Non-invasive detection of a femoral-to-radial arterial pressure gradient in intensive care patients with vasoactive agents

International audienceAbstract Background In patient requiring vasopressors, the radial artery pressure may underestimate the true central aortic pressure leading to unnecessary interventions. When using a femoral and a radial arterial line, this femoral-to-radial arterial pressure gradient (FR-APG) can be detected. Our main objective was to assess the accuracy of non-invasive blood pressure (NIBP) measures; specifically, measuring the gradient between the NIBP obtained at the brachial artery and the radial artery pressure and calculating the non-invasive brachial-to-radial arterial pressure gradient (NIBR-APG) to detect an FR-APG. The secondary objective was to assess the prevalence of the FR-APG in a targeted sample of critically ill patients. Methods Adult patients in an intensive care unit requiring vasopressors and instrumented with a femoral and a radial artery line were selected. We recorded invasive radial and femoral arterial pressure, and brachial NIBP. Measurements were repeated each hour for 2 h. A significant FR-APG (our reference standard) was defined by either a mean arterial pressure (MAP) difference of more than 10 mmHg or a systolic arterial pressure (SAP) difference of more than 25 mmHg. The diagnostic accuracy of the NIBR-APG (our index test) to detect a significant FR-APG was estimated and the prevalence of an FR-APG was measured and correlated with the NIBR-APG. Results Eighty-one patients aged 68 [IQR 58–75] years and an SAPS2 score of 35 (SD 7) were included from which 228 measurements were obtained. A significant FR-APG occurred in 15 patients with a prevalence of 18.5% [95%CI 10.8–28.7%]. Diabetes was significantly associated with a significant FR-APG. The use of a 11 mmHg difference in MAP between the NIBP at the brachial artery and the MAP of the radial artery led to a specificity of 92% [67; 100], a sensitivity of 100% [95%CI 83; 100] and an AUC ROC of 0.93 [95%CI 0.81–0.99] to detect a significant FR-APG. SAP and MAP FR-APG correlated with SAP ( r 2 = 0.36; p < 0.001) and MAP ( r 2 = 0.34; p < 0.001) NIBR-APG. Conclusion NIBR-APG assessment can be used to detect a significant FR-APG which occur in one in every five critically ill patients requiring vasoactive agents

A synthetic glycosaminoglycan mimetic (RGTA) modifies natural glycosaminoglycan species during myogenesis

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A synthetic glycosaminoglycan mimetic (RGTA) modifies natural glycosaminoglycan species during myogenesis

International audienceCrucial events in myogenesis rely on the highly regulated spatiotemporal distribution of cell surface heparan sulfate proteoglycans to which are associated growth factors, thus creating a specific microenvironment around muscle cells. Most growth factors involved in control of myoblast growth and differentiation are stored in the extracellular matrix through interaction with specific sequences of glycosaminoglycan oligosaccharides, mainly heparan sulfate (HS). Different HS subspecies revealed by specific antibodies, have been shown to provide spatiotemporal regulation during muscle development. We have previously shown that glycosaminoglycan (GAG) mimetics called RGTA (ReGeneraTing Agent), stimulate muscle precursor cell growth and differentiation. These data suggest an important role of GAGs during myogenesis; however, little is yet known about the different species of GAGs synthesized during myogenesis and their metabolic regulation. We therefore quantified GAGs during myogenesis of C2.7 cells and show that the composition of GAG species was modified during myogenic differentiation. In particular, HS levels were increased during this process. In addition, the GAG mimetic RGTA, which stimulated both growth and differentiation of C2.7 cells, increased the total amount of GAG produced by these cells without significantly altering their rate of sulfation. RGTA treatment further enhanced HS levels and changed its sub-species composition. Although mRNA levels of the enzymes involved in HS biosynthesis were almost unchanged during myogenic differentiation, heparanase mRNA levels decreased. RGTA did not markedly alter these levels. Here we show that the effects of RGTA on myoblast growth and differentiation are in part mediated through an alteration of GAG species and provide an important insight into the role of these molecules in normal or pathologic myogenic processes

Molecular Properties and Pharmacokinetic Behavior of Cetirizine, a Zwitterionic H 1 -Receptor Antagonist

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Drotrecogin alfa (Activated) in adults with septic shock

There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.)