| Delirium tremens | |
|---|---|
| Classification and external resources | |
| ICD-10 | F10.4 |
| ICD-9 | 291.0 |
| DiseasesDB | 3543 |
| eMedicine | med/524 |
| MeSH | D000430 |
Delirium tremens 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, DT and death if not properly managed. Withdrawal from other drugs which are not sedative-hypnotics, such as opioids, marijuana, cocaine etc. do not have major medical complications and withdrawal is therefore not life threatening.[4] When caused by alcohol, it occurs only in individuals 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. Prior use of both benzodiazepines and alcohol can compound the symptoms and is the most dangerous, especially if untreated.
In the U.S., fewer than 50% 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]
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The main symptoms are confusion, diarrhea, disorientation and agitation and other signs of severe autonomic instability (fever, tachycardia, hypertension).[5] Other common symptoms include intense perceptual disturbance such as visions of insects, snakes or rats (or stereotypically, pink elephants or tiny figures). These may be hallucinations, or illusions related to the environment, e.g., patterns on the wallpaper that the patient perceives as giant spiders attacking him or her. Unlike hallucinations associated with schizophrenia, delirium tremens hallucinations are primarily visual, but are also associated with tactile hallucinations such as sensations of something crawling on the subject — a phenomenon known as formication.
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 individuals 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 individuals experience seizures.
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 due to abrupt cessation of tranquilizer drugs of the barbiturate or benzodiazepine classes in an individual with a 'heavy' (relatively speaking) 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 individuals. These DT's 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 DT's, though ironically they are the cause of them in all too 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 are 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 (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.[6]
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 regain 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. 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.[7] 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.[8] 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. Although used rarely, an alcohol drip may be prescribed to sedate severe patients, who will then need to be "weaned" off of the alcohol.
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