Transcript Adams VA, Collin GH: The Wernicke – Korsakoff Syndrome 2 nd ed

Thiamine
Hydrochloride
Track A
September 15, 2003
Barcelona
Lewis R. Goldfrank, MD
Professor and Chairman of Emergency Medicine
New York University Medical Center
Bellevue Hospital Center
New York University School of Medicine
Medical Director, New York City Poison Center
Recommended Dietary Thiamine
1 mg/day
0.5 mg/1000kcal
Thiamine depletion develops within 18 days in
thiamine free diet.
Normally: organ meats, yeast, eggs, green leafy
vegetables.
Poorly absorbed in the presence of ethanol.
J Nutr 1965;85:297-304.
The Role of Pyruvate in Intermediary Metabolism
Diet
Glucose
NADH
Glucose
Pyruvate
Glycogen
NAD+
Lactate
Pyruvate Dehydrogenase
Thiamine
Acetyl CoA
TCA
Cycle
Fatty Acid
Synthesis
Essential Enzymatic Processes
Entry into Krebs
pyruvate dehydrogenase complex
Krebs Cycle
 ketoglutarate dehydrogenase
Pentose phosphate pathway
transketolase
Pathophysiology

Decreased activity thiamine dependent
carbohydrate enzymes

Impaired cerebral energy metabolism

Focal lactate accumulation in addition to
tissue acidosis

Decreased production of
neurotransmitters: GABA and Acetyl
choline
Coronal section of midbrain, pons and medulla from Wernicke’s
encephalopathy. Hemorrhages in the nuclei around the aqueduct
and fourth ventricle. Atrophy mammillary bodies.
Predisposition for
Thiamine Deficiency

Ethanol

Genetic cocarboxylase deficiency

Starvation



Anorexia nervosa
Fad diets
Hyperemesis gravidarum

AIDS (Metab Brain Dis 1991;6:207)

Prolonged administration IV fluids

Thiamine – deficient parenteral nutrition

The elderly
(Acad Emerg Med 2000;7:1156.)

Renal failure (Hemodialysis)

Congestive Heart Failure (furosemide)
(Am J Med 1995;98:485.)
Clinical Manifestations
Thiamine Deficiency
Early

Anorexia

Weight loss

Irritability
Late

High output congestive heart failure (Beriberi)

Chronic sensory and motor peripheral
polyneuritis
Wernicke’s Encephalopathy (1881)
 Acute neuropsychiatric syndrome
 Ophthalmoplegia
 Altered mental status
 Ataxia

classic triad (16%) therefore a clinical diagnosis
Korsakoff’s Psychosis (1887)
 Anterograde and
 Retrograde amnesia
 Confabulation
 Develop after Wernicke’s established
Ophthalmoplegia
Bilateral ptosis (L > R)
Palsy of upward conjugate gaze.
Day 3
Ptosis has disappeared.
Gaze palsy has improved.
Ophthalmologic Findings

Horizontal nystagmus (85%)

Bilateral VI nerve palsy (54%)

Conjugate gaze palsy (45%)
Wernicke-Korsakoff Mortality
Mortality 17% in first 3 weeks without treatment
60% at several months persistent nystagmus
With treatment ocular palsies resolve in hours
Adams VA, Collin GH: The Wernicke – Korsakoff Syndrome 2nd ed.
Philadelphia, FA Davis, 1989.
Neuropsychiatric Abnormalities in 229 Cases of
the Wernicke-Korsakoff Syndrome at the Time of
the Initial Examination
Number
Percent
Stupor
9
4
Coma
2
1
Alcohol abstinence syndrome
36
16
Global confusional state
128
56
Disorder of memory*
131
57
No mental abnormality
23
10
Adams VA, Collin GH: The Wernicke – Korsakoff Syndrome 2nd ed.
Philadelphia, FA Davis, 1989.
Wet Beriberi
 High output biventricular failure
 Peripheral vasodilation
 Volume overload
 Tachycardia
 Wide pulse pressure
 Depressed left ventricular function
with decreased ejection fraction
Q J Med 1981;200:359-375.
Does Glucose Loading Precipitate
Acute Wernickes Encephalopathy
A 79-year-old chronic schizophrenic patient is
admitted with sepsis.
She is noted to be
cachectic, hypothermic, and have horizontal
nystagmus. After 2 liters of D5W disorientation
and a 6th nerve palsy develop, but respond to
thiamine.
A 45-year-old male with endstage renal disease is
started on CAPD. There is a 6 month history of
anorexia accompanied by a 20 lb weight loss.
Over 48 hours of hypertonic PD she develops
disorientation and nystagmus that respond to
thiamine.
Irish J Med Sci 1981;150:301.
Does Glucose Loading Precipitate Acute
Wernicke’s Encephalopathy?
A 36 year old male with a history of moderate
alcohol intake develops myoglobinuric renal failure
after a traffic crash. Daily hemodialysis is required.
After 5 days of D20W infusion confusion,
nystagmus, and 6th nerve palsies develop.
Symptoms resolve within 12 hours of initiation of
parenteral thiamine therapy.
Irish J. Med.Sci 1981;150:301
When Should Thiamine Be Given?
 Before glucose?
 After glucose?
 With glucose?
How Should Thiamine Be Given?
IM vs. IV?
989 Patients receives 100 mg of thiamine by
intravenous bolus.
Adverse reactions were noted in 12 (1.1%)

11 patients had minor local reactions

1 patient (0.093%) had generalized
pruritus
Wrenn KD: Ann Emerg Med 1989;18:857.
Efficacy of Thiamine

100 mg or more intravenous
(? Intramuscular) necessary for adequate
coenzyme levels

Repeat dosage 100 mg intravenous (? P0)daily
for 10 – 14 days

Folic acid facilitates thiamine absorption