PACUPod is your trusted source for AI-infused evidence-based insights tailored to advanced clinical pharmacists and physicians. Each episode dives into the latest primary literature, covering medication-focused studies across emergency medicine and critical care. We break down study designs, highlight key findings, and objectively discuss clinical implications—without the hype—so you stay informed and ready to apply new evidence in practice. Whether you’re preparing for board certification or striving for excellence in patient care, PACUPod helps you make sense of the data, one study at a time.
Hey there, EM pharmacists! Welcome to PACULit's daily literature update. Today, I want to talk about an interesting paper that explores the role of thiamine as a metabolic resuscitator after in-hospital cardiac arrest. The article is titled “Thiamine as a metabolic resuscitator after in hospital cardiac arrest,” published in *Resuscitation* in May two thousand twenty-four. The authors are Berg and colleagues.
So, let's dive into the study design. This was a randomized, double-blind, placebo-controlled Phase Two trial. The population included adult patients who had experienced an in-hospital cardiac arrest within the preceding twelve hours, were mechanically ventilated, and presented with a lactate level of three millimoles per liter or greater. Randomization was stratified based on the patient's baseline lactate level: either greater than five millimoles per liter or less than or equal to five millimoles per liter. Patients received either five hundred milligrams of intravenous thiamine or a placebo every twelve hours for a total of three days. The primary outcome was lactate levels, assessed at baseline, six, twelve, twenty-four, and forty-eight hours post-arrest. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase activity, and overall mortality.
Now, for the key findings. Overall, the study found no significant difference in lactate levels between the thiamine and placebo groups. At forty-eight hours, the mean difference in lactate was one point five millimoles per liter, with a ninety-five percent confidence interval ranging from negative three point one to six point one, and a global p-value of zero point eighty-eight, which indicates no statistically significant effect. Additionally, no significant differences were observed in any of the secondary outcomes, including oxygen consumption or pyruvate dehydrogenase activity. The trial was actually halted prematurely after enrolling only thirty-six patients due to concerns raised by the Data Safety and Monitoring Board regarding potential harm observed in an unplanned subgroup analysis. In this specific unplanned subgroup analysis examining mortality, patients who were randomized with a baseline lactate level greater than five millimoles per liter had a mortality rate of ninety-two percent, which was eleven out of twelve patients, in the thiamine group compared to sixty-seven percent, or eight out of twelve patients, in the placebo group. Conversely, in patients randomized with a lactate level less than or equal to five millimoles per liter, mortality was seventeen percent, or one out of six patients, in the thiamine group versus sixty-seven percent, or four out of six patients, in the placebo group. While these differences in mortality within subgroups were not statistically significant on their own, a statistically significant interaction, with a p-value of zero point zero three, was identified between the randomization lactate level and the effect of thiamine on survival.
To put this in context, elevated lactate levels are, you know, a known marker associated with increased mortality following cardiac arrest. Thiamine, an essential cofactor for pyruvate dehydrogenase, plays a critical role in aerobic metabolism. Previous research, specifically a mouse model of cardiac arrest by Kun and colleagues in two thousand sixteen, demonstrated that thiamine administration could improve pyruvate dehydrogenase activity, leading to enhanced survival and better neurologic outcomes. There's also a related Phase Two out-of-hospital cardiac arrest trial by Berg and colleagues in two thousand twenty-four that similarly showed no overall lactate benefit but did identify an interaction with baseline lactate, also leading to early termination. In contrast, a pilot study in septic shock patients by Fisher and colleagues in two thousand sixteen suggested that thiamine could decrease lactate, especially in deficient patients. And Maitra and colleagues, in two thousand nineteen, discussed the mechanism of thiamine as a pyruvate dehydrogenase cofactor and lactate modulator in critical illness. Furthermore, Marik and colleagues, in two thousand seventeen, reported that thiamine replacement reduced mortality in septic shock patients with deficiency. So, there's been this ongoing interest in thiamine's role in metabolic resuscitation.
From a clinical perspective, these findings do not support the routine use of thiamine as a metabolic resuscitator after in-hospital cardiac arrest. As emergency medicine pharmacists, we should exercise caution, especially in patients presenting with high baseline lactate levels, until further, larger data become available. This trial really highlights the need for ongoing monitoring and future research to potentially identify specific subgroups who might benefit or, you know, unfortunately, be harmed by thiamine administration in this setting.
Now, like any study, this one has its strengths and limitations. Its strengths include being randomized, double-blind, and placebo-controlled, which are important for minimizing bias. It also used stratified randomization based on lactate, and measured multiple metabolic outcomes. However, the study's primary limitations are its small sample size of only thirty-six patients and its early termination. The significant findings related to mortality came from an unplanned subgroup analysis, which, coupled with the limited power due to the small sample size, means these findings should be interpreted with significant caution. Also, as a single-center trial, its generalizability may be limited.
In conclusion, this single-center, early-terminated trial suggests that thiamine administration after in-hospital cardiac arrest did not reduce overall lactate levels or improve metabolic outcomes. The observed interaction between baseline lactate and thiamine's effect on survival, though from an unplanned subgroup analysis and limited by small sample sizes, does suggest a complex response that clearly warrants further investigation. That wraps up today's update—thanks for listening, and see you in the next episode for more clinical pharmacy insights.