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Alcohol Toxicity and Withdrawal

By Gerald F. O’Malley, DO; Rika O’Malley, MD

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Patient Education

Alcohol (ethanol) is a CNS depressant. Large amounts consumed rapidly can cause respiratory depression, coma, and death. Large amounts chronically consumed damage the liver and many other organs. Alcohol withdrawal manifests as a continuum, ranging from tremor to seizures, hallucinations, and life-threatening autonomic instability in severe withdrawal (delirium tremens). Diagnosis is clinical.

About half of adults in the US are current drinkers, 20% are former drinkers, and 30 to 35% are lifetime abstainers. Alcohol use is also becoming an increasing problem in preteens and teenagers. For most drinkers, the frequency and amount of alcohol consumption does not impair physical or mental health or the ability to safely carry out daily activities. However, acute alcohol intoxication is a significant factor in injuries, particularly those due to interpersonal violence, suicide, and motor vehicle crashes.

Chronic alcohol abuse interferes with the ability to socialize and work. About 7 to 10% of adults meet criteria for an alcohol use disorder (abuse or dependence) in any given year. Binge drinking, defined as consuming 5 drinks per occasion for men and 4 drinks per occasion for women, is a particular problem among younger people.


One serving of alcohol (one 12-oz can of beer, one 6-oz glass of wine, or 1.5 oz of distilled liquor) contains 10 to 15 g of ethanol. Alcohol is absorbed into the blood mainly from the small bowel, although some is absorbed from the stomach. Alcohol accumulates in blood because absorption is more rapid than oxidation and elimination. The concentration peaks about 30 to 90 min after ingestion if the stomach was previously empty.

About 5 to 10% of ingested alcohol is excreted unchanged in urine, sweat, and expired air; the remainder is metabolized mainly by the liver, where alcohol dehydrogenase converts ethanol to acetaldehyde. Acetaldehyde is ultimately oxidized to CO2 and water at a rate of 5 to 10 mL/h (of absolute alcohol); each milliliter yields about 7 kcal. Alcohol dehydrogenase in the gastric mucosa accounts for some metabolism; much less gastric metabolism occurs in women.

Alcohol exerts its effects by several mechanisms. Alcohol binds directly to gamma-aminobutyric acid (GABA) receptors in the CNS, causing sedation. Alcohol also directly affects cardiac, hepatic, and thyroid tissue.

Chronic effects

Tolerance to alcohol develops rapidly; similar amounts cause less intoxication. Tolerance is caused by adaptational changes of CNS cells (cellular, or pharmacodynamic, tolerance) and by induction of metabolic enzymes. People who develop tolerance may reach an incredibly high blood alcohol content (BAC). However, ethanol tolerance is incomplete, and considerable intoxication and impairment occur with a large enough amount. But even these drinkers may die of respiratory depression secondary to alcohol overdose.

Alcohol-tolerant people are susceptible to alcoholic ketoacidosis, especially during binge drinking. Alcohol-tolerant people are cross-tolerant to many other CNS depressants (eg, barbiturates, nonbarbiturate sedatives, benzodiazepines).

The physical dependence accompanying tolerance is profound, and alcohol withdrawal has potentially fatal adverse effects.

Chronic heavy alcohol intake typically leads to liver disorders (eg, fatty liver, alcoholic hepatitis, cirrhosis); the amount and duration required vary (see Alcoholic Liver Disease). Patients with a severe liver disorder often have coagulopathy due to decreased hepatic synthesis of coagulation factors, increasing the risk of significant bleeding due to trauma (eg, from falls or vehicle crashes) and of GI bleeding (eg, due to gastritis, from esophageal varices due to portal hypertension); alcohol abusers are at particular risk of GI bleeding.

Chronic heavy intake also commonly causes the following:

Indirect long-term effects include undernutrition, particularly vitamin deficiencies.

On the other hand, low to moderate levels of alcohol consumption ( 1 to 2 drinks/day) may decrease the risk of death due to cardiovascular disorders. Numerous explanations, including increased high density lipoprotein (HDL) levels and a direct antithrombotic effect, have been suggested. Nonetheless, alcohol should not be recommended for this purpose, especially when there are several safer, more effective approaches to reduce cardiovascular risk.

Special populations

Young children who drink alcohol are at significant risk of hypoglycemia because alcohol impairs gluconeogenesis and their smaller stores of glycogen are rapidly depleted. Women may be more sensitive than men, even on a per-weight basis, because their gastric (first-pass) metabolism of alcohol is less. Drinking during pregnancy increases the risk of fetal alcohol syndrome.

Symptoms and Signs

Acute effects

Symptoms progress proportionately to the BAC. Actual levels required to cause given symptoms vary with tolerance, but in typical users

  • 20 to 50 mg/dL: Tranquility, mild sedation, and some decrease in fine motor coordination

  • 50 to 100 mg/dL: Impaired judgment and a further decrease in coordination

  • 100 to 150 mg/dL: Unsteady gait, nystagmus, slurred speech, loss of behavioral inhibitions, and memory impairment

  • 150 to 300 mg/dL: Delirium and lethargy (likely)

Emesis is common with moderate to severe intoxication; because emesis usually occurs with obtundation, aspiration is a significant risk.

In most US states, the legal definition of intoxication is a BAC of 0.08 to 0.10% ( 80 to 100 mg/dL); 0.08% is used most commonly.

Toxicity or overdose

In alcohol-naive people, a BAC of 300 to 400 mg/dL often causes unconsciousness, and a BAC 400 mg/dL may be fatal. Sudden death due to respiratory depression or arrhythmias may occur, especially when large quantities are drunk rapidly. This problem is emerging in US colleges but has been known in other countries where it is more common. Other common effects include hypotension and hypoglycemia.

The effect of a particular BAC varies widely; some chronic drinkers seem unaffected and appear to function normally with a BAC in the 300 to 400 mg/dL range, whereas nondrinkers and social drinkers are impaired at a BAC that is inconsequential in chronic drinkers.

Chronic effects

Stigmata of chronic use include Dupuytren contracture of the palmar fascia, vascular spiders, and, in men, signs of hypogonadism and feminization (eg, smooth skin, lack of male-pattern baldness, gynecomastia, testicular atrophy). Undernutrition may lead to enlarged parotid glands.


A continuum of symptoms and signs of CNS (including autonomic) hyperactivity may accompany cessation of alcohol intake.

A mild alcohol withdrawal syndrome includes tremor, weakness, headache, sweating, hyperreflexia, and GI symptoms. Symptoms usually begin within about 6 h of cessation. Some patients have generalized tonic-clonic seizures (called alcoholic epilepsy, or rum fits) but usually not > 2 in short succession.

Alcoholic hallucinosis (hallucinations without other impairment of consciousness) follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 h. Hallucinations are typically visual. Symptoms may also include auditory illusions and hallucinations that frequently are accusatory and threatening; patients are usually apprehensive and may be terrified by the hallucinations and by vivid, frightening dreams.

Alcoholic hallucinosis may resemble schizophrenia, although thought is usually not disordered and the history is not typical of schizophrenia. Symptoms do not resemble the delirious state of an acute organic brain syndrome as much as does delirium tremens (DT) or other pathologic reactions associated with withdrawal. Consciousness remains clear, and the signs of autonomic lability that occur in DT are usually absent. When hallucinosis occurs, it usually precedes DT and is transient.

Delirium tremens usually begins 48 to 72 h after alcohol withdrawal; anxiety attacks, increasing confusion, poor sleep (with frightening dreams or nocturnal illusions), profuse sweating, and severe depression also occur. Fleeting hallucinations that arouse restlessness, fear, and even terror are common. Typical of the initial delirious, confused, and disoriented state is a return to a habitual activity; eg, patients frequently imagine that they are back at work and attempt to do some related activity.

Autonomic lability, evidenced by diaphoresis and increased pulse rate and temperature, accompanies the delirium and progresses with it. Mild delirium is usually accompanied by marked diaphoresis, a pulse rate of 100 to 120 beats/min, and a temperature of 37.2 to 37.8° C. Marked delirium, with gross disorientation and cognitive disruption, is accompanied by significant restlessness, a pulse of > 120 beats/min, and a temperature of > 37.8° C; risk of death is high.

During delirium tremens, patients are suggestible to many sensory stimuli, particularly to objects seen in dim light. Vestibular disturbances may cause them to believe that the floor is moving, the walls are falling, or the room is rotating. As the delirium progresses, resting tremor of the hand develops, sometimes extending to the head and trunk. Ataxia is marked; care must be taken to prevent self-injury. Symptoms vary among patients but are usually the same for a particular patient with each recurrence.


  • Usually clinical

  • Acute: BAC, evaluation to rule out hypoglycemia and occult trauma and possible co-ingestion

  • Chronic: CBC, magnesium, liver function tests, and PT/PTT

  • Withdrawal: Evaluation to rule out CNS injury and infection

In acute intoxication, laboratory tests, except for fingerstick glucose to rule out hypoglycemia and tests to determine BAC, are generally not helpful; diagnosis is usually made clinically. Confirmation by breath or blood alcohol levels is useful for legal purposes (eg, to document intoxication in drivers or employees who appear impaired). However, finding a low BAC in patients who have altered mental status and smell of alcohol is helpful because it expedites the search for an alternate cause.

Clinicians should not assume that a high BAC in patients with apparently minor trauma accounts for their obtundation, which may be due to intracranial injury or other abnormalities. Such patients should also have toxicology tests to search for evidence of toxicity due to other substances.

Chronic alcohol abuse and dependence are clinical diagnoses; experimental markers of long-term use have not proved sufficiently sensitive or specific for general use. Screening tests such as AUDIT (Alcohol Use Disorders Identification Test) or the CAGE questionnaire can be used. However, heavy alcohol users may have a number of metabolic derangements that are worth screening for, so CBC, electrolytes (including magnesium), liver function tests (including coagulation profile [PT/PTT]), and serum albumin are often recommended.

In severe withdrawal and toxicity, symptoms may resemble those of CNS injury or infection, so medical evaluation with CT and lumbar puncture may be needed. Patients with mild symptoms do not require routine testing unless improvement is not marked within 2 to 3 days. A clinical assessment tool for severity of alcohol withdrawal is available.


  • Supportive measures

  • For withdrawal, benzodiazepines and sometimes also phenobarbital or propofol

Toxicity or overdose

Treatment of alcohol toxicity may include the following:

  • Airway protection

  • Sometimes IV fluids with thiamin, Mg, and vitamins

The first priority is ensuring an adequate airway; endotracheal intubation and mechanical ventilation are required for apnea or inadequate respirations. IV hydration is needed for hypotension or evidence of volume depletion but does not significantly enhance ethanol clearance. When IV fluids are used, a single dose of thiamin 100 mg IV is given to treat or prevent Wernicke encephalopathy. Many clinicians also add multivitamins and Mg to the IV fluids.

Disposition of the acutely intoxicated patient depends on clinical response, not a specific BAC.


Patients with severe alcohol withdrawal or delirium tremens should be managed in an ICU until these symptoms abate. Treatment may include the following to prevent Wernicke-Korsakoff syndrome and other complications:

  • IV thiamin

  • Benzodiazepines

Thiamin 100 mg IV is given to prevent Wernicke-Korsakoff syndrome.

Alcohol-tolerant people are cross-tolerant to some drugs commonly used to treat withdrawal (eg, benzodiazepines).

Benzodiazepines are the mainstay of therapy. Dosage and route depend on degree of agitation, vital signs, and mental status. Diazepam, given 5 to 10 mg IV or po hourly until sedation occurs, is a common initial intervention; lorazepam 1 to 2 mg IV or po is an alternative. Chlordiazepoxide 50 to 100 mg po q 4 to 6 h, then tapered, is an older acceptable alternative for less severe cases of withdrawal. Phenobarbital may help if benzodiazepines are ineffective, but respiratory depression is a risk with concomitant use.

Phenothiazines and haloperidol are not recommended initially because they may lower the seizure threshold. For patients with a significant liver disorder, a short-acting benzodiazepine (lorazepam) or one metabolized by glucuronidation (oxazepam) is preferred. (Note: Benzodiazepines may cause intoxication, physical dependence, and withdrawal in alcoholics and therefore should not be continued after the detoxification period. Carbamazepine 200 mg po qid may be used as an alternative and then tapered.) For severe hyperadrenergic activity or to reduce benzodiazepine requirements, short-term therapy (12 to 48 h) with titrated beta-blockers (eg, metoprolol 25 to 50 mg po or 5 mg IV q 4 to 6 h) and clonidine 0.1 to 0.2 mg IV q 2 to 4 h can be used.

A seizure, if brief and isolated, needs no specific therapy; however, some clinicians routinely give a single dose of lorazepam 1 to 2 mg IV as prophylaxis against another seizure. Repeated or longer-lasting (ie, > 2 to 3 min) seizures should be treated and often respond to lorazepam 1 to 3 mg IV. Routine use of phenytoin is unnecessary and unlikely to be effective. Outpatient therapy with phenytoin is rarely indicated for patients with simple alcohol withdrawal seizures when no other source of seizure activity has been identified because seizures occur only under the stress of alcohol withdrawal, and patients who are withdrawing or heavily drinking may not take the anticonvulsant.

Delirium tremens may be fatal and thus must be treated promptly with high-dose IV benzodiazepines, preferably in an ICU. Dosing is higher and more frequent than in mild withdrawal. Very high doses of benzodiazepines may be required, and there is no maximum dose or specific treatment regimen. Diazepam 5 to 10 mg IV or lorazepam 1 to 2 mg IV q 10 min is given as needed to control delirium; some patients require several hundred milligrams over the first few hours. Patients refractory to high-dose benzodiazepines may respond to phenobarbital 120 to 240 mg IV q 20 min as needed.

Severe drug-resistant DT can be treated with a continuous infusion of lorazepam, diazepam, midazolam, or propofol, usually with concomitant mechanical ventilation. Physical restraints should be avoided if possible to minimize additional agitation, but patients must not be allowed to elope, remove IVs, or otherwise endanger themselves. Intravascular volume must be maintained with IV fluids, and large doses of vitamins B and C, particularly thiamin, must be given promptly. Appreciably elevated temperature with DT is a poor prognostic sign.

* This is the Professional Version. *