Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C
| Autor: | Rachel M Peiris, Anton Trask-Marino, Nobuki Okazaki, Yugeesh R Lankadeva, Roger G. Evans, Fumitaka Yanase, Tom A M Vale, Clive N. May, Anthony Dornom, Ian Birchall, Rinaldo Bellomo |
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| Rok vydání: | 2020 |
| Předmět: |
Sodium ascorbate
Mean arterial pressure Resuscitation antioxidant Critical Care and Intensive Care Medicine sepsis Sepsis coronavirus disease 2019 03 medical and health sciences chemistry.chemical_compound Online Laboratory Investigation 0302 clinical medicine Heart rate Medicine Kidney Vitamin C hypoxia business.industry 030208 emergency & critical care medicine medicine.disease medicine.anatomical_structure acute kidney injury 030228 respiratory system chemistry Anesthesia Shock (circulatory) ComputingMethodologies_DOCUMENTANDTEXTPROCESSING medicine.symptom business sodium ascorbate |
| Zdroj: | Critical Care Medicine |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/ccm.0000000000004770 |
| Popis: | Supplemental Digital Content is available in the text. Objectives: 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. Design: Interventional study. Setting: Research Institute. Subjects: Adult Merino ewes. Interventions: 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). Measurements and Main Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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