Delirium tremens: Difference between revisions

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	Delirium tremens;
ICD-10	F10.4
ICD-9	291.0
DiseasesDB	3543
MedlinePlus	000766
MeSH	D000430

VisualWikitext

Revision as of 18:04, 11 August 2012

For patient information, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: the horrors; rum fits; the shakes; shaking delirium; trembling madness; DT's

Overview

Delirium tremens 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).

Pathophysiology

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.

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 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 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".

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.

Causes

Differentiating Delirium Tremens from other Disease

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..

Epidemiology and Demographics

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%.

Risk Factors

Head injury
CNS infection
Sepsis
Drug abuse
Malnutrition
Alcoholism that has existed for more than 10 years

Natural History, Complications and Prognosis

Complications

Adrenergic storm causes a few complications which include (but are not limited to)

Diagnosis

Symptoms

The main symptoms are

Other common symptoms include

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.

@@ Line 27: / Line 27: @@
 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<sub>A</sub>-chloride receptor complex for the inhibitory neurotransmitter [[Gamma-aminobutyric acid|GABA]]. Constant consumption of [[alcoholic beverage]]s (and the consequent chronic sedation) causes a counterregulatory response in the brain in attempt to re-achieve [[homeostasis]].  This causes [[downregulation]] of these [[Receptor (biochemistry)|receptor]]s, 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 GABA<sub>A</sub> 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 nervous system|sympathetic]] activation is unopposed. This is also known as an "[[adrenergic]] storm".
-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 receptor]]s 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.
+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 receptor]]s 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.
 ==Causes==

v t e WHO ICD-10 mental and behavioral disorders (F · 290–319)
Neurological/symptomatic	Dementia (Alzheimer's disease, multi-infarct dementia, Pick's disease, Creutzfeldt-Jakob disease, Huntington's disease, Parkinson's disease, AIDS dementia complex, Frontotemporal dementia) · Delirium · Post-concussion syndrome
Psychoactive substance	Intoxication (drunkenness) · Physical dependence (alcohol dependence, opioid dependency, cocaine dependence) · Withdrawal (benzodiazepine withdrawal, delirium tremens) · Amnesic: (Korsakoff's syndrome)
Psychotic disorder	Schizophrenia (disorganized schizophrenia) · Schizotypal personality disorder · Delusional disorder · Folie à deux · Schizoaffective disorder
Mood (affective)	Mania · Bipolar disorder · Clinical depression · Cyclothymia · Dysthymia
Neurotic, stress-related and somatoform	Agoraphobia · Anxiety disorder · Panic disorder · Generalized anxiety disorder · Social Anxiety Disorder · OCD · Acute stress reaction · PTSD · Adjustment disorder · Conversion disorder (Ganser syndrome) · Somatoform disorder · Somatization disorder · Neurasthenia
Physiological/physical behavioural	Eating disorder (anorexia nervosa, bulimia nervosa) · Sleep disorder (dyssomnia, insomnia, hypersomnia, parasomnia, night terror, nightmare) · Sexual dysfunction (erectile dysfunction, premature ejaculation, vaginismus, dyspareunia, hypersexuality) · Postpartum depression
Adult personality and behaviour	Personality disorder · Passive-aggressive behavior · Kleptomania · Trichotillomania · Voyeurism · Factitious disorder · Munchausen syndrome · Ego-dystonic sexual orientation
Mental retardation	Mental retardation
Psychological development (developmental disorder)	Specific: speech and language (expressive language disorder, aphasia, expressive aphasia, receptive aphasia, Landau-Kleffner syndrome, lisp) · Scholastic skills (dyslexia, dysgraphia, Gerstmann syndrome) · Motor function (developmental dyspraxia) Pervasive: Autism · Rett syndrome · Asperger syndrome
Behavioural and emotional, childhood and adolescence onset	ADHD · Conduct disorder · Oppositional defiant disorder · Separation anxiety disorder · Selective mutism · Reactive attachment disorder · Tic disorder · Tourette syndrome · Speech (stuttering · cluttering)