Glucose before Thiamine for Wernicke Encephalopathy: A Literature Review

Abstract

Background

The prevailing teaching in medical school curricula and in medical textbooks is that if thiamine deficiency is suspected, thiamine supplementation should be given before administering glucose.

Objective

We sought to evaluate the published evidence describing the commonly held belief that thiamine supplementation must be given before glucose in hypoglycemic patients to prevent Wernicke encephalopathy.

Methods

Articles were identified through computerized searches of MEDLINE and other online sources. Pertinent references were traced back to their sources and also included in the literature review. The quality and content of each article was evaluated by the authors using the American Academy of Emergency Medicine literature review guidelines.

Results

Nineteen papers were ultimately identified and evaluated. No evidence rose above the level of case report/series. There were 13 case reports/series, 4 animal studies, and 2 expert opinion articles. True clinical research about the question of whether or not a glucose load can precipitate acute onset of Wernicke encephalopathy is lacking.

Conclusions

Mounting case report evidence suggests that prolonged glucose supplementation without the addition of thiamine can be a risk factor for the development of Wernicke encephalopathy. Based on our findings, a delay in giving glucose to hypoglycemic patients cannot be recommended at this time, although prompt thiamine supplementation after or concurrent with a return to normoglycemia is recommended.

Introduction

Wernicke encephalopathy is an uncommonly recognized neurological disorder caused by prolonged thiamine (vitamin B1) deficiency. In the United States, it is most commonly seen in alcoholics, but can also be found in any malnourished state; patients with hyperemesis gravidarum, intestinal obstruction, acquired immunodeficiency syndrome, gastric bypass, and malignancies are commonly cited 1, 2, 3, 4, 5. The typical symptoms include confusion, ocular abnormalities, and ataxia. Prolonged thiamine deficiency can lead to the development of Korsakoff syndrome, characterized by permanent mental impairment with confabulation and memory deficits.

Wernicke encephalopathy was first described in 1881 by Carl Wernicke and was originally named “polioencephalitis hemorrhagica superioris” due to its appearance on autopsy (6). It took 60 years for the link to be made to nutritional deficiency by case reports and confirmed by animal models 7, 8.

Thiamine acts as a coenzyme for the decarboxylation of pyruvate to acetyl coenzyme A; this bridges anaerobic glycolysis and the Krebs cycle. Thiamine is also a coenzyme within the Krebs cycle and in the hexose monophosphate shunt (9). A lack of thiamine causes inhibition of anaerobic glycolysis, the process by which glucose is converted into usable energy in the form of adenosine triphosphate (ATP); in starvation, when glucose stores are depleted, the brain suffers most acutely as it relies almost entirely on glucose for energy and there is little thiamine available to act as cofactor for the conversion of any small amount of remaining glucose to ATP. Some damage may also be due to an accumulation in the brain of toxic intermediates, such as lactate (Figure 1) 1, 5. Alcoholics are particularly prone to this deficiency due to decreased intake of thiamine, decreased absorption from the gastrointestinal tract in the presence of alcohol, and inability to use thiamine effectively secondary to lack of magnesium (also from malnutrition) as a cofactor for the binding of thiamine to thiamine-dependent enzymes (6).

The prevailing teaching in medical school curricula and in medical textbooks is that if thiamine deficiency is suspected, thiamine supplementation should be given before administering glucose 10, 11. The theory behind this is that if a thiamine-deficient patient is given a glucose load, meager thiamine stores would rapidly be exhausted, glycolysis further limited, and Wernicke encephalopathy would promptly ensue 9, 12, 13, 14.

This is an important topic, as many alcoholics present to the emergency department with a change in mental status; this can be commonly due to alcohol intoxication, alcoholic ketoacidosis, or thiamine deficiency, as well as other non-alcohol-related causes of acute mental status change. Alcoholic ketoacidosis frequently presents with low blood glucose, and low blood glucose itself could be the cause of an acute change in mental status as the brain is starved of its main source of fuel. Many physicians would assume, due to their instruction in medical school and understanding of thiamine-deficiency pathophysiology, that patients with low blood glucose and suspicion for malnutrition should be given thiamine before glucose. However, because the risks of prolonged hypoglycemia include coma and death, we conducted a literature search to evaluate the source of this medical dogma and to investigate whether or not thiamine needs to be given before glucose in all situations to prevent precipitation or worsening of Wernicke encephalopathy.