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.

Sepsis is a common and frequently fatal condition, with recent estimates suggesting that nearly 20% of all deaths are sepsis related.¹ Although one modeling study estimated that overall sepsis mortality improved between 1990 and 2017, sepsis survivors often experience residual organ injury.² To date, therapies for sepsis management remain early antimicrobials, effective treatment of the infection source, and supportive care.