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Antioxidant and anti-inflammatory therapy worsens cognitive and psychological outcomes following sepsis

Antioxidant and anti-inflammatory therapy given to sepsis survivors led to worse cognitive and psychological scores after 6 months

The provision of antioxidant and anti-inflammatory treatment for sepsis survivors gave rise to lower cognitive and psychological scores compared to placebo after 6 months, according to a randomised trial by the VICTAS investigators.

Evidence suggests that patients with sepsis exhibit long-term neurological sequelae, particularly substantial declines in cognitive function. In fact, the Sepsis Alliance highlights that the presence of Post-traumatic stress disorder, depression and anxiety are not unusual among sepsis survivors. It is thought that the presence of oxidative damage is an important factor in post-sepsis cognitive impairment. Additionally, in animal models, deficiency of the vitamin thiamine, also enhances oxidative stress and inflammatory response changes and some preliminary data indicates a synergistic effect of vitamin C and hydrocortisone on endothelial barrier protection in patients with sepsis. Given these findings, was it possible that triple combination therapy with vitamin C, hydrocortisone and thiamine, made a positive impact on cognitive, psychological and functional outcomes in those who survive sepsis?

The VICTAS trial attempted to answer this question and randomised 1:1, sepsis survivors to either triple combination therapy, consisting of intravenous vitamin C, thiamine and hydrocortisone or placebo. The combination was administered within 4 hours of randomisation and every 6 hours thereafter for up to 96 hours. The outcomes of interest were cognitive performance, risk of posttraumatic stress disorder and functional status, all of which were assessed 6 months after randomisation.

Antioxidant, anti-inflammatory treatment outcomes

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A total of 213 participants with a median age of 57 years (52.6% male) were included and randomised to the triple therapy (108) or placebo.

At 6 months, the triple therapy group had significantly lower immediate memory (i.e., cognitive) scores than placebo participants (adjusted odds ratio, aOR = 0.49, 95% CI 0.26 – 0.89, p = 0.02) and a higher odds of posttraumatic stress disorder (aOR = 3.51, 95% CI 1.18 – 10.40, p = 0.02). In contrast, there was a lower odds among triple group participants, of receiving formal psychiatric, psychological, or mental health care during the 6 months after discharge. However, there were no significant differences in measures of functional support.

The authors concluded that in sepsis survivors, treatment with vitamin C, thiamine, and hydrocortisone made worse, cognitive and psychological outcomes and made no difference to functional outcomes at 6 months compared to placebo.

Roberson SW et al. Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial. JAMA Netw Open 2023

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