Lewis R. Goldfrank, MD

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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
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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 196585297-304.
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The Role of Pyruvate in Intermediary Metabolism
Diet Glucose Glycogen G
lucose Pyruvate Lactate
NADH NAD
Glycolysis
Pyruvate Dehydrogenase Thiamine
Acetyl CoA
TCA Cycle
Fatty Acid Synthesis
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Essential Enzymatic Processes Entry into
Krebs pyruvate dehydrogenase complex Krebs
Cycle ? ketoglutarate dehydrogenase Pentose
phosphate pathway transketolase
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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
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Coronal section of midbrain, pons and medulla
from Wernickes encephalopathy. Hemorrhages in
the nuclei around the aqueduct and fourth
ventricle. Atrophy mammillary bodies.
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Predisposition for Thiamine
Deficiency ? Ethanol ? Genetic
cocarboxylase deficiency ? Starvation ?
Anorexia nervosa ? Fad diets ? Hyperemesis
gravidarum
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? AIDS (Metab Brain Dis 19916207) ?
Prolonged administration IV fluids ? Thiamine
deficient parenteral nutrition ? The elderly
(Acad Emerg Med 200071156.) ? Renal
failure (Hemodialysis) ? Congestive Heart
Failure (furosemide) (Am J Med 199598485.)
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Clinical Manifestations Thiamine
Deficiency Early ? Anorexia ? Weight
loss ? Irritability Late ? High output
congestive heart failure (Beriberi) ? Chronic
sensory and motor peripheral polyneuritis
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Wernickes Encephalopathy (1881) ? Acute
neuropsychiatric syndrome ? Ophthalmoplegia ?
Altered mental status ? Ataxia ? classic
triad (16) therefore a clinical
diagnosis Korsakoffs Psychosis (1887) ?
Anterograde and ? Retrograde
amnesia ? Confabulation ? Develop after
Wernickes established
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Ophthalmoplegia Bilateral ptosis (L gt R) Palsy
of upward conjugate gaze. Day 3 Ptosis
has disappeared. Gaze palsy has improved.
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Ophthalmologic Findings ? Horizontal
nystagmus (85) ? Bilateral VI nerve palsy
(54) ? Conjugate gaze palsy (45)
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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.
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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.
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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
1981200359-375.
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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 1981150301.
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Does Glucose Loading Precipitate Acute Wernickes
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 1981150301
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When Should Thiamine Be Given? ? Before
glucose? ? After glucose? ? With glucose?
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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 198918857.
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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