- Clinical science
Alcohol-related disorders
Summary
Alcohol-related disorders, including alcohol intoxication, alcohol use disorder (AUD), and alcohol withdrawal, are a group of conditions associated with disruptive patterns of alcohol use. Alcohol intoxication is the acute onset of behavioral and psychomotor impairment shortly after an episode of drinking. Alcohol use disorder (AUD) is characterized by clinically significant psychosocial and behavioral problems associated with alcohol use. Alcohol withdrawal develops after a sudden cessation or reduction of alcohol use in patients with a history of excessive drinking. The diagnosis of an alcohol-related disorder can be established using the DSM-5 criteria. The most important aspect of management for all alcohol-related disorders is the cessation of alcohol use. Therapeutic management is guided by the severity of the disorder.
See breakdown of ethanol for a review of alcohol metabolism pathways.
Alcohol intoxication
- Definition: : a temporary condition in which excessive consumption of alcohol alters a person's consciousness, cognition, perception, judgment, affect, and/or behavior
- Pathophysiology: The majority of alcohol consumed is absorbed by the proximal small intestine. Only a small amount of alcohol gets absorbed by the oral, esophageal, and/or gastric mucosa.
- Clinical features
Mild intoxication (BAC 0.01–0.1%, < 100 mg/dL) | Moderate intoxication (BAC 0.1–0.3%, 10–300 mg/dL) | Severe intoxication (BAC > 0.3%; > 300 mg/dL) |
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In the US, the maximum legal limit for driving under the influence of alcohol is a BAC of 0.08%.
Because alcohol has a long absorption time (approx. 40 min), patients with alcohol intoxication may deteriorate over time.
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Treatment
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Agitation and/or aggression management
- Sedation with benzodiazepines or typical antipsychotics (e.g., haloperidol)
- Mechanical restraints may be used for individuals who pose a danger to themselves and/or others if de-escalation and medication strategies have been unsuccessful.
- Aggressive fluid therapy
- Thiamine: for Wernicke encephalopathy prophylaxis or treatment
- Correction of electrolyte disbalance, hypoglycemia, and hypothermia
- Thorough assessment for occult trauma (e.g., imaging), if suspected
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Agitation and/or aggression management
Haloperidol may worsen respiratory depression secondary to alcohol intoxication!
References:[1][2][3][4][5][6][7][8]
Alcohol use disorder
AUD is a chronic condition in which an uncontrolled pattern of alcohol use leads to significant physical, psychological, and social impairment or distress. Not all individuals who drink heavily develop AUD, and not all individuals with AUD have a history of heavy alcohol use.
Epidemiology
- Alcohol consumption results in > 3 million deaths worldwide per year.
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Prevalence [9]
- US lifetime prevalence is ∼ 29%
- More common in Native Americans and Alaska Natives than in other US ethnicities
- Peak incidence: 21–34 years
- Sex: ♂ > ♀ (2.5:1) [10]
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Associated comorbidities
- Childhood ADHD
- Conduct disorder
- Personality disorders (most commonly borderline personality disorder)
- Anxiety, mood disorders (e.g., depression, bipolar disorder), and psychosis
- Other substance-related disorders (e.g., stimulants, sedatives, cannabis, and other)
- Cognitive dysfunction
References: [11][9][12][13][14]
Etiology
- Genetic factors
- Neurobiological factors
- Psychosocial factors
- Family history of AUD [15]
- Environmental influence: e.g., social pressure to consume alcohol
References:[12][16]
Diagnostics
Diagnosis of AUD begins with a screening test, which is followed by a confirmatory test based on patient history. Commonly used screening tests include AUDIT-C and CAGE tests. Diagnosis is confirmed if the patient history meets the DSM-V criteria for AUD.
Screening
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AUDIT-C test
- Three questions based on the Alcohol Use Disorders Identification Test (AUDIT)
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Evaluation
- Every response is given a score from 0 to 4 points.
- The total score can range from 0 to 12.
- A positive test suggests the presence of an alcohol use disorder.
- ≥ 4 in men
- ≥ 3 in women
Question | Response | Score |
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How often did you have a drink containing alcohol in the past year? | Never | 0 |
≤ Monthly | 1 | |
2–4 times a month | 2 | |
2–3 times a week | 3 | |
≥ 4 times a week | 4 | |
How many drinks did you have on a typical day when you were drinking in the past year? | 1–2 | 0 |
3–4 | 1 | |
5–6 | 2 | |
7–9 | 3 | |
≥ 10 | 4 | |
How often did you have ≥ 6 drinks on one occasion in the past year? | Never | 0 |
< Once per month | 1 | |
Monthly | 2 | |
Weekly | 3 | |
Daily or almost daily | 4 |
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CAGE test
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A series of four questions (CAGE) is used to screen for AUD
- Cut down drinking: Have you ever felt you should cut down on your drinking?
- Annoyed: Have people annoyed you by criticizing your drinking?
- Guilty: Have you ever felt guilty about drinking?
- Eye-opener: Have you ever felt you needed a drink first thing in the morning (eye-opener) to steady your nerves or to overcome a hangover?
- Every “yes” response counts as one point.
- The CAGE test is considered positive for AUD if ≥ 2 questions are answered in the affirmative.
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A series of four questions (CAGE) is used to screen for AUD
Diagnostic criteria (according to DSM-5)
- 11 criteria based on the patient's history within the past 12 months
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A diagnosis of AUD is established once ≥ 2 criteria are met.
- Drinking more or over a longer period than intended
- Tried to cut down or stop more than once, but couldn't
- Spends a lot of time drinking or recovering from aftereffects
- Strong desire to drink alcohol
- Drinking has a negative impact on everyday function (social, work etc)
- Continued drinking despite social or interpersonal problems
- Given up interests and activities that were important because of drinking
- Drinking in physically hazardous situations more than once
- Continued drinking despite physical or psychological problems
- Increasing amount of drinks to maintain same effects as before
- Features of withdrawal when the effects of alcohol wear off (see alcohol withdrawal below)
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Severity
- Mild: presence of 2–3 criteria
- Moderate: presence of 4–5 criteria
- Severe: presence of ≥ 6 criteria
Laboratory tests
- AUD is a clinical diagnosis, and laboratory tests are not usually required, although they may provide evidence of problematic alcohol use in patients who cannot provide a conclusive history.
- Acute alcohol intoxication: high BAC
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Chronic alcohol intoxication
- Liver damage: ↑ γ-GT, ↑ ALT, ↑ AST (AST is only higher than ALT when liver parenchyma is significantly damaged)
- Carbohydrate-deficient transferrin (CDT)
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Malnutrition and bone marrow damage
- ↓ Folic acid, ↓ vitamin B12 (cobalamin), ↓ vitamin B1 (thiamine), ↓ vitamin B6 (pyridoxine), ↓ vitamin D, ↓ vitamin K
- Megaloblastic anemia (↓ Hb, ↑ MCV), thrombocytopenia
ToAST 2 ALcohol (AST levels are at least 2 times higher than those of ALT in case of alcoholic hepatitis)
References:[17][12][16][18][19][20]
Treatment
- See counseling on alcohol abuse
- Psychosocial support (e.g., Alcoholics Anonymous)
- Pharmacotherapy (to promote alcohol cessation)
- Naltrexone (first-line agent): reduces cravings for alcohol
- Disulfiram: exacerbates intoxication symptoms and induces negative conditioning
- Acamprosate: blocks central glutamate receptors and reduces cravings for alcohol
- Topiramate or gabapentin: for patients who do not tolerate or respond to other medications
- Vitamin supplementation
References:[21][4][6][22][23]
Complications
- Erosive gastritis
- Dilated cardiomyopathy
- Pancreatitis
- Cirrhosis
- Alcoholic liver disease
- Alcoholic cerebellar degeneration
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Marchiafava–Bignami disease
- Definition: degeneration and necrosis of the corpus callosum, almost exclusively as a result of malnutrition due to chronic alcohol use
- Clinical features
- Zieve syndrome
- Central pontine myelinolysis
- Meningitis
- Mood disturbance: anxiety, depression, irritability, aggression
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Vitamin deficiency
- Vitamin B1 deficiency (thiamine deficiency): Wernicke-Korsakoff syndrome
- Vitamin B6 deficiency: peripheral neuropathy
- Vitamin B9 deficiency (folate deficiency): megaloblastic anemia
- Vitamin B12 deficiency: subacute combined degeneration of spinal cord; (funicular myelosis), megaloblastic anemia
- Cytochrome P-450 induction
- In pregnancy: fetal alcohol syndrome
Alcohol withdrawal
- Caused by a sudden reduction or cessation of alcohol intake after a prolonged period of heavy drinking
- Onset and duration vary among different syndromes.
- May be assessed using the CIWA-Ar score
- Delirium tremens is the most severe form of alcohol withdrawal.
Individuals with chronic alcohol use often develop withdrawal symptoms 48–72 hours after hospitalization because they do not have access to alcohol in the hospital.
Minor withdrawal
- Onset: 6–36 hours after last drink
- Clinical features
- Duration: 24–48 hours
Withdrawal seizures
- Onset: 6–48 hours after last drink
- Clinical features: : brief, generalized tonic-clonic seizure (usually a single episode)
Alcoholic hallucinosis
- Onset: 12–48 hours after last drink
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Clinical features
- Consciousness is usually intact.
- Normal vital signs
- Auditory and/or visual hallucinations are common; (tactile hallucinations are also possible).
- Delusions
- Duration: 24–48 hours after onset
Delirium tremens
- Definition: persistent alteration of consciousness and sympathetic hyperactivity due to alcohol withdrawal
- Onset: most commonly occurs 48–96 hours after last drink
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Clinical features
- Symptoms of altered mental status
- Impaired consciousness and disorientation
- Visual and tactile hallucinations (usually small moving objects, e.g., mice, crawling insects)
- Increased suggestibility
- Symptoms of autonomic instability
- Tachycardia
- Hypertension
- Sweating
- Nausea
- Symptoms of neurological impairment
- Generalized tonic-clonic seizures
- Rest and intention tremor (first high-frequency, then low-frequency)
- Hyperreflexia
- Symptoms of altered mental status
- Duration: 1–5 days
In contrast to patients with alcoholic hallucinosis, patients with delirium tremens have impaired consciousness and abnormal vital signs.
Treatment
- IV fluid therapy and electrolyte disbalance correction
- Thiamine: for Wernicke encephalopathy prophylaxis or treatment (administer prior to glucose)
- Dextrose
- Folate and multivitamins
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IV benzodiazepines for control of psychomotor agitation and seizures
- Long-acting (e.g., diazepam, chlordiazepoxide) OR
- Short-acting (e.g., lorazepam; , oxazepam): especially for patients with liver disease
- Anticonvulsants (e.g. carbamazepine): if seizures persist despite benzodiazepines administration
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Antipsychotics (e.g., haloperidol, risperidone)
- May be used for management of psychotic symptoms (never as independent medication)
- Should be avoided, if possible, or administered in low doses
Lorazepam, Oxazepam, and Temazepam are preferred in those who drink a LOT because they are not metabolized by the liver and therefore safe in alcoholic liver disease.
In the case of alcohol withdrawal seizures, benzodiazepines are preferred over other anticonvulsants to prevent further seizures.
References:[1][2][3][4][5][6][7][8]
Alcoholic ketoacidosis
- Definition: elevated anion gap metabolic acidosis due to increased production of ketone bodies with normal or low glucose levels resulting from the combined effects of alcohol and starvation on glucose metabolism
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Etiology
- Most commonly occurs in malnourished individuals with AUD
- Associated with recent episodes of binge drinking complicated by poor food intake, dehydration, and vomiting
- Onset: typically occurs 1–2 days after cessation of drinking
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Pathophysiology: accumulation of ketone bodies (see ketogenesis) as a result of:
- Depleted glycogen stores in the liver (malnutrition/decreased carbohydrate intake)
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Increased lipolysis and free fatty acid release
- Decreased energy intake (e.g., starvation) → decreased insulin secretion and excess secretion of glucagon, catecholamines, and cortisol
- Increased NADH:NAD+ ratio: chronic alcohol intake → impaired hepatic gluconeogenesis → hypoglycemia → decreased insulin secretion
- Volume depletion (e.g., vomiting, poor oral fluid intake) → impaired renal perfusion → decreased ability to excrete ketone bodies
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Clinical features
- Nausea, vomiting, and abdominal pain
- Tachypnea
- Features of dehydration and electrolyte imbalance (e.g., hyponatremia, hypokalemia, hypophosphatemia), including hypotension and altered mental status
- Features of alcohol withdrawal: e.g., tremors, seizures, tachycardia
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Diagnostics
- Arterial blood gas analysis: elevated anion gap metabolic acidosis
- Ketonemia (acetoacetate, β-hydroxybutyrate, acetone in blood) and ketonuria
- Blood glucose: low, normal, or only moderately increased
- Blood ethanol: not detectable or low
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Treatment
- Initially: parenteral administration of thiamine to prevent Wernicke encephalopathy
- Followed by: IV fluid therapy with 5% dextrose in 0.9% saline
- Correction of electrolyte imbalances
- Treatment of alcohol withdrawal and complications of chronic alcohol abuse (see alcohol withdrawal management in “Treatment” above)
- Prognosis: The condition is reversible with appropriate treatment.
In contrast to diabetic ketoacidosis, blood glucose levels are normal or low in alcoholic ketoacidosis.
References:[1][2][3][4][5][6][7][8]