# Thaimine as an adjunct metabolic resuscitator in cardiac arrest

> **NIH NIH K24** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $121,238

## Abstract

ABSTRACT
There are currently no medicinal interventions demonstrated to consistently improve the low survival rate
and high incidence of organ injury after out-of-hospital cardiac arrest (OHCA). Among those who initially
survive OHCA, death from arrest-related injury to organs remains frustratingly high, and other-organ injuries
are common and often debilitating among OHCA arrest patients who survive to discharge.[1] While cerebral
injury is the most lethal[2] and most prevalent organ injury, acute kidney injury (AKI) is also common and is
associated with mortality and adverse outcomes such as the need for dialysis[3,4]. Our group is currently
engaged in a randomized trial to test if thiamine (vitamin B1) protects the brain after cardiac arrest by
improving aerobic metabolism reflected in the reduction of lactic acidosis. However, ongoing research
conducted by our group and others has raised new and equally important questions. With this K-24 proposal,
we plan to address two of these questions by adding new sub-studies to this trial. The first sub-study tests
the hypothesis that thiamine protects not just the brain but also the kidney after cardiac arrest, while
the second sub-study tests the hypothesis that cardiac arrest patients have abnormally low pools of
a-lipoic acid (LA), another critical mediator of aerobic metabolism, which may place a cap on the
efficacy of thiamine therapy. The rationale for the first sub-study is based on recent evidence linking
decreased aerobic metabolism in the kidney to renal failure in critical illnesses,[5,6] the stimulatory effect of
thiamine on aerobic metabolism, and our randomized trial in sepsis showing that thiamine protected kidney
function.[7] The second sub-study is based on our preliminary data suggesting that thiamine may not fully
restore cellular oxygen consumption after cardiac arrest. Because aerobic glucose metabolism requires both
lipoic acid and thiamine as cofactors for two key enzymes, even subacute lipoic acid deficiencies may place
a cap on the efficacy of thiamine as a metabolic resuscitator. Experimental provision of LA has been shown
to protect against ischaemic brain and kidney injury; these findings contribute to the rationale for examining
LA in the context of our existing trial. Together, these studies will advance thiamine as a potential post-arrest
intervention for AKI and deepen our understanding of the relationship of other key metabolic components in
critical illness, while also providing an excellent platform to mentor future patient-oriented researchers. This
award will provide an established and highly productive clinical researcher and mentor with both project and
mentoring support and allow continued expansion of his outstanding translational research training program
in the Center for Resuscitation Science (CRS) at BIDMC. The breadth of experiments in the scientific portion
of the proposal (clinical trial design/execution and patient-based laboratory work) along with the ...

## Key facts

- **NIH application ID:** 9976798
- **Project number:** 2K24HL127101-06
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Michael William Donnino
- **Activity code:** K24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $121,238
- **Award type:** 2
- **Project period:** 2015-09-09 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976798

## Citation

> US National Institutes of Health, RePORTER application 9976798, Thaimine as an adjunct metabolic resuscitator in cardiac arrest (2K24HL127101-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9976798. Licensed CC0.

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