MEDizzy - A 52-year-old man presents to the emergency department with

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Combined Neurology XII

A 52-year-old man presents to the emergency department with altered mental status and somnolence. He smells strongly of alcohol and his blood alcohol level confirms your suspicion of intoxication. Two days after admitting the patient you begin to notice new-onset tremors, tachycardia, and hypertension. There is no history of epilepsy. What is the next most important medication to add for this patient, assuming initial standard therapy has been started?

ExplanationC. This patient has suspected alcohol intoxication. Symptoms include confusion, somnolence, ataxia, dysarthria, hypotension (later hypertension), impaired judgment, and tachycardia. When this is suspected, intravenous thiamine has been classically recommended, and should be given prior to intravenous glucose administration to avoid precipitation of Wernicke’s encephalopathy due to acute thiamine deficiency. However, more recent literature raises questions regarding the validity of this practice. Thiamine is converted to thiamine pyrophosphate, which acts as a cofactor in several metabolic pathways necessary in energy metabolism. When there is a high metabolic demand (such as after a glucose load) in the setting of thiamine deficiency, cellular damage occurs and Wernicke’s encephalopathy may result. Wernicke’s encephalopathy is characterized by confusion/mental status changes, ataxia, ophthalmoplegia, and nystagmus. The chronic phase of Wernicke’s encephalopathy, known as Korsakoff syndrome, is associated with anterograde amnesia, although there are components also of retrograde amnesia. MRI findings in Wernicke’s encephalopathy may include petechial hemorrhages classically in the mammillary bodies, but also in hypothalamus, medial thalami, and periaqueductal gray matter, sometimes even extending into the medulla, with atrophy seen in chronic stages. Acute thiamine deficiency does not typically lead to changes in the caudate nucleus. Alcohol and other sedative-hypnotic drugs affect not only the basic structures of the reward circuit but also several other structures that use GABA as a neurotransmitter. GABA is one of the most widespread neurotransmitters in several parts of the brain, including the cortex, the cerebellum, hippocampus, amygdala, and superior and inferior colliculi. Alcohol exerts its effects by stimulation of the GABAA receptor, similar to the mechanism of action of benzodiazepines. This is why benzodiazepines are used to prevent withdrawal symptoms. Alcohol also inhibits glutamate induced excitation, which leads to additive CNS-depressant effects. Chronic alcohol use has detrimental multisystemic effects. Alcohol withdrawal can be quite severe and can even lead to death if not treated appropriately. Minor withdrawal symptoms begin within 6 to 36 hours from the last drink and include headache, tremors, diaphoresis, palpitations, insomnia, gastrointestinal upset, diarrhea, anorexia, agitation, and anxiety. Mentation is preserved during this period. Seizures can occur generally 6 to 48 hours after the last drink. Alcoholic hallucinosis begins at 12 to 48 hours and includes hallucinations (mostly visual but can also be auditory and tactile), intact orientation, and stable vital signs. Delirium tremens occurs at 48 to 96 hours if adequate prophylaxis is not initiated and is characterized by delirium, hallucinations, disorientation, agitation, encephalopathy, hypertension, tachycardia, arrhythmias, low-grade fever, and diaphoresis. In severe cases, delirium tremens can be fatal. β-Blockers and calcium channel blockers can be used for hypertension and tachycardia, although these will merely mask symptoms. Use of phenytoin or other anticonvulsants is appropriate in those with seizures and pre-existing epilepsy. This history is not present in the patient described, and antiepileptic agents are not indicated in this case. Benzodiazepines such as lorazepam should be given as scheduled doses to prevent withdrawal symptoms (including seizures), and these are the most important medications to add in this setting. Alcohol withdrawal symptoms often occur in unrecognized alcoholic patients who are admitted for surgeries or other reasons. Zolpidem is a nonbenzodiazepine hypnotic used to treat insomnia, and not indicated in this setting.