Use of Thiamine for Wernicke’s Encephalopathy in Alcoholics Presenting to the Emergency Department

By: Jacqueline Meaney, PharmD Candidate c/o 2015, University at Buffalo: School of Pharmacy and Pharmaceutical Sciences

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Chronic alcohol consumption may lead to a deficiency in thiamine (Vitamin B₁), which can lead to alcohol-induced brain damage. Since thiamine is a cofactor for essential pathways in the brain, decreased levels of thiamine in the body can interfere with brain cell function. The causes of thiamine deficiency in chronic alcoholics include inadequate nutritional intake, decreased absorption of thiamine from the gastrointestinal (GI) tract, impaired thiamine storage, and reduced thiamine phosphorylation.^1,2 Thiamine deficiency can cause serious brain disorders such as Wernicke–Korsakoff syndrome (WKS). WKS is the presence of both Wernicke’s encephalopathy (WE) and Korsakoff’s syndrome (KS). WKS presents acutely in thiamine deficiency as Wernicke’s encephalopathy, and then progresses into the chronic disorder known as Karsakoff’s syndrome.³ WE is characterized by a triad of symptoms, including ocular disturbances, mental status changes, and ataxia. Additional symptoms may include hypotension, tachycardia, hypothermia, and seizures. If left untreated, WE can be fatal.⁴ Severe or insufficiently treated cases of Wernicke’s encephaloptathy can result in Korsakoff’s syndrome, which is a chronic neurologic disorder characterized by the onset of severe memory impairment.¹ Because of the low levels of thiamine reported in 30–80% of alcoholic patients and the severity of WKS, it is important to be able to recognize and treat WE in alcoholics presenting to the emergency department (ED). Here we will review literature on the use of thiamine in alcoholics.^1,2

It is well-established that chronic alcoholics presenting with Wernicke’s encephalopathy requires immediate treatment with intravenous (IV) or intramuscular (IM)    thiamine.⁵ If WE is left untreated or is insufficiently treated with only low doses of thiamine or oral thiamine, the mortality rate may reach up to 20%.^2,6 Even though oral thiamine may be less invasive to administer, it is not sufficient for the treatment due to extremely variable absorption and poor bioavailability.² It is difficult to determine whether an alcoholic has WE based solely on signs and symptoms. As a result, it is recommended that all alcoholics presenting to the emergency department be administered parenteral thiamine, either for prevention or treatment of the disease. The  benefits of thiamine treatment in preventing the progression of WE far exceeds the risk associated with parenteral thiamine administration.^3,5,7,8

The current recommendations for the use of thiamine are based mostly on case reports and clinical experience rather than on clinical trials. A 2004 meta-analysis demonstrated that there is insufficient evidence from randomized controlled trials (RCTs) to guide practitioners in dosing, frequency or duration of thiamine treatment for prevention or treatment of WE.^9-11 Current literature suggests that 200-500mg of IV or IM thiamine be administered until symptoms resolve.¹ European and British guidelines recommend using 250mg of IM or IV thiamine three times daily for 3-5 days to avoid consequences of thiamine deficiency, which includes WE.⁴

WE is diagnosed at autopsy in 80% of cases, indicating that it is a commonly missed diagnosis in alcoholics.⁴ Since WE varies in presentation and can be easily mistaken for other disorders, and the prognosis depends on the speed at which thiamine deficiency is reversed, thiamine must be administered to all alcoholics, with or without signs of WE. Maintaining high serum levels of thiamine restores cognitive function, though the exact dosing for effective treatment is still under research.^9,12,13

SOURCES:

1. Oudman E, Van der Stigchel S, Postma A, et al. A case of chronic Wernicke’s encephalopathy: A neuropsychological study front psychiatry. Front Psychiatry. 2014; 5(1): 59. Accessed August 28, 2014.
2. Cook CCH, Hallwood PM, Thomson AD. B-vitamin deficiency and neuro-psychiatric syndromes in alcohol misuse. Alcohol Alcohol. 1998; 33(3):17-336. Accessed August 30, 2014. http://alcalc.oxfordjournals.org/content/33/4/317.long.
3. Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007; 6(3): 442–55. Accessed August 29, 2014.
4. Kopelman MD. Disorders of memory. Brain.2002; 125(7):2152–90. Accessed August 28, 2014.
5. Thomson AD, Marshall EJ. The natural history of Wernicke’s encephalopathy and Korsakoff’s psychosis. Alcohol Alcohol. 2006; 41(8):151–8. Accessed August 29, 2014.
6. Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics. 2012; 53(4):507–16. Accessed August 30^h, 2014.
7. Talbot PA. Timing of efficacy of thiamine in Wernicke’s disease in alcoholics at risk. J Correct Health Care.2011; 17(1):46-50. Accessed August 30, 2014.
8. Day E, Bentham P, Callaghan R, et al. Thiamine for Wernicke-Korsakoff syndrome in people at risk from alcohol abuse. Cochrane Database Syst Rev. 2004; 5(1):403-33. Accessed August 30, 2014.
9. Thomson AD, Marshall EJ. Time to act on the inadequate management of Wernicke’s encephalopathy in the UK. Alcohol Alcohol. 2013; 48(2):4–8. Accessed August 27, 2014.
10. Isenberg-Grzeda E, Chabon B, Nicolson SE. Prescribing thiamine to inpatients with alcohol use disorders: how well are we doing? J Addict Med. 2014; 8(3):1–5. Accessed August 30, 2014.
11. Oudman E, Wijnia JW. BNF recommendations for the treatment of Wernicke’s encephalopathy: lost in translation? Alcohol Alcohol. 2014; 49(8):118. Accessed August 27^th, 2014.
12. Kopelman MD, Thomson AD, Guerrini I, et al. The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol Alcohol. 2009; 44(5):148–54. Accessed August 30, 2014.
13. Pitel AL, Zahr NM, Jackson K, et al. Signs of preclinical Wernicke’s encephalopathy and thiamine levels as predictors of neuropsychological deficits in alcoholism without Korsakoff’s syndrome. Neuropsychopharmacology. 2011; 36(3): 580–588. Accessed August 28, 2014.