eMedicine Specialties > Emergency Medicine > Neurology
Delirium Tremens: Treatment & Medication
Updated: Oct 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Emergency Department Care
Morbidity and mortality from delirium tremens (DT) are secondary to a hyperadrenergic state and other associated medical problems (eg, infections, fluid and electrolyte abnormalities). The goal is to blunt the hyperadrenergic state and treat associated medical problems.
- Secure airway appropriately
- Oxygen supplementation
- Large-bore intravenous line
- Fluid resuscitation with crystalloid solution
- Cardiac monitor
- Bedside glucose testing with supplementation if needed
- Thiamine administration (100 mg IV) to treat or prevent Wernicke encephalopathy
- Sedation with benzodiazepines
- Check electrolytes, replace as needed
- Physical restraints often needed to ensure patient and staff safety (use in conjunction with chemical restraints)
Medication
Parenteral benzodiazepines are the drugs of choice for treatment of delirium tremens (DT). Patients may require massive doses to achieve sedation. In patients refractory to benzodiazepine therapy alone, barbiturates or propofol should be added.4
Benzodiazepines are the medication of choice because they have a high therapeutic index and superior anticonvulsant effects. They act on the benzodiazepine-GABA-chloride receptor complex having a similar GABA potentiating effect to alcohol. No clear evidence suggests superiority of any particular benzodiazepine, but longer-acting benzodiazepines such as diazepam and chlordiazepoxide are generally preferred. Diazepam has an ideal pharmacologic profile because of its rapid onset of action and prolonged duration of effects due to active metabolites, allowing the dose to be safely and rapidly escalated until control of the patient’s symptoms is achieved.
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. Symptom-triggered therapy with intermittent boluses is superior to a fixed dose taper or infusion of benzodiazepines.5,6 Therapy may be guided by the CIWA-A score, an assessment tool used to determine the severity of alcohol withdrawal.
Barbiturates such as phenobarbital and pentobarbital are also useful to treat delirium tremens. However, compared with benzodiazepines, they have a lower therapeutic index and can cause respiratory depression and hypotension. Barbiturates should be reserved for patients refractory to or unable to take benzodiazepines.7 These patients all need ICU monitoring, and many will need to be intubated and mechanically ventilated.
Propofol has been described in case series to be successful in the treatment of refractory delirium tremens in intubated patients. It has effects on NMDA and GABA receptors.
Ethanol is not recommended as there is little evidence regarding its use in withdrawal, and it has many potential adverse effects such as hepatotoxicity, hyponatremia, hypoglycemia, hypotension, and depression of level of consciousness.
Adjuvant therapies4
Neuroleptics have been shown to be inferior to sedative-hypnotics in reducing mortality and duration of alcohol withdrawal delirium. Drugs such as haloperidol (Haldol) should not be used, as they lower seizure threshold and can prolong QTc, while doing nothing to address the underlying pathophysiology.
Sympatholytic agents such as clonidine and beta-blockers have been studied in mild-moderate ethanol withdrawal. There is no evidence regarding their effectiveness in delirium tremens. These drugs decrease sympathetic drive improving hypertension and tachycardia but have no GABA effects and hence are ineffective in preventing seizures. For this reason, they should not be used as sole therapies. Beta-blockers may be helpful to prevent cardiac complications in withdrawal patients with known coronary artery disease. However, use of these drugs is controversial as normalization of vitals signs may mask progression of withdrawal, leading to inadequate treatment of withdrawal. When benzodiazepines are used appropriately, with escalation of dose to clinical effect, sympatholytics are rarely necessary.
Anticonvulsants carbamazepine and valproic acid have been shown to be effective in treatment of mild-to-moderate withdrawal. No role exists for use of phenytoin in treatment of ethanol withdrawal or withdrawal seizures. However, it can be used to treat underlying primary seizure disorder.
Phenytoin is not helpful in patients with delirium tremens and seizures. Benzodiazepines or barbiturates effectively treat both seizures and other manifestations of delirium tremens.
Benzodiazepines
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 neuro-inhibitory effects. First-line agents for delirium tremens.
Diazepam (Valium)
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 5 min after IV administration. Has active metabolite (desmethyl-diazepam) that has longer duration of action than diazepam.
Adult
5-10 mg IV, redose q5-15min until sedated
Large cumulative doses may be required to treat DTs
Pediatric
Not established
Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, or MAOIs
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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, especially if used intramuscularly
Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease
Lorazepam (Ativan)
Short onset of effect and intermediate half-life. Can be given IM in patients lacking IV access.
Adult
1-4 mg IV, redose q5-15 min
Pediatric
Not established
Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, or MAOIs
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Chlordiazepoxide (Librium)
Depresses all levels of CNS including limbic and reticular formation, possibly by increasing GABA activity.
Adult
50-100 mg IV q5-15min until sedated
Pediatric
Not established
Coadministration with alcohols, phenothiazines, barbiturates, or MAOIs increases CNS toxicity; cisapride can increase levels significantly
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Barbiturates
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 is common at large doses. Ventilatory support may be required.
Phenobarbital (Luminal, Barbital)
Has 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 respiratory depression may occur, especially after previous benzodiazepine therapy, early mechanical ventilation should be considered.
Adult
130 mg IV over 1-2 min q5-15min until sedated
Pediatric
Not established
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
Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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; patients with refractory alcohol withdrawal requiring barbiturates may need intubation and mechanical ventilation
Pentobarbital (Nembutal)
Short-acting barbiturate with sedative, hypnotic, and anticonvulsant properties and can produce all levels of CNS mood alteration.
Adult
100 mg IV over 1-2 min q5-15min until sedated
Pediatric
Not established
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 corticosteroid and digitoxin effects through induction of hepatic microsomal enzymes, which increase metabolism; decreases theophylline levels and may decrease effects; may decrease verapamil bioavailability
Documented hypersensitivity; liver failure
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Patient may become tolerant to hypnotic effects; caution in hypovolemic shock, respiratory dysfunction, renal dysfunction, previous addiction to sedative hypnotics, and CHF; patients with refractory alcohol withdrawal requiring barbiturates may need intubation and mechanical ventilation
General Anesthetic
Propofol is an anesthetic agent with action at NMDA and GABA receptors. It has advantages of rapid onset of action and rapid metabolic clearance. It is a good alternative for alcohol withdrawal resistant to benzodiazepines. Because of respiratory depression, intubation is required.
Propofol (Diprivan)
Phenolic compound that is a sedative-hypnotic agent used for induction and maintenance of anesthesia or sedation. Has also been shown to have anticonvulsant properties.
Adult
Bolus IV injection of 0.5 mg/kg q10s to a total dose of 2-2.5 mg/kg or by continuous infusion at 25-75 mcg/kg/min
Pediatric
Not established
Reduce propofol dose when administered concomitantly with benzodiazepines, opiates, phenothiazines, ethanol, and narcotics; propofol may potentiate neuromuscular blockade of vecuronium; theophylline may weaken effects of propofol, and dose increase may be needed
Documented hypersensitivity; those who are not mechanically ventilated
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Do not administer with blood or blood products using the same IV catheter; patients may develop apnea; may experience a decrease in systemic vascular resistance leading to hypotension; patients requiring propofol for control of DTs generally require intubation
Vitamins and Nutrients
These agents are used to treat the hypoglycemia, nutrient, and electrolyte deficiencies associated with DTs.
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 often are magnesium deficient due to a poor nutritional status and malabsorption. Magnesium stabilizes membranes, helps in the maintenance of potassium and calcium homeostasis, and may protect against seizures and arrhythmias.
Patients suffering from alcoholism may also develop hypoglycemia due to malnutrition and poor glycogen stores. Additionally, gluconeogenesis is impaired due to a relative reduced redox state resulting from alcohol metabolism, which uses NAD+ as a cofactor for alcohol dehydrogenase and aldehyde dehydrogenase. The relative excess of NADH shifts the pyruvate-to-lactate ratio toward lactate, decreasing the substrate for gluconeogenesis.
Dextrose 50% (D-Glucose)
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
0.5-1 mg/kg IV bolus
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Caution when administering parenteral fluids to patients receiving corticosteroids or corticotropin, especially if solution contains sodium ions
Do not administer if blood sugar levels are extremely high, and avoid in severely dehydrated patients
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Sudden onset or worsening of Wernicke encephalopathy, following glucose, may occur in thiamine-deficient patients; administer after or together with thiamine in suspected thiamine deficiency. However, dextrose administration should never be delayed pending the availability of thiamine in patients with significant hypoglycemia; instead, the dextrose should be given in this case followed as soon a possible by the thiamine once it is available. 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
Thiamine (Vitamin B-1)
Used to treat thiamine deficiency, including Wernicke encephalopathy syndrome.
Adult
100 mg IV
Pediatric
50 mg IV initially, followed by 10-25 mg/d IV/IM
None reported
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use
Folic acid (Folate)
Dietary deficiency of folic acid common in alcoholics. Folic acid is an important cofactor for enzymes used in production of RBCs.
Adult
1 mg IV
Pediatric
Administer as in adults
Increase in seizure frequency and decrease in subtherapeutic levels of phenytoin reported when used concurrently
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
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
Magnesium sulfate
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 effects by blocking the NMDA receptor. Monitor carefully; large doses 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
2 g in 50 mL of D5W over 20 min IV
Pediatric
25-50 mg/kg/dose IV; maximum single dose of 2 g may also be administered and repeated if hypomagnesemia persists
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
Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
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
More on Delirium Tremens |
| Overview: Delirium Tremens |
| Differential Diagnoses & Workup: Delirium Tremens |
 Treatment & Medication: Delirium Tremens |
| Follow-up: Delirium Tremens |
| References |
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Further Reading
Keywords
DT, delirium tremens, delirium tremens symptoms, alcohol withdrawal delirium, alcohol withdrawal hallucinosis, ethanol abstinence, rum fits, ethanol withdrawal, ethanol alcohol withdrawal, ethanol withdrawal seizures
