Emergency management for patients with suspected Wernicke's encephalopathy
Parenteral administration of high-dose thiamine is the required treatment for all patients with suspected Wernicke's encephalopathy.[1]Galvin R, Bråthen G, Ivashynka A, et al. Guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408-18.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03153.x/full
http://www.ncbi.nlm.nih.gov/pubmed/20642790?tool=bestpractice.com
[23]Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007 May;6(5):442-55.
http://www.ncbi.nlm.nih.gov/pubmed/17434099?tool=bestpractice.com
However, given the lack of quality evidence and global consensus for dosing, preparation, and timing, there is often significant variability in thiamine administration in emergency treatment.[1]Galvin R, Bråthen G, Ivashynka A, et al. Guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408-18.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03153.x/full
http://www.ncbi.nlm.nih.gov/pubmed/20642790?tool=bestpractice.com
[69]Cantu-Weinstein A, Branning R, Alamir M, et al. Diagnosis and treatment of Wernicke's encephalopathy: a systematic literature review. Gen Hosp Psychiatry. 2024 Mar-Apr;87:48-59.
http://www.ncbi.nlm.nih.gov/pubmed/38306946?tool=bestpractice.com
[80]Novo-Veleiro I, Mateos-Díaz AM, Rosón-Hernández B, et al. Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: a multicenter retrospective study. Drug Alcohol Depend. 2023 Nov 1;252:110961.
https://www.sciencedirect.com/science/article/pii/S0376871623011997?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/37748425?tool=bestpractice.com
[81]Day GS, Ladak S, Curley K, et al. Thiamine prescribing practices within university-affiliated hospitals: a multicenter retrospective review. J Hosp Med. 2015 Apr;10(4):246-53.
http://www.ncbi.nlm.nih.gov/pubmed/25652810?tool=bestpractice.com
In the absence of randomised controlled trial data affirming a specific dose, high doses of thiamine are favoured given the favourable risk-benefit ratio.[1]Galvin R, Bråthen G, Ivashynka A, et al. Guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408-18.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03153.x/full
http://www.ncbi.nlm.nih.gov/pubmed/20642790?tool=bestpractice.com
[82]Thomson A, Guerrini I, Marshall EJ. Incidence of adverse reactions to parenteral thiamine in the treatment of Wernicke's encephalopathy, and recommendations. Alcohol Alcohol. 2019 Dec 1;54(6):609-14.
https://academic.oup.com/alcalc/article/54/6/609/5576058
http://www.ncbi.nlm.nih.gov/pubmed/31565743?tool=bestpractice.com
Treatment duration is guided by clinical response. Ophthalmoplegia is likely to be the first sign to respond following thiamine repletion, with complete recovery after a few hours except for a residual fine horizontal nystagmus in up to 60% of patients.[17]Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff syndrome: a clinical and pathological study of 245 patients, 82 with post-mortem examinations. Contemp Neurol Ser. 1971;7:1-206.
http://www.ncbi.nlm.nih.gov/pubmed/5162155?tool=bestpractice.com
Ataxia may resolve over several days but can be incomplete. Improvement in mental status often takes several weeks to be observed. The European Federation of Neurological Societies advise that urgent parenteral administration of thiamine should be continued until there is no further improvement in signs and symptoms. However, the UK National Institute of Health and Care Excellence (NICE) recommends that treatment be continued for a minimum of 5 days, unless Wernicke's encephalopathy is excluded.[1]Galvin R, Bråthen G, Ivashynka A, et al. Guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408-18.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03153.x/full
http://www.ncbi.nlm.nih.gov/pubmed/20642790?tool=bestpractice.com
[66]National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis and management of physical complications. Apr 2017 [internet publication].
https://www.nice.org.uk/guidance/cg100
Alongside thiamine replacement, nutritional deficits should be corrected in patients with alcohol-use disorders and those with other risk factors for Wernicke's encephalopathy.[80]Novo-Veleiro I, Mateos-Díaz AM, Rosón-Hernández B, et al. Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: a multicenter retrospective study. Drug Alcohol Depend. 2023 Nov 1;252:110961.
https://www.sciencedirect.com/science/article/pii/S0376871623011997?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/37748425?tool=bestpractice.com
[83]Flannery AH, Adkins DA, Cook AM. Unpeeling the evidence for the banana bag: evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med. 2016 Aug;44(8):1545-52.
http://www.ncbi.nlm.nih.gov/pubmed/27002274?tool=bestpractice.com
[84]Jophlin L, Liu TY, McClain CJ. Nutritional deficiencies in alcohol use disorder/alcohol-associated liver disease. Curr Opin Gastroenterol. 2024 Mar 1;40(2):112-7.
http://www.ncbi.nlm.nih.gov/pubmed/38193343?tool=bestpractice.com
Magnesium deficiency often coexists alongside thiamine deficiency and its correction is critical given it is a cofactor required for normal functioning of several thiamine-dependent enzymes.[48]Ott M, Werneke U. Wernicke's encephalopathy - from basic science to clinical practice. part 1: understanding the role of thiamine. Ther Adv Psychopharmacol. 2020;10:2045125320978106.
https://journals.sagepub.com/doi/10.1177/2045125320978106
http://www.ncbi.nlm.nih.gov/pubmed/33447357?tool=bestpractice.com
Supplementation with water-soluble vitamins, especially niacin (vitamin B3) and pyridoxine (vitamin B6), is also recommended as patients with Wernicke's encephalopathy are often deficient in these vitamins.[23]Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007 May;6(5):442-55.
http://www.ncbi.nlm.nih.gov/pubmed/17434099?tool=bestpractice.com
The most common adverse effect associated with parenteral administration of thiamine is injection site reactions, which tend to be mild and self-limited.[85]Aldhaeefi M, McLaughlin K, Goodberlet M, et al. Evaluation of the safety of 500 mg intravenous push thiamine at a tertiary academic medical center. Sci Prog. 2022 Apr-Jun;105(2):368504221096539.
https://journals.sagepub.com/doi/10.1177/00368504221096539
http://www.ncbi.nlm.nih.gov/pubmed/35491726?tool=bestpractice.com
Although rare, anaphylaxis has been observed following parenteral administration of thiamine.[82]Thomson A, Guerrini I, Marshall EJ. Incidence of adverse reactions to parenteral thiamine in the treatment of Wernicke's encephalopathy, and recommendations. Alcohol Alcohol. 2019 Dec 1;54(6):609-14.
https://academic.oup.com/alcalc/article/54/6/609/5576058
http://www.ncbi.nlm.nih.gov/pubmed/31565743?tool=bestpractice.com
[85]Aldhaeefi M, McLaughlin K, Goodberlet M, et al. Evaluation of the safety of 500 mg intravenous push thiamine at a tertiary academic medical center. Sci Prog. 2022 Apr-Jun;105(2):368504221096539.
https://journals.sagepub.com/doi/10.1177/00368504221096539
http://www.ncbi.nlm.nih.gov/pubmed/35491726?tool=bestpractice.com
[86]Juel J, Pareek M, Langfrits CS, et al. Anaphylactic shock and cardiac arrest caused by thiamine infusion. BMJ Case Rep. 2013 Jul 12;2013:bcr2013009648.
http://www.ncbi.nlm.nih.gov/pubmed/23853017?tool=bestpractice.com
Patients should be monitored for severe adverse reactions or anaphylaxis and administration of thiamine should be immediately stopped where noted.
Some guidance suggests that thiamine must be administered before any glucose infusion as intravenous glucose may precipitate Wernicke's encephalopathy in thiamine-deficient individuals.[1]Galvin R, Bråthen G, Ivashynka A, et al. Guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408-18.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03153.x/full
http://www.ncbi.nlm.nih.gov/pubmed/20642790?tool=bestpractice.com
[23]Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007 May;6(5):442-55.
http://www.ncbi.nlm.nih.gov/pubmed/17434099?tool=bestpractice.com
However, there is a lack of consensus regarding this approach and little evidence to suggest that dextrose administration should be delayed if it is required.[87]Schabelman E, Kuo D. Glucose before thiamine for Wernicke encephalopathy: a literature review. J Emerg Med. 2012 Apr;42(4):488-94.
http://www.ncbi.nlm.nih.gov/pubmed/22104258?tool=bestpractice.com
If the patient is acutely symptomatic from hypoglycaemia, parenteral thiamine should be administered concurrently with (or as soon as possible following) glucose-containing intravenous fluids.[64]American Society of Addiction Medicine. The ASAM clinical practice guideline on alcohol withdrawal management. J Addict Med. 2020 May/Jun;14(3s suppl 1):1-72.
https://journals.lww.com/journaladdictionmedicine/fulltext/2020/06001/the_asam_clinical_practice_guideline_on_alcohol.1.aspx
http://www.ncbi.nlm.nih.gov/pubmed/32511109?tool=bestpractice.com