Microcirculatory alterations induced by sedation in intensive care patients. Effects of midazolam alone and in association with sufentanil

INTRODUCTION: Sedation is widely used in intensive care unit (ICU) patients to limit the risk of pulmonary barotrauma and to decrease oxygen needs. However, adverse effects of cc5128sedation have not been fully evaluated; in particular, effects of benzodiazepine and opiates on microcirculation have not been extensively studied. The aim of this study was to evaluate the microcirculatory effects of a sedation protocol commonly prescribed in the ICU. METHODS: Ten non-septic patients under controlled ventilation requiring sedation for therapeutic purposes were enrolled in a prospective observational study conducted in an ICU of a university hospital. Sedation was conducted in two successive steps: first, each patient received midazolam (0.1 mg/kg per hour after a bolus of 0.05 mg/kg, then adapted to reach a Ramsay score of between 3 and 5). Second, after one hour, sufentanil was added (0.1 μg/kg per hour after a bolus of 0.1 μg/kg). Arterial pressure, heart rate, cardiac output determined by transthoracic impedance, transcutaneous oxygen (tcPO(2)) and carbon dioxide (tcPCO(2)) pressures, and microcirculatory blood flow determined by laser Doppler flowmetry at rest and during a reactive hyperaemia challenge were measured before sedation (NS period), one hour after midazolam infusion (H period), and one hour after midazolam-sufentanil infusion (HS period). RESULTS: Arterial pressure decreased in both sedation periods, but heart rate, cardiac output, tcPO(2), and tcPCO(2 )remained unchanged. In both sedation periods, microcirculatory changes occurred with an increase in cutaneous blood flow at rest (H period: 207 ± 25 perfusion units [PU] and HS period: 205 ± 25 PU versus NS period: 150 ± 22 PU, p < 0.05), decreased response to ischaemia (variation of blood flow to peak: H period: 97 ± 16 PU and HS period: 73 ± 9 PU versus NS period: 141 ± 14 PU, p < 0.05), and attenuation of vasomotion. CONCLUSION: Sedation with midazolam or a combination of midazolam and sufentanil induces a deterioration of vasomotion and microvascular response to ischaemia, raising the question of whether this effect may further alter tissue perfusion when already compromised, as in septic patients

Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk factors, and outcome

INTRODUCTION: The aim of this study was to determine incidence, risk factors, and impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas maltophilia. METHODS: This prospective observational case-control study, which was a part of a cohort study, was conducted in a 30-bed ICU during a three year period. All immunocompetent patients hospitalised >48 hours were eligible. Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were excluded. Patients without ICU-acquired S. maltophilia who developed an ICU-acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all patients at ICU admission and weekly. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired S. maltophilia and for ICU mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU-acquired colonisation and/or infection and were all successfully matched with 76 controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p < 0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] = 1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 ± 16 versus 7 ± 11 days, p < 0.001), and duration of ICU stay (29 ± 21 versus 15 ± 17 days, p < 0.001) were significantly higher in cases than in controls. In addition, ICU-acquired infection related to S. maltophilia was independently associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044). CONCLUSION: COPD and duration of antibiotic treatment are independent risk factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is associated with increased morbidity and mortality rates. ICU-acquired infection related to S. maltophilia is an independent risk factor for ICU mortality

Evaluation de la précharge dépendance au cours de la chirurgie aortique sous rénale (un indice dynamique non-invasif)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The effects of acute transfer to freshwater on ion transporters of the pharyngeal cavity in European seabass (Dicentrarchus labrax)

International audienceGene expression of key ion transporters (the Na+/K+-ATPase NKA, the Na+, K+-2Cl− cotransporter NKCC1, and CFTR) in the gills, opercular inner epithelium, and pseudobranch of European seabass juveniles (Dicentrarchus labrax) were studied after acute transfer up to 4 days from seawater (SW) to freshwater (FW). The functional remodeling of these organs was also studied. Handling stress (SW to SW transfer) rapidly induced a transcript level decrease for the three ion transporters in the gills and operculum. NKA and CFTR relative expression level were stable, but in the pseudobranch, NKCC1 transcript levels increased (up to 2.4-fold). Transfer to FW induced even more organ-specific responses. In the gills, a 1.8-fold increase for NKA transcript levels occurs within 4 days post transfer with also a general decrease for CFTR and NKCC1. In the operculum, transcript levels are only slightly modified. In the pseudobranch, there is a transient NKCC1 increase followed by 0.6-fold decrease and 0.8-fold CFTR decrease. FW transfer also induced a density decrease for the opercular ionocytes and goblet cells. Therefore, gills and operculum display similar trends in SW-fish but have different responses in FW-transferred fish. Also, the pseudobranch presents contrasting response both in SW and in FW, most probably due to the high density of a cell type that is morphologically and functionally different compared to the typical gill-type ionocyte. This pseudobranch-type ionocyte could be involved in blood acid-base regulation masking a minor osmotic regulatory capacity of this organ compared to the gills

Survival improvement conferred by the Pseudoalteromonas sp. NC201 probiotic in Litopenaeus stylirostris exposed to Vibrio nigripulchritudo infection and salinity stress

This study aimed to investigate the potential protection conferred by the probiotic strain NC201 against biotic and abiotic stresses in Pacific blue shrimp Litopenaeus stylirostris that had received the probiotic throughout their lives. The presence of NC201 in shrimp hemolymph was investigated over the course of 24 h, before exposure to bacterial or physical stress. Results showed that NC201 had invaded the shrimp hemolymph 2 h following administration, but had completely disappeared by 48 h. NC201 identification through morphotype observation was confirmed by MALDI-TOF biotyping and results also indicated that NC201 and Pseudoalteromonas piscicida are closely related. A challenge by immersion was carried out on subadults using Vibrio nigripulchritudo at 105 CFU/ml. Cumulative mortality was two-fold lower in the treated group (24%) than in the control group (48%) at 144 h post infection. The probiotic in the shrimp hemolymph was diminished in infectious conditions compared with non-infectious ones and V. nigripulchritudo prevalence was simultaneously lower in animals treated with NC201. The relative expression of genes coding lysozyme and penaeidin 3 was evaluated 24 h post infection and their transcript numbers were found to be lower in probiotic animals than in control animals for both genes. Hyposaline stress was also used to evaluate the benefits of NC201 treatment on early juveniles and subadults. At low salinities, animals showed an increased survival rate when treated with NC201, by 10 and 17.5% at 48 h post stress, respectively. Moreover, in subadults treated with the probiotic, a better recovery of the plasmatic osmolality was observed. All these results confirm that NC201 is a good candidate probiotic for shrimp aquaculture

Functional DIversification of Big-Defensins and the shaping of oyster microbiota

International audienc

G protein-dependent signaling triggers a β-arrestin-scaffolded p70S6K/ rpS6 module that controls 5'TOP mRNA translation

International audienceMany interaction partners of β-arrestins intervene in the control of mRNA translation. However, how β-arrestins regulate this cellular process has been poorly explored. In this study, we show that β-arrestins constitutively assemble a p70S6K/ribosomal protein S6 (rpS6) complex in HEK293 cells and in primary Sertoli cells of the testis. We demonstrate that this interaction is direct, and experimentally validate the interaction interface between β-arrestin 1 and p70S6K predicted by our docking algorithm. Like most GPCRs, the biological function of follicle-stimulating hormone receptor (FSHR) is transduced by G proteins and β-arrestins. Upon follicle-stimulating hormone (FSH) stimulation, activation of G protein–dependent signaling enhances p70S6K activity within the β-arrestin/p70S6K/rpS6 preassembled complex, which is not recruited to the FSHR. In agreement, FSH-induced rpS6 phosphorylation within the β-arrestin scaffold was decreased in cells depleted of Gαs. Integration of the cooperative action of β-arrestin and G proteins led to the translation of 5′ oligopyrimidine track mRNA with high efficacy within minutes of FSH input. Hence, this work highlights new relationships between G proteins and β-arrestins when acting cooperatively on a common signaling pathway, contrasting with their previously shown parallel action on the ERK MAP kinase pathway. In addition, this study provides insights into how GPCR can exert trophic effects in the cell