Rationale for mega-dose vitamin C treatment in sepsis
Intravenous administration of a mega-dose of sodium ascorbate (150
g/~40 kg 7-h) in established ovine hyperdynamic sepsis,
induced by infusion of live Escherichia. coli , caused a
remarkable improvement in the clinical state from malaise, lethargy and
somnolence to an alert, responsive,
mobile state (Lankadeva et al., 2021). MAP was restored to pre-septic
levels with reduced noradrenaline requirements, which decreased to zero
in 4 of 5 cases. Mega-dose vitamin C increased arterial blood oxygen
levels, indicative of improvements in lung function, restored body
temperature from febrile to normal levels and reduced arterial blood
lactate indicating improved metabolic function. The treatment also
reversed renal medullary hypoperfusion and hypoxia, accompanied by a
reversal in septic AKI, as shown by dramatic increases in urine flow and
creatinine clearance leading to a normalisation of plasma creatinine
levels.
The re-distribution of intra-renal perfusion in ovine septic AKI
(Calzavacca, Evans, Bailey, Bellomo & May, 2015) is accompanied by
reduced gene expression of renal medullary endothelial nitric oxide
synthase (eNOS) (Langenberg, Bagshaw, May & Bellomo, 2008). The
reversal of renal medullary microcirculatory dysfunction by vitamin C
may result from its ability to increase eNOS activity and thus nitric
oxide bioavailability (Ladurner et al., 2012). Furthermore, the
antioxidant effects of vitamin C are likely to reduce mitochondrial
dysfunction and cellular injury.