Thiamine alone rather than in combination with ascorbic acid is associated with improved survival in septic shock

Background Sepsis and septic shock are common causes of ICU admission with devastating outcomes. Adjunctive therapies are urgently needed, and the use of high dose of vitamin B1 and C have recently gained interest. However, on the basis of a perceived possible synergic effect, most trials have never tested the combination of thiamine and ascorbic acid, with a separate assessment of the effect of each individual component. In this context, while the association of thiamine and ascorbic acid was not found to improve survival rates, potentially harmful effects were found when administering ascorbic acid alone. We have conducted a retrospective cohort study, comparing ICU mortality of septic shock patients receiving standard treatment, thiamine alone or a combination of thiamine and ascorbic acid. Results A total of 1800 patients were included, 1260 receiving standard care, 436 receiving only thiamine and 104 patients receiving a thiamine / ascorbic acid combination. Using doubly robust estimation of the treatment effect, combining propensity score weighting and variables adjustment, we found thiamine alone to be associated with a decrease in ICU mortality compared to the use of a thiamine / ascorbic acid combination (Hazar Ratio equal to 0.60, 95% Confidence Interval [0.36;0.99], p=0.048). Conclusions In septic shock patients, administration of thiamine is associated with improved ICU mortality when used alone rather than when associated with ascorbic acid. This result strengthens the evidence showing a lack of effectiveness of the ascorbic acid / thiamine combination reported in recent randomized controlled trials. Furthermore, it argues in favor of the need for further trials investigating the effect of thiamine in septic ICU patients as an adjunctive therapy.