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Title: | Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C. | Austin Authors: | Lankadeva, Yugeesh R;Peiris, Rachel M;Okazaki, Nobuki;Birchall, Ian E;Trask-Marino, Anton;Dornom, Anthony;Vale, Tom A M;Evans, Roger G;Yanase, Fumitaka ;Bellomo, Rinaldo ;May, Clive N | Affiliation: | Department of Physiology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, VIC, Australia School of Medicine, University of Melbourne, VIC, Australia Intensive Care Neuropathology Laboratory, Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC, Australia Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC, Australia Centre for Integrated Critical Care, Department of Medicine and Radiology, University of Melbourne, VIC, Australia Department of Anesthesiology and Resuscitology, Okayama University, Okayama, Japan |
Issue Date: | Feb-2021 | Date: | 2020-11-25 | Publication information: | Critical Care Medicine 2021; 49(2): e179-e190 | Abstract: | Oxidative 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. Interventional study. Research Institute. Adult Merino ewes. Sheep 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). Sepsis-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. IV 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/25444 | DOI: | 10.1097/CCM.0000000000004770 | Journal: | Critical Care Medicine | PubMed URL: | 33239507 | Type: | Journal Article |
Appears in Collections: | Journal articles |
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