The Effect of Intravenous Sodium Ascorbate on Secondary Brain Injury in a Cohort of Severe Traumatic Brain Injury patients: The Orange Concentrate Randomised Control Trial.

None listed

In response to the onset of significant inflammatory signalling following severe traumatic brain injury, ascorbate (vitamin C) concentrations rapidly fall to levels associated with severe deficiency. Without replacement, the ascorbate levels remain reduced for the duration of the inflammatory response. There is mounting evidence that replacing ascorbate plasma levels during an inflammatory response may be beneficial, particularly to the brain. Ascorbate is known to be an essential co-factor in several brain metabolic processes. These processes include reducing oxidative stress, maintaining microcirculatory homeostasis and maintaining normalm function of several key enzyme systems, including endothelial nitric oxide synthase (eNOS). In addition, ascorbate is involved in brain energy production, and is required for the production of a significant number of neurotransmitters. It is clear from multiple animal and human studies that deficiency in ascorbate leads to a pro-inflammatory state and worsening organ failure. In response to traumatic brain injury, brain ascorbate levels fall markedly in line with body concentrations. The magnitude of plasma level ascorbate decrease, which often reaches levels associated with scurvy in critical illness, has been shown to correlate with severity of both neurological injury and more general injury severity. Ascorbate supplementation has been shown to reduce the severity of secondary brain injury in multiple animal studies. There is a need to further evaluate the role of intravenous sodium ascorbate in the setting of human brain injury. To this end the authors propose to conduct a small feasibility study in the Australian setting to establish the efficacy of the proposed intervention and to evaluate the effect of intravenous sodium ascorbate on patients suffering from severe traumatic brain injury.