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      Cardiovascular determinants of resuscitation from sepsis and septic shock

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          Abstract

          Background

          We hypothesized that the cardiovascular responses to Surviving Sepsis Guidelines (SSG)-defined resuscitation are predictable based on the cardiovascular state.

          Methods

          Fifty-five septic patients treated by SSG were studied before and after volume expansion (VE), and if needed norepinephrine (NE) and dobutamine. We measured mean arterial pressure (MAP), cardiac index (CI), and right atrial pressure (Pra) and calculated pulse pressure and stroke volume variation (PPV and SVV), dynamic arterial elastance (Ea dyn), arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees), Ees/Ea (VAC), LV ejection efficiency (LVeff), mean systemic pressure analogue (Pmsa), venous return pressure gradient (Pvr), and cardiac performance (Eh), using standard formulae.

          Results

          All patients were hypotensive (MAP 56.8 ± 3.1 mmHg) and tachycardic (113.1 ± 7.5 beat min −1), with increased lactate levels (lactate = 5.0 ± 4.2 mmol L −1) with a worsened VAC. CI was variable but > 2 L min −1 M −2 in 74%. Twenty-eight-day mortality was 48% and associated with admission lactate, blood urea nitrogen (BUN), and creatinine levels but not cardiovascular state. In all patients, both MAP and CI improved following VE, as well as cardiac contractility (Ees). Fluid administration improved Pra, Pmsa, and Pvr in all patients, whereas both HR and Ea decreased after VE, thus normalizing VAC. CI increases were proportional to baseline PPV and SVV. CI increases proportionally decreased PPV and SVV. VE increased MAP > 65 mmHg in 35/55 patients. MAP responders had higher PPV, SVV, and Ea dyn than non-responders. NE was given to 20/55 patients in septic shock, but increased MAP > 65 mmHg in only 12. NE increased Ea, Ea dyn, Pra, Pmsa, and VAC while decreasing HR, PPV, SVV, and LVeff. MAP responders had higher pre-NE Ees and lower VAC. Dobutamine was given to 6/8 patients who remained hypotensive following NE. It increased Ees, MAP, CI, and LVeff, while decreasing HR, Pra, and VAC. At all times and all steps of the protocol, CI changes were proportional to Pvr changes independent of treatment.

          Conclusions

          The cardiovascular response to SSG-based resuscitation is highly heterogeneous but predictable from pre-treatment measures of cardiovascular state.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2414-9) contains supplementary material, which is available to authorized users.

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          Most cited references33

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

            To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".
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              Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.

              Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively. In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
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                Author and article information

                Contributors
                412-647-8109 , pinsky@pitt.edu
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                15 April 2019
                15 April 2019
                2019
                : 23
                : 118
                Affiliations
                [1 ]ISNI 0000 0004 1756 8209, GRID grid.144189.1, Department of Anesthesia and Critical Care Medicine, , Azienda Ospedaliero Universitaria Pisana, ; Pisa, Italy
                [2 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Critical Care Medicine, , University of Pittsburgh, ; 1215.4 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA 15213 USA
                Author information
                http://orcid.org/0000-0001-6166-700X
                Article
                2414
                10.1186/s13054-019-2414-9
                6466803
                30987647
                13fee521-f34f-45aa-a373-e9170a3670d7
                © The Author(s). 2019

                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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 January 2019
                : 29 March 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                heart-lung interactions,blood volume,ventriculo-arterial coupling,effective circulating blood volume,norepinephrine,clinical trial

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