|Classification and external resources|
Delirium tremens (Latin for "shaking frenzy", also referred to as The DTs, "the horrors", or "the shakes.") is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813. Benzodiazepines are the treatment of choice for delirium tremens (DT).
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 and cocaine do not have major medical complications, and are not life-threatening. 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 some cases, convulsions and death if not treated.
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.
In the U.S., less than 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. 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 to 15%.
The main symptoms of delirium tremens are nightmares, agitation, global confusion, disorientation, visual and  auditory hallucinations, fever, hypertension, diaphoresis, and other signs of autonomic hyperactivity (tachycardia and hypertension). These symptoms may appear suddenly but can develop 2–3 days after cessation of drinking heavily with its highest intensity on the fourth or fifth day. Also, these "symptoms are characteristically worse at night". In general DT is considered as the most severe manifestation of alcohol withdrawal, which occurs 3–10 days following the last drink. 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 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 15% 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 patients experience seizures.
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 (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.
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 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"; 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. 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.
Delirium tremens due to alcohol withdrawal can be treated with benzodiazepines. High doses may be necessary to prevent mortality. 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.
Here you can share your comments or contribute with more information, content, resources or links about this topic.