Cardiac Arrest, Lactic Acidosis, Shock, Thiamin Deficiency
Conditions
Keywords
cardiac arrest, thiamine, oxygen consumption, lactate, shock
Brief summary
This study is to evaluate whether thiamine can increase oxygen consumption and lower lactate in patients who initially survive an in-hospital cardiac arrest. Patients who are successfully resuscitated after an in-hospital cardiac arrest and who are on mechanical ventilation in the intensive care unit will be enrolled, and will get either thiamine or placebo. Their oxygen consumption and lactate will be measured at serial time points and compared between groups. The investigators' hypothesis is that thiamine will help restore the body's ability to metabolize oxygen normally (aerobic metabolism), leading to an increase in oxygen consumption and a decrease in lactate.
Detailed description
In-hospital cardiac arrest often leads to shock and organ failure, and low oxygen consumption and high lactate are associated with worse outcome. Thiamine is a B vitamin necessary to maintain the body's ability to use oxygen effectively, and the investigators have found that many patients are thiamine deficient after cardiac arrest. The investigators have also found that thiamine can decrease lactate in thiamine-deficient patients who are critically ill. Patients in this study will be randomized to receive either thiamine or placebo every 12 hours for 2 days after surviving an in-hospital cardiac arrest. The investigators will measure oxygen consumption continuously during that time with a monitor attached to the ventilator tubing, and will also measure lactate and other lab values at several time points.
Interventions
DRUGThiamine
Thiamine 500mg IV twice daily for 2 days
OTHERplacebo
100mL normal saline IV every 12 hours for 2 days
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patient (age \> 18 years) * Cardiac arrest occurring while admitted to the hospital, with sustained (\>20 minutes) return of spontaneous circulation (ROSC) * Mechanically ventilated at the time of enrollment * Within 12 hours of cardiac arrest event
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 * Comfort measures only or anticipated withdrawal of support within 24 hours * Severe agitation * Protected populations (pregnant women, prisoners)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lactate | 2 days | The investigators will evaluate the median lactate level over two days, compared between groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen Consumption | 2 days | The investigators will evaluate the mean oxygen consumption over two days, compared between groups |
| Pyruvate Dehydrogenase | 2 days | The investigators will evaluate the median pyruvate dehydrogenase levels over two days, compared between groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thiamine Intervention: Thiamine 500mg IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points.
Thiamine: Thiamine 500mg IV twice daily for 2 days | 18 |
| Placebo Intervention: Placebo (100mL normal saline) IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points.
placebo: 100mL normal saline IV every 12 hours for 2 days | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Already on thiamine | 1 | 0 |
| Overall Study | Clinical indication for thiamine | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Extubated prior to study drug | 0 | 1 |
| Overall Study | Transitioned to comfort-measures only prior to meeting fraction of inspired oxygen (FiO2) criteria | 1 | 0 |
Baseline characteristics
| Characteristic | Thiamine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69 years | 72.5 years | 69.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 14 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 8 Participants |
| Initial Rhythm Asystole | 1 Participants | 2 Participants | 3 Participants |
| Initial Rhythm Pulseless Electrical Activity | 13 Participants | 12 Participants | 25 Participants |
| Initial Rhythm Ventricular Fibrillation/Pulseless Ventricular Tachycardia | 4 Participants | 4 Participants | 8 Participants |
| Minutes to Return of Spontaneous Circulation (ROSC) | 11 minutes | 10.5 minutes | 11 minutes |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Other/Not Reported | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Race White | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 18 | 12 / 18 |
| other Total, other adverse events | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Lactate
The investigators will evaluate the median lactate level over two days, compared between groups
Time frame: 2 days
Population: A total of 5 patients in the thiamine group and 4 patients in placebo group missing lactate at 48-hours due to death; these values were imputed using a 20 percent increase prior to calculating the below medians and IQRs. There was one additional patient in the thiamine group whose lactate at 48-hours was not imputed as it was missing due to non-death reasons, leading to n = 17 for thiamine (instead of 18).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thiamine | Lactate | 1.9 mmol/L |
| Placebo | Lactate | 1.8 mmol/L |
p-value: 0.995% CI: [-3.1, 6.1]Mixed Models Analysis
Secondary
Oxygen Consumption
The investigators will evaluate the mean oxygen consumption over two days, compared between groups
Time frame: 2 days
Population: 22 patients had metabolic data at 48 hours, n = 11 in placebo, n = 11 in thiamine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thiamine | Oxygen Consumption | 3.83 Area under the Curve VO2 (mL/kg/min) | Standard Deviation 0.94 |
| Placebo | Oxygen Consumption | 3.48 Area under the Curve VO2 (mL/kg/min) | Standard Deviation 1.27 |
Comparison: AUC-VO2 normally distributed, used a linear regression model to compare mean AUC-VO2 between treatment groups controlling for average temperature.p-value: 0.4295% CI: [-1.29, 0.56]Regression, Linear
Secondary
Pyruvate Dehydrogenase
The investigators will evaluate the median pyruvate dehydrogenase levels over two days, compared between groups
Time frame: 2 days
Population: Only 12 patients in Thiamine and 13 patients in Placebo alive and with non-missing PDH specific activity values at 48-hours.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thiamine | Pyruvate Dehydrogenase | 1.2 mini OD unit/min/mg protein |
| Placebo | Pyruvate Dehydrogenase | 1.1 mini OD unit/min/mg protein |
p-value: 0.0795% CI: [-0.9, 0.3]Mixed Models Analysis