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Ms. J, 42, was admitted to the OB-GYN service for a routine vaginal hysterectomy to treat dysfunctional uterine bleeding. In the presurgical history, she described having a few drinks daily. Shortly after a successful uncomplicated procedure, the patient became tremulous and was given several doses of lorazepam.
Two days after surgery, the patient became delirious. She complained of tactile and visual hallucinations, her level of consciousness waxed and waned, and she showed significant autonomic instability. A psychiatry consult was ordered. The consult team recommended IV fluids, IV diazepam, and haloperidol, supplemented with a multivitamin and 100 mg/d of thiamine. When the patient’s delirium resolved within 4 days, a more detailed discussion revealed a history of alcohol abuse and withdrawal seizures.
It is not uncommon for a patient to develop acute alcohol withdrawal and delirium tremens (DTs) while recovering from routine surgery. Delirium tremens remains a medical emergency, even though advances have reduced its associated mortality rates (Box).1-7
Psychiatrists who know the risk factors for DTs—also termed alcohol withdrawal delirium—can identify and protect patients who are susceptible to this life-threatening complication. We describe the clinical features of DTs, potential predisposing factors, theories behind its mechanisms, and strategies for preventing and managing DTs in patients experiencing alcohol withdrawal.
Clinical features
Disorientation and confusion are the hallmark features of DTs. Other clinical manifestations include vivid hallucinations, extreme tremulousness, autonomic hyperactivity, sweating, tachycardia, and agitation. Men experiencing DTs seem to demonstrate a greater degree of autonomic hyperactivity than women.8
Symptoms usually arise in the alcoholic patient between the third and fifth days of abstinence but have been known to occur several weeks after a patient’s last drink. Symptoms usually resolve within a few days9 but have been known to resolve within hours in some patients and to persist for several months in others.10
Differential diagnosis. Clinicians often fail to differentiate alcohol hallucinosis from DTs. Alcohol hallucinosis—which occurs in 3 to 10% of patients with severe alcohol withdrawal11 —manifests as auditory, visual, or tactile hallucinations with a clear sensorium. Patients experiencing DTs also may experience hallucinations but with confusion, disorientation, and severe autonomic hyperactivity. Unlike DTs, alcohol hallucinosis is not fatal.9
DTs also should be differentiated from:
- other causes of delirium, such as medication or infection. If the cause is identified and removed, the delirium should gradually resolve.
- Wernicke’s encephalopathy—caused by glucose exposure in the thiamine-deficient alcoholic—which is characterized by confusion, ophthalmoplegia, and ataxia.
Completing a thorough history and physical exam, talking to family members, and reviewing past medical charts are often the best ways to differentiate DTs from other conditions.
What causes DTs?
Vitamin deficiencies were initially thought to cause alcohol withdrawal.3 More recent evidence points toward multiple neuroadaptive changes in the brain associated with chronic alcohol exposure.12 Although numerous neurotransmitter systems may play a role in alcohol withdrawal, recent research has focused on glutamate13 and gamma-aminobutyric acid (GABA).14
Approximately 1.5 to 2 million Americans seek treatment for alcohol abuse or dependence each year.1 As many as 71% of these patients manifest symptoms of alcohol withdrawal.2 Of those individuals who experience alcohol withdrawal, delirium tremens (DTs) may occur in up to 5%.3-5 Utilizing these percentages, it can be estimated that as many as 50,000 to 70,000 individuals develop DTs each year in the United States alone.
Although the incidence of DTs can be assumed to be relatively low, the condition should be considered a medical emergency. Studies list mortality rates for DTs as high as 15% and as low as 2 to 3%.7,8
The brain seems to compensate for alcohol’s enhancement of GABA (inhibitory) neurons by up-regulating excitatory neurons (glutamate). Alcohol has been shown to have some effects on neurons.15 The implication is that withdrawing alcohol triggers an “excitatory state” until the brain can readjust the fine balance between excitation and inhibition, a process that takes weeks to months. Some changes may never reverse because of the neurotoxic effects of alcohol and alcohol withdrawal.
Repeated alcohol exposure and withdrawal may lead to neuroadaptive changes in the brain and to more severe withdrawal symptoms, such as DTs. Repeated alcohol withdrawal episodes can produce a kindling effect. As outlined by Becker, kindling occurs “when a weak electrical or chemical stimulus, which initially causes no overt behavioral responses, results in the appearance of behavioral effects, such as seizures, when it is administered repeatedly.”16 Thus, repeated alcohol withdrawal worsens future episodes and eventually leads to alcohol withdrawal seizures.
Whereas most of these theories apply to alcohol withdrawal, they are also compatible with the neuronal mechanisms that may underlie DTs. Alcohol withdrawal and DTs share the presence of a “hyperactive state.” Most likely, DTs is the progression to more severe or pronounced neuroadaptive changes seen in mild to moderate alcohol withdrawal. One could certainly imagine that the possible neurotoxic effects of alcohol, alcohol withdrawal, and repeated detoxifications could sensitize the CNS to the more severe symptoms seen in DTs. Infection and metabolic abnormalities may also enhance the progression. Unfortunately, why some but not all patients experiencing alcohol withdrawal progress to DTs is unknown.
Table 1
RISK FACTORS FOR DELIRIUM TREMENS
| Comorbid medical illness (with electrolyte, fluid abnormalities)* |
| History of delirium tremens* |
| Blood alcohol level >300 mg/dL on presentation* |
| Presentation after an alcohol withdrawal seizure* |
| Older age* |
| Longer history of alcohol dependence |
| Intense alcohol craving |
| Abnormal liver function |
| * Supported with studies and/or in the medical literature |
| Source: Saitz R. Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22(1):5-12. |
Table 2
STRATEGIES TO PREVENT AND TREAT DELIRIUM TREMENS
| Assess risk for DTs with a thorough history, including collaborative family information and medical charts |
| Admit patients with a history of serious withdrawal symptoms or potential for inpatient detoxification (based on degree of tolerance) |
| Check complete lab values (chemistry panel, liver function tests including ALT and AST, complete blood count, blood alcohol level, GGT, and others if relevant), and correct any fluid, vitamin, or electrolyte abnormalities |
| Treat comorbid medical conditions |
| Differentiate DTs from alcohol hallucinosis, other causes of delirium, and Wernicke’s encephalopathy |
| Consider giving benzodiazepines along with low-dose neuroleptics, if appropriate, and monitor for disinhibition/ confusion and extrapyramidal symptoms, respectively |
| Place the patient in a low-stimulation environment with frequent monitoring |
Predisposing risk factors
Past withdrawal complicated by seizures or DTs is the single best predictor of future alcohol withdrawal symptoms.17 Also consider the following patients to be at elevated risk:
- any individual who presents with a blood alcohol level >300 mg/dl or after experiencing a withdrawal seizure9
- patients with comorbid medical conditions, such as electrolyte abnormalities, infection, or poorly treated cardiovascular or respiratory diseases
- older persons, who tend to be susceptible to delirium associated with hospitalization, medical illnesses such as urinary tract infections or pneumonia, or use of certain medications.18
Potential risk factors for developing DTs are summarized in Table 1.1 Although few studies have been done, clinicians can use these factors as a guide for aggressively preventing DTs in at-risk patients.
Managing and preventing DTs
Management. Drug therapy is considered crucial to quell withdrawal symptoms and reduce the risk of death.19 Patients usually are treated with one of several benzodiazepines (such as chlordiazepoxide, diazepam, oxazepam, or lorazepam) to decrease autonomic instability and reduce seizure risk during acute alcohol withdrawal. Although dosages of these medications are estimated based on drinking history, some general starting ranges are often used in clinical practice:
- chlordiazepoxide, 50 to 100 mg tid
- lorazepam, 1 to 2 mg every 4 hours
- oxazepam, 15 to 30 mg qid
- diazepam, 10 to 20 mg tid/qid.
Treating DTs often requires the use of IV benzodiazepines because of their quick onset of action and benefit for acutely agitated patients who have difficulty taking medications by mouth.
Prevention. Correcting fluid and electrolyte abnormalities may be critical in preventing DTs (Table 2). In one study of patients who died while experiencing DTs, only 25% received adequate fluid replacement, which can be as much as 6 liters per day.20 Ideally, comorbid conditions should be addressed early in presentation and before DTs develop.21
High-dose benzodiazepine therapy does not completely protect a patient from DTs or reduce its duration,22 but it may reduce mortality. A meta-analysis of prospective, placebocontrolled trials reported a risk reduction of 4.9 cases of DTs per 100 patients treated with benzodiazepines. Mortality also seems to have been reduced in patients with DTs who were treated with sedative hypnotics.9 Benzodiazepines may cause increased confusion and disinhibition, as is frequently seen when patients with dementia are treated with these agents.23
Neuroleptics such as haloperidol have been used to prevent and treat DTs, but studies of their ability to reduce mortality have produced inconsistent results. What’s more, neuroleptics can reduce the seizure threshold and produce extrapyramidal symptoms.23 Atypical antipsychotics may offer a safer alternative, although more studies are needed to evaluate whether they decrease the occurrence and severity of DTs.
In summary, a rational approach to preventing and treating DTs is to:
- manage comorbid medical illnesses, and correct fluid and electrolyte abnormalities
- place the patient in a safe, low-stimulation environment with frequent monitoring
- use benzodiazepines judiciously.
Related resources
- National Institute on Alcohol Abuse and Alcoholism.
- www.niaaa.nih.gov
- 1995;30(6):765-70 (a thorough review of benzodiazepine use in alcohol withdrawal).
Drug brand names
- Chlordiazepoxide • Librium
- Diazepam • Valium
- Haloperidol • Haldol
- Lorazepam • Ativan
- Oxazepam • Serax
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.
1. Saitz R. Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22(1):5-12.
2. Saitz R, Redmond MS, Mayo-Smith MF, et al. Individualized treatment for alcohol withdrawal. Randomized, double-blind, controlled trial. JAMA 1994;272:519-23.
3. Victor M, Adams RD. The effect of alcoholism on the nervous system. Research Publication of the Association for Research on Nervous and Mental Disorders 1953;32:526-73.
4. Victor M, Braush C. The role of abstinence in the genesis of alcoholic epilepsy. Epilepsia 1967;8:1-20.
5. Sellars EM, Kalant H. Alcohol intoxication and withdrawal. N Engl J Med 1976;294:757-62.
6. Victor M. Treatment of alcoholic intoxication and the withdrawal syndrome. Psychosomat Med 1966;28:636-50.
7. Guthrie S. The treatment of alcohol withdrawal. Pharmacotherapy 1989;9:131-43.
8. Trevisan LA, Boutrous N, Petrakis I, Krystal JH. Complications of alcohol withdrawal. Alcohol World 1998;22(1):61-66.
9. Mayo-Smith MF. Management of alcohol intoxication, overdose, and withdrawal. In: Graham AW, Schultz TK (eds). Principles of addiction medicine (2nd ed). Chevy Chase, MD: American Society of Addiction Medicine, 1998;434-41.
10. Wolf KM, Shaughnessy AF, Middleton DB. Prolonged delirium tremens requiring massive doses of medication. J Am Board Fam Pract 1993;6:502-4.
11. Platz WE, Oberlaender FA, Seidel ML. The phenomenology of perceptual hallucinations in alcohol-induced delirium tremens. Psychopathology 1995;28:247-55.
12. Littleton J. Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World 1998;22(1):13-24.
13. Hoffman PL, Rabe CS, Grant KA, Valverius P, Hudspith M, Tabakoff B. Ethanol and the NMDA receptor. Alcohol 1990;7(3):229-31.
14. Morrow AL, Montpied P, Lingford-Hughes A, Paul SM. Chronic ethanol and pentobarbital administration in the rat: effects on GABAA receptor function and expression in brain. Alcohol 1990;7(3):237-44.
15. Begleiter H Kissin B (eds) The pharmacology of alcohol and alcohol dependence. New York: Oxford University Press, 1996.
16. Becker HC. Kindling in alcohol withdrawal. Alcohol World 1998;22(1):25-33.
17. Gold M, Miller N. Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence. Am Fam Phys 1998;58:139-46.
18. Kraemer K, Mayo-Smith MF, Calkins R. Pharmacological management of alcohol withdrawal: a meta analysis of evidence-based practical guidelines. JAMA 1997;278:144-51.
19. Shaw GK. Detoxification: the use of benzodiazepines. Alcohol Alcohol 1995;30(6):765-70.
20. Victor M. Diagnosis and treatment of alcohol withdrawal states. Pract Gastroenteritis 1983;7(5):6-15.
21. Myrick H, Anton R. Treatment of alcohol withdrawal. Alcohol Health Res World 1998;22(1):38-43.
22. Hersh D, Kranzler HR, Meyer RE. Persistent delirium following cessation of heavy alcohol consumption: diagnostic and treatment implications. Am J Psychiatry 1997;154(6):846-51.
23. Myrick H, Anton R. Clinical management of alcohol withdrawal. CNS Spectrums 2000;5(2):22-32.
Ms. J, 42, was admitted to the OB-GYN service for a routine vaginal hysterectomy to treat dysfunctional uterine bleeding. In the presurgical history, she described having a few drinks daily. Shortly after a successful uncomplicated procedure, the patient became tremulous and was given several doses of lorazepam.
Two days after surgery, the patient became delirious. She complained of tactile and visual hallucinations, her level of consciousness waxed and waned, and she showed significant autonomic instability. A psychiatry consult was ordered. The consult team recommended IV fluids, IV diazepam, and haloperidol, supplemented with a multivitamin and 100 mg/d of thiamine. When the patient’s delirium resolved within 4 days, a more detailed discussion revealed a history of alcohol abuse and withdrawal seizures.
It is not uncommon for a patient to develop acute alcohol withdrawal and delirium tremens (DTs) while recovering from routine surgery. Delirium tremens remains a medical emergency, even though advances have reduced its associated mortality rates (Box).1-7
Psychiatrists who know the risk factors for DTs—also termed alcohol withdrawal delirium—can identify and protect patients who are susceptible to this life-threatening complication. We describe the clinical features of DTs, potential predisposing factors, theories behind its mechanisms, and strategies for preventing and managing DTs in patients experiencing alcohol withdrawal.
Clinical features
Disorientation and confusion are the hallmark features of DTs. Other clinical manifestations include vivid hallucinations, extreme tremulousness, autonomic hyperactivity, sweating, tachycardia, and agitation. Men experiencing DTs seem to demonstrate a greater degree of autonomic hyperactivity than women.8
Symptoms usually arise in the alcoholic patient between the third and fifth days of abstinence but have been known to occur several weeks after a patient’s last drink. Symptoms usually resolve within a few days9 but have been known to resolve within hours in some patients and to persist for several months in others.10
Differential diagnosis. Clinicians often fail to differentiate alcohol hallucinosis from DTs. Alcohol hallucinosis—which occurs in 3 to 10% of patients with severe alcohol withdrawal11 —manifests as auditory, visual, or tactile hallucinations with a clear sensorium. Patients experiencing DTs also may experience hallucinations but with confusion, disorientation, and severe autonomic hyperactivity. Unlike DTs, alcohol hallucinosis is not fatal.9
DTs also should be differentiated from:
- other causes of delirium, such as medication or infection. If the cause is identified and removed, the delirium should gradually resolve.
- Wernicke’s encephalopathy—caused by glucose exposure in the thiamine-deficient alcoholic—which is characterized by confusion, ophthalmoplegia, and ataxia.
Completing a thorough history and physical exam, talking to family members, and reviewing past medical charts are often the best ways to differentiate DTs from other conditions.
What causes DTs?
Vitamin deficiencies were initially thought to cause alcohol withdrawal.3 More recent evidence points toward multiple neuroadaptive changes in the brain associated with chronic alcohol exposure.12 Although numerous neurotransmitter systems may play a role in alcohol withdrawal, recent research has focused on glutamate13 and gamma-aminobutyric acid (GABA).14
Approximately 1.5 to 2 million Americans seek treatment for alcohol abuse or dependence each year.1 As many as 71% of these patients manifest symptoms of alcohol withdrawal.2 Of those individuals who experience alcohol withdrawal, delirium tremens (DTs) may occur in up to 5%.3-5 Utilizing these percentages, it can be estimated that as many as 50,000 to 70,000 individuals develop DTs each year in the United States alone.
Although the incidence of DTs can be assumed to be relatively low, the condition should be considered a medical emergency. Studies list mortality rates for DTs as high as 15% and as low as 2 to 3%.7,8
The brain seems to compensate for alcohol’s enhancement of GABA (inhibitory) neurons by up-regulating excitatory neurons (glutamate). Alcohol has been shown to have some effects on neurons.15 The implication is that withdrawing alcohol triggers an “excitatory state” until the brain can readjust the fine balance between excitation and inhibition, a process that takes weeks to months. Some changes may never reverse because of the neurotoxic effects of alcohol and alcohol withdrawal.
Repeated alcohol exposure and withdrawal may lead to neuroadaptive changes in the brain and to more severe withdrawal symptoms, such as DTs. Repeated alcohol withdrawal episodes can produce a kindling effect. As outlined by Becker, kindling occurs “when a weak electrical or chemical stimulus, which initially causes no overt behavioral responses, results in the appearance of behavioral effects, such as seizures, when it is administered repeatedly.”16 Thus, repeated alcohol withdrawal worsens future episodes and eventually leads to alcohol withdrawal seizures.
Whereas most of these theories apply to alcohol withdrawal, they are also compatible with the neuronal mechanisms that may underlie DTs. Alcohol withdrawal and DTs share the presence of a “hyperactive state.” Most likely, DTs is the progression to more severe or pronounced neuroadaptive changes seen in mild to moderate alcohol withdrawal. One could certainly imagine that the possible neurotoxic effects of alcohol, alcohol withdrawal, and repeated detoxifications could sensitize the CNS to the more severe symptoms seen in DTs. Infection and metabolic abnormalities may also enhance the progression. Unfortunately, why some but not all patients experiencing alcohol withdrawal progress to DTs is unknown.
Table 1
RISK FACTORS FOR DELIRIUM TREMENS
| Comorbid medical illness (with electrolyte, fluid abnormalities)* |
| History of delirium tremens* |
| Blood alcohol level >300 mg/dL on presentation* |
| Presentation after an alcohol withdrawal seizure* |
| Older age* |
| Longer history of alcohol dependence |
| Intense alcohol craving |
| Abnormal liver function |
| * Supported with studies and/or in the medical literature |
| Source: Saitz R. Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22(1):5-12. |
Table 2
STRATEGIES TO PREVENT AND TREAT DELIRIUM TREMENS
| Assess risk for DTs with a thorough history, including collaborative family information and medical charts |
| Admit patients with a history of serious withdrawal symptoms or potential for inpatient detoxification (based on degree of tolerance) |
| Check complete lab values (chemistry panel, liver function tests including ALT and AST, complete blood count, blood alcohol level, GGT, and others if relevant), and correct any fluid, vitamin, or electrolyte abnormalities |
| Treat comorbid medical conditions |
| Differentiate DTs from alcohol hallucinosis, other causes of delirium, and Wernicke’s encephalopathy |
| Consider giving benzodiazepines along with low-dose neuroleptics, if appropriate, and monitor for disinhibition/ confusion and extrapyramidal symptoms, respectively |
| Place the patient in a low-stimulation environment with frequent monitoring |
Predisposing risk factors
Past withdrawal complicated by seizures or DTs is the single best predictor of future alcohol withdrawal symptoms.17 Also consider the following patients to be at elevated risk:
- any individual who presents with a blood alcohol level >300 mg/dl or after experiencing a withdrawal seizure9
- patients with comorbid medical conditions, such as electrolyte abnormalities, infection, or poorly treated cardiovascular or respiratory diseases
- older persons, who tend to be susceptible to delirium associated with hospitalization, medical illnesses such as urinary tract infections or pneumonia, or use of certain medications.18
Potential risk factors for developing DTs are summarized in Table 1.1 Although few studies have been done, clinicians can use these factors as a guide for aggressively preventing DTs in at-risk patients.
Managing and preventing DTs
Management. Drug therapy is considered crucial to quell withdrawal symptoms and reduce the risk of death.19 Patients usually are treated with one of several benzodiazepines (such as chlordiazepoxide, diazepam, oxazepam, or lorazepam) to decrease autonomic instability and reduce seizure risk during acute alcohol withdrawal. Although dosages of these medications are estimated based on drinking history, some general starting ranges are often used in clinical practice:
- chlordiazepoxide, 50 to 100 mg tid
- lorazepam, 1 to 2 mg every 4 hours
- oxazepam, 15 to 30 mg qid
- diazepam, 10 to 20 mg tid/qid.
Treating DTs often requires the use of IV benzodiazepines because of their quick onset of action and benefit for acutely agitated patients who have difficulty taking medications by mouth.
Prevention. Correcting fluid and electrolyte abnormalities may be critical in preventing DTs (Table 2). In one study of patients who died while experiencing DTs, only 25% received adequate fluid replacement, which can be as much as 6 liters per day.20 Ideally, comorbid conditions should be addressed early in presentation and before DTs develop.21
High-dose benzodiazepine therapy does not completely protect a patient from DTs or reduce its duration,22 but it may reduce mortality. A meta-analysis of prospective, placebocontrolled trials reported a risk reduction of 4.9 cases of DTs per 100 patients treated with benzodiazepines. Mortality also seems to have been reduced in patients with DTs who were treated with sedative hypnotics.9 Benzodiazepines may cause increased confusion and disinhibition, as is frequently seen when patients with dementia are treated with these agents.23
Neuroleptics such as haloperidol have been used to prevent and treat DTs, but studies of their ability to reduce mortality have produced inconsistent results. What’s more, neuroleptics can reduce the seizure threshold and produce extrapyramidal symptoms.23 Atypical antipsychotics may offer a safer alternative, although more studies are needed to evaluate whether they decrease the occurrence and severity of DTs.
In summary, a rational approach to preventing and treating DTs is to:
- manage comorbid medical illnesses, and correct fluid and electrolyte abnormalities
- place the patient in a safe, low-stimulation environment with frequent monitoring
- use benzodiazepines judiciously.
Related resources
- National Institute on Alcohol Abuse and Alcoholism.
- www.niaaa.nih.gov
- 1995;30(6):765-70 (a thorough review of benzodiazepine use in alcohol withdrawal).
Drug brand names
- Chlordiazepoxide • Librium
- Diazepam • Valium
- Haloperidol • Haldol
- Lorazepam • Ativan
- Oxazepam • Serax
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.
Ms. J, 42, was admitted to the OB-GYN service for a routine vaginal hysterectomy to treat dysfunctional uterine bleeding. In the presurgical history, she described having a few drinks daily. Shortly after a successful uncomplicated procedure, the patient became tremulous and was given several doses of lorazepam.
Two days after surgery, the patient became delirious. She complained of tactile and visual hallucinations, her level of consciousness waxed and waned, and she showed significant autonomic instability. A psychiatry consult was ordered. The consult team recommended IV fluids, IV diazepam, and haloperidol, supplemented with a multivitamin and 100 mg/d of thiamine. When the patient’s delirium resolved within 4 days, a more detailed discussion revealed a history of alcohol abuse and withdrawal seizures.
It is not uncommon for a patient to develop acute alcohol withdrawal and delirium tremens (DTs) while recovering from routine surgery. Delirium tremens remains a medical emergency, even though advances have reduced its associated mortality rates (Box).1-7
Psychiatrists who know the risk factors for DTs—also termed alcohol withdrawal delirium—can identify and protect patients who are susceptible to this life-threatening complication. We describe the clinical features of DTs, potential predisposing factors, theories behind its mechanisms, and strategies for preventing and managing DTs in patients experiencing alcohol withdrawal.
Clinical features
Disorientation and confusion are the hallmark features of DTs. Other clinical manifestations include vivid hallucinations, extreme tremulousness, autonomic hyperactivity, sweating, tachycardia, and agitation. Men experiencing DTs seem to demonstrate a greater degree of autonomic hyperactivity than women.8
Symptoms usually arise in the alcoholic patient between the third and fifth days of abstinence but have been known to occur several weeks after a patient’s last drink. Symptoms usually resolve within a few days9 but have been known to resolve within hours in some patients and to persist for several months in others.10
Differential diagnosis. Clinicians often fail to differentiate alcohol hallucinosis from DTs. Alcohol hallucinosis—which occurs in 3 to 10% of patients with severe alcohol withdrawal11 —manifests as auditory, visual, or tactile hallucinations with a clear sensorium. Patients experiencing DTs also may experience hallucinations but with confusion, disorientation, and severe autonomic hyperactivity. Unlike DTs, alcohol hallucinosis is not fatal.9
DTs also should be differentiated from:
- other causes of delirium, such as medication or infection. If the cause is identified and removed, the delirium should gradually resolve.
- Wernicke’s encephalopathy—caused by glucose exposure in the thiamine-deficient alcoholic—which is characterized by confusion, ophthalmoplegia, and ataxia.
Completing a thorough history and physical exam, talking to family members, and reviewing past medical charts are often the best ways to differentiate DTs from other conditions.
What causes DTs?
Vitamin deficiencies were initially thought to cause alcohol withdrawal.3 More recent evidence points toward multiple neuroadaptive changes in the brain associated with chronic alcohol exposure.12 Although numerous neurotransmitter systems may play a role in alcohol withdrawal, recent research has focused on glutamate13 and gamma-aminobutyric acid (GABA).14
Approximately 1.5 to 2 million Americans seek treatment for alcohol abuse or dependence each year.1 As many as 71% of these patients manifest symptoms of alcohol withdrawal.2 Of those individuals who experience alcohol withdrawal, delirium tremens (DTs) may occur in up to 5%.3-5 Utilizing these percentages, it can be estimated that as many as 50,000 to 70,000 individuals develop DTs each year in the United States alone.
Although the incidence of DTs can be assumed to be relatively low, the condition should be considered a medical emergency. Studies list mortality rates for DTs as high as 15% and as low as 2 to 3%.7,8
The brain seems to compensate for alcohol’s enhancement of GABA (inhibitory) neurons by up-regulating excitatory neurons (glutamate). Alcohol has been shown to have some effects on neurons.15 The implication is that withdrawing alcohol triggers an “excitatory state” until the brain can readjust the fine balance between excitation and inhibition, a process that takes weeks to months. Some changes may never reverse because of the neurotoxic effects of alcohol and alcohol withdrawal.
Repeated alcohol exposure and withdrawal may lead to neuroadaptive changes in the brain and to more severe withdrawal symptoms, such as DTs. Repeated alcohol withdrawal episodes can produce a kindling effect. As outlined by Becker, kindling occurs “when a weak electrical or chemical stimulus, which initially causes no overt behavioral responses, results in the appearance of behavioral effects, such as seizures, when it is administered repeatedly.”16 Thus, repeated alcohol withdrawal worsens future episodes and eventually leads to alcohol withdrawal seizures.
Whereas most of these theories apply to alcohol withdrawal, they are also compatible with the neuronal mechanisms that may underlie DTs. Alcohol withdrawal and DTs share the presence of a “hyperactive state.” Most likely, DTs is the progression to more severe or pronounced neuroadaptive changes seen in mild to moderate alcohol withdrawal. One could certainly imagine that the possible neurotoxic effects of alcohol, alcohol withdrawal, and repeated detoxifications could sensitize the CNS to the more severe symptoms seen in DTs. Infection and metabolic abnormalities may also enhance the progression. Unfortunately, why some but not all patients experiencing alcohol withdrawal progress to DTs is unknown.
Table 1
RISK FACTORS FOR DELIRIUM TREMENS
| Comorbid medical illness (with electrolyte, fluid abnormalities)* |
| History of delirium tremens* |
| Blood alcohol level >300 mg/dL on presentation* |
| Presentation after an alcohol withdrawal seizure* |
| Older age* |
| Longer history of alcohol dependence |
| Intense alcohol craving |
| Abnormal liver function |
| * Supported with studies and/or in the medical literature |
| Source: Saitz R. Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22(1):5-12. |
Table 2
STRATEGIES TO PREVENT AND TREAT DELIRIUM TREMENS
| Assess risk for DTs with a thorough history, including collaborative family information and medical charts |
| Admit patients with a history of serious withdrawal symptoms or potential for inpatient detoxification (based on degree of tolerance) |
| Check complete lab values (chemistry panel, liver function tests including ALT and AST, complete blood count, blood alcohol level, GGT, and others if relevant), and correct any fluid, vitamin, or electrolyte abnormalities |
| Treat comorbid medical conditions |
| Differentiate DTs from alcohol hallucinosis, other causes of delirium, and Wernicke’s encephalopathy |
| Consider giving benzodiazepines along with low-dose neuroleptics, if appropriate, and monitor for disinhibition/ confusion and extrapyramidal symptoms, respectively |
| Place the patient in a low-stimulation environment with frequent monitoring |
Predisposing risk factors
Past withdrawal complicated by seizures or DTs is the single best predictor of future alcohol withdrawal symptoms.17 Also consider the following patients to be at elevated risk:
- any individual who presents with a blood alcohol level >300 mg/dl or after experiencing a withdrawal seizure9
- patients with comorbid medical conditions, such as electrolyte abnormalities, infection, or poorly treated cardiovascular or respiratory diseases
- older persons, who tend to be susceptible to delirium associated with hospitalization, medical illnesses such as urinary tract infections or pneumonia, or use of certain medications.18
Potential risk factors for developing DTs are summarized in Table 1.1 Although few studies have been done, clinicians can use these factors as a guide for aggressively preventing DTs in at-risk patients.
Managing and preventing DTs
Management. Drug therapy is considered crucial to quell withdrawal symptoms and reduce the risk of death.19 Patients usually are treated with one of several benzodiazepines (such as chlordiazepoxide, diazepam, oxazepam, or lorazepam) to decrease autonomic instability and reduce seizure risk during acute alcohol withdrawal. Although dosages of these medications are estimated based on drinking history, some general starting ranges are often used in clinical practice:
- chlordiazepoxide, 50 to 100 mg tid
- lorazepam, 1 to 2 mg every 4 hours
- oxazepam, 15 to 30 mg qid
- diazepam, 10 to 20 mg tid/qid.
Treating DTs often requires the use of IV benzodiazepines because of their quick onset of action and benefit for acutely agitated patients who have difficulty taking medications by mouth.
Prevention. Correcting fluid and electrolyte abnormalities may be critical in preventing DTs (Table 2). In one study of patients who died while experiencing DTs, only 25% received adequate fluid replacement, which can be as much as 6 liters per day.20 Ideally, comorbid conditions should be addressed early in presentation and before DTs develop.21
High-dose benzodiazepine therapy does not completely protect a patient from DTs or reduce its duration,22 but it may reduce mortality. A meta-analysis of prospective, placebocontrolled trials reported a risk reduction of 4.9 cases of DTs per 100 patients treated with benzodiazepines. Mortality also seems to have been reduced in patients with DTs who were treated with sedative hypnotics.9 Benzodiazepines may cause increased confusion and disinhibition, as is frequently seen when patients with dementia are treated with these agents.23
Neuroleptics such as haloperidol have been used to prevent and treat DTs, but studies of their ability to reduce mortality have produced inconsistent results. What’s more, neuroleptics can reduce the seizure threshold and produce extrapyramidal symptoms.23 Atypical antipsychotics may offer a safer alternative, although more studies are needed to evaluate whether they decrease the occurrence and severity of DTs.
In summary, a rational approach to preventing and treating DTs is to:
- manage comorbid medical illnesses, and correct fluid and electrolyte abnormalities
- place the patient in a safe, low-stimulation environment with frequent monitoring
- use benzodiazepines judiciously.
Related resources
- National Institute on Alcohol Abuse and Alcoholism.
- www.niaaa.nih.gov
- 1995;30(6):765-70 (a thorough review of benzodiazepine use in alcohol withdrawal).
Drug brand names
- Chlordiazepoxide • Librium
- Diazepam • Valium
- Haloperidol • Haldol
- Lorazepam • Ativan
- Oxazepam • Serax
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.
1. Saitz R. Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22(1):5-12.
2. Saitz R, Redmond MS, Mayo-Smith MF, et al. Individualized treatment for alcohol withdrawal. Randomized, double-blind, controlled trial. JAMA 1994;272:519-23.
3. Victor M, Adams RD. The effect of alcoholism on the nervous system. Research Publication of the Association for Research on Nervous and Mental Disorders 1953;32:526-73.
4. Victor M, Braush C. The role of abstinence in the genesis of alcoholic epilepsy. Epilepsia 1967;8:1-20.
5. Sellars EM, Kalant H. Alcohol intoxication and withdrawal. N Engl J Med 1976;294:757-62.
6. Victor M. Treatment of alcoholic intoxication and the withdrawal syndrome. Psychosomat Med 1966;28:636-50.
7. Guthrie S. The treatment of alcohol withdrawal. Pharmacotherapy 1989;9:131-43.
8. Trevisan LA, Boutrous N, Petrakis I, Krystal JH. Complications of alcohol withdrawal. Alcohol World 1998;22(1):61-66.
9. Mayo-Smith MF. Management of alcohol intoxication, overdose, and withdrawal. In: Graham AW, Schultz TK (eds). Principles of addiction medicine (2nd ed). Chevy Chase, MD: American Society of Addiction Medicine, 1998;434-41.
10. Wolf KM, Shaughnessy AF, Middleton DB. Prolonged delirium tremens requiring massive doses of medication. J Am Board Fam Pract 1993;6:502-4.
11. Platz WE, Oberlaender FA, Seidel ML. The phenomenology of perceptual hallucinations in alcohol-induced delirium tremens. Psychopathology 1995;28:247-55.
12. Littleton J. Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World 1998;22(1):13-24.
13. Hoffman PL, Rabe CS, Grant KA, Valverius P, Hudspith M, Tabakoff B. Ethanol and the NMDA receptor. Alcohol 1990;7(3):229-31.
14. Morrow AL, Montpied P, Lingford-Hughes A, Paul SM. Chronic ethanol and pentobarbital administration in the rat: effects on GABAA receptor function and expression in brain. Alcohol 1990;7(3):237-44.
15. Begleiter H Kissin B (eds) The pharmacology of alcohol and alcohol dependence. New York: Oxford University Press, 1996.
16. Becker HC. Kindling in alcohol withdrawal. Alcohol World 1998;22(1):25-33.
17. Gold M, Miller N. Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence. Am Fam Phys 1998;58:139-46.
18. Kraemer K, Mayo-Smith MF, Calkins R. Pharmacological management of alcohol withdrawal: a meta analysis of evidence-based practical guidelines. JAMA 1997;278:144-51.
19. Shaw GK. Detoxification: the use of benzodiazepines. Alcohol Alcohol 1995;30(6):765-70.
20. Victor M. Diagnosis and treatment of alcohol withdrawal states. Pract Gastroenteritis 1983;7(5):6-15.
21. Myrick H, Anton R. Treatment of alcohol withdrawal. Alcohol Health Res World 1998;22(1):38-43.
22. Hersh D, Kranzler HR, Meyer RE. Persistent delirium following cessation of heavy alcohol consumption: diagnostic and treatment implications. Am J Psychiatry 1997;154(6):846-51.
23. Myrick H, Anton R. Clinical management of alcohol withdrawal. CNS Spectrums 2000;5(2):22-32.
1. Saitz R. Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22(1):5-12.
2. Saitz R, Redmond MS, Mayo-Smith MF, et al. Individualized treatment for alcohol withdrawal. Randomized, double-blind, controlled trial. JAMA 1994;272:519-23.
3. Victor M, Adams RD. The effect of alcoholism on the nervous system. Research Publication of the Association for Research on Nervous and Mental Disorders 1953;32:526-73.
4. Victor M, Braush C. The role of abstinence in the genesis of alcoholic epilepsy. Epilepsia 1967;8:1-20.
5. Sellars EM, Kalant H. Alcohol intoxication and withdrawal. N Engl J Med 1976;294:757-62.
6. Victor M. Treatment of alcoholic intoxication and the withdrawal syndrome. Psychosomat Med 1966;28:636-50.
7. Guthrie S. The treatment of alcohol withdrawal. Pharmacotherapy 1989;9:131-43.
8. Trevisan LA, Boutrous N, Petrakis I, Krystal JH. Complications of alcohol withdrawal. Alcohol World 1998;22(1):61-66.
9. Mayo-Smith MF. Management of alcohol intoxication, overdose, and withdrawal. In: Graham AW, Schultz TK (eds). Principles of addiction medicine (2nd ed). Chevy Chase, MD: American Society of Addiction Medicine, 1998;434-41.
10. Wolf KM, Shaughnessy AF, Middleton DB. Prolonged delirium tremens requiring massive doses of medication. J Am Board Fam Pract 1993;6:502-4.
11. Platz WE, Oberlaender FA, Seidel ML. The phenomenology of perceptual hallucinations in alcohol-induced delirium tremens. Psychopathology 1995;28:247-55.
12. Littleton J. Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World 1998;22(1):13-24.
13. Hoffman PL, Rabe CS, Grant KA, Valverius P, Hudspith M, Tabakoff B. Ethanol and the NMDA receptor. Alcohol 1990;7(3):229-31.
14. Morrow AL, Montpied P, Lingford-Hughes A, Paul SM. Chronic ethanol and pentobarbital administration in the rat: effects on GABAA receptor function and expression in brain. Alcohol 1990;7(3):237-44.
15. Begleiter H Kissin B (eds) The pharmacology of alcohol and alcohol dependence. New York: Oxford University Press, 1996.
16. Becker HC. Kindling in alcohol withdrawal. Alcohol World 1998;22(1):25-33.
17. Gold M, Miller N. Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence. Am Fam Phys 1998;58:139-46.
18. Kraemer K, Mayo-Smith MF, Calkins R. Pharmacological management of alcohol withdrawal: a meta analysis of evidence-based practical guidelines. JAMA 1997;278:144-51.
19. Shaw GK. Detoxification: the use of benzodiazepines. Alcohol Alcohol 1995;30(6):765-70.
20. Victor M. Diagnosis and treatment of alcohol withdrawal states. Pract Gastroenteritis 1983;7(5):6-15.
21. Myrick H, Anton R. Treatment of alcohol withdrawal. Alcohol Health Res World 1998;22(1):38-43.
22. Hersh D, Kranzler HR, Meyer RE. Persistent delirium following cessation of heavy alcohol consumption: diagnostic and treatment implications. Am J Psychiatry 1997;154(6):846-51.
23. Myrick H, Anton R. Clinical management of alcohol withdrawal. CNS Spectrums 2000;5(2):22-32.