Thiamine as a metabolic resuscitator in septic shock: a randomized, double-blind, placebo-controlled, pilot trial

Abstract

Background: Thiamine is essential for aerobic metabolism. We have preciously found that thiamine levels are low and inversely correlated with lactate levels in patients with sepsis. Objectives: To determine if the administration of thiamine mitigates elevated lactate levels in patients with septic shock. Methods: We performed a randomized, double-blind, placebocontrolled, two-center trial from 01/10 to 10/14. We enrolled patients with septic shock, elevated lactate (≥ 3 mmol/L) and no obvious competing cause of lactate elevation. Patients received thiamine 200 mg or placebo IV twice/day for seven days. Primary outcome was lactate levels at 24 h. Secondary outcomes included the SOFA score at 24 h and mortality. Lactate levels at 24 h were compared between groups using Wilcoxon Rank Sum test and categorical variables were compared using the Fisher's exact test. Lactate values at 24 h, for those who died before 24 h, were imputed according to a predefined plan. We performed a preplanned analysis in those with baseline thiamine deficiency (≤ 7 nmol/L). Results: We enrolled 88 patients; 43 received thiamine and 45 placebo. Baseline characteristics were similar between groups (Table 175). We found no overall statistical significant difference in 24 h lactate levels between thiamine and placebo groups (2.5 [IQR: 1.5 - 3.4] vs. 2.6 [IQR: 1.6 - 5.1], p = 0.40). Fewer patients in the thiamine group had lactate levels > 4 mmol/L at 24 hours (21% vs. 38%, p = 0.10) and this was statistically significant if only evaluating survivors at 24-hours (7% vs. 33%, p = 0.03) though our pre-planned analysis was to impute data. We found no difference in 24 h SOFA score or mortality. A total of 28 (35%) patients were thiamine deficient. Of the deficient patients, those receiving thiamine had statistically significant lower lactate levels at 24 h (2.1 [IQR: 1.4 - 2.5] vs. 3.1 [IQR: 1.9 - 8.3], p = 0.03, Donnino Figure 1) and more patients in the placebo group had a lactate > 4 mmol/L (38% vs. 7%, p = 0.07). Mortality in the thiamine and placebo groups was 13% and 46%, respectively (p = 0.10). Conclusion: Thiamine deficiency is prevalent in septic shock. Thiamine did not decrease overall difference in median lactate levels at 24 hours. In the subset of patients with thiamine deficiency, there were statistically significant lower lactate levels at 24 hours in the intervention group and a large, although non-significant, difference in mortality. (Figure Presented).