Thiamine as a metabolic resuscitator after in-hospital cardiac arrest

Abstract

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 ≥ 3mmol/L were included. Randomization was stratified by lactate >5 or ≤5 mmol/L. Thiamine 500mg 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 ≤ 5mmol/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.