• Br J Anaesth · Aug 2024

    Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis.

    • Clive N May, Connie P Ow, Ruslan V Pustovit, Darius J Lane, Alemayehu H Jufar, Anton Trask-Marino, Rachel M Peiris, Adam Gunn, Lindsea C Booth, Mark P Plummer, Rinaldo Bellomo, and Yugeesh R Lankadeva.
    • Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia. Electronic address: clive.may@florey.edu.au.
    • Br J Anaesth. 2024 Aug 1; 133 (2): 316325316-325.

    BackgroundThe mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis.MethodsSepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg-1 over 30 min+0.5 g kg-1 h-1 for 6.5 h) or vehicle (n=6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70-80 mm Hg.ResultsAt 23 h of sepsis, MAP (mean [sem]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] μM) decreased (both P<0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P<0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all PTreatment<0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both PGroupxTime<0.01), and increased plasma ascorbate (20 000 [300] μM; PGroup<0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate.ConclusionsMegadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load.Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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