The most award winning
healthcare information source.
TRUSTED FOR FOUR DECADES.
Authors: Phillip A. Brewer, MD, Assistant Professor of Surgery,Yale University School of Medicine, New Haven, CT.
Gail D’Onofrio, MD, FACEP, Assistant Clinical Professor of Surgery, Yale University School of Medicine, New Haven, CT; and Boston University School of Medicine, Boston, MA.
Peer Reviewers: Lewis Goldfrank, MD, Director of Emergency Medicine, Bellevue Hospital and New York University Medical Center; Associate Professor of Clinical Medicine, New York University, New York, NY.
The problems of recognition, prevention, treatment, and appropriate disposition, can be all the more challenging because of the patients’ background of substance abuse and the need to differentiate between overlapping causes of mental status changes. Probably the two most important tasks in caring for this population are recognition of the need for immediate evaluation to rule out traumatic or infectious CNS condition, and deciding whether to admit to a hospital, refer to an in-patient substance-abuse treatment unit, or refer for out-patient management that includes alcohol counseling.
Alcohol abuse and the risk of alcohol withdrawal syndrome are under-recognized by physicians. This is illustrated in a study of 100 acute orthopedic admissions that found that only 37% of patients had an adequate drinking record correctly identifying alcohol problems.1 In the population that was identified as problem drinkers, action was taken in only 36% of cases, usually after withdrawal symptoms appeared. Otherwise, no action was taken, even when it was recognized that the admission was the direct consequence of drinking.
This article deals with a spectrum of alcohol-related complications that are grouped under the term alcohol withdrawal syndromes (AWS). These complications range in severity from hangover and insomnia, tremor and tachycardia, to life-threatening delirium tremens. Their common mechanism is rebound of the altered metabolic and neurohormonal physiology of ethanol exposure when ethanol is abruptly withdrawn or reduced. Chronic effects of ethanol, such as congestive cardiomyopathy and alcoholic neuropathy, lie outside the scope of this article and will not be discussed unless they have a direct bearing on AWS.
Approximately 111 million Americans age 12 and over are current alcohol users.2 There are an estimated 22 million alcoholics in the United States and more than 107,000 alcohol-related deaths per year.2,3 Up to one-third of adult inpatients have problems related to alcohol, and 20% of the total national expenditure for hospital care is related to alcohol abuse.4,5 Alcoholism is the leading cause of morbidity and mortality in the United States. One study determined that 40% of all patients presenting to the ED in the evening had been drinking and had blood alcohol concentrations (BAC) greater than 80 mg/dL.6 The economic impact of alcohol abuse and alcoholism is monumental. It is estimated that the cost to the nation is anywhere from $130 billion to $200 billion per year.5
Alcohol abuse refers to patterns of problem drinking that result in health consequences, social problems, or both.3 Alcohol dependence, often called alcoholism, refers to a disease that is characterized by abnormal alcohol-seeking behavior that leads to impaired control over drinking.3
Alcohol dependence by DSM-IV7 criteria is characterized by development of three or more of the following symptoms over a 12-month period: loss of control over use, development of tolerance or withdrawal symptoms, inability to fulfill roles, neglect of activities, and continued use despite problems.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines a patient at risk for alcohol-related problems as: a man who consumes more than 14 drinks per week or four drinks per occasion, a woman who consumes more than seven drinks per week or more than three drinks per occasion; or anyone who gives one or more positive answers to the CAGE that have occurred in the past year.8(See Table 1.)
Assessment of individuals should include questions regarding alcohol use. The physician is then able to recognize not only the patient who is presenting in a withdrawal state but also those who are at risk. Relying on breath alcohol and self-report alone have been shown to be inadequate screening tests for alcohol abuse, with sensitivities as low as 20% to 29%, respectively.9
Screening and assessment tools, such as the CAGE and the brief MAST surveys, are helpful in establishing patterns of alcohol use and the presence of physiological dependency.10,11 (See Table 1 and Table 2.) CAGE is a short, four-item survey that assesses lifetime consumption of alcohol and is easy to remember and administer. One or more positive answers requires further assessment. The brief MAST (Michigan Alcoholism Screening Test) survey is a 10-item subset of the original 25-item MAST, with weighted responses. Cherpitel found that when used to identify alcohol dependence in patients in an ED setting, a cutoff of two or more positive answers on the CAGE had an accuracy of 84%, with a sensitivity of 76% and a specificity of 90%. When using a cutoff score of 4 with the brief MAST, she reported an accuracy of 67%, with a sensitivity of 48% and a specificity of 89%.12
Cyr and Wartman reported a 91.5% sensitivity in identifying alcohol dependency when the two following questions from the MAST survey were used: "Have you ever had a drinking problem?", and "Have you had a drink within the last 24 hours?"13
After screening for alcohol abuse and dependency, the physician should make an assessment of the risk of progression to AWS. It is preferable to predict and prevent AWS rather than wait for the onset of symptoms.
Ethanol produces long-term metabolic and histologic changes in a variety of organ systems. These changes account for most of the effects of withdrawal from chronic ethanol exposure, and many have direct implications for prevention and treatment of withdrawal syndromes.
Metabolism of Ethanol. Ethanol (ETOH) is rapidly absorbed by the gastric and intestinal mucosa and enters the bloodstream. It is eliminated in small quantities by the lungs and kidneys but is primarily metabolized by the liver. With repeated exposure, alcohol dehydrogenase is induced, and, at higher concentrations, the microsomal P450 enzyme system is also engaged in ETOH metabolism. The quantity of alcohol present in one shot of spirits, one 4 oz. glass of wine, or one 12 oz. beer will raise the blood alcohol level by approximately 25 mg/dL in the average adult, who will metabolize ETOH at the rate of about 15-25 mg/dL/h, assuming normal liver function. The time at which the BAC begins to fall depends on the quantity of ethanol present in the gut and the point at which there is no further absorption. Repeat breath analysis of ETOH concentration may actually show a rise during the first hour or two after presentation.
Chronic CNS Effects. Long-term exposure to ethanol modifies certain neurotransmission sites in the CNS. Withdrawal from alcohol results in rebound hyperstimulation and some degree of neuronal death.14
The N-methyl-D-aspartate (NMDA) type of glutamate receptor, which is specifically inhibited by ethanol, plays a role in neuronal development. Its inhibition is thought to be the mechanism underlying fetal alcohol syndrome as well as neuronal demise by up-regulation of chronically ethanol-inhibited hippocampal cells.15 Compensatory glutamate-mediated hyperstimulation of the NMDA receptor during withdrawal produces excitotoxic cell death and may cause epileptiform seizure activity. This is particularly true following drinking binges, and administration of antagonists of NMDA may be protective. Withdrawal-induced synaptic excitation mediated by the NMDA receptor is accompanied by increased calcium spikes. Some calcium-channel antagonists are effective in preventing withdrawal seizures.16,17
Alcohol also potentiates the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The activity of the neuronal chloride ion channel linked to the A-type GABA receptor is increased during acute exposure to high alcohol levels.18 This receptor is the site of action of benzodiazepines and may partly explain their benefit in alcohol withdrawal. Alcohol’s affect on GABAA may contribute to alcohol’s anxiolytic, sedative, and motor impairment actions.3 Hyperexcitability and seizures may develop in alcohol withdrawal from a compensatory change in the number or function of GABAA receptors following chronic alcohol exposure.3 Growth hormone and corticosterone are also implicated in the mediation of withdrawal syndromes.19,20
Effects on the Heart and Cardiovascular System. Alcoholism is often associated with the abuse of tobacco as well as cocaine, which cause coronary artery disease and hypertension. Both adrenaline and noradrenaline secretion are increased during withdrawal from alcohol in dependent subjects, resulting in the tachycardia and hypertension seen in withdrawal states. Acute myocardial ischemia may ensue.21
Alcoholic Ketoacidosis. Alcoholic ketoacidosis (AKA) is defined as a wide anion gap metabolic acidosis, with ketonemia occurring in the dehydrated, fasting, chronic alcoholic who is undergoing withdrawal from ethanol and in whom other causes of metabolic acidosis have been ruled out.22 (See Table 3.) It is rapidly reversible and has a low mortality when recognized.
When glucose and glycogen are depleted, free fatty acids are mobilized as a secondary source of energy. The Krebs cycle is inhibited by a high NADH/NAD ratio. This further increases fatty acid production, most of which is converted from acetoacetate to beta-hydroxybutyrate. The former, but not the latter, is detected by urine ketone reagent strips, Acetest tablets, or the nitroprusside test. Combined with preexisting dehydration, an anion gap acidosis ensues.
The hallmarks of AWS constitute a continuum of signs and symptoms, ranging from tremulousness to delirium tremens. At one time, alcohol withdrawal was divided into stages.23 However, since the full spectrum of symptoms varies greatly and overlaps in duration and temporal sequence, it is more clinically helpful to define a constellation of signs and symptoms ranging from mild/minor phenomena to severe/major phenomena.76
Mild Alcohol Withdrawal. Mild withdrawal usually occurs less than 24 hours after cessation of or decrease in alcohol intake. It may include tremulousness, anxiety, nausea, vomiting, diaphoresis, hyperreflexia, and minor autonomic hyperactivity.
Severe Alcohol Withdrawal. Severe withdrawal occurs more than 24 hours and up to five days after cessation of or decrease in alcohol intake. It is characterized by disorientation, agitation, hallucinations, and severe autonomic derangement.
Table 4 summarizes the characteristics of mild, moderate, and severe withdrawal that are useful for diagnosis and assessment. The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale is a well-validated instrument for the assessment of severity of alcohol withdrawal for use in inpatient settings. Points are assigned for categories of symptoms and signs including: nausea and vomiting, tremor, sweats, anxiety, agitation, tactile and visual disturbances, headache, and an abnormal orientation and sensorium.24 Higher scores reflect more serious withdrawal states. A quantitative score also allows for objective monitoring and evaluation of interventions.
A variety of circumstances may lead to cessation of drinking, including incarceration, acute illness or injury, depletion of funds, retail closings on Sundays, nausea and vomiting, and, finally, a decision to quit drinking. Whatever the circumstance, the progression to AWS is frequently predictable, and the physician must recognize the symptoms of withdrawal as well as the situations in which the patient is at risk for developing AWS.
Hangover. Hangover is often overlooked in classifications of alcohol withdrawal, perhaps because it occurs after acute as well as chronic alcohol exposure. It is the mildest form of withdrawal, occurring within several hours of cessation. It consists of a period of psychomotor impairment that follows an acute exposure to inebriating quantities of alcohol. Severity of hangover symptoms is a risk factor for subsequent alcohol dependency, perhaps because individuals prone to severe hangover develop a pattern of relieving symptoms by further drinking, known as an "eye-opener."25
Even in the naive drinker, such exposure may result in neurochemical changes that persist for up to 48 hours. Performance on discrimination tasks was tested in rats and found to be impaired 18 hours after a single exposure to 4 g/kg of ETOH.26 Three rebound hypotheses were proposed: an opponent-process physiological rebound from intoxication; a toxic reaction to ethanol or its metabolites; and, circadian dysrhythmia induced by acute ethanol intoxication.27 In addition to these hypotheses, dehydration secondary to the diuretic effect of ethanol is also a likely factor.
Alcohol Withdrawal Tremor. Barring additional alcohol intake, the chronic drinker develops increasing tremors and craving for alcohol during the first 8-12 hours of observation, which peaks at 24-48 hours. The patient may also experience insomnia, tachycardia, anxiety, and nausea at this stage. The drinker may calm "the shakes" at this point by consuming additional alcohol.
Alcohol Withdrawal Hallucinations. Alcohol withdrawal hallucinations are noted as early as 24 hours after the last drink and last approximately as long. They occur in about a quarter of cases and are usually visual but less frequently will be auditory or combined auditory and visual.28 Binding of mediator analogs by dopaminergic receptors in the visual cortex in rats is altered during withdrawal from alcohol, and this may account for the visual disturbances that accompany AWS.29 They are not necessarily linked to other aspects of the syndrome, such as adrenergic hyperstimulation, and may occur as an isolated phenomenon. In early-stage AWS, they are recognized by the patient as hallucinations. In late-stage AWS, they are perceived as real and may provoke extreme fear and anxiety.
Delirium Tremens. Delirium tremens (DT) is a severe, life-threatening complication of alcohol withdrawal. It is characterized by increasingly pronounced disorientation, agitation, and autonomic stimulation, with hypertension, tachycardia, hyperthermia, and profound diaphoresis. Mortality rates of up to 20% have been noted in the past but have improved gradually with the development of intensive care units, more aggressive investigation of traumatic and infectious complications, better fluid replacement, rapid cooling of critical hyperthermia, and the advent of benzodiazepines.23, 30-32
Onset typically occurs approximately 48 hours after cessation of drinking. The mild tremor and lucid hallucinations of early withdrawal give way to delirium and agitation. The patient begins to pull at imaginary objects or at his or her clothing and sheets. Life-threatening hyperthermia, which results from increased motor activity and is exacerbated by volume depletion may develop, with temperatures reaching 104°F or greater.
Dehydration is a critical factor in the appearance of DT and may be severe. Of the 39 fatalities described by Tavel et al, dehydration was a factor in all cases in which volume status was noted.31 Mechanisms of fluid depletion include profuse diaphoresis, increased pulmonary losses related to fever and tachypnea, nausea, vomiting, diarrhea, and decreased oral intake secondary to increasing confusion. A recent study found elevated alpha-atrial natriuretic peptide in every patient who went on to develop DT.33 This suggests an even greater need for aggressive fluid and electrolyte replacement in DT.
One cannot assume that alcohol withdrawal accounts for the entire clinical picture of a patient who presents with these symptoms. The following illnesses must be considered, particularly those which can also produce any or all of the symptoms of DT: alcohol intoxication, other toxins, hypoglycemia, sepsis, severe dehydration, CNS infection, hepatic insufficiency, cerebral injury and/or hemorrhage, and seizure (post-ictal).
Alcohol-Related Seizure. Seizures related to alcohol are a common cause of adult convulsions. The term "alcohol withdrawal seizures" was originally described by Victor and Brausch in adult patients who were confirmed alcoholics of many years’ duration.28 They reported these seizures as occurring in approximately 10% of people withdrawing from alcohol. They found them to be generalized tonic-clonic (95%), often multiple (60%), and usually occurring 7-48 hours after cessation of drinking (90%). Most were noted to have normal EEGs (90%). They reported the time interval from first to last seizure was less than six hours in 85% of patients. Other studies substantiate the withdrawal component of seizures in the alcohol-dependent patient. Hillbom and Hjelm-Jager and Rathlev et al reported increased seizure frequency with decreased access to alcohol.34,35 Rathlev et al found that 66% of patients seized during the time when alcohol was not available due to state laws, suggesting decreasing alcohol intake may be a precipitating factor, and that patients who seize with elevated alcohol levels may, in fact, be at lower levels than they are accustomed to.
In addition, other factors independent of abstinence may predispose the alcohol-dependent patient to seize. Recently, Ng et al reported that alcohol itself may induce seizures.36 The fact that patients seize who have high blood alcohol levels, and that many patients with seizures related to alcohol do not exhibit other signs or symptoms of withdrawal, support this possibility.
Alcohol itself may also exacerbate other existing conditions, such as epilepsy.37-39 To add to the complexity, chronic alcohol abusers have an increased frequency of structural alterations, including brain infarction, hemorrhagic stroke, and subarachnoid hemorrhage, that may contribute to seizures.40-43 Because of the multifactorial origin of seizures in the setting of acute and chronic alcoholism, the term alcohol-related seizure (ARS) is frequently used instead of alcohol withdrawal seizure.44
Repeated episodes of alcohol withdrawal may lead to an increase in the severity of subsequent episodes and a lower seizure threshold through a process known as kindling.45-47 Individuals who have had five or more alcohol detoxifications have a greater risk of withdrawal seizures.48
Assessment and management are often made difficult by acute intoxication or the altered mentation associated with chronic alcoholism and withdrawal states. This is never an excuse for substandard care, and timely use of sedating drugs may facilitate delivery of care. In the patient who appears to be inebriated, alcohol intoxication must be confirmed by measuring breath or blood alcohol levels.
Evaluation of the Patient with Symptoms of Alcohol Withdrawal Syndrome. Initial Assessment. A quick assessment of airway, breathing, and circulatory status must begin the evaluation. Tachycardia, fever, and hypertension or hypotension may be found. In the patient with moderate to severe signs of withdrawal, a secure IV should be placed. In case of frank mental status changes with CNS depression, administer naloxone 2 mg IV. A rapid blood glucose determination should be made; and if necessary 25 mL of D50 may be given IV, preceded by thiamine 100 mg IV to prevent precipitating acute Wernicke’s encephalopathy.
The AWS may be confused with a variety of illnesses, including hypoglycemia, acute schizophrenia, head trauma, infection, thryotoxicosis, anticholinergic poisoning, withdrawal from other sedative-hypnotic type drugs, and drug-induced psychosis. The physician should keep this differential diagnosis in mind when eliciting the history, performing the physical exam, and ordering lab tests.
History. Obtain as thorough a history as possible. In the uncooperative, confused, or comatose patient, interview secondary sources (i.e., family, friends, police, or EMS personnel) and search medical records. In particular, look for prior episodes of AWS. Pay particular attention to a history of recent trauma, known seizure disorder unrelated to alcohol use, use of prescription or street drugs (such as anticholinergic agents including neuroleptics and decongestants/OTC sedatives, cocaine, and stimulants), and psychiatric illness.
Physical Exam. The examination of the alcoholic patient can be a taxing exercise, particularly if the patient is abusive, violent, or unkempt. However, it must be done rigorously in order to reveal occult, potentially life-threatening injuries or illness. A systematic evaluation of fluid status, degree of withdrawal, and search for signs consistent with precipitating or concomitant illness must be performed. Early sedation may be necessary in order to perform the exam and proceed with further care.
The neurological exam should look for dilated pupils consistent with catecholamine surge, focality of seizures indicative of intracerebral lesions, degree of tremor, and orientation. Examine the head, neck, and musculoskeletal system for signs of trauma. Any sign of hepatic insufficiency, including bleeding or bruising, roving eye movements, jaundice, and hepatomegaly or ascites, must be noted. Tongue injury and soiled clothes may signal the post-ictal state.
Laboratory Tests. Specific tests should depend upon the presentation of the patient and potential for co-existing medical illnesses. All patients need rapid blood glucose determinations. Depending on the clinical situation, electrolytes determinations, including phosphorus, magnesium, and calcium, renal and liver function tests, amylase, coagulation studies, specific toxicologic screens, and urine analysis may be necessary. Lumbar punctures may be necessary to rule out infection and encephalitis. Chest x-rays and head CTs may be of value in diagnosing infection or trauma in selected patients.
Assessment of Alcohol-Related Seizures. As with other conditions, a complete history must be obtained for all patients presenting with a seizure. The patient, family, bystanders, and/or paramedics should be interviewed. Identification and treatment of life-threatening causes of seizures is a priority. (See Table 5.) The physical exam includes obtaining vital signs, including core temperature, inspection for signs of trauma, and a careful neurological examination to detect focal deficits. The importance of serial neurological examinations cannot be overemphasized.
Emergent head CT scans should be performed on those patients who present with new-onset seizures, a change in pattern from previous seizures, and a focal or deteriorating neurological exam. In a study that followed CT scans in 259 patients with new-onset AWS, 10 (3.9%) had unsuspected intracranial lesions leading to altered clinical management.49
Laboratory tests should include a fingerstick for glucose determination and a rapid alcohol breath analysis as part of the initial screening. A complete electrolyte panel, including magnesium, calcium, creatinine, and blood urea nitrogen, should be obtained in new-onset seizures. Cocaine use is associated with seizures, and a urine assay for cocaine metabolites should also be considered. In recurrent ARS, laboratory studies may be limited to glucose, alcohol, and, if appropriate, anticonvulsant levels.
Treatment Regimens. Benzodiazepines are the mainstay of therapy due to their rapid absorption and cross-tolerance with alcohol. They have been shown in randomized trials to treat the symptoms of withdrawal and reduce the frequency of seizures and delirium tremens.50-57 The benzodiazepines have anticonvulsant activity, minimal respiratory and cardiac depression, and can be administered parenterally. Long-acting benzodiazepines, such as diazepam and chlordiazepoxide, have active metabolites that offer a tapering effect and often preclude additional dosing. For patients unable to take oral medications, the elderly, or those with a prolonged prothrombin time secondary to hepatic dysfunction, lorazepam may be an alternative. Multiple dosing schedules have been used, ranging from front-loading with large amounts of drug, to fixed-schedule dosing, to only symptom-triggered therapy.55,56,58,59 Other drug therapies, such as beta-blockers and clonidine, have been used for the treatment of AWS but have not been shown to be as effective as monotherapy in moderate/severe withdrawal, nor in patients with significant underlying medical problems. Table 6 refers to treatment strategies for patients with mild-to-moderate withdrawal, with and without intact oral intake, and severe withdrawal. Specific problems to correct are addressed: adrenergic hyperactivity, dehydration, nutritional deficiency, hypoglycemia, and hyperthermia.
Severe AWS is a true medical emergency requiring rapid intervention. All aspects of treatment listed in Table 6 must be addressed. Physical restraints must be applied to prevent injury pending adequate sedation, which must be accomplished quickly in order to allow an adequate assessment of underlying conditions. In addition to sedation, rehydration is extremely important because dehydration is a significant contributing factor to mortality in AWS. Proper fluid management also protects the restrained, hyperthermic, agitated patient from possible acute tubular necrosis (ATN) due to rhabdomyolysis. Light and noise exacerbate the agitation and delirium of AWS, and the patient should be placed in a quiet room with subdued lighting under constant, direct observation. Significant control of symptoms should be obtained, and aggressive therapy must continue during and after the transition to an inpatient unit.
Seizures in the Alcohol-Dependent Patient. Currently, there is no uniform standard of care for the patient who presents with an alcohol-related seizure (ARS). There is great variation in practice patterns, ranging from early discharge at resolution of the post-ictal state, to admission either to six-hour observation units based on Victor and Brausch’s data on inpatient beds.28
The ideal drug for the prevention and treatment of ARS would exhibit a rapid onset of action, cross-tolerance with ethanol, metabolism independent of liver function, and yet still be safe with little or no abuse potential. Benzodiazepines possess many of these qualities, and, with short-acting agents such as lorazepam now available, their administration accompanied by proper oxygen and cardiac monitoring has been proven to be safe and effective with few adverse reactions.60,61 Several studies have suggested that benzodiazepines alone are sufficient to prevent ARS.50-52 Lorazepam is well-suited to the treatment of ARS because of its unique pharmacological and pharmacokinetic properties. It has been shown to be a potent anticonvulsant with minimal depressant effects on respiration and circulation.53,62,63 Lorazepam’s duration of seizure control is longer than diazepam. The elimination half-life is approximately 13 hours, without active metabolites. Lorazepam is conjugated to form an inactive glucuronide that is excreted in the urine. Therefore, its elimination half-life is not substantially prolonged in patients with liver dysfunction such as cirrhosis.64,39 The combination of minimal accumulation in the plasma after multidose therapy, metabolism that is unaffected by concurrent drug therapy (i.e., cimetidine, disulfiram, ethanol), disease states such as cirrhosis, its lower abuse potential compared to other benzodiazepines, and the fact that its metabolism is not altered in the elderly, make it an ideal drug for the population of patients with ARS.53,65-68
In light of the above, patients presenting with an ARS should receive an IV dose of 2 mg of lorazepam as soon as possible. The heart rate, blood pressure, and oxygen saturation for the initial one hour after drug administration should be monitored. Additional doses of lorazepam may be administered for recurrent seizures. Treat other conditions such as hypoglycemia as they are identified. Observe the patient for six hours after the first seizure. Those patients with recurrent seizures after treatment with lorazepam or who appear to develop other symptoms of AWS should be considered as for hospital admission.
Several studies have shown phenytoin to be ineffective in the treatment of recurrent ARS.70-72 However, patients with known CNS structural defects or positive EEGs indicating an epileptogenic focus should be placed on long-term anticonvulsant therapy and encouraged to be compliant with their medication.73 Patients who are noncompliant with their anticonvulsants and take them erratically may be at increased risk for seizures.74 Repeated visits by alcohol-dependent patients with documentation indicating poor compliance with long-term anticonvulsant therapy should prompt consultation with a neurologist regarding discontinuation of the therapy.
Alcoholic Ketoacidosis. Fluid and glucose deficiencies are involved, and therapy is aimed at their replacement.23 IV hydration with 5% dextrose in normal saline, or in 0.5N saline, will both replenish fluid losses and provide necessary glucose; along with nutritional meals, this will eliminate further production of fatty acids and allow for reconstitution of normal NADH/NAD ratios.
Hospitalization. The two indications for hospital admission of the patient in or at risk for AWS are the presence of any condition requiring inpatient management, and any condition that, if not properly treated as an outpatient, is likely to worsen and require subsequent admission at a higher level of care. In severe AWS, admission to an intensive care unit is obligatory.
In the presence of alcohol dependency and an illness interfering with the patient’s mobility or ability to maintain oral intake of food and fluids, hospitalization is indicated unless it can be clearly demonstrated that the patient has an adequate support system ensuring his or her ability to return for admission should outpatient therapy fail.
If admission is indicated for reasons other than alcohol use, every effort should be made to screen the patient for dependency, and this information must be transmitted to the admitting physician. Adequate surveillance for and prevention of AWS may then be instituted.
Referral to inpatient or outpatient detoxification. Patients with a diagnosis of alcohol dependency and no life-threatening signs of withdrawal requiring hospitalization should be considered for admission to an outpatient or inpatient detoxification unit. Availability of such treatment, particularly for the uninsured patient, is variable depending on the locale. In some areas, there are state-operated or state-financed facilities which offer both voluntary and involuntary treatment for alcohol detoxification. In addition, there are many privately run detoxification facilities, but most do not accept patients without insurance. The severely dependent alcoholic, who is often described as the "frequent flyer," is capable of recovery given the right circumstances if left in the cycle of recurrent binges, has a high five-year mortality rate.75
Programs for outpatient detoxification from alcohol do exist but require a structured environment and a motivated, oriented patient. Close monitoring is required in order to transfer to inpatient care if needed. Unless admission to such a program can be arranged and all of the above are criteria met, sending a patient home who is withdrawing or at risk for withdrawal is not advisable. It will invariably result in a continuation of drinking, complicated withdrawal, or a visit to the emergency department in a more advanced withdrawal state.
The "upstream" approach to medicine states that rather than standing by the river bank and attempting to save drowning people, one can go upstream and attack the problem at its origin. Repeated short-term management of alcoholics without proper referral to treatment programs is the "downstream" approach and is destined to perpetuate the problem of recurrent presentation of alcoholic patients with increasingly life-threatening symptoms. A major impediment to referral is the scarcity of resources. As the frontline physicians in the management of patients with alcohol-related problems, primary care physicians and emergency physicians must work collectively and individually to improve the availability of substance abuse treatment services, including creating and operating short-term detoxification facilities.
AWS is a spectrum of minor to life-threatening complications of cessation of alcohol intake after heavy, usually chronic, exposure to ethanol. It is incumbent upon the physician to screen for patients who are at risk for AWS, to recognize ongoing symptoms of AWS, and to treat accordingly.
With proper treatment, mortality and morbidity from AWS can be reduced to a minimum, provided AWS is anticipated or recognized and managed appropriately.
1. Hamilton MR, Menkes DB. How alert are hospital doctors to alcohol misuse among acute orthopedic patients? N Z Med J 1992;105:167-169.
2. NCADI. 1995 National Household Survey of Alcohol and Drug Abuse. Advanced Data: 1996;275:1-15.
3. U.S. Secretary of Health and Human Services. Eighth Special Report to the U.S. Congress on Alcohol and Health. 1993.
4. Rice DP, Kellman S, Miller LS, et al. Estimates of economic costs of alcohol and drug abuse and mental illness, 1985 and 1988. Pub Health Rep 1991;106:280-292.
5. Burke TR. The economic impact of alcohol abuse and alcoholism. Pub Health Rep 1988;103:564-568.
6. Holt S, Stewart IC, Dixon JMJ, et al. Alcohol and the emergency services patient. BMJ 1980;281:638-640.
7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder. 4th ed. Washington, DC:1994.
8. U.S. Department of Health and Human Services, National Institutes of Health, National Institutes of Alcohol Abuse and Alcoholism. The Physician’s Guide to Helping Patients with Alcohol Problems. NIH Publication N. 95-3769; 1995.
9. Cherpitel CJ. Screening for alcohol problems in the emergency department. Ann Emerg Med 1995;26:158-166.
10. Mayfield DG, McLeod G, Hall P. The CAGE questionnaire: Validation of a new instrument. Am J Psychiatr 1974;131:1121-1123.
11. Pokorny AO, Miller BA, Kaplan HB. The brief MAST: A shortened version of the Michigan Alcoholism Screening Test. Am J Psychiatry 1972;129:342-345.
12. Cherpitel CJ. Screening instruments for alcohol problems in the emergency room. J Stud Alcohol 1995;56:695-700.
13. Cyr MG, Wartman SA. The effectiveness of routine screening questions in the detection of alcoholism. JAMA 1988;259:51-54.
14. Hunt WA. Are binge drinkers more at risk of developing brain damage? Alcohol 1993;10:559-561.
15. Hoffman PL, Tabakoff B. The role of the NMDA receptor in ethanol withdrawal. EXS 1994;71: 61-70.
16. Whittington MA, Lambert JD, Little HJ. Increased NMDA receptor and calcium channel activity underlying ethanol withdrawal hyperexcitability. Alcohol Alcohol 1995;30:105-14.
17. Watson WP, Little HJ. Interactions between diltiazem and ethanol: Differences from those seen with dihydropyridine calcium channel antagonists. Psychopharmacology. 1994;114:329-336.
18. Aguayo LG. Ethanol potentiates the GABAA activates Cl- currents in mouse hippocampal and cortical neurons. Eur J Pharmacol 1990;187:127-130.
19. Dettling M, Heinz A, Dufeu P, et al. Dopaminergic responsivity in alcoholism: Trait, state, or residual marker? Am Rev Psych 1995;152:1317-1321.
20. Roberts AJ, Crabbe JC, Keith LD. Corticosterone increases severity of acute withdrawal from ethanol, pentobarbital, and diazepam in mice. Psychopharmacol 1994;115:278-284.
21. Dennison H, Jern S, Jagenburg R, et al. Influence of increased adrenergic activity and magnesium depletion on cardiac rhythm in alcohol withdrawal. Br Heart J 1994;72:554-560.
22. Wrenn KD, Slovis CM, Minion GE, et al. The syndrome of alcoholic ketoacidosis. Am J Med 1991;91:119-28.
23. Victor M, Adams RD. The effect of alcohol on the nervous system. Res Publ Assoc Nerv Ment Dis 1953;32:526.
24. Sullivan JT, Sykora K, Shneiderman, et al. Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353-57.
25. Earlywine M. Personality risk for alcoholism covaries with hangover symptoms. Addict Behav 1993;18:415-420.
26. Gauvin DV, Goulden KL, Holloway FA. State-dependent stimulus control: Cueing attributes of ethanol hangover in rats. Alcohol Clin Exp Res 1993;17:1210-1214.
27. Gauvin DV, Change EY, Holloway FA. Recent developments in alcoholism: Biobehavioral correlates. Recent Dev Alcohol 1993;11:281-11304.
28. Victor M, Brausch C. The role of abstinence in the genesis of alcoholic epilepsy. Epilepsy 1967;8:1-20.
29. Gil-Martin E, Fernandez-Briera A, Fernandez-Lopez A, et al. Effect of chronic treatment with ethanol and withdrawal of ethanol on binding of [3H]SCH23390 to D1 dopamine receptors in rat visual cortex and hippocampus. Neuropharmacol 1994;33:1203-1209.
30. Isbell H, Fraser HF, Wikler A, et al. An experimental study of "rum fits" and delirium tremens. Q J Stud Alcohol 1955;16:1-33.
31. Tavel ME, Davidson W, Batterton TD. A critical analysis of mortality associated with delerium tremens: review of 39 fatalities in a nine-year period. Am J Med Sci 1961;242:18-29.
32. Victor M, Adas RD. The effect of alcohol on the nervous system. Res Publ Assoc Nerv Ment Dis 1953;32:526.
33. Bezzegh A, Nyuli L, Kovacs GL. Alpha-atrial natriuretic peptide, aldosterone secretion and plasma renin activity during ethanol withdrawal: A correlation with the onset of delerium tremens. Alcohol 1991;8:333-336.
34. Hillbom M, Hjelm-Jager M. Should alcohol withdrawal seizures be treated with anti-epileptic drugs? Acta Neurol Scand 1984;69:39-42.
35. Rathlev N, Shieh T, Callum M. Etiology of alcohol withdrawal seizures and their occurrence in relation to the decreased availability of alcohol. Ann Emerg Med 1992;21:663. Abstract.
36. Ng SKC, Hauser WA, Brust JCM, et al. Alcohol consumption and withdrawal in new-onset seizures. N Eng J Med 1988;319:666-673.
37. Chan A. Alcoholism and epilepsy. Epilepsia. 1985;25:323. Abstract.
38. Devetag F, Mandich G, Zaiotti G, et al. Alcoholic epilepsy: Review of a series and proposed classification and etiopathogenesis. Ital J Neurol Sci 1983;3:275.
39. Lennox WG. Alcohol and epilepsy. Q J Stud Alcohol 1941;2:1.
40. Gill JS, Shipley MJ, Tsementzis SA, et al. Alcohol consumptiona risk factor for hemorrhagic and non-hemorrhagic stroke. Am J Med 1991;90:489-497.
41. Hillbom M, Kaste M. Alcohol intoxication: A risk factor for primary subarachnoid hemorrhage. Neurology 1982;32:706.
42. Hillbom M, Kaste M. Does ethanol intoxication promote brain infarction in young adults? Lancet 1978;2:1181-1183.
43. Weisberg L. Alcoholic intracerebral hemorrhage. Stroke 1988;19:1565-1569.
44. McMicken, D, Freedland E. Alcohol-related seizures: Pathophysiology, differential diagnosis, evaluation, and treatment. Emerg Clin North Am 1994;12:1057-1079.
45. Browne M, Anton R, Malcolm R, et al. Alcohol detoxification and withdrawal seizures: Clinical support for a kindling hypotheses. Biol Psychiatry 1988;23:507-514.
46. Pinel J. Alcohol withdrawal seizures: Implications of kindling. Pharmac Biochem Behav 1980;13:225-231.
47. Lechtenberg R, Worner T. Seizure risk with recurrent alcohol detoxification. Arch Neurol 1990;47:535-538.
48. Lechtenberg R, Worner TM. Relative kindling effect of detoxification and non-detoxification admissions in alcoholics. Alcohol Alcohol 1991;26:221-225.
49. Earnest M, Felman H, Marx J, et al. Intracranial lesions shown by CT in 259 cases of first alcohol-related seizures. Neurol 1988;38:1 561-1562.
50. Devenyi P, Harrison M. Prevention of alcohol withdrawal seizures with oral diazepam loading. Can Med Assoc J 1985;132:798-800.
51. Haddox VO, Bidder TG, Waldron LE, et al. Clorazepate use may prevent alcohol withdrawal convulsions. West J Med 1987;146:695-696.
52. Marx JA, Berner J, Bar-Or D, et al. Prophylaxis of alcohol withdrawal seizures: A prospective study. Ann Emerg Med 1986;15:637. Abstract.
53. Greenblatt D, Shader R. Benzodiazepines in Clinical Practice. New York: Raven; 1974.
54. Turner RC, Lichstein PR, Peden JG, et al. Alcohol withdrawal syndromes: A review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med 1989;4:432-444.
55. Greenblatt DJ, Shader RI, Abernethy DR. Current status of benzodiazepines. N Engl J Med 1983;309:410-416.
56. Kaim SC, Klett CJ, Rothfeld B. Treatment of acute alcohol withdrawal state: A comparison of four drugs. 1969;125:1640-1646.
57. Institute of Medicine. Prevention and Treatment of Alcohol Problems. Washington, DC: National Academy Press; 1990:268-269.
58. Saitz R, et al. Individualized treatment for alcohol withdrawal: A randomized, double-blind controlled trial. JAMA 1994;272:519.
59. Saitz R. Alcohol withdrawal: A nationwide survey of inpatient treatment practices. J Gen Intern Med 1995;10:479-487
60. Comer WH, Elliott HW, Nomof N. Pharmacology of parenterally administered lorazepam in man. J lnt Med Res 1973;1:216.
61. Elliott HW, Nomof N, Navarro G, et al. Comer WH. Central nervous system and cardiovascular effects of lorazepam. Clin Pharmacol Ther 1971;12:468-481.
62. Walker JE, Homan RW, Vasko MR, et al. Lorazepam in status epilepticus. Ann Neurol 1979;6:207-213.
63. Leppik IE, Derivan AT, Homan RW, et al. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983;249:1452-1454.
64. Miller WC, McCurdy L. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome. Clin Ther 1984;6:364-370.
65. Sellers R et al. Diazepam loading: Simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 1983; 34:822.
66. Hoyumpa AM. Disposition and elimination of minor tranquilizers in the aged and in patients with liver disease. South Med J 1978;71:23-28.
67. Kraus JW, Desmond PV, Marshall JP, et al. Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 1978;24:411.
68. Kraus JW, Marshall JP, Johnson R, et al. Lorazepam elimination in liver disease. Gastroenterol 1977;73:1228.
69. D’Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam prevents recurrent alcohol related seizures. Acad Emerg Med 1995;2:366.
70. Alldredge B, Lowenstein D, Simon R. Placebo-controlled trial of intravenous diphenylhydantoin for short-term treatment of alcohol withdrawal seizures. Am J Med 1989;87:645-648.
71. Chance J. Emergency department treatment of alcohol withdrawal seizures with phenytoin. Ann Emerg Med 1991;20:520-522.
72. Rathlev NK, D’Onofrio G, Fish SS, et al. The efficacy of phenytoin in the prevention of recurrent alcohol withdrawal seizures. Ann Emerg Med 1992;21:661-662. Abstract.
73. Sellers E. Alcohol, barbiturate and benzodiazepine withdrawal syndromes: Clinical management. Can Med Assoc J 1988;39:11311-11318.
74. Sellers EM, Giles HG, Greenblatt DJ, et al. Differential effects on benzodiazepine disposition by disulfiram and ethanol. Arzneimittelforsch 1980;30:882-886.
75. Saadi H. Presentation Pattern of Recurrent Alcoholic Patients in the Emergency Department. New Haven: Yale University School of Public Health; 1995.
76. McMicken DB. Alcohol withdrawal syndromes. Emerg Med Clin North Am 1990;8:805-816.
77. Saitz R. Recognition and management of occult alcohol withdrawal. Hosp Pract 1995;30.
Physician CME Questions
6. Which statement regarding the CAGE screening tool is incorrect?
a. Have you ever felt the need to cut down on your drinking?
b. Have you ever associated with drinkers?
c. Have you ever felt guilty about something you’ve done when you’ve been drinking?
d. Have you ever had an eye-opener in the morning to get going?
7. Alcohol withdrawal syndromes include:
a. delirium tremens.
d. all of the above.
8. Which is true regarding the treatment of alcohol withdrawal?
a. Treatment should begin only when symptoms occur.
b. When alcohol dependency is established, appropriate action must be taken to prevent or treat withdrawal symptoms.
c. All patients should receive a standard dose of benzodiazepines.
d. Only a few patients with alcohol dependency will eventually need to be treated for withdrawal on admission to the hospital.
9. All of the following diagnoses of patients with alcohol dependency require hospital admission except:
a. boxer’s fracture of non-dominant hand.
b. nausea and vomiting with evidence of dehydration.
c. severe withdrawal.