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QSOX1, a sulfhydryl oxidase, was shown to be upregulated in the heart upon acute heart failure (AHF). The aim of the study was to unravel QSOX1 roles during AHF. We generated and characterized mice with QSOX1 gene deletion. The QSOX1−/− mice were viable but adult male exhibited a silent dilated cardiomyopathy. The QSOX1−/− hearts were characterized by low protein SERCA2a levels associated with a calcium homeostasis alteration, high levels of the endoplasmic reticulum (ER) chaperone proteins Grp78/Bip, and of the ER apoptosis sensor CHOP, indicating a chronic unfolded protein response (UPR). Importantly the QSOX1invalidation led to overexpression of two ER oxidases, ERO1-α and PRDX4. Acute stress was induced by isoproterenol injection (ISO, 300 mg/kg/12 h) for 2 days. In both groups, the PERK UPR pathway was transiently activated 6 h after the first ISO injection as indicated by eIF2 phosphorylation. By day-3 after the onset of stress, both WT and QSOX1−/− mice exhibited AHF profile but while high cardiac QSOX1 level was induced in WT hearts, ERO1-α and PRDX4 levels drop down in QSOX1−/−. At that time, QSOX1−/− hearts exhibited an enhanced inflammation (CD68+ cells and Galectin-3 expression) and oxidative stress (DHE staining and oxyblot) when compared to WT ones. In conclusion, the lack of QSOX1 promotes the upregulation of two ER oxidases ERO1α and PRDX4 that likely rescues oxidative protein folding in the hearts. However, signs of chronic ER stress remained present and were associated with a dilated cardiomyopathy. The superimposition of acute stress allowed us to propose that QSOX1 participate to the early response to cardiac stress but not to immediate UPR response. Taken altogether, the data indicated that QSOX1 is required 1) for a proper protein folding in the endo/sarcoplasmic reticulum (ER/SR) and 2) for resolution and protective response during acute stress.

Dynamic indices, such as pulse pressure variation (PPV), are inaccurate predictors of fluid responsiveness in mechanically ventilated patients with low tidal volume. This study aimed to test whether changes in continuous cardiac index (CCI), PPV, and stroke volume variation (SVV) after a mini-fluid challenge (100 ml of fluid during 1 min) could predict fluid responsiveness in these patients.We prospectively studied 49 critically ill, deeply sedated, and mechanically ventilated patients (tidal volume8 ml kg(-1) of ideal body weight) without cardiac arrhythmias, in whom a fluid challenge was indicated because of circulatory failure. The CCI, SVV (PiCCO™; Pulsion), and PPV (MP70™; Philips) were measured before and after 100 ml of colloid infusion during 1 min, and then after the additional infusion of 400 ml during 14 min. Responders were defined as subjects with a ≥15% increase in cardiac index (transpulmonary thermodilution) after the full (500 ml) fluid challenge. Areas under the receiver operating characteristic curves (AUCs) and the grey zones were determined for changes in CCI (ΔCCI100), SVV (ΔSVV100), and PPV (ΔPPV100) after 100 ml fluid challenge.Twenty-two subjects were responders. The ΔCCI100 predicted fluid responsiveness with an AUC of 0.78. The grey zone was large and included 67% of subjects. The ΔSVV100 and ΔPPV100 predicted fluid responsiveness with AUCs of 0.91 and 0.92, respectively. Grey zones were small, including ≤12% of subjects for both indices.The ΔSVV100 and ΔPPV100 predict fluid responsiveness accurately and better than ΔCCI100 (PiCCO™; Pulsion) in patients with circulatory failure and ventilated with low volumes.

La comprehension des troubles acidobasiques se fonde sur une demarche diagnostique simple et hierarchisee se reposant sur l’equation d’Henderson-Hasselbalch. Apres avoir determine la composante metabolique, le calcul du trou anionique plasmatique (TAP) permet de quantifier les anions indoses. Physiologiquement, il est de 12 ± 2 mEq/l. Neanmoins, dans le cadre de troubles acidobasiques complexes, son calcul peut etre pris en defaut, et il est necessaire de corriger certains parametres. L’albumine en est le principal a prendre en compte afin de determiner le TAP corrige (TAPc), l’hypoalbuminemie etant alcalinisante. Le TAPc peut egalement etre diminue par une grande hyperphosphoremie ou l’augmentation de certains cations (Ca2+, Mg2+, hypergammaglobulinemie). Toute variation de la natremie sans variation proportionnelle de la chloremie peut egalement modifier le TAPc. L’utilisation du rapport ΔTAPc/ΔHCO 3 − et du rapport Cl/Na constitue une approche complementaire au calcul du TAPc, utile dans les desordres acidobasiques mixtes.

L’insuffisance circulatoire aigue retrouvee dans le choc septique engendre des anomalies macrocirculatoires et microcirculatoires aboutissant a une hypoxie tissulaire. Le gradient veinoarteriel de PCO2 est la difference de pression partielle de CO2 entre le sang veineux mele (gapPCO2) ou veineux central (ΔPCO2) et le sang arteriel. Il depend du debit cardiaque (DC), de la production globale de CO2 et de la relation entre PCO2 et contenu en CO2. Differents travaux ont prouve qu’il n’etait pas un marqueur d’hypoxie tissulaire, mais bien un indicateur de la capacite du sang veineux a eliminer le CO2 genere par les tissus peripheriques. La mesure du ΔPCO2 durant la prise en charge d’un patient en choc septique pourrait etre utile afin de decider comment faut-il poursuivre la reanimation, en depit d’une saturation veineuse centrale en oxygene (SvcO2) superieure a 70 % associee a une lactatemie augmentee. Parce qu’une hyperlactatemie n’est pas un facteur discriminant dans la determination de la source de ce stress cellulaire, un ΔPCO2 augmente (> 6 mmHg) pourrait etre utilise afin d’identifier les patients qui restent encore insuffisamment reanimes. L’objectif de diminution du ΔPCO2 constitue une cible therapeutique afin de delivrer un DC adapte a la demande metabolique. Par ailleurs, l’utilisation du ΔPCO2 peut aider a adapter la therapeutique en titrant un traitement inotrope pour ajuster le transport de l’oxygene (TO2) a la production de CO2 ou bien en choisissant entre transfusion sanguine et remplissage vasculaire ou traitement inotrope chez les patients avec une SvcO2 diminuee. La combinaison du ΔPCO2 avec un parametre derive de l’oxygenation, la difference arterioveineuse de contenu en oxygene, constitue le rapport ΔPCO2/C(a-vc)O2 qui est un parametre complementaire d’identification du metabolisme anaerobie global.

Understanding the acid-base disorders relies on a structured diagnostic approach, based on Henderson-Hasselbalch’s equation. After the diagnosis of metabolic acidosis, the calculation of the plasmatic anion gap (AG) evaluates the excess of unmeasured anions. The reference range is 12±2 mEq/L. However, in the case of complex disorders, we need to correct the calculation with some parameters to get the true AG. Albumin is the most clinically relevant variable to adjust for in the calculation of AG (albumin-corrected anion gap) because it is the most abundant of circulating proteins, and hypoalbuminemia has an alkalizing effect.

Background To evaluate the ability of the central venous-to-arterial CO2 content and tension differences to arteriovenous oxygen content difference ratios (∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2, respectively), blood lactate concentration, and central venous oxygen saturation (ScvO2) to detect the presence of global anaerobic metabolism through the increase in oxygen consumption (VO2) after an acute increase in oxygen supply (DO2) induced by volume expansion (VO2/DO2 dependence). Methods We prospectively studied 98 critically ill mechanically ventilated patients in whom a fluid challenge was decided due to acute circulatory failure related to septic shock. Before and after volume expansion (500 mL of colloid solution), we measured cardiac index, VO2, DO2, ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios, lactate, and ScvO2. Fluid-responders were defined as a ≥15 % increase in cardiac index. Areas under the receiver operating characteristic curves (AUC) were determined for these variables. Results Fifty-one patients were fluid-responders (52 %). DO2 increased significantly (31 ± 12 %) in these patients. An increase in VO2 ≥ 15 % (“VO2-responders”) concurrently occurred in 57 % of the 51 fluid-responders (45 ± 16 %). Compared with VO2-non-responders, VO2-responders were characterized by higher lactate levels and higher ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios. At baseline, lactate predicted a fluid-induced increase in VO2 ≥ 15 % with AUC of 0.745. Baseline ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios predicted an increase of VO2 ≥ 15 % with AUCs of 0.965 and 0.962, respectively. Baseline ScvO2 was not able to predict an increase of VO2 ≥ 15 % (AUC = 0.624). Conclusions ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios are more reliable markers of global anaerobic metabolism than lactate. ScvO2 failed to predict the presence of global tissue hypoxia. Electronic supplementary material The online version of this article (doi:10.1186/s13613-016-0110-3) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text, The objective of this study was to examine the repeatability of blood gas (BG) parameters and their derived variables such as the central venous-to-arterial carbon dioxide tension difference (▵Pco2) and the ratio of ▵Pco2 over the central arteriovenous oxygen content difference (▵Pco2/C(a-cv)O2) and to determine the smallest detectable changes in individual patients. A total of 192 patients with arterial and central venous catheters were included prospectively. Two subsequent arterial and central venous blood samples were collected immediately one after the other and analyzed using the same point-of-care BG analyzer. The samples were analyzed for arterial and venous BG parameters, ▵Pco2, and ▵Pco2/C(a-cv)O2 ratio. Repeatability was expressed as the smallest detectable difference (SDD) and the least significant change (LSC). A change in value of these parameters exceeding the SDD or the LSC should be regarded as real. The SDDs for arterial carbon dioxide tension, arterial oxygen saturation, central venous oxygen saturation (ScvO2), and ▵Pco2 were small: ±2.06 mm Hg, ±1.23%, 2.92%, and ±1.98 mm Hg, respectively, whereas the SDDs for arterial oxygen tension (Pao2) and ▵Pco2/C(a-cv)O2 were high: ±9.09 mm Hg and ±0.57 mm Hg/mL, respectively. The LSCs (%) for these variables were 5.06, 1.27, 4.44, 32.4, 9.51, and 38.5, respectively. The repeatability of all these variables was good except for Pao2 and ▵Pco2/C(a-cv)O2 ratio for which we observed an important inherent variability. Expressed as SDD, a ScvO2 change value of at least ±3% should be considered as true. The clinician must be aware that an apparent change in these variables in an individual patient might represent only an inherent variation.

The objective of this study was to assess the impact of fiber-optic laryngoscopy (FOL) on the weaning process from mechanical ventilation in critically ill patients with a positive cuff leak test (CLT) as compared with the current recommended strategy based on corticosteroids. In this prospective observational pilot study conducted over a 1-year period in a 15-bed ICU, CLT was systematically performed before extubation in all intubated patients having passed a spontaneous breathing trial (SBT). After the endotracheal tube cuff was deflated, cuff leak volume (CLVol) was assessed during assisted controlled ventilation. When CLT was positive (CLVol

Background To evaluate the effects of acute hyperventilation on the central venous-to-arterial carbon dioxide tension difference (∆PCO2) in hemodynamically stable septic shock patients. Methods Eighteen mechanically ventilated septic shock patients were prospectively included in the study. We measured cardiac index (CI), ∆PCO2, oxygen consumption (VO2), central venous oxygen saturation (ScvO2), and blood gas parameters, before and 30 min after an increase in alveolar ventilation (increased respiratory rate by 10 breaths/min). Results Arterial pH increased significantly (from 7.35 ± 0.07 to 7.42 ± 0.09, p