Treatment of Alcohol Withdrawal
Alcoholism is defined as a pattern of uncontrolled drinking leading to medical, legal, and psychosocial adverse consequences. It is a major public health problem costing well over a $100 billion dollars annually in the United States alone, with nearly 14 million Americans afflicted. The first episode of alcohol intoxication usually occurs in the midteens. The onset of alcohol dependence peaks in the 20s to 30s. The first evidence of alcohol withdrawal is not likely to occur until several features of dependence have developed.
Alcohol dependence can be screened with the CAGE questionnaire. The CAGE questionnaire is a brief assessment with excellent sensitivity. The clinician should suspect alcoholism if he/she elicits three or more positive answers to the following:
1. Have you often tried to Cut down on your drinking?
2. Have you often been Annoyed by others complaining about your drinking?
3. Have you often felt Guilty about your drinking?
4. Have you often taken a morning drink as an Eye-opener?
Patients who respond positively to three or more questions should be considered at high risk for alcohol dependence and undergo a thorough medical and psychological diagnostic evaluation.
Alcohol dependence is frequently marked by alcohol withdrawal when alcohol intake is stopped or reduced. The following will focus on minor withdrawal, major withdrawal (DT's), withdrawal seizures and the treatment issues for each.
- Signs of alcohol withdrawal occur in 13% to 71% of those presenting for detoxification. About 15% of those hospitalized for detoxification develop withdrawal seizures. The prevalence estimates for delirium tremens vary with the population studied; 0.6% in non-medical detoxification centers, and perhaps 5% overall in those undergoing withdrawal.
- The proposed mechanism of alcohol withdrawal involves the adaptation of the central nervous system to repeated exposure of alcohol on inhibitory GABA A-type neuro-receptors and excitatory NMDA receptors. Animal studies reveal that chronic ethanol administration results in reduced GABA-mediated chloride flux through GABA A-type receptors, indicating tolerance. Chronic ethanol exposure also leads to unregulated NMDA receptor complexes, possibly resulting in the neuronal hyperexcitability that can present clinically as alcohol withdrawal seizures, anxiety, and sleep disturbances.
- The alcohol withdrawal syndrome can be defined as either minor or major. Minor withdrawal criteria are met if the patient has at least three of the following:
- Temperature >38.3
- Systolic blood pressure >160
- Diastolic blood pressure >110
- Pulse >110
- Nausea and vomiting
- Some of the objective signs of withdrawal can be masked by even low doses of beta-adrenergic antagonists, such as propranolol. Criteria 1-4 and 6 above could all be below diagnostic threshold if a patient has been taking a beta-adrenergic antagonist, leading to delirium tremens as the first sign of withdrawal. Certain populations, such as those treated with propranolol for portal hypertension, are at higher risk for masked withdrawal and may present to medical care with delirium tremens.
- Uncomplicated minor alcohol withdrawal may begin within 12-18 hours after the cessation of drinking or simply the reduction of usual intake. It tends to peak between 24-48 hours, and usually subsides in 5-7 days. Major alcohol withdrawal or delirium tremens typically begins within 48-72 hours of the last drink, with peaking of symptoms on days 4 and 5. Major withdrawal may persist from 3 days to several weeks.
- Major withdrawal or delirium tremens (DT's) is marked by all the signs and symptoms of minor withdrawal plus delirium. Delirium tremens classically begins about three to five days after stopping or decreasing alcohol intake. However, the DT's may occur up to two weeks after the last drink. There is marked autonomic hyperactivity with elevation of the pulse and blood pressure. Confusion, perceptual disturbances with visual and auditory hallucinations, and marked agitation are prominent features. Often there are associated medical problems such as pneumonia, pancreatitis, subdural hematoma, or myocardial infarction. Patients are often dehydrated and may have multiple fluid and electrolyte imbalances. The mortality rate was as high as 40% in the early part of the 20th century. Improvements in recognition and treatment have led to a decrease in the mortality to approximately 5%.
- Alcoholic patients presenting with delirium should be monitored closely for delirium tremens. Importantly, other causes of delirium should be considered given that medical comorbidity may be present. Stoudemire suggests the medical workup for delirium include a thorough medical history and complete physical examination. The following laboratory tests should be performed:
- Complete blood count with white cell differential
- Serum electrolytes
- Liver function tests
- Blood urea nitrogen
- Fasting blood sugar
- B12 and folate levels
- Stool guaiac
- Urinalysis including toxicology screen
MANAGEMENT OF ALCOHOL WITHDRAWAL
Benzodiazepines are the treatment of choice in the pharmacologic management of alcohol withdrawal. Chlordiazepoxide (Librium) and lorazepam (Ativan) are most frequently used because their long half-lives provide for a smoother taper. In general, lorazepam is preferred over longer acting agents, such as chlordiazepoxide for patients with liver disease and in the elderly. For patients who meet criteria for withdrawal, one of these protocols may be followed:
1. Chlordiazepoxide 50 mg q4 hr for 6 doses, then
1. Lorazepam 2 mg q4 hr x6 doses, then
2. Chlordiazepoxide 50 mg q6 hr for 4 doses, then
2. Lorazepam 2 mg q6 hr x4 doses, then
3. Chlordiazepoxide 25 mg q4 hr for 6 doses, then
3. Lorazepam 1 mg q4 hr x6 doses, then
4. Chlordiazepoxide 25 mg q6 hr for 4 doses
4. Lorazepam 1 mg q6 hr x4 doses
- The drug is discontinued after the last dose. Lorazepam can be substituted for chlordiazepoxide at a ratio of 1 mg of lorazepam to 25 mg of chlordiazepoxide. Doses should be withheld for nystagmus, sedation, ataxia, or dysarthria. Because the patient is often nutritionally depleted, thiamine 100 mg either intramuscularly or intravenously, folate 1 mg, and a multivitamin should be given daily. Thiamine should be given to every patient suspected of alcoholism prior to the administration of dextrose or food to prevent the development of Wernicke's encephalopathy.
MANAGEMENT OF DELIRIUM TREMENS
- The withdrawal protocol may prevent the development of delirium tremens. For patients in delirium tremens, a suggested regimen is to give 2 mg intravenous lorazepam, increasing the dose until the patient is calm but not obtunded. Adjunctive Haloperidol can be used for agitation and psychosis, when benzodiazepines alone are not effective. However, antipsychotics alone are not effective in the management of delirium tremens. One can combine 5 mg Haloperidol and 2-4 mg lorazepam and administer this every 2 hours until agitation is controlled. Flexibility in dosing is extremely important as simple tapering of the medication according to a schedule may leave the patient inadequately covered for major withdrawal. Clinicians should follow vital signs and the clinical examination. The patient may be comfortable when mild sedation is maintained throughout the course of delirium. The taper should be continued from the dose at which mild sedation is obtained.
- Other medications that have been used to treat withdrawal include ethanol, barbiturates, carbamazepine, propofol, beta-blockers, and centrally acting alpha2-agonists, such as clonidine. None have been as well studied as the benzodiazepines. They may mask the hemodynamic signs of withdrawal, or even cause delirium themselves. Attempting to use ethanol is especially problematic since intravenous administration requires close monitoring of blood concentrations because of toxicity at higher doses. Administering ethanol in the form of beverage alcohol often causes more problems than it solves because of drug interaction issues, unpredictable absorption. Moreover, there is the wide variability in tolerance; well-known hepatic, gastrointestinal, hematologic, and neurologic toxicity, and exacerbation of delirious states. Moreover, since the effectiveness of ethanol has never been proven, its use has been discouraged.
MANAGEMENT OF ALCOHOL-WITHDRAWAL SEIZURES
- Alcohol-withdrawal seizures occur about 6 to 48 hours after stopping alcohol. One third of those having a seizure go on to develop delirium tremens. The seizures usually occur as 1 to 6 generalized tonic-clonic convulsions, which are self-limited. In some series, 10% of patients with chronic alcoholism have recurrent seizures. Other seizure patterns should raise the suspicion of alternative etiologies, such as intra-cranial masses, meningitis, and epilepsy. In most cases of alcohol withdrawal seizures, adding anticonvulsants to benzodiazepines is unnecessary, unless the patient develops status epilepticus. Lorazepam, administered intravenously, usually aborts status epilepticus. Dilantin loading may be done if necessary, but this should be administered with cardiac monitoring. In general, it is unnecessary to prescribe prophylactic anticonvulsants for alcohol withdrawal seizures.
- These are general guidelines for the management of most cases of alcohol withdrawal. The UIHC Consultation-Liaison Psychiatry Service and the Chemical Dependency Center are available for assistance.
- Cook CC, Hallwood PM, Thomson A## B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol & Alcoholism 1998;33(4):317-36
- Erwin WE, Williams DB, Speir WA: Delirium tremens. Southern Medical Journal 1998;91(5):425-32
- Etherington JM: Emergency management of acute alcohol problems. Part 1: Uncomplicated withdrawal [see comments]. Canadian Family Physician 1996; 42:2186-90
- Etherington JM: Emergency management of acute alcohol problems. Part 2: Alcohol-related seizures, delirium tremens, and toxic alcohol ingestion. Canadian Family Physician 1996;42:2423-31
- Lejoyeux M, Solomon J, Ades J: Benzodiazepine treatment for alcohol-dependent patients. Alcohol & Alcoholism 1998;33(6):563-75
- Litten RZ, Allen J, Fertig J: Pharmacotherapies for alcohol problems: a review of research with focus on developments since 1991 [see comments]. Alcoholism: Clinical & Experimental Research 1996;20(5):859-76
- Mayo-Smith MF: Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal [see comments]. Jama 1997;278(2):144-51
- McCowan C, Marik P: Refractory delirium tremens treated with propofol: a case series. Critical Care Medicine 2000;28(6):1781-4
- Myrick H, Anton RE: Clinical Management of Alcohol Withdrawal. CNS Spectrums 2000;5(2):22-32
- Peppers MP: Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease. Pharmacotherapy 1996;16(1):49-57
- Saitz R, O'Malley SS: Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Medical Clinics of North America 1997;81(4):881-907
- Stoudemire A, Fogel BS, Greenberg DB (eds): Psychiatric Care of the Medical Patient. New York, Oxford University Press, 2000
- Tabakoff B, PhD. ,, Hoffman PL, Ph.D. : Neurobiology of Alcohol, in Textbook of Substance Abuse Treatment. Edited by Galanter M, M.D. ,, Kleber HD, M.D. Washington, DC, The American Psychiatric Press, 1999, pp 3-9
- Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, Handforth A, Faught E, Calabrese VP, Uthman BM, Ramsay RE, Mamdani MB: A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group [see comments]. New England Journal of Medicine 1998;339(12):792-8
- van Klei WA, Havenaar JM, Klijn FA, van Dijk A: [Ethanol for treatment of delirium in alcohol dependent patients on intensive care units in the Netherlands: efficacy not proven]. Nederlands Tijdschrift voor Geneeskunde 2000;144(15):710-3
- Williams D, McBride AJ: The drug treatment of alcohol withdrawal symptoms: a systematic review. Alcohol & Alcoholism 1998;33(2):103-15
- Yamaguchi S, Mishio M, Okuda Y, Kitajima T: [A patient with drug abuse who developed multiple psychotic symptoms during sedation with propofol]. Masui - Japanese Journal of Anesthesiology 1998; 47(5):589-92