French Ministry of Health and the Société Française d'Anesthésie Réanimation.

No abstract

; for the FLASH Trial Group IMPORTANCE It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. OBJECTIVE To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. INTERVENTIONS Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 AM the following day. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. RESULTS Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, −3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, −0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17). CONCLUSIONS AND RELEVANCE Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients.

NCT01311765.

In mammalians, toll-like receptors (TLR) signal-transduction pathways induce the expression of a variety of immune-response genes, including inflammatory cytokines. It is therefore plausible to assume that TLRs are mediators in glial cells triggering the release of cytokines that ultimately kill DA neurons in the substantia nigra in Parkinson disease (PD). Accordingly, recent data indicate that TLR4 is up-regulated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in a mouse model of PD. Here, we wished to evaluate the role of TLR4 in the acute mouse MPTP model of PD: TLR4-deficient mice and wild-type littermates control mice were used for the acute administration way of MPTP or a corresponding volume of saline. We demonstrate that TLR4-deficient mice are less vulnerable to MPTP intoxication than wild-type mice and display a decreased number of Iba1+ and MHC II+ activated microglial cells after MPTP application, suggesting that the TLR4 pathway is involved in experimental PD.

BackgroundMuscle wasting in critically ill patients is associated with negative clinical outcomes. Ultrasound quadriceps femoris muscle assessment may constitute a convenient tool to evaluate muscle wasting. Nevertheless, its reliability remains uncertain. Our primary aim was to study the intra- and inter-observer reliability of this technique. Our secondary aim was to assess the evolution of the quadriceps muscle during the first 3 weeks after ICU admission and its possible association with nutritional intake.MethodsThis observational study included patients expected to stay more than 7 days in the ICU. Ultrasound quadriceps muscle thickness was measured with a 12 MHz linear transducer, by two trained physicians, on D1, D3, D5, D7 and D21. Two measurements sites were evaluated: on the midpoint or on the two-thirds of the length between the anterior superior iliac spine and the upper border of the patella. Intra and inter-observer reliability was assessed by calculating the intra-class correlation coefficient (ICC).ResultsA total of 280 ultrasound quadriceps thickness measurements were performed on 29 critically ill patients. Intra-observer reliability’s ICC was 0.74 [95% CI 0.63; 0.84] at the “midpoint” site and 0.83 [95% CI 0.75; 0.9] at the “two-thirds” site. Inter-observer reliability’s ICC was 0.76 [95% CI, 0.66; 0.86] at the “midpoint” site and 0.81 [95% CI, 0.7; 0.9] at the “two-thirds” site. Quadriceps femoris muscle thickness decreased over 16% within the first week after ICU admission. No correlation was found between muscle loss and caloric (p = 0.96) or protein (p = 0.80) debt over the first week.ConclusionThe assessment by ultrasonography of the quadriceps muscle thickness reveals good intra- and inter-observer reliability and may constitute a promising tool to evaluate the effect of nutritional-based interventions on muscle wasting in critically ill patients.Trial registration“Committee for the Protection of Human Subjects in Biomedical Research” - Paris Ile de France VI Pitié-Salpêtrière – 10/07/2014.French Data Protection Committee (“Commission Nationale Informatique et Libertés”) - #1771144.

Intraoperative transfusion of packed red blood cells, pretransplantation renal replacement therapy and APACHE II score are predictors for the development of delirium in intensive care unit patients post-OLT and are associated with increased hospital lengths of stay and mortality.

A precise evaluation of the brain damage in the first days of severe traumatic brain injured (TBI) patients is still uncertain despite numerous available cerebral evaluation methods and imaging. In 5-10% of severe TBI patients, clinicians remain concerned with prolonged coma and long-term marked cognitive impairment unexplained by normal morphological T2 star, flair, and diffusion magnetic resonance imaging (MRI). For this reason, we prospectively assessed the potential value of magnetic resonance spectroscopy (MRS) of the brain stem to evaluate the functionality of the consciousness areas. Forty consecutive patients with severe TBI were included. Single voxel proton MRS of the brain stem and morphological MRI of the whole brain were performed at day 17.5 +/- 6.4. Disability Rating Scale and Glasgow Outcome Scale (GOS) were evaluated at 18 months posttrauma. MRS appeared to be a reliable tool in the exploration of brainstem metabolism in TBI. Three different spectra were observed (normal, cholinergic reaction, or neuronal damage) allowing an evaluation of functional damage. MRS disturbances were not correlated with anatomical MRI lesions suggesting that the two techniques are strongly complementarity. In two GOS 2 vegetative patients with normal morphological MRI, MRS detected severe functional damage of the brainstem (NAA/Cr < 1.50) that was described as "invisible brain stem damage." MRI and MRS taken separately could not distinguish patients GOS 3 (n = 7) from GOS 1-2 (n = 11) and GOS 4-5 (n = 20). However, a principal component analysis of combined MRI and MRS data enabled a clear-cut separation between GOS 1-2, GOS 3, and GOS 4-5 patients with no overlap between groups. This study showed that combined MRI and MRS provide a reliable evaluation of patients presenting in deep coma, specially when there are insufficient MRI lesions of the consciousness pathways to explain their status. In the first few days post-trauma metabolic (brainstem spectroscopy) and morphological (T2 star and Flair) MRI studies can predict the long-term neurological outcome, especially the persistent vegetative states and minimally conscious state.