Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis.
| Autor: | May CN; 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., Ow CP; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Pustovit RV; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Lane DJ; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Jufar AH; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Trask-Marino A; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Peiris RM; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Gunn A; Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Booth LC; Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Plummer MP; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Intensive Care, Royal Adelaide Hospital, Adelaide, VIC, Australia., Bellomo R; Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia; Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia; Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia., Lankadeva YR; 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. |
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| Jazyk: | angličtina |
| Zdroj: | British journal of anaesthesia [Br J Anaesth] 2024 Aug; Vol. 133 (2), pp. 316-325. Date of Electronic Publication: 2024 Jul 02. |
| DOI: | 10.1016/j.bja.2024.04.058 |
| Abstrakt: | Background: The 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. Methods: Sepsis 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. Results: At 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 P Conclusions: Megadose 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.) |
| Databáze: | MEDLINE |
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