The Alcohol Withdrawal Syndrome

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The Alcohol Withdrawal Syndrome Downloaded from jnnp.bmj.com on February 13, 2010 - Published by group.bmj.com The alcohol withdrawal syndrome A McKeon, M A Frye and Norman Delanty J Neurol Neurosurg Psychiatry 2008 79: 854-862 originally published online November 6, 2007 doi: 10.1136/jnnp.2007.128322 Updated information and services can be found at: http://jnnp.bmj.com/content/79/8/854.full.html These include: References This article cites 115 articles, 40 of which can be accessed free at: http://jnnp.bmj.com/content/79/8/854.full.html#ref-list-1 Email alerting Receive free email alerts when new articles cite this article. Sign up in the service box at the top right corner of the online article. Topic collections Articles on similar topics can be found in the following collections Memory disorders (neurology) (2797 articles) Epilepsy and seizures (4241 articles) Unwanted effects / adverse reactions (945 articles) Alcohol-related disorders (1568 articles) Delirium (1255 articles) Drugs misuse (including addiction) (2940 articles) Memory disorders (psychiatry) (4300 articles) Drugs: musculoskeletal and joint diseases (8176 articles) Notes To order reprints of this article go to: http://jnnp.bmj.com/cgi/reprintform To subscribe to Journal of Neurology, Neurosurgery & Psychiatry go to: http://jnnp.bmj.com/subscriptions Downloaded from jnnp.bmj.com on February 13, 2010 - Published by group.bmj.com Review The alcohol withdrawal syndrome A McKeon,1 M A Frye,2 Norman Delanty1 1 Department of Neurology and ABSTRACT every 26 hospital bed days being attributable to Clinical Neurosciences, The alcohol withdrawal syndrome (AWS) is a common some degree of alcohol misuse.5 Despite this Beaumont Hospital, Dublin, and management problem in hospital practice for neurologists, Royal College of Surgeons in substantial problem, a survey of NHS general Ireland, Dublin, Ireland; psychiatrists and general physicians alike. Although some hospitals conducted in 2000 and 2003 indicated 2 Department of Psychiatry, patients have mild symptoms and may even be managed that only 12.8% had a dedicated alcohol worker.6 In Mayo Clinic, Rochester, MN, in the outpatient setting, others have more severe addition, few guidelines exist promoting the USA symptoms or a history of adverse outcomes that requires initiation of clear and uniform AWS treatment 7–9 Correspondence to: close inpatient supervision and benzodiazepine therapy. protocols. Andrew McKeon, Department of Many patients with AWS have multiple management Neurology, Gonda 8 South, issues (withdrawal symptoms, delirium tremens, the PATHOPHYSIOLOGY Mayo Clinic, 200 1st St Sw, Wernicke–Korsakoff syndrome, seizures, depression, Rochester, MN 55905, USA; Alcohol has an effect on multiple neurotransmitter [email protected] polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary systems in the brain. Pharmacological, electrophy- siological (both often undertaken in a rat model of Received 25 June 2007 approach. Although AWS may be complex, careful Revised 12 October 2007 evaluation and available treatments should ensure safe ethanol withdrawal) and genetic studies have Accepted 17 October 2007 detoxification for most patients. helped to elucidate the mechanisms of AWS. Published Online First Acute alcohol ingestion has an inhibitory effect at 6 November 2007 N-methyl-D-aspartate (NMDA) receptors, redu- cing excitatory glutamatergic transmission,10 11 The alcohol withdrawal syndrome (AWS) consists and has an agonistic effect at gamma-aminobutyric of symptoms and signs arising in alcohol-depen- acid type-A (GABA ) receptors. During prolonged dent individuals, typically within 24–48 hours of A exposure to alcohol, NMDA receptors are upregu- consumption of their last drink. Although AWS lated and GABA receptors are downregulated, occurs intentionally in those seeking abstinence, it A leading to tolerance.12 The roles are reversed during may arise unexpectedly in an alcohol-dependent abstinence, with enhanced NMDA receptor func- patient, after an admission to hospital. Although tion, reduced GABAergic transmission and dysre- alcohol withdrawal is common and usually mild, gulation of the dopaminergic system, leading to the abrupt cessation of alcohol consumption by a many of the symptoms and signs of AWS.13 14 patient with alcohol dependence may lead to Although GABA levels increase in both plasma delirium tremens (a severe dysautonomic and and CSF during withdrawal,15 symptoms of with- encephalopathic state) and withdrawal seizures, drawal still evolve due to downregulation of both of which may be fatal. The following should GABA receptors during prior prolonged alcohol be addressed by the treating doctor (fig 1): A exposure. GABA and GABA mechanisms are also confirming the diagnosis; choosing an appropriate A B critical for the development of anxiety-like beha- drug regimen and setting for management of viour that is induced by repeated ethanol intoxica- alcohol withdrawal; monitoring for and treating tions and withdrawals16. Altered numbers and other complications related to alcohol dependence functions of NMDA (particularly NR1 and NR2B (including Wernicke’s encephalopathy (WE), phy- subtypes17) and GABA receptors resulting from sical trauma and depression). In this paper, we A chronic alcohol exposure may be partly responsible review the literature on AWS, and discuss our for alcohol withdrawal seizures. Electro- views regarding an approach to management. physiologically, alterations in neurotransmitter receptor function translate into an absence of EPIDEMIOLOGY inhibitory postsynaptic potentials and currents in The prevalence of alcohol withdrawal in the ethanol-withdrawn rats.18 In addition, voltage- general population is low (,5% in US adults in dependent calcium influx modulates neurotrans- 1995), but is higher among those admitted for mitter release and expression of genes that regulate detoxification and rehabilitation for alcohol abuse production of NMDA and GABA receptor proteins; (up to 86%).1 In a UK national survey conducted in the continued presence of alcohol increases vol- 2002, 38% of male respondents and 23% of female tage-operated calcium channel expression and respondents self-reported hazardous drinking (5 or contributes to alcohol tolerance and AWS.19 more drinks for a man or 3 or more drinks for a Acamprosate, an abstinence-promoting drug, prob- woman) on a typical drinking day.2 However, in ably has its effect through antagonism of gluta- the setting of medical practice, this figure is higher, mate receptor subtype-5 and NMDA receptors, with the prevalence of alcohol abuse or dependence thus inhibiting the rise in glutamate that occurs reaching 20% of hospital inpatients,3 and up to during AWS.20 Dopaminergic transmission is 40% of patients attending Accident and Emergency enhanced during AWS (high plasma homo- departments.4 The cost of alcoholism is a large vallinic acid has been observed in patients with burden on the UK economy, and was estimated to delirium tremens21) and may play a role in cost the NHS £1.5 billion in 2000/2001, with 1 in hallucination formation;22 23 increased dopamine 854 J Neurol Neurosurg Psychiatry 2008;79:854–862. doi:10.1136/jnnp.2007.128322 Downloaded from jnnp.bmj.com on February 13, 2010 - Published by group.bmj.com Review By definition, the patient must have two or more of the following after cessation or reduction of alcohol use that has been heavy or prolonged: autonomic hyperactivity (sweating, tachycardia); increased hand tremor; insomnia; nausea or vomiting; transient visual, tactile, or auditory hallucinations or illusions; psychomotor agitation; anxiety and tonic-clonic seizures. Although, often, AWS is mild and does not require treatment, if severe it may be complicated by alcohol with- drawal seizures and delirium tremens (characterised by a severe hyperadrenergic state, disorientation, impaired attention and consciousness, as well as visual and auditory hallucinations).31 The chronic heavy user of alcohol is the typical patient who develops alcohol withdrawal seizures, which are thought to occur secondary to a kindling effect of recurrent detoxifica- tions.32 Although distinct from a true alcohol withdrawal seizure, young people with primary generalised epilepsy may present with a seizure in association with alcohol consumption and sleep deprivation on the previous night. In order to establish the risk of developing AWS and its complications, and to identify other alcohol-related problems, a Figure 1 Algorithm for management of uncomplicated alcohol careful alcohol history should be obtained. This allows for early withdrawal. detection, prevention and treatment of AWS. The components of the alcohol history are: estimating consumption (types of alcoholic drink consumed, volume, frequency and drinking receptor-binding density (D2 in the dorsal striatum and D1 in pattern); establishing if the patient is alcohol dependent the amygdala) has also been observed.24 The potential impor- (daily drinking, drinking early in the day, rating the priority tance of the amygdala and the striatum in the pathophysiology of alcohol in the patient’s life, previous medical interventions of alcohol withdrawal has also been suggested by persisting high required in relation to drinking); and establishing whether levels of cyclic guanosine 39,59-monophosphate (cGMP) in these 25 problems have arisen in relation to drinking (social, domestic, regions in rats. Neurons in the deep layers of the superior emotional, occupational,
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