Alcohol Toxicity and Withdrawal

Alcohol-tolerant people are susceptible to alcoholic ketoacidosis, especially during binge drinking. Alcohol-tolerant people are cross-tolerant to many other central nervous system 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 Alcohol-Related 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 gastrointestinal bleeding (eg, due to gastritis, from esophageal varices due to portal hypertension); alcohol abusers are at particular risk of gastrointestinal bleeding.

Chronic heavy intake also commonly causes the following:

• Gastritis

• Pancreatitis

• Cardiomyopathy, often accompanied by arrhythmias and hypertension

• Peripheral neuropathy

• Brain damage, including Wernicke encephalopathy, Korsakoff psychosis, Marchiafava-Bignami disease, and alcohol-related dementia

• Certain cancers (eg, liver, head and neck, esophageal), especially when drinking is combined with smoking

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 (1). 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.

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 due to lower activity of alcohol dehydrogenase in the gastric mucosa. Drinking during pregnancy may result in fetal alcohol spectrum disorder.

1. 1. Piano MR: Alcohol's effects of the cardiovascular system. Alcohol Res 38(2):219–241, 2017.

Symptoms progress proportionately to blood alcohol content (BAC). Actual levels required to cause given symptoms vary with tolerance, but in typical users the following occur:

• 20 to 50 mg/dL (4.3 to 10.9 mmol/L): Tranquility, mild sedation, and some decrease in fine motor coordination

• 50 to 100 mg/dL (10.9 to 21.7 mmol/L): Impaired judgment and a further decrease in coordination

• 100 to 150 mg/dL (21.7 to 32.6 mmol/L): Unsteady gait, nystagmus, slurred speech, loss of behavioral inhibitions, and memory impairment

• 150 to 300 mg/dL (32.6 to 65.1 mmol/L): Delirium and lethargy (likely)

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

In US states, the legal definition of intoxication is a BAC of ≥ 0.08% (≥ 80 mg/dL, [17.4 mmol/L]); 0.08% is used most commonly.

In alcohol-naïve people, a BAC of 300 to 400 mg/dL (65.1 to 86.8 mmol/L) often causes unconsciousness, and a BAC ≥ 400 mg/dL (86.8 mmol/L) may be fatal. Sudden death due to respiratory depression or arrhythmias may occur, especially when large quantities are drunk rapidly. 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 (65.1 to 86.8 mmol/L) range, whereas nondrinkers and social drinkers are impaired at a BAC that is inconsequential in chronic drinkers.

Stigmata of chronic use include 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 central nervous system (including autonomic) hyperactivity may accompany cessation of alcohol intake.

A mild alcohol withdrawal syndrome includes tremor, weakness, headache, sweating, hyperreflexia, and gastrointestinal symptoms. Tachycardia may be present and blood pressure can be slightly elevated. Symptoms usually begin within about 6 hours of cessation. Some patients have generalized tonic-clonic seizures (called alcohol-related seizure, or rum fits) but usually not > 2 in short succession. Seizures generally occur 6 to 48 hours after cessation of alcohol.

Alcoholic hallucinosis (hallucinations without other impairment of consciousness) follows abrupt cessation from prolonged, excessive alcohol use, usually within 12 to 24 hours. 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 hours 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/minute, 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/minute, 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.

Treatment of alcohol toxicity may include the following:

• Airway protection

• Sometimes IV fluids with thiamin, magnesium, and vitamins

The first priority is ensuring an adequate airwayWernicke encephalopathy. Many clinicians also add multivitamins and magnesium 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 intensive care unit until these symptoms abate. Treatment may include

• IV thiamin to prevent Wernicke encephalopathy

Thiamin 100 mg IV is given to prevent Wernicke encephalopathy.

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

Benzodiazepines

1).

A seizure,>

Delirium tremens

1. 1. American Society of Addiction Medicine: Alcohol Withdrawal Management Guideline. Accessed October 3, 2022.