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Article Last Updated: Jul 2, 2007
Delirium tremens (DT) is a potentially fatal form of ethanol (alcohol) withdrawal. Symptoms of ethanol withdrawal and DT have been recognized for hundreds of years, but the debate over their etiology continued into the 1950s. The work of Victor and Adams as well as Isbell finally demonstrated the symptoms related to ethanol abstinence.
Symptoms may begin a few hours after the cessation of ethanol but may not peak until 48-72 hours. Emergency physicians must recognize that the presenting symptoms may not be severe and identify those at risk for developing DT. For patients in DT, early recognition and therapy are necessary to prevent significant morbidity and death.
DT is caused by the direct effect that ethanol has on the benzodiazepine-GABAa-chloride receptor complex. Persistent effects of ethanol lead to the down-regulation of the receptor complex. When ethanol is withdrawn, a functional decrease in the inhibitory neurotransmitter GABA is seen. This results in an unopposed increase in sympathetic activity with a resultant increase in plasma and urinary catecholamines. Ethanol also acts as an N-methyl D-aspartate receptor antagonist. Withdrawal of ethanol leads to increased activity of these excitatory neural receptors.
Only 5% of patients with ethanol withdrawal progress to DT.
Approximately 10% of males and 3-5% of females are alcoholic; 5% of each group experiences DT.
Adolescence to late adulthood is typical.
A large number of pharmacologic agents have been used to treat DT; however, benzodiazepines are the medication of choice because they have a high therapeutic index and interact with ethanol on the benzodiazepine-GABAa-chloride receptor complex. Benzodiazepines such as diazepam have an ideal pharmacologic profile because of their rapid onset of action and prolonged duration of effects. Benzodiazepine dose required may be highly variable and should be titrated until the patient is calm and peaceful. For some patients, several hundred milligrams of a diazepam equivalent may be required over the first few hours.
Barbiturates such as phenobarbital and pentobarbital also are useful to treat DT despite their lower therapeutic indexes. Barbiturates may be required (rarely) for patients refractory to benzodiazepine treatment.
Do not use phenothiazines because they lower the seizure threshold and do not affect the benzodiazepine-GABAa-chloride receptor complex.
Ethanol is effective in blunting withdrawal symptoms, but it is no longer indicated because of associated electrolyte abnormalities, potential worsening of gastritis, hepatitis, and pancreatitis. Ethanol use may promote continued ethanol usage.
Phenytoin is probably not helpful in most patients with DT and seizures. Benzodiazepines or barbiturates treat seizures and manifestations of DT.
These agents bind to benzodiazepine receptors in the benzodiazepine-GABAa-chloride receptor complex to enhance the binding of GABA, causing enhanced chloride flux, hyperpolarization of the membrane, and neural inhibitory effects.
| Drug Name | Diazepam (Valium) |
|---|---|
| Description | Because of rapid onset, prolonged duration of effects, and high therapeutic index, diazepam is drug of choice. Volumes of literature exist regarding usage of diazepam for ethanol withdrawal. Onset of action is within a couple of min after IV administration. Has active metabolite (desmethyl-diazepam) that has longer duration of action than diazepam. |
| Adult Dose | 5-10 mg IV bolus q5-15min until sedated Large cumulative doses may be required to treat DT |
| Pediatric Dose | 0.05-0.3 mg/kg/dose IV over 2-3 min q15-30min until sedated; not to exceed 5 mg/dose |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma |
| Interactions | Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, or MAOIs |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity) |
| Drug Name | Lorazepam (Ativan) |
|---|---|
| Description | Sedative hypnotic in benzodiazepine class that has short onset of effect and relatively long half-life. Monitor patient's BP after administering dose and adjust as necessary. |
| Adult Dose | 1-2 mg IV bolus q5-15min until sedated |
| Pediatric Dose | 0.1 mg/kg IV slowly over 2-5 min; repeat prn in 10-15 min at a dose of 0.05 mg/kg IV administered slowly until sedated; not to exceed 4 mg/dose |
| Contraindications | Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma |
| Interactions | Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, or MAOIs |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Because of delayed peak onset of action, sedation may not peak for 20-30 min; cumulative effects of repeated bolus may cause sudden onset of oversedation or respiratory depression Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease |
| Drug Name | Chlordiazepoxide (Librium) |
|---|---|
| Description | Depresses all levels of CNS including limbic and reticular formation, possibly by increasing GABA activity. Parenteral form usually used initially. |
| Adult Dose | 50-100 mg IV q5-15min until sedated |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma |
| Interactions | Coadministration with alcohols, phenothiazines, barbiturates, or MAOIs increases CNS toxicity; cisapride can increase levels significantly |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Cumulative effects of repeated bolus may cause sudden onset of oversedation or respiratory depression Caution in low albumin levels or hepatic failure, as diazepam toxicity may increase |
These agents have direct effects on benzodiazepine-GABAa-chloride receptor complex in enhancing chloride flux. Barbiturates may be useful in patients refractory to benzodiazepines. Respiratory depression may be common at large doses. Ventilatory support may be required in most patients receiving high-dose barbiturates. Because of their lower therapeutic index, benzodiazepines should be considered the DOC.
| Drug Name | Phenobarbital (Luminal, Barbita) |
|---|---|
| Description | Have direct effects on benzodiazepine-GABAa-chloride receptor complex in enhancing chloride flux. May be useful in patients refractory to benzodiazepines. Exhibits anticonvulsant properties in anesthetic doses. Because a barbiturate-induced depression may occur, especially after previous benzodiazepine therapy, early mechanical ventilation should be considered. |
| Adult Dose | 130 mg IV over 1-2 min q5-15min until sedated |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis |
| Interactions | Coadministration with alcohol may produce additive CNS effects and death; may decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities may also occur) |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema |
| Drug Name | Pentobarbital (Nembutal) |
|---|---|
| Description | Short-acting barbiturate with sedative, hypnotic, and anticonvulsant properties and can produce all levels of CNS mood alteration. |
| Adult Dose | 100 mg IV over 1-2 min q5-15min until sedated |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; liver failure |
| Interactions | Concomitant use with alcohol may produce additive CNS effects and death; chloramphenicol may inhibit metabolism; may enhance chloramphenicol metabolism; MAOIs may enhance sedative effects; valproic acid appears to decrease metabolism, increasing toxicity; can decrease effects of anticoagulants (patients may require dosage adjustments if barbiturates added to or withdrawn from regimen); may decrease oral contraceptive effect by induction of microsomal enzymes (alternate form of birth control suggested); may decrease corticosteroid and digitoxin effects through induction of hepatic microsomal enzymes, which increase metabolism; decreases theophylline levels and may decrease effects; may decrease verapamil bioavailability |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Patient may become tolerant to hypnotic effects; caution in hypovolemic shock, respiratory dysfunction, renal dysfunction, previous addiction to sedative hypnotics, and CHF |
These agents are used to treat the hypoglycemia and nutrient deficiencies associated with DT.
Alcoholics usually are deficient in thiamine, which functions as a cofactor for a number of important enzymes, such as pyruvate dehydrogenase, transketolase, and alpha-ketoglutarate dehydrogenase. Deficiency leads to Wernicke encephalopathy, peripheral neuropathy, cardiomyopathy, and metabolic acidosis.
Alcoholics usually are magnesium deficient due to a poor nutritional status and malabsorption from ethanol. Magnesium stabilizes membranes, helps in the maintenance of potassium and calcium homeostasis, and may protect against seizures and arrhythmias.
| Drug Name | Dextrose 50% (D-Glucose) |
|---|---|
| Description | Monosaccharide absorbed from intestine and distributed, stored, and used by tissues. Parenterally injected dextrose used in patients unable to obtain adequate oral intake. Direct oral absorption results in rapid increase of blood glucose concentrations. Effective in small doses; no evidence of toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake, with minimal fluid volume. Use 1 ampule of 50 mL of a 50% glucose solution (25 g). |
| Adult Dose | 0.5-1 mg/kg IV bolus |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Do not administer to a patient in diabetic coma if blood sugar levels are extremely high, and avoid in severely dehydrated patients Do not administer concentrated solution if intraspinal or intracranial hemorrhage is present; avoid in dehydrated patients with DT, hepatic coma, or glucose-galactose malabsorption syndrome |
| Interactions | Caution when administering parenteral fluids to patients receiving corticosteroids or corticotropin, especially if solution contains sodium ions |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Extravasation may cause significant tissue necrosis when used IV; isolated reports of nausea, which may also occur with hypoglycemia, have been recorded; dextrose solutions administered IV can result in dilution of serum electrolyte concentrations and overhydration when fluid overload exists; caution in congested states or pulmonary edema |
| Drug Name | Thiamine (Vitamin B-1) |
|---|---|
| Description | Used to treat thiamine deficiency, including Wernicke encephalopathy syndrome. |
| Adult Dose | 100 mg IV |
| Pediatric Dose | 50 mg IV initially, followed by 10-25 mg/d IV/IM |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy, following glucose, may occur in thiamine-deficient patients; administer before or together with dextrose-containing fluids in suspected thiamine deficiency |
| Drug Name | Folic acid (Folate) |
|---|---|
| Description | Dietary deficiency of folic acid common in alcoholics. Folic acid is an important cofactor for enzymes used in production of RBCs. |
| Adult Dose | 1 mg PO/IV |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Increase in seizure frequency and decrease in subtherapeutic levels of phenytoin reported when used concurrently |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Benzyl alcohol may be contained in some products as a preservative (associated with a fatal gasping syndrome in premature infants); resistance to treatment may occur in patients with alcoholism and deficiencies of other vitamins |
| Drug Name | Magnesium sulfate |
|---|---|
| Description | Used to treat and prevent seizures. Decreases amount of acetylcholine liberated at endplate by motor nerve impulse. Blocks neuromuscular transmission associated with seizure activity. Magnesium also has CNS depressant effect. Monitor carefully; may cause respiratory depression, hyporeflexia, and bradycardia. Infusion should be discontinued if reflexes are absent or if magnesium levels exceed 6-8 mEq/L. Calcium chloride, 10 mL IV of a 10% solution, can be given as antidote for clinically significant hypermagnesemia. |
| Adult Dose | 2 g in 50 mL of D5W over 20 min IV |
| Pediatric Dose | 25-50 mg/kg/dose IV; maximum single dose of 2 g may also be administered and repeated if hypomagnesemia persists |
| Contraindications | Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis |
| Interactions | Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, or succinylcholine; may increase CNS effects and toxicity of CNS depressants or betamethasone; may increase cardiotoxicity of ritodrine |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Magnesium may alter cardiac conduction, leading to heart block in digitalized patients; respiratory rate, deep tendon reflexes, and renal function should be monitored when electrolyte is administered parenterally; caution when administering, since may produce significant hypertension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia |
Article Last Updated: Jul 2, 2007