# Thiamine As A Metabolic Resuscitator In Cardiac Arrest

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $432,500

## Abstract

Abstract
Sudden cardiac arrest is a major public health problem, afflicting over 535,000 persons in North America each
year with dismal event survival rates near 10%. There is currently no medicinal intervention demonstrated to
have a beneficial effect on post-arrest outcome with targeted temperature management arguably being the
only intervention known to potentially improve post-cardiac arrest brain injury and survival. Thus, new therapies
aimed at reducing the mortality and morbidity in post-cardiac arrest patients are essential. Thiamine is an
essential co-factor of pyruvate dehydrogenase (PDH), the enzyme responsible for the conversion of pyruvate
into acetyl-CoA and entry into the Krebs Cycle (aerobic metabolism). Previous investigators have found that
post-arrest patients exhibit “venous hyperoxia” or “luxurious perfusion” – the systemic and cerebral inhibition of
oxygen consumption despite the presence of adequate oxygen delivery. Our preliminary data confirms the
finding of depressed cellular oxygen consumption and puts forth the novel data that this depression can be
overcome with the administration of in vitro thiamine as demonstrated by improved mortality and neurological
morbidity in a mouse model of cardiac arrest. In a murine model of cardiac arrest, we found that intravenous
thiamine increased PDH activity, improved cerebral oxygen consumption, mitigated histological injury to
various areas of the brain, improved survival, and improved good neurological outcome. While our murine
model suggests thiamine may be effective independent of deficiency, we did additionally find that upwards of
44% of post-arrest patients were thiamine deficient similar to rates in septic shock. Based on these data, we
hypothesize that the administration of thiamine in post-cardiac arrest patients will mitigate lactic acidosis,
improve cellular oxygen consumption, and improve clinical outcome. To test this hypothesis, we will perform a
prospective, Phase II randomized pilot study providing thiamine versus placebo for post-cardiac arrest patients.
Our primary endpoint will be attenuation of lactic acidosis in the thiamine group as compared to the placebo
arm. Lactate serves not only as a surrogate for mortality but also as a parameter that would be directly
modified by thiamine. Our secondary endpoints will include determination of whether thiamine will improve
cellular oxygen consumption, increase PDH activity, attenuate biomarkers indicative of neurological injury, and
improve clinical endpoints of neurological injury and organ-injury. The long-term goal of this line of research is
to evaluate thiamine as an adjunctive therapy for post-cardiac arrest patients. Thiamine is safe, inexpensive,
and easily administered – thus, if our hypothesis is proven true and future research proves efficacy, adoption of
this adjunctive therapy is feasible and significant.

## Key facts

- **NIH application ID:** 10143278
- **Project number:** 5R01HL136705-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Michael William Donnino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,500
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143278

## Citation

> US National Institutes of Health, RePORTER application 10143278, Thiamine As A Metabolic Resuscitator In Cardiac Arrest (5R01HL136705-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10143278. Licensed CC0.

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