• Michael W Donnino, Katherine M Berg, Jacob Vine, Lakshman Balaji, Noa Berlin, Michael N Cocchi, Ari Moskowitz, Maureen Chase, Franklin Li, Shivani Mehta, Jeremy Silverman, Stanley Heydrick, Xiaowen Liu, Anne V Grossestreuer, and BIDMC Center for Resuscitation Science at the time of their contributions.
• Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Rosenberg 2, Boston, MA 02215, USA; Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Rosenberg 2, Boston, MA 02215, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Rosenberg 2, Boston, MA 02215, USA. Electronic address: mdonnino@bidmc.harvard.edu.
• Resuscitation. 2024 Feb 28: 110158110158.

IntroductionThiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients.MethodsSingle center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality.ResultsOf 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes.ConclusionIn this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.Copyright © 2024. Published by Elsevier B.V.

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