Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study

Abstract

Objective: To determine if intravenous thiamine would reduce lactate in patients with septic shock.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Two US hospitals.

Patients: Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014.

Interventions: Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge.

Measurements and main results: The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047).

Conclusion: Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Figure 1. CONSORT flow diagram

Out of 715 patients with septic shock and elevated lactate, 88 were included in the analysis.

Figure 2. Lactate levels over time

Lactate levels at baseline (time of study drug) and 6, 12 and 24 hours thereafter according to treatment group in the full study group (left) and in the thiamine deficient cohort (right). The boxplots represent the 1^st quartiles, median, and 3^rd quartile. The whiskers represent the 10^th and 90^th percentile and the “+” is the mean.

Figure 3. Kaplan Meier survival curves

Survival curves for the thiamine and placebo groups in the full study group (left) and the thiamine deficient group (right). Patients were censored at hospital discharge. The graph is truncated at 30 days for illustrative purposes. Vertical lines represents censored patients and the p-value is from the log-rank test.