Delirium tremens

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Overview
Delirium tremens (colloquially, the DTs, "the horrors", "the shakes" or "rum fits;" literally, "shaking delirium" or "trembling madness" in Latin) is an acute episode of delirium that is usually caused by withdrawal or abstinence, from alcohol following habitual excessive drinking, or benzodiazepines or barbiturates (and other major tranquilizers). Delirium tremens can also appear after a rapid reduction in the amount of alcohol being consumed by heavy drinkers, or a rapid reduction of intake of benzodiazepines or barbiturates. Caused by alcohol, it only occurs in individuals with a history of constant, long-term alcohol consumption. Occurrence due to benzodiazepine or barbiturate withdrawal does not require as long a period of consistent intake of such drugs. Prior use of both tranquilizers and alcohol can compound the symptoms, and while extremely rare, is the most dangerous especially if untreated. Barbiturates are generally accepted as being extremely dangerous, both due to overdose potential and addiction potential including the extreme withdrawal syndrome that usually is marked by delirium tremens upon discontinuation. Due to this, barbiturates are rarely used ambulatory anymore, being replaced by the generally accepted less dangerous benzodiazepines, which however still cause a similar withdrawal syndrome.

Five percent of acute ethanol withdrawal cases progress to delirium tremens. Unlike the withdrawal syndrome associated with opiate addiction (generally), delirium tremens (and alcohol withdrawal in general) can be fatal. Mortality can be up to 35% if untreated; if treated early, death rates range from 5-15%.

Symptoms
The main symptoms are confusion, disorientation and agitation. Other common symptoms include intense hallucinations such as visions of insects, snakes or rats (or stereotypically, pink elephants). These may be related to the environment, e.g., drawings on wallpaper that the patient would perceive as giant spiders attacking him or her. Unlike hallucinations associated with schizophrenia, delirium tremens hallucinations are primarily visual, but associated with tactile hallucinations such as sensations of something crawling on the subject - a phenomenon known as formication. Delirium tremens can sometimes be associated with severe, uncontrollable tremors of the extremities and secondary symptoms such as anxiety, panic attacks and paranoia.

Delirium tremens (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 alcohol-dependent people and carries up to 5% mortality with treatment and up to 35% mortality without treatment. 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 individuals experience seizures as well.

Causes
Delirium tremens can occur after a period of heavy alcohol drinking, especially when the person does not eat enough food. It may also be triggered by head injury, infection, or illness in people with a history of heavy use of alcohol.

It is most common in people who have a history of alcohol withdrawal, especially in those who drink the equivalent of 7 - 8 pints of beer (or 1 pint of "hard" alcohol) every day for several months. Delirium tremens also commonly affects those with a history of habitual alcohol use or alcoholism that has existed for more than 10 years.

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-GABAA-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 re-achieve homeostasis.

This causes downregulation of these receptors, as well as an up-regulation in the production of excitatory neurotransmitters such as norepinephrine, dopamine, epinephrine, and serotonin - all of which further the drinker's tolerance to alcohol and may intensify tonic-clonic seizures. When alcohol is no longer consumed, these down-regulated GABAA 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". Effects of this "adrenergic storm" 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 upregulation, 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 upregulated, contributing to the delirium and neurotoxicity (by excitotoxicity) of withdrawal. Direct measurements of central norepinephrine and its metabolites is in direct correlation to the severity of the alcohol withdrawal syndrome.

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
Pharmacotherapy is symptomatic and supportive. Typically the patient is kept sedated with benzodiazepines, such as diazepam (Valium), lorazepam (Ativan) or oxazepam (Serax) and in extreme cases low-levels of antipsychotics, such as haloperidol until symptoms subside. 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 minimise visual misinterpretations such as the visual hallucinations mentioned above.

Cultural references

 * Literature
 * In Fyodor Dostoyevsky's The Brothers Karamazov, Ivan Karamazov suffers from delirium tremens.
 * In George Eliot's Middlemarch, John Raffles suffers and eventually dies from delirium tremens.
 * In Mark Twain's The Adventures of Huckleberry Finn, Huck's father suffers from delirium tremens.
 * Jack Kerouac's Big Sur discusses his experiences with delirium tremens.
 * In Joseph Conrad's Lord Jim, the chief engineer of the Patna is described as having the condition which results in his being hospitalized.
 * Australian writer, Henry Lawson, who was himself an alcoholic, refers in numerous short stories to the "jim-jams", a colloquialism for the "DTs".
 * In Aleksis Kivi's novel Seven Brothers, Simeoni has delirium tremens and hallucinates that the devil takes him on a huge tower made of boot leather and shows him the future of the world.
 * In Charlotte Perkins Gilman's "The Yellow Wallpaper" the term is referenced.
 * The George Orwell book, Burmese Days features an alcoholic character known as Mr Lackersteen who suffers from delirium tremens.
 * Ignacio Solares’ Delirium tremens (1979) is a work of non-fiction that collects stories of nightmarish visions experienced by alcoholics when undergoing delirium tremens. Solares’ father had experienced delirium tremens when Solares was a boy.


 * Theater/film/television
 * In a line from the stage and movie version of West Side Story, Lieutenant Shrank asks, "How's your old man's DT's Arab?"
 * Delirium tremens is also referenced in Eugene O'Neill's play The Hairy Ape. Yank, the principal character in the play, cites the condition as the cause of his mother's death when referring to his troubled childhood.
 * In the 1945 Billy Wilder film The Lost Weekend, the main character, played by Ray Milland, suffers delirium tremens after fleeing a detoxification ward following a weekend of binge drinking. In the movie, Milland's delirium comes in the form of a bat that perches on an apartment wall and devours a mouse tucked into a crack in the plaster.
 * In Blake Edwards's 1965 film "Days of Wine and Roses", Jack Lemmon's character, Joe Clay, experiences delirium tremens before detoxing and discovering Alcoholics Anonymous.
 * Another cultural reference is in Smokey and the Bandit II.
 * In the 1995 film Leaving Las Vegas, Nicolas Cage portrays a character who experiences this symptom following binge drinking and withdrawal.
 * In the television show Strangers with Candy, the main character suffers from delirium tremens due to decades of drinking.
 * In the television show "M*A*S*H", one of "Hot Lips" Hoolihan's nurses and best friend, Helen Whitfield, suffers from delirium tremens.
 * In the movie Fried Green Tomatoes Smokey suffers from alcoholic tremor while attempting to eat corn with a fork. He is then given a bottle of whiskey by Idgy Threadgood in order to prevent the development of delirium tremens.
 * In an episode of Coronation Street Jamie's mother, an alcoholic is seen shaking on the sofa with DT after promising to go cold turkey
 * In Jean-Pierre Melville's Le Cercle Rouge, Yves Montand's character Jensen experiences delirium tremens.


 * Music
 * Hard Rock band Aerosmith mentions it in their song "Falling in Love (Is Hard on the Knees)." "I'm Jonesin' on love / Yeah I got the DTs."
 * Irish folk singer, Christy Moore, sang a song titled "Delirium Tremens," which appears on his Ordinary Man album. It is a comedic trawl through a protagonist's visions, with such lines as "I dreamt Ian Paisley was sayin' the Rosary, and Mother Teresa was takin' the pill." He finds the visions so scary (culminating in being in a jacuzzi with Margaret Thatcher "that oul whore in Number 10"), that he vows never to drink again.
 * "Delirium Tremens" is the title of a song contained in the disk "Enemigos Intimos" published on 1998 by BMG España featuring Fito Paez and Joaquin Sabina


 * Comics
 * In the comic series, Preacher, the Irish vampire Cassidy swears off drinking, and suffers from delirium tremens.
 * Two Asterix albums feature a perpetually drunk Roman legionnaire named Tremensdelirius.