Thiamine therapy

Wernicke-Korsakoff syndrome is a relatively uncommon but important entity characterized by paralysis of the external eye muscles, ataxia, and a confused state that can progress to coma and death. It is associated with thiamin deficiency but is rarely seen in the absence of alcoholism. Because of the importance of thiamine in this pathologic condition and the absence of toxicity associated with thiamine administration, all patients suspected of having Wernicke-Korsakoff syndrome (including virtually all patients who present to the emergency department with altered consciousness, seizures, or both) should receive thiamine therapy. Often, the ocular signs, ataxia, and confusion improve promptly upon administration of thiamine. However, most patients are left with a chronic disabling memory disorder known as Korsakoff s psychosis. 

The major objective of drug therapy in the alcohol withdrawal period is prevention of seizures, delirium, and arrhythmias. Potassium, magnesium, and phosphate balance should be restored as rapidly as is consistent with renal function. Thiamine therapy is initiated in all cases. Persons in mild alcohol withdrawal do not need any other pharmacologic assistance. 

Thiamin therapy for alcoholics may involve a single injection oflO mg thiamin or 50 mg oral thiamin propyl disulfide. The latter compound is a fat-soluble version of thiamin that permits absorption of the vitamin where alcohol-induced damage would prevent efficient absorption of thiamin itself. Thiamin pnopyldisuT fide is converted in the body to thiamin. 

Karachahas, N., et al., 2005. High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats. Ann N Y Acad Sci. 1043,777-783. 

Following thiamine therapy in the acute state, one may obtain a dramatic response, which essentially confirms the diagnosis (Squirrell, 2004). Improvement in ophthalmoplegia is often the first sign of treatment benefit and may occur within hours (Koontz et al, 2004 Doherty et al, 2002). Ataxia may take days to weeks but 25% of cases may not improve at all. Residual peripheral neuropathy is also not... 

Babaei-Jadidi, R., Karachalias, N., Kupich, C., Ahmed, N., and Thornalley, P.J., 2004. High-dose thiamine therapy counters dyslipidaemia in strepto-zotocin-induced diabetic rats. Diabetologia. 47 2235-2246. 

Alcoholism. Alcoholics make up abrout 10% of the first admissions to psychiatric wards. They possess some of the same symptoms noted in thiamin deficiency, and indeed respond to thiamin therapy. Often Korsakoff s syndrome— confusion, confabulation, fear, impaired learning, delirium— is associated with alcoholism. Vitamin therapy helps to restore the individual s attentiveness, alertness, and responsiveness. 

The normal values for thiamine in human blood vary from 25-80 mpg/ml (average of 27 cases), from 110-370 mfig/ml in urine (27 cases), and from 13-17 mpg/ml in cerebrospinal fluid (45 cases). These specimens were obtained from normal subjects, receiving no vitamin therapy and in the fasting state, to eliminate dietary influences. The... 

Individuals on long-term diuretic therapy may also experience elevated levels of homocysteine, an amino acid regulated by folate. High homocysteine levels increase the risk of heart disease. Thiamin, or vitamin Bj, depletion is another possible side effect of loop diuretics. Individuals with thiamin deficiencies are at risk for fatigue, heart enlargement, muscle cramps, heart rate irregularities, and impaired mental function. 

After documenting a serum vitamin B12 deficiency, the patient should receive 300 mg oral thiamine each week and 1,000 g intramuscular hydroxocobalamin each week for 10 weeks.The sooner this therapy begins, the better the prognosis. The hydroxocobalamin fc>rm of vitamin B12 appears to be more effective than cyanocobalamin. In terms of recovery from the amblyopia, cessation of smoking or drinking does not appear to produce remission unless the patient concurrently improves their diet.Thus it is unnecessary and, in practice, difficult to persuade patients who are habitual abusers of tobacco and alcohol to stop the use of such agents. Improvement of dietary status seems to be the most important factor in recovery. 

DT s) commonly receive intravenous thiamine as part of their in-hospital therapy. 

Yip SF, Yeung YM, Tsui EY. Severe neurotoxicity following arsenic therapy for acute promyelocytic leukemia potentiation by thiamine deficiency. Blood 2002 99(9) 3481-2. 

In addition to discontinuation of the NRTT, L-car-nitine, riboflavin, and thiamine have been used in isolated reports but with unclear fherapeutic role [106, 111-113] Many of these patients have been treated with high-dose intravenous sodium bicarbonate. Hemodialysis [114] and continuous venovenous hemodiafiltra-tion [85] have been used to reduce the lactic acidosis, even in the absence of significant kidney injury. Lactic acidosis transiently and modestly improved after administration of dichloroacetate in one report [99]. The benefit of any of these therapies remains unclear. 

Thiamin deficiency in alcoholics may be caused by decreased intake, reduced absorption, and impaired ability to use ihe absorbed vitamin. The ataxia and ocular symptoms associated with the deficiency in alcoholics are known as Wernicke s disease. Vitamin therapy can provide relief from nystagmus within a few hours of treatment and from ataxia within several weeks. The treatment of alcoholics also involves the supply of other nutrients lacking in the diet, such as folate, vitamin B12, and protein. Left imtreated, patients suffering from Wernicke s disease continue to develop Korsakoff s psychosis, which involves amnesia and confusion. Only about 25% of patients with Korsakoff s psychosis can be completely cured by thiamin treatment, which must be continued for a few weeks or months. The two conditions just described constitute the Wemicke-Korsakoff syndrome. The S5mdrome was named after two researchers. Karl Wernicke, a German, noted impaired or paralyzed eye movements and imstable walking and disorientation in his patients, most of whom were alcoholics. Polyneuropathy, a weakness of the hands, calves, and feet, was also noted. Sergei Korsakoff, a Russian, observed amnesia and confusion and an inability to learn new names or tasks in alcoholic patients. 

The mainstay of medical treatment of patients with ethanol toxicity is supportive care. In general, a conservative approach is recommended for ethanol intoxication. Supportive therapy for overdose may include treatment for respiratory depression, hypotension, and altered glucose or thiamine levels. If the ingestion occurred within one hour of presentation, placing a nasogastric tube and evacuating the stomach contents can prove helpful. In patients with chronic ethanol abuse, therapy may include administration of thiamine to prevent neurologic injury. The administration of medications to cause emesis is not recommended because of the rapid onset of CNS depression as well as aspiration risks. 

Dose for deficiency Thiamine 30-60 mg/d Riboflavin 5-25 mg/d Prophylactic 3 mg/d Nicotinic acid or niacin Prevention 5-20 mg/d Deficit 50-100 mg/d Pellagra 300-500 mg in three divided doses Hyperlipidemia 1-2 g/d in three divided doses Pyridoxine 25-100 mg/d Isoniazid therapy prophylaxis 25-20 mg/d Peripheral neuritis 50-200 mg/d... 

Dietary supplements such as thiamine, calcium, magnesium, omega-3 fatty acids, and herbal products have been reported to be effective in the treatment of both premenstrual and menstrual pain syndromes, but few have been evaluated for the treatment of dysmenorrhea. Other modes of therapy for menstrual pain include biofeedback, transcutaneous electrical nerve stimulation, spinal manipulation, and application of local heat. Acupuncture has been... 

Vitamin status also may be affected by drugs (Table 135-15). For example, sulfasalazine therapy has been noted to cause a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamin concentrations. Furthermore, some drug therapy outcomes may be affected by vitamin intake. The ingestion of megadoses of folic acid may decrease methotrexate s therapeutic effect, whereas changes in an individual s usual vitamin K intake may cause variability in warfarin s anticoagulation effects. 

Thiamin Deficiency and T)ependency. Merck Manml of Diagnosis and Therapy. Available from . 

Contraindications Thiamine patients with renal dysfunction Riboflavin patients with renal dysfunction Niacin or nicotinic acid hypersensitivity to niacin or tartrazine active peptic ulcer, severe hypotension, hepatic dysfunction, arterial hemorrhaging Caution diabetes mellitus, gallbladder disease, gout, history of jaundice or Uver disease. Pyridoxine IV therapy in cardiac patients Caution megadosage in pregnancy... 

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