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Alcohol withdrawal symptoms develop in individuals with a history of heavy and prolonged consumption of alcohol who abruptly stop or reduce their drinking. The spectrum of alcohol withdrawal symptoms includes hand tremors, headache, loss of appetite, nausea and vomiting, diaphoresis, insomnia, tachycardia, hypertension, fever, psychomotor agitation, hyperarousal, craving, and anxiety, as well as the more serious manifestations of seizures, hallucinations, and delirium. The abrupt withdrawal of alcohol from the brain of chronic heavy drinkers is thought to reduce inhibitory neurotransmission through γ-aminobutyric acid and enhance excitatory neurotransmission through glutamate, but not all heavy drinkers experience withdrawal when stopping or cutting back their consumption.8,9,10
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Alcohol withdrawal symptoms exist on a continuum from uncomplicated to moderate and severe, may begin as early as 2 to 6 hours after reduction in alcohol consumption, and can persist for up to 2 weeks. Up to 5% of patients in withdrawal progress to delirium tremens; those with a prior history are at greatest risk. Convulsions occur in 5% to 15%, and delirium tremens occurs in less than 5%. Deaths from delirium tremens among patients receiving early and aggressive treatment have declined from 35% in the early twentieth century to 5% in the current period.8,9,10
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The first step in successful treatment is to identify alcohol withdrawal early and distinguish withdrawal from mimics. The most common mimics include toxic-metabolic abnormalities (hyponatremia, hypoglycemia, hypomagnesemia, diabetic ketoacidosis, Wernicke's encephalopathy), toxic alcohol ingestions (ethylene glycol, methanol), prescription or illicit drug ingestions (opioids, sedative-hypnotics, antihistamines), neurologic abnormalities (primary generalized seizures, withdrawal seizures), subdural or epidural hematoma, hypovolemic trauma, infection, and sepsis.
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Gastritis, peptic ulcer disease, and pancreatitis are comorbidities with symptoms that often require abrupt cessation of alcohol consumption, leading to withdrawal. The gathering of collateral history, thorough serial examinations of the undressed patient, repeated monitoring of vital signs, measurement of oxygen saturation and bedside finger stick for blood glucose, laboratory assessment of metabolic conditions, and imaging as clinically indicated can detect most comorbidities.
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ALCOHOL WITHDRAWAL SEIZURES
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Alcohol withdrawal seizures are diffuse tonic-clonic seizures. According to the landmark observations by Victor and Brausch,11 alcohol withdrawal seizures occur as early as 6 hours after the decrease in intake or the last drink, and 90% occur within 48 hours. Approximately 40% of patients have a single seizure, and 60% have multiple generalized seizures. Victor and Brausch reported that one-third of patients with alcohol withdrawal seizures develop delirium tremens, with the seizures terminating before the development of delirium. An alcohol withdrawal seizure may be brief, with a short or no postictal period.10 The diagnosis of alcohol withdrawal seizures requires the exclusion of traumatic brain injury, hypoxia, hypoglycemia, structural lesions, infections, use of illicit drugs, idiopathic epilepsy, withdrawal from other recreational drugs, and withdrawal from prescription medications. Focal seizures suggest a focal cerebral lesion. Also consider noncompliance with antiseizure medications (in those with idiopathic or posttraumatic seizures).12
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ALCOHOL WITHDRAWAL HALLUCINATIONS (ALCOHOL-INDUCED PSYCHOTIC DISORDER)
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Alcohol-induced withdrawal hallucinations or alcohol-induced psychotic disorder may develop as an isolated finding 12 to 48 hours after decreasing or abstaining from alcohol. Auditory hallucinations predominate over visual and tactile hallucinations. Psychosis, paranoia, and agitation may last from days to weeks. Alcohol-induced psychotic disorder has a high risk for suicide and co-occurs with other psychiatric diagnoses. Patients with hallucinations lasting for >6 months have the worst prognosis; however, the prognosis is more favorable if abstinence can be maintained.13
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ALCOHOL WITHDRAWAL DELIRIUM TREMENS
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Alcohol withdrawal delirium tremens is characterized by acute and fluctuating disturbances in consciousness, confusion, psychomotor agitation, inattention and impairment in cognitive and perceptual function (hallucinations) unrelated to preexisting or established dementia.8,9,10 Patients often develop life-threatening fluid, metabolic, and electrolyte imbalances. Among the risk factors associated with alcohol withdrawal delirium are past withdrawal seizure and delirium, severe dependence and prior detoxification history, high and long duration of alcohol intake, older age, use of other drugs, genetic polymorphism, and comorbidity.8,9,10
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TREATMENT OF ALCOHOL WITHDRAWAL SYNDROMES
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The goals of therapy for alcohol withdrawal are to alleviate autonomic hyperactivity and agitation, halt progression to delirium tremens, and if possible, provide motivation for and access to detoxification to promote long-term abstinence.5,8,9,10 General therapy is the substitution of a benzodiazepine for alcohol (Table 292-1).5,8,9,10 Benzodiazepine equivalents are lorazepam 1 milligram = midazolam 2 milligrams = diazepam 5 milligrams = chlordiazepoxide 25 milligrams. Oral diazepam has a rapid onset of action, and the onset of action of IV diazepam is almost immediate. IM diazepam absorption is erratic, so do not give it IM. Duration of action of diazepam is 20 to 50 hours, and metabolism is hepatic, with the major metabolite (desmethyldiazepam) having a half-life of 20 to 50 hours. Chlordiazepoxide is only available as an oral medication, has a long half-life of up to 28 hours, and has extensive hepatic metabolism with its major active long-acting metabolite, desmethyldiazepam. Lorazepam can be given PO, IM, or IV. Onset of action when given IV is within minutes, and duration of action is 8 hours. Lorazepam is metabolized rapidly by the liver with inactive metabolites excreted by the kidneys and recognized as the benzodiazepine most tolerated by patients with advanced liver disease.8,9,10 Midazolam can be given IV or IM, but for delirium tremens, it is typically given IV. IV onset of action is 3 to 5 minutes.
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Give individualized symptom-triggered therapy rather than fixed-schedule dosing. Symptom-triggered regimens result in less drug and shorter duration of treatment than fixed-drug dosing.15 The Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA) is the most commonly used validated, structured instrument for guiding continuing treatment once a diagnosis of alcohol withdrawal is established.16 It has not been validated specifically for ED use, and comorbid conditions and medications make it difficult to score the Clinical Institute Withdrawal Assessment accurately. The CIWA score ranges from 0 to 67 and tracks 10 variables, with a 0 to 7 ranking for nine variables and a 0 to 4 ranking for the last variable (orientation and clouding of sensorium), where 0 is none and 7 (or 4) is the most severe manifestation of the variable. The variables are nausea/vomiting; tremor; paroxysmal sweats; anxiety; agitation; tactile disturbance; auditory disturbance; visual disturbance; headache; and orientation and clouding of sensorium (0 to 4 rank). A score <8 represents mild withdrawal; score of 9 to 15 moderate withdrawal, and score >15 severe withdrawal.17
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Drug Therapy for Uncomplicated Alcohol Withdrawal
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For patients meeting criteria for uncomplicated alcohol withdrawal without seizures, hallucination, or delirium, the recommended first-line treatment is a benzodiazepine (Table 292-1).8,9,10 Because no specific benzodiazepine is more effective than the others, physician choice, institutional availability, cost, and patient factors are taken into consideration.10
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Drug Therapy for Alcohol Withdrawal Seizures
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Benzodiazepines are effective in protecting against seizures and reducing recurrent seizures in alcohol withdrawal.18,19 A prospective randomized ED trial demonstrated a 3% seizure recurrence rate with a single dose of IV lorazepam, 2 milligrams, compared with 24% among patients receiving placebo.20 Phenytoin is not recommended for prevention of further alcohol-related seizures and should not be used unless the patient has an underlying structural lesion. Repeated loading of phenytoin may, in fact, lower the seizure threshold.20,21
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Drug Therapy for Alcohol Withdrawal Hallucinosis (Alcohol-Induced Psychotic Disorder)
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Antipsychotic therapy with alcohol abstinence is the recommended treatment. There is no long-term need for antipsychotic medication for abstinent patients once symptoms remit. Because patients with alcohol-induced psychotic disorder could be at risk for suicide, admission is recommended.13
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Drug Therapy for Alcohol Withdrawal Delirium
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Alcohol withdrawal delirium develops within 3 to 5 days of the last drink and generally lasts 48 to 72 hours, but may last longer. The current practice guideline published by the American Society of Addiction Medicine recommends the use of sedative-hypnotics in high enough doses to quickly control agitation, minimize adverse events, and achieve light somnolence with arousal when stimulated.9 A benzodiazepine is the initial treatment of choice (Table 292-1). If symptoms are unresponsive to adequate doses of benzodiazepines, additional agents include phenobarbital, propofol, or haloperidol.22,23,24 Phenobarbital or propofol typically requires intubation. Propofol's central nervous system mechanism of action is thought to be similar to that of ethanol. Adverse effects of propofol include hypotension, and prolonged use >48 h and >5 milligrams/kg/h can cause propofol infusion syndrome,25,26 with dysrhythmias, heart failure, hyperkalemia, lipemia, metabolic acidosis, and rhabdomyolysis. Antipsychotics such as haloperidol, droperidol, or ziprasidone should be reserved for psychosis or continued agitation (see chapter 287, "Acute Agitation") only after adequate benzodiazepines are administered.
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Patients with delirium require thorough diagnostic assessment, aggressive treatment of co-occurring illnesses, supportive care, prevention of aspiration, and treatment of hyperthermia, dehydration, hypoglycemia, and electrolyte imbalance. Thiamine, 100 milligrams, and folate, 1 milligram, should be considered. Treat hypomagnesemia with IV magnesium. A benefit from magnesium therapy in the absence of hypomagnesemia is not established.27 Physical restraints may be temporarily needed until chemical restraint is achieved; a quiet, calm, supportive environment with low stimuli contributes to successful management.8,9,10
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Patients with mild or moderate uncomplicated alcohol withdrawal that responds well to initial ED treatment, without trauma or major medical comorbidities, with no suicidal or homicidal ideation, and without a seizure disorder can be managed successfully in a detoxification unit or discharged to a supportive family with referral to an outpatient program. Indications for admission include advanced age, mild or moderate withdrawal that does not respond well to ED treatment, the presence of active medical comorbidities, a prior history of delirium tremens, and alcohol withdrawal seizures. Consider intensive care unit admission for moderate withdrawal with comorbid conditions or severe withdrawal in which sedative requirements necessitate intubation or close monitoring to prevent respiratory compromise.