IntroductionIn septic shock, pulse pressure or cardiac output variation during passive leg raising are preload dependence indices reliable at predicting fluid responsiveness. Therefore, they may help to identify those patients who need intravascular volume expansion, while avoiding unnecessary fluid administration in the other patients. However, whether their use improves septic shock prognosis remains unknown. The aim of this study was to assess the clinical benefits of using preload dependence indices to titrate intravascular fluids during septic shock.MethodsIn a single-center randomized controlled trial, 60 septic shock patients were allocated to preload dependence indices-guided (preload dependence group) or central venous pressure-guided (control group) intravascular volume expansion with 30 patients in each group. The primary end point was time to shock resolution, defined by vasopressor weaning.ResultsThere was no significant difference in time to shock resolution between groups (median (interquartile range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload dependence groups, respectively). The daily amount of fluids administered for intravascular volume expansion was higher in the control than in the preload dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P = 0.01), and the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to 183) mL, P = 0.04). Physiologic variable values did not change over time between groups, except for plasma lactate (time over group interaction, P <0.01). Mortality was not significantly different between groups (23% in the preload dependence group versus 47% in the control group, P = 0.10). Intravascular volume expansion was lower in the preload dependence group for patients with lower simplified acute physiology score II (SAPS II), and the opposite was found for patients in the upper two SAPS II quartiles. The amount of intravascular volume expansion did not change across the quartiles of severity in the control group, but steadily increased with severity in the preload dependence group.ConclusionsIn patients with septic shock, titrating intravascular volume expansion with preload dependence indices did not change time to shock resolution, but resulted in less daily fluids intake, including red blood cells, without worsening patient outcome.Trial registrationClinicaltrials.gov NCT01972828. Registered 11 October 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0734-3) contains supplementary material, which is available to authorized users.

DAD is present in the majority of patients with nonresolving ARDs and its frequency is no different across the three ARDS stages. On this basis, the systematic use of steroids in nonresolving ARDS is not recommended.

BackgroundPredicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1.MethodsThis study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration.ResultsThere were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80–1.00) and 0.65 (95% CI, 0.46–0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67–100), and specificity of 89% (95% CI, 72–100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24–0.80) and 0.59 (95% CI, 0.31–0.88), respectively.ConclusionsChange in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting.Trial registrationClinicalTrials.gov, NCT01965574. Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1881-0) contains supplementary material, which is available to authorized users.

Innovative single cell technologies such as mass cytometry (CyTOF) widen possibilities to deeply improve characterisation of immune alterations mechanisms in human diseases. So far, CyTOF has not been used in sepsis – a condition characterized by complex immune disorders. Here, we evaluated feasibility of CyTOF analysis in patients with septic shock. We designed a mass cytometry panel of 25 extracellular markers to study mononuclear cells from 5 septic shock patients and 5 healthy donors. We explored single-cell data with global and specific unsupervised approaches such as heatmaps, SPADE and viSNE. We first validated relevance of our CyTOF results by highlighting established immune hallmarks of sepsis, such as decreased monocyte HLA-DR expression and increased expressions of PD1 and PD-L1 on CD4 T cells and monocytes. We then showed that CyTOF analysis reveals novel aspects of sepsis-induced immune alterations, e.g. B cell shift towards plasma cell differentiation and uniform response of several monocyte markers defining an immune signature in septic patients. This proof of concept study demonstrates CyTOF suitability to analyse immune features of septic patients. Mass cytometry could thus represent a powerful tool to identify novel pathophysiological mechanisms and therapeutic targets for immunotherapy in septic shock patients.

Background: Hypotension is a frequent complication of intermittent hemodialysis (IHD) performed in intensive care units (ICUs). Passive leg raising (PLR) combined with continuous measurement of cardiac output is highly reliable to identify preload dependence, and may provide new insights into the mechanisms involved in IHD-related hypotension. The aim of this study was to assess prevalence and risk factors of preload dependence-related hypotension during IHD in the ICU. Methods: A single-center prospective observational study performed on ICU patients undergoing IHD for acute kidney injury and monitored with a PiCCO® device. Primary end points were the prevalence of hypotension (defined as a mean arterial pressure below 65 mm Hg) and hypotension associated with preload dependence. Preload dependence was assessed by the passive leg raising test, and considered present if the systolic ejection volume increased by at least 10 % during the test, as assessed continuously by the PiCCO® device. Results: Forty-seven patients totaling 107 IHD sessions were included. Hypotension was observed in 61 IHD sessions (57 %, CI 95% : 47-66 %) and was independently associated with inotrope administration, higher SOFA score, lower time lag between ICU admission and IHD session, and lower MAP at IHD session onset. Hypotension associated with preload dependence was observed in 19 % (CI 95% : 10-31 %) of sessions with hypotension, and was associated with mechanical ventilation, lower SAPS II, higher pulmonary vascular permeability index (PVPI) and dialysate sodium concentration at IHD session onset. ROC curve analysis identified PVPI and mechanical ventilation as the only variables with significant diagnostic performance to predict hypotension associated with preload dependence (respective AUC: 0.68 (CI 95% : 0.53-0.83) and 0.69 (CI 95% : 0.54-0.85). A PVPI ≥ 1.6 at IHD session onset predicted occurrence of hypotension associated with preload dependence during IHD with a sensitivity of 91 % (CI 95% : 59-100 %), and a specificity of 53 % (CI 95% : 42-63 %). Conclusions: The majority of hypotensive episodes occurring during intermittent hemodialysis are unrelated to preload dependence and should not necessarily lead to reduction of fluid removal by hemodialysis. However, high PVPI at IHD session onset and mechanical ventilation are risk factors of preload dependence-related hypotension, and should prompt reduction of planned fluid removal during the session, and/or an increase in session duration.

Recruitment maneuvers (RM) consist of a ventilatory strategy that increases the transpulmonary pressure transiently to reopen the recruitable lung units in acute respiratory distress syndrome (ARDS). The rationales to use RM in ARDS are that there is a massive loss of aerated lung and that once the end-inspiratory pressure surpasses the regional critical opening pressure of the lung units, those units are likely to reopen. There are different methods to perform RM when using the conventional ICU ventilator. The three RM methods that are mostly used and investigated are sighs, sustained inflation, and extended sigh. There is no standardization of any of the above RM. Meta-analysis recommended not to use RM in routine in stable ARDS patients but to run them in case of life-threatening hypoxemia. There are some concerns regarding the safety of RM in terms of hemodynamics preservation and lung injury as well. The rapid rising in pressure can be a factor that explains the potential harmful effects of the RM. In this review, we describe the balance between the beneficial effects and the harmful consequences of RM. Recent animal studies are discussed.

BACKGROUND:We wanted to assess whether there was a significant relationship between recruited lung volume (V rec ) and change in density on digital processed chest x-ray measured at 2 different levels of inspiratory plateau pressure corresponding to 2 PEEP levels in patients with acute lung injury or ARDS. METHODS: In 14 subjects, PEEP 5 cm H 2 O and 15 cm H 2 O were prospectively applied in a random order for 10 min. At the end of each period, chest x-ray was taken using a digital portable device, and a pressure-volume curve of the respiratory system was performed. We also assessed P aO 2 , and the static and the dynamic (C dyn,rs ) compliance of the respiratory system. Change in end-expiratory lung volume between tidal breath and relaxation volume of the respiratory system was determined. Radiological attenuation was measured on chest x-rays in 4 regions of interest in the right lung, and in 3 regions of interest in the left lung, drawn in posterior intercostal spaces from top to bottom, by using dedicated software. The ratio of lung density in each region between PEEP 15 and PEEP 5 (rP15/P5) and their arithmetic mean (P15/P5) were computed. V rec was determined from the pressure-volume curves. RESULTS: The median value of rP15/P5 in the 98 lung levels was 0.91 (0.80 -1.01), which was significantly different from 1 (P < .001). The values of rP15/P5 were not significantly different between the lung levels. The median values of V rec and P15/P5 were 288 (173-402) mL and 0.90 (0.80 -0.97), respectively. There was a significant negative correlation between V rec and P15/P5 (R ‫؍‬ ؊0.77, P ‫؍‬ .01). The reduction in P15/P5 tended to correlate with the increase in C dyn,rs (R ‫؍‬ ؊0.49, P ‫؍‬ .077) or in P aO 2 (R ‫؍‬ ؊0.53, P ‫؍‬ .05) between PEEP 15 cm H 2 O and PEEP 5 cm H 2 O. CONCLUSIONS: Digital chest x-ray done at the bedside in acute lung injury/ARDS subjects was able to detect a reduction in density between PEEP 5 cm H 2 O and PEEP 15 cm H 2 O, which correlated with V rec .

During mechanical ventilation airways stay open and close around ZEEP in control but are closed above ZEEP after lavage. Inflexion point might reflect onset of airways closure in control. Pressure at maximal compliance increase was not a marker of complete airways closure. In control and lavage, pressure at maximal compliance increase and zero-volume intercept were reasonably equivalent.