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      Lactate kinetics in ICU patients using a bolus of 13C-labeled lactate

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          Abstract

          Background

          Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied.

          Aim

          To establish and validate a feasible method to study lactate kinetics in critically ill patients.

          Methods

          Healthy volunteers ( n = 6) received a bolus dose of 13C-labeled lactate (20 μmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance ( R a) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients ( n = 10).

          Results

          R a for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 μmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques.

          Conclusion

          This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients.

          Trial registration

          ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true

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          Most cited references25

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          The Surviving Sepsis Campaign Bundle

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            Blood lactate is an important energy source for the human brain.

            Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 mumol per kg bw per min), and during 30 mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89+/-0.08, 3.9+/-0.3, and 6.9+/-1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06+/-0.01 to an uptake of 0.16+/-0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28+/-0.16 mmol/min. Most (13)C-label from cerebral [1-(13)C]lactate uptake was released as (13)CO(2) with 100%+/-24%, 86%+/-15%, and 87%+/-30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8%+/-2%, 19%+/-4%, and 27%+/-4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.
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              Lactate and shock state: the metabolic view.

              Bruno Levy (2006)
              The conventional view in severe sepsis or septic shock is that most of the lactate that accumulates in the circulation is due to cellular hypoxia and the onset of anaerobic glycolysis. A number of papers have suggested that lactate formation during sepsis is not due to hypoxia. I discuss this hypothesis and outline the recent advances in the understanding of lactate metabolism in shock. Numerous experimental data have demonstrated that stimulation of aerobic glycolysis - that is, glycolysis not attributable to oxygen deficiency - and glycogenolysis occurs not only in resting, well-oxygenated skeletal muscles but also during experimental haemorrhagic shock and experimental sepsis, and is closely linked to stimulation of sarcolemmal Na+/K+ -ATPase under epinephrine stimulation. A human study of hyperkinetic septic shock demonstrated that skeletal muscle is a leading source of lactate production by exaggerated aerobic glycolysis through Na+/K+ -ATPase stimulation. There is increasing evidence that sepsis is accompanied by a hypermetabolic state, with enhanced glycolysis and hyperlactataemia. This should not be rigorously interpreted as an indication of hypoxia. It now appears, at least in the hyperkinetic state, that increased lactate production and concentration as a result of hypoxia are often the exception rather than the rule.
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                Author and article information

                Contributors
                Jonathan.grip@ki.se
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                10 February 2020
                10 February 2020
                2020
                : 24
                : 46
                Affiliations
                [1 ]Clinical Science Intervention and Technology (CLINTEC), Department of Anesthesiology and Intensive Care, Karolinska Inititutet, Huddinge, Sweden
                [2 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Perioperative Medicine and Intensive Care, , Karolinska University Hospital, ; Huddinge, Sweden
                [3 ]ISNI 0000 0004 1937 0490, GRID grid.10223.32, Division of Critical Care, Department of Medicine, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand
                Author information
                http://orcid.org/0000-0001-9735-4160
                Article
                2753
                10.1186/s13054-020-2753-6
                7011254
                32041652
                ce06b101-2e33-4703-89ae-f5efe2e1428d
                © The Author(s). 2020

                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
                : 11 November 2019
                : 27 January 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100013347, European Society of Intensive Care Medicine;
                Award ID: Clinical Research Award 2018
                Funded by: Lars Bindslevs Memorial Fund
                Award ID: 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Emergency medicine & Trauma
                lactate,lactate kinetics,labeled lactate,stable isotope,icu,method validation

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