ArticleCritical care medicine2021
Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C.
Article in Critical care medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials.Diabetes & metabolic syndromePooled it
- Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.Critical care (London, England) · 2023Trial
- Effect Evaluation of Norepinephrine on Cardiac Function in Patients with Sepsis by Cardiac Ultrasound Imaging.Computational and mathematical methods in medicine · 2022Trial
- Intravenous megadose sodium ascorbate normalises elevations in intracranial pressure and restores pressor responsiveness to norepinephrine in ovine Gram-negative sepsis.Scientific reports · 2026Article
- Animal models of critical illness in the Asia-Pacific region: current practices, shared challenges, and future directions.Intensive care medicine experimental · 2026Review
- Sodium ascorbate versus ascorbic acid in sepsis: a narrative review of emerging cardiovascular and neurological benefits.Critical care (London, England) · 2026Review
- A preclinical randomised controlled dose optimization of megadose sodium ascorbate for reversal of gram-negative sepsis-induced cardiovascular, brain and kidney dysfunction.Critical care (London, England) · 2025Article
- Vitamin C is associated with improved outcomes in patients with sepsis-induced myocardial injury: insights from the MIMIC-IV database.BMC infectious diseases · 2025Article
- Effects of glucagon-like peptide-1 on systemic hemodynamics, kidney function, and intrarenal oxygenation in sheep with sepsis-associated acute kidney injury.Scientific reports · 2025Article
- Effects of tempol on renal medullary tissue hypoxia in an ovine model of Gram-negative septic acute kidney injury.Experimental physiology · 2025Article
- Unravelling the paradox of vitamin C research in sepsis.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2025Review
- Rinaldo Bellomo: A clinician with a passion for preclinical research.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2025Article
- Evaluating skeletal muscle wasting and weakness in models of critical illness.Clinical science (London, England : 1979) · 2025Review
- Early, very high-dose, and prolonged vitamin C administration in murine sepsis.Scientific reports · 2025Article
- Vitamin C improves 28-day survival in patients with sepsis-associated acute kidney injury in the intensive care unit: a retrospective study.Frontiers in nutrition · 2025Article
- Postoperative sepsis-associated neurocognitive disorder: mechanisms, predictive strategies, and treatment approaches.Frontiers in medicine · 2025Review
- An ovine septic shock model of live bacterial infusion.Intensive care medicine experimental · 2024Article
- Article
- Article
- Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury.Intensive care medicine experimental · 2024Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesOxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C at megadoses. We have therefore investigated the safety and efficacy of megadose sodium ascorbate in sepsis.
designInterventional study.
settingResearch Institute. SUBJECTS: Adult Merino ewes.
interventionsSheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg). MEASUREMENTS AND MAIN
resultsSepsis-induced fever (41.4 ± 0.2°C; mean ± se), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial Po2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue Po2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01). Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary Po2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg). We confirmed these physiologic findings in a coronavirus disease 2019 patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.
conclusionsIV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.
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