Delirium tremens

"DTs" redirects here. For the acronym, see DTS (disambiguation).

For the beer, see Delirium Tremens (beer). For the Gold Rush town in California formerly with this name, see Omega, California.

Delirium tremens
Classification and external resources
ICD-10	F10.4
ICD-9	291.0
DiseasesDB	3543
eMedicine	med/524
MeSH	D000430

Delirium tremens (Latin for "shaking frenzy", also referred to as The DTs, "the horrors," "jazz hands," "giving the invisible man a handshake", "spirit fingers" or "the shakes.") is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813.^[1][2] Benzodiazepines are the treatment of choice for delirium tremens (DT).^[3]

Withdrawal from sedative-hypnotics other than alcohol, such as benzodiazepines or barbiturates, can also result in seizures, delirium tremens, and death if not properly managed. Withdrawal from other drugs which are not sedative-hypnotics such as caffeine, cocaine, etc. does not have major medical complications, and is not life-threatening.^[4] Withdrawal reactions as a result of physical dependence on alcohol is the most dangerous and can be fatal. It often creates a full blown effect which is physically evident through shivering, palpitations, sweating and in some cases, convulsions and death if not treated.^[5]

When caused by alcohol, it occurs only in patients with a history of alcoholism. Occurrence of a similar syndrome due to benzodiazepines does not require as long a period of consistent intake of such drugs. Benzodiazepines are relatively safe in overdose when taken alone; however, if the overdose includes the use of other sedative drugs, alcohol in particular, it could lead to dangerous side effects.^[6]

In the U.S., fewer than about 50% to 60% of alcoholics will develop any significant withdrawal symptoms upon cessation of alcohol intake, and of these, only 5% of cases of acute ethanol withdrawal progress to DT.^[1] Unlike the withdrawal syndrome associated with opiate dependence, DT (and alcohol withdrawal in general) can be fatal. Mortality was as high as 35% before the advent of intensive care and advanced pharmacotherapy; in the modern era of medicine, death rates range from 5-15%.^[1]

Similar hyperirritability and hallucinosis can be caused by magnesium deficiency.^[7]

Symptoms

The main symptoms of Delirium Tremens are confusion, diarrhea, insomnia, nightmares, disorientation and agitation and other signs of severe autonomic instability (fever, tachycardia, hypertension).^[8] These symptoms may appear suddenly but can develop 2–3 days after cessation of drinking heavily with its highest peak/ intensity on the fourth or fifth day.^[9] Also, these "symptoms are characteristically worse at night".^[10] Other common symptoms include intense perceptual disturbance such as visions of insects, snakes, or rats. These may be hallucinations, or illusions related to the environment, e.g., patterns on the wallpaper or in the peripheral vision that the patient falsely perceives as a resemblance to the morphology of an insect. Unlike hallucinations associated with schizophrenia, delirium tremens hallucinations are primarily visual, in the peripheral field of vision, but are also associated with tactile hallucinations such as sensations of something crawling on the subject — a phenomenon known as formication. Delirium Tremens usually includes extremely intense feelings of "impending doom". Severe anxiety and feelings of imminent death are symptomatic of DT.

DT can sometimes be associated with severe, uncontrollable tremors of the extremities and secondary symptoms such as anxiety, panic attacks and paranoia. Confusion is often noticeable to onlookers as patients will have trouble constructing simple sentences or making basic logical calculations. In many cases, people who rarely speak out of turn will have an increased tendency for gaffes even though they are sober.

DT should be distinguished from alcoholic hallucinosis, the latter occurring in approximately 20% of hospitalized alcoholics and not carrying a significant mortality. In contrast, DT occurs in 5-10% of alcoholics and carries up to 5% mortality with treatment and up to 35% mortality without treatment.^[2] DT is characterized by the presence of altered sensorium; that is, a complete hallucination without any recognition of the real world. DT has extreme autonomic hyperactivity (high pulse, blood pressure, and rate of breathing), and 35-60% of patients have a fever. Some patients experience seizures.

Causes

Delirium tremens is mainly caused after a long period of drinking, being stopped abruptly and experiencing withdrawal. It may also be triggered by head injury, infection, or illness in people with a history of heavy use of alcohol. Yet another cause of delirium tremens is abrupt cessation of tranquilizer drugs of the barbiturate or benzodiazepine classes in a patient with a relatively strong addiction to them.

Because these tranquilizers' primary pharmacological and physiological effects stem from their manipulation of the GABA chemical and transmitter somatic system, the same endogenous neurotransmitter system affected by alcohol, delirium tremens can occur upon abrupt cessation of dosage in heavily dependent patients. These DTs are much the same as those caused by alcohol and so is the attendant withdrawal syndrome of which they are a manifestation. That is the primary reason benzodiazepines are such an effective treatment for DTs, despite also being the cause of them in many cases. Because the primary psychoactive chemical constituent of both ethanol and the tranquilizers of the barbiturate and benzodiazepine class both mimic GABA so effectively that the brain mistakes them for GABA, the brain, in its desire to equalize an unbalanced chemical system, 'orders' the abrupt cessation of the production of endogenous GABA, (this cessation becoming more and more marked as the addiction becomes stronger and higher and higher doses are needed to cause intoxication) which in addition to its sedative effects, is an immensely important regulatory neurotransmitter that controls the heart rate, blood pressure, and seizure threshold among myriad other important autonomic nervous subsystems.

Delirium tremens is most common in people who have a history of alcohol withdrawal, especially in those who drink the equivalent of 7 to 8 US pints (3310–3790 ml or 5.83–6.66 imp pt) of beer or 1 US pint (473 ml or 16.65 imp fl oz) of distilled beverage daily. Delirium tremens also commonly affects those with a history of habitual alcohol use or alcoholism that has existed for more than 10 years.^[11]

The exact pharmacology of ethanol is not fully understood; however, it is theorized that delirium tremens is caused by the effect of alcohol on the benzodiazepine-GABA_A-chloride receptor complex for the inhibitory neurotransmitter GABA. Constant consumption of alcoholic beverages (and the consequent chronic sedation) causes a counterregulatory response in the brain in attempt to regain homeostasis.

This causes downregulation of these receptors, as well as an up-regulation in the production of excitatory neurotransmitters, primarily glutamate, and also such as norepinephrine, dopamine, epinephrine, and serotonin, all of which further the drinker's tolerance to alcohol. When alcohol is no longer consumed, these down-regulated GABA_A receptor complexes are so insensitive to GABA that the typical amount of GABA produced has little effect; compounded with the fact that GABA normally inhibits action potential formation, there are not as many receptors for GABA to bind to — meaning that sympathetic activation is unopposed. This is also known as an "adrenergic storm"; the effects of which can include (but are not limited to) tachycardia, hypertension, hyperthermia, hyperreflexia, diaphoresis, heart attack, cardiac arrhythmia, stroke, anxiety, panic attacks, paranoia, and agitation.

This is all made worse by excitatory neurotransmitter up-regulation, so not only is sympathetic nervous system over-activity unopposed by GABA, there is also more of the serotonin, norepinephrine, dopamine, epinephrine, and particularly glutamate. Excitory NMDA receptors are also up-regulated, contributing to the delirium and neurotoxicity (by excitotoxicity) of withdrawal. Direct measurements of central norepinephrine and its metabolites are in direct correlation to the severity of the alcohol withdrawal syndrome.^[12] It is possible that psychological (i.e., non-physical) factors also play a role, especially those of infections, malnutrition, or other underlying medical disorders, often related to alcoholism.

Treatment

Delirium tremens due to alcohol withdrawal can be treated with benzodiazepines. High doses may be necessary to prevent mortality.^[13] Pharmacotherapy is symptomatic and supportive. Typically the patient is kept sedated with benzodiazepines, such as diazepam (Valium), lorazepam (Ativan), chlordiazepoxide (Librium), or oxazepam (Serax) and in extreme cases low-levels of antipsychotics, such as haloperidol or even stronger benzodiazepines like temazepam (Restoril) or midazolam (Versed) until symptoms subside. Older drugs such as paraldehyde and clomethiazole were the traditional treatment but these have now largely been superseded by the benzodiazepines, although they may still be used as an alternative in some circumstances. Acamprosate is often used to augment treatment, and is then carried on into long term use to reduce the risk of relapse. If status epilepticus is present, seizures are treated accordingly. Controlling environmental stimuli can also be helpful, such as a well-lit but relaxing environment to minimize visual misinterpretations such as the visual hallucinations mentioned above.

In the media

• Writer Jack Kerouac details his experiences with delirium tremens in his book Big Sur.^[14]
• In the 1945 film The Lost Weekend, an alcoholic writer, played by Ray Milland, is admitted to a hospital's alcoholic ward in the throes of delirium tremens.
• In the 1962 film Days of Wine and Roses, public relations man Joe Clay (played by Jack Lemmon) is committed to a sanitorium twice. In the first instance, he is held in a straitjacket and in a padded room while experiencing delirium tremens. In the second instance, Joe is committed after breaking into a liquor store and afterwards wakes in the sanitorium, strapped down to a table and sweating profusely, whereupon his Alcoholics Anonymous sponsor Jim Hungerford (played by Jack Klugman) informs him that "For two days there was a little green man chasing you around with pruning shears."
• In the 2003 film The Last Samurai, Nathan Algren, a disenchanted ex-United States Army captain and an alcoholic, who is traumatized by his experience fighting in the Civil War and the Indian Wars, played by Tom Cruise , is treated by the Hirotaro family in the throes of delirium tremens after being captured in battle with samurai troops led by Katsumoto.
• In Leaving Las Vegas, the main character, Ben Sanderson, suffers from the DT's after a huge drinking binge and furiously rushes to his liquor supply to prevent them from continuing.
• In the novel L'Assommoir (1876), by French author Emile Zola, the husband of the heroine Gervaise, an alcoholic roofer named Coupeau, succumbs to delirium tremens in a Parisian hospital.
• Ethan Thomas, protagonist of Condemned 2, has become an alcoholic since the events of the previous game and must regularly consume whiskey to prevent the violent shaking of his delirium tremens from spoiling his aim.
• The protagonist of Malcolm Lowry's 1947 novel Under the Volcano suffers from delirium tremens.

See also

• Alcohol dementia
• Alcohol detoxification
• Delusional parasitosis
• Excited delirium

References

1. ^ ^{a b c} Michael Burns; James Price & Michael E Lekawa (2008). "Delirium Tremens: eMedicine Critical Care". emedicine.medscape.com. http://emedicine.medscape.com/article/166032-overview. Retrieved 2009-06-23. 
2. ^ ^{a b} Gossman, William (2007). "Delirium Tremens: eMedicine Emergency Medicine". emedicine.medscape.com. http://emedicine.medscape.com/article/791802-overview. Retrieved 2009-06-23. 
3. ^ Gossman, William (2007). "Delirium Tremens: Treatment & Medication". emedicine.medscape.com. http://emedicine.medscape.com/article/791802-treatment. Retrieved 2009-06-23. 
4. ^ Galanter, Marc; Kleber, Herbert D (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abuse Treatment (4th ed.). United States of America: American Psychiatric Publishing Inc. p. 58. ISBN 978-1585622764. http://books.google.com/?id=6wdJgejlQzYC. 
5. ^ David Healy (3 December 2008). Psychiatric Drugs Explained. Elsevier Health Sciences. pp. 237–. ISBN 9780702029974. http://books.google.com/books?id=ikTJViYMPIEC&pg=PA237. Retrieved 30 November 2010. 
6. ^ Robert E. Hales; American Psychiatric Publishing (2008). The American Psychiatric Publishing textbook of psychiatry. American Psychiatric Pub. pp. 396–. ISBN 9781585622573. http://books.google.com/books?id=2RzFWRIAsPAC&pg=PA396. Retrieved 30 November 2010. 
7. ^ http://jama.ama-assn.org/content/174/1/77.extract The Clinical Expression of Magnesium Deficiency
8. ^ A UK medical student blog, Information on DT and alcohol withdrawal, retrieved on January 25, 2009.
9. ^ Hales R., Yudofsky S., and Talbott J. 1999 Textbook of Psychiatry 3rd Ed. London: The American Psychiatric Press.
10. ^ Gelder et al, 2005 p188 Psychiatry 3rd Ed. oxford:New York.
11. ^ "MedlinePlus Medical Encyclopedia: Delirium tremens". www.nlm.nih.gov. http://www.nlm.nih.gov/medlineplus/ency/article/000766.htm#Causes,%20incidence,%20and%20risk%20factors. Retrieved 2009-06-23. 
12. ^ Linnoila, Markku (1989). "Alcohol withdrawal syndrome and sympathetic nervous system function - Biological Research at National Institute of Alcohol Abuse and Alcoholism". findarticles.com. http://findarticles.com/p/articles/mi_m0847/is_n4_v13/ai_8276920/. Retrieved 2009-06-23. 
13. ^ Wolf KM, Shaughnessy AF, Middleton DB (1993). "Prolonged delirium tremens requiring massive doses of medication". J Am Board Fam Pract 6 (5): 502–4. PMID 8213241. 
14. ^ Summary and analysis of novel

External links

Psychiatry portal

• Medline Encyclopedia: Delirium Tremens
• eMedicine Delirium Tremens