The Thiamine Administration After Cardiac Surgery Trial

Study Overview
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Brief Summary
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Thiamine (Vitamin B1) is essential for cell function and as a co-factor of the enzyme Pyruvate Dehydrogenase to initiate the Krebs cycle and thus the aerobic metabolism of glucose. We hypothesize that thiamine supplementation improves the clearance of lactate in the first 24 hours after cardiac surgery with extracorporeal circulation in patients with high lactate concentration.

Detailed Description
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Thiamine (Vitamin B1) is essential for cell function and as a co-factor of the enzyme Pyruvate Dehydrogenase to initiate the Krebs cycle and thus the aerobic metabolism of glucose. Thiamine deficiency, can be caused by alcoholism or bariatric surgery and is associated with severe complications such as Wernicke's encephalopathy or Beri-Beri syndrome. Thiamine deficiency can also be the cause for an increase in lactate levels due to the transformation of pyruvate to lactate. An increase in lactate levels is associated with a worse prognostic. A decrease is, on the contrary, associated with an improved prognostic, during CPR and also after cardiac arrest. Recently, studies have shown that thiamine deficiency is underdiagnosed in ICU patients. On top of this, extra-corporeal circulation can worsen this deficiency. This could explain why certain on-pump cardiac surgery patients have increased lactate levels post-operatively, despite optimal blood pressure, cardiac output, diuresis, peripheral perfusion Donnino et al have shown that in a sepsis context thiamine administration improved lactate clearance during the first 24 hours of ICU admission and improved mortality rates at 28 days post-ICU admission. Therefore, the hypothesis of this study is that thiamine supplementation improves the clearance of lactate in the first 24 hours after cardiac surgery with extracorporeal circulation in patients with high lactate concentration.

Official Title
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The Thiamine Administration After Cardiac Surgery Trial

Conditions
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Lactate Blood Increase, Thiamine Deficiency

Intervention / Treatment
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* Drug: Thiamine 500 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients scheduled for elective cardiac surgery with extra-corporeal circulation in the CHU de Charleroi between November 2020 and December 2021. Written informed consent will be obtained from each patient/ family member participating in the study. Exclusion Criteria: Patients already supplemented with vitamins Patients with an allergy to thiamine Patients who are priorly treated with linezolide, antiretrovirals and/or metformin treatment within 48 hours preoperatively Patients with mitochondrial disorders Patients with Child Pugh C cirrhosis Patients with a history of epilepsy with tonic-clonic movements postoperatively. Pregnant patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a monocentric randomized, controlled, double blind study in patients undergoing elective cardiac surgery with extra corporal circulation. Anesthesia management of these patients is standardised in terms of volume-controlled ventilation, fluid and inotropes management. Randomization of 100 patients for the administration, of a solution of 500 mg of Thiamine Hydrocloride in a solution of 100 ml of NaCl 0.9% versus a solution of 100 ml of NaCl 0.9% alone in adult patients (≥ 18 years-old) with a lactate ≥ 2 mmol / L in the first 6 hours of ICU admission.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thiamine<br>Patients in this arm will receive a solution of 500 mg of Thiamine Hydrocloride in a solution of 100 ml of NaCl 0.9%. | Drug: Thiamine 500 MG<br>* A solution of 500 mg of Thiamine Hydrocloride in a solution of 100 ml of NaCl 0.9% will be administered post-cardiac surgery in patients with lactate levels ≥ 2 mmol / L in the first 6 hours post-ICU admission.<br>* Other names: Thiamine;|
| Placebo Comparator: Placebo<br>Patients in this arm will receive a solution of 100 ml of NaCl 0.9% alone. | Drug: Placebo<br>* 100 ml of NaCl 0.9% will be administered in the placebo group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate | Lactate level will be specifically be measured 24h post-ICU admission to evaluate the effect of thiamine versus placebo. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid balance | The influence of thiamine/placebo on the use of volume expansion during ICU stay will also be evaluated | 48 hours | 
| Inotropes | The influence of thiamine: placebo on the use of inotropes during ICU stay will also be evaluated | 48 hours | 
| Mechanical ventilation | The influence of thiamine/ placebo on extubation time will also be evaluated. | 48 hours | 
| Length of ICU stay | The influence of thiamine/ placebo on ICU discharge will also be evaluated. | 5 days | 
| Length of hospital stay | The influence of thiamine/ placebo on hospital discharge will also be evaluated. | 30 days |