Thiamine as a Metabolic Resuscitator After Cardiac Arrest (THACA)

This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on lactate, cellular oxygen consumption, global oxygen consumption and biomarkers of neurologic injury after out-of-hospital cardiac arrest (OHCA). .

This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on lactate, cellular oxygen consumption, global oxygen consumption and biomarkers of neurologic injury after out-of-hospital cardiac arrest (OHCA). Patients who have sustained return of spontaneous circulation (ROSC) after OHCA and have a lactate of 3 or greater will be eligible for the study. Enrolled patients will be randomized to intravenous thiamine 500mg twice daily for 5 doses or matching placebo (100cc normal saline). Blood will be drawn at several time points and patients will be connected to a noninvasive monitor for continuous measurement of global oxygen consumption. The primary endpoint is change in lactate level. Secondary endpoints include change in pyruvate dehydrogenase activity, change in cellular and global oxygen consumption, change in NSE and S100 (biomarkers of neurologic injury) and CPC-E score (a score that assesses neurologic and functional impairment) at hospital discharge, 30 and 90 days.

A randomization list was prepared by an independent statistician using 1:1 randomization in blocks of four. This list will be provided to the research pharmacy, and the research pharmacy will be the only unblinded people involved with the study, and will have no patient contact or role in the analysis or other aspects of the study. Thiamine is colorless and odorless, and the 500mg dose is mixed in 100mL of normal saline. Placebo will be 100mL of normal saline and is indistinguishable in appearance from thiamine. Study team, clinical team and patient and family will all be blind to the allocation.

Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.

Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.

Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.

Absolute PDH Quantity. Please note that the measurement of Absolute PDH Quantity is done using a relative quantity assay, and that PDH is an enzyme and not a stable protein; therefore the units of measure cannot be provided in "mg" and are instead listed in "mini OD unit/min/mg protein".

Count/Proportion of Patients Scoring a Favorable CPC, defined as a score of 1 or 2. Cerebral performance category scores range from 1-5. Lower scores mean better outcomes.

SOFA score over time. SOFA score: Sequential Organ Failure Assessment Score, ranges from 0-24, higher scores mean worse outcomes.

Determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria for Stage 3 acute kidney injury/kidney failure.

Absolute Cellular Oxygen Consumption Rate: We use two measures to capture Oxygen Consumption Rate; the basal respiration and the maximal respiration.

Inclusion Criteria: Adult patient (age ≥ 18 years) Cardiac arrest occurring with sustained (> 20 minutes) return of spontaneous circulation (ROSC) Within 4.5 hours of cardiac arrest event Lactate >/=3 Exclusion Criteria: Clinical indication for thiamine administration (alcoholism, known or highly suspected deficiency) or treatment with thiamine beyond the amount found in a standard multivitamin within the last 10 days Traumatic etiology of arrest Comfort measures only or anticipated withdrawal of support within 24 hours Protected populations (pregnant women, prisoners) Known allergy to thiamine