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Internal Medicine Journal 44 (2014)
H O W I T R E AT
Thiamine in the treatment of Wernicke encephalopathy in
patients with alcohol use disorders
N. Latt and G. Dore
Northern Sydney Drug and Alcohol Service, Royal North Shore Hospital, Sydney, New South Wales, Australia
Key words:
thiamine, Wernicke encephalopathy, alcohol
use disorder.
Correspondence
Noeline Latt, Northern Sydney Drug and
Alcohol Service, Level 1, 2C Herbert Street,
Royal North Shore Hospital, St Leonards, NSW
2065, Australia.
Email: noelineline.latt@health.nsw.gov.au
Received 11 November 2013; accepted 17 June
2014.
doi:10.1111/imj.12522
Introduction
Wernicke encephalopathy is an acute neuropsychiatric
emergency due to thiamine deficiency.1–4 It occurs
mainly, but not exclusively, in malnourished alcohol-
dependent patients, or as a consequence of malnutrition
from other causes (Table 1).
Wernicke encephalopathy is readily reversible if
treated with adequate doses of parenteral thiamine, pref-
erably within the first 48–72 h of the onset of symp-
toms.3,4 Failure to treat Wernicke encephalopathy with
adequate doses of thiamine may lead to death in up to
20% of cases,1,5 or progression to Korsakoff syndrome.6
Autopsy studies report a prevalence of Wernicke
encephalopathy between 0.4% and 2.8%,5,7–10 with Aus-
tralia having the highest prevalence (1.1–2.8%) in the
Western world;1,2,5,11 in patients with alcohol use disor-
ders, the prevalence increases to 12.5%.1,2,10
Korsakoff syndrome, a chronic largely irreversible
sequela of untreated, or inadequately treated Wernicke
encephalopathy, is characterised by dense anterograde
amnesia and short-term memory loss associated with
compensatory confabulation, with relative preservation
of long-term memory and other cognitive skills.
Funding: None.
Conflict of interest: None.
© 2014 The Authors
Internal Medicine Journal © 2014 Royal Australasian College of Physicians
Abstract
Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to
thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid
death or progression to Korsakoff syndrome with largely irreversible brain damage.
Wernicke Korsakoff syndrome refers to a condition where features of Wernicke
encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the
cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted
guidelines with regard to its optimal dose, mode of administration, frequency of admin-
istration or duration of treatment. Currently, different dose recommendations are being
made. We present recommendations for the assessment and treatment of Wernicke
encephalopathy based on literature review and our clinical experience.
Korsakoff syndrome is difficult to differentiate from other
causes of dementia, and 20% of cases will require long-
term institutionalised care.12 Korsakoff syndrome pre-
ceded by, or occurring concurrently with acute Wernicke
encephalopathy due to repeated episodes of clinical or
subclinical thiamine deficiency, results in Wernicke
Korsakoff syndrome.3,4,13,14
Current issues regarding diagnosis
and treatment of Wernicke
encephalopathy/Wernicke
Korsakoff syndrome
The clinical diagnosis of Wernicke encephalopathy is
missed in 75–80% of cases1–3,11 as the classical triad of gait
ataxia, eye signs (nystagmus, ophthalmoplegia) and
global confusion, as described by Karl Wernicke in 1881,
is seen in only 16–20% of patients.1,2,10 To compound the
problem, Wernicke encephalopathy is not only difficult to
differentiate from drunkenness and other causes of con-
fusion, but it also often coexists with other disorders that
cause confusion, such as alcohol withdrawal, benzodiaz-
epine withdrawal, sepsis, hypoxia, hepatic encephalopa-
thy and head injury.
We do not know how many Australians in aged care
facilities and psychiatric institutions with ‘dementia’ have
911
Latt & Dore
Table 1 Other common causes of Wernicke encephalopathy in non-
alcoholic patients
Cancer
Gastrointestinal surgery
Hyperemesis gravidarum
Starvation/fasting
Gastrointestinal disease
AIDS
Malnutrition
Dialysis and renal disease
Parenteral nutrition
Vomiting
Psychiatric disease, for example, eating disorders,
schizophrenia
Others, including infections, intoxication, thyroid disease,
iatrogenic, unbalanced diet, hypoxic encephalopathy,
diarrhoea, unknown
Adapted from Galvin et al.5 AIDS, acquired immune deficiency syndrome.
Wernicke Korsakoff syndrome/Korsakoff syndrome as a
result of undiagnosed or inadequately treated Wernicke
encephalopathy.
Table 2 illustrates the lack of universally accepted
guidelines or consensus regarding the optimal dose
regimen for thiamine. While a study found that 200 mg
thiamine I/M once daily for 2 days is superior to smaller
doses,21 the Cochrane review concluded that there is
‘insufficient evidence from randomised controlled trials
to guide clinicians in the dose, frequency, route or dura-
tion of thiamine treatment for prophylaxis against or
treatment of Wernicke Korsakoff syndrome’.22
Recommendations for assessment,
diagnosis and treatment of
Wernicke encephalopathy/Wernicke
Korsakoff syndrome
1 Have a high index of suspicion of Wernicke
encephalopathy/Wernicke Korsakoff syndrome in con-
fused patients with alcohol use disorders and/or dietary
deficiency/malnourishment or any other deficiency
states, particularly those who are living alone
2 Good history taking. Ask about the quantity, frequency,
pattern, duration of alcohol use, and time of last use;
enquire about nutrition, vomiting or diarrhoea; seek col-
laborative information from family/friends; also take a
history of benzodiazepine and other substance misuse
3 Clinical examination. Excess alcohol affects almost every
system of the body, so examine all body systems to look
for evidence of alcohol-related harm; look for signs of
poor self care and protein calorie malnutrition, for
example cheilitis, glossitis, bleeding gums, etc; note that
alcohol provides calories but does not contain
912
micronutrients or vitamins, so a malnourished alcohol-
dependent patient may not necessarily appear emaciated
18.1% Consider Wernicke encephalopathy/Wernicke
16.8% Korsakoff syndrome in patients with two of the
12.2% following:5,23,24
10.2%
7.7% • Dietary deficiency/malnourishment and a history of
5.0% alcohol use disorder, or any other deficiency states
4.2% (Table 1)
3.8 • Oculomotor abnormalities: nystagmus, ophthal-
3.8%
moplegia (gaze palsy, VI nerve palsy – diplopia)
2.4%
• Cerebellar dysfunction (gait ataxia, nystagmus)
2.4%
• Confusion (either an altered mental state or mild
0.3–3% memory impairment).
Other symptoms and signs that have been described in
Wernicke encephalopathy include irritability, tachycardia,
hypotension, hypo or hyperthermia, hearing loss, sei-
zures, spastic paraparesis, delirium, coma, acute psychosis,
miosis, anisocoria (unequal pupil size), papilloedema and
retinal haemorrhages.1,18
Wernicke encephalopathy should be included in the
differential diagnosis of all patients presenting with con-
fusion, acute delirium, acute brain syndrome or acute
ataxia.8,9,18
4 Investigations. Routine investigations: electrolytes, urea
and creatinine; full blood count; liver function tests;
Coags; thyroid function tests; blood sugar level; serum
magnesium; B12; folate; calcium; phosphate; blood
alcohol concentrations (note that raised gamma
glutamyltransferase and macrocytosis may sometimes be
useful biological markers of excess alcohol).
Other investigations. A normal computed tomography of
the brain does not rule out the diagnosis of Wernicke
encephalopathy. A brain magnetic resonance imaging
supports the diagnosis of Wernicke encephalopathy,23,24
but it is important not to delay treatment with thiamine
while waiting for the results. For the same reason, esti-
mation of thiamine, thiamine pyrophosphate levels and
low erythrocyte transketolase activity,8,9 while helpful, is
not routinely performed.
Formal neuropsychological testing determines the
degree of cognitive impairment.
Treatment of Wernicke
encephalopathy/Wernicke
Korsakoff syndrome with thiamine
replacement therapy
Thiamine is an essential cofactor for transketolase,
alpha-ketoglutarate dehydrogenase and pyruvate
dehydrogenase in the pathways of carbohydrate metabo-
lism. Chronic alcohol consumption results in thiamine
deficiency by causing inadequate nutritional intake,
© 2014 The Authors
Internal Medicine Journal © 2014 Royal Australasian College of Physicians
 Table 2 Some guidelines for thiamine replacement dosage regimen in alcohol-dependent patients with Wernicke encephalopathy/Wernicke Korsakoff syndrome (WE/WKS)
© 2014 The Authors
Prophylaxis for patients with suspected WE/WKS or at high risk of WE/WKS
(a) 100 mg I/M t.d.s for 3–5 days
(b) (UK)250 mg I/M daily for 3–5 days
(a) At least 100 mg I/M for 3–5 days
(b) 500 mg I/M daily for 3–5 days (UK)
Follow with oral thiamine as an outpatient
(a) For healthy, low-risk patients: >300 mg orally daily
(during detoxification)
Internal Medicine Journal © 2014 Royal Australasian College of Physicians
(b) For malnourished/unwell high-risk patients: 250 mg I/M
or I/V once daily for 3–5 days, or until no further
improvement is seen
(a) Low-risk patients: 100 mg orally daily
(b) Patients who drink excess alcohol:100–200 mg I/M or I/V
daily for 3 days and then 100 mg orally daily
Prophylaxis
(a) For healthy patients with good dietary intake: 100 mg
t.d.s orally
(b) For chronic drinkers with poor diet: 300 mg I/M or I/V for
3–5 days, followed by 300 mg orally for several weeks
100 mg IV or I/M on Day 1, and then 100 mg orally daily
913
Treatment of patients with a definitive diagnosis of WE/WKS
(a) At least 100 mg I/V for 5 days
(b) 500 mg t.d.s for 2 days; if no response, discontinue; if
there is response continue with 250 mg I/M or I/V for
5 days
(a) At least 100 mg t.d.s I/V for 5 days
(b) 500 mg I/V t.d.s. for 2 days; if no response discontinue; if
there is response, continue with 250 mg I/m or I/V daily for
5 days, or longer if improvement continues (UK)
200 mg I/M or I/V t.d.s (preferably I/V)
>500 mg I/M or I/V for 3–5 days, followed by 250 mg once
daily for a further 3–5 days depending on response
500 mg I/V infusion over 30 min t.d.s for 2–3 days, and then
250 mg I/M or I/V for 3–5 days, or until clinical
improvement is seen
Treatment of
250–500 mg in 100 mL saline over 30 min intravenous
infusion t.d.s for 3 days (recommended) or if, less
preferred 100 mg I/V once daily
500 mg thiamine I/V infused over 30 min t.d.s. for 2 days
and 500 mg I/V or I/M once daily for an additional 5 days
in combination with other B vitamins
500 mg I/M or I/V for 3–5 days, followed by oral or
parenteral thiamine 300 mg for 1–2 weeks
100 mg I/V or I/M daily for 3 days and then orally
Reference
Royal College of Physicians (UK)3
NB: In the UK , 250 mg thiamine is present in an
ampoule of high potency B complex vitamins
(Pabrinex)
Oxford Specialist Handbooks: Addiction Medicine (Latt
et al., 2009).15
European Federation of Neurological Sciences (EFNS)
guidelines (Galvin et al., 2010)5
British Association for Psychopharmacology (BAP)
guidelines (Lingford-Hughes et al., 2012)16
Etg Therapeutics Guidelines
(http://etg.hcn.com.au/tgc/gig/5209.htn)17
Reference
Wernicke encephalopathy, Best Practice, BMJ Evidence
Centre18
http://bestpractice.bmj.com.acs.hnc.com.au
Charness et al.8,9
www.UpToDate.com
Guidelines for the treatment of alcohol problems Australian
Department of Health and Ageing. Commonwealth of
Australia (Haber et al., 2009)19
NSW Drug and Alcohol Withdrawal Clinical Practice
Guidelines. Mental health and Drug & Alcohol, NSW
Department of Health 200720
Thiamine in Wernicke’s encephalopathy
Latt & Dore
decreased absorption and impaired utilisation.3,4,11,12,25
Thus, although the daily requirement of thiamine is only
1–2 mg, some clinicians recommend very initial high
doses of parenteral thiamine (500–1500 mg daily) to
enable diffusion of thiamine across the blood brain barrier
to restore vitamin status,18,26 prevent irreversible brain
damage,12 improve clinical signs27,28 and prevent death.1,2
Thiamine is typically administered either intramuscu-
larly or intravenously for 5 days.1,12,29,30 The three times a
day dosage regimen is based on the short half-life of
thiamine (96 min or less).12,27,28,31
Although there is currently no evidence to determine
precise doses of thiamine in the prevention or treat-
ment of Wernicke encephalopathy/Wernicke Korsakoff
syndrome, until further studies are available, the follow-
ing recommendations are based on available literature
(Table 3).
Table 3 Recommended thiamine regimen for hospital in-patients with
Wernicke encephalopathy/Wernicke Korsakoff syndrome
Treatment of patients with a Depending on the state of malnutrition:
definitive diagnosis of At least 200–500 mg t.d.s I/V for 5–7
Wernicke days, followed by oral thiamine,
encephalopathy/Wernicke 100 mg t.d.s. for 1–2 weeks, then
Korsakoff syndrome 100 mg daily thereafter
Prophylactic treatment of (I/M if I/V not possible)
patients with suspected or At least 100–200 mg t.d.s. IM or IV for
at risk of Wernicke 3–5 days, followed by oral
encephalopathy/Wernicke thiamine,100 mg t.d.s. for 1–2 weeks
Korsakoff syndrome and 100 mg daily thereafter
Precautions to be taken when
administering parenteral thiamine
1 Monitor for anaphylaxis, and have appropriate facil-
ities for resuscitation and for treating anaphylaxis readily
available, viz. adrenaline, corticosteroids.
Anaphylaxis has been reported at the rate of approxi-
mately four per one million pairs of ampoules of Pabrinex
(a pair of high potency vitamins available in the UK
containing 500 mg of thiamine (1:250000 I/V administra-
tions).12,32 (The incidence of penicillin induced anaphy-
laxis of one to four episodes per 10 000 administrations.)
I/M thiamine is reported to have a lower incidence of
anaphylactic reactions than I/V administration.15 In Aus-
tralia, where thiamine is only available as 100 mg
ampoules, the Australian Adverse Drug Reaction Advisory
Committee (ADRAC) database reports two cases of ana-
914
phylactic shock (1991, 1997) and four anaphylactoid reac-
tions (1993, 1993, 2001 and 2004) (ADRAC, pers. comm.
2012).
2 Administer intravenous thiamine slowly, preferably by
slow infusion in 100-mL normal saline over 15–30 min.
Other measures for the management
of Wernicke encephalopathy/Wernicke
Korsakoff syndrome
• Nurse confused patient 1:1 in a dimly lit, quiet room,
reassure, orientate
• Regular 2–4 hourly observations, blood pressure,
pulse, respiration (O2 saturation), temperature, neuro-
logical observations, Alcohol Withdrawal Score (AWS)20
or Clinical Institute Withdrawal Assessment for Alcohol
score (CIWA-AR).33 If AWS ≥5, or the CIWA-AR score
≥10, sedate with diazepam (taking special precautions in
patients with concurrent hypoxia, hepatic encephalopa-
thy or head injury)
• Avoid dehydration, maintain fluid and electrolyte
balance
• Exclude, and treat, any concurrent causes of acute
brain syndrome/delirium
• Always administer I/V or I/M thiamine before a
glucose drip or a carbohydrate load as a glucose load may
precipitate acute Wernicke encephalopathy
• Ensure that serum magnesium levels are normal; mag-
nesium is an essential cofactor in many thiamine-
dependent enzymes, and low levels of magnesium have
been implicated in thiamine deficiency and Wernicke
encephalopathy,34 and failure to respond to parenteral
thiamine replacement3,4,25
• Add oral multivitamin supplements.
Outpatient management
Advise all patients with alcohol dependence to strive
for a goal of total abstinence from alcohol, together
with a healthy lifestyle, exercise, and regular nutritious
meals supplemented with oral thiamine 100 mg daily
and multivitamins. In addition, patients with ongoing
cognitive impairment require memory training tech-
niques, a familiar environment, and a strong supportive
network of family, carers and various community
services.
For the 20% of patients with Korsakoff syndrome who
require long-term institutionalised care, finding appro-
priate supported accommodation is challenging and may
require a guardianship order.
© 2014 The Authors
Internal Medicine Journal © 2014 Royal Australasian College of Physicians

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