Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C.
Crit Care Med
; 49(2): e179-e190, 2021 02 01.
Article
in English
| MEDLINE | ID: covidwho-947682
ABSTRACT
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 MAINRESULTS:
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Ascorbic Acid
/
Sepsis
/
Escherichia coli Infections
/
Antioxidants
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Animals
Language:
English
Journal:
Crit Care Med
Year:
2021
Document Type:
Article
Affiliation country:
Ccm.0000000000004770
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