index

HE DEPENDS ON YOU
TO SPOT THE SIGNS

Date of preparation: February 2013
UK/PAB/12/0055a
content
WE
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WE
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Thiamine deficiency
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Signs
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Incidence of signs
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Consequences
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Suspect WE
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Guidelines
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Guidelines
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NICE
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SIGN
 
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Pabrinex®
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Pabrinex®
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Oral thiamine
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Parenteral thiamine
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Pabrinex® IV
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IV optimal dosing
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Pabrinex® IM
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IM optimal dosing
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Patient algorithm
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Pabrinex® summary
 
summary

OFFER PABRINEX®
TO THOSE AT RISK
OF WE OR WITH
SUSPECTED WE 1,2

Maintain a high level of suspicion for the
possibility of WE 1


Early and adequate Pabrinex® treatment may
help prevent long-term brain injury1


Pabrinex® is recommended by NICE and SIGN1,2

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. SIGN guidelines 74. The management of harmful drinking and alcohol dependence in primary care. A national clinical guideline. September 2003, updated December 2004. Available at www.sign.ac.uk/guidelines/fulltext/74/index.html [accessed January 2013].

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Adcetris mechanism of action
we-1

THE CONSEQUENCES ARE
CLEAR EVEN WHEN THE
DIAGNOSIS ISN'T

Wernicke’s encephalopathy (WE )
results from thiamine deficiency and
can lead to irreversible brain damage1

WE is reversible if treated early1

WE is substantially underdiagnosed2

WE is likely to be more common than we think1

The common signs of WE are difficult to differentiate from drunkenness3

1. Thomson AD et al. Practical Gastroenterol 2009;33(6):21–30.

2. Galvin R et al. Eur J Neurol 2010;17(12):1408−1418.

3. Sechi G, Serra A. Lancet Neurol 2007;6(5):442–455.

4. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

we-2

WERNICKE’S ENCEPHALOPATHY (WE )
RESULTS FROM THIAMINE DEFICIENCY
AND CAN LEAD TO IRREVERSIBLE
BRAIN DAMAGE1

Adapted from Thomson et al. 2009.1

1. Thomson AD et al. Practical Gastroenterol 2009;33(6):21–30.

we-3

KEY CLINICAL SIGNS
OF WE (CLASSIC TRIAD)

1. Harper CG et al. J Neurosurg Psychiatry 1986;49:341−345.

we-4

INCIDENCE OF CLINICAL SIGNS OF
WERNICKE−KORSAKOFF SYNDROME (WKS )*

WE is substantially underdiagnosed1

Adapted from Harper et al.1986.2
* WKS is a term encompassing two disorders, Wernicke’s encephalopathy and Korsakoff’s syndrome

1. Galvin R et al. Eur J Neurol 2010;17(12):1408−1418.

2. Harper CG et al. J Neurosurg Psychiatry 1986;49:341−345.

we-5

INADEQUATE TREATMENT
CAN HAVE CATASTROPHIC
CONSEQUENCES1

“Early and adequate treatment with thiamine, by the appropriate route, can reverse the induced biochemical changes in the brain and prevent the development of structural lesions”2

Untreated WE can lead to:3
- Korsakoff’s syndrome (KS), resulting in
  permanent brain damage
- Death

85%
of patients
with WE
develop KS

UP TO
20%
of patients with
WE die

£

Up to 25% of patients
with KS need long-term
institutionalisation3

Adapted from Day et al. 2008.3

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. Thomson AD et al. Practical Gastroenterol 2009;33(6):21–30.

3. Day E et al. Cochrane Database Syst Rev 2008;(1):CD004033.

we-6

SUSPECT WE WHEN A PATIENT
IS A HARMFUL OR
DEPENDENT DRINKER1

WE is likely to be more common than we think2

~7 out of 10 patients with WE are only diagnosed at post-mortem3

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. Thomson AD et al. Practical Gastroenterol 2009;33(6):21–30.

3. Galvin R et al. Eur J Neurol 2010;17(12):1408−1418.

4. Sechi G, Serra A. Lancet Neurol 2007;6(5):442–455.

nice a


Harmful or dependent drinker?

Malnourished or at risk of malnourishment?
or
Decompensated liver disease?

Attend an emergency department?
or
Admitted to hospital with an acute
illness or injury?

Offer parenteral thiamine (Pabrinex®)
followed by oral thiamine

Acute withdrawal?
or
Before and during a planned medically
assisted alcohol withdrawal?

Offer oral thiamine

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Adapted from NICE guidelines.1

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1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

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PABRINEX® − RECOMMENDED
BY NICE1

Harmful or dependent drinker?


Malnourished or at risk of malnourishment
or
Decompensated liver disease
and in addition
Attend an emergency department
or
Admitted to hospital with an acute
illness or injury

Suspected WE ?

Offer parenteral thiamine (Pabrinex®)
followed by oral thiamine

Adapted from NICE guidelines.1

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

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Maintain a high level of suspicion for the possibility of WE,
particularly if the person is intoxicated1


Parenteral treatment should be given for a minimum
of 5 days, unless WE is excluded1


Oral thiamine treatment should follow parenteral therapy1

#

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. Pabrinex Intravenous High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

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PABRINEX® − RECOMMENDED
BY SIGN1

Detoxification may precipitate WE, which must
be treated urgently with Pabrinex®1

Any patient who presents with unexplained
neurological symptoms or signs during
detoxification should be referred for
specialist assessment1

1. SIGN guidelines 74. The management of harmful drinking and alcohol dependence in primary care. A national clinical guideline. September 2003, updated December 2004. Available at www.sign.ac.uk/guidelines/fulltext/74/index.html [accessed January 2013].

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Diarrhoea

Vomiting

Physical illness

Weight loss

Poor diet

Alcohol detoxification with features
putting them at risk of WE?


Alcohol detoxification with signs
of possible WE?*

Treat with Pabrinex® IM in the GP
surgery, A&E department, outpatient
clinic or day hospital


Treat with Pabrinex® IV or IM,
ideally in an inpatient setting

Adapted from SIGN guidelines.1
* Confusion, ataxia (especially truncal ataxia), ophthalmoplegia, nystagmus, memory disturbance, hypothermia and hypotension, or coma1
Facilities for treating anaphylactic reaction should be available whenever Pabrinex® is administered2

1. SIGN guidelines 74. The management of harmful drinking and alcohol dependence in primary care. A national clinical guideline. September 2003, updated December 2004. Available at www.sign.ac.uk/guidelines/fulltext/74/index.html [accessed January 2013].

2. Pabrinex Intramuscular High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

sign

PABRINEX® − RECOMMENDED
BY NICE
AND SIGN1,2

NICE and SIGN recommends Pabrinex® for people at high risk of WE or with suspected/acute WE 1,2


Due to the concern of long-term brain injury, NICE recommends that patients for whom there is even a low index of suspicion for WE should be treated with parenteral thiamine1


The SmPC states the only approved dosage regimen for Pabrinex®3,4

#
#

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. SIGN guidelines 74. The management of harmful drinking and alcohol dependence in primary care. A national clinical guideline. September 2003, updated December 2004. Available at www.sign.ac.uk/guidelines/fulltext/74/index.html [accessed January 2013].

3. Pabrinex Intravenous High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

4. Pabrinex Intramuscular High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

paba-1

PABRINEX® - THE CLEAR CHOICE
FOR SUSPECTED OR ACUTE WE

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rx
paba-2

ORAL THIAMINE IS INADEQUATE FOR
THE TREATMENT OF SUSPECTED WE1

Oral thiamine is poorly absorbed even in good health:2

1 IN 3 NON-MALNOURISHED
PEOPLE CAN HAVE ABSORPTION
REDUCED BY 50% WITH ALCOHOL2

In chronic alcohol misusers, malnutrition can reduce
intestinal thiamine absorption by ~70%2

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.u k/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. Thomson AD et al. Alcohol Alcohol 2002;37(6):513–521.

paba-3

CORRECTION OF WE REQUIRES HIGH BLOOD
CONCENTRATIONS OF THIAMINE, WHICH CAN
ONLY RESULT FROM PARENTERAL THERAPY1

High plasma thiamine levels provided by parenteral therapy permit
rapid diffusion across the blood-brain barrier
pab b
pab c

Adapted from Thomson et al 2002

1. Thomson AD et al. Alcohol Alcohol 2002;37(6):513-521.

pabb-1

PABRINEX® IV - OPTIMAL DOSING FOR
SUSPECTED OR ACUTE WE

Minimum 5-day treatment if WE is suspected (unless WE is excluded)1

pabb-1

Facilities for treating anaphylaxis should be available whenever Pabrinex® is administered2

1. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

2. Pabrinex Intravenous High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

pabb-2

PABRINEX® IV - OPTIMAL DOSING
FOR SUSPECTED OR ACUTE WE

Mix

2 to 3 pairs of
ampoules per dose
before infusion1

Dilute

with 50 to 100 ml
of physiological
saline or
glucose 5%1

Infuse

over 30 minutes
every 8 hours1
Minimum 5-day
treatment if WE is
suspected (unless
WE is excluded)2
pabb-1

1. Pabrinex Intravenous High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

2. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

pabb-3

PABRINEX® IM - OPTIMAL DOSING FOR
SUSPECTED OR ACUTE WE

pabb-3

Facilities for treating anaphylaxis should be available whenever Pabrinex® is administered1

1. Pabrinex Intramuscular High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

pabb-4

PABRINEX® IM - OPTIMAL DOSING
FOR SUSPECTED OR ACUTE WE

Mix

1 pair of IM ampoules per
dose before injection3

Inject

slowly high into the
gluteal muscle, 5 cm
below the iliac crest3

Offer Pabrinex® IM as part of a community detoxification programme1,2

pabb-1

1. SIGN guidelines 74. The management of harmful drinking and alcohol dependence in primary care. A national clinical guideline. September 2003, updated December 2004. Available at www.sign.ac.uk/guidelines/fulltext/74/index.html [accessed January 2013].

2. Thomson AD, Marshall EJ. Alcohol Alcohol 2006;41(2):159–167.

3. Pabrinex Intramuscular High Potency Solution for Injection, Summary of Product Characteristics; Jan 2013.

pabb-5

WHAT HAPPENS TO YOUR
A&E PATIENTS WHEN THEY
START A TREATMENT
COURSE OF PABRINEX®?

iv-pair

WHAT IS A PABRINEX® IV PAIR?

AMPOULE 1:
White stripe around ampoule


- Thiamine hydrochloride BP

- Riboflavin (as phosphate sodium BP)

- Pyridoxine hydrochloride BP

- Ascorbic acid BP

- Nicotinamide BP

- Anhydrous glucose BP

AMPOULE 2:
Black stripe around ampoule

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im-pair

WHAT IS A PABRINEX® IM PAIR?

AMPOULE 1:
Larger ampoule


- Thiamine hydrochloride BP

- Riboflavin (as phosphate sodium BP)

- Pyridoxine hydrochloride BP

- Ascorbic acid BP

- Nicotinamide BP

AMPOULE 2:
Smaller ampoule

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pabc-1

REFER ON

CARE OF THE ELDERLY

GASTROENTEROLOGY

LIVER WARD

ORTHOPAEDICS

MEDICAL ADMISSIONS UNIT

SURGERY

COMMUNITY SERVICES

OTHER

submit
CARE OF THE ELDERLY GASTROENTEROLOGY SURGERY LIVER WARD MEDICAL ADMISSIONS UNIT ORTHOPAEDICS COMMUNITY SERVICES OTHER

HAVE YOU CONSIDERED THESE FACTORS?

DOES YOUR HOSPITAL HAVE A PABRINEX® PROTOCOL IN LINE WITH THE NICE/SIGN GUIDELINES ON DOSING AND DURATION OF TREATMENT?

IN THE DEPARTMENT(S) YOU HAVE IDENTIFIED WHO WOULD BE RESPONSIBLE FOR CONTINUING THE PABRINEX® TREATMENT PLAN YOU INITIATED FOR THAT PATIENT?

IS THIS PERSON FAMILIAR WITH THE PABRINEX® PROTOCOL?

HAVE YOU RECENTLY SPOKEN WITH THIS PERSON ABOUT THE PABRINEX® PROTOCOL?

pabc-2

PABRINEX® - THE CLEAR CHOICE
FOR SUSPECTED OR ACUTE WE

Prompt therapy with thiamine may be a life-saving measure1

Correction of WE requires high blood concentrations of thiamine,
which can only result from parenteral therapy2

Oral thiamine is inadequate for the treatment of suspected WE 3

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1. Sechi G, Serra A. Lancet Neurol 2007;6(5):442–455.

2. Thomson AD et al. Alcohol Alcohol 2002;37(6):513–521.

3. NICE clinical guideline 100. Alcohol use disorders: diagnosis and clinical management of alcohol-related physical complications. June 2010. Available at www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf [accessed January 2013].

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