Alcohol Withdrawal, Lactic Acidosis, Magnesium Deficiency, Vitamin B1 Deficiency, Wernicke Encephalopathy
Conditions
Brief summary
Patients who suffer Alcohol Use Disorder (AUD) have a 30-80% incidence of thiamine deficiency causing Wernicke's Encephalopathy (WE). Intravenous (IV) thiamine replacement is standard practice in the treatment of alcoholic patients presenting to the Accident & Emergency (A&E) department, however routine co-supplementation with magnesium (administered IV as magnesium sulphate ), which is required as a co-factor for thiamine in some metabolic processes, e. g. on the activity of the enzyme transketolase in red blood cells, is not routine practice in the treatment of these patients. Without correction of concomitant magnesium deficiency there may be impaired utilisation of thiamine resulting in a failure to treat WE. This study is designed to determine if administration of magnesium to AUD patients affects red cell transketolasae and serum lactate concentrations by itself, or only acts to increase the effect of thiamine on the activity of this enzyme.
Detailed description
This is a 3- arm randomised, open label, controlled study in a cohort of alcoholic patients admitted through A&E. Patients will be randomised to concurrent infusion of one of the following: * Arm 1: IV thiamine * Arm 2: IV magnesium sulphate followed by delayed IV thiamine * Arm 3: IV thiamine and IV magnesium sulphate Thiamine will be administered as IV Pabrinex, a compound preparation which also contains B vitamins and vitamin C. Administration of IV Pabrinex is standard care in this patient group and magnesium sulphate is routinely co-administered at Glasgow Royal Infirmary.
Interventions
DRUGMagnesium Sulfate
Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes
DRUGPabrinex
standard treatment
Sponsors
Glasgow Royal Infirmary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a 3- arm randomised, open label, controlled study in a cohort of alcoholic patients admitted through A&E. Patients will be randomised to concurrent infusion of one of the following: * Arm 1: IV thiamine * Arm 2: IV magnesium sulphate followed by delayed IV thiamine * Arm 3: IV thiamine and IV magnesium sulphate Thiamine will be administered as IV Pabrinex, a compound preparation which also contains B vitamins and vitamin C. Administration of IV Pabrinex is standard care in this patient group and magnesium sulphate is routinely co-administered at Glasgow Royal Infirmary.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Male or non-pregnant or breastfeeding females ≥18 years of age For women of child-bearing potential a negative pregnancy test will be required prior to treatment. (Women of non-childbearing potential are defined as those defined as women who are post-menopausal or permanently sterilised (e.g. hysterectomy, tubal occlusion, bilateral salpingectomy). • Chronic alcohol dependence as confirmed by * FAST questionnaire * GMAWS scale
Exclusion criteria
* Unable to give consent * Less than 18 years of age * Chronic renal or hepatic failure/hepatic encephalopathy (investigator assessment as documented in past medical history i.e. Clinical Portal.) * Known hypersensitivity or previous allergy to any of the active substances in either trial medication, or to excipients * Severe concurrent medical condition that would prevent participation in study procedures (e.g. myasthenia gravis, clinically significant cardiac disease, or cardiac failure with severe pulmonary oedema)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Erythrocyte transketolase activity | 0 and 2 hours | this is a biochemical marker of thiamine activity measured in units per gram of haemoglobin |
| Change in serum lactate | 0 and 2 hours | Biochemical marker of metabolic dysfunction (expressed as mmol/L) |
| Change in rate of resolution of alcohol withdrawal syndrome | days | time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| lactate dehydrogenase | 0 and 2 hours | biochemical (expressed in mmol/L) |
| establish baseline micronutrient status of patients with alcohol withdrawal syndrome | o and 2 hours | biochemical |
| pre and post magnesium | 0 and 2 hours | biochemical (expressed in mmol/L) |
| pre and post red cell thiamine | 0 and 2 hours | biochemical |
Countries
United Kingdom
Outcome results
None listed