According to the 2020 American Society of Addiction Medicine guidelines, thiamine should be administered to prevent Wernicke encephalopathy for inpatient management of alcohol withdrawal. The typical dosing regimen is intravenous (IV) or intramuscular (IM) administration of 100 mg/day for 3 to 5 days. For patients admitted to the intensive care units (ICUs), an alcohol withdrawal management protocol with close monitoring of worsening signs and symptoms and development of Wernicke encephalopathy is necessary. Based on the evidence discussed in the Flannery AH et al. article [Table 3], the guidelines highlight abandoning the “banana bag” approach and adopting administration of high-dose individual ingredients, including thiamine, magnesium sulfate, folate for patients with signs and/or symptoms consistent with Wernicke encephalopathy. [1]
A 2021 review acknowledges the variabilities in hospital protocols regarding dosing and approaches of nutrient replacement in alcohol withdrawal syndrome. The authors evaluated different international guidelines [Table 1] and provide immediate repletion strategies based on clinically evident symptoms for isolated nutritional deficiencies [Table 4]. [2]
A 2016 review discusses the common vitamin and electrolyte deficiencies in patients with alcohol use disorder (AUD). Thiamine is often given to prevent or treat Wernicke’s encephalopathy and Korsakoff syndrome, and inadequate dosing may lead to permanent structural changes to the brain and subsequent short-term memory loss. Determining the true risk of thiamine deficiency and making an accurate diagnosis of can be challenging. However, the European Federation of Neurological Societies (EFNS) indicate that two of four features must be present: nutritional deficiency, ocular abnormalities, ataxia, or mental status changes or memory impairment. Critically ill thiamine-depleted patients with significant AUD will require supplementation of thiamine above the daily required intake of 1.5 mg due to decreased dietary intake, impaired absorption, decreased conversion to its active phosphorylated form, and inadequate brain tissue supply. In patients with Wernicke encephalopathy, the commonly used 100 mg dose in the banana bag is typically ineffective, and doses of 1 g of thiamine within 24 hours may be required. [3]
The pharmacokinetics of thiamine in critically ill patients suggest that dosing intervals of every 8 to 12 hours may lead to optimal levels for blood-brain barrier transport; therefore, the typical 24-hour continuous infusion of banana bags would not allow for passive absorption of thiamine into the central nervous system (CNS). For patients with suspected or diagnosed Wernicke encephalopathy, a minimum of 200 mg of thiamine should be used to improve symptoms, as suggested by a randomized trial. Royal College of Physicians recommends > 500 mg of thiamine QD or BID for 3 to 5 days for prevention or treatment, while the EFNS recommends 200 mg TID in suspected or manifested Wernicke encephalopathy. The overall anaphylactic reaction associated with IV thiamine is relatively low, and continuous infusion instead of IV injection may further decrease the risk. Overall, the authors suggest taking thiamine out of banana bags and administering 200 to 500 mg every 8 hours for ≥ 72 hours or until WE is ruled out. [3]
Folate deficiencies may lead to megaloblastic anemia and neurologic sequelae of alcohol withdrawal, including confusion, sleep disturbances, depression, and psychosis, in addition to an increased risk for seizures caused by hyperhomocysteinemia. Patients with alcohol use disorder have impaired ability to absorb folate even if dietary intake is adequate. Despite the limited evidence of folate supplementation in this scenario, the authors recommend folate supplementation be considered at a dose of 400 to 1000 μg IV for several days after admission. Due to the risk of neurotoxicity, over-supplementation (> 5 mg/day) is not recommended. Oral therapy can be given without future alcohol consumption. [3]
Patients with chronic AUD have increased magnesium elimination leading to magnesium deficiency and ineffective thiamine treatment in Wernicke encephalopathy. Hypomagnesemia associated with CNS alterations may occur due to reduced brain magnesium concentrations in chronic alcohol users. Having adequate magnesium concentrations can help reduce the risk of cardiac arrhythmias and seizures; however, there is limited evidence for the guidance of magnesium replacement. The authors recommend approximately 1 mEq/kg of magnesium in divided doses on the first day followed by 0.5 mEq/kg/day in divided doses over the next 3 days, equivalent to 4.5 g/day of magnesium sulfate for a 70-kg adult, followed by 2 to 3 g/day thereafter. [3]
At the time of this review, there was no published data investigating the efficacy or safety of multivitamin injection in patients with alcohol withdrawal. While there may still be potential benefits of IV multivitamins in AUD patients presenting with less common nutritional deficiencies such as scurvy or pellagra, the authors believe a substantial treatment effect is unlikely to occur and recommend evaluating specifically for suspected nutritional deficiencies based on symptoms and available laboratory tests instead of using low doses of vitamins and minerals provided by IV multivitamin. [3]
Based on a comparison of dextrose versus salt-containing fluids in patients with alcoholic ketoacidosis, which found acidosis to resolve quicker in patients receiving dextrose, the authors recommend using dextrose-containing fluids for the banana bag in patients who may have alcoholic ketoacidosis unless volume resuscitation and maintenance fluids are being managed with a separate IV. [3]
Thiamine deficiency in alcohol withdrawal can lead to Wernicke’s encephalopathy, an acute reversible neuropsychiatric syndrome that may progress to irreversible anterograde amnesia known as Korsakoff syndrome. The dosage of thiamine recommended depends on whether the patient is at risk for Wernicke’s encephalopathy or has an established diagnosis of Wernicke’s. Various sources recommend different doses based on prophylaxis, treatment, and alcohol status [Table 4]. [4]
Thiamine, also known as vitamin B1, is a water-soluble vitamin found in food. Glucose and chronic alcohol use cause blood thiamine levels to deplete and can increase the risk for encephalopathy and peripheral neuropathy. A dose of 100 mg/day for 3 to 4 days is recommended for patients with alcohol withdrawal syndrome (AWS) to avoid neurological complications, including encephalopathy. [5]
A systematic review analyzing the clinical management of patients in alcohol withdrawal describes the prevention of Wernicke’s encephalopathy, a neurological syndrome that occurs due to chronic thiamine deficiency. Parenteral thiamine can be given to patients with alcohol withdrawal symptoms to attain thiamine levels quicker than the oral dosage form and prevent Wernicke’s encephalopathy. Patients in alcohol withdrawal should receive at least 250 mg thiamine by parenteral route once daily for the first 3-5 days. Patients with suspected Wernicke’s encephalopathy should receive thiamine 500 mg/day for 3-5 days. Continue for a total of 2 weeks if there is clinical improvement. Thiamine is traditionally coadministered with glucose to ensure thiamine supplementation is not forgotten. Reported allergic reactions to thiamine are rare. [6]