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Time course of fluid responsiveness in sepsis: the fluid challenge revisiting (FCREV) study.

ABSTRACT: BACKGROUND:Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20?min later could affect the results of the FC. METHODS:This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500?mL crystalloids over 10?min. Fluid responsiveness was defined as a >?15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T0), at the end of FC (T10), then 10 (T20) and 20?min (T30) after the end of FC. RESULTS:From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64?±?14?years, median IGS II 53 [43-63], median SOFA score 10 [8-12]). Among the 76/143 (53%) patient responders to FC at T10, 37 patients were transient responders (TR), i.e., became non-responders (NR) at T30 (49%, 95%CI?=?[37-60]), and 39 (51%, 95%CI?=?[38-62]) patients were persistent responders (PR), i.e., remained responders at T30. Among the 67 NR at T10, 4 became responders at T30, (6%, 95%CI?=?[1.9-15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups. CONCLUSIONS:This study shows that 51.3% of initial responders have a persistent response to fluid 30?min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent. TRIAL REGISTRATION:ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014.

SUBMITTER: Roger C

PROVIDER: S-EPMC6524325 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Project description:BackgroundMini-fluid challenge is a well tested and effective tool to predict fluid responsiveness under various clinical conditions. However, mini-fluid challenge has never been tested in patients with end-stage liver disease. This study investigated whether infusion of 150 ml albumin 5% can predict fluid responsiveness in cirrhotic patients following liver transplant.MethodsFifty patients receiving living donor liver transplant were included in the analysis. Mini-fluid challenge composed of 150 ml of albumin 5% administered over 1 min in three consecutive 50-ml fluid boluses. An additional 350 ml was then infused at a constant rate over 15 min (for a total of 500 ml). Stroke volume (SV) was measured as the product of the subaortic velocity time integral (VTI) and left ventricular outflow tract (LVOT) area. Fluid responsiveness was defined as an increase in SV by ≥15% after the infusion.ResultsFifty patients were enrolled in the study. Fourteen patients were classified with Child A, 15 patients with Child B, and 21 patients with Child C cirrhosis. Thirty four patients were fluid responders and 16 patients were fluid non-responders. After 150 ml of albumin 5%, the SV increased significantly in our cohort. The area under receiver operating curve (AUROC) was 0.7 (95% confidence interval [CI] 0.5-0.8, P = 0.005). In subgroup analysis, the SV increased significantly after mini fluid challenge in the Child A group (P = 0.017) but not Child B or C groups (P = 0.3 and 0.29, respectively). The AUROC for mini-fluid challenge in the Child A group was 0.86 (95% confidence interval [CI] 0.6-0.9, P = 0.0004), while mini-fluid challenge failed to discriminate between responders and non-responders in Child B and C groups.ConclusionA mini-fluid challenge of 150 ml albumin 5% can predict fluid responsiveness in liver transplant patients with fair sensitivity and specifiicty. Subgroup analyis revealed that minifluid challenge can predict fluid responsiveness in patients with Child A cirrhosis but not patients with Child B or C cirrhosis.Trial registrationNCT03396159 . (Prospective registered). Initial registration date was 10/01/2018.

Project description:TNF time course series of HelA tet off cells cultured in presence or absence of Dox TNF is a pro-inflammatory cytokine that controls expression of inflammatory genetic networks. Although the Nuclear Factor-kB (NF-kB) pathway is crucial for mediating cellular TNF responses, the complete spectrum of NF-kB dependent genes is unknown. In this study, we used a tetracycline-regulated cell line expressing an NF-kB inhibitor to systematically identify NF-kB dependent genes. A microarray data set generated from a time course of TNF stimulation in the presence or absence of NF-kB signaling was analyzed. Methods: Cell culture, treatment and transfection-The human cervical epithelioid carcinoma cell line HeLa expressing tTA (HeLa Tet-Off) pBI-EGFP- IkBa Mut was constructed earlier (23). HeLa Tet-Off were grown in medium containing 90 % Dulbecco’s Modified Eagle’s Medium (DMEM), 10 % heat-inactivated fetal bovine serum (FBS), 4mM L-glutamine, 0.1 mM non-essential amino acids, 1 mM sodium pyruvate, 100 mg/ml G418, 100 units /ml penicillin G sodium, and 100 mg/ml streptomycin sulfate in a humidified atmosphere of 5 % CO2. For TNF stimulation, freshly isolated cells were split into two cultures, one group maintained in Dox, the other without for 7 d, a time at which IkBa Mut expression was maximal. Thereafter, recombinant human (rh) TNFa (25 ng/ml, final concentration) was added directly to the culture medium for indicated times prior to harvest. Oligonucleotide probe based microarray-Hu95Av2 GeneChip (Affymetrix Inc, Santa Clara, CA) containing 12,626 sequenced human genes were hybridized according to the manufacturer’s recommendations and washed using both non-stringent (1 M NaCl, 25 °C) and stringent (1 M NaCl, 50 °C) conditions prior to staining with phycoerythrin streptavidin (10 mg/ml final). Arrays were scanned using a Gene Array Scanner (Hewlett Packard) and analyzed using the Gene Chip Analysis Suite 5 software (Affymetrix Inc). For each gene, 16-20 probe pairs are immobilized as ~25-mer oligonucleotides that hybridize throughout the mRNA; each probe pair is represented as a perfect match (PM) oligonucleotide and a mismatch (MM) oligonucleotide as hybridization control. The the Absolute Call [e.g., the gene is detected (“present”) or not (“absent”)] and the Signal Intensity (measure of mRNA abundance) is determined. Four independent experiments were performed identically including control (0 h ), 1, 3 and 6 h TNF stimulation (25 ng/ml) in the presence or absence of Doxycyline (2 mg/ml) in growth medium. These are indicated as 180, 181, 220 and 266 series, and are considered replicates of each other. Keywords: time-course

Project description:Object: The aim of this study was to investigate metabolite levels in cerebrospinal fluid (CSF) in their time-dependent course after aneurysmal subarachnoid hemorrhage (aSAH) comparing them to patients harboring unruptured intracranial aneurysms. Methods: Eighty CSF samples of 16 patients were analyzed. The study population included patients undergoing endovascular/microsurgical treatment of ruptured intracranial aneurysms (n = 8), which were assessed for 9 days after aSAH. Control samples were collected from the basal cisterns in elective aneurysm surgery (n = 8). The CSF samples were consecutively collected with extraventricular drain (EVD) placement/intraoperatively, 6 h later, and daily thereafter (day 1-9). The endogenous metabolites were analyzed with a targeted quantitative and quality controlled metabolomics approach using the AbsoluteIDQ®p180Kit. Differences inbetween timepoints and compared to the control group were evaluated. Results: Numerous alterations of amino acid (AA) levels were detected within the first hours after bleeding. The highest mean concentrations occurred 1 week after aSAH. AA levels were continuously increasing over time starting 6 h after aSAH. Taurine concentration was highest briefly after aSAH starting to decrease already after 6 h (vs. day 1-9, p = 0.02). The levels of sphingomyelins/ phosphatidylcholines/ lysophosphatidylcholines/mono-unsaturated fatty acid chain were highly elevated on day 0 (compared to other timepoints or controls, p < 0.01) and decreased over the next several days to concentrations comparable to the control group. Carnitine concentrations were decreased after SAH (vs. day 7, p < 0.01), while they recovered within the next day. The Fischer ratio of branched-chain AA to aromatic AA was lowest immediately after SAH and increased in 7 days (p < 0.001). Conclusion: AA levels in CSF increased overtime and often differ from patients without SAH. There was a peak concentration of structural AA within the first 6 h after aneurysm treatment. Time-dependent alterations of CSF metabolites and compounds may elucidate pathophysiological processes after aSAH, providing potential predictors assessed non-invasively by routine lab testing.

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Time course of fluid responsiveness in sepsis: the fluid challenge revisiting (FCREV) study.

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