Delirium tremens

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

Delirium tremens (Latin for "shaking frenzy", also referred to as DTs, "the horrors", "the bottleache", "quart mania", "ork orks", "gallon distemper", "the zoots", "barrel fever", "the shakes", "the 750 itch", "pint paralysis") 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.^[3]

Withdrawal from sedative-hypnotics other than alcohol, such as benzodiazepines, or barbiturates, can also cause seizures, delirium tremens, and death if not properly managed. Withdrawal from other drugs that are not sedative-hypnotics such as caffeine or cocaine do not have major medical complications, and are not life-threatening.^[4] Withdrawal reactions due to physical dependence on alcohol are the most dangerous and can be fatal. They often lead to physical effects including shivering, palpitations, sweating and, in the most extreme cases, convulsions and death if not treated.^[5]

When caused by alcohol, it occurs in patients with a history of alcoholism and/or persons who have constantly been very drunk for several days in a row. Occurrence of a similar syndrome due to benzodiazepines does not require as long a period of consistent intake of such drugs. Unlike benzodiazepines, alcohol is also an NMDA receptor antagonist, causing increased glutamate activity with prolonged and/or profoundly heavy use. Rebound increased glutamate signaling produces excitotoxicity, giving alcohol abuse and subsequent withdrawal the ability to cause severe, irreversible brain damage, particularly to the white matter. Delirium tremens is a very serious condition that requires aggressive treatment to reduce risk of serious neurological insult, epileptogenesis, and/or death.

In the United States, less than 60% of alcoholics will develop any significant withdrawal symptoms after stopping alcohol intake, and of these, only 5% of cases of acute ethanol withdrawal progress to DT.^[1] Unlike the withdrawal syndrome associated with opioid 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 to 15%.^[1]

Similar hyperirritability and hallucinosis can be caused by magnesium deficiency.^[6]

Signs and symptoms

The main symptoms of delirium tremens are nightmares, agitation, global confusion, disorientation, visual and ^[7] auditory hallucinations, tactile hallucinations, fever, high blood pressure, heavy sweating, and other signs of autonomic hyperactivity (fast heart rate and high blood pressure). These symptoms may appear suddenly but can develop 2–3 days after stopping drinking heavily with its highest intensity on the fourth or fifth day.^[8] Also, these "symptoms are characteristically worse at night".^[9] In general, DT is considered the most severe manifestation of alcohol withdrawal and occurs 3–10 days following the last drink.^[7] 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, and 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 common DT symptoms.

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 those with DT will have trouble forming 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 of which occurs in approximately 20% of hospitalized alcoholics and does not carry a significant mortality. In contrast, DT occurs in 5–10% of alcoholics and carries up to 15% 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, leading to the biochemical regulation cascade. 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 ethanol and tranquilizers such as barbiturates and benzodiazepines function as positive allosteric modulators at GABAA receptors, the brain, in its desire to equalize an unbalanced chemical system, triggers the abrupt cessation of the production of endogenous GABA. This cessation becomes more and more marked as the addiction becomes stronger and as higher doses are needed to cause intoxication. In addition to having sedative properties, GABA 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 (3 to 4 l) of beer or 1 US pint (0.5 l) 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.^[10]

The exact pharmacology of ethanol is not fully understood; however, it is theorized that delirium tremens is caused by the effect of alcohol on GABA receptors. 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, fever, sleep hyperhidrosis, 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.^[11] It is possible that psychological (i.e., non-physical) factors also play a role, in addition to other factors such as 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.^[12] 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.

Alcoholic beverages can also be prescribed as a treatment for delirium tremens,^[13] but this practice is not universally supported.^[14]

Popular culture

• Writer Jack Kerouac details his experiences with delirium tremens in his book Big Sur.^[15]
• In the 1945 film The Lost Weekend, an alcoholic writer named Don, played by Ray Milland, is admitted to a hospital's alcoholic ward. As one of the other alcoholic patients appears to go into delirium tremens, Don escapes the hospital and heads home to drink. Following his last consumption of liquor, he experiences DTs when an illusion of a small rodent crawls out of a hole in the wall. He then hallucinates a bat flying through the room as the bat proceeds to devour the small rodent.
• 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 (Tom Cruise), 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, is treated by the Hirotaro family in the throes of delirium tremens after being captured in battle with samurai troops led by Katsumoto.
• In the film Leaving Las Vegas, the main character, Ben Sanderson (Nicolas Cage), suffers from the DTs after a drinking binge, and rushes to his liquor supply to prevent them from continuing.
• In the novel L'Assommoir (1876), by French author Émile Zola, the husband of the heroine Gervaise, an alcoholic roofer named Coupeau, succumbs to delirium tremens in a Parisian hospital.
• Ethan Thomas, protagonist of the video game 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.
• In the M*A*S*H episode "Bottoms Up", an alcoholic nurse gets delirium tremens.
• In the film Everything Must Go, the character Nick Halsey (played by Will Ferrell) suffers from delirium tremens in the movie.
• In the "Birthmarks" episode of season 5 of the television series House MD, a patient who is an alcoholic suffers from delirium tremens while being treated in the hospital.
• In the 1989 CBS Hallmark Hall of Fame television movie My Name Is Bill W., Bill Wilson (co-founder of Alcoholics Anonymous) is admitted to the hospital where one of the doctors claims Bill is going through the early stages of delirium tremens. Later in the movie, he is strapped down to a bed appearing to once again have the symptoms of DTs.
• The fraternity letters Delta Tau Chi (ΔΤΧ) from Animal House could be a reference to delirium tremens or possibly detox.
• Irish folk singer Christy Moore wrote a song titled Delirium Tremens, humorously describing a man going through the symptoms, which features on his 1985 album Ordinary Man.
• In the 2013 Bollywood movie Matru Ki Bijlee Ka Mandola, the character Harry Mandola (played by Pankaj Kapur) suffers from DT, and has hallucinations of a grinning pink buffalo.
• In the third episode of the third season of television show Perception, Dr. Daniel Pierce interviews a suspect who is suffering from DT.
• On the 26th of December 1989 Huyghe Brewery in Melle, Belgium started the production of a brand of golden ale they call "Delirium Tremens". The beer is still produced today and has a Beer Advocate score of 92 and is distributed world wide.
• In the 1974 TV film The Morning After, an alcoholic named Charlie Lester, Dick Van Dyke, In a desperate attempt to stop drinking, Charlie takes a vacation and goes alone to a seaside resort. He winds up passed out on the beach. He suffers a terrifying attack of delirium tremens and wakes up in a mental ward.
• In the 2015 mini-comic adaptation of the novel Dead Endings, the main character is drawn with a graphical representation of Delirium Tremens as she interacts with her companion at a bar.

See also

• Alcohol dementia
• Alcohol detoxification
• Delusional parasitosis
• Excited delirium
• Seeing pink elephants

References

External links

• MedlinePlus Encyclopedia Delirium Tremens
• Delirium Tremens (DTs) at eMedicine