), T(2), and T(3). Heart rate and cardiac output increased significantly more with epinephrine than with dopexamine–norepinephrine, whereas. GMBF increased significantly more with dopexamine–norepinephrine than with epinephrine between T(1 )and T(3 )(median values 106, 137, 133, and 165 versus 76, 91, 90, and 125 units of relative flux at T(0), T(1), T(2 )and T(3), respectively). Malondialdehyde similarly increased in both groups between T(1 )and T(3). CONCLUSION: In septic shock, at doses that induced the same effect on MAP, dopexamine–norepinephrine enhanced GMBF more than epinephrine did. No difference was observed on oxidative stress

Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study

INTRODUCTION: Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients. METHODS: A prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded. RESULTS: Sixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups. CONCLUSION: Continuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844

Incidence and prognosis of sustained arrhythmias in critically III patients,”

Rationale: Sustained arrhythmias are common in postoperative and cardiac intensive care units (ICUs), but their incidence and prognosis in general ICUs have never been reported. Objectives: To estimate the incidence and prognosis of sustained arrhythmias in a general ICU population. Methods: Prospective, multicenter, 1-month inception cohort study. Measurements and Main Results: A total of 1,341 patients were included: 12% (163/1,341) had sustained arrhythmias, including 8% (113/1,341) and 2% (30/1,341) with supraventricular and ventricular arrhythmias, respectively, and 2% (30/1,341) with conduction abnormalities. In-hospital death rates were 17% (205/1,178) in patients without arrhythmia and 29% (33/113

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Impact de la mise en place d’un réseau régional de pharmacovigilance sur la notification d’effets indésirables : bilan à 3 ans

Objectif. Stimuler la notification des effets indésirables et améliorer l’information sur la sécurité du médicament dans le territoire du centre régional de pharmacovigilance de Rennes. Méthodes. Mise en place d’un réseau avec les onze principaux établissements publics du territoire. Animation du réseau par un pharmacien dédié à l’aide d’une visioconférence mensuelle et d’une lettre d’information trimestrielle. Identification d’un correspondant spécifique dans chaque établissement qui diffuse les documents aux professionnels de santé et devient leur interlocuteur de proximité en pharmacovigilance. Résultats. Après 3 ans de fonctionnement (2010-2013), la qualité et l’utilité des échanges sont jugées satisfaisantes par les correspondants. Le nombre de notifications d’effets indésirables et de demandes de renseignements a été multiplié respectivement par 3,4 et 2,4 entre 2008 et 2013. Conclusion. L’existence d’un coordonnateur dédié et de correspondants locaux constitue un élément déterminant du succès du réseau. L’impact sur la notification est notable. Le réseau va être élargi aux établissements privés du territoire