Alcohol-Related Disease - Clinical Tree

As eloquently stated by Paracelsus in the 16th century, “all substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.”

Key Concepts

Moderate alcohol consumption is defined as one or two drinks/day for men and one drink/day for women.
DSM–5 integrates alcohol abuse and alcohol dependence into a single disorder called alcohol use disorder (AUD), with mild, moderate, and severe sub-classifications.
Benzodiazepines are the main treatment of alcohol withdrawal and alcohol withdrawal-induced seizures. Minor alcohol withdrawal occurs as early as 6 h and usually peaks at 24–36 h after the cessation of or significant decrease in alcohol intake.
Major alcohol withdrawal occurs after 24 h and usually peaks at 50 h (but may take up to 5 days) after the decrease or termination of drinking.
Delirium tremens is the extreme end of the alcohol withdrawal spectrum; it consists of gross tremors, profound confusion, fever, incontinence, and frightening visual hallucinations.
Alcohol withdrawal seizures occur 6–48 h after the cessation of drinking, with 60% of patients experiencing multiple seizures within a 6-h period.
Alcohol withdrawal should be assessed and managed using a validated scale, such as the CIWA-Ar scale.
Brief intervention and screening (SBIRT— s creening, b rief i ntervention, and r eferral to t reatment) can reduce alcohol consumption and is feasible and effective in the emergency department.

Foundations

Excess alcohol consumption places a significant burden on individuals and society. Globally, alcohol consumption is the seventh leading risk factor for both death and the burden of disease and injury. 2016 data from the World Health Organization (WHO) state that 5.3% of all deaths globally were attributable to alcohol consumption. The overall costs associated with alcohol use represent more than 1% of the gross national product in high- and middle-income countries, with the costs of social harm (e.g., violence and road accidents) being far greater than health costs alone. In short, except for tobacco, alcohol accounts for a higher burden of disease than any other drug.

From 2002 to 2010, the rate of emergency department (ED) visits for alcohol-related diagnoses increased by 38%. In addition to the number of visits, current National Hospital Ambulatory Care survey data indicates that the total time and the length of stay (LOS) for ethanol-related visits are increasing as well.

Twenty-seven percent of the US population admits to alcohol misuse. Alcohol misuse accounts for more than 100,000 deaths in the United States every year, making it the fourth leading preventable cause of death in the United States and the 12th leading cause of death overall and is associated with over 200 diseases. ^, Alcoholism permeates all levels of society. Studies reveal a complex association between alcohol consumption and socioeconomic status (SES), where people of lower SES show greater susceptibility to the damaging effects of alcohol.

Alcohol use and misuse also have social and financial costs, with estimates of over $220 billion in societal costs in the United States annually. The literature refers to harmful, hazardous, and risky drinking interchangeably as a pattern of drinking that increases the risk of harm for the person consuming alcohol or others. The International Classification of Disease 10th Revision (ICD-10), draft ICD-11, and the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-4) use the term “alcohol dependence.” Alcohol dependence is a result of repeated use leading to a person having impaired control over the use of alcohol despite physical, psychological, and social harms. The fifth edition of the Diagnostic and Statistical Manual (DSM-5) combines diagnostic criteria for alcohol abuse and dependence under the term “alcohol use disorder,” with severity modifiers of “mild,” “moderate,” or “severe,” based on the number of criteria met. DSM-5 AUD of moderate or greater severity is essentially equivalent to DSM-4 and ICD-10 criteria for alcohol dependence. DSM–5 integrates alcohol abuse and alcohol dependence into a single disorder called alcohol use disorder (AUD), with mild, moderate, and severe sub-classifications.

At least 24% to 31% of ED patients meet National Institute Alcohol Abuse and Alcoholism (NIAAA) criteria for “at-risk” or heavy drinking. At-risk drinking is defined as an average of 14 or more standard drinks/week or 5 or more per occasion for men and 7 or more drinks weekly or 3 or more per occasion for women and people older than 65 years. ( Table 137.1 : Terms and Definitions of Unhealthy Alcohol Use. )

TABLE 137.1

Terms and Definitions of Unhealthy Alcohol Use

Data from US Preventive Services Task Force, Curry SJ, Krist AH, et al. Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement. JAMA . 2018;320(18):1899–1909.

Term	Source	Definition
Low-risk use/lower-risk use	ASAM	Consumption of alcohol below the amount identified as hazardous and in situations not defined as hazardous
Risky/at-risk use	NIAAA	Consumption of alcohol above the recommended daily, weekly, or per-occasion amounts but not meeting criteria for alcohol use disorder
		For all women and men 65 years or older: No more than 3 drinks/day and no more than 7 drinks/week for men (21 to 64 years): No more than 4 drinks/day and no more than 14 drinks/week
		Should avoid alcohol completely: Adolescents, women who are pregnant or trying to get pregnant, and adults who plan to drive a vehicle or operate machinery, are taking medication that interacts with alcohol, or have a medical condition that can be aggravated by alcohol
		For adolescents: NIAAA defines moderate- and high-risk use based on days of alcohol use in the past year, by age group: Moderate risk:
		Ages 12–15 years: 1 day/year
		Ages 16–17 years: 6 days/year
		Age 18 years: 12 days/year
		Highest risk: Age 11 years: 1 day
		Ages 12–15 years: 6 days
		Age 16 years: 12 days
		Age 17 years: 24 days
		Age 18 years: 52 days
Unhealthy use	ASAM	Any alcohol use that increases the risk or likelihood of health consequences (hazardous use [see below]) or has already led to health consequences (harmful use [see below])
Hazardous use	WHO	A pattern of substance use that increases the risk of harmful consequences; in contrast to harmful use, hazardous use refers to patterns of use that are of public health significance, despite the absence of a current alcohol use disorder ¡ท the individual user
	ASAM	Alcohol use that increases the risk or likelihood of health consequences; does not include alcohol use that has already led to health consequences
Harmful use	WHO	A pattern of drinking that is already causing damage to health; the damage may be either physical (e.g., liver damage from chronic drinking) or mental (e.g., depressive episodes secondary to drinking)
		The description for ICD-10 code F10.l, also labeled “Alcohol Abuse” in the 2018 ICD-10-CM codebook
	ASAM	Consumption of alcohol that results in health consequences in the absence of addiction
Alcohol use disorder	DSM-5	A maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by 2 (or more) of the following, occurring within a 12-month period:
		1. Having times when the patient drank more, or longer, than intended
		2. More than once wanted to cut down or stop, tried It, but could not
		3. Spending a lot of time drinking or being sick/getting over the aftereffects of drinking
		4. Wanting to drink so badly that they could not think of anything else
		5. Found that drinking (or being sick from drinking) often interfered with taking care of home or family responsibilities, caused problems at work, or caused problems at school
		6. Continuing to drink even though it was causing trouble with family and friends
		7. Given up or cut back on activities that were important or interesting ¡ท order to drink
		8. More than once gotten into situations while or after drinking that increased the chances of getting hurt (e.g., driving, swimming, unsafe sexual behavior)
		9. Continued to drink even though it was causing depression or anxiety, other health problems, or causing memory blackouts
		10. Having to drink much more than previously ¡ท order to get the desired effect, or finding that the usual number of drinks had much less effect than previously
		11. Experiencing the symptoms of withdrawal after the effects of alcohol were wearing off, such as trouble sleeping, shakiness, restlessness, nausea, sweating, racing heart, or seizure
		Severity is determined based on the number of symptoms present: Mild: 2–3 symptoms
		Moderate: 4–5 symptoms
		Severe: ≥6 symptoms
Binge drinking/heavy drinking	NIAAA	A pattern of drinking that brings blood alcohol concentration levels to 0.08 g/dL, which typically occurs after 4 drinks for women and 5 drinks for men-in about 2 h
Episodes	SAMHSA	Drinking ≥5 alcoholic drinks on the same occasion on at least 1 day in the past 30 days
Heavy drinking	SAMHSA	Drinking ≥5 drinks on the same occasion on each of ≥5 days in the past 30 days
Alcohol dependence	WHO/ICD -10-CM	≥3 of the following at some time during the previous year:
		A strong desire or sense of compulsion to take the substance
		Difficulties in controlling substance-taking behavior in terms of its onset, termination, or levels of use
		A physiological withdrawal state when substance use has ceased or been reduced, as evidenced by the characteristic withdrawal syndrome for the substance; or use of the same (or a closely related) substance with the intention of relieving or avoiding withdrawal symptoms
		Evidence of tolerance, such that increased doses of the psychoactive substance are required ¡ท order to achieve effects originally produced by lower doses (clear examples of this are found in alcohol- and opiate-dependent individuals who may take daily doses sufficient to incapacitate or kill nontolerant users)
		Progressive neglect of alternative pleasures or interests because of psychoactive substance use, increased amount of time necessary to obtain or take the substance, or to recover from its effects
		Persisting with substance use despite clear evidence of overtly harmful consequences, such as harm to the liver through excessive drinking, depressive mood states consequent to periods of heavy substance use, or drug-related impairment of cognitive functioning; efforts should be made to determine that the user was actually, or could be expected to be, aware of the nature and extent of the harm
Abbreviations: ASAM. American Society of Addiction Medicine; DSM-5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; ICD-10-CM. International Classification of Diseases. Tenth Revision Clinical Modification NIAAA. National Institute on Alcohol Abuse and		Alcoholism; SAMHSA. Substance Abuse and Mental Health Services Administration; WHO. World Health Organization.

^a According to the American Society of Addiction Medicine, the preferred term; is “heavy drinking episode.”

Patients, their families, and society, in general, should be aware that AUDs are not a result of any individual weakness or moral failing but arise from a complex interaction of individual, social, cultural, and biological factors. Most people with AUD are difficult to identify because they are likely to have jobs and families and to present with general complaints, such as malaise, insomnia, anxiety, sadness, or a range of medical problems.

In 2013, the US Preventive Services Task Force (USPSTF) recommended that clinicians screen adults 18 years or older for alcohol misuse and provide brief behavioral counseling interventions to those engaged in risky or hazardous drinking behaviors. Of the available screening tools, the USPSTF determined that 1-item to 3-item screening instruments have the best accuracy for assessing unhealthy alcohol use in adults 18 years or older. These instruments include the abbreviated Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) and the NIAAA-recommended Single Alcohol Screening Questionnaire (SASQ). This high burden of alcohol-related injury and disease indicates a need to increase awareness of AUD and its effective treatment options (see Box 137.3 ).

BOX 137.3

AUDIT-C Questions

Adapted from Miller LB, Brennan-Cook J, Turner B, et al. Utilizing an Evidence-Based Alcohol Screening Tool for Identification of Alcohol Misuse. J Addict Nurs . 2018;29(2):90–95.

1.
How often did you have a drink containing alcohol in the past year?
- a.
  Never (0 points)
- b.
  Monthly or less (1 point)
- c.
  Two to four times a month (2 points)
- d.
  Two to three times per week (3 points)
- e.
  Four or more times a week (4 points)
2.
How many drinks containing alcohol did you have on a typical day when you were drinking in the past year?
- a.
  0–2 (0 points)
- b.
  3–4(1 point)
- c.
  5–6 (2 points)
- d.
  7–9 (3 points)
- e.
  10 or more (4 points)
3.
How often did you have six or more drinks on one occasion in the past year?
- a.
  Never (0 points)
- b.
  Less than monthly (1 point)
- c.
  Monthly (2 points)
- d.
  Weekly (3 points)
- e.
  Daily or almost daily (4 points)

Metabolism of Alcohol

While some alcohol is absorbed in the stomach, the vast majority is absorbed in the small intestine. It is distributed uniformly to all organ systems, including the placenta. Although 2% to 10% of alcohol is excreted through the lungs, urine, and sweat, most is metabolized to acetaldehyde, primarily by alcohol dehydrogenase (ADH). The oxidation of alcohol is a complex process involving three enzyme systems, all contained in the hepatocyte. Acetaldehyde is then quickly converted to carbon dioxide and water, primarily through aldehyde dehydrogenase (ALDH). The common forms of ADH decrease the alcohol concentration in blood by about 4.5 mmol/L ethanol/h (the equivalent of about one drink/h):

where NAD is nicotinamide adenine dinucleotide and NADH is reduced nicotinamide adenine dinucleotide.

At least two variations of ADH genes ( ADH1B∗2 and ADH1C∗1 ) produce a slightly more rapid breakdown of alcohol and therefore potentially faster production of acetaldehyde, which is rapidly metabolized by ALDH2 . However, about 40% of Asian people (Japanese, Chinese, and Koreans) have an inactive ALDH2 mutation that results in much higher acetaldehyde levels after drinking than normal. About 10% of people who are homozygous for this gene form cannot drink alcohol without becoming sick and have almost no risk of AUD, whereas those who are heterozygous have a relatively low rate of AUD.

An alternative pathway, the microsomal ethanol-oxidizing system (MEOS), is induced by chronic alcohol exposure. The primary component of the MEOS is the molecule cytochrome P ₄₅₀ , which exists in several variants. The variant most important for alcohol metabolism is cytochrome P ₄₅₀ 2E1 (CYP2E1). Many effects of alcoholism are produced by the toxic byproducts (hydrogen, acetaldehyde), acceleration of the metabolism of other drugs, and activation of hepatotoxic compounds by these metabolic pathways.

Although the liver is the major site of ethanol metabolism, other tissues contribute to its metabolism. ADH is found in the gastric mucosa, but the gastric metabolism of alcohol is decreased in women and those of Asian descent. This increased bioavailability of ethanol or decreased first-pass metabolism may explain the greater vulnerability of women to acute and chronic complications of alcohol.

Alcohol metabolism has two elimination rates. The alcohol elimination rate approximates zero-order kinetics (constant rate) for lower ethanol levels and first-order kinetics (amount of drug removed over time is proportional to the concentration of the drug) for higher levels, especially in chronic alcoholics; most likely, through induction of the MEOS pathway, the elimination rate is increased at higher blood levels.

The absorption and elimination rates of alcohol vary by individual and depend on many factors. There is enormous variation among patients in the rate of elimination of ethanol from the blood, ranging from 9 to 36 mg/dL/h in published data. Although the clearance rate may be as high as 36 mg/dL/h in some chronic drinkers, 20 mg/dL/h is a reasonable rate to assume in a typical intoxicated ED patient.

Physiologic effects vary directly with the blood alcohol level ( Table 137.2 ). Diminished fine motor control and impaired judgment appear with alcohol concentrations as low as 20 mg/dL (0.02 mg%), but wide individual variability exists. Chronic alcoholics can exhibit impressive tolerance. The blood alcohol concentration of a person cannot be accurately determined without quantitative testing. More than 50% of the adult population is obviously intoxicated with a level of 150 mg/dL (0.15 mg%). As the ethanol level rises, the patient’s level of consciousness declines, eventually ending in a coma. Death is caused by aspiration or respiratory depression.

TABLE 137.2

Physiologic Effects and Blood Ethanol Levels

Blood Ethanol Concentration (mg/dL)	Effects ^a
20–50	Diminished fine motor control
50–100	Impaired judgment, impaired coordination
100–150	Difficulty with gait and balance
150–250	Lethargy, difficulty sitting upright without assistance
300	Coma in the novice drinker
400	Respiratory depression

a These effects are for the occasional drinker. Chronic drinkers can function at much higher alcohol concentrations because of tolerance. On the other hand, patients may become comatose with low levels of alcohol in mixed alcohol-drug overdose.

Clinical Features

Alcohol Withdrawal Syndrome

Alcohol is a central nervous system (CNS) depressant. Chronic alcohol use results in a down-regulation of γ-aminobutyric acid (GABA) receptor activity and disinhibition of the dopaminergic reward pathway. This down-regulation of GABA receptors is thought to lead to an increase in the desirable effects of alcohol and vulnerability for dependence due to the presence of increased synaptic GABA. The hallmark of alcohol withdrawal is CNS excitation, with increased cerebrospinal fluid, plasma, and urinary catecholamine levels. Alcohol withdrawal syndrome (AWS) is a continuum of syndromes that begins after a decrease in the amount of intake of ethanol. Therefore, only a reduction, not the abrupt cessation, of ethanol intake may result in withdrawal.

AWS is often divided into three sets of symptoms. The first set consists of autonomic hyperactivity, which appears within hours of the last drink and usually peaks within 24 hours.

Symptoms may occur as early as 6 hours after cessation of or a significant decrease in alcohol intake and usually peaks at 24 to 36 hours. It is characterized by mild autonomic hyperactivity—anorexia, nausea, vomiting, anxiety, coarse tremor, tachycardia, hypertension, hyperreflexia, and sleep disturbances such as insomnia and vivid dreams.

The second symptom set includes additional neuronal excitation, with epileptiform seizures and global confusion, usually occurring within 24 to 48 hours of abstinence and usually peaks at 50 hours after cessation of or a significant decrease in alcohol intake but occasionally takes up to 5 days. The syndrome is characterized by pronounced anxiety, insomnia, irritability, tremor, anorexia, tachycardia, hyperreflexia, hypertension, fever, decreased seizure threshold, visual and auditory hallucinations, and finally delirium.

The third set of symptoms features delirium tremens or alcohol withdrawal delirium (AWD). While only 5% of patients hospitalized for alcohol withdrawal have delirium tremens, this syndrome is a life-threatening manifestation of alcohol withdrawal and consists of gross tremor, frightening visual hallucinations, profound confusion, agitation, and a hyperadrenergic state characterized by a temperature above 101°F (≈38.5°C), blood pressure higher than 140/90 mm Hg, and tachycardia. It seldom appears before the third post abstinence day.

The criteria for withdrawal delirium, as described in Box 137.1 , are delirium and alcohol withdrawal. Alcohol withdrawal is the most common alcohol-related illness that may require inpatient admission and is associated with adverse events such as uncontrolled agitation with the potential for over-sedation, generalized seizures, and prolonged hospital stay. Emergency clinicians should be familiar with the commonly used withdrawal rating instrument known as the Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar). See Table 137.3 .

BOX 137.1

DSM-5 Criteria for Withdrawal Delirium (Delirium Tremens)

From the American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Washington DC: American Psychiatric Publishing; 2013.

Criteria for Alcohol Withdrawal

Cessation of or reduction in heavy and prolonged use of alcohol
At least two of eight possible symptoms after reduced use of alcohol:
- Autonomic hyperactivity
- Hand tremor
- Insomnia
- Nausea or vomiting
- Transient hallucinations or illusions
- Psychomotor agitation
- Anxiety
- Generalized tonic-clonic seizures

Criteria for Delirium

Decreased attention and awareness
Disturbance in attention, awareness, memory, orientation, language, visuospatial ability, perception, or all these abilities change from the normal level and fluctuate in severity during the day
No evidence of coma or other evolving neurocognitive disorders

TABLE 137.3

Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)

Adapted from Sullivan JT, Sykora K, Schneiderman, J, et al. Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Br J Addict . 1989;84:1353–1357.

Components of Scale	Most Severe Manifestations
Nine items ^a
Nausea or vomiting	Constant nausea with vomiting
Tremor	Severe tremor, even with arms extended
Paroxysmal sweats	Drenching sweats
Anxiety	Acute panic
Tactile disturbances (e.g., itching, numbness, sensation of bugs crawling on or under the skin)	Continuous hallucinations
Auditory disturbances (e.g., sensitivity to sound, hearing things that are not there)	Continuous hallucinations
Visual disturbances (e.g., sensitivity to brightness and color, seeing things that are not there)	Continuous hallucinations
Headache, sensation of a band around the head	Extremely severe headache
Agitation	Pacing during most of an interview with clinician or thrashing about
One item—orientation and clouding of sensorium ^b

a Scored on a scale ranging from 0 (no symptoms) to 7 (most severe symptoms).

b Scored on a scale ranging from 0 (no symptoms) to 4 (disoriented with respect to place or person).

Alcohol-Related Seizures

Patients presenting to the ED with seizures should be questioned about alcohol intake ( Box 137.2 ). Of seizure patients presenting to an ED, 20% to 40% will have their seizures related to alcohol use or abuse. The primary consideration in the initial care of seizure patients who regularly consume alcohol is the recognition of treatable, life-threatening causes. Alcohol may act in one of several ways to produce seizures in patients by its partial or absolute withdrawal after a period of chronic intake by, an acute alcohol-related metabolic disorder (e.g., hypoglycemia, hyponatremia), an acute event leading to cerebral trauma, precipitation of seizures in patients with idiopathic or posttraumatic epilepsy, or lowering of the seizure threshold in patients with prior existing intracerebral disease states.

BOX 137.2

Differential Diagnosis of Alcohol-Related Seizures

Withdrawal (alcohol or drugs)
Exacerbation of idiopathic or posttraumatic seizures
Acute intoxication (e.g., amphetamines, anticholinergics, cocaine, isoniazid, organophosphates, phenothiazines, tricyclic antidepressants, salicylates, lithium)
Metabolic (e.g., hypoglycemia, hyponatremia, hypernatremia, hypocalcemia, hepatic failure)
Infectious (e.g., meningitis, encephalitis, brain abscess)
Trauma (e.g., intracranial hemorrhage)
Cerebrovascular accident
Sleep deprivation
Noncompliance with anticonvulsants

Alcohol Withdrawal Seizures

Withdrawal seizures may occur 6 to 48 hours after the cessation of drinking. Of patients with seizures, 90% have one to six generalized tonic-clonic seizures, and 60% experience multiple seizures within a 6-hour period. The incidence of partial seizures, common with posttraumatic epilepsy, is increased during alcohol withdrawal. The term alcohol withdrawal seizure is reserved for seizures with these characteristics. The term alcohol-related seizure is used to refer to all seizures in the aggregate associated with alcohol use, including this subset of alcohol withdrawal seizures.

Alcoholic Hallucinosis

Alcoholic hallucinosis is clinically distinct from delirium tremens and is characterized by hallucinations presenting within 12 to 24 hours of abstinence and resolve within 24 to 48 hours, in contrast to delirium tremens that presents at least 48 to 72 hours after abstinence. Hallucinations are typically visual, although tactile hallucinations have been described. Alcoholic hallucinosis is also generally not associated with autonomic instability such as tachycardia, hypertension, or hyperthermia.

Cardiovascular Effects

Acute and chronic ethanol consumption can affect the mechanical function of the heart, produce dysrhythmias, and exacerbate coronary artery disease (CAD). It may alter myocardial function by direct toxic effects, by associated hypertension, or indirectly by altering specific electrolytes. Acute intoxication can decrease cardiac output in alcoholic and nonalcoholic patients with preexisting cardiac disease (see Table 137.4 ).

Table 137.4

Cardiovascular Effects of Alcohol

Data from Klatsky AL. Alcohol and cardiovascular diseases: where do we stand today? J Intern Med . 2015;278(3):238-–250.

Condition	Probable Relationship With Alcohol		Potential Epidemiological Consequences
	Lighter drinking ^a	Heavier drinking ^b
Dilated Cardiomyopathy	Unrelated	One (of several) causes; ? requires cofactors	↑ risk of HF, AF, cardioembolic stroke and HS if on ACs
Systemic HTN	Little or none	Probably causal in susceptible persons	↑ risk of HF, AF, IS, and HS
CAD	Protective	? less protective or ↑ risk	↑ risk of HF, cardioembolic stroke, and AF; t risk of HS if on ACs
Supraventricular arrhythmia	Little or none	Probably a causal factor, especially with binges	↑ risk of cardioembolic stroke, and HS if on ACs
HS	? unrelated or slight ↑ risk	↑ risk	Disability and ↑ risk of VTE
IS	Protective	Probable ↑ risk; varies with subtype	Disability and ↑ risk of VTE
Heart failure	Indirectly protective	Varies with underlying CV condition	Disability and ↑ risk of VTE

AC , Anticoagulant; AF , atrial fibrillation; CAD, coronary artery disease; HS , hemorrhagic stroke; HTN , hypertension;; IS , Ischemic stroke; VTE, venous thromboembolism; cv, cardiovascular; t, increase; 4, decrease; ?, possibly.

a Less than three standard-sized drinks per day; ^b Three or more standard-sized drinks per day.

Studies have linked moderate alcohol consumption (two drinks/day in men and one drink/day in women) with a reduced risk of cardiovascular disease. There is a strong biological plausibility that moderate wine consumption may have a positive effect on organs and systems. Whether the positive effect of wine on health is attributed to ethanol, to wine micro-constituents, or to their synergistic effect, is still unanswered. Low to moderate alcohol consumption decreases platelet aggregation, raises plasma levels of endogenous tissue plasminogen activator, and lowers insulin resistance and likely poses little cardiovascular risk.

Heavy alcohol consumption has a detrimental effect on those with preexisting CAD. It reduces exercise tolerance, induces coronary vasoconstriction, and raises heart rate and blood pressure. These patients also have a significantly higher incidence of peripheral arterial disease. The additive cardiovascular effects of ethanol and nicotine contribute to dysrhythmias and sudden death in patients with CAD.

Alcohol abuse is a known risk factor for the development of alcoholic cardiomyopathy which presents as a dilated cardiomyopathy that can lead to heart failure. ^, Heavy drinkers have increased odds of having a prolonged QTc interval and supraventricular dysrhythmias. Supraventricular (usually atrial fibrillation) and ventricular (usually transitory ventricular tachycardia) dysrhythmias, commonly referred to as “holiday heart,” have been documented in alcoholic patients who have been drinking heavily. Tachydysrhythmias as a result of episodic drinking commonly revert to sinus rhythm with abstinence and do not require immediate intervention if the patient is hemodynamically stable.

Pulmonary Effects

There is a clear and statistically significant relationship between alcohol consumption and the risk of community-acquired pneumonia (CAP). Consuming drinks that contain 10 to 20 g of alcohol per day is linked to an 8% increased risk of acquiring CAP. Pneumococcal pneumonia is the most common type of pneumonia in both healthy individuals and heavy alcohol users. In addition, Klebsiella pneumoniae also is increased in people with AUD and seems to cause disproportionate rates of lung infection and high mortality in this population.

For centuries, it has been known that people with AUD are more likely to have pulmonary infections such as pneumonia and tuberculosis. Over the past two decades, it has become clear that other conditions such as RSV and ARDS also are linked to high-risk alcohol consumption.

Gastrointestinal and Hepatic Effects

Esophagus and Stomach

Alcoholic patients have a higher incidence of esophagitis, gastric cancer, and esophageal carcinoma than in the general population. Acute alcohol ingestion also decreases lower esophageal sphincter pressure, delays gastric emptying, and disrupts the normal gastric mucosal barrier. Alcohol consumption, because of its inherent toxicity, has been shown to eliminate infection of the gastric mucosa by Helicobacter pylori. Forceful or persistent emesis can lead to a Mallory-Weiss tear or more severely, Boerhaave syndrome.

Gastrointestinal Bleeding

Alcohol is closely associated with gastrointestinal (GI) bleeding. Causes and contributing factors include Mallory-Weiss tears, esophagitis, esophageal varices, acute and chronic gastritis, thrombocytopenia, portal hypertensive gastropathy, qualitative and quantitative platelet disorders, and prolonged clotting times. Alcohol may exacerbate gastric mucosal damage when it is combined with nonsteroidal antiinflammatory drugs (NSAIDs), but ethanol itself is not a risk factor for peptic ulcer disease. Peptic ulcer disease is the most common cause of bleeding in alcoholic patients with upper GI hemorrhage, as well as in those who do not regularly consume alcohol.

Liver Damage

Hepatic damage has been recognized for centuries as the hallmark of chronic alcohol abuse. Above a certain quantity, alcoholic consumption can elicit a spectrum of liver lesions among which steatosis is present in nearly all drinkers who consume in excess of 40 g/day regularly. The activation of the immune system with the production of cytokines such as tumor necrosis factor-alpha is one of the earliest events in many types of liver injury. This cascade stimulates Kupffer cells and the production of other cytokines that together enlist inflammatory cells, kill hepatocytes, and initiate healing through fibrogenesis.

Alcoholic liver disease is the most common liver disorder in the Western Hemisphere and, along with hepatitis C (HCV), is a leading cause of liver transplantation. Alcohol use is associated with more persistent HCV infection and more extensive liver damage than no alcohol use because of interactions between alcohol use and HCV that affect immune responses, cytotoxicity, and oxidative stress. No safe level of alcohol consumption has been determined for patients with HCV.

Alcoholic Hepatitis

Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25% to 35% in 1 month) in the setting of chronic alcohol use. It is a clinical syndrome characterized by right upper quadrant pain, a tender enlarged liver, fever, jaundice, leukocytosis, and altered liver function test results. aspartate transaminase (AST) levels are usually less than 400 IU/L, and ALT levels are typically less than half the AST level. It is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens.

Alcoholic hepatitis has a range of clinical manifestations from mildly symptomatic hepatomegaly to fulminant hepatic failure. The severity of the disease can be estimated in the ED by a prolonged prothrombin time/international normalized ratio (INR) or with the use of the Maddrey discriminant factor. The ABIC ( a ge, b ilirubin, I NR, c reatinine) score and model for end-stage liver disease (MELD) are also helpful in predicting mortality in these patients.

Cirrhosis

The causal association between alcohol intake and alcoholic liver disease has been well documented, yet liver cirrhosis develops in only 10% to 20% of heavy drinkers. Cirrhosis is the disruption of the normal architecture of the liver by scarring and regenerating nodules of parenchyma. Alcoholism is the most common cause of cirrhosis in the United States and is responsible for approximately 48% of all cirrhotic-induced deaths. Alcoholic cirrhosis usually requires 10 to 15 years of chronic drinking, often punctuated by one or more episodes of acute alcoholic hepatitis. The clinical outcome is determined by the development of complications of portal hypertension and hepatic dysfunction. Alteration of the normal hepatic architecture by fibrosis and nodule formation may eventually lead to portal hypertension. Portal hypertension may be complicated by ascites and esophageal varices. Although cirrhosis is irreversible, its progression may be halted with abstinence.

Pancreatitis and Malabsorption

The association of ethanol with acute and chronic pancreatitis is well established, but the exact pathogenesis is unclear. Hypotheses include reflux of duodenal contents and bile into the pancreatic duct, obstruction by a plug of pancreatic juice rich in proteins, and a direct toxic effect of ethanol.

The diagnosis of alcoholic pancreatitis can be difficult because asymptomatic alcoholics may have an elevated amylase level. Conversely, up to 30% of patients with acute alcoholic pancreatitis have an amylase value within normal limits. The serum lipase level rises after amylase, remains elevated longer, and is a more reliable indicator of alcoholic pancreatitis, especially when it is more than three times the normal range.

Neurologic Effects

Neuropathy

A symmetric sensorimotor polyneuropathy is common with chronic alcohol abuse, usually in the lower extremities. It is thought to be a combination of nutritional deficiency with thiamine or vitamin B ₁₂ deficit and a direct neurotoxic effect of alcohol. Burning pain and paresthesia are common complaints. Findings on physical examination include loss of light touch, decreased pinprick sensation, and reduced lower extremity deep tendon reflexes. Distal muscle weakness is a delayed finding. The neuropathy may lead to nonhealing ulcers on the feet. Treatment of alcoholic neuropathy is abstinence, adequate diet, and thiamine. Complete recovery is rare.

So-called “Saturday night palsy” or “honeymooner’s syndrome” is a wrist drop caused by radial nerve compression. The patient usually has spent the night with his or her arm drooped over the back of a chair, bench, or companion; compressing the radial nerve against the humerus producing neurapraxia. Loss of function due to radial nerve neuropraxia usually returns after a few weeks to months.

Wernicke-Korsakoff Syndrome

There are high rates of dementia reported in patients with AUD, and up to 25% when all types of severe cognitive impairment are considered. Previously, two main disorders were described: Wernicke-Korsakoff syndrome (WKS) and alcohol-related dementia (ARD). Now, the DSM-5 introduces major neurocognitive disorder as an alternative term to dementia, with a subtype related to substance or medication use. WKS and ARD could be a direct result of alcohol neurotoxicity or the consequence of a concurrent underlying pathology (such as thiamine deficiency) or both (neurotoxicity associated with nutritional deficiencies).

Although they are similar pathologically and are caused by thiamine deficiency, Wernicke and Korsakoff syndromes are clinically distinct. Wernicke encephalopathy, a medical emergency with a mortality rate of approximately 17%, remains a clinical diagnosis and is often unrecognized. Contemporary criteria require two of these signs—dietary deficiencies, oculomotor abnormalities (nystagmus being the most common), cerebellar dysfunction, and an altered mental state or mild memory impairment. Mental abnormalities include lethargy, inattentiveness, abulia, and impaired memory, progressing without treatment to coma.

Korsakoff psychosis or amnesic state also called an alcohol-induced persisting amnestic disorder, is a disorder with recent memory impairment, inability to learn new information or recall previously learned information, apathy, and confabulation. Although it is common, confabulation is not essential for the diagnosis. Whereas 80% of patients with acute Wernicke’s encephalopathy have Korsakoff syndrome, age older than 40 years and many years of heavy alcohol use are additional risk factors.

Treatment of WKS consists of abstinence, adequate diet, and thiamine. The ophthalmoplegia and nystagmus usually have a good response to thiamine administration within hours to days. The ataxia and mental changes may take days to weeks to improve and usually have a poorer prognosis. Less than 25% of patients show any real recovery, 50% show some recovery, and the remainder show no response, despite adequate thiamine replacement. Because magnesium is a cofactor for this enzyme system, its serum levels should be corrected. Patients with WKS require admission with thiamine and magnesium repletion.

Alcoholic Cerebellar Degeneration

Characterized by ataxia of the extremities, cerebellar ataxia of alcoholism results in a wide-based stance and uncoordinated gait. Lower extremity involvement predominates, although the arms may rarely be involved. Pathologic changes consist of the degeneration of elements in the cerebellum, especially the Purkinje cells. The diagnosis is based on history, physical examination, and findings on magnetic resonance imaging or computed tomography (CT), which shows severe cerebellar atrophy. Treatment consists of abstinence, adequate nutrition, and thiamine.

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