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 Thiamine Hydrochloride Track A September 15, 2003 Barcelona

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:

Diet GlucoseGlycogen GlucosePyruvateLactate Pyruvate Dehydrogenase Thiamine TCA Cycle Fatty Acid Synthesis Acetyl CoA Glycolysis The Role of Pyruvate in Intermediary Metabolism NADHNAD+

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 2 nd ed. Philadelphia, FA Davis, 1989.

Neuropsychiatric Abnormalities in 229 Cases of the Wernicke-Korsakoff Syndrome at the Time of the Initial Examination NumberPercent Stupor94 Coma21 Alcohol abstinence syndrome3616 Global confusional state12856 Disorder of memory*13157 No mental abnormality2310 Adams VA, Collin GH: The Wernicke – Korsakoff Syndrome 2 nd 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:

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 D 5 W disorientation and a 6 th 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 D 20 W infusion confusion, nystagmus, and 6 th 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