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      Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy

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          Abstract

          In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the “four D’s” of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are “When to start intravenous fluids?”, “When to stop intravenous fluids?”, “When to start de-resuscitation or active fluid removal?” and finally “When to stop de-resuscitation?” In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.

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          Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

          Background In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. Methods We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. Results Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). Conclusions More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
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            Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.

            Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI). To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients. Prospective, open-label, sequential period pilot study of 760 patients admitted consecutively to the intensive care unit (ICU) during the control period (February 18 to August 17, 2008) compared with 773 patients admitted consecutively during the intervention period (February 18 to August 17, 2009) at a university-affiliated hospital in Melbourne, Australia. During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin. The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) classification. Secondary post hoc analysis outcomes included the need for renal replacement therapy (RRT), length of stay in ICU and hospital, and survival. RESULTS Chloride administration decreased by 144 504 mmol (from 694 to 496 mmol/patient) from the control period to the intervention period. Comparing the control period with the intervention period, the mean serum creatinine level increase while in the ICU was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P <.001), and the use of RRT was 10% (95% CI, 8.1%-12%; n = 78) vs 6.3% (95% CI, 4.6%-8.1%; n = 49) (P = .005). After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P <.001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge. CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT. Clinicaltrials.gov Identifier: NCT00885404.
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              Fluid challenges in intensive care: the FENICE study

              Background Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. Methods This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. Results 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500–1000). The median time was 24 min (40–60 min), and the median rate of FC was 1000 [500–1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57–61 %). In 43 % (CI 41–45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34–37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20–24 %). No safety variable for the FC was used in 72 % (CI 70–74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. Conclusions The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-3850-x) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                +32 2 476 3101 , manu.malbrain@uzbrussel.be
                niels.vanregenmortel@zna.be
                b.saugel@uke.de
                brechtdt@hotmail.com
                vangaalpieterjan@skynet.be
                olivier.joannes-boyau@chu-bordeaux.fr
                jean-louis.teboul@aphp.fr
                todd.rice@vanderbilt.edu
                m.mythen@ucl.ac.uk
                xavier.monnet@aphp.fr
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                22 May 2018
                22 May 2018
                2018
                : 8
                : 66
                Affiliations
                [1 ]ISNI 0000 0004 0626 3362, GRID grid.411326.3, Intensive Care Unit, , University Hospital Brussels (UZB), ; Laarbeeklaan 101, 1090 Jette, Belgium
                [2 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Faculteit Geneeskunde en Farmacie, , Vrije Universiteit Brussel (VUB), ; Brussels, Belgium
                [3 ]ISNI 0000 0004 0608 3935, GRID grid.416667.4, Intensive Care Unit, ZiekenhuisNetwerk Antwerpen, , ZNA Stuivenberg, ; Lange Beeldekensstraat 267, 2060 Antwerpen 6, Belgium
                [4 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Department of Anesthesiology, Centre of Anesthesiology and Intensive Care Medicine, , University Medical Centre Hamburg-Eppendorf, ; Hamburg, Germany
                [5 ]ISNI 0000 0004 0593 7118, GRID grid.42399.35, Service d’Anesthésie-Réanimation 2, , CHU Bordeaux, ; 33000 Bordeaux, France
                [6 ]ISNI 0000 0001 2171 2558, GRID grid.5842.b, Medical Intensive Care Unit, Hopitaux universitaires Paris-Sud, AP-HP, , Université Paris-Sud, ; Le Kremlin-Bicetre, France
                [7 ]University College London Hospitals, National Institute of Health Research Biomedical Research Centre, London, UK
                [8 ]ISNI 0000 0001 2264 7217, GRID grid.152326.1, Division of Allergy, Pulmonary and Critical Care Medicine, , Vanderbilt University School of Medicine, ; Nashville, TN USA
                Article
                402
                10.1186/s13613-018-0402-x
                5964054
                29789983
                8142c761-81bd-4766-aadd-525a6f4d3b50
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 12 September 2017
                : 23 April 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Emergency medicine & Trauma
                fluids,fluid therapy,fluid management,fluid stewardship,four d’s,four indications,four hits,four phases,four questions,resuscitation,antibiotics,drug,dose,duration,de-escalation,de-resuscitation,maintenance,replacement,goal-directed therapy,monitoring,fluid responsiveness,passive leg raising

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