TY - JOUR
T1 - Thiamine as a metabolic resuscitator after in-hospital cardiac arrest
AU - Berg, Katherine M.
AU - Grossestreuer, Anne V.
AU - Balaji, Lakshman
AU - Moskowitz, Ari
AU - Berlin, Noa
AU - Cocchi, Michael N.
AU - Morton, Andrea C.
AU - Li, Franklin
AU - Mehta, Shivani
AU - Peradze, Natia
AU - Silverman, Jeremy
AU - Liu, Xiaowen
AU - Donnino, Michael W.
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Cardiac arrest
KW - Oxygen consumption
KW - Thiamine
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U2 - 10.1016/j.resuscitation.2024.110160
DO - 10.1016/j.resuscitation.2024.110160
M3 - Article
C2 - 38428722
AN - SCOPUS:85187570242
SN - 0300-9572
JO - Resuscitation
JF - Resuscitation
M1 - 110160
ER -