Thiamine as a metabolic resuscitator after out-of-hospital cardiac arrest.

INTRODUCTION: Thiamine 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. METHODS: Single 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. RESULTS: Of 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. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.

Thiamine as a metabolic resuscitator after in-hospital cardiac arrest.

INTRODUCTION: Elevated lactate is associated with mortality after cardiac arrest. Thiamine, a cofactor of pyruvate dehydrogenase, is necessary for aerobic metabolism. In a mouse model of cardiac arrest, thiamine improved pyruvate dehydrogenase activity, survival and neurologic outcome. AIM: To determine if thiamine would decrease lactate and increase oxygen consumption after in-hospital cardiac arrest. METHODS: Randomized, double-blind, placebo-controlled phase II trial. Adult patients with arrest within 12 hours, mechanically ventilated, with lactate ≥ 3 mmol/L were included. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. Thiamine 500 mg or placebo was administered every 12 hours for 3 days. The primary outcome of lactate was checked at baseline, 6, 12, 24, and 48 hours, and compared using a linear mixed model, accounting for repeated measures. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase, and mortality. RESULTS: Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis. There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88) or any secondary outcomes. In those with randomization lactate > 5 mmol/L, mortality was 92% (11/12) with thiamine and 67% (8/12) with placebo (p = 0.32). In those with randomization lactate ≤ 5 mmol/L mortality was 17% (1/6) with thiamine and 67% (4/6) with placebo (p = 0.24). There was a significant interaction between randomization lactate and the effect of thiamine on survival (p = 0.03). CONCLUSIONS: In this single center trial thiamine had no overall effect on lactate after in-hospital cardiac arrest.