Ethanol readily crosses the blood–brain barrier , enabling the brain alterations to begin soon after drinking. Signs of intoxication in nonalcoholic persons begin at blood levels about 60 mg/dl, and gross intoxication occurs at levels of 120–150 mg/dl. In alcoholics, intoxication may not occur until blood levels are as high as 150 mg/dl. Signs of intoxication consist of varying degrees of euphoria, exhilaration, excitement, loss of restraint, irregular behavior, slurred speech, incoordination of movement, gait ataxia , irritability, and combativeness. While the biochemical effects are incompletely understood, the net result appears to be excitation of brain activity. There are a variety of metabolic abnormalities that may accompany alcohol intoxication, including hypoglycemia, lactic acidosis, hypokalemia, and hypophosphatemia. Other systemic manifestations of alcohol intoxication can include tachycardia, peripheral vasodilation, and volume depletion—leading to low blood pressure and inability to maintain body temperature causing hypothermia.

At higher blood levels, brain functions deteriorate with the development of lethargy, stupor, and coma, suggesting ethanol now produces inhibition of brain activity. Alcoholic coma is seen at blood levels around 300 mg/dl, and respiratory failure develops at levels of > 400 mg/dl. Comatose patients often require intubation and mechanical ventilation until the alcohol is cleared from the systemic circulation.

In the setting of chronic alcohol use , if alcohol intake is abruptly reduced, within hours as blood alcohol levels fall or are absent, an alcohol withdrawal syndrome can develop. Early alcohol withdrawal is characterized by autonomic hyperactivity (tremulousness, sweating, nausea, vomiting, and anxiety). Later alcohol withdrawal can include those early symptoms and also result in excessive neuronal excitation (confusion, agitation, delusions, hallucination, and seizures).

Stage 1 alcohol withdrawal is characterized by tremulousness, feeling anxious, and sometimes nausea and vomiting. Tremor (“shakes” or “jitters”) develops in over 50 % of individual in withdrawal. The tremors begin about 6 h after the last drink and worsen over the next 2–3 days (Fig. 19.1). The tremor is present at rest and with action. It is 6–8 Hz and irregular in character. Patients may also have an increased startle response. The mental status remains relatively clear but the patients feel uncomfortable. The tremor can be treated with benzodiazepines. It is also often “self-treated” by additional alcohol consumption (e.g. “an eye-opener”) to resolve the tremulousness sensation . Some patients will go on to further stages of withdrawal. Risk factors for a more severe withdrawal course include prior withdrawal episodes, advanced age, male sex, comorbid conditions (e.g. liver disease), and higher daily intake of alcohol.

Stage 2 alcohol withdrawal occurs at 1–2 days after the last alcohol consumption. The tremulousness may worsen and be accompanied by agitation and hyperactivity. The autonomic symptoms of tachycardia, hypertension, and diaphoresis begin, and the tremor described above becomes more apparent. Patients are typically lucid at this stage but may have disordered sleep and experience insomnia . Stage 2 can worsen into stage 3 withdrawal which incorporates the features of stage 2 but includes seizures (described below). At 3–5 days from last alcohol consumption, stage 4 alcohol withdrawal or delirium tremens can occur. This is discussed later in this chapter.

The Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA-Ar) is commonly used to assess patient symptoms during alcohol withdrawal in the medical setting. It contains ten items and requires interaction from the patient. Stage 1 alcohol withdrawal is a score of less than 10. A score of greater than 10 is suggestive of more severe withdrawal that likely will require evaluation and possible admission to a medical facility .

Alcohol withdrawal seizures occur in nearly 5 % of individuals who have been steadily drinking for years and then abruptly stop . For example, undiagnosed alcoholics who are hospitalized may experience a seizure the day after admission . The primarily generalized seizure occurs 7–72 h after alcohol cessation with a peak of 12–48 h (Fig. 19.1). Patients tend to have 1–4 seizures over several hours. Status epilepticus is rare.

Alcohol withdrawal seizures are partly a diagnosis of exclusion. The mechanism for withdrawal seizures is unknown but thought to result from a hyperactive brain (due to alcohol withdrawal), accompanying low serum magnesium, and elevated arterial pH from respiratory alkalosis. In keeping with this, half of patients withdrawing from ethanol have an abnormal electroencephalogram (EEG) , manifesting myoclonic or convulsive responses to flashing lights.

Fifty percent of patients brought to the ER with possible alcohol withdrawal seizures have another identifiable etiology. These patients often have a seizure aura (implying a focal origin for the seizure), history of serious head trauma while intoxicated, atypical seizures, abnormal neurologic exam , or signs of systemic infection. Neuroimaging studies can identify subdural hematomas, hemispheric contusions or infarctions, intracerebral masses (brain abscess , neurocysticercosis, tumors, vascular malformations), or meningitis. Neurologic exam should not show acute signs that cannot be attributed to chronic alcohol usage. The blood alcohol level should be zero or very low and the CSF exam, if done, is normal. Some patients have known epilepsy whose seizure was actually triggered by drinking alcohol and stopping their anticonvulsant medications .

Administration of benzodiazepines (lorazepam or diazepam) usually prevents further seizures during the critical withdrawal period. Phenytoin administration does not prevent seizures. Patients who permanently stop drinking do not have future seizures. Controversy exists as to whether administration of anticonvulsants prevents subsequent alcohol withdrawal seizures . Since patients often stop their anticonvulsants during drinking spells, the combination of alcohol and anticonvulsant withdrawal may actually increase their risk of future seizures.

Delirium tremens (DT) or stage 4 alcohol withdrawal syndrome is a serious but uncommon complication of alcohol withdrawal (less than 8 % of hospital admissions for alcoholism) and presents with profound delirium and autonomic nervous system overactivity. Patients have marked confusion , agitation, hallucinations, tremors , and sleeplessness. Signs of increased autonomic nervous system activity include fever, tachycardia, dilated pupils, and profuse sweating. Clinical signs begin 2–5 days after alcohol withdrawal and may be preceded by withdrawal seizures (Fig. 19.1). Life-threatening events include high fever, dehydration, hypotension, cardiac arrhythmias, and secondary complications of trauma (from the agitation) or alcohol-associated medical conditions (liver failure, gastrointestinal bleeding, systemic infection, or pancreatitis).

Treatment aims at reducing agitation and maintaining fluid and electrolyte balance. Lorazepam given repeatedly intravenously or intramuscularly is required for sedation. Repeated doses of sedating medications like lorazepam are helpful in reducing withdrawal symptoms but can lead to respiratory failure requiring intubation and respiratory support. Patients require replacement of up to 4–10 L of fluid per 24 h to prevent dehydration and circulatory collapse. Serum potassium and magnesium levels are usually low and require correction .

The duration of DTs lasts 2–7 days with most cases ending by day 3. Recovering patients regain alertness and ability to cooperate but seldom have any memory for the acute illness. The mortality rate is 10 %.