As with other sedative agents, management of severe ethanol overdose requires ventilatory support in an intensive care unit (Table 117-1). Hypovolemia, acid-base or electrolyte imbalance, and abnormal temperature also require attention. Obstreperous or violent patients should not receive sedatives (including neuroleptic agents), which can push them into stupor and respiratory depression. Analeptics are also contraindicated. Hemodialysis or peritoneal dialysis can be considered for BECs above 600 mg/dL; for severe acidosis; for severely intoxicated children; and for concurrent ingestion of methanol, ethylene glycol, or other dialyzable drugs. Ethanol is often taken with other drugs, legal and illicit.

TABLE 117-1 Treatment of Acute Ethanol Intoxication

For Obstreperous or Violent Patients

Isolation, calming environment, reassurance; avoidance of sedatives

Close observation

For Stuporous or Comatose Patients

If hypoventilation is present, artificial respiration in an intensive care unit

If serum glucose is in doubt, intravenous 50% glucose with parenteral thiamine

Careful monitoring of blood pressure; correction of hypovolemia or acid-base imbalance

Consideration of hemodialysis if patient is severely acidotic, deeply comatose, or apneic

Avoidance of emetics or gastric lavage

Avoidance of analeptics

Consideration of other possible causes of coma in an alcoholic patient

Ethanol Dependence and Withdrawal

“Hangover,” characterized by headache, nausea, sweating, and nervousness, can occur in anyone after a brief period of heavy drinking. “Ethanol withdrawal,” in contrast, signifies physical dependence. Early symptoms—usually within a day or two of abstinence—include combinations of tremor, hallucinations, and seizures. Appearing later is the syndrome of delirium tremens.

The most common ethanol withdrawal symptom is tremulousness, which often appears in the morning after at least several days of drinking and is usually promptly relieved by ethanol. If drinking cannot continue, tremor becomes more intense, with insomnia, agitation, facial and conjunctival flushing, sweating, nausea, and tachycardia. Mentation is usually intact. In some patients, tremor can persist for weeks or longer.

Approximately 25% of ethanol-dependent patients develop perceptual disturbances, including nightmares, illusions, and hallucinations, which are most often visual and in which imagery consists of insects, animals, or people. Insight varies. Hallucinations tend to be fragmentary, lasting minutes at a time for several days. Auditory hallucinations with a threatening context sometimes last much longer but rarely evolve into a persistent hallucinatory state with paranoid delusions.

Ethanol can precipitate seizures in any epileptic person. “Ethanol-related seizures” occur in alcoholic persons not otherwise epileptic. Traditionally considered a withdrawal phenomenon, these seizures sometimes occur during active drinking or after more than a week of abstinence, which is suggestive of more than one mechanism. The minimum duration of drinking necessary to cause seizures is unknown, but as little as 50 g of absolute ethanol daily increases risk. Seizures are usually generalized tonic-clonic and occur singly or in a brief cluster. Status epilepticus and focal features are infrequent. Ethanol-related seizures can accompany tremor or hallucinosis, or they can occur in otherwise asymptomatic subjects. Diagnosis depends on an accurate history and exclusion of other cerebral lesions. A patient with prior ethanol-related seizures might on a later emergency department visit have seizures caused by hypoglycemia, central nervous system infection, or cerebral trauma.

Delirium tremens usually begins between 48 and 72 hours after the last drink, often in a patient who is hospitalized for another reason. Symptoms may either follow withdrawal seizures or be the first manifestation of withdrawal. Seizures are not a feature of delirium tremens, which consists of tremor, delirium, hallucinations, and autonomic instability. Symptoms usually begin and end abruptly and last from hours to a few days. Patients are agitated and severely inattentive, with coarse tremor, fever, tachycardia, and profuse sweating. The mortality rate is as high as 15%; death is usually from other diseases such as pneumonia or cirrhosis but sometimes from unexplained shock or no apparent cause.

Treatment of ethanol withdrawal begins with prevention or reduction of early symptoms (Table 117-2). Benzodiazepines, which have cross-tolerance with ethanol, should be given to recently abstinent alcoholic persons or those with mild early withdrawal symptoms. Neuroleptic agents, which are not cross-tolerant with ethanol and which lower seizure threshold, should be avoided except in patients whose only symptoms are hallucinations or in whom hallucinations have outlasted other withdrawal symptoms. Ethanol should be avoided because it has a low margin of safety and is directly toxic to organs, including the brain.

TABLE 117-2 Treatment of Ethanol Withdrawal

Prevention or Reduction of Early Symptoms

Diazepam, 5-20 mg; chlordiazepoxide, 25-100 mg; or lorazepam, 1-4 mg, PO or IV, repeated hourly until sedation or mild intoxication; successive daily doses tapered, with resumption of higher dose if withdrawal symptoms recur@

Thiamine, 100 mg, and multivitamins, IM or IV

Magnesium, potassium, and calcium replacement as needed

Delirium Tremens

Diazepam, 10 mgIV, or lorazepam, 2 mgIV or IM, repeated every 5 to 15 min until patient is calmed; maintenance dose every 1-4h, PRN

If refractory to benzodiazepines, phenobarbital 260 mgIV, repeated in 30 min, PRN

If refractory to phenobarbital, pentobarbital, 3-5 mg/kgIV, with endotracheal intubation and repeated doses to produce general anesthesia

Careful attention to fluid and electrolyte balance; several liters of saline per day, or even pressors, may be needed

Cooling blanket or alcohol sponges for high fever

Prevention or correction of hypoglycemia

Thiamine and multivitamin replacement

Consideration of coexisting illness (e.g., liver failure, pancreatitis, meningitis, subdural hematoma)

IM, intramuscularly; IV, intravenously; PO, orally; PRN, as needed.

Phenytoin is of no value in preventing seizures during withdrawal. Parenteral lorazepam given to patients after an ethanol withdrawal seizure reduces the likelihood of seizure recurrence. Status epilepticus during ethanol withdrawal is treated as in other situations. Long-term anticonvulsants are usually not indicated in patients with ethanol withdrawal seizures; drinkers do not take them, and abstainers do not need them. Epileptic alcoholic patients whose seizures are triggered by ethanol do need anticonvulsant therapy, even though compliance is unlikely.

Hypomagnesemia, common during early withdrawal, is treated with magnesium sulfate. Hypokalemia and hypocalcemia may also be present. Thiamine and multivitamins should be given parenterally.

Delirium tremens is a medical emergency necessitating intensive care (see Table 117-2). In contrast to other withdrawal syndromes, once delirium tremens is present, symptoms are not immediately reversible with any agent. Parenteral benzodiazepines are given in titrated (and sometimes huge) doses. Patients with liver disease are very sensitive to sedative drugs, and in some patients, as delirium tremens clears, hepatic encephalopathy takes its place. General management of delirium tremens includes attention to fluid and electrolyte balance, cardiorespiratory monitoring, and consideration of coexisting illnesses.

Nutritional Disorders Associated with Alcoholism

Many alcoholic patients have deficiencies of thiamine and other vitamins, and a number of neurological disorders have been attributed to these deficiencies. It is increasingly evident, however, that direct ethanol toxicity also plays a role in these disorders. Vitamin deficiency is discussed further in Chapter 109.

Wernicke-Korsakoff Syndrome

Wernicke’s and Korsakoff’s syndromes share the same pathology, but they are clinically distinct. They are the result of thiamine deficiency, but direct ethanol neurotoxicity could be contributory. Full-blown Wernicke’s syndrome consists of the triad of abnormal mentation, eye movements, and gait. Korsakoff’s syndrome is a purely mental disorder differing qualitatively from Wernicke’s syndrome.

The mental abnormalities of Wernicke’s syndrome usually evolve over days or weeks, with inattentiveness, indifference, lethargy, and impaired memory. Selective amnesia is unusual. Abnormal eye movements begin with nystagmus and abducens or horizontal gaze paresis and progress to complete external ophthalmoplegia. Ptosis is rare, and pupillary light reactivity is normal. Truncal ataxia may prevent standing, but dysarthria and limb ataxia are unusual. Of importance, however, is that mental symptoms, including progression to coma, can occur in the absence of abnormal eye movements or ataxia. Many affected patients also have peripheral neuropathy, and some have autonomic signs, including tachycardia, postural hypotension, and sudden circulatory collapse after exertion. Beriberi heart disease is rare, however. The diagnosis of Wernicke’s syndrome is usually based on history and examination. Decreased blood transketolase (a thiamine-requiring enzyme) is the most specific available laboratory test.

In most patients, the more purely amnestic syndrome of Korsakoff emerges as the other mental symptoms of Wernicke’s syndrome respond to treatment. Amnesia is both anterograde and retrograde, and alertness, attentiveness, and behavior are relatively preserved. Confabulation is frequent, especially early in the course, and patients sometimes are lacking in insight to the point of anosognosia.

Histopathological lesions of Wernicke-Korsakoff syndrome affect principally the medial thalamus and hypothalamus, the periaqueductal midbrain, and the pons and medulla beneath the fourth ventricle. There are neuronal and axonal loss, gliosis, prominent blood vessels, and sometimes petechial hemorrhages. The anterior cerebellar vermis can exhibit loss of Purkinje cells.

Untreated Wernicke-Korsakoff syndrome is fatal, and the mortality rate is 10% among treated patients, often the result of concomitant liver failure, sepsis, or delirium tremens. Treatment consists of parenteral thiamine and multivitamins, 50 to 100 mg/day. Fluid and electrolyte imbalance (including hypomagnesemia) require attention, and tachycardia and postural hypotension mandate strict bed rest. With thiamine treatment, ocular abnormalities begin to improve within a few hours and, with the exception of residual nystagmus, usually clear within a few days. Mental symptoms improve either completely or with residual chronic Korsakoff’s amnesia. Gait ataxia also improves, although often incompletely.

Alcoholic Cerebellar Degeneration

Degeneration of the anterior cerebellar vermis is common in patients with acute Wernicke’s syndrome, but it more often occurs alone. Gait ataxia without limb ataxia or dysarthria is the typical presentation, evolving over weeks to months. Ataxia of this type is less likely to improve with nutritional supplementation than is the ataxia associated with Wernicke’s syndrome.

Alcoholic Polyneuropathy

Alcoholic sensorimotor polyneuropathy begins with paresthesias in the feet and sometimes with burning or lancinating pain. Impaired vibratory sense is usually the earliest sign; proprioception is preserved until other sensory loss is substantial. Weakness also begins distally in the legs but may progress proximally and involve the arms. Peripheral autonomic abnormalities can include urinary and fecal incontinence, hypothermia, hypotension, cardiac arrhythmia, and altered sweat patterns. The cerebrospinal fluid is usually normal except for occasional mild protein elevation.

Pathologically, both axons and myelin are degenerated. Both nutritional deficiency and ethanol toxicity appear to be causal in most patients. Clinical studies reveal that pure thiamine deficiency results in a rapidly progressive, largely motor neuropathy, whereas the neuropathy of non–thiamine-deficient alcoholic patients is largely sensory and slowly progressive.

Peripheral nerve pressure palsies, especially involving the radial and peroneal nerves, are common in alcoholic patients.

Alcoholic Amblyopia

Progressing over days or weeks, alcoholic amblyopia consists of central or centrocecal scotomas and temporal disc pallor. Pathologically, there is demyelination of the optic nerves, chiasm, and tracts, especially affecting the maculopapular bundle. Amblyopia does not progress to total blindness. Improvement follows nutritional supplementation even in subjects who continue to drink, but direct toxicity from ethanol (as well as from compounds in tobacco smoke) may play a contributory role.

Pellagra

Alcoholics with nicotinic acid deficiency develop pellagra, with dermatological, gastrointestinal, and neurological symptoms that include amnesia, delusions, hallucinations, and delirium. Improvement follows treatment with nicotinic acid plus other vitamins, deficiency of which can contribute to symptoms.

Nonnutritional Neurological Complications of Alcoholism

Alcoholic Liver Disease

Altered mention in an alcoholic patient should always raise the possibility of hepatic encephalopathy, which can accompany intoxication, withdrawal, Wernicke’s syndrome, meningitis, cerebral trauma, or other alcoholic states and which can be precipitated by sedative medications. Also encountered in alcoholic cirrhotic patients is a syndrome of altered mentation, myoclonus, and progressive myelopathy after portocaval shunting. In acquired chronic hepatocerebral degeneration, repeated bouts of hepatic coma result in a syndrome of dementia, ataxia, tremor, choreoathetosis, muscular rigidity, and asterixis.

Hypoglycemia

Alcoholic persons often do not eat properly and have reduced glycogen stores, and the metabolism of ethanol to acetaldehyde and acetyl–coenzyme A depletes nicotinamide adenine dinucleotide levels. The resulting impairment of gluconeogenesis causes hypoglycemia with altered behavior, seizures, coma, or focal neurological deficit. Of note is that symptoms can occur during active drinking and so are mistaken for intoxication or ethanol-related seizures. Without prompt treatment with intravenous 50% dextrose, residual symptoms, including dementia, are common.

Ethanol stimulates intestinal release of secretion, which aggravates reactive hypoglycemia by enhancing insulin release. Children are especially susceptible to this form of hypoglycemia.

Alcoholic Ketoacidosis

Starvation, increased lipolysis, and impaired fatty acid oxidation during heavy drinking result in the accumulation of β-hydroxybutyric acid and lactic acid and in alcoholic ketoacidosis. The patient has often interrupted a binge when overcome by anorexia and then develops vomiting, dehydration, confusion, obtundation, and hyperventilation. The blood glucose level can be low, normal, or moderately elevated. Serum insulin levels are low. When β-hydroxybutyrate is the major ketone present, the nitroprusside test result can be negative. Treatment includes infusion of glucose (and thiamine), correction of dehydration, and attention to electrolyte abnormalities. Small amounts of bicarbonate can be given, but insulin is seldom needed.

Infection

Alcoholic persons are immunosuppressed, and central nervous system infection should always be suspected in drinkers with altered mentation.

Trauma

Alcoholic persons are trauma prone, and coexisting coagulopathy increases the risk of intracranial or spinal hemorrhage. As with other alcoholic complications, abnormal mental status secondary to subdural or intraparenchymal hematoma can be too readily attributed to drunkenness.

Stroke

As with coronary artery disease, numerous epidemiological studies have shown that low-to-moderate ethanol intake reduces the risk of ischemic stroke, whereas heavy intake increases it. For hemorrhagic stroke, any ethanol intake increases risk in a dose-dependent manner. In the United States, the protective effect holds for men and women and for blacks, whites, and Hispanics, and it is conferred by wine, beer, and spirits. Some studies describe a special benefit of red wine, perhaps related to antioxidant properties of its flavanoid content. In asymptomatic subjects, moderate ethanol consumption reduces the risk of both carotid atherosclerosis and leukoaraiosis. Ethanol has numerous effects that could influence stroke risk. Acutely and chronically, ethanol raises blood pressure. It lowers blood levels of low-density lipoproteins, raises levels of high-density lipoproteins, decreases fibrinolysis, and has both positive and negative effects on C-reactive protein, platelet reactivity, and cerebral vasoconstriction. Alcoholic cardiomyopathy predisposes to cardioembolic stroke.

Alcoholic Myopathy

Alcoholic myopathy consists of a spectrum. At its mildest, the serum creatine kinase is elevated, but there are no symptoms. At its most severe, there are acute rhabdomyolysis and myoglobinuria. In the middle of the spectrum is rapidly progressive proximal weakness resembling polymyositis. The cause is ethanol toxicity, not nutritional deficiency, and symptoms sometimes emerge during a binge. Alcoholic cardiomyopathy often coexists. Symptoms improve with abstinence.

Marchiafava-Bignami Disease

Nearly always occurring in alcoholic patients, Marchiafava-Bignami disease produces symptoms greatly exceeding what would be predicted by the pathology: namely, demyelination within the middle zone of the corpus callosum. The earliest symptoms are usually mental, including psychosis and dementia, followed by seizures, fluctuating hemiparesis, aphasia, dyskinesias, and ataxia, with progression to coma and death over months. The lesions can be seen with magnetic resonance imaging, which sometimes reveals spontaneous remission. The cause is unknown.

Alcoholic Dementia

A long-standing controversy is whether ethanol as a direct neurotoxin can cause progressive cognitive decline in the absence nutritional deficiency, cerebral trauma, or other indirect mechanisms. Properly controlled studies reveal dose-related neuropathological changes and impaired learning in animals receiving ethanol, and a variety of neuropathological abnormalities are described in the brains of cognitively impaired heavy drinkers without evident nutritional deficiency. It is possible that ethanol neurotoxicity and thiamine deficiency are synergistic in their effects on cognitive function.

On the other hand, several attempts to identify a safe dose threshold for alcoholic dementia, similar to ethanol’s effects on ischemic stroke, found that low-to-moderate amounts reduce the risk of both vascular dementia and Alzheimer’s dementia, whereas higher levels of intake increase the risk. Protection is conferred by spirits, beer, and wine. The protective mechanism is unknown but might be related to the antioxidant properties of alcoholic beverages, especially red wine.

Fetal Alcohol Syndrome

In utero exposure to ethanol causes congenital malformations and delayed psychomotor development. The fetal alcohol syndrome consists of cerebral dysfunction, growth deficiency, and distinctive faces; less often there are abnormalities of the skeleton, heart, urogenital organs, skin, and muscles (Table 117-3). Some children of alcoholic mothers have borderline or retarded intellect without other features of fetal alcohol syndrome (“fetal alcohol effects”), and each anomaly of fetal alcohol syndrome can occur alone or in combination with others.

TABLE 117-3 Major Clinical Features of Fetal Alcohol Syndrome

Central nervous system	Mental retardation
	Microcephaly
	Hypotonia
	Poor coordination
	Hyperactivity
Impaired growth	Prenatal for length and weight
	Postnatal for length and weight
	Diminished adipose tissue
	Abnormal facies
Eyes	Short palpebral fissures
Nose	Short, upturned
Nose	Hypoplastic philtrum
Mouth	Thin vermilion lip borders
	Retrognathia in infancy
	Micrognathia or prognathia in adolescence
Maxilla	Hypoplastic