Epidemiology

The disastrous effects and widespread incidence of alcoholism are well known to the emergency physician. Almost all societies that consume alcohol show related health and social problems.¹ Motor vehicle collisions, drowning, suicides, homicides, divorce, violent crime, child abuse, unemployment, and disruption of the family are often either directly or indirectly associated with excessive alcohol consumption. The tragic effects of alcohol not only affect the individual drinker but also have far-reaching implications for the family, community, and workplace. In the United States, an estimated 7.6 million visits to the emergency department (ED) a year are related to alcohol, accounting for 7.9% of all ED visits.² Table 185-1 lists the causes of death related to alcohol abuse.

Alcohol is the most common recreational drug taken by Americans, and per capita consumption is increasing. An estimated 18 million alcoholics live in the United States; with more than 85,000 alcohol-related deaths each year, resulting in 2.3 million years of potential life lost,³ alcohol is the third leading cause of preventable death in the United States.⁴ Alcoholism permeates all levels of society and is a preventable cause of morbidity and mortality, with a cost to the nation estimated to be greater than $185 billion annually.⁵

The alcohol-use disorders consist of alcohol dependence, alcohol abuse, and dependence or harmful use. These disorders are common in all developed countries and are more prevalent in men than in women, with lower but still substantial rates in developing countries. However, most people with alcohol-use disorders 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.

Diagnosis

Alcohol dependence is associated with major physiologic consequences and life impairment. Dependence can be identified as repetitive problems, affecting three or more areas of life, and about 80% of people who are diagnosed with dependence at any point still have alcohol-related problems when they are assessed a year or more later.⁶ Dependence criteria are reliable across different ages, sexes, and most cultural groups. Alcohol abuse is defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), as one or more problems with functioning in a 12-month period in a person without dependence: failure in obligations; alcohol use in hazardous situations; recurrent legal problems; or continued use despite social or interpersonal problems.⁷

Pathophysiology

Definition and Natural History

A precise definition of alcoholism is difficult. A proposed definition encompassing the features of alcoholism is “a primary chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations.” The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with and use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be periodic or continuous.⁸ Alcoholism is present when drinking adversely affects an individual’s physical health, ability to function in society, or interpersonal relationships.

Hazardous or “at-risk” drinking is defined by the National Institute on Alcohol Abuse and Alcoholism as the following:

Harmful drinkers present with negative consequences related to alcohol.

The natural history of alcoholism is variable, and it may appear in any patient despite age or social status. The age at onset of alcoholism continues to decrease. Up to 6% of high school seniors drink daily, and it is not unusual to see children younger than 16 years who have already graduated from an alcohol detoxification program.⁹ Many individuals also begin drinking heavily after the age of 60 years.

The DSM-IV has two categories for substance disorders that include alcohol abuse: (1) substance abuse and (2) substance dependence.⁷ The chronic substance abuse of alcohol eventually leads to acquired tolerance, a condition in which larger and larger doses of alcohol are required for the same effect.

Principles of Disease

The neurophysiology of alcohol withdrawal is complex and not fully understood. Chronic alcohol consumption has a depressant effect on the central nervous system (CNS). The hallmark of alcohol withdrawal is CNS excitation with increased cerebrospinal fluid, plasma, and urinary catecholamine levels. Chronic alcohol consumption affects central adrenergic alpha receptors, glutamate, central adrenergic beta receptors, the inhibitory neurotransmitter γ-aminobutyric acid (GABA), and dopamine turnover.¹⁵

Differential Considerations

Alcohol withdrawal syndrome can initially be confused with acute schizophrenia, encephalitis, drug-induced psychosis, thyrotoxicosis, anticholinergic poisoning, and withdrawal from other drugs of the sedative-hypnotic type. It may be difficult to differentiate between alcohol withdrawal and alcohol-induced hypoglycemia.

Signs of alcohol withdrawal usually begin 6 to 24 hours after a decrease in the patient’s usual intake of alcohol. If patients manifest withdrawal 3 to 4 days or more after their last drink, drugs with a longer half-life should be considered. The barbiturate and benzodiazepine withdrawal syndromes usually progress more slowly, with a higher frequency of seizures later (7 days versus 2 days), and status epilepticus is more common than with alcohol withdrawal.

Clinical Features

Isbell’s classic study in 1955 confirmed the relationship between alcohol and the withdrawal syndrome.¹⁶ He documented that the severity of signs and symptoms depends on both the dose and the duration of ethanol consumption. The withdrawal syndrome may occur any time after the blood alcohol level starts to fall. Therefore, only a reduction, not the abrupt cessation, of ethanol intake may result in withdrawal.

Minor alcohol withdrawal occurs as early as 6 hours and usually peaks at 24 to 36 hours after cessation of or significant decrease in alcohol intake. It is characterized by mild autonomic hyperactivity: nausea, anorexia, coarse tremor, tachycardia, hypertension, hyper-reflexia, sleep disturbances (e.g., insomnia, vivid dreams), and anxiety.¹⁷

Major alcohol withdrawal occurs after more than 24 hours and usually peaks at 50 hours but occasionally takes up to 5 days to be manifested after the decline or termination of drinking. The syndrome is characterized by pronounced anxiety, insomnia, irritability, tremor, anorexia, tachycardia, hyper-reflexia, hypertension, fever, decreased seizure threshold, auditory and more commonly visual hallucinations, and finally delirium.¹⁸

Delirium tremens is a life-threatening manifestation of alcohol withdrawal and consists of gross tremor, frightening visual hallucinations, profound confusion, agitation, and a hyperadrenergic syndrome characterized by temperature above 101° F, blood pressure higher than 140/90 mm Hg, and tachycardia. It seldom appears before the third post-abstinence day. Only 5% of patients hospitalized for alcohol withdrawal have delirium tremens.

Management

Family, friends, bystanders, or paramedics often give more reliable historical data than the patient does. Accurate vital signs are essential. This may require a rectal temperature. Hyperthermia, hypothermia, tachypnea, or tachycardia may suggest serious disorders that often accompany the alcohol-dependent patient. These disorders should be considered during this first assessment.

A rapid, thorough examination should be performed with attention to the level of consciousness, signs of hepatic failure, or coagulopathy. Signs of trauma are sought, such as subcutaneous emphysema, ecchymosis, subconjunctival hemorrhage, hemotympanum, or Battle’s sign, and palpation is done for occult injuries. The neurologic examination should search for focal findings, including central facial nerve palsy, hemiparesis, and asymmetry of pupillary response.

The alcohol withdrawal syndrome should be promptly recognized and treated to provide relief from anxiety and hallucinations; to halt progression to major withdrawal and withdrawal seizures; to allow detection of a treatable primary psychiatric illness; to prepare the patient for long-term alcohol abstinence with the lowest risk of new drug dependence; and to calm the patient and allow adequate examination for the detection of medical illnesses that typically accompany alcoholism, such as gastritis, dehydration, pancreatitis, pneumonia, electrolyte disorders, and hepatitis.

In combination with appropriate chemical sedation, detention by reasonable restraint may be an option to prevent potential injury that patients may inflict on themselves or the hospital staff. These appropriate measures need to be instituted, and decision-challenged patients should not be permitted to sign an “against medical advice” form and be discharged.

Patients suffering from alcohol withdrawal should receive pharmacologic intervention along with supportive care. The ideal drug for alcohol withdrawal would have a rapid onset, wide margin of safety, metabolism not dependent on liver function, and limited abuse potential. Although no one drug class fits all these requirements, benzodiazepines are clearly the mainstay of treatment.

Emergency Department and Outpatient Approaches

Outpatient treatment consists of lorazepam, 1 to 2 mg three times a day in a tapering dose for 3 to 6 days; chlordiazepoxide, 25 to 100 mg three times a day, in a tapering dose for 3 to 6 days; or diazepam, 30 mg once a day tapered during 5 days, depending on the severity of symptoms. Adequate diet, abstinence, and participation in a rehabilitation program in the community are also desirable. Any patient requiring 300 mg of chlordiazepoxide or 60 mg of diazepam per day to control withdrawal should be considered for admission. Patients with major alcohol withdrawal (disorientation, hallucinations, diaphoresis, or fever) are admitted.

Adjunctive Therapy

Patients being treated for major alcohol withdrawal may be given thiamine (100 mg IV) and magnesium (2 g IV). Although magnesium sulfate does not decrease the severity of withdrawal symptoms, the incidence of delirium, or seizures, it carries no significant risk (with adequate renal function).

If volume depletion is present, it can be corrected with normal saline. Reversal of electrolyte and metabolic disorders (hypomagnesemia, hypophosphatemia, hypokalemia, and acidosis) benefits the patient, but it does not abate the withdrawal syndrome.

Alcohol Withdrawal Seizures

Descriptions of alcohol withdrawal seizures are based on data collected by Victor and Brausch.³⁰ Seizures occurred 6 to 48 hours after the cessation of drinking. Ninety percent had one to six generalized tonic-clonic seizures. Sixty percent experienced multiple seizures within a 6-hour period. However, seizure recurrence can be reduced to 3% with lorazepam administration after the initial seizure.³¹ The incidence of partial seizures, common with post-traumatic epilepsy, is increased in alcohol withdrawal. The term alcohol withdrawal seizure is reserved for seizures with the characteristics described by Victor and Brausch.³⁰ 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 seizure.

Patients Presenting with Normal Findings on Neurologic Examination

Patients with an Abnormal Neurologic Presentation

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 both alcoholic and nonalcoholic patients with preexisting cardiac disease.³⁸

Studies have linked moderate alcohol consumption (two to four drinks per day in men and one or two in women) to a protective effect from CAD. Low to moderate alcohol consumption decreases platelet aggregation, raises plasma levels of endogenous tissue plasminogen activator,³⁹ and lowers insulin resistance. Experimental data suggest that alcohol may have antioxidant properties, produce effects on smooth muscles through interactions with nitric oxide, and alter plasma total homocysteine levels.^40,41 The red versus white wine hypothesis rests on human studies showing short-term cardiovascular benefits achieved by de-alcoholized red but not white wine and many studies on isolated tissues or organs assessing the effects of polyphenols in red wine, especially resveratrol. Therefore, red wine potentially has beneficial effects beyond alcohol content.⁴²

Studies suggest that moderate alcohol consumption, through a reduced risk of CAD, may also protect individuals from congestive heart failure (Box 185-2).⁴³ All of these beneficial effects are lost in heavy drinkers, in whom chronic alcoholism is associated with hypertension and congestive cardiomyopathy.

Up to one third of chronic alcoholic patients have left ventricular dysfunction demonstrated by radionuclide ventriculography, usually coexisting with skeletal muscle disease. Those who stop using alcohol may have an improved ejection fraction during the course of 3 years.⁴⁴ Although the primary functional abnormality of alcoholic cardiomyopathy was thought to be a depression in systolic function, it is now appreciated that an impairment in diastolic function is present in one third of alcoholics who have a normal systolic function; in many, systolic dysfunction and diastolic dysfunction coexist. Excess alcohol consumption affects not only the cardiomyocytes but striated skeletal muscle as well. Women appear to be more sensitive than men to the toxic effects of alcohol on striated muscle and are at greater risk for cardiomyopathy and myopathy as well as for skeletal myopathy for any given lifetime amount of alcohol.⁴⁴

Heavy alcohol consumption has a detrimental effect on those with preexisting CAD. It can reduce exercise tolerance, induce coronary vasoconstriction, and raise heart rate and blood pressure.⁴⁵ Additive cardiovascular effects of ethanol and nicotine contribute to dysrhythmias and sudden death in patients with CAD. In one study, nearly half the patients with alcohol withdrawal had prolongation of the QT interval. Prolonged QT can precipitate a dysrhythmia, resulting in sudden death.⁴⁶ There is an increased incidence of sudden death among heavy drinkers regardless of concomitant CAD or smoking.

Supraventricular (usually atrial fibrillation) and ventricular (usually transitory ventricular tachycardia) dysrhythmias, labeled “holiday heart,” have been documented in alcoholic patients who have been drinking heavily. One study reported that alcohol contributes to or causes new-onset atrial fibrillation in approximately two thirds of patients younger than 65 years. 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.

Alcohol also affects cardiac function indirectly by lowering potassium and magnesium levels. Data from the Framingham Heart Study indicate that patients with lower levels of potassium and magnesium have higher rates of dysrhythmias.⁴⁷

Pulmonary Effects

Alcohol reduces the mobilization of alveolar macrophages and their bactericidal capacity. Their impairment is greatest in alcoholics with hepatic cirrhosis. In alcoholic patients, the lungs are more vulnerable to oxidative stress and injury. There is evidence that chronic alcohol consumption decreases the level of glutathione, promoting inflammation and remodeling of the lung tissue.⁴⁸ These effects, along with aspiration, decreased airway sensitivity, concomitant smoking, and malnutrition, probably account for the increased incidence of pneumonia, particularly lobar pneumonia, among alcoholic patients.⁴⁹ Alcohol abuse is also associated with an increased likelihood of intensive care unit admission and a longer hospital length of stay than for non-alcoholic patients with community-acquired pneumonia.⁵⁰

At least 80% of alcoholics are smokers, making it difficult to distinguish between alcohol-induced and tobacco-induced injury to the lungs. The high prevalence of respiratory disease in alcoholics is largely caused by smoking. Patients with sepsis and chronic alcohol abuse are at least twice as likely to require mechanical ventilation and have a twofold to fourfold risk for development of the acute respiratory distress syndrome.⁵⁰

Alcohol induces bronchospasm in some asthmatics and increases ventricular ectopy and sleep apnea in patients with chronic obstructive pulmonary disease. Alcoholic patients with hepatic cirrhosis can have hypoxemia as a result of precapillary shunting in their lungs. Hyperventilation and respiratory alkalosis are also seen with hepatic cirrhosis. One or two drinks per day has been found to decrease the risk of pulmonary embolus and deep venous thrombosis in elderly patients.⁵¹

Gastrointestinal and Hepatic Effects

Neurologic Effects

Infections

Experimental and clinical data support the conclusion that alcohol is a potent immunomodulatory agent. Chronic alcohol abuse (≥8 drinks/day) leads to immunosuppression.⁷⁶ Animal and human studies have implicated acute and chronic ethanol ingestion in causing decreased serum bactericidal activity, impaired mononuclear phagocyte function, diminished cell-mediated immune functions, reduced delayed hypersensitivity reaction, and defective polymorphonuclear neutrophils. Neutropenia may be found in up to 8% of hospitalized alcoholics.⁷⁷

Alcohol ingestion prevents the normal delivery (chemotaxis) of polymorphonuclear neutrophils to sites of bacterial infection. Chronic alcohol exposure depresses the development and expression of cell-mediated immunity. This depression may contribute to the high incidence of tuberculosis and head, neck, and upper gastrointestinal cancers in alcoholics. Alcohol’s suppression of macrophage function reduces the reticuloendothelial system’s ability to clear particles. This may contribute to spontaneous bacteremia, spontaneous bacterial peritonitis, and pneumonia. Primary antibody response to new antigens is also depressed. Malnutrition and liver failure also contribute to an immunocompromised state in the alcoholic.

The most common infection in alcoholism is pneumonia. Associated risk factors for pneumonia in alcoholics include smoking, decreased ciliary function, decreased surfactant production, depressed cough reflex, malnutrition, and poor oral hygiene. Although alcoholic patients may contract a variety of bacterial pneumonias, Streptococcus pneumoniae is still the most common organism. Periods of alcoholic stupor with incomplete glottic closure and subsequent aspiration can lead to aspiration pneumonia or lung abscess. Klebsiella pneumoniae, classically associated with alcoholism, is currently more common in patients with cytotoxic chemotherapy, hematologic malignant disease, and transplantation than in the chronic alcoholic. In addition, these infections now tend to be nosocomial rather than community acquired.⁷⁷

Chronic alcoholism is also associated with a threefold increase of tuberculosis.⁷⁸ Alcoholism itself does not seem to influence the long-term relapse rates in tuberculous patients if they have closely supervised therapy of adequate duration. Homeless alcoholic patients are an important reservoir of tuberculosis in the United States.

Spontaneous bacterial peritonitis occurs in cirrhotic patients with ascites and has a high mortality rate (50-90%). A common presentation consists of fever, abdominal pain, and leukocytosis. Escherichia coli, K. pneumoniae, and S. pneumoniae are the most common bacteria cultured from the ascitic fluid. Patients with new ascites and fever should have a diagnostic paracentesis as part of their evaluation.

Hepatitis C appears to be related to concomitant injection drug use rather than the direct effect of alcohol abuse. Alcoholism is associated with a high prevalence of unsafe sexual behavior and human immunodeficiency virus (HIV) seropositivity,⁷⁹ with greater immunologic changes in HIV-1–positive patients who also consume alcohol.⁸⁰

Fever in the chronic alcoholic may result from a vast array of causes. The most common infection remains pneumonia. Occult urinary tract infections are more common than expected. The most common noninfectious causes of fever are alcohol withdrawal and alcoholic hepatitis. A leukocytosis is associated with both, often making the differentiation from infection difficult. Both infectious and noninfectious causes may coexist, and there may be multiple sources of infection. Most febrile alcoholics without an identifiable source are best served by hospitalization.

Endocrine Effects

Alcohol dependence adversely affects many endocrine systems. Both peripheral thyroid hormone dysfunction and central hypothalamic-pituitary-thyroid axis deregulation are seen.⁸¹ Male hypogonadism and feminism are seen in chronic male alcoholics. Alcohol’s effects on both the testes and the hypothalamus decrease testosterone production in men.⁸² Alcohol may cause impotence by CNS sedation, secondary depression, or decreased testosterone production. Decreased testosterone, increased estrogen (in patients with liver disease), and increased prolactin can lead to decreased libido, feminization, and gynecomastia in male alcoholics and to abnormalities in lactation and menstruation in women. In female alcoholics, increased levels of testosterone and estrogen are found. Estrogen replacement therapy may increase hormonal levels threefold and thus increase the risk of cholelithiasis and breast cancer.⁸³

Metabolic Effects

Hematologic Effects

The alcoholic presents with myriad hematologic abnormalities. The direct toxic effect of ethanol and its metabolites, secondary nutritional deficiency, and hepatic disease, individually or in combination, affect red blood cells, white blood cells, platelets, hemostasis, and the immune system.⁹² Macrocytosis is the most common hematologic manifestation of the chronic alcoholic. It may be caused by folate deficiency, reticulocytosis (the younger reticulocytes are larger), liver disease (producing an abnormal lipid coating of the red blood cell membrane), or vitamin B₁₂ deficiency. The most common condition is idiopathic macrocytosis of alcoholism.

Oncologic Effects

Worldwide, 389,000 annual cases of cancer representing 3.6% of all cancers are alcohol related.94,95 Although alcohol itself is not carcinogenic, its metabolite, acetaldehyde, is emerging as an important contributor, being able to form stable DNA adducts, to trigger mutations in tumor suppressors and oncogenes, and to interfere with DNA repair. Smoking certainly has an additional role as a cause of neoplasia and is difficult to isolate in these studies.

Chronic alcohol use is associated with an increased incidence of upper alimentary and respiratory tract cancers with a clear dose-response relationship. Specifically, alcohol increases the risk of cancer of the mouth, pharynx, larynx, lung, esophagus, liver, and pancreas.⁹⁶ Chronic hepatitis B infection may sensitize the liver to alcohol, producing hepatocellular carcinoma. Women who drink two to five drinks per day have a relative risk of 1.41 for invasive breast cancer compared with nondrinkers.⁹⁷ There is also a significant increase in endometrial cancer risk among postmenopausal women who consume more than two alcoholic drinks/day.⁹⁸ Moderate alcohol consumption leads to an increased risk of colorectal and prostate cancer.⁹⁹

Hypothermia

Acute alcohol ingestion is one of the most common precipitating factors for accidental hypothermia and occurs in 33 to 73% of patients presenting with a core temperature below 35° C.¹⁰⁰ Alcohol exacerbates hypothermia of other causes with depressed hypothalamic thermoregulation, peripheral vasodilation producing heat loss, CNS depression, sepsis, inability to shiver, hypoglycemia, and increased risk of environmental exposure. Hypothermia may be the presentation of Wernicke’s syndrome, possibly caused by lesions of the posterior hypothalamus, hypoglycemia, or sepsis. Intoxicated patients may have slower rewarming rates.

Psychiatric Effects

Forty-five percent of alcohol-dependent adults are diagnosed with one or more additional psychiatric conditions during their lifetime. Of alcoholic men admitted to a psychiatric ward, approximately 40% have another psychiatric disorder unrelated to substance abuse, in particular, antisocial personality disorder, schizophrenia, mood disorders, and anxiety disorders.

Depression and antisocial personality are the two most common psychiatric disorders that correlate with alcoholism, with a prevalence of 30 to 60% in most studies. Chronic alcohol use can produce an imbalance in the serotoninergic system. This imbalance may lead to increased anxiety, aggression, and depression. Interestingly, aggressive behavior is more strongly linked to depression than to alcohol dependence.¹⁰¹ Secondary depression may be caused by alcoholism, or the primary affective disorder may be present with secondary alcoholism. Mild depressive symptoms are also common in alcohol withdrawal. Antisocial individuals are at high risk for alcoholism and drug dependence, although an unstable, unhappy childhood environment appears to be more important than alcohol to the development of sociopathy. Alcohol increases the lifetime risk of suicide, with 17% of all alcoholics eventually dying by suicide.^102,103 Alcoholism, major depression, and antisocial personality all predispose to suicide, and interaction among the three is particularly dangerous, but the acute risk on any day is difficult to assess.

An alcoholic patient who presents with an apparent psychiatric disorder poses a diagnostic dilemma. Does the patient have a primary affective disorder with secondary alcoholism, or is the patient manifesting anxiety or depressive behavior because of alcoholism? In general, alcoholic patients with psychiatric disorders are best treated with medications that are specific for their psychiatric condition.¹⁰⁴ Many alcoholics with mild depression have spontaneous resolution of symptoms with abstinence. Nevertheless, depression meeting DSM-IV criteria is best treated with antidepressants.^105,106 If abstinence can be achieved, underlying psychiatric disorders are more easily diagnosed and treated.

Enhanced Metabolism and Toxic Metabolites

Most alcohol is metabolized by ADH. A small percentage of alcohol is metabolized by the MEOS–cytochrome P₄₅₀ system, which is also responsible for the metabolism of many drugs. The MEOS metabolic pathway is enhanced in chronic alcoholics, which is associated with the acceleration of the degradation of these other drugs. For example, the half-lives of warfarin, phenytoin, and isoniazid are 50% shorter in abstaining alcoholics than in nondrinkers. Barbiturates, diazepam, propranolol, and rifampin may have increased rates of clearance and shorter half-lives when they are taken by chronic alcoholics. This effect can persist for days to weeks after the cessation of drinking.58,108

Acetaminophen is the most widely used analgesic in the United States and is often recommended to alcoholic patients instead of NSAIDs to prevent gastritis. Chronic alcohol ingestion may enhance acetaminophen hepatotoxicity by accelerating the biotransformation to a toxic metabolite on the basis of a few case reports of severe or lethal acetaminophen toxicity in alcoholics taking therapeutic doses. Increased vulnerability seems to occur immediately after cessation of drinking. A synergistic effect apparently occurs with alcohol, fasting, and acetaminophen use in combination with depleted glutathione stores. A prospective observational study suggested that acute ethanol intake may be associated with a lower risk of hepatotoxicity after acetaminophen overdose.¹⁰⁹ Greatly elevated AST levels (3000-48,000 in one series), increased ALT levels, and greatly elevated prothrombin/INR times help distinguish acetaminophen hepatotoxicity from alcoholic hepatitis.¹⁰⁷

Additive or Synergistic Effects

Alcohol has long been known to have additive or even synergistic effects with several drugs. Acute intoxication decreases the rate of drug metabolism, which is at least partially explained by competition for the same enzymatic process in the liver. For example, ethanol has additive sedative effects when it is taken with first-generation antihistamines, barbiturates, cyclic antidepressants, benzodiazepines, phenothiazines, propoxyphene, propofol, and narcotics. Alcohol may also increase the activity of methyldopa and nitroglycerin. Alcohol can increase tetracycline levels by 30%. Selective serotonin reuptake inhibitors do not appear to affect alcohol kinetics or psychomotor performance.

When cocaine and ethanol are taken concomitantly, the unique metabolite, cocaethylene, is a neurologically active compound that is significantly more toxic than cocaine to the heart, liver, and brain and more addicting and more lethal than cocaine alone. Cocaethylene produces a higher incidence of confusion, lower mean Glasgow Coma Scale (GCS) scores, and a higher incidence of violent trauma and more often requires endotracheal intubation.¹¹⁰ Hemodynamically, these patients demonstrate an elevated heart rate (1.5-5 times normal) and blood pressure higher than with either drug alone. Sudden death is increased 18- to 25-fold above that associated with use of cocaine alone. Plasma levels of cocaine in this combined group were higher than in those who used cocaine alone.¹¹¹

Ethanol increases aspirin-induced prolongation of bleeding time and reduces the metabolism of warfarin, leading to increased anticoagulant effects. There is an increased risk of upper gastrointestinal bleeding when alcohol is combined with NSAIDs. This may be the most dangerous additive or synergistic effect of alcohol.¹¹²

Disulfiram and Similar Reactions

Most patients pretreated with disulfiram (Antabuse) who then consume even small amounts of alcohol experience an extremely unpleasant reaction. These patients have a hypersensitivity to ethanol and experience a direct response within 15 minutes and lasting 30 minutes to several hours. The reaction consists of skin flushing on the head that spreads to the trunk along with nausea, vomiting, headache, chest and abdominal discomfort, diaphoresis, vertigo, palpitations, and confusion. A severe reaction may produce hypotension, seizures, and dysrhythmias. Disulfiram-ethanol reaction is thought to occur by the accumulation of acetaldehyde secondary to inhibition of the aldehyde dehydrogenase enzyme, which may be deficient in many Asians, or another unknown toxic factor. This incapacitating reaction has been used to discourage chronic alcohol ingestion.

A similar but milder disulfiram-ethanol–like reaction has been described when alcohol combines with several different drugs. The reaction may occur days to weeks after the last dose of medication. Four cephalosporins (cefamandole, cefoperazone, cefotetan, moxalactam), metronidazole, chloramphenicol, griseofulvin, nitrofurantoin, sulfonamides, all sulfonylureas, and chloral hydrate have produced this reaction in combination with alcohol. Life-threatening toxic reactions between griseofulvin and small amounts of alcohol have been reported.¹¹³ Treatment for disulfiram reaction is usually just observation, an antiemetic for symptoms and intravenous fluids, and rarely dopamine for severe hypotension.

Oral Hypoglycemics

Profound hypoglycemia can occur when alcohol and oral hypoglycemic agents are combined. Patients taking metformin may have an increased risk for development of lactic acidosis when it is combined with heavy drinking. A disulfiram-ethanol–like reaction has been described with many hypoglycemic agents.¹⁰⁸

Acute Intoxication

Acute intoxication alone seldom requires admission. However, combined alcohol-drug overdose or associated medical, psychiatric, or social problems may require hospitalization. Acute alcohol intoxication is a diagnosis of exclusion reached after adequate observation to ensure that the altered mental status resolves.

Alcohol levels that may be tolerated by an adult can be lethal in children. It is prudent to admit children with acute intoxication unless close psychosocial follow-up can be ensured. Children presenting with hypoglycemia or medical complications should be admitted. Child abuse or neglect should be considered.

Alcohol Withdrawal

Patients with signs of major withdrawal (fever, hallucinations, confusion, extreme agitation) require admission. Patients with mild alcohol withdrawal can be observed in the ED. After 4 to 6 hours of observation and treatment, the alert, oriented patient whose vital signs, physical examination findings, and results of appropriate laboratory analysis are within normal limits may be released with appropriate medications and aftercare instructions. Nevertheless, the patient requires treatment for the underlying disease of alcoholism and should be advised or referred accordingly.

Seizures

Patients experiencing their first alcohol-related seizure may be admitted. Admission allows initiation of drug therapy, diagnostic evaluation, and continued monitoring of the patient’s status. However, the alcoholic patient with a first-time alcohol-related seizure may be discharged to a suitable social situation when the patient’s alcohol withdrawal is mild and controlled either by supportive care or with low-dose benzodiazepines; the diagnostic workup, including a head CT scan, is unremarkable; the patient has had fewer than two seizures; and the patient has been observed to be alert and oriented, with normal vital signs, physical examination findings, and laboratory study results, during the 6 hours since the last seizure, and appropriate outpatient follow-up can be ensured.

Patients with a documented history of alcohol-related seizure can be discharged if they have had no more than two alcohol-related seizures during a 6-hour period with a lucid interval between seizures and are observed to be seizure free and at baseline mental and physical status for at least 6 hours after their last alcohol-related seizure. Three to five brief, self-limited seizures may occur with alcohol withdrawal seizure. Nevertheless, admission for patients with two or more seizures is advised because of the potential for deterioration to status epilepticus. This is especially appropriate in the malnourished, immunocompromised, homeless, or noncompliant alcoholic patient.

Patients with partial seizures or focal neurologic findings on physical examination require admission unless these findings are previously documented. Patients with seizures associated with head trauma or with mixed alcohol-drug withdrawal are admitted. Status epilepticus or recurrent seizures during ED observation indicate a lack of seizure control also requiring hospitalization.

Psychiatric and Social Problems

Alcoholic patients requiring admission with acute intoxication, alcohol-related seizure, alcohol withdrawal, or medical or surgical disorders are usually best managed in acute care units rather than by a general psychiatric service. Some psychiatric and social conditions in the alcoholic can be better handled on a general psychiatric unit: psychosis, exacerbation of schizophrenia, depression with suicidal tendencies, any patient who is a danger to self or others, or alcoholic hallucinosis with an otherwise clear sensorium.

Patients who are no longer able to care for themselves may also require admission. Although these patients’ ultimate destination is a rehabilitation center or a board-and-care program, hospitalization may be necessary to rule out medical or psychiatric illness and to treat impending withdrawal symptoms. Patients who wish to stop drinking are usually admitted to a detoxification unit for treatment of impending withdrawal. Data and interest are increasing for outpatient drug therapy in alcohol dependence. The U.S. Food and Drug Administration has approved disulfiram, naltrexone, acamprosate, and topiramate for treatment of alcohol dependence.¹⁰⁴ There is growing evidence that patients with alcohol dependence who carry a particular variant of an opioid receptor gene are more likely to respond to naltrexone, raising the possibility that genetic tests may one day guide medication selection.¹³⁸ Naltrexone, ondansetron, acamprosate, and acamprosate plus naltrexone have had mixed results facilitating abstinence.^139,140 The role of medications in combination with behavioral therapy is actively investigated.^141,142

Several other medications are under active study and are sometimes prescribed for alcoholism treatment on an unapproved or off-label basis. Baclofen, because of its anticraving action and safety, could have an important role for treatment of alcohol-dependent patients with advanced liver disease.¹⁴³ Gabapentin is used as monotherapy or as an add-on pharmacotherapy in outpatient settings in the control of alcohol consumption and craving and in helping patients achieve abstinence.¹⁴⁴ Ondansetron may show benefit in early-onset but not in late-onset alcoholics.¹⁴⁵

Brief intervention has reduced alcohol consumption in some well-designed ED studies but not in others.146,147 Alcohol dependence and a positive screen for alcohol-related injuries are decreased after screening and brief intervention.¹⁴⁸ Internet-based interventions show promise for reducing alcohol consumption, especially among those meeting criteria for hazardous or harmful drinking.¹⁴⁹ Telephone contact after the ED visit may be another effective tool to screen injured patients for hazardous drinking and to offer brief intervention while avoiding interruptions to patient flow.¹⁵⁰ Referral and brief intervention are warranted.¹⁵¹ Most communities have either an Alcoholics Anonymous (AA) chapter or a treatment center for anyone who desires help with alcohol. In smaller communities, clergy or social workers can usually arrange rehabilitation.

Alcohol kills—it kills the alcoholic and it kills unintended victims by the acts of inebriated persons. Whereas medical, psychological, or social problems bring the alcoholic to the ED, the underlying problem is alcoholism and the ultimate goal is abstinence. This disease surely progresses if alcoholism is not first recognized and the patient is never given the opportunity to participate in a rehabilitation program.¹⁵² The emergency physician can intervene on behalf of the patient and the public.

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